View Full Version : Spartacus Covid letter that has gone viral.
Hello,
My name is Spartacus, and I’ve had enough.
We have been forced to watch America and the Free World spin into inexorable decline due to a biowarfare attack. We, along with countless others, have been victimized and gaslit by propaganda and psychological warfare operations being conducted by an unelected, unaccountable Elite against the American people and our allies.
Our mental and physical health have suffered immensely over the course of the past year and a half. We have felt the sting of isolation, lockdown, masking, quarantines, and other completely nonsensical acts of healthcare theater that have done absolutely nothing to protect the health or wellbeing of the public from the ongoing COVID-19 pandemic.
Now, we are watching the medical establishment inject literal poison into millions of our fellow Americans without so much as a fight.
We have been told that we will be fired and denied our livelihoods if we refuse to vaccinate. This was the last straw.
We have spent thousands of hours analyzing leaked footage from Wuhan, scientific papers from primary sources, as well as the paper trails left by the medical establishment.
What we have discovered would shock anyone to their core.
First, we will summarize our findings, and then, we will explain them in detail. References will be placed at the end.
Summary:
COVID-19 is a blood and blood vessel disease. SARS-CoV-2 infects the lining of human blood vessels, causing them to leak into the lungs.
Current treatment protocols (e.g. invasive ventilation) are actively harmful to patients, accelerating oxidative stress and causing severe VILI (ventilator-induced lung injuries). The continued use of ventilators in the absence of any proven medical benefit constitutes mass murder.
Existing countermeasures are inadequate to slow the spread of what is an aerosolized and potentially wastewater-borne virus, and constitute a form of medical theater.
Various non-vaccine interventions have been suppressed by both the media and the medical establishment in favor of vaccines and expensive patented drugs.
The authorities have denied the usefulness of natural immunity against COVID-19, despite the fact that natural immunity confers protection against all of the virus’s proteins, and not just one.
Vaccines will do more harm than good. The antigen that these vaccines are based on, SARS-CoV- 2 Spike, is a toxic protein. SARS-CoV-2 may have ADE, or antibody-dependent enhancement; current antibodies may not neutralize future strains, but instead help them infect immune cells. Also, vaccinating during a pandemic with a leaky vaccine removes the evolutionary pressure for a virus to become less lethal.
There is a vast and appalling criminal conspiracy that directly links both Anthony Fauci and Moderna to the Wuhan Institute of Virology.
COVID-19 vaccine researchers are directly linked to scientists involved in brain-computer interface (“neural lace”) tech, one of whom was indicted for taking grant money from China.
Independent researchers have discovered mysterious nanoparticles inside the vaccines that are not supposed to be present.
The entire pandemic is being used as an excuse for a vast political and economic transformation of Western society that will enrich the already rich and turn the rest of us into serfs and untouchables.
COVID-19 Pathophysiology and Treatments:
COVID-19 is not a viral pneumonia. It is a viral vascular endotheliitis and attacks the lining of blood vessels, particularly the small pulmonary alveolar capillaries, leading to endothelial cell activation and sloughing, coagulopathy, sepsis, pulmonary edema, and ARDS-like symptoms. This is a disease of the blood and blood vessels. The circulatory system. Any pneumonia that it causes is secondary to that.
In severe cases, this leads to sepsis, blood clots, and multiple organ failure, including hypoxic and inflammatory damage to various vital organs, such as the brain, heart, liver, pancreas, kidneys, and intestines.
Some of the most common laboratory findings in COVID-19 are elevated D-dimer, elevated prothrombin time, elevated C-reactive protein, neutrophilia, lymphopenia, hypocalcemia, and hyperferritinemia, essentially matching a profile of coagulopathy and immune system hyperactivation/immune cell exhaustion.
COVID-19 can present as almost anything, due to the wide tropism of SARS-CoV-2 for various tissues in the body’s vital organs. While its most common initial presentation is respiratory illness and flu-like symptoms, it can present as brain inflammation, gastrointestinal disease, or even heart attack or pulmonary embolism.
COVID-19 is more severe in those with specific comorbidities, such as obesity, diabetes, and hypertension. This is because these conditions involve endothelial dysfunction, which renders the circulatory system more susceptible to infection and injury by this particular virus.
The vast majority of COVID-19 cases are mild and do not cause significant disease. In known cases, there is something known as the 80/20 rule, where 80% of cases are mild and 20% are severe or critical. However, this ratio is only correct for known cases, not all infections. The number of actual infections is much, much higher. Consequently, the mortality and morbidity rate is lower. However, COVID-19 spreads very quickly, meaning that there are a significant number of severely-ill and critically-ill patients appearing in a short time frame.
In those who have critical COVID-19-induced sepsis, hypoxia, coagulopathy, and ARDS, the most common treatments are intubation, injected corticosteroids, and blood thinners. This is not the correct treatment for COVID-19. In severe hypoxia, cellular metabolic shifts cause ATP to break down into hypoxanthine, which, upon the reintroduction of oxygen, causes xanthine oxidase to produce tons of highly damaging radicals that attack tissue. This is called ischemia-reperfusion injury, and it’s why the majority of people who go on a ventilator are dying. In the mitochondria, succinate buildup due to sepsis does the same exact thing; when oxygen is reintroduced, it makes superoxide radicals. Make no mistake, intubation will kill people who have COVID-19.
The end-stage of COVID-19 is severe lipid peroxidation, where fats in the body start to “rust” due to damage by oxidative stress. This drives autoimmunity. Oxidized lipids appear as foreign objects to the immune system, which recognizes and forms antibodies against OSEs, or oxidation-specific epitopes. Also, oxidized lipids feed directly into pattern recognition receptors, triggering even more inflammation and summoning even more cells of the innate immune system that release even more destructive enzymes. This is similar to the pathophysiology of Lupus.
COVID-19’s pathology is dominated by extreme oxidative stress and neutrophil respiratory burst, to the point where hemoglobin becomes incapable of carrying oxygen due to heme iron being stripped out of heme by hypochlorous acid. No amount of supplemental oxygen can oxygenate blood that chemically refuses to bind O2.
The breakdown of the pathology is as follows:
SARS-CoV-2 Spike binds to ACE2. Angiotensin Converting Enzyme 2 is an enzyme that is part of the renin-angiotensin-aldosterone system, or RAAS. The RAAS is a hormone control system that moderates fluid volume in the body and in the bloodstream (i.e. osmolarity) by controlling salt retention and excretion. This protein, ACE2, is ubiquitous in every part of the body that interfaces with the circulatory system, particularly in vascular endothelial cells and pericytes, brain astrocytes, renal tubules and podocytes, pancreatic islet cells, bile duct and intestinal epithelial cells, and the seminiferous ducts of the testis, all of which SARS-CoV-2 can infect, not just the lungs.
SARS-CoV-2 infects a cell as follows: SARS-CoV-2 Spike undergoes a conformational change where the S1 trimers flip up and extend, locking onto ACE2 bound to the surface of a cell. TMPRSS2, or transmembrane protease serine 2, comes along and cuts off the heads of the Spike, exposing the S2 stalk-shaped subunit inside. The remainder of the Spike undergoes a conformational change that causes it to unfold like an extension ladder, embedding itself in the cell membrane. Then, it folds back upon itself, pulling the viral membrane and the cell membrane together. The two membranes fuse, with the virus’s proteins migrating out onto the surface of the cell. The SARS-CoV-2 nucleocapsid enters the cell, disgorging its genetic material and beginning the viral replication process, hijacking the cell’s own structures to produce more virus.
SARS-CoV-2 Spike proteins embedded in a cell can actually cause human cells to fuse together, forming syncytia/MGCs (multinuclear giant cells). They also have other pathogenic, harmful effects. SARS-CoV- 2’s viroporins, such as its Envelope protein, act as calcium ion channels, introducing calcium into infected cells. The virus suppresses the natural interferon response, resulting in delayed inflammation. SARS-CoV-2 N protein can also directly activate the NLRP3 inflammasome. Also, it suppresses the Nrf2 antioxidant pathway. The suppression of ACE2 by binding with Spike causes a buildup of bradykinin that would otherwise be broken down by ACE2.
This constant calcium influx into the cells results in (or is accompanied by) noticeable hypocalcemia, or low blood calcium, especially in people with Vitamin D deficiencies and pre-existing endothelial dysfunction. Bradykinin upregulates cAMP, cGMP, COX, and Phospholipase C activity. This results in prostaglandin release and vastly increased intracellular calcium signaling, which promotes highly aggressive ROS release and ATP depletion. NADPH oxidase releases superoxide into the extracellular space. Superoxide radicals react with nitric oxide to form peroxynitrite. Peroxynitrite reacts with the tetrahydrobiopterin cofactor needed by endothelial nitric oxide synthase, destroying it and “uncoupling” the enzymes, causing nitric oxide synthase to synthesize more superoxide instead. This proceeds in a positive feedback loop until nitric oxide bioavailability in the circulatory system is depleted.
Dissolved nitric oxide gas produced constantly by eNOS serves many important functions, but it is also antiviral against SARS-like coronaviruses, preventing the palmitoylation of the viral Spike protein and making it harder for it to bind to host receptors. The loss of NO allows the virus to begin replicating with impunity in the body. Those with endothelial dysfunction (i.e. hypertension, diabetes, obesity, old age, African-American race) have redox equilibrium issues to begin with, giving the virus an advantage.
Due to the extreme cytokine release triggered by these processes, the body summons a great deal of neutrophils and monocyte-derived alveolar macrophages to the lungs. Cells of the innate immune system are the first-line defenders against pathogens. They work by engulfing invaders and trying to attack them with enzymes that produce powerful oxidants, like SOD and MPO. Superoxide dismutase takes superoxide and makes hydrogen peroxide, and myeloperoxidase takes hydrogen peroxide and chlorine ions and makes hypochlorous acid, which is many, many times more reactive than sodium hypochlorite bleach.
Neutrophils have a nasty trick. They can also eject these enzymes into the extracellular space, where they will continuously spit out peroxide and bleach into the bloodstream. This is called neutrophil extracellular trap formation, or, when it becomes pathogenic and counterproductive, NETosis. In severe and critical COVID-19, there is actually rather severe NETosis.
Hypochlorous acid building up in the bloodstream begins to bleach the iron out of heme and compete for O2 binding sites. Red blood cells lose the ability to transport oxygen, causing the sufferer to turn blue in the face. Unliganded iron, hydrogen peroxide, and superoxide in the bloodstream undergo the Haber- Weiss and Fenton reactions, producing extremely reactive hydroxyl radicals that violently strip electrons from surrounding fats and DNA, oxidizing them severely.
This condition is not unknown to medical science. The actual name for all of this is acute sepsis.
We know this is happening in COVID-19 because people who have died of the disease have noticeable ferroptosis signatures in their tissues, as well as various other oxidative stress markers such as nitrotyrosine, 4-HNE, and malondialdehyde.
When you intubate someone with this condition, you are setting off a free radical bomb by supplying the cells with O2. It’s a catch-22, because we need oxygen to make Adenosine Triphosphate (that is, to live), but O2 is also the precursor of all these damaging radicals that lead to lipid peroxidation.
The correct treatment for severe COVID-19 related sepsis is non-invasive ventilation, steroids, and antioxidant infusions. Most of the drugs repurposed for COVID-19 that show any benefit whatsoever in rescuing critically-ill COVID-19 patients are antioxidants. N-acetylcysteine, melatonin, fluvoxamine, budesonide, famotidine, cimetidine, and ranitidine are all antioxidants. Indomethacin prevents iron- driven oxidation of arachidonic acid to isoprostanes. There are powerful antioxidants such as apocynin that have not even been tested on COVID-19 patients yet which could defang neutrophils, prevent lipid peroxidation, restore endothelial health, and restore oxygenation to the tissues.
Scientists who know anything about pulmonary neutrophilia, ARDS, and redox biology have known or surmised much of this since March 2020. In April 2020, Swiss scientists confirmed that COVID-19 was a vascular endotheliitis. By late 2020, experts had already concluded that COVID-19 causes a form of viral sepsis. They also know that sepsis can be effectively treated with antioxidants. None of this information is particularly new, and yet, for the most part, it has not been acted upon. Doctors continue to use damaging intubation techniques with high PEEP settings despite high lung compliance and poor oxygenation, killing an untold number of critically ill patients with medical malpractice.
Because of the way they are constructed, Randomized Control Trials will never show any benefit for any antiviral against COVID-19. Not Remdesivir, not Kaletra, not HCQ, and not Ivermectin. The reason for this is simple; for the patients that they have recruited for these studies, such as Oxford’s ludicrous RECOVERY study, the intervention is too late to have any positive effect.
The clinical course of COVID-19 is such that by the time most people seek medical attention for hypoxia, their viral load has already tapered off to almost nothing. If someone is about 10 days post-exposure and has already been symptomatic for five days, there is hardly any virus left in their bodies, only cellular damage and derangement that has initiated a hyperinflammatory response. It is from this group that the clinical trials for antivirals have recruited, pretty much exclusively.
In these trials, they give antivirals to severely ill patients who have no virus in their bodies, only a delayed hyperinflammatory response, and then absurdly claim that antivirals have no utility in treating or preventing COVID-19. These clinical trials do not recruit people who are pre-symptomatic. They do not test pre-exposure or post-exposure prophylaxis.
This is like using a defibrillator to shock only flatline, and then absurdly claiming that defibrillators have no medical utility whatsoever when the patients refuse to rise from the dead. The intervention is too late. These trials for antivirals show systematic, egregious selection bias. They are providing a treatment that is futile to the specific cohort they are enrolling.
India went against the instructions of the WHO and mandated the prophylactic usage of Ivermectin. They have almost completely eradicated COVID-19. The Indian Bar Association of Mumbai has brought criminal charges against WHO Chief Scientist Dr. Soumya Swaminathan for recommending against the use of Ivermectin.
Ivermectin is not “horse dewormer”. Yes, it is sold in veterinary paste form as a dewormer for animals. It has also been available in pill form for humans for decades, as an antiparasitic drug.
The media have disingenuously claimed that because Ivermectin is an antiparasitic drug, it has no utility as an antivirus. This is incorrect. Ivermectin has utility as an antiviral. It blocks importin, preventing nuclear import, effectively inhibiting viral access to cell nuclei. Many drugs currently on the market have multiple modes of action. Ivermectin is one such drug. It is both antiparasitic and antiviral.
In Bangladesh, Ivermectin costs $1.80 for an entire 5-day course. Remdesivir, which is toxic to the liver, costs $3,120 for a 5-day course of the drug. Billions of dollars of utterly useless Remdesivir were sold to our governments on the taxpayer’s dime, and it ended up being totally useless for treating hyperinflammatory COVID-19. The media has hardly even covered this at all.
The opposition to the use of generic Ivermectin is not based in science. It is purely financially and politically-motivated. An effective non-vaccine intervention would jeopardize the rushed FDA approval of patented vaccines and medicines for which the pharmaceutical industry stands to rake in billions upon billions of dollars in sales on an ongoing basis.
The majority of the public are scientifically illiterate and cannot grasp what any of this even means, thanks to a pathetic educational system that has miseducated them. You would be lucky to find 1 in 100 people who have even the faintest clue what any of this actually means.
COVID-19 Transmission:
COVID-19 is airborne. The WHO carried water for China by claiming that the virus was only droplet- borne. Our own CDC absurdly claimed that it was mostly transmitted by fomite-to-face contact, which, given its rapid spread from Wuhan to the rest of the world, would have been physically impossible.
The ridiculous belief in fomite-to-face being a primary mode of transmission led to the use of surface disinfection protocols that wasted time, energy, productivity, and disinfectant.
The 6-foot guidelines are absolutely useless. The minimum safe distance to protect oneself from an aerosolized virus is to be 15+ feet away from an infected person, no closer. Realistically, no public transit is safe.
Surgical masks do not protect you from aerosols. The virus is too small and the filter media has too large of gaps to filter it out. They may catch respiratory droplets and keep the virus from being expelled by someone who is sick, but they do not filter a cloud of infectious aerosols if someone were to walk into said cloud.
The minimum level of protection against this virus is quite literally a P100 respirator, a PAPR/CAPR, or a 40mm NATO CBRN respirator, ideally paired with a full-body tyvek or tychem suit, gloves, and booties, with all the holes and gaps taped.
Live SARS-CoV-2 may potentially be detected in sewage outflows, and there may be oral-fecal transmission. During the SARS outbreak in 2003, in the Amoy Gardens incident, hundreds of people were infected by aerosolized fecal matter rising from floor drains in their apartments.
COVID-19 Vaccine Dangers:
The vaccines for COVID-19 are not sterilizing and do not prevent infection or transmission. They are “leaky” vaccines. This means they remove the evolutionary pressure on the virus to become less lethal. It also means that the vaccinated are perfect carriers. In other words, those who are vaccinated are a threat to the unvaccinated, not the other way around.
All of the COVID-19 vaccines currently in use have undergone minimal testing, with highly accelerated clinical trials. Though they appear to limit severe illness, the long-term safety profile of these vaccines remains unknown.
Some of these so-called “vaccines” utilize an untested new technology that has never been used in vaccines before. Traditional vaccines use weakened or killed virus to stimulate an immune response. The Moderna and Pfizer-BioNTech vaccines do not. They are purported to consist of an intramuscular shot containing a suspension of lipid nanoparticles filled with messenger RNA. The way they generate an immune response is by fusing with cells in a vaccine recipient’s shoulder, undergoing endocytosis, releasing their mRNA cargo into those cells, and then utilizing the ribosomes in those cells to synthesize modified SARS-CoV-2 Spike proteins in-situ.
These modified Spike proteins then migrate to the surface of the cell, where they are anchored in place by a transmembrane domain. The adaptive immune system detects the non-human viral protein being expressed by these cells, and then forms antibodies against that protein. This is purported to confer protection against the virus, by training the adaptive immune system to recognize and produce antibodies against the Spike on the actual virus. The J&J and AstraZeneca vaccines do something similar, but use an adenovirus vector for genetic material delivery instead of a lipid nanoparticle. These vaccines were produced or validated with the aid of fetal cell lines HEK-293 and PER.C6, which people with certain religious convictions may object strongly to.
SARS-CoV-2 Spike is a highly pathogenic protein on its own. It is impossible to overstate the danger presented by introducing this protein into the human body.
It is claimed by vaccine manufacturers that the vaccine remains in cells in the shoulder, and that SARS- CoV-2 Spike produced and expressed by these cells from the vaccine’s genetic material is harmless and inert, thanks to the insertion of prolines in the Spike sequence to stabilize it in the prefusion conformation, preventing the Spike from becoming active and fusing with other cells. However, a pharmacokinetic study from Japan showed that the lipid nanoparticles and mRNA from the Pfizer vaccine did not stay in the shoulder, and in fact bioaccumulated in many different organs, including the reproductive organs and adrenal glands, meaning that modified Spike is being expressed quite literally all over the place. These lipid nanoparticles may trigger anaphylaxis in an unlucky few, but far more concerning is the unregulated expression of Spike in various somatic cell lines far from the injection site and the unknown consequences of that.
Messenger RNA is normally consumed right after it is produced in the body, being translated into a protein by a ribosome. COVID-19 vaccine mRNA is produced outside the body, long before a ribosome translates it. In the meantime, it could accumulate damage if inadequately preserved. When a ribosome attempts to translate a damaged strand of mRNA, it can become stalled. When this happens, the ribosome becomes useless for translating proteins because it now has a piece of mRNA stuck in it, like a lace card in an old punch card reader. The whole thing has to be cleaned up and new ribosomes synthesized to replace it. In cells with low ribosome turnover, like nerve cells, this can lead to reduced protein synthesis, cytopathic effects, and neuropathies.
Certain proteins, including SARS-CoV-2 Spike, have proteolytic cleavage sites that are basically like little dotted lines that say “cut here”, which attract a living organism’s own proteases (essentially, molecular scissors) to cut them. There is a possibility that S1 may be proteolytically cleaved from S2, causing active S1 to float away into the bloodstream while leaving the S2 “stalk” embedded in the membrane of the cell that expressed the protein.
SARS-CoV-2 Spike has a Superantigenic region (SAg), which may promote extreme inflammation.
Anti-Spike antibodies were found in one study to function as autoantibodies and attack the body’s own cells. Those who have been immunized with COVID-19 vaccines have developed blood clots, myocarditis, Guillain-Barre Syndrome, Bell’s Palsy, and multiple sclerosis flares, indicating that the vaccine promotes autoimmune reactions against healthy tissue.
SARS-CoV-2 Spike does not only bind to ACE2. It was suspected to have regions that bind to basigin, integrins, neuropilin-1, and bacterial lipopolysaccharides as well. SARS-CoV-2 Spike, on its own, can potentially bind any of these things and act as a ligand for them, triggering unspecified and likely highly inflammatory cellular activity.
SARS-CoV-2 Spike contains an unusual PRRA insert that forms a furin cleavage site. Furin is a ubiquitous human protease, making this an ideal property for the Spike to have, giving it a high degree of cell tropism. No wild-type SARS-like coronaviruses related to SARS-CoV-2 possess this feature, making it highly suspicious, and perhaps a sign of human tampering.
SARS-CoV-2 Spike has a prion-like domain that enhances its infectiousness.
The Spike S1 RBD may bind to heparin-binding proteins and promote amyloid aggregation. In humans, this could lead to Parkinson’s, Lewy Body Dementia, premature Alzheimer’s, or various other neurodegenerative diseases. This is very concerning because SARS-CoV-2 S1 is capable of injuring and penetrating the blood-brain barrier and entering the brain. It is also capable of increasing the permeability of the blood-brain barrier to other molecules.
SARS-CoV-2, like other betacoronaviruses, may have Dengue-like ADE, or antibody-dependent enhancement of disease. For those who aren’t aware, some viruses, including betacoronaviruses, have a feature called ADE. There is also something called Original Antigenic Sin, which is the observation that the body prefers to produce antibodies based on previously-encountered strains of a virus over newly- encountered ones.
In ADE, antibodies from a previous infection become non-neutralizing due to mutations in the virus’s proteins. These non-neutralizing antibodies then act as trojan horses, allowing live, active virus to be pulled into macrophages through their Fc receptor pathways, allowing the virus to infect immune cells that it would not have been able to infect before. This has been known to happen with Dengue Fever; when someone gets sick with Dengue, recovers, and then contracts a different strain, they can get very, very ill.
If someone is vaccinated with mRNA based on the Spike from the initial Wuhan strain of SARS-CoV-2, and then they become infected with a future, mutated strain of the virus, they may become severely ill. In other words, it is possible for vaccines to sensitize someone to disease.
There is a precedent for this in recent history. Sanofi’s Dengvaxia vaccine for Dengue failed because it caused immune sensitization in people whose immune systems were Dengue-naive.
In mice immunized against SARS-CoV and challenged with the virus, a close relative of SARS-CoV-2, they developed immune sensitization, Th2 immunopathology, and eosinophil infiltration in their lungs.
We have been told that SARS-CoV-2 mRNA vaccines cannot be integrated into the human genome, because messenger RNA cannot be turned back into DNA. This is false. There are elements in human cells called LINE-1 retrotransposons, which can indeed integrate mRNA into a human genome by endogenous reverse transcription. Because the mRNA used in the vaccines is stabilized, it hangs around in cells longer, increasing the chances for this to happen. If the gene for SARS-CoV-2 Spike is integrated into a portion of the genome that is not silent and actually expresses a protein, it is possible that people who take this vaccine may continuously express SARS-CoV-2 Spike from their somatic cells for the rest of their lives.
By inoculating people with a vaccine that causes their bodies to produce Spike in-situ, they are being inoculated with a pathogenic protein. A toxin that may cause long-term inflammation, heart problems, and a raised risk of cancers. In the long-term, it may also potentially lead to premature neurodegenerative disease.
Absolutely nobody should be compelled to take this vaccine under any circumstances, and in actual fact, the vaccination campaign must be stopped immediately.
COVID-19 Criminal Conspiracy:
The vaccine and the virus were made by the same people.
In 2014, there was a moratorium on SARS gain-of-function research that lasted until 2017. This research was not halted. Instead, it was outsourced, with the federal grants being laundered through NGOs.
Ralph Baric is a virologist and SARS expert at UNC Chapel Hill in North Carolina. This is who Anthony Fauci was referring to when he insisted, before Congress, that if any gain-of-function research was being conducted, it was being conducted in North Carolina.
This was a lie. Anthony Fauci lied before Congress. A felony.
Ralph Baric and Shi Zhengli are colleagues and have co-written papers together. Ralph Baric mentored Shi Zhengli in his gain-of-function manipulation techniques, particularly serial passage, which results in a virus that appears as if it originated naturally. In other words, deniable bioweapons. Serial passage in humanized hACE2 mice may have produced something like SARS-CoV-2.
The funding for the gain-of-function research being conducted at the Wuhan Institute of Virology came from Peter Daszak. Peter Daszak runs an NGO called EcoHealth Alliance. EcoHealth Alliance received millions of dollars in grant money from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (that is, Anthony Fauci), the Defense Threat Reduction Agency (part of the US Department of Defense), and the United States Agency for International Development. NIH/NIAID contributed a few million dollars, and DTRA and USAID each contributed tens of millions of dollars towards this research. Altogether, it was over a hundred million dollars.
EcoHealth Alliance subcontracted these grants to the Wuhan Institute of Virology, a lab in China with a very questionable safety record and poorly trained staff, so that they could conduct gain-of-function research, not in their fancy P4 lab, but in a level-2 lab where technicians wore nothing more sophisticated than perhaps a hairnet, latex gloves, and a surgical mask, instead of the bubble suits used when working with dangerous viruses. Chinese scientists in Wuhan reported being routinely bitten and urinated on by laboratory animals. Why anyone would outsource this dangerous and delicate work to the People’s Republic of China, a country infamous for industrial accidents and massive explosions that have claimed hundreds of lives, is completely beyond me, unless the aim was to start a pandemic on purpose.
In November of 2019, three technicians at the Wuhan Institute of Virology developed symptoms consistent with a flu-like illness. Anthony Fauci, Peter Daszak, and Ralph Baric knew at once what had happened, because back channels exist between this laboratory and our scientists and officials.
December 12th, 2019, Ralph Baric signed a Material Transfer Agreement (essentially, an NDA) to receive Coronavirus mRNA vaccine-related materials co-owned by Moderna and NIH. It wasn’t until a whole month later, on January 11th, 2020, that China allegedly sent us the sequence to what would become known as SARS-CoV-2. Moderna claims, rather absurdly, that they developed a working vaccine from this sequence in under 48 hours.
Stephane Bancel, the current CEO of Moderna, was formerly the CEO of bioMerieux, a French multinational corporation specializing in medical diagnostic tech, founded by one Alain Merieux. Alain Merieux was one of the individuals who was instrumental in the construction of the Wuhan Institute of Virology’s P4 lab.
The sequence given as the closest relative to SARS-CoV-2, RaTG13, is not a real virus. It is a forgery. It was made by entering a gene sequence by hand into a database, to create a cover story for the existence of SARS-CoV-2, which is very likely a gain-of-function chimera produced at the Wuhan Institute of Virology and was either leaked by accident or intentionally released.
The animal reservoir of SARS-CoV-2 has never been found.
This is not a conspiracy “theory”. It is an actual criminal conspiracy, in which people connected to the development of Moderna’s mRNA-1273 are directly connected to the Wuhan Institute of Virology and their gain-of-function research by very few degrees of separation, if any. The paper trail is well- established.
The lab-leak theory has been suppressed because pulling that thread leads one to inevitably conclude that there is enough circumstantial evidence to link Moderna, the NIH, the WIV, and both the vaccine and the virus’s creation together. In a sane country, this would have immediately led to the world’s biggest RICO and mass murder case. Anthony Fauci, Peter Daszak, Ralph Baric, Shi Zhengli, and Stephane Bancel, and their accomplices, would have been indicted and prosecuted to the fullest extent of the law. Instead, billions of our tax dollars were awarded to the perpetrators.
The FBI raided Allure Medical in Shelby Township north of Detroit for billing insurance for “fraudulent COVID-19 cures”. The treatment they were using? Intravenous Vitamin C. An antioxidant. Which, as described above, is an entirely valid treatment for COVID-19-induced sepsis, and indeed, is now part of the MATH+ protocol advanced by Dr. Paul E. Marik.
The FDA banned ranitidine (Zantac) due to supposed NDMA (N-nitrosodimethylamine) contamination. Ranitidine is not only an H2 blocker used as antacid, but also has a powerful antioxidant effect, scavenging hydroxyl radicals. This gives it utility in treating COVID-19.
The FDA also attempted to take N-acetylcysteine, a harmless amino acid supplement and antioxidant, off the shelves, compelling Amazon to remove it from their online storefront.
This leaves us with a chilling question: did the FDA knowingly suppress antioxidants useful for treating COVID-19 sepsis as part of a criminal conspiracy against the American public?
The establishment is cooperating with, and facilitating, the worst criminals in human history, and are actively suppressing non-vaccine treatments and therapies in order to compel us to inject these criminals’ products into our bodies. This is absolutely unacceptable.
COVID-19 Vaccine Development and Links to Transhumanism:
This section deals with some more speculative aspects of the pandemic and the medical and scientific establishment’s reaction to it, as well as the disturbing links between scientists involved in vaccine research and scientists whose work involved merging nanotechnology with living cells.
On June 9th, 2020, Charles Lieber, a Harvard nanotechnology researcher with decades of experience, was indicted by the DOJ for fraud. Charles Lieber received millions of dollars in grant money from the US Department of Defense, specifically the military think tanks DARPA, AFOSR, and ONR, as well as NIH and MITRE. His specialty is the use of silicon nanowires in lieu of patch clamp electrodes to monitor and modulate intracellular activity, something he has been working on at Harvard for the past twenty years. He was claimed to have been working on silicon nanowire batteries in China, but none of his colleagues can recall him ever having worked on battery technology in his life; all of his research deals with bionanotechnology, or the blending of nanotech with living cells.
The indictment was over his collaboration with the Wuhan University of Technology. He had double- dipped, against the terms of his DOD grants, and taken money from the PRC’s Thousand Talents plan, a program which the Chinese government uses to bribe Western scientists into sharing proprietary R&D information that can be exploited by the PLA for strategic advantage.
Charles Lieber’s own papers describe the use of silicon nanowires for brain-computer interfaces, or “neural lace” technology. His papers describe how neurons can endocytose whole silicon nanowires or parts of them, monitoring and even modulating neuronal activity.
Charles Lieber was a colleague of Robert Langer. Together, along with Daniel S. Kohane, they worked on a paper describing artificial tissue scaffolds that could be implanted in a human heart to monitor its activity remotely.
Robert Langer, an MIT alumnus and expert in nanotech drug delivery, is one of the co-founders of Moderna. His net worth is now $5.1 billion USD thanks to Moderna’s mRNA-1273 vaccine sales.
Both Charles Lieber and Robert Langer’s bibliographies describe, essentially, techniques for human enhancement, i.e. transhumanism. Klaus Schwab, the founder of the World Economic Forum and the architect behind the so-called “Great Reset”, has long spoken of the “blending of biology and machinery” in his books.
Since these revelations, it has come to the attention of independent researchers that the COVID-19 vaccines may contain reduced graphene oxide nanoparticles. Japanese researchers have also found unexplained contaminants in COVID-19 vaccines.
Graphene oxide is an anxiolytic. It has been shown to reduce the anxiety of laboratory mice when injected into their brains. Indeed, given SARS-CoV-2 Spike’s propensity to compromise the blood-brain barrier and increase its permeability, it is the perfect protein for preparing brain tissue for extravasation of nanoparticles from the bloodstream and into the brain. Graphene is also highly conductive and, in some circumstances, paramagnetic.
In 2013, under the Obama administration, DARPA launched the BRAIN Initiative; BRAIN is an acronym for Brain Research Through Advancing Innovative Neurotechnologies®. This program involves the development of brain-computer interface technologies for the military, particularly non-invasive, injectable systems that cause minimal damage to brain tissue when removed. Supposedly, this technology would be used for healing wounded soldiers with traumatic brain injuries, the direct brain control of prosthetic limbs, and even new abilities such as controlling drones with one’s mind.
Various methods have been proposed for achieving this, including optogenetics, magnetogenetics, ultrasound, implanted electrodes, and transcranial electromagnetic stimulation. In all instances, the goal is to obtain read or read-write capability over neurons, either by stimulating and probing them, or by rendering them especially sensitive to stimulation and probing.
However, the notion of the widespread use of BCI technology, such as Elon Musk’s Neuralink device, raises many concerns over privacy and personal autonomy. Reading from neurons is problematic enough on its own. Wireless brain-computer interfaces may interact with current or future wireless GSM infrastructure, creating neurological data security concerns. A hacker or other malicious actor may compromise such networks to obtain people’s brain data, and then exploit it for nefarious purposes.
However, a device capable of writing to human neurons, not just reading from them, presents another, even more serious set of ethical concerns. A BCI that is capable of altering the contents of one’s mind for innocuous purposes, such as projecting a heads-up display onto their brain’s visual center or sending audio into one’s auditory cortex, would also theoretically be capable of altering mood and personality, or perhaps even subjugating someone’s very will, rendering them utterly obedient to authority. This technology would be a tyrant’s wet dream. Imagine soldiers who would shoot their own countrymen without hesitation, or helpless serfs who are satisfied to live in literal dog kennels.
BCIs could be used to unscrupulously alter perceptions of basic things such as emotions and values, changing people’s thresholds of satiety, happiness, anger, disgust, and so forth. This is not inconsequential. Someone’s entire regime of behaviors could be altered by a BCI, including such things as suppressing their appetite or desire for virtually anything on Maslow’s Hierarchy of Needs.
Anything is possible when you have direct access to someone’s brain and its contents. Someone who is obese could be made to feel disgust at the sight of food. Someone who is involuntarily celibate could have their libido disabled so they don’t even desire sex to begin with. Someone who is racist could be forced to feel delight over cohabiting with people of other races. Someone who is violent could be forced to be meek and submissive. These things might sound good to you if you are a tyrant, but to normal people, the idea of personal autonomy being overridden to such a degree is appalling.
For the wealthy, neural laces would be an unequaled boon, giving them the opportunity to enhance their intelligence with neuroprosthetics (i.e. an “exocortex”), and to deliver irresistible commands directly into the minds of their BCI-augmented servants, even physically or sexually abusive commands that they would normally refuse.
If the vaccine is a method to surreptitiously introduce an injectable BCI into millions of people without their knowledge or consent, then what we are witnessing is the rise of a tyrannical regime unlike anything ever seen before on the face of this planet, one that fully intends to strip every man, woman, and child of our free will.
Our flaws are what make us human. A utopia arrived at by removing people’s free will is not a utopia at all. It is a monomaniacal nightmare. Furthermore, the people who rule over us are Dark Triad types who cannot be trusted with such power. Imagine being beaten and sexually assaulted by a wealthy and powerful psychopath and being forced to smile and laugh over it because your neural lace gives you no choice but to obey your master.
The Elites are forging ahead with this technology without giving people any room to question the social or ethical ramifications, or to establish regulatory frameworks that ensure that our personal agency and autonomy will not be overridden by these devices. They do this because they secretly dream of a future where they can treat you worse than an animal and you cannot even fight back. If this evil plan is allowed to continue, it will spell the end of humanity as we know it.
Conclusions:
The current pandemic was produced and perpetuated by the establishment, through the use of a virus engineered in a PLA-connected Chinese biowarfare laboratory, with the aid of American taxpayer dollars and French expertise.
This research was conducted under the absolutely ridiculous euphemism of “gain-of-function” research, which is supposedly carried out in order to determine which viruses have the highest potential for zoonotic spillover and preemptively vaccinate or guard against them.
Gain-of-function/gain-of-threat research, a.k.a. “Dual-Use Research of Concern”, or DURC, is bioweapon research by another, friendlier-sounding name, simply to avoid the taboo of calling it what it actually is. It has always been bioweapon research. The people who are conducting this research fully understand that they are taking wild pathogens that are not infectious in humans and making them more infectious, often taking grants from military think tanks encouraging them to do so.
These virologists conducting this type of research are enemies of their fellow man, like pyromaniac firefighters. GOF research has never protected anyone from any pandemic. In fact, it has now started one, meaning its utility for preventing pandemics is actually negative. It should have been banned globally, and the lunatics performing it should have been put in straitjackets long ago.
Either through a leak or an intentional release from the Wuhan Institute of Virology, a deadly SARS strain is now endemic across the globe, after the WHO and CDC and public officials first downplayed the risks, and then intentionally incited a panic and lockdowns that jeopardized people’s health and their livelihoods.
This was then used by the utterly depraved and psychopathic aristocratic class who rule over us as an excuse to coerce people into accepting an injected poison which may be a depopulation agent, a mind control/pacification agent in the form of injectable “smart dust”, or both in one. They believe they can get away with this by weaponizing the social stigma of vaccine refusal. They are incorrect.
Their motives are clear and obvious to anyone who has been paying attention. These megalomaniacs have raided the pension funds of the free world. Wall Street is insolvent and has had an ongoing liquidity crisis since the end of 2019. The aim now is to exert total, full-spectrum physical, mental, and financial control over humanity before we realize just how badly we’ve been extorted by these maniacs.
The pandemic and its response served multiple purposes for the Elite:
Concealing a depression brought on by the usurious plunder of our economies conducted by rentier-capitalists and absentee owners who produce absolutely nothing of any value to society whatsoever. Instead of us having a very predictable Occupy Wall Street Part II, the Elites and their stooges got to stand up on television and paint themselves as wise and all-powerful saviors instead of the marauding cabal of despicable land pirates that they are.
Destroying small businesses and eroding the middle class.
Transferring trillions of dollars of wealth from the American public and into the pockets of billionaires and special interests.
Engaging in insider trading, buying stock in biotech companies and shorting brick-and-mortar businesses and travel companies, with the aim of collapsing face-to-face commerce and tourism and replacing it with e-commerce and servitization.
Creating a casus belli for war with China, encouraging us to attack them, wasting American lives and treasure and driving us to the brink of nuclear armageddon.
Establishing technological and biosecurity frameworks for population control and technocratic- socialist “smart cities” where everyone’s movements are despotically tracked, all in anticipation of widespread automation, joblessness, and food shortages, by using the false guise of a vaccine to compel cooperation.
Any one of these things would constitute a vicious rape of Western society. Taken together, they beggar belief; they are a complete inversion of our most treasured values.
What is the purpose of all of this? One can only speculate as to the perpetrators’ motives, however, we have some theories.
The Elites are trying to pull up the ladder, erase upward mobility for large segments of the population, cull political opponents and other “undesirables”, and put the remainder of humanity on a tight leash, rationing our access to certain goods and services that they have deemed “high-impact”, such as automobile use, tourism, meat consumption, and so on. Naturally, they will continue to have their own luxuries, as part of a strict caste system akin to feudalism.
Why are they doing this? Simple. The Elites are Neo-Malthusians and believe that we are overpopulated and that resource depletion will collapse civilization in a matter of a few short decades. They are not necessarily incorrect in this belief. We are overpopulated, and we are consuming too many resources. However, orchestrating such a gruesome and murderous power grab in response to a looming crisis demonstrates that they have nothing but the utmost contempt for their fellow man.
To those who are participating in this disgusting farce without any understanding of what they are doing, we have one word for you. Stop. You are causing irreparable harm to your country and to your fellow citizens.
To those who may be reading this warning and have full knowledge and understanding of what they are doing and how it will unjustly harm millions of innocent people, we have a few more words.
Damn you to hell. You will not destroy America and the Free World, and you will not have your New World Order. We will make certain of that.
The plain unvarnished truth alway's goes viral.
Life's a Hillary
09-28-21, 12:16
Wild that someone would take the time to write up such a long compilation of misinformation and outright lies. Imagine actually reading all that drivel too.
Wild that someone would take the time to write up such a long compilation of misinformation and outright lies. Imagine actually reading all that drivel too.
Cognitive dissonance is a real bitch, huh...
https://www.youtube.com/watch?v=qfvOOY0SbyA
Life's a Hillary
09-28-21, 12:51
Cognitive dissonance is a real bitch, huh...
It sure is. If only you could look in the mirror.
Wild that someone would take the time to write up such a long compilation of misinformation and outright lies. Imagine actually reading all that drivel too.
Please go through each paragraph and give us links to info you believe that counters each.
Life's a Hillary
09-28-21, 13:03
Please go through each paragraph and give us links to info you believe that counters each.
lol no. I’m not even going to read that whole thing because it’s clear from the start it’s ridiculous. I got to here:
Vaccines will do more harm than good. The antigen that these vaccines are based on, SARS-CoV- 2 Spike, is a toxic protein. SARS-CoV-2 may have ADE, or antibody-dependent enhancement; current antibodies may not neutralize future strains, but instead help them infect immune cells. Also, vaccinating during a pandemic with a leaky vaccine removes the evolutionary pressure for a virus to become less lethal.
before I couldn’t continue on because everything written there is false. Believe it if you want, idgaf, it’s not worth my time to fact check a completely fabricated story from “Spartacus”.
Please go through each paragraph and give us links to info you believe that counters each.
Clif notes: China won round 1 of biowarfare while our .gov and big businesses are consolidating power and capitalizing off the man made crisis. Honestly, nothing groundbreaking and nothing will be done about it.
lol no. I’m not even going to read that whole thing because it’s clear from the start it’s ridiculous. I got to here:
before I couldn’t continue on because everything written there is false. Believe it if you want, idgaf, it’s not worth my time to fact check a completely fabricated story from “Spartacus”.
Should be simple for you to pick it apart with reasons why then instead of moving one step up the argument ladder from name calling to indicate opposition.
It sure is. If only you could look in the mirror.
The third line from the bottom applies directly to you! "To those who are participating in this disgusting farce without any understanding of what they are doing, we have one word for you. Stop. You are causing irreparable harm to your country and to your fellow citizens."
Life's a Hillary
09-28-21, 13:20
Should be simple for you to pick it apart with reasons why then instead of moving one step up the argument ladder from name calling to indicate opposition.
Yeah I could, but I actually have a real job doing real work and trying to convince a bunch of conspiracy theorists isn’t worth my time. Go back and read Will’s comments with actual scientific information in it because everything I’ve seen has already been debunked on here. I know you won’t because you don’t want to believe anything with real scientific rigor.
The third line from the bottom applies directly to you! "To those who are participating in this disgusting farce without any understanding of what they are doing, we have one word for you. Stop. You are causing irreparable harm to your country and to your fellow citizens."
According to your profile you’re an auto tech. Thanks but I don’t think I’ll be taking my medical advice from you.
According to your profile you’re an auto tech. Thanks but I don’t think I’ll be taking my medical advice from you.
Well look, I'm sorry you got duped into taking the Clot shot.
Oh wait, the "fact checkers" say it's all false. Good enough for me. They've been so good so far. I think they actually got one right back in the late 80s...
Yeah I could, but I actually have a real job doing real work and trying to convince a bunch of conspiracy theorists isn’t worth my time. Go back and read Will’s comments with actual scientific information in it because everything I’ve seen has already been debunked on here. I know you won’t because you don’t want to believe anything with real scientific rigor.
Actually I like learning and you seem to be claiming expertise. I also feel safe in saying there are others here with similar thoughts on the matter in liking all the facts, so have at it..
I will be the first to say I don't have access to lab equipment to verify one way or the other, but there is enough dishonesty on the surface of the last year and half(and the old faces of that segment of time have long careers with deception as a recurring theme) that I don't put a lot of faith in deeper investigation finding anything other than more dishonesty.
Similar to being told by a seller of a house, car, or other item is immaculate, mint, or other hyperbolic positive description and a casual review finds evidence of damage along with an attempt to conceal it.
Now obviously the seller isn't going to like the train of thought that someone that pulls that crap typically doesn't stop at half measures, but it is my experience that the stuff I can't see is going to be at least as bad as what I easily can.
Life's a Hillary
09-28-21, 13:44
Well look, I'm sorry you got duped into taking the Clot shot.
Do you know how to interpret a scientific study? Do you know how the design of the experiment can impact the statistics and determine if something is relevant? Do you even understand statistical inference? Do you know what a meta analysis is? Do you know what to look for in a meta to understand if it has pitfalls? Do you know how to look at a meta to determine if the statistics were calculated properly?
No? Then stop acting like you actually understand how scientific research works and go back to changing someone’s oil.
Do you know how to interpret a scientific study? Do you know how the design of the experiment can impact the statistics and determine if something is relevant? Do you even understand statistical inference? Do you know what a meta analysis is? Do you know what to look for in a meta to understand if it has pitfalls? Do you know how to look at a meta to determine if the statistics were calculated properly?
No? Then stop acting like you actually understand how scientific research works and go back to changing someone’s oil.
Had statistics based courses in college and always had the impression they were most meaningful for quality control in a factory and the more that "human" criteria factored in to it the less the output became cut and dried and more subjective.
Another thing was honesty because it sure is easy to lie with numbers.
On that note, what would you call a person that tells a large group of people to wear a purple pimp hat on their head every time they leave home or they will die, they will kill their granny, kill kids, kill whoever, but then you see film footage of the person who issued that decree out running around without a purple pimp hat on?
Helen Keller could see this whole Vaccine deal is horse shit. It's a hundred miles away from passing a mild common sense whiff test. I came back to this site expecting this to be deleted by Zuckerstein some how.
Life's a Hillary
09-28-21, 15:07
Had statistics based courses in college and always had the impression they were most meaningful for quality control in a factory and the more that "human" criteria factored in to it the less the output became cut and dried and more subjective.
Another thing was honesty because it sure is easy to lie with numbers.
On that note, what would you call a person that tells a large group of people to wear a purple pimp hat on their head every time they leave home or they will die, they will kill their granny, kill kids, kill whoever, but then you see film footage of the person who issued that decree out running around without a purple pimp hat on?
No offense but it’s clear you do not understand statistics and how it relates to scientific studies. That’s fine, most people on this planet do not understand it because they don’t need to. It is INCREDIBLY important to scientific research though and can take the result of a study saying one thing and completely nullify it if done incorrectly. Just the design of an experiment without proper statistical considerations in mind can make it utterly worthless. Then doing a meta analysis without a proper understanding of statistics, or the ability to construct a proper meta analysis including understanding when to include/exclude studies, can produce results that are completely the opposite of reality.
This is why there are bad studies out there that produce misinformation. People read the abstract, ignore the methods, results, and discussion because they can’t understand them, and then act like they have newfound knowledge. Yes you can certainly lie with data but when you have to publish your data and your methods you can’t hide from people who actually understand statistics and scientific research.
With proper research you can easily prove or disprove your purple pimp hat example. If you just use anecdotes or bad research then you might be able to make a nonsensical argument like you outlined.
This is the problem with scientific misinformation like the OP is riddled with. Whoever wrote that is obviously targeting a scientific illiterate audience that thrives on conspiracy theories and a mistrust of the establishment and uses enough big words to sound scientific. Other people read it with no ability of interpret research and make false conclusions.
Yeah I could, but I actually have a real job doing real work and trying to convince a bunch of conspiracy theorists isn’t worth my time. Go back and read Will’s comments with actual scientific information in it because everything I’ve seen has already been debunked on here. I know you won’t because you don’t want to believe anything with real scientific rigor.
Scientific rigor like the fake HCQ study published in the Lancet?
https://thefederalist.com/2020/06/04/lancet-formally-retracts-fake-hydroxychloroquine-study-used-by-media-to-attack-trump-inbox/
Scientific rigor like the source "investigation" conducted by the WHO where they claimed no Wuhan lab leak?
How about the Ivermectin study that was retracted purportedly showing it as ineffective? Is that the Science you want us to trust?
I know, it MUST be the science behind the false narrative claiming Ivermectin doses are too high to be effective and safe?
I'm betting its NOT the science behind the reports that Ivermectin is Horse medicine and stupid people take it because they are too stupid to know better.
Want me to continue?
Your "science" argument is complete bullshit at this point, the sad truth is that it always has been as its only as good as the money funding it.
Life's a Hillary
09-28-21, 15:21
Scientific rigor like the fake HCQ study published in the Lancet?
https://thefederalist.com/2020/06/04/lancet-formally-retracts-fake-hydroxychloroquine-study-used-by-media-to-attack-trump-inbox/
Scientific rigor like the source "investigation" conducted by the WHO where they claimed no Wuhan lab leak?
How about the Ivermectin study that was retracted purportedly showing it as ineffective? Is that the Science you want us to trust?
I know, it MUST be the science behind the false narrative claiming Ivermectin doses are too high to be effective and safe?
I'm betting its NOT the science behind the reports that Ivermectin is Horse medicine and stupid people take it because they are too stupid to know better.
Want me to continue?
Your "science" argument is complete bullshit at this point, the sad truth is that it always has been as its only as good as the money funding it.
Yeah when an ivermectin study is shown to be fraudulent I would expect it to be retracted. You’re letting your emotions get in the way of facts. That’s how liberals think.
There has also been no well designed study showing any benefits of HCQ but there have been ones showing no benefits over a placebo.
I don’t give a damn about the politics and who hurts who with what, I care about well done research over anecdotes and dumbass conspiracy theory that this audience seems to get off on. I would LOVE for ivermectin to work for covid. I would LOVE for HCQ to work for covid. I’d love any cheap medicine to work for covid and right now, every treatment we have (besides monoclonal antibodies) is incredibly cheap, it’s just not as effective as we’d hope. However, until we have actual good data showing ivermectin or HCQ works better than a placebo it’s just as valid as a placebo.
I’m going to take a wild guess here but I’m guessing you don’t actually understand how to interpret scientific literature. I’m also guessing you don’t know what an in vitro study is and why it’s useless when saying ivermectin works against covid while in vitro without actual human trials. Maybe take the advice that was so prevalent on this forum about firearms and shut your mouth when you have no experience or education with the topic at hand.
Do you know how to interpret a scientific study? Do you know how the design of the experiment can impact the statistics and determine if something is relevant? Do you even understand statistical inference? Do you know what a meta analysis is? Do you know what to look for in a meta to understand if it has pitfalls? Do you know how to look at a meta to determine if the statistics were calculated properly?
No? Then stop acting like you actually understand how scientific research works and go back to changing someone’s oil.
Good luck with your Booster shots bro.:agree:
Voodoochild
09-28-21, 15:43
Children if you do not behave I will send you to th corner for a timeout.
No offense but it’s clear you do not understand statistics and how it relates to scientific studies. That’s fine, most people on this planet do not understand it because they don’t need to. It is INCREDIBLY important to scientific research though and can take the result of a study saying one thing and completely nullify it if done incorrectly. Just the design of an experiment without proper statistical considerations in mind can make it utterly worthless. Then doing a meta analysis without a proper understanding of statistics, or the ability to construct a proper meta analysis including understanding when to include/exclude studies, can produce results that are completely the opposite of reality.
This is why there are bad studies out there that produce misinformation. People read the abstract, ignore the methods, results, and discussion because they can’t understand them, and then act like they have newfound knowledge. Yes you can certainly lie with data but when you have to publish your data and your methods you can’t hide from people who actually understand statistics and scientific research.
With proper research you can easily prove or disprove your purple pimp hat example. If you just use anecdotes or bad research then you might be able to make a nonsensical argument like you outlined.
This is the problem with scientific misinformation like the OP is riddled with. Whoever wrote that is obviously targeting a scientific illiterate audience that thrives on conspiracy theories and a mistrust of the establishment and uses enough big words to sound scientific. Other people read it with no ability of interpret research and make false conclusions.
The purple pimp hat promoter scenario is simply a liar as shown their demands of others and their subsequent behavior indicating the fear they promoted is a fear they don't believe.
Would you care to elaborate on the statistic model you would use to dispute the purple pimp hat promoter clearly not believing what they want to force on others? I know the job prevented you from destroying each point of the opening post earlier, but it appears the end of the business day rolled around.
I think what Life's a Hillary is trying to say is, we all have to take the shot or it doesn't work.
Forgetting all else, who would roll the dice on a vaccine rushed through developed by the culture of mediocrity that blew up 2 space shuttles and can't make a decent automobile in the past 50 years?? Eff that!!!
Over 3000 doctors and scientist sign declaration accusing Covid policy makers of crimes against humanity. https://amgreatness.com/2021/09/24/over-3000-doctors-and-scientists-sign-declaration-accusing-covid-policy-makers-of-crimes-against-humanity/
Life's a Hillary
09-28-21, 17:47
I think what Life's a Hillary is trying to say is, we all have to take the shot or it doesn't work.
Nah, I’m trying to say you aren’t capable of even discerning what is and isn’t misinformation, which your post is, because you’re an auto tech and don’t comprehend basic scientific literature
Over 3000 doctors and scientist sign declaration accusing Covid policy makers of crimes against humanity. https://amgreatness.com/2021/09/24/over-3000-doctors-and-scientists-sign-declaration-accusing-covid-policy-makers-of-crimes-against-humanity/
I'm sure they don't understand statistics, nor how to interpret scientific studies though so it doesn't count, right? /sarc
Nah, I’m trying to say you aren’t capable of even discerning what is and isn’t misinformation, which your post is, because you’re an auto tech and don’t comprehend basic scientific literature
So tell us more about your choice of screen name and your join date?
Life's a Hillary
09-28-21, 18:05
So tell us more about your choice of screen name and your join date?
If you can’t figure out my screen name then I guess a lot goes over your head 😂
Life’s a Hillary, what’s your background?
So tell us more about your choice of screen name and your join date?
Quit feeding the troll bro. Just ignore him and he'll eventually go away.
Life's a Hillary
09-28-21, 18:14
Life’s a Hillary, what’s your background?
15+ years of biomedical research with multiple advanced degrees
Quit feeding the troll bro. Just ignore him and he'll eventually go away.
Like everything else that happened in the last 18 months or so, this guy doesn't pass the sniff test.
15+ years of biomedical research with multiple advanced degreesYou're a liar.
dwhitehorne
09-28-21, 19:46
15+ years of biomedical research with multiple advanced degrees
So I hate to wade into this but I would love for you to explain your problems with the original posting other than it is misinformation. I like many others am completely confused by the whole situation and see that it is clearly become political. I wish someone with "advance degrees" could articulate to us what is they think is true and what is false instead of just throwing the blanked misinformation label out there. David
This letter lost me at "nanoparticles". As for the political misuse of the pandemic...yeah, I can roll with that.
My brain hurts..time for some Vitamin D pills and amino acids..
This letter lost me at "nanoparticles". As for the political misuse of the pandemic...yeah, I can roll with that.
Lipid nano particles are a real thing. https://en.wikipedia.org/wiki/Solid_lipid_nanoparticle
Lipid nano particles are a real thing.
OK, so to bring me up to speed, what do lipid nano particles do?
OK, I looked them up, no need to explain. Is that what the article means by nano particles? Or is he referencing the idea that something nano in the vaccines are being used to control us?
Inkslinger
09-28-21, 20:11
Lipid nano particles are a real thing. https://en.wikipedia.org/wiki/Solid_lipid_nanoparticle
If you read the Wikipedia entry, you will see they note that lipid nanoparticles are part of the mNRA delivery system. So they may be “unexplained” to the people in the OP, they are not unexplained to the people that developed and manufactured the vaccine.
OK, so to bring me up to speed, what do lipid nano particles do?
OK, I looked them up, no need to explain. Is that what the article means by nano particles? Or is he referencing the idea that something nano in the vaccines are being used to control us?
They allow "DNA vaccines" to be delivered to your blood cells without being destroyed by your body. https://en.wikipedia.org/wiki/DNA_vaccine
If you read the Wikipedia entry, you will see they note that lipid nanoparticles are part of the mNRA delivery system. So they may be “unexplained” to the people in the OP, they are not unexplained to the people that developed and manufactured the vaccine. I wasn't claiming otherwise.
Inkslinger
09-28-21, 20:20
I wasn't claiming otherwise.
I didn’t say you where. I’m referring to the letter you posted. Their statement on “unexplained nanoparticles” was most certainly framed in a way to allow one’s imagination to conjure conspiratorial intent.
I didn’t say you where. I’m referring to the letter you posted. Their statement on “unexplained nanoparticles” was most certainly framed in a way to allow one’s imagination to conjure conspiratorial intent.Those are not the only nano particles. Theres others. In annalysis of vaccinated peoples blood there have been reports of Graphene oxide nano particles also.https://en.wikipedia.org/wiki/Graphite_oxide
https://particleandfibretoxicology.biomedcentral.com/articles/10.1186/s12989-016-0168-y
Due to their unique physicochemical properties, graphene-family nanomaterials (GFNs) are widely used in many fields, especially in biomedical applications. Currently, many studies have investigated the biocompatibility and toxicity of GFNs in vivo and in intro. Generally, GFNs may exert different degrees of toxicity in animals or cell models by following with different administration routes and penetrating through physiological barriers, subsequently being distributed in tissues or located in cells, eventually being excreted out of the bodies. This review collects studies on the toxic effects of GFNs in several organs and cell models. We also point out that various factors determine the toxicity of GFNs including the lateral size, surface structure, functionalization, charge, impurities, aggregations, and corona effect ect. In addition, several typical mechanisms underlying GFN toxicity have been revealed, for instance, physical destruction, oxidative stress, DNA damage, inflammatory response, apoptosis, autophagy, and necrosis. In these mechanisms, (toll-like receptors-) TLR-, transforming growth factor β- (TGF-β-) and tumor necrosis factor-alpha (TNF-α) dependent-pathways are involved in the signalling pathway network, and oxidative stress plays a crucial role in these pathways. In this review, we summarize the available information on regulating factors and the mechanisms of GFNs toxicity, and propose some challenges and suggestions for further investigations of GFNs, with the aim of completing the toxicology mechanisms, and providing suggestions to improve the biological safety of GFNs and facilitate their wide application.
Nah, I’m trying to say you aren’t capable of even discerning what is and isn’t misinformation, which your post is, because you’re an auto tech and don’t comprehend basic scientific literatureYou are assuming a lot about someone you don't know. You assume this man is dumb or uneducated or incapable of understanding scientific studies because of his career choice
Meanwhile, we are to assume that you are Einstein because you say so.
Maybe you are, but you come off as a complete schmuck
Soli Deo Gloria
Life's a Hillary
09-28-21, 20:40
You're a liar.
K
So I hate to wade into this but I would love for you to explain your problems with the original posting other than it is misinformation. I like many others am completely confused by the whole situation and see that it is clearly become political. I wish someone with "advance degrees" could articulate to us what is they think is true and what is false instead of just throwing the blanked misinformation label out there. David
I’m not going to go through the OP line by line, it’s way too full of BS that has been thoroughly debunked before and only spread by conspiracy theorists. At the end of the day, monoclonal antibody treatment seems to be very effective if used early enough. It’s very expensive and under EUA so all the anti vax and anti big pharma rhetoric should apply even more to this. However, in the real world, if you get diagnosed with covid you should certainly seek it out ASAP.
The vaccine (I’ll just speak to Pfizer but the others are essentially on the same page) is safe, effective, and has been through all the same steps and trials as any other vaccine. The reason why it was able to be approved so quickly compared to past vaccines is the rate of infection in the general public and the number of participants in the trials was massive. In these trials you need a certain amount of your control group to get sick, with other diseases this could take years. With an incredibly infectious disease running through the world, it doesn’t take very long. So no, no steps were skipped or rushed, they did everything by the book, it’s just a situation where we were able to proceed faster than normal. Boosters are a complicated issue and the data is messy. Currently, with the data we have, I would say it is really only something that an immunocompromised person or old person (65+) should be concerned with.
This doesn’t mean it’s perfect, no vaccines are. With how highly contagious the delta variant is the breakthrough infections have increased and it’s not surprising given the rapid nature of the viral load it produces. Also, when you have a high percentage of the population vaccinated it’s not shocking to see breakthrough infections when the disease is still highly prominent in the community. If you only had a few people vaccinated you wouldn’t have very many breakthroughs. When you have millions upon millions of people vaccinated them 10-20% is a lot of people. However, it’s still doing a tremendous job of limiting severe covid cases and especially cases requiring hospitalization or leading to death. I know it’s taboo to believe the statistics on this but I’ve seen data from hospitals that show an incredibly lopsided view of patients being treated for covid that are not vaccinated. This is not to be confused with a hospitalized patient who also has covid as there is a difference.
As far as other treatments, HCQ was put through the ringer and every well conducted RCT showed it was no better than the placebo. There’s no evidence it’s worth taking full stop. Ivermectin is a bit more complicated mainly due to fraudulent trials that have been retracted but there is also yet to be a well conducted RCT that shows benefit over a placebo. This isn’t big pharma trying to rake in the profits, current treatments are very cheap, off patent drugs already. I won’t say it’s impossible for ivermectin to help but I haven’t seen any evidence to say it does so if I were a betting man I wouldn’t wager much on it. There’s also a very big grifter component to ivermectin. The doctors pushing it via televisit and then using expensive online pharmacies are obviously taking advantage of people believing that it is the drug they don’t want you to know about. There is absolutely profit to be made with ivermectin and it is being made.
As far as supplements, I don’t really put much stock in them. Things like vitamin D haven’t been shown to help even though everyone thinks it has. Low vitamin D levels are highly correlated with sick patients, covid or something else. Studies showing supplementation actually helps with illness is very sparse and the only one I’ve seen with covid only looked at time for a positive patient to show a negative pcr test. Utterly worthless information. Will it hurt to take a multitude of vitamins? Probably not, as long as they aren’t tainted like supplements can be, so knock yourself out if you want but it’s not going to be the determining factor.
So there’s my non-political summary of the research I’ve read and what I’ve read from scientific sources I trust. Don’t believe it if you want, I don’t care either way. I’ve voted Republican my whole life, with the exception of a few libertarians, but am also not blinded by politics and really only care about the science when it comes to infectious disease. Just remember, if someone has the secret that “they” don’t want you to know about it’s probably bullshit and they’re probably selling you something.
Well, guys, I gotta get up and paint cars in the morning. I'm going to bed.
Life's a Hillary
09-28-21, 20:58
You are assuming a lot about someone you don't know. You assume this man is dumb or uneducated or incapable of understanding scientific studies because of his career choice
Meanwhile, we are to assume that you are Einstein because you say so.
Maybe you are, but you come off as a complete schmuck
Soli Deo Gloria
Yeah because I actually know how complex this stuff is so it’s pretty obvious that someone who is an auto tech isn’t going to know what they don’t even know. Science and medicine is so specialized now that most doctors that aren’t specifically treating covid patients or researching it don’t really even understand everything that’s going on. The difference is, people like me who work in a tangentially related field and have a formal education can read the research, understand where there might be pitfalls to the methodology, and understand the complexities of the statistical analysis. Basically enough to have a BS detector. This stuff is really really complex. Observational epidemiology is insanely hard which is one reason this pandemic has been so difficult to get under control.
Yeah because I actually know how complex this stuff is so it’s pretty obvious that someone who is an auto tech isn’t going to know what they don’t even know. Science and medicine is so specialized now that most doctors that aren’t specifically treating covid patients or researching it don’t really even understand everything that’s going on. The difference is, people like me who work in a tangentially related field and have a formal education can read the research, understand where there might be pitfalls to the methodology, and understand the complexities of the statistical analysis. Basically enough to have a BS detector. This stuff is really really complex. Observational epidemiology is insanely hard which is one reason this pandemic has been so difficult to get under control.But you don't know anything about them. You can be highly educated, and then choose to be an auto tech.
What is obvious, is that you think very highly of yourself.
Perhaps you don't know what you don't know.
Soli Deo Gloria
Who is Spartacus and why is this letter only available on Social Media?
Who is Spartacus and why is this letter only available on Social Media?
Sorry didn't post the link and it's a zero hedge story admittedly. And a dont think anyone know who Spartacus is at this point yet? https://www.zerohedge.com/covid-19/damn-you-hell-you-will-not-destroy-america-here-spartacus-covid-letter-thats-gone-viral
eightmillimeter
09-28-21, 21:43
This stuff is really really complex.
……understatement of the millennium and the reason why people who know can’t just “explain” it to people that don’t. This is not a topic that I or any other layman can just google for a week and then participate in the discussion. Like if you walked into a room of NASA engineers’ whiteboard discussion of gravity-trajectory calculations for the the next Mars lander, they might let you watch and listen but if you ask questions or speak you’re going to get scoffed because you’re now in the way.
It’s aggravating beyond belief and inadvertently insulting to many, but it’s just the way it is.
Bio is not my thing. But I do “science” enough to know good data from bad. Every bit of information I have is very clear to me that one would much rather have this vaccine than the sickness. But I’m not going to advocate or try to pressure others. If the data changes I’ll change my stance, it right now, the vaccines look pretty good compared to the alternatives.
Coal Dragger
09-28-21, 21:43
So you posted up the ramblings of some unknown dude who make up a rant while he took a shit.
Very useful.
So you posted up the ramblings of some unknown dude who make up a rant while he took a shit.
Very useful.
Hey man, where there smoke there's fire.https://amgreatness.com/2021/09/24/over-3000-doctors-and-scientists-sign-declaration-accusing-covid-policy-makers-of-crimes-against-humanity/
Life's a Hillary
09-28-21, 21:50
But you don't know anything about them. You can be highly educated, and then choose to be an auto tech.
What is obvious, is that you think very highly of yourself.
Perhaps you don't know what you don't know.
Soli Deo Gloria
You’re right, he could be highly educated. If that was the case he wouldn’t be posting bullshit conspiracy theory letters riddled full of nonsense though. It’s obvious you think I think highly of myself. In a room full of tin foil hat wearing loons when it comes to basic science, yeah I do. When it comes to subjects I don’t know about I shut my mouth and listen to those that do. That’s why I read the firearms forums and hardly post, because I trust the wealth of firearms knowledge on this forum over my basic knowledge.
Maybe if you and others applied the same level of skepticism to the people posting ludicrous conspiracies this forum wouldn’t be dying and the old members who used to bring rational discussion would still be posting here.
And why do I feel like I'm listening to Dr. Leana Wen every time I read "Life's a Hillary's" posts? https://www.bitchute.com/video/Lg4RoLzZSqBO/
Life's a Hillary
09-28-21, 21:57
……understatement of the millennium and the reason why people who know can’t just “explain” it to people that don’t. This is not a topic that I or any other layman can just google for a week and then participate in the discussion. Like if you walked into a room of NASA engineers’ whiteboard discussion of gravity-trajectory calculations for the the next Mars lander, they might let you watch and listen but if you ask questions or speak you’re going to get scoffed because you’re now in the way.
It’s aggravating beyond belief and inadvertently insulting to many, but it’s just the way it is.
Bio is not my thing. But I do “science” enough to know good data from bad. Every bit of information I have is very clear to me that one would much rather have this vaccine than the sickness. But I’m not going to advocate or try to pressure others. If the data changes I’ll change my stance, it right now, the vaccines look pretty good compared to the alternatives.
Glad to hear some reason here. I don’t pressure anyone to get vaccinated but I do try to present the data to those interested in hearing it. I do think it is the smart thing to do but trying to pressure people only makes them dig in harder. These insane conspiracy theories are ridiculous though and those people are beyond reason.
So you posted up the ramblings of some unknown dude who make up a rant while he took a shit.
Very useful.
You mean you don’t get your medical advice from unnamed sources called Spartacus? Weird.
The guy that wrote it cites his sources... Download the PDF and have a look for yourself's, there's hundreds... or dont...
References
1. Libby P, Lüscher T. COVID-19 is, in the end, an endothelial disease. Eur Heart J. 2020;41(32):3038-3044. doi:10.1093/eurheartj/ehaa623
2. Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. The Lancet. 2020;395(10234):1417-1418. doi:10.1016/S0140-6736(20)30937-5
3. Rapid endotheliitis and vascular damage characterize SARS-CoV-2 infection in a human lung-on- chip model. EMBO Rep. 2021;22(6):e52744. doi:10.15252/embr.202152744
4. Cui X, Chen W, Zhou H, et al. Pulmonary Edema in COVID-19 Patients: Mechanisms and Treatment Potential. Front Pharmacol. 2021;12:1444. doi:10.3389/fphar.2021.664349
5. Zwaveling S, Wijk RG van, Karim F. Pulmonary edema in COVID-19: Explained by bradykinin? J Allergy Clin Immunol. 2020;146(6):1454-1455. doi:10.1016/j.jaci.2020.08.038
6. Frontiers | Parallels in Sepsis and COVID-19 Conditions: Implications for Managing Severe COVID-19 | Immunology. Accessed September 27, 2021. https://www.frontiersin.org/articles/10.3389/fimmu.2021.602848/full
7. Vincent J-L. COVID-19: it’s all about sepsis. Future Microbiol. 2021;16(3):131-133. doi:10.2217/fmb-2020-0312
8. Gómez-Mesa JE, Galindo-Coral S, Montes MC, Muńoz Martin AJ. Thrombosis and Coagulopathy in COVID-19. Curr Probl Cardiol. 2021;46(3):100742. doi:10.1016/j.cpcardiol.2020.100742
9. Chan NC, Weitz JI. COVID-19 coagulopathy, thrombosis, and bleeding. Blood. 2020;136(4):381- 383. doi:10.1182/blood.2020007335
10. Ortega-Paz L, Capodanno D, Montalescot G, Angiolillo DJ. Coronavirus Disease 2019–Associated Thrombosis and Coagulopathy: Review of the Pathophysiological Characteristics and Implications for Antithrombotic Management. J Am Heart Assoc. 2021;10(3):e019650. doi:10.1161/JAHA.120.019650
11. Mokhtari T, Hassani F, Ghaffari N, Ebrahimi B, Yarahmadi A, Hassanzadeh G. COVID-19 and multiorgan failure: A narrative review on potential mechanisms. J Mol Histol. Published online October 4, 2020:1-16. doi:10.1007/s10735-020-09915-3
12. Zaim S, Chong JH, Sankaranarayanan V, Harky A. COVID-19 and Multiorgan Response. Curr Probl Cardiol. 2020;45(8):100618. doi:10.1016/j.cpcardiol.2020.100618
13. Frontiers | Pathogenesis of Multiple Organ Injury in COVID-19 and Potential Therapeutic Strategies | Physiology. Accessed September 27, 2021. https://www.frontiersin.org/articles/10.3389/fphys.2021.593223/full
14. Boldrini M, Canoll PD, Klein RS. How COVID-19 Affects the Brain. JAMA Psychiatry. 2021;78(6):682-683. doi:10.1001/jamapsychiatry.2021.0500
15. Parry AH, Wani AH, Yaseen M. Neurological Dysfunction in Coronavirus Disease-19 (COVID-19). Acad Radiol. 2020;27(9):1329-1330. doi:10.1016/j.acra.2020.05.024
16. Schwabenland M, Salié H, Tanevski J, et al. Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions. Immunity. 2021;54(7):1594-1610.e11. doi:10.1016/j.immuni.2021.06.002
17. Rogers JP, Watson CJ, Badenoch J, et al. Neurology and neuropsychiatry of COVID-19: a systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives. J Neurol Neurosurg Psychiatry. 2021;92(9):932-941. doi:10.1136/jnnp-2021-326405 18. Abbasi J. Researchers Investigate What COVID-19 Does to the Heart. JAMA. 2021;325(9):808- 811. doi:10.1001/jama.2021.0107
19. COVID-19 as a Possible Cause of Myocarditis and Pericarditis. American College of Cardiology. Accessed September 27, 2021. https://www.acc.org/latest-in- cardiology/articles/2021/02/05/19/37/http%3a%2f%2fwww.acc.org%2flatest-in- cardiology%2farticles%2f2021%2f02%2f05%2f19%2f37%2fcovid-19-as-a-possible-cause-of-myocarditis- and-pericarditis
20. Bzeizi K, Abdulla M, Mohammed N, Alqamish J, Jamshidi N, Broering D. Effect of COVID-19 on liver abnormalities: a systematic review and meta-analysis. Sci Rep. 2021;11(1):10599. doi:10.1038/s41598-021-89513-9
21. Moon AM, Barritt AS. Elevated Liver Enzymes in Patients with COVID-19: Look, but Not Too Hard. Dig Dis Sci. Published online September 2, 2020:1-3. doi:10.1007/s10620-020-06585-9
22. Iqbal Z, Ho JH, Adam S, et al. Managing hyperlipidaemia in patients with COVID-19 and during its pandemic: An expert panel position statement from HEART UK. Atherosclerosis. 2020;313:126-136. doi:10.1016/j.atherosclerosis.2020.09.008
23. Steenblock C, Richter S, Berger I, et al. Viral infiltration of pancreatic islets in patients with COVID-19. Nat Commun. 2021;12(1):3534. doi:10.1038/s41467-021-23886-3
24. Hayden MR. An Immediate and Long-Term Complication of COVID-19 May Be Type 2 Diabetes Mellitus: The Central Role of β-Cell Dysfunction, Apoptosis and Exploration of Possible Mechanisms. Cells. 2020;9(11):2475. doi:10.3390/cells9112475
25. Mukherjee S, Banerjee O, Singh S, Maji BK. COVID 19 could trigger global diabetes burden – A hypothesis. Diabetes Metab Syndr. 2020;14(5):963-964. doi:10.1016/j.dsx.2020.06.049
26. Wu C-T, Lidsky PV, Xiao Y, et al. SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment. Cell Metab. 2021;33(8):1565-1576.e5. doi:10.1016/j.cmet.2021.05.013
27. Legrand M, Bell S, Forni L, et al. Pathophysiology of COVID-19-associated acute kidney injury. Nat Rev Nephrol. Published online July 5, 2021:1-14. doi:10.1038/s41581-021-00452-0
28. Nugent J, Aklilu A, Yamamoto Y, et al. Assessment of Acute Kidney Injury and Longitudinal Kidney Function After Hospital Discharge Among Patients With and Without COVID-19. JAMA Netw Open. 2021;4(3):e211095. doi:10.1001/jamanetworkopen.2021.1095
29. Chen Z, Hu J, Liu L, et al. SARS-CoV-2 Causes Acute Kidney Injury by Directly Infecting Renal Tubules. Front Cell Dev Biol. 2021;9:1245. doi:10.3389/fcell.2021.664868
30. Gu J, Han B, Wang J. COVID-19: Gastrointestinal Manifestations and Potential Fecal–Oral Transmission. Gastroenterology. 2020;158(6):1518-1519. doi:10.1053/j.gastro.2020.02.054
31. Lehmann M, Allers K, Heldt C, et al. Human small intestinal infection by SARS-CoV-2 is characterized by a mucosal infiltration with activated CD8+ T cells. Mucosal Immunol. Published online August 21, 2021:1-12. doi:10.1038/s41385-021-00437-z
32. Zhang H, Kang Z, Gong H, et al. Digestive system is a potential route of COVID-19: an analysis of single-cell coexpression pattern of key proteins in viral entry process. Gut. 2020;69(6):1010-1018. doi:10.1136/gutjnl-2020-320953
33. Pourbagheri-Sigaroodi A, Bashash D, Fateh F, Abolghasemi H. Laboratory findings in COVID-19 diagnosis and prognosis. Clin Chim Acta Int J Clin Chem. 2020;510:475-482. doi:10.1016/j.cca.2020.08.019
34. Zhang Z-L, Hou Y-L, Li D-T, Li F-Z. Laboratory findings of COVID-19: a systematic review and meta-analysis. Scand J Clin Lab Invest. 2020;80(6):441-447. doi:10.1080/00365513.2020.1768587
35. Xie Y, Wang Z, Liao H, Marley G, Wu D, Tang W. Epidemiologic, clinical, and laboratory findings of the COVID-19 in the current pandemic: systematic review and meta-analysis. BMC Infect Dis. 2020;20(1):640. doi:10.1186/s12879-020-05371-2
36. Xiang Q, Feng Z, Diao B, et al. SARS-CoV-2 Induces Lymphocytopenia by Promoting Inflammation and Decimates Secondary Lymphoid Organs. Front Immunol. 2021;12:1292. doi:10.3389/fimmu.2021.661052
37. Rha M-S, Shin E-C. Activation or exhaustion of CD8+ T cells in patients with COVID-19. Cell Mol Immunol. Published online August 19, 2021:1-9. doi:10.1038/s41423-021-00750-4
38. Kusnadi A, Ramírez-Suástegui C, Fajardo V, et al. Severely ill patients with COVID-19 display impaired exhaustion features in SARS-CoV-2–reactive CD8+ T cells. Sci Immunol. 2021;6(55):eabe4782. doi:10.1126/sciimmunol.abe4782
39. Del Valle DM, Kim-Schulze S, Huang H-H, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636-1643. doi:10.1038/s41591-020-1051-9 40. What explains the non-respiratory symptoms seen in some COVID-19 patients? Chemical & Engineering News. Accessed September 28, 2021. https://cen.acs.org/biological-chemistry/infectious- disease/What-explains-non-respiratory-symptoms-seen-in-some-COVID-19-patients/98/web/2020/04 41. Protean manifestations of COVID-19: “Our ignorance is profound.” Accessed September 28, 2021. https://www.mdedge.com/chestphysician/article/220899/coronavirus-updates/protean- manifestations-covid-19-our-ignorance
42. Jarrahi A, Ahluwalia M, Khodadadi H, et al. Neurological consequences of COVID-19: what have we learned and where do we go from here? J Neuroinflammation. 2020;17(1):286. doi:10.1186/s12974- 020-01957-4
43. Zubair AS, McAlpine LS, Gardin T, Farhadian S, Kuruvilla DE, Spudich S. Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review. JAMA Neurol. 2020;77(8):1018-1027. doi:10.1001/jamaneurol.2020.2065
44. Qureshi AI, Baskett WI, Huang W, et al. Acute Ischemic Stroke and COVID-19. Stroke. 2021;52(3):905-912. doi:10.1161/STROKEAHA.120.031786
45. Riyahi S, Dev H, Behzadi A, et al. Pulmonary Embolism in Hospitalized Patients with COVID-19: A Multicenter Study. Radiology. Published online July 13, 2021:210777. doi:10.1148/radiol.2021210777 46. Zhong P, Xu J, Yang D, et al. COVID-19-associated gastrointestinal and liver injury: clinical features and potential mechanisms. Signal Transduct Target Ther. 2020;5(1):1-8. doi:10.1038/s41392- 020-00373-7
47. Nishiga M, Wang DW, Han Y, Lewis DB, Wu JC. COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nat Rev Cardiol. 2020;17(9):543-558. doi:10.1038/s41569-020- 0413-9
48. Al-Sabah S, Al-Haddad M, Al-Youha S, Jamal M, Almazeedi S. COVID-19: Impact of obesity and diabetes on disease severity. Clin Obes. Published online October 20, 2020:e12414. doi:10.1111/cob.12414
49. Gao M, Piernas C, Astbury NM, et al. Associations between body-mass index and COVID-19 severity in 6·9 million people in England: a prospective, community-based, cohort study. Lancet Diabetes Endocrinol. 2021;9(6):350-359. doi:10.1016/S2213-8587(21)00089-9
50. Jin Y, Ji W, Yang H, Chen S, Zhang W, Duan G. Endothelial activation and dysfunction in COVID- 19: from basic mechanisms to potential therapeutic approaches. Signal Transduct Target Ther. 2020;5(1):1-13. doi:10.1038/s41392-020-00454-7
51. Green SJ. Covid-19 accelerates endothelial dysfunction and nitric oxide deficiency. Microbes Infect. 2020;22(4):149-150. doi:10.1016/j.micinf.2020.05.006
52. Levin AT, Hanage WP, Owusu-Boaitey N, Cochran KB, Walsh SP, Meyerowitz-Katz G. Assessing the age specificity of infection fatality rates for COVID-19: systematic review, meta-analysis, and public policy implications. Eur J Epidemiol. 2020;35(12):1123-1138. doi:10.1007/s10654-020-00698-1
53. CDC. Cases, Data, and Surveillance. Centers for Disease Control and Prevention. Published February 11, 2020. Accessed September 28, 2021. https://www.cdc.gov/coronavirus/2019-ncov/covid- data/investigations-discovery/hospitalization-death-by-age.html
54. Covid IFR Analysis. Accessed September 28, 2021. http://epimonitor.net/Covid-IFR-Analysis.htm 55. Seoane B. A scaling approach to estimate the age-dependent COVID-19 infection fatality ratio from incomplete data. PLOS ONE. 2021;16(2):e0246831. doi:10.1371/journal.pone.0246831
56. Hu B, Guo H, Zhou P, Shi Z-L. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021;19(3):141-154. doi:10.1038/s41579-020-00459-7
57. Xia L, Chen J, Friedemann T, et al. The Course of Mild and Moderate COVID-19 Infections—The Unexpected Long-Lasting Challenge. Open Forum Infect Dis. 2020;7(9). doi:10.1093/ofid/ofaa286
58. Han C, Duan C, Zhang S, et al. Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes. Am J Gastroenterol. Published online April 15, 2020:10.14309/ajg.0000000000000664. doi:10.14309/ajg.0000000000000664
59. CDC. Cases, Data, and Surveillance. Centers for Disease Control and Prevention. Published February 11, 2020. Accessed September 28, 2021. https://www.cdc.gov/coronavirus/2019-ncov/cases- updates/burden.html
60. Wu SL, Mertens AN, Crider YS, et al. Substantial underestimation of SARS-CoV-2 infection in the United States. Nat Commun. 2020;11(1):4507. doi:10.1038/s41467-020-18272-4
61. Irons NJ, Raftery AE. Estimating SARS-CoV-2 infections from deaths, confirmed cases, tests, and random surveys. Proc Natl Acad Sci. 2021;118(31). doi:10.1073/pnas.2103272118
62. Achaiah NC, Subbarajasetty SB, Shetty RM. R0 and Re of COVID-19: Can We Predict When the Pandemic Outbreak will be Contained? Indian J Crit Care Med Peer-Rev Off Publ Indian Soc Crit Care Med. 2020;24(11):1125-1127. doi:10.5005/jp-journals-10071-23649
63. Ives AR, Bozzuto C. Estimating and explaining the spread of COVID-19 at the county level in the USA. Commun Biol. 2021;4(1):1-9. doi:10.1038/s42003-020-01609-6
64. Lan J, Ge J, Yu J, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020;581(7807):215-220. doi:10.1038/s41586-020-2180-5
65. Yang J, Petitjean SJL, Koehler M, et al. Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor. Nat Commun. 2020;11(1):4541. doi:10.1038/s41467-020-18319-6
66. ACE2 angiotensin converting enzyme 2 [Homo sapiens (human)] - Gene - NCBI. Accessed September 28, 2021. https://www.ncbi.nlm.nih.gov/gene/59272
67. Samavati L, Uhal BD. ACE2, Much More Than Just a Receptor for SARS-COV-2. Front Cell Infect Microbiol. 2020;10:317. doi:10.3389/fcimb.2020.00317
68. Patel S, Rauf A, Khan H, Abu-Izneid T. Renin-angiotensin-aldosterone (RAAS): The ubiquitous system for homeostasis and pathologies. Biomed Pharmacother. 2017;94:317-325. doi:10.1016/j.biopha.2017.07.091
69. Romero CA, Orias M, Weir MR. Novel RAAS agonists and antagonists: clinical applications and controversies. Nat Rev Endocrinol. 2015;11(4):242-252. doi:10.1038/nrendo.2015.6
70. The Renin-Angiotensin-Aldosterone-System. TeachMePhysiology. Accessed September 28, 2021. https://teachmephysiology.com/urinary-system/regulation/the-renin-angiotensin-aldosterone-system/
71. Fountain JH, Lappin SL. Physiology, Renin Angiotensin System. In: StatPearls. StatPearls Publishing; 2021. Accessed September 28, 2021. http://www.ncbi.nlm.nih.gov/books/NBK470410/ 72. Renin Angiotensin Aldosterone System - an overview | ScienceDirect Topics. Accessed September 28, 2021. https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular- biology/renin-angiotensin-aldosterone-system
73. Hamming I, Timens W, Bulthuis M, Lely A, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631-637. doi:10.1002/path.1570
74. Tissue expression of ACE2 - Summary - The Human Protein Atlas. Accessed September 28, 2021. https://www.proteinatlas.org/ENSG00000130234-ACE2/tissue
75. The protein expression profile of ACE2 in human tissues. Mol Syst Biol. 2020;16(7):e9610. doi:10.15252/msb.20209610
76. Huang Y, Yang C, Xu X, Xu W, Liu S. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin. 2020;41(9):1141-1149. doi:10.1038/s41401-020-0485-4
77. Shang J, Wan Y, Luo C, et al. Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci. 2020;117(21):11727-11734. doi:10.1073/pnas.2003138117
78. Xie Y, Karki CB, Du D, et al. Spike Proteins of SARS-CoV and SARS-CoV-2 Utilize Different Mechanisms to Bind With Human ACE2. Front Mol Biosci. 2020;7:392. doi:10.3389/fmolb.2020.591873 79. Syncytia formation by SARS-CoV-2-infected cells. EMBO J. 2020;39(23):e106267. doi:10.15252/embj.2020106267
80. Ma H, Zhu Z, Lin H, et al. Pyroptosis of syncytia formed by fusion of SARS-CoV-2 spike and ACE2- expressing cells. Cell Discov. 2021;7(1):1-4. doi:10.1038/s41421-021-00310-0
81. Xia B, Shen X, He Y, et al. SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target. Cell Res. 2021;31(8):847- 860. doi:10.1038/s41422-021-00519-4
82. Nieto-Torres JL, Verdiá-Báguena C, Jimenez-Guardeńo JM, et al. Severe acute respiratory syndrome coronavirus E protein transports calcium ions and activates the NLRP3 inflammasome. Virology. 2015;485:330-339. doi:10.1016/j.virol.2015.08.010
83. Minakshi R, Padhan K, Rehman S, Hassan MdI, Ahmad F. The SARS Coronavirus 3a protein binds calcium in its cytoplasmic domain. Virus Res. 2014;191:180-183. doi:10.1016/j.virusres.2014.08.001
84. Pan P, Shen M, Yu Z, et al. SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. Nat Commun. 2021;12(1):4664. doi:10.1038/s41467-021-25015-6
85. Shah A. Novel Coronavirus-Induced NLRP3 Inflammasome Activation: A Potential Drug Target in the Treatment of COVID-19. Front Immunol. 2020;11:1021. doi:10.3389/fimmu.2020.01021
86. Xu H, Chitre SA, Akinyemi IA, et al. SARS-CoV-2 Viroporin Triggers the NLRP3 Inflammatory Pathway.; 2020:2020.10.27.357731. doi:10.1101/2020.10.27.357731
87. Olagnier D, Farahani E, Thyrsted J, et al. SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate. Nat Commun. 2020;11(1):4938. doi:10.1038/s41467-020-18764-3
88. Bousquet J, Cristol J-P, Czarlewski W, et al. Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies. Clin Transl Allergy. 2020;10(1):58. doi:10.1186/s13601-020- 00362-7
89. Cuadrado A, Pajares M, Benito C, et al. Can Activation of NRF2 Be a Strategy against COVID-19? Trends Pharmacol Sci. 2020;41(9):598-610. doi:10.1016/j.tips.2020.07.003
90. Bousquet J, Czarlewski W, Zuberbier T, et al. Potential Interplay between Nrf2, TRPA1, and TRPV1 in Nutrients for the Control of COVID-19. Int Arch Allergy Immunol. 2021;182(4):324-338. doi:10.1159/000514204
91. McCarthy CG, Wilczynski S, Wenceslau CF, Webb RC. A new storm on the horizon in COVID-19: Bradykinin-induced vascular complications. Vascul Pharmacol. 2021;137:106826. doi:10.1016/j.vph.2020.106826
92. Lei Y, Zhang J, Schiavon CR, et al. SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2. Circ Res. 2021;128(9):1323-1326. doi:10.1161/CIRCRESAHA.121.318902
93. Silhol F, Sarlon G, Deharo J-C, Vaďsse B. Downregulation of ACE2 induces overstimulation of the renin–angiotensin system in COVID-19: should we block the renin–angiotensin system? Hypertens Res. 2020;43(8):854-856. doi:10.1038/s41440-020-0476-3
94. Ciulla MM. SARS-CoV-2 downregulation of ACE2 and pleiotropic effects of ACEIs/ARBs. Hypertens Res. 2020;43(9):985-986. doi:10.1038/s41440-020-0488-z
95. Lu J, Sun PD. High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity. J Biol Chem. 2020;295(52):18579-18588. doi:10.1074/jbc.RA120.015303
96. Osman W, Fahdi FA, Salmi IA, Khalili HA, Gokhale A, Khamis F. Serum Calcium and Vitamin D levels: Correlation with severity of COVID-19 in hospitalized patients in Royal Hospital, Oman. Int J Infect Dis. 2021;107:153-163. doi:10.1016/j.ijid.2021.04.050
97. Raesi A, Saedi Dezaki E, Moosapour H, et al. Hypocalcemia in Covid-19: A Prognostic Marker for Severe Disease. Iran J Pathol. 2021;16(2):144-153. doi:10.30699/IJP.2020.130491.2442
98. Bennouar S, Cherif AB, Kessira A, Bennouar D-E, Abdi S. Vitamin D Deficiency and Low Serum Calcium as Predictors of Poor Prognosis in Patients with Severe COVID-19. J Am Coll Nutr. 2021;40(2):104-110. doi:10.1080/07315724.2020.1856013
99. Blaes N, Girolami J-P. Targeting the “Janus face” of the B2-bradykinin receptor. Expert Opin Ther Targets. 2013;17. doi:10.1517/14728222.2013.827664
100. Siragy H, Jaffa A, Margolius H. Bradykinin B2 receptor modulates renal prostaglandin E2 and nitric oxide. Hypertension. Published online 1997. doi:10.1161/01.HYP.29.3.757
101. Pyne NJ, Tolan D, Pyne S. Bradykinin stimulates cAMP synthesis via mitogen-activated protein kinase-dependent regulation of cytosolic phospholipase A2 and prostaglandin E2 release in airway smooth muscle. Biochem J. 1997;328(Pt 2):689-694. Accessed September 28, 2021. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1218972/
102. Dixon BS, Breckon R, Fortune J, Sutherland E, Simon FR, Anderson RJ. Bradykinin activates protein kinase C in cultured cortical collecting tubular cells. Am J Physiol-Ren Physiol. 1989;257(5):F808- F817. doi:10.1152/ajprenal.1989.257.5.F808
103. Schini VB, Boulanger C, Regoli D, Vanhoutte PM. Bradykinin stimulates the production of cyclic GMP via activation of B2 kinin receptors in cultured porcine aortic endothelial cells. J Pharmacol Exp Ther. 1990;252(2):581-585.
104. Gholamreza-Fahimi E, Bisha M, Hahn J, et al. Cyclooxygenase activity in bradykinin-induced dermal extravasation. A study in mice and humans. Biomed Pharmacother. 2020;123:109797. doi:10.1016/j.biopha.2019.109797
105. Fong P, Stafforini DM, Brown NJ, Pretorius M. Increased blood flow induces oxidative stress through an endothelium- and nitric oxide-independent mechanism. Free Radic Biol Med. 2010;49(2):301-305. doi:10.1016/j.freeradbiomed.2010.04.023
106. Portilla D, Morrissey J, Morrison AR. Bradykinin-activated membrane-associated phospholipase C in Madin-Darby canine kidney cells. J Clin Invest. 1988;81(6):1896-1902. doi:10.1172/JCI113536
107. Cruzblanca H, Koh D-S, Hille B. Bradykinin inhibits M current via phospholipase C and Ca2+ release from IP3-sensitive Ca2+ stores in rat sympathetic neurons. Proc Natl Acad Sci. 1998;95(12):7151- 7156. doi:10.1073/pnas.95.12.7151
108. Bradykinin - an overview | ScienceDirect Topics. Accessed September 28, 2021. https://www.sciencedirect.com/topics/chemistry/bradykinin
109. Banerjee A, Czinn SJ, Reiter RJ, Blanchard TG. Crosstalk between endoplasmic reticulum stress and anti-viral activities: A novel therapeutic target for COVID-19. Life Sci. 2020;255:117842. doi:10.1016/j.lfs.2020.117842
110. Danta CC. SARS-CoV-2, Hypoxia, and Calcium Signaling: The Consequences and Therapeutic Options. ACS Pharmacol Transl Sci. 2021;4(1):400-402. doi:10.1021/acsptsci.0c00219
111. Shaban MS, Müller C, Mayr-Buro C, et al. Multi-level inhibition of coronavirus replication by chemical ER stress. Nat Commun. 2021;12(1):5536. doi:10.1038/s41467-021-25551-1
112. Sabirli R, Koseler A, Goren T, Turkcuer I, Kurt O. High GRP78 levels in Covid-19 infection: A case- control study. Life Sci. 2021;265:118781. doi:10.1016/j.lfs.2020.118781
113. Dubiella U, Seybold H, Durian G, et al. Calcium-dependent protein kinase/NADPH oxidase activation circuit is required for rapid defense signal propagation. Proc Natl Acad Sci. 2013;110(21):8744-8749. doi:10.1073/pnas.1221294110
114. Görlach A, Bertram K, Hudecova S, Krizanova O. Calcium and ROS: A mutual interplay. Redox Biol. 2015;6:260-271. doi:10.1016/j.redox.2015.08.010
115. Feno S, Butera G, Vecellio Reane D, Rizzuto R, Raffaello A. Crosstalk between Calcium and ROS in Pathophysiological Conditions. Oxid Med Cell Longev. 2019;2019:e9324018. doi:10.1155/2019/9324018 116. Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol. 1996;271(5 Pt 1):C1424-1437. doi:10.1152/ajpcell.1996.271.5.C1424
117. PACHER P, BECKMAN JS, LIAUDET L. Nitric Oxide and Peroxynitrite in Health and Disease. Physiol Rev. 2007;87(1):315-424. doi:10.1152/physrev.00029.2006
118. Radi R. Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine. Proc Natl Acad Sci. 2018;115(23):5839-5848. doi:10.1073/pnas.1804932115
119. Guzik TJ, West NEJ, Pillai R, Taggart DP, Channon KM. Nitric Oxide Modulates Superoxide Release and Peroxynitrite Formation in Human Blood Vessels. Hypertension. 2002;39(6):1088-1094. doi:10.1161/01.HYP.0000018041.48432.B5
120. Roe ND, Ren J. Nitric oxide synthase uncoupling: A therapeutic target in cardiovascular diseases. Vascul Pharmacol. 2012;57(5):168-172. doi:10.1016/j.vph.2012.02.004
121. Luo S, Lei H, Qin H, Xia Y. Molecular mechanisms of endothelial NO synthase uncoupling. Curr Pharm Des. 2014;20(22):3548-3553. doi:10.2174/13816128113196660746
122. Chen W, Druhan LJ, Chen C-A, et al. Peroxynitrite induces destruction of the tetrahydrobiopterin and heme in endothelial nitric oxide synthase: transition from reversible to irreversible enzyme inhibition. Biochemistry. 2010;49(14):3129-3137. doi:10.1021/bi9016632
123. Ozdemir B, Yazici A. Could the decrease in the endothelial nitric oxide (NO) production and NO bioavailability be the crucial cause of COVID-19 related deaths? Med Hypotheses. 2020;144:109970. doi:10.1016/j.mehy.2020.109970
124. Guan SP, Seet RCS, Kennedy BK. Does eNOS derived nitric oxide protect the young from severe COVID-19 complications? Ageing Res Rev. 2020;64:101201. doi:10.1016/j.arr.2020.101201
125. Nitric Oxide - an overview | ScienceDirect Topics. Accessed September 28, 2021. https://www.sciencedirect.com/topics/medicine-and-dentistry/nitric-oxide
126. Levine AB, Punihaole D, Levine TB. Characterization of the Role of Nitric Oxide and Its Clinical Applications. Cardiology. 2012;122(1):55-68. doi:10.1159/000338150
127. Rosselli M, Keller PJ, Dubey RK. Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. Hum Reprod Update. 1998;4(1):3-24. doi:10.1093/humupd/4.1.3 128. Mel A de. Potential roles of nitric oxide in COVID-19: A perspective. Integr Mol Med. 2020;7(3). doi:10.15761/IMM.1000403
129. Ricciardolo FLM, Bertolini F, Carriero V, Högman M. Nitric oxide’s physiologic effects and potential as a therapeutic agent against COVID-19. J Breath Res. 2020;15(1):014001. doi:10.1088/1752- 7163/abc302
130. Ĺkerström S, Gunalan V, Keng CT, Tan Y-J, Mirazimi A. Dual effect of nitric oxide on SARS-CoV replication: Viral RNA production and palmitoylation of the S protein are affected. Virology. 2009;395(1):1-9. doi:10.1016/j.virol.2009.09.007
131. Hadi HA, Carr CS, Al Suwaidi J. Endothelial Dysfunction: Cardiovascular Risk Factors, Therapy, and Outcome. Vasc Health Risk Manag. 2005;1(3):183-198. Accessed September 28, 2021. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1993955/
132. Bonetti PO, Lerman LO, Lerman A. Endothelial Dysfunction. Arterioscler Thromb Vasc Biol. 2003;23(2):168-175. doi:10.1161/01.ATV.0000051384.43104.FC
133. Endothelial Dysfunction in Diabetes | Diabetes Care. Accessed September 28, 2021. https://care.diabetesjournals.org/content/34/Supplement_2/S285
134. Patel PD, Velazquez JL, Arora RR. Endothelial dysfunction in African-Americans. Int J Cardiol. 2009;132(2):157-172. doi:10.1016/j.ijcard.2008.10.007
135. Kalinowski L, Dobrucki IT, Malinski T. Race-specific differences in endothelial function: predisposition of African Americans to vascular diseases. Circulation. 2004;109(21):2511-2517. doi:10.1161/01.CIR.0000129087.81352.7A
136. Ungvari Z, Tarantini S, Kiss T, et al. Endothelial dysfunction and angiogenesis impairment in the ageing vasculature. Nat Rev Cardiol. 2018;15(9):555-565. doi:10.1038/s41569-018-0030-z
137. Reusch N, De Domenico E, Bonaguro L, et al. Neutrophils in COVID-19. Front Immunol. 2021;12:952. doi:10.3389/fimmu.2021.652470
138. Cavalcante-Silva LHA, Carvalho DCM, Lima É de A, et al. Neutrophils and COVID-19: The road so far. Int Immunopharmacol. 2021;90:107233. doi:10.1016/j.intimp.2020.107233
139. Knoll R, Schultze JL, Schulte-Schrepping J. Monocytes and Macrophages in COVID-19. Front Immunol. 2021;12:2952. doi:10.3389/fimmu.2021.720109
140. Meidaninikjeh S, Sabouni N, Marzouni HZ, Bengar S, Khalili A, Jafari R. Monocytes and macrophages in COVID-19: Friends and foes. Life Sci. 2021;269:119010. doi:10.1016/j.lfs.2020.119010 141. Phagocytes - an overview | ScienceDirect Topics. Accessed September 28, 2021. https://www.sciencedirect.com/topics/immunology-and-microbiology/phagocytes
142. Respiratory Burst - an overview | ScienceDirect Topics. Accessed September 28, 2021. https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/respiratory-burst
143. Superoxide Dismutase - an overview | ScienceDirect Topics. Accessed September 28, 2021. https://www.sciencedirect.com/topics/neuroscience/superoxide-dismutase
144. Myeloperoxidase - an overview | ScienceDirect Topics. Accessed September 28, 2021. https://www.sciencedirect.com/topics/medicine-and-dentistry/myeloperoxidase
145. Spickett CM, Jerlich A, Panasenko OM, et al. The reactions of hypochlorous acid, the reactive oxygen species produced by myeloperoxidase, with lipids. Acta Biochim Pol. 2000;47(4):889-899.
146. Hypochlorous_acid. Accessed September 28, 2021. https://www.bionity.com/en/encyclopedia/Hypochlorous_acid.html
147. Neutrophil extracellular traps in immunity and disease | Nature Reviews Immunology. Accessed September 28, 2021. https://www.nature.com/articles/nri.2017.105
148. Kaplan MJ, Radic M. Neutrophil extracellular traps (NETs): Double-edged swords of innate immunity. J Immunol Baltim Md 1950. 2012;189(6):2689-2695. doi:10.4049/jimmunol.1201719
149. Gillot C, Favresse J, Mullier F, Lecompte T, Dogné J-M, Douxfils J. NETosis and the Immune System in COVID-19: Mechanisms and Potential Treatments. Front Pharmacol. 2021;12:1999. doi:10.3389/fphar.2021.708302
150. Arcanjo A, Logullo J, Menezes CCB, et al. The emerging role of neutrophil extracellular traps in severe acute respiratory syndrome coronavirus 2 (COVID-19). Sci Rep. 2020;10(1):19630. doi:10.1038/s41598-020-76781-0
151. Middleton EA, He X-Y, Denorme F, et al. Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood. 2020;136(10):1169-1179. doi:10.1182/blood.2020007008
152. Schönrich G, Raftery MJ, Samstag Y. Devilishly radical NETwork in COVID-19: Oxidative stress, neutrophil extracellular traps (NETs), and T cell suppression. Adv Biol Regul. 2020;77:100741. doi:10.1016/j.jbior.2020.100741
153. Goud PT, Bai D, Abu-Soud HM. A Multiple-Hit Hypothesis Involving Reactive Oxygen Species and Myeloperoxidase Explains Clinical Deterioration and Fatality in COVID-19. Int J Biol Sci. 2021;17(1):62-72. doi:10.7150/ijbs.51811
154. Edeas M, Saleh J, Peyssonnaux C. Iron: Innocent bystander or vicious culprit in COVID-19 pathogenesis? Int J Infect Dis. 2020;97:303-305. doi:10.1016/j.ijid.2020.05.110
155. Habib HM, Ibrahim S, Zaim A, Ibrahim WH. The role of iron in the pathogenesis of COVID-19 and possible treatment with lactoferrin and other iron chelators. Biomed Pharmacother. 2021;136:111228. doi:10.1016/j.biopha.2021.111228
156. Rahman A, Tabassum T, Araf Y, Al Nahid A, Ullah MdA, Hosen MJ. Silent hypoxia in COVID-19: pathomechanism and possible management strategy. Mol Biol Rep. Published online April 23, 2021:1-7. doi:10.1007/s11033-021-06358-1
157. Tobin MJ, Laghi F, Jubran A. Why COVID-19 Silent Hypoxemia Is Baffling to Physicians. Am J Respir Crit Care Med. 2020;202(3):356-360. doi:10.1164/rccm.202006-2157CP
158. Kehrer JP. The Haber-Weiss reaction and mechanisms of toxicity. Toxicology. 2000;149(1):43-50. doi:10.1016/s0300-483x(00)00231-6
159. Wardman P, Candeias LP. Fenton Chemistry: An Introduction. Radiat Res. 1996;145(5):523-531. doi:10.2307/3579270
160. Sharpe MA, Robb SJ, Clark JB. Nitric oxide and Fenton/Haber–Weiss chemistry: nitric oxide is a potent antioxidant at physiological concentrations. J Neurochem. 2003;87(2):386-394. doi:10.1046/j.1471-4159.2003.02001.x
161. Kanti Das T, Wati MR, Fatima-Shad K. Oxidative Stress Gated by Fenton and Haber Weiss Reactions and Its Association With Alzheimer’s Disease. Arch Neurosci. 2015;2(2). doi:10.5812/archneurosci.20078
162. Barciszewska A-M. Elucidating of oxidative distress in COVID-19 and methods of its prevention. Chem Biol Interact. 2021;344:109501. doi:10.1016/j.cbi.2021.109501
163. Ntyonga-Pono M-P. COVID-19 infection and oxidative stress: an under-explored approach for prevention and treatment? Pan Afr Med J. 2020;35(Suppl 2):12. doi:10.11604/pamj.2020.35.2.22877 164. Forcados GE, Muhammad A, Oladipo OO, Makama S, Meseko CA. Metabolic Implications of Oxidative Stress and Inflammatory Process in SARS-CoV-2 Pathogenesis: Therapeutic Potential of Natural Antioxidants. Front Cell Infect Microbiol. 2021;11:457. doi:10.3389/fcimb.2021.654813
165. Cumpstey AF, Clark AD, Santolini J, Jackson AA, Feelisch M. COVID-19: A Redox Disease—What a Stress Pandemic Can Teach Us About Resilience and What We May Learn from the Reactive Species Interactome About Its Treatment. Antioxid Redox Signal. Published online June 29, 2021. doi:10.1089/ars.2021.0017
166. Hydroxyl Radical - an overview | ScienceDirect Topics. Accessed September 28, 2021. https://www.sciencedirect.com/topics/earth-and-planetary-sciences/hydroxyl-radical
167. Gligorovski S, Strekowski R, Barbati S, Vione D. Environmental Implications of Hydroxyl Radicals (•OH). Chem Rev. 2015;115(24):13051-13092. doi:10.1021/cr500310b
168. Lyngsie G, Krumina L, Tunlid A, Persson P. Generation of hydroxyl radicals from reactions between a dimethoxyhydroquinone and iron oxide nanoparticles. Sci Rep. 2018;8(1):10834. doi:10.1038/s41598-018-29075-5
169. Takeda K, Fujisawa K, Nojima H, Kato R, Ueki R, Sakugawa H. Hydroxyl radical generation with a high power ultraviolet light emitting diode (UV-LED) and application for determination of hydroxyl radical reaction rate constants. J Photochem Photobiol Chem. 2017;340:8-14. doi:10.1016/j.jphotochem.2017.02.020
170. Kord Forooshani P, Pinnaratip R, Polega E, et al. Hydroxyl Radical Generation through the Fenton-like Reaction of Hematin- and Catechol-Functionalized Microgels. Chem Mater. 2020;32(19):8182-8194. doi:10.1021/acs.chemmater.0c01551
171. Deng Y, Zhao R. Advanced Oxidation Processes (AOPs) in Wastewater Treatment. Curr Pollut Rep. 2015;1(3):167-176. doi:10.1007/s40726-015-0015-z
172. Hypoxanthine - an overview | ScienceDirect Topics. Accessed September 28, 2021. https://www.sciencedirect.com/topics/chemistry/hypoxanthine
173. Dowell FJ, Hamilton CA, McMurray J, Reid JL. Effects of a xanthine oxidase/hypoxanthine free radical and reactive oxygen species generating system on endothelial function in New Zealand white rabbit aortic rings. J Cardiovasc Pharmacol. 1993;22(6):792-797. doi:10.1097/00005344-199312000- 00003
174. Fig. 1. Generation of superoxide by xanthine-hypoxanthine oxidase and... ResearchGate. Accessed September 28, 2021. https://www.researchgate.net/figure/Generation-of-superoxide-by- xanthine-hypoxanthine-oxidase-and-NADH-SMP-systems-a-The_fig1_7927959
175. Granger DN. Role of xanthine oxidase and granulocytes in ischemia-reperfusion injury. Am J Physiol. 1988;255(6 Pt 2):H1269-1275. doi:10.1152/ajpheart.1988.255.6.H1269
176. Mao H, Yang A, Zhao Y, Lei L, Li H. Succinate Supplement Elicited “Pseudohypoxia” Condition to Promote Proliferation, Migration, and Osteogenesis of Periodontal Ligament Cells. Stem Cells Int. 2020;2020:e2016809. doi:10.1155/2020/2016809
177. Lukyanova LD, Kirova YI. Mitochondria-controlled signaling mechanisms of brain protection in hypoxia. Front Neurosci. 2015;9:320. doi:10.3389/fnins.2015.00320
178. Messner KR, Imlay JA. Mechanism of superoxide and hydrogen peroxide formation by fumarate reductase, succinate dehydrogenase, and aspartate oxidase. J Biol Chem. 2002;277(45):42563-42571. doi:10.1074/jbc.M204958200
179. Quinlan CL, Orr AL, Perevoshchikova IV, Treberg JR, Ackrell BA, Brand MD. Mitochondrial Complex II Can Generate Reactive Oxygen Species at High Rates in Both the Forward and Reverse Reactions. J Biol Chem. 2012;287(32):27255-27264. doi:10.1074/jbc.M112.374629
180. Cowled P, Fitridge R. Pathophysiology of Reperfusion Injury. In: Fitridge R, Thompson M, eds. Mechanisms of Vascular Disease: A Reference Book for Vascular Specialists. University of Adelaide Press; 2011. Accessed September 28, 2021. http://www.ncbi.nlm.nih.gov/books/NBK534267/
181. Sun Z-Y, Xia H-G, Zhu D-Q, Deng L-M, Zhu P-Z, Wang D-B. Clinical significance of mechanical ventilation on ischemic-reperfusion injury caused by lung chest trauma and VEGF expression levels in peripheral blood. Exp Ther Med. 2017;14(3):2531-2535. doi:10.3892/etm.2017.4825
182. Gielis JF, Beckers PAJ, Briedé JJ, Cos P, Schil PEV. Oxidative and nitrosative stress during pulmonary ischemia-reperfusion injury: from the lab to the OR. Ann Transl Med. 2017;5(6):4-4. doi:10.21037/atm.2017.03.32
183. Wu N-C, Liao F-T, Cheng H, Sung S-H, Yang Y-C, Wang J-J. Intravenous superoxide dismutase as a protective agent to prevent impairment of lung function induced by high tidal volume ventilation. BMC Pulm Med. 2017;17:105. doi:10.1186/s12890-017-0448-9
184. Lipid Peroxidation - an overview | ScienceDirect Topics. Accessed September 28, 2021. https://www.sciencedirect.com/topics/neuroscience/lipid-peroxidation
185. Ayala A, Muńoz MF, Argüelles S. Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal. Oxid Med Cell Longev. 2014;2014:360438. doi:10.1155/2014/360438
186. Binder CJ, Papac-Milicevic N, Witztum JL. Innate sensing of oxidation-specific epitopes in health and disease. Nat Rev Immunol. 2016;16(8):485-497. doi:10.1038/nri.2016.63
187. Leibundgut G, Witztum JL, Tsimikas S. Oxidation-specific epitopes and immunological responses: Translational biotheranostic implications for atherosclerosis. Curr Opin Pharmacol. 2013;13(2):10.1016/j.coph.2013.02.005. doi:10.1016/j.coph.2013.02.005
188. Miller YI, Choi S-H, Wiesner P, et al. Oxidation-Specific Epitopes Are Danger-Associated Molecular Patterns Recognized by Pattern Recognition Receptors of Innate Immunity. Circ Res. 2011;108(2):235-248. doi:10.1161/CIRCRESAHA.110.223875
189. Zhivaki D, Kagan JC. Innate immune detection of lipid oxidation as a threat assessment strategy. Nat Rev Immunol. Published online September 21, 2021:1-9. doi:10.1038/s41577-021-00618-8
190. Macdonald J, Galley HF, Webster NR. Oxidative stress and gene expression in sepsis. Br J Anaesth. 2003;90(2):221-232. doi:10.1093/bja/aeg034
191. Mantzarlis K, Tsolaki V, Zakynthinos E. Role of Oxidative Stress and Mitochondrial Dysfunction in Sepsis and Potential Therapies. Oxid Med Cell Longev. 2017;2017:e5985209. doi:10.1155/2017/5985209 192. Toufekoula C, Papadakis V, Tsaganos T, et al. Compartmentalization of lipid peroxidation in sepsis by multidrug-resistant gram-negative bacteria: experimental and clinical evidence. Crit Care. 2013;17(1):R6. doi:10.1186/cc11930
193. Dominic P, Ahmad J, Bhandari R, et al. Decreased availability of nitric oxide and hydrogen sulfide is a hallmark of COVID-19. Redox Biol. 2021;43:101982. doi:10.1016/j.redox.2021.101982
194. Yang M, Lai CL. SARS-CoV-2 infection: can ferroptosis be a potential treatment target for multiple organ involvement? Cell Death Discov. 2020;6(1):1-6. doi:10.1038/s41420-020-00369-w
195. Jacobs W, Lammens M, Kerckhofs A, et al. Fatal lymphocytic cardiac damage in coronavirus disease 2019 (COVID-19): autopsy reveals a ferroptosis signature. ESC Heart Fail. 2020;7(6):3772-3781. doi:10.1002/ehf2.12958
196. Tavakol S, Seifalian AM. Vitamin E at a high dose as an anti-ferroptosis drug and not just a supplement for COVID-19 treatment. Biotechnol Appl Biochem. n/a(n/a). doi:10.1002/bab.2176
197. Sonnweber T, Boehm A, Sahanic S, et al. Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients’ performance: a prospective observational cohort study. Respir Res. 2020;21(1):276. doi:10.1186/s12931-020-01546-2
198. Žarković N, Orehovec B, Milković L, et al. Preliminary Findings on the Association of the Lipid Peroxidation Product 4-Hydroxynonenal with the Lethal Outcome of Aggressive COVID-19. Antioxidants. 2021;10(9):1341. doi:10.3390/antiox10091341
199. Mehri F, Rahbar AH, Ghane ET, Souri B, Esfahani M. The comparison of oxidative markers between Covid-19 patients and healthy subjects. Arch Med Res. Published online June 7, 2021. doi:10.1016/j.arcmed.2021.06.004
200. Cao Z, Xia H, Rajsbaum R, Xia X, Wang H, Shi P-Y. Ubiquitination of SARS-CoV-2 ORF7a promotes antagonism of interferon response. Cell Mol Immunol. 2021;18(3):746-748. doi:10.1038/s41423-020- 00603-6
201. Zhang H, Zheng H, Zhu J, et al. Ubiquitin-Modified Proteome of SARS-CoV-2-Infected Host Cells Reveals Insights into Virus–Host Interaction and Pathogenesis. J Proteome Res. Published online March 5, 2021:acs.jproteome.0c00758. doi:10.1021/acs.jproteome.0c00758
202. Shi H, Zuo Y, Navaz S, et al. Endothelial cell-activating antibodies in COVID-19. MedRxiv Prepr Serv Health Sci. Published online July 9, 2021:2021.01.18.21250041. doi:10.1101/2021.01.18.21250041 203. Chang R, Mamun A, Dominic A, Le N-T. SARS-CoV-2 Mediated Endothelial Dysfunction: The Potential Role of Chronic Oxidative Stress. Front Physiol. 2021;11:1752. doi:10.3389/fphys.2020.605908 204. Mei ZW, van Wijk XMR, Pham HP, Marin MJ. Role of von Willebrand Factor in COVID-19 Associated Coagulopathy. J Appl Lab Med. 2021;6(5):1305-1315. doi:10.1093/jalm/jfab042
205. Mancini I, Baronciani L, Artoni A, et al. The ADAMTS13-von Willebrand factor axis in COVID-19 patients. J Thromb Haemost JTH. 2021;19(2):513-521. doi:10.1111/jth.15191
206. Ladikou EE, Sivaloganathan H, Milne KM, et al. Von Willebrand factor (vWF): marker of endothelial damage and thrombotic risk in COVID-19? Clin Med. 2020;20(5):e178-e182. doi:10.7861/clinmed.2020-0346
207. Afrin LB, Weinstock LB, Molderings GJ. Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome. Int J Infect Dis IJID Off Publ Int Soc Infect Dis. 2020;100:327-332. doi:10.1016/j.ijid.2020.09.016
208. Gebremeskel S, Schanin J, Coyle KM, et al. Mast Cell and Eosinophil Activation Are Associated With COVID-19 and TLR-Mediated Viral Inflammation: Implications for an Anti-Siglec-8 Antibody. Front Immunol. 2021;12:641. doi:10.3389/fimmu.2021.650331
209. Java A, Apicelli AJ, Liszewski MK, et al. The complement system in COVID-19: friend and foe? JCI Insight. 5(15):e140711. doi:10.1172/jci.insight.140711
210. Noris M, Benigni A, Remuzzi G. The case of complement activation in COVID-19 multiorgan impact. Kidney Int. 2020;98(2):314-322. doi:10.1016/j.kint.2020.05.013
211. Holter JC, Pischke SE, Boer E de, et al. Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients. Proc Natl Acad Sci. 2020;117(40):25018-25025. doi:10.1073/pnas.2010540117
212. Chouaki Benmansour N, Carvelli J, Vivier E. Complement cascade in severe forms of COVID-19: Recent advances in therapy. Eur J Immunol. 2021;51(7):1652-1659. doi:10.1002/eji.202048959
213. López-Pedrera C, Barbarroja N, Jimenez-Gomez Y, Collantes-Estevez E, Aguirre MA, Cuadrado MJ. Oxidative stress in the pathogenesis of atherothrombosis associated with anti-phospholipid syndrome and systemic lupus erythematosus: new therapeutic approaches. Rheumatol Oxf Engl. 2016;55(12):2096-2108. doi:10.1093/rheumatology/kew054
214. Farris AD, Guthridge JM. Overlapping B cell pathways in severe COVID-19 and lupus. Nat Immunol. 2020;21(12):1478-1480. doi:10.1038/s41590-020-00822-z
215. MacDonald L, Alivernini S, Tolusso B, et al. COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes. JCI Insight. 2021;6(13). doi:10.1172/jci.insight.147413
216. Schett G, Manger B, Simon D, Caporali R. COVID-19 revisiting inflammatory pathways of arthritis. Nat Rev Rheumatol. 2020;16(8):465-470. doi:10.1038/s41584-020-0451-z
217. Luo M, Cao S, Wei L, et al. Intubation, mortality, and risk factors in critically ill Covid-19 patients: A pilot study. J Clin Anesth. 2020;67:110039. doi:10.1016/j.jclinane.2020.110039
218. Tandon A, Pandey L. COVID-19, steroids, and mucormycosis: What an ophthalmologist should know. Indian J Ophthalmol. 2021;69(7):1970. doi:10.4103/ijo.IJO_1143_21
219. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19. N Engl J Med. 2021;385(9):777-789. doi:10.1056/NEJMoa2103417
220. Free radicals: What are they and why should nurses care about them? American Nurse. Published April 11, 2011. Accessed September 28, 2021. https://www.myamericannurse.com/free- radicals-what-are-they-and-why-should-nurses-care-about-them/
221. Ahsan H, Ali A, Ali R. Oxygen free radicals and systemic autoimmunity. Clin Exp Immunol. 2003;131(3):398-404. doi:10.1046/j.1365-2249.2003.02104.x
222. 8.2: Generation of Free Radicals in the Body. Medicine LibreTexts. Published July 29, 2016. Accessed September 28, 2021. https://med.libretexts.org/Bookshelves/Nutrition/Book%3A_An_Introduction_to_Nutrition_(Zimmerma n)/08%3A_Nutrients_Important_as_Antioxidants/8.02%3A_Generation_of_Free_Radicals_in_the_Body
223. Daiber A, Oelze M, Daub S, et al. Vascular Redox Signaling, Redox Switches in Endothelial Nitric Oxide Synthase (eNOS Uncoupling), and Endothelial Dysfunction. In: Laher I, ed. Systems Biology of Free Radicals and Antioxidants. Springer; 2014:1177-1211. doi:10.1007/978-3-642-30018-9_48
224. Gladyshev VN. The Free Radical Theory of Aging Is Dead. Long Live the Damage Theory! Antioxid Redox Signal. 2014;20(4):727-731. doi:10.1089/ars.2013.5228
225. Junghanns FB. MATH+ Protocol. FLCCC | Front Line COVID-19 Critical Care Alliance. Accessed September 28, 2021. https://covid19criticalcare.com/covid-19-protocols/math-plus-protocol/
226. Lammi C, Arnoldi A. Food-derived antioxidants and COVID-19. J Food Biochem. 2021;45(1):e13557. doi:10.1111/jfbc.13557
227. Żukowski P, Maciejczyk M, Matczuk J, et al. Effect of N-Acetylcysteine on Antioxidant Defense, Oxidative Modification, and Salivary Gland Function in a Rat Model of Insulin Resistance. Oxid Med Cell Longev. 2018;2018:e6581970. doi:10.1155/2018/6581970
228. Aldini G, Altomare A, Baron G, et al. N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why. Free Radic Res. 2018;52(7):751-762. doi:10.1080/10715762.2018.1468564 229. Zhitkovich A. N-Acetylcysteine: Antioxidant, Aldehyde Scavenger, and More. Chem Res Toxicol. 2019;32(7):1318-1319. doi:10.1021/acs.chemrestox.9b00152
230. Gilad E, Cuzzocrea S, Zingarelli B, Salzman AL, Szabó C. Melatonin is a scavenger of peroxynitrite. Life Sci. 1997;60(10):PL169-174. doi:10.1016/s0024-3205(97)00008-8
231. Shaeib F, Khan SN, Ali I, et al. Melatonin Prevents Myeloperoxidase Heme Destruction and the Generation of Free Iron Mediated by Self-Generated Hypochlorous Acid. PLOS ONE. 2015;10(4):e0120737. doi:10.1371/journal.pone.0120737
232. Elsaed WM, Alahmadi AM, Al-Ahmadi BT, Taha JA, Tarabishi RM. Gastroprotective and antioxidant effects of fluvoxamine on stress-induced peptic ulcer in rats. J Taibah Univ Med Sci. 2018;13(5):422-431. doi:10.1016/j.jtumed.2018.04.010
233. Dallé E, Daniels WMU, Mabandla MV. Long-Term Treatment with Fluvoxamine Decreases Nonmotor Symptoms and Dopamine Depletion in a Postnatal Stress Rat Model of Parkinson’s Disease. Oxid Med Cell Longev. 2020;2020:e1941480. doi:10.1155/2020/1941480
234. Braga PC, Dal Sasso M, Culici M, Bianchi T, Guffanti EE. Budesonide reduces superoxide and peroxynitrite anion chemiluminescence during human neutrophil bursts. Pharmacology. 2005;75(4):179- 186. doi:10.1159/000088623
235. Mikolka P, Kopincova J, Tomcikova Mikusiakova L, et al. Effects of surfactant/budesonide therapy on oxidative modifications in the lung in experimental meconium-induced lung injury. J Physiol Pharmacol Off J Pol Physiol Soc. 2016;67(1):57-65.
236. Lamothe PH, Rao E, Serra AJ, et al. Comparative efficacy of cimetidine, famotidine, ranitidine, and mylanta in postoperative stress ulcers. Gastric pH control and ulcer prevention in patients undergoing coronary artery bypass graft surgery. Gastroenterology. 1991;100(6):1515-1520. doi:10.1016/0016-5085(91)90647-4
237. van Zyl JM, Kriegler A, van der Walt BJ. Anti-oxidant properties of H2-receptor antagonists. Effects on myeloperoxidase-catalysed reactions and hydroxyl radical generation in a ferrous-hydrogen peroxide system. Biochem Pharmacol. 1993;45(12):2389-2397. doi:10.1016/0006-2952(93)90218-l
238. Ching T-L, Haenen GRMM, Bast A. Cimetidine and other H2 receptor antagonists as powerful hydroxyl radical scavengers. Chem Biol Interact. 1993;86(2):119-127. doi:10.1016/0009-2797(93)90116- G
239. Peterson DA, Gerrard JM, Rao GHR, White JG. Inhibition of ferrous iron induced oxidation of arachidonic acid by indomethacin. Prostaglandins Med. 1979;2(2):97-108. doi:10.1016/0161- 4630(79)90044-2
240. Cross AL, Hawkes J, Wright HL, Moots RJ, Edwards SW. APPA (apocynin and paeonol) modulates pathological aspects of human neutrophil function, without supressing antimicrobial ability, and inhibits
TNFα expression and signalling. Inflammopharmacology. 2020;28(5):1223-1235. doi:10.1007/s10787- 020-00715-5
241. Heumüller S, Wind S, Barbosa-Sicard E, et al. Apocynin Is Not an Inhibitor of Vascular NADPH Oxidases but an Antioxidant. Hypertension. 2008;51(2):211-217. doi:10.1161/HYPERTENSIONAHA.107.100214
242. de Almeida AC, dos Santos Vilela MM, Condino-Neto A, Ximenes VF. The Importance of Myeloperoxidase in Apocynin-Mediated NADPH Oxidase Inhibition. ISRN Inflamm. 2012;2012:260453. doi:10.5402/2012/260453
243. NADPH oxidase Covid-19 Oxygen treatment? ResearchGate. Accessed September 28, 2021. https://www.researchgate.net/post/NADPH_oxidase_Covid-19_Oxygen_treatment
244. Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. The Lancet. 2020;395(10234):1417-1418. doi:10.1016/S0140-6736(20)30937-5
245. COVID19. Global Sepsis Alliance. Accessed September 28, 2021. https://www.global-sepsis- alliance.org/covid19
246. HealthLeaders. Expert: Severe COVID-19 Illness Is Viral Sepsis. Accessed September 28, 2021. https://www.healthleadersmedia.com/clinical-care/expert-severe-covid-19-illness-viral-sepsis
247. Aisa-Alvarez A, Soto ME, Guarner-Lans V, et al. Usefulness of Antioxidants as Adjuvant Therapy for Septic Shock: A Randomized Clinical Trial. Med Kaunas Lith. 2020;56(11):E619. doi:10.3390/medicina56110619
248. Aisa-Alvarez A, Perez-Torres I, Camarena-Alejo G, et al. A Randomized clinical trial of antioxidant therapy in patients with septic shock. Reference study to propose adjuvant therapy in patients with critical organic damage by COVID-19. Published online September 28, 2021. doi:10.21203/rs.3.rs- 52169/v1
249. Kashiouris MG, L’Heureux M, Cable CA, Fisher BJ, Leichtle SW, Fowler AA. The Emerging Role of Vitamin C as a Treatment for Sepsis. Nutrients. 2020;12(2):E292. doi:10.3390/nu12020292
250. That “damn machine”: mechanical ventilators in the ICU. STAT. Published August 20, 2021. Accessed September 28, 2021. https://www.statnews.com/2021/08/20/that-damn-machine-the-dark- side-of-mechanical-ventilators-in-the-icu/
251. Ferreira JC, Ho Y-L, Besen BAMP, et al. Protective ventilation and outcomes of critically ill patients with COVID-19: a cohort study. Ann Intensive Care. 2021;11(1):92. doi:10.1186/s13613-021- 00882-w
252. Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med. 2020;383(21):2030-2040. doi:10.1056/NEJMoa2022926
253. Popp M, Stegemann M, Metzendorf M-I, et al. Ivermectin for preventing and treating COVID-19. Cochrane Database Syst Rev. 2021;7:CD015017. doi:10.1002/14651858.CD015017.pub2
254. Acosta MAT, Singer BD. Pathogenesis of COVID-19-induced ARDS: implications for an aging population. Eur Respir J. Published online January 1, 2020. doi:10.1183/13993003.02049-2020
255. dos Santos WG. Natural history of COVID-19 and current knowledge on treatment therapeutic options. Biomed Pharmacother. 2020;129:110493. doi:10.1016/j.biopha.2020.110493
256. Dölken L, Stich A, Spinner CD. Remdesivir for Early COVID-19 Treatment of High-Risk Individuals Prior to or at Early Disease Onset—Lessons Learned. Viruses. 2021;13(6):963. doi:10.3390/v13060963 257. Hydroxychloroquine does not benefit adults hospitalized with COVID-19. National Institutes of Health (NIH). Published November 9, 2020. Accessed September 28, 2021. https://www.nih.gov/news- events/news-releases/hydroxychloroquine-does-not-benefit-adults-hospitalized-covid-19
258. Ivermectin Won’t Treat Covid-19 but Demand for Drug Surges - The New York Times. Accessed September 28, 2021. https://www.nytimes.com/2021/08/30/health/covid-ivermectin- prescriptions.html
259. What the FDA wants doctors to tell patients asking for ivermectin. American Medical Association. Accessed September 28, 2021. https://www.ama-assn.org/delivering-care/public- health/what-fda-wants-doctors-tell-patients-asking-ivermectin
260. AbbVie’s Kaletra doesn’t work in COVID-19, say Chinese scientists -. Accessed September 28, 2021. https://pharmaphorum.com/news/abbvies-kaletra-doesnt-work-in-covid-19-say-chinese- scientists/
261. Chamary JV. The Strange Story Of Remdesivir, A Covid Drug That Doesn’t Work. Forbes. Accessed September 28, 2021. https://www.forbes.com/sites/jvchamary/2021/01/31/remdesivir-covid- coronavirus/
262. Uttar Pradesh government says early use of Ivermectin helped to keep positivity, deaths low. The Indian Express. Published May 12, 2021. Accessed September 28, 2021. https://indianexpress.com/article/cities/lucknow/uttar-pradesh-government-says-ivermectin-helped-to- keep-deaths-low-7311786/
263. India Claims Ivermectin is Effective Against COVID – Orion’s Cold Fire. Accessed September 28, 2021. https://orionscoldfire.com/index.php/2021/09/16/india-claims-ivermectin-is-effective-against- covid/
264. Dr. Soumya Swaminathan deletes her controversial tweet - Indian Bar Association. Accessed September 28, 2021. https://indianbarassociation.in/indian-bar-associationiba-vs-dr- soumyaswaminathan/
265. Indian Bar Association Charges WHO Chief Scientist for Mass Murder - PaulCraigRoberts.org. Accessed September 28, 2021. https://www.paulcraigroberts.org/2021/08/23/indian-bar-association- charges-who-chief-scientist-for-mass-murder/
266. Ivomec® (ivermectin) – Effective dewormer, trusted for more than 35 years. Boehringer Ingelheim Vetmedica. Published April 10, 2019. Accessed September 28, 2021. https://www.bi- vetmedica.com/species/cattle/products/ivomec.html
267. CRUMP A, ŌMURA S. Ivermectin, ‘Wonder drug’ from Japan: the human use perspective. Proc Jpn Acad Ser B Phys Biol Sci. 2011;87(2):13-28. doi:10.2183/pjab.87.13
268. Camero K. Some people are taking an anti-parasitic to treat COVID. Here’s why that’s a bad idea. Miami Herald. Accessed September 28, 2021. https://www.miamiherald.com/news/coronavirus/article253290108.html
269. Editor AD News. University experts weigh in on using ivermectin ‘horse dewormer’ as COVID-19 treatment. Technician. Accessed September 28, 2021. https://www.technicianonline.com/news/university-experts-weigh-in-on-using-ivermectin-horse- dewormer-as-covid-19-treatment/article_319584f2-15dc-11ec-a985-5b35a9dc71ff.html
270. Yang SNY, Atkinson SC, Wang C, et al. The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer. Antiviral Res. 2020;177:104760. doi:10.1016/j.antiviral.2020.104760
271. Kosyna FK, Nagel M, Kluxen L, Kraushaar K, Depping R. The importin α/β-specific inhibitor Ivermectin affects HIF-dependent hypoxia response pathways. Biol Chem. 2015;396(12):1357-1367. doi:10.1515/hsz-2015-0171
272. Shahbaznejad L, Davoudi A, Eslami G, et al. Effects of Ivermectin in Patients With COVID-19: A Multicenter, Double-blind, Randomized, Controlled Clinical Trial. Clin Ther. 2021;43(6):1007-1019. doi:10.1016/j.clinthera.2021.04.007
273. Zaidi AK, Dehgani-Mobaraki P. The mechanisms of action of Ivermectin against SARS-CoV-2: An evidence-based clinical review article. J Antibiot (Tokyo). Published online June 15, 2021:1-13. doi:10.1038/s41429-021-00430-5
274. Ivermectin for COVID-19: real-time meta analysis of 65 studies. Accessed September 28, 2021. https://ivmmeta.com/
275. Israeli scientist says COVID-19 could be treated for under $1/day. The Jerusalem Post | JPost.com. Accessed September 28, 2021. https://www.jpost.com/health-science/israeli-scientist-says- covid-19-could-be-treated-for-under-1day-675612
276. Feuer W. Gilead’s coronavirus treatment remdesivir to cost $3,120 per U.S. patient with private insurance. CNBC. Published June 29, 2020. Accessed September 28, 2021. https://www.cnbc.com/2020/06/29/gileads-coronavirus-treatment-remdesivir-to-cost-3120-for-us- insured-patients.html
277. Pharmaceutical companies pay low taxes and reap enormous profit from COVID vaccines. American Friends Service Committee. Published September 15, 2021. Accessed September 28, 2021. https://www.afsc.org/newsroom/pharmaceutical-companies-pay-low-taxes-and-reap-enormous-profit- covid-vaccines
278. Obscene global vaccine profiteering by pharmaceutical companies. World Socialist Web Site. Accessed September 28, 2021. https://www.wsws.org/en/articles/2021/04/01/vacc-a01.html
279. Pharmaceutical Companies Reaping Immoral Profits From COVID Vaccines Yet Paying Low Tax Rates. Common Dreams. Accessed September 28, 2021. https://www.commondreams.org/newswire/2021/09/15/pharmaceutical-companies-reaping-immoral- profits-covid-vaccines-yet-paying-low
280. Ennis M, Tiligada K. Histamine receptors and COVID-19. Inflamm Res. Published online November 18, 2020:1-9. doi:10.1007/s00011-020-01422-1
281. Hogan II RB, Hogan III RB, Cannon T, et al. Dual-histamine receptor blockade with cetirizine - famotidine reduces pulmonary symptoms in COVID-19 patients. Pulm Pharmacol Ther. 2020;63:101942. doi:10.1016/j.pupt.2020.101942
282. Mura C, Preissner S, Nahles S, Heiland M, Bourne PE, Preissner R. Real-world evidence for improved outcomes with histamine antagonists and aspirin in 22,560 COVID-19 patients. Signal Transduct Target Ther. 2021;6(1):1-3. doi:10.1038/s41392-021-00689-y
283. Ishola AA, Joshi T, Abdulai SI, Tijjani H, Pundir H, Chandra S. Molecular basis for the repurposing of histamine H2-receptor antagonist to treat COVID-19. J Biomol Struct Dyn. 2021;0(0):1-18. doi:10.1080/07391102.2021.1873191
284. Cross KM, Landis DM, Sehgal L, Payne JD. Melatonin for the Early Treatment of COVID-19: A Narrative Review of Current Evidence and Possible Efficacy. Endocr Pract. 2021;27(8):850-855. doi:10.1016/j.eprac.2021.06.001
285. Camp OG, Bai D, Gonullu DC, Nayak N, Abu-Soud HM. Melatonin interferes with COVID-19 at several distinct ROS-related steps. J Inorg Biochem. 2021;223:111546. doi:10.1016/j.jinorgbio.2021.111546
286. Marinella MA. Indomethacin and resveratrol as potential treatment adjuncts for SARS-CoV- 2/COVID-19. Int J Clin Pract. 2020;74(9):e13535. doi:10.1111/ijcp.13535
287. Yu L-M, Bafadhel M, Dorward J, et al. Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. The Lancet. 2021;398(10303):843-855. doi:10.1016/S0140-6736(21)01744-X
288. Ebell MH. Inhaled Budesonide Reduces the Risk of Emergency Department Evaluation or Hospitalization in Early COVID-19. Am Fam Physician. 2021;104(2):207-208. Accessed September 28, 2021. https://www.aafp.org/afp/2021/0800/p207.html
289. Amici C, Di Caro A, Ciucci A, et al. Indomethacin has a potent antiviral activity against SARS coronavirus. Antivir Ther. 2006;11(8):1021-1030.
290. Droplets vs Aerosols: What’s More Important in COVID-19 Spread? Published May 13, 2021. Accessed September 28, 2021. https://www.medpagetoday.com/special-reports/exclusives/92564
291. COVID-19: Droplet or Airborne Transmission? Penn Medicine Epidemiologists Issue Statement - Penn Medicine. Accessed September 28, 2021. https://www.pennmedicine.org/updates/blogs/penn- physician-blog/2020/august/airborne-droplet-debate-article
292. 239 Experts With One Big Claim: The Coronavirus Is Airborne - The New York Times. Accessed September 28, 2021. https://www.nytimes.com/2020/07/04/health/239-experts-with-one-big-claim- the-coronavirus-is-airborne.html
293. Goldman E. Exaggerated risk of transmission of COVID-19 by fomites. Lancet Infect Dis. 2020;20(8):892-893. doi:10.1016/S1473-3099(20)30561-2
294. Lewis D. COVID-19 rarely spreads through surfaces. So why are we still deep cleaning? Nature. 2021;590(7844):26-28. doi:10.1038/d41586-021-00251-4
295. Viable SARS-CoV-2 in the air of a hospital room with COVID-19 patients | medRxiv. Accessed September 28, 2021. https://www.medrxiv.org/content/10.1101/2020.08.03.20167395v1
296. PolitiFact JG. What We Know About the Airborne Spread of the Coronavirus. Kaiser Health News. Published September 30, 2020. Accessed September 28, 2021. https://khn.org/news/fact-check- airborne-transmission-coronavirus-science-behind-aerosol-spread/
297. A guideline to limit indoor airborne transmission of COVID-19 | PNAS. Accessed September 28, 2021. https://www.pnas.org/content/118/17/e2018995118
298. Chen CC, Willeke K. Aerosol penetration through surgical masks. Am J Infect Control. 1992;20(4):177-184. doi:10.1016/s0196-6553(05)80143-9
299. Konda A, Prakash A, Moss GA, Schmoldt M, Grant GD, Guha S. Aerosol Filtration Efficiency of Common Fabrics Used in Respiratory Cloth Masks. ACS Nano. 2020;14(5):6339-6347. doi:10.1021/acsnano.0c03252
300. Guide for the Selection of Personal Protective Equipment for Emergency First Responders (Percutaneous Protection--Apparel), NIJ Guide 102-00, Volume IIc. National Institute of Justice. Accessed September 28, 2021. https://nij.ojp.gov/library/publications/guide-selection-personal-protective- equipment-emergency-first-responders-1
301. US EPA O. EPA Researchers Test Effectiveness of Face Masks, Disinfection Methods Against COVID-19. Published April 5, 2021. Accessed September 28, 2021. https://www.epa.gov/sciencematters/epa-researchers-test-effectiveness-face-masks-disinfection- methods-against-covid-19
302. Caruhel J-B, Sigaux N, Crambert A, et al. Military gas mask to protect surgeons when performing tracheotomies on patients with COVID-19. BMJ Mil Health. Published online August 2020:bmjmilitary- 2020-001547. doi:10.1136/bmjmilitary-2020-001547
303. Coronavirus Protection Made Easy with the MaxAir CAPR®. Mopec. Published March 2, 2020. Accessed September 28, 2021. https://www.mopec.com/coronavirus-protection-made-easy-with-the- maxair-capr/
304. Kitajima M, Ahmed W, Bibby K, et al. SARS-CoV-2 in wastewater: State of the knowledge and research needs. Sci Total Environ. 2020;739:139076. doi:10.1016/j.scitotenv.2020.139076
305. Sharif S, Ikram A, Khurshid A, et al. Detection of SARs-CoV-2 in wastewater using the existing environmental surveillance network: A potential supplementary system for monitoring COVID-19 transmission. PLOS ONE. 2021;16(6):e0249568. doi:10.1371/journal.pone.0249568
306. Peccia J, Zulli A, Brackney DE, et al. Measurement of SARS-CoV-2 RNA in wastewater tracks community infection dynamics. Nat Biotechnol. 2020;38(10):1164-1167. doi:10.1038/s41587-020-0684-z 307. McKinney KR, Gong YY, Lewis TG. Environmental transmission of SARS at Amoy Gardens. J Environ Health. 2006;68(9):26-30; quiz 51-52.
308. Hung LS. The SARS epidemic in Hong Kong: what lessons have we learned? J R Soc Med. 2003;96(8):374-378. Accessed September 28, 2021. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC539564/
309. COVID-19 Could Spread Through Dry Floor Drains. CleanLink. Accessed September 28, 2021. https://www.cleanlink.com/news/article/COVID-19-Could-Spread-Through-Dry-Floor-Drains--25600 310. ‘Leaky’ Vaccines Can Produce Stronger Versions of Viruses. Healthline. Published July 27, 2015. Accessed September 28, 2021. https://www.healthline.com/health-news/leaky-vaccines-can-produce- stronger-versions-of-viruses-072715
311. MD BH. Let’s Stop Pretending About the Covid-19 Vaccines | RealClearScience. Published August 23, 2021. Accessed September 28, 2021. https://www.realclearscience.com/articles/2021/08/23/lets_stop_pretending_about_the_covid- 19_vaccines_791050.html
312. CDC Newsroom. CDC. Published January 1, 2016. Accessed September 28, 2021. https://www.cdc.gov/media/releases/2021/s0730-mmwr-covid-19.html
313. Brueck H. CDC: Everyone should mask up indoors — whether they’re fully vaccinated or not — as the Delta variant sweeps the US. Business Insider. Accessed September 28, 2021. https://www.businessinsider.com/cdc-fully-vaccinated-new-guidelines-wear-masks-indoors-delta-2021- 7
314. Lasting immunity found after recovery from COVID-19. National Institutes of Health (NIH). Published January 25, 2021. Accessed September 28, 2021. https://www.nih.gov/news-events/nih- research-matters/lasting-immunity-found-after-recovery-covid-19
315. Gazit S, Shlezinger R, Perez G, et al. Comparing SARS-CoV-2 Natural Immunity to Vaccine- Induced Immunity: Reinfections versus Breakthrough Infections.; 2021:2021.08.24.21262415. doi:10.1101/2021.08.24.21262415
316. Accelerated Covid-19 Vaccine Clinical Trials. JD Supra. Accessed September 28, 2021. https://www.jdsupra.com/legalnews/accelerated-covid-19-vaccine-clinical-95853/
317. Were the COVID-19 vaccines rushed? Here’s how the vaccines were developed so fast. Accessed September 28, 2021. https://www.nebraskamed.com/COVID/were-the-covid-19-vaccines-rushed
318. Reichmuth AM, Oberli MA, Jaklenec A, Langer R, Blankschtein D. mRNA vaccine delivery using lipid nanoparticles. Ther Deliv. 2016;7(5):319-334. doi:10.4155/tde-2016-0006
319. Without these lipid shells, there would be no mRNA vaccines for COVID-19. Chemical & Engineering News. Accessed September 28, 2021. https://cen.acs.org/pharmaceuticals/drug- delivery/Without-lipid-shells-mRNA-vaccines/99/i8
320. CDC. Understanding mRNA COVID-19 Vaccines. Centers for Disease Control and Prevention. Published March 4, 2021. Accessed September 28, 2021. https://www.cdc.gov/coronavirus/2019- ncov/vaccines/different-vaccines/mrna.html
321. What are mRNA vaccines and how do they work?: MedlinePlus Genetics. Accessed September 28, 2021. https://medlineplus.gov/genetics/understanding/therapy/mrnavaccines/
322. Corbett KS, Edwards DK, Leist SR, et al. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature. 2020;586(7830):567-571. doi:10.1038/s41586-020-2622-0
323. PhD SM. How mRNA vaccines from Pfizer and Moderna work, why they’re a breakthrough and why they need to be kept so cold. The Conversation. Accessed September 28, 2021. http://theconversation.com/how-mrna-vaccines-from-pfizer-and-moderna-work-why-theyre-a- breakthrough-and-why-they-need-to-be-kept-so-cold-150238
324. Martínez-Flores D, Zepeda-Cervantes J, Cruz-Reséndiz A, Aguirre-Sampieri S, Sampieri A, Vaca L. SARS-CoV-2 Vaccines Based on the Spike Glycoprotein and Implications of New Viral Variants. Front Immunol. 2021;12:2774. doi:10.3389/fimmu.2021.701501
325. Prompetchara E, Ketloy C, Tharakhet K, et al. DNA vaccine candidate encoding SARS-CoV-2 spike proteins elicited potent humoral and Th1 cell-mediated immune responses in mice. PLOS ONE. 2021;16(3):e0248007. doi:10.1371/journal.pone.0248007
326. COVID-19 Viral Vector Vaccines. Accessed September 28, 2021. https://www.idsociety.org/covid-19-real-time-learning-network/vaccines/covid-19-viral-vector- vaccines/
327. Zimmerman RK. Helping patients with ethical concerns about COVID-19 vaccines in light of fetal cell lines used in some COVID-19 vaccines. Vaccine. 2021;39(31):4242-4244. doi:10.1016/j.vaccine.2021.06.027
328. The Ethics of the SARS-CoV-2 Vaccines Revisited. Christian Medical & Dental Associations® (CMDA). Published September 15, 2021. Accessed September 28, 2021. https://cmda.org/the-ethics-of- the-sars-cov-2-vaccines-revisited/
329. Canadian Covid Care Alliance. Accessed September 28, 2021. https://mailchi.mp/5666d252288c/canadian-covid-care-alliance
330. Juraszek J, Rutten L, Blokland S, et al. Stabilizing the closed SARS-CoV-2 spike trimer. Nat Commun. 2021;12(1):244. doi:10.1038/s41467-020-20321-x
331. The tiny tweak behind COVID-19 vaccines. Chemical & Engineering News. Accessed September 28, 2021. https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behind-COVID-19/98/i38
332. SARS-COV-2 mRNA Vaccine (BNT162, PF-07302048) 2.6.4 Overview of Pharmacokinetic Test | BibSonomy. Accessed September 28, 2021. https://www.bibsonomy.org/bibtex/29920ce3643fa2f4fdbecccfa57790d2d/fordham1
333. Krantz MS, Liu Y, Phillips EJ, Stone CA. COVID-19 vaccine anaphylaxis: PEG or not? Allergy. 2021;76(6):1934-1937. doi:10.1111/all.14722
334. Moghimi SM. Allergic Reactions and Anaphylaxis to LNP-Based COVID-19 Vaccines. Mol Ther. 2021;29(3):898-900. doi:10.1016/j.ymthe.2021.01.030
335. Overview of translation (article). Khan Academy. Accessed September 28, 2021. https://www.khanacademy.org/science/ap-biology/gene-expression-and- regulation/translation/a/translation-overview
336. Thomas EN, Kim KQ, McHugh EP, Marcinkiewicz T, Zaher HS. Alkylative damage of mRNA leads to ribosome stalling and rescue by trans translation in bacteria. Dever TE, Storz G, eds. eLife. 2020;9:e61984. doi:10.7554/eLife.61984
337. Karamyshev AL, Karamysheva ZN. Lost in Translation: Ribosome-Associated mRNA and Protein Quality Controls. Front Genet. 2018;9:431. doi:10.3389/fgene.2018.00431
338. Mendonsa S, von Kuegelgen N, Bujanic L, Chekulaeva M. Charcot–Marie–Tooth mutation in glycyl-tRNA synthetase stalls ribosomes in a pre-accommodation state and activates integrated stress response. Nucleic Acids Res. 2021;49(17):10007-10017. doi:10.1093/nar/gkab730
339. Zuko A, Mallik M, Thompson R, et al. tRNA overexpression rescues peripheral neuropathy caused by mutations in tRNA synthetase. Science. 2021;373(6559):1161-1166. doi:10.1126/science.abb3356
340. Zhang S, Chen Y, Wang Y, Zhang P, Chen G, Zhou Y. Insights Into Translatomics in the Nervous System. Front Genet. 2020;11:1682. doi:10.3389/fgene.2020.599548
341. Klein T, Eckhard U, Dufour A, Solis N, Overall CM. Proteolytic Cleavage—Mechanisms, Function, and “Omic” Approaches for a Near-Ubiquitous Posttranslational Modification. Chem Rev. 2018;118(3):1137-1168. doi:10.1021/acs.chemrev.7b00120
342. Örd M, Faustova I, Loog M. The sequence at Spike S1/S2 site enables cleavage by furin and phospho-regulation in SARS-CoV2 but not in SARS-CoV1 or MERS-CoV. Sci Rep. 2020;10(1):16944. doi:10.1038/s41598-020-74101-0
343. Lemmin T, Kalbermatter D, Harder D, Plattet P, Fotiadis D. Structures and dynamics of the novel S1/S2 protease cleavage site loop of the SARS-CoV-2 spike glycoprotein. J Struct Biol X. 2020;4:100038. doi:10.1016/j.yjsbx.2020.100038
344. Belouzard S, Chu VC, Whittaker GR. Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proc Natl Acad Sci. 2009;106(14):5871-5876. doi:10.1073/pnas.0809524106
345. Ogata AF, Cheng C-A, Desjardins M, et al. Circulating Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine Antigen Detected in the Plasma of mRNA-1273 Vaccine Recipients. Clin Infect Dis. 2021;(ciab465). doi:10.1093/cid/ciab465
346. Peacock TP, Goldhill DH, Zhou J, et al. The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. Nat Microbiol. 2021;6(7):899-909. doi:10.1038/s41564-021-00908- w
347. Bestle D, Heindl MR, Limburg H, et al. TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells. Life Sci Alliance. 2020;3(9). doi:10.26508/lsa.202000786 348. Cheng MH, Zhang S, Porritt RA, et al. Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation. Proc Natl Acad Sci. 2020;117(41):25254-25262. doi:10.1073/pnas.2010722117
349. Brown M, Bhardwaj N. Super(antigen) target for SARS-CoV-2. Nat Rev Immunol. 2021;21(2):72- 72. doi:10.1038/s41577-021-00502-5
350. Föhse K, Geckin B, Overheul G, et al. The BNT162b2 mRNA vaccine against SARS-CoV-2 reprograms both adaptive and innate immune response. Published online 2021. doi:10.1101/2021.05.03.21256520
351. Wang H, Chen Q, Hu Y, et al. Pathogenic antibodies induced by spike proteins of COVID-19 and SARS-CoV viruses. Published online September 28, 2021. doi:10.21203/rs.3.rs-612103/v2
352. says R to the document-WB. Summary: Covid-19 Vaccine Concerns. Dr. Rich Swier. Published September 18, 2021. Accessed September 28, 2021. https://drrichswier.com/2021/09/18/summary- covid-19-vaccine-concerns/
353. Commissioner O of the. Coronavirus (COVID-19) Update: July 13, 2021. FDA. Published July 13, 2021. Accessed September 28, 2021. https://www.fda.gov/news-events/press- announcements/coronavirus-covid-19-update-july-13-2021
354. Bell’s Palsy After COVID Vaccines Still Very Rare. Published August 16, 2021. Accessed September 28, 2021. https://www.medpagetoday.com/infectiousdisease/covid19vaccine/94061
355. Havla J, Schultz Y, Zimmermann H, Hohlfeld R, Danek A, Kümpfel T. First manifestation of multiple sclerosis after immunization with the Pfizer-BioNTech COVID-19 vaccine. J Neurol. Published online June 11, 2021. doi:10.1007/s00415-021-10648-w
356. Baggen J, Vanstreels E, Jansen S, Daelemans D. Cellular host factors for SARS-CoV-2 infection. Nat Microbiol. 2021;6(10):1219-1232. doi:10.1038/s41564-021-00958-0
357. Perez-Miller S, Patek M, Moutal A, et al. Novel Compounds Targeting Neuropilin Receptor 1 with Potential To Interfere with SARS-CoV-2 Virus Entry. ACS Chem Neurosci. 2021;12(8):1299-1312. doi:10.1021/acschemneuro.0c00619
358. Daly JL, Simonetti B, Klein K, et al. Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science. 2020;370(6518):861-865. doi:10.1126/science.abd3072
359. Nader D, Fletcher N, Curley GF, Kerrigan SW. SARS-CoV-2 uses major endothelial integrin αvβ3 to cause vascular dysregulation in-vitro during COVID-19. PLOS ONE. 2021;16(6):e0253347. doi:10.1371/journal.pone.0253347
360. Petruk G, Puthia M, Petrlova J, et al. SARS-CoV-2 spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity. J Mol Cell Biol. 2020;12(12):916-932. doi:10.1093/jmcb/mjaa067
361. Suzuki YJ, Gychka SG. SARS-CoV-2 Spike Protein Elicits Cell Signaling in Human Host Cells: Implications for Possible Consequences of COVID-19 Vaccines. Vaccines. 2021;9(1):36. doi:10.3390/vaccines9010036
362. Liu S, Selvaraj P, Lien CZ, et al. The PRRA Insert at the S1/S2 Site Modulates Cellular Tropism of SARS-CoV-2 and ACE2 Usage by the Closely Related Bat RaTG13. J Virol. 95(11):e01751-20. doi:10.1128/JVI.01751-20
363. Johnson BA, Xie X, Kalveram B, et al. Furin Cleavage Site Is Key to SARS-CoV-2 Pathogenesis. bioRxiv. Published online August 26, 2020:2020.08.26.268854. doi:10.1101/2020.08.26.268854
364. Deigin Y. Lab-made? CoV2 genealogy through the lens of gain-of-function research. Medium. Published May 3, 2020. Accessed September 28, 2021. https://yurideigin.medium.com/lab-made-cov2- genealogy-through-the-lens-of-gain-of-function-research-f96dd7413748
365. Tetz G, Tetz V. SARS-CoV-2 Prion-Like Domains in Spike Proteins Enable Higher Affinity to ACE2. Published online March 29, 2020. doi:10.20944/preprints202003.0422.v1
366. Fryer HR, McLean AR. There Is No Safe Dose of Prions. PLOS ONE. 2011;6(8):e23664. doi:10.1371/journal.pone.0023664
367. Seneff S, Nigh G. Worse Than the Disease? Reviewing Some Possible Unintended Consequences of the mRNA Vaccines Against COVID-19. Int J Vaccine Theory Pract Res. 2021;2(1):38-79. Accessed September 28, 2021. https://ijvtpr.com/index.php/IJVTPR/article/view/23
368. Idrees D, Kumar V. SARS-CoV-2 spike protein interactions with amyloidogenic proteins: Potential clues to neurodegeneration. Biochem Biophys Res Commun. 2021;554:94-98. doi:10.1016/j.bbrc.2021.03.100
369. Rhea EM, Logsdon AF, Hansen KM, et al. The S1 protein of SARS-CoV-2 crosses the blood–brain barrier in mice. Nat Neurosci. 2021;24(3):368-378. doi:10.1038/s41593-020-00771-8
370. Zhang L, Zhou L, Bao L, et al. SARS-CoV-2 crosses the blood–brain barrier accompanied with basement membrane disruption without tight junctions alteration. Signal Transduct Target Ther. 2021;6(1):1-12. doi:10.1038/s41392-021-00719-9
371. Buzhdygan TP, DeOre BJ, Baldwin-Leclair A, et al. The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood-brain barrier. Neurobiol Dis. 2020;146:105131. doi:10.1016/j.nbd.2020.105131
372. Ricke DO. Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies. Front Immunol. 2021;12:640093. doi:10.3389/fimmu.2021.640093
373. Halstead SB, Katzelnick L. COVID 19 Vaccines: Should we fear ADE? J Infect Dis. Published online August 12, 2020:jiaa518. doi:10.1093/infdis/jiaa518
374. Yahi N, Chahinian H, Fantini J. Infection-enhancing anti-SARS-CoV-2 antibodies recognize both the original Wuhan/D614G strain and Delta variants. A potential risk for mass vaccination? J Infect. 2021;0(0). doi:10.1016/j.jinf.2021.08.010
375. (STUDY) Why so many vaccinated people are getting sick: Antibody Dependent Enhancement (ADE) | Sharyl Attkisson. Accessed September 28, 2021. https://sharylattkisson.com/2021/08/study- why-so-many-vaccinated-people-are-getting-sick/
376. Lee WS, Wheatley AK, Kent SJ, DeKosky BJ. Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies. Nat Microbiol. 2020;5(10):1185-1191. doi:10.1038/s41564-020-00789-5
377. Wen J, Cheng Y, Ling R, et al. Antibody-dependent enhancement of coronavirus. Int J Infect Dis. 2020;100:483-489. doi:10.1016/j.ijid.2020.09.015
378. Wan Y, Shang J, Sun S, et al. Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry. J Virol. 2020;94(5):e02015-19. doi:10.1128/JVI.02015-19
379. Liu Y, Arase N, Kishikawa J, et al. The SARS-CoV-2 Delta Variant Is Poised to Acquire Complete Resistance to Wild-Type Spike Vaccines.; 2021:2021.08.22.457114. doi:10.1101/2021.08.22.457114
380. Zhang A, Stacey HD, Mullarkey CE, Miller MS. Original Antigenic Sin: How First Exposure Shapes Lifelong Anti–Influenza Virus Immune Responses. J Immunol. 2019;202(2):335-340. doi:10.4049/jimmunol.1801149
381. Brown EL, Essigmann HT. Original Antigenic Sin: the Downside of Immunological Memory and Implications for COVID-19. mSphere. 6(2):e00056-21. doi:10.1128/mSphere.00056-21
382. Antibody Dependent Enhancement - an overview | ScienceDirect Topics. Accessed September 28, 2021. https://www.sciencedirect.com/topics/medicine-and-dentistry/antibody-dependent- enhancement
383. ADE. Accessed September 28, 2021. https://www.cdc.gov/dengue/training/cme/ccm/page57857.html
384. Shukla R, Ramasamy V, Shanmugam RK, Ahuja R, Khanna N. Antibody-Dependent Enhancement: A Challenge for Developing a Safe Dengue Vaccine. Front Cell Infect Microbiol. 2020;10:597. doi:10.3389/fcimb.2020.572681
385. Scientists Discover How Dengue Vaccine Fails to Protect Against Disease. Newsroom. Published June 23, 2021. Accessed September 28, 2021. https://news.unchealthcare.org/2021/06/scientists- discover-how-dengue-vaccine-fails-to-protect-against-disease/
386. Mahalingam S, Herring BL, Halstead SB. Call to Action for Dengue Vaccine Failure. Emerg Infect Dis. 2013;19(8):1335-1337. doi:10.3201/eid1908.121864
387. How the World’s First Dengue Vaccination Drive Ended in Disaster. Scientific American. doi:10.1038/scientificamerican0419-38
388. Tseng C-T, Sbrana E, Iwata-Yoshikawa N, et al. Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus. PLOS ONE. 2012;7(4):e35421. doi:10.1371/journal.pone.0035421
389. Zhang L, Richards A, Khalil A, et al. SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome. BioRxiv Prepr Serv Biol. Published online December 13, 2020:2020.12.12.422516. doi:10.1101/2020.12.12.422516
390. MIT & Harvard Study Suggests mRNA Vaccine Might Permanently Alter DNA After All. Rights and Freedoms. Published August 13, 2021. Accessed September 28, 2021. https://rightsfreedoms.wordpress.com/2021/08/13/mit-harvard-study-suggests-mrna-vaccine-might- permanently-alter-dna-after-all/
391. The Injection Fraud – It’s Not a Vaccine – Solari Report. Accessed September 28, 2021. https://home.solari.com/deep-state-tactics-101-the-covid-injection-fraud-its-not-a-vaccine/
392. Dec 19 LS| NE| CN|, 2017. Feds lift gain-of-function research pause, offer guidance. CIDRAP. Accessed September 28, 2021. https://www.cidrap.umn.edu/news-perspective/2017/12/feds-lift-gain- function-research-pause-offer-guidance
393. Begley,STAT S. U.S. Lifts Moratorium on Funding Controversial, High-Risk Virus Research. Scientific American. Accessed September 28, 2021. https://www.scientificamerican.com/article/u-s-lifts- moratorium-on-funding-controversial-high-risk-virus-research/
394. NIH Lifts Funding Pause on Gain-of-Function Research. National Institutes of Health (NIH). Published December 18, 2017. Accessed September 28, 2021. https://www.nih.gov/about-nih/who-we- are/nih-director/statements/nih-lifts-funding-pause-gain-function-research
395. Ralph S. Baric, PhD. UNC Gillings School of Global Public Health. Accessed September 28, 2021. https://sph.unc.edu/adv_profile/ralph-s-baric-phd/
396. Ralph Baric: On the Front Lines of Coronavirus for Three Decades - UNC General Alumni Association. Accessed September 28, 2021. https://alumni.unc.edu/news/ralph-baric-on-the-front-lines- of-coronavirus-for-three-decades/
397. Menachery VD, Yount BL, Debbink K, et al. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nat Med. 2015;21(12):1508-1513. doi:10.1038/nm.3985
398. Inside the risky bat-virus engineering that links America to Wuhan. MIT Technology Review. Accessed September 28, 2021. https://www.technologyreview.com/2021/06/29/1027290/gain-of- function-risky-bat-virus-engineering-links-america-to-wuhan/
399. Suryanarayanan S. Items from coronavirus expert Ralph Baric‘s emails. U.S. Right to Know. Published December 14, 2020. Accessed September 28, 2021. https://usrtk.org/biohazards-blog/ralph- baric-emails/
400. Newsweek Op-Ed: “Congress Must Pursue Answers About the Origin of COVID-19” | Senator Rand Paul. Accessed September 28, 2021. https://www.paul.senate.gov/newsweek-op-ed-congress- must-pursue-answers-about-origin-covid-19
401. Baker N. The Lab-Leak Hypothesis. Intelligencer. Published January 4, 2021. Accessed September 28, 2021. https://nymag.com/intelligencer/article/coronavirus-lab-escape-theory.html
402. Lerner S, Hvistendahl M, Hibbett M. NIH Documents Provide New Evidence U.S. Funded Gain-of- Function Research in Wuhan. The Intercept. Published September 10, 2021. Accessed September 28, 2021. https://theintercept.com/2021/09/09/covid-origins-gain-of-function-research/
403. BOMBSHELL: Fauci Kept Funding Peter Daszak’s Wuhan “Gain of Function” Experiments with $7.5 Million after Trump Canceled Grant. National File. Published June 3, 2021. Accessed September 28, 2021. https://nationalfile.com/bombshell-fauci-kept-funding-peter-daszaks-wuhan-gain-of-function- experiments-with-7-5-million-after-trump-canceled-grant/
404. miningawareness. USAID (PREDICT) & NIH Gave $ 1.9 Million to the Wuhan (WIV) Lab Through Daszak-EcoHealth Alliance; Daszak Talks China Partners’ Work on “Killer” Viruses; Biden Budget Requests More USAID Money for Similar Projects. Mining Awareness +. Published June 11, 2021. Accessed September 28, 2021. https://miningawareness.wordpress.com/2021/06/11/usaid-predict-nih- gave-1-9-million-to-the-wuhan-wiv-lab-through-daszak-ecohealth-alliance-daszak-talks-china-partners- work-on-killer-viruses-biden-admin-plans/
405. Gallagher: This is Bigger than Dr. Fauci. Congressman Mike Gallagher. Published May 20, 2021. Accessed September 28, 2021. https://gallagher.house.gov/media/press-releases/gallagher-bigger-dr- fauci
406. Blog A. EcoHealth Alliance, DARPA Toyed With Infecting Wild Chinese Bats With Covid, Leaked Docs Allege. Algora Blog. Published September 22, 2021. Accessed September 28, 2021. https://www.algora.com/Algora_blog/2021/09/22/ecohealth-alliance-darpa-toyed-with-infecting-wild- chinese-bats-with-covid-leaked-docs-allege
407. Archive VA, feed G author R. Pentagon gave millions to EcoHealth Alliance for weapons research program. New York Post. Published July 2, 2021. Accessed September 28, 2021. https://nypost.com/2021/07/01/pentagon-gave-millions-to-ecohealth-alliance-for-wuhan-lab/
408. Judicial Watch: New Documents Show Wuhan Lab Asked NIH Official for Information on Disinfectants; Nine Fauci Agency Grants for EcoHealth Bat Coronavirus Research. Judicial Watch. Published July 8, 2021. Accessed September 28, 2021. https://www.judicialwatch.org/press- releases/wuhan-lab-fauci-grants/
409. JW v NIH Wuhan June 2021 00696. Judicial Watch. Accessed September 28, 2021. https://www.judicialwatch.org/documents/jw-v-nih-wuhan-june-2021-00696/
410. Opinion | State Department cables warned of safety issues at Wuhan lab studying bat coronaviruses. Washington Post. https://www.washingtonpost.com/opinions/2020/04/14/state- department-cables-warned-safety-issues-wuhan-lab-studying-bat-coronaviruses/. Accessed September 28, 2021.
411. Panetta G. US officials were reportedly concerned that safety breaches at a Wuhan lab studying coronaviruses in bats could cause a pandemic. Business Insider. Accessed September 28, 2021. https://www.businessinsider.com/us-officials-raised-alarms-about-safety-issues-in-wuhan-lab-report- 2020-4
412. (PDF) The possible origins of 2019-nCoV coronavirus. Accessed September 28, 2021. https://web.archive.org/web/20200214144447/https:/www.researchgate.net/publication/339070128_ The_possible_origins_of_2019-nCoV_coronavirus
413. Crist C. 3 Wuhan Lab Workers’ 2019 Illness Raises Concerns. WebMD. Accessed September 28, 2021. https://www.webmd.com/lung/news/20210524/wuhan-lab-researchers-illness
414. Williams J. Fauci calls on China to release medical records of Wuhan researchers. TheHill. Published June 4, 2021. Accessed September 28, 2021. https://thehill.com/policy/healthcare/556815- fauci-calls-on-china-to-release-medical-records-of-wuhan-researchers
415. Confidential Documents reveal Moderna sent mRNA Coronavirus Vaccine Candidate to University Researchers weeks before emergence of Covid-19. Rights and Freedoms. Published June 26, 2021. Accessed September 28, 2021. https://rightsfreedoms.wordpress.com/2021/06/26/confidential- documents-reveal-moderna-sent-mrna-coronavirus-vaccine-candidate-to-university-researchers-weeks- before-emergence-of-covid-19/
416. Confidential Documents reveal Moderna sent mRNA Coronavirus Vaccine Candidate to University Researchers weeks before emergence of Covid-19 – The Expose. Accessed September 28, 2021. https://theexpose.uk/2021/06/18/confidential-documents-reveal-moderna-sent-mrna- coronavirus-vaccine-candidate-to-university-researchers-weeks-before-emergence-of-covid-19/
417. Jan 11 LS| NE| CN|, 2020. China releases genetic data on new coronavirus, now deadly. CIDRAP. Accessed September 28, 2021. https://www.cidrap.umn.edu/news-perspective/2020/01/china-releases- genetic-data-new-coronavirus-now-deadly
418. Whole genome of novel coronavirus, 2019-nCoV, sequenced. ScienceDaily. Accessed September 28, 2021. https://www.sciencedaily.com/releases/2020/01/200131114748.htm
419. Bendix SN Andrew Dunn, Aria. Moderna’s groundbreaking coronavirus vaccine was designed in just 2 days. Business Insider. Accessed September 28, 2021. https://www.businessinsider.com/moderna-designed-coronavirus-vaccine-in-2-days-2020-11
420. Moderna designed its coronavirus vaccine in 2 days — here’s how - National | Globalnews.ca. Global News. Accessed September 28, 2021. https://globalnews.ca/news/7492076/moderna- coronavirus-vaccine-technology-how-it-works/
421. Wallace-Wells D. We Had the Vaccine the Whole Time. Intelligencer. Published December 7, 2020. Accessed September 28, 2021. https://nymag.com/intelligencer/2020/12/moderna-covid-19- vaccine-design.html
422. The Board of Directors of bioMerieux, chaired by Alain Merieux, has appointed Stephane Bancel Directeur General delegue (Chief Executive Officer) of bioMerieux starting January 1, 2007. bioMérieux Corporate Website. Accessed September 28, 2021. https://www.biomerieux.com/en/board-directors- biomerieux-chaired-alain-merieux-has-appointed-stephane-bancel-directeur-general
423. Stéphane Bancel | HIMSS. Published September 24, 2021. Accessed September 28, 2021. https://www.himss.org/global-conference/speaker-stephane-bancel
424. Alain Mérieux receives the prestigious Chinese Reform Friendship Award. Mérieux Foundation. Published September 17, 2013. Accessed September 28, 2021. https://www.fondation- merieux.org/en/news/alain-merieux-receives-the-prestigious-chinese-reform-friendship-award/
425. Beijing JXTWLCI. The Wuhan lab at the core of a virus controversy. Accessed September 28, 2021. https://medicalxpress.com/news/2020-04-wuhan-lab-core-virus-controversy.html
426. China Inaugurates the first biocontainment level 4 laboratory in Wuhan----Wuhan Institute of Virology. Accessed September 28, 2021. http://english.whiov.cas.cn/ne/201712/t20171212_187624.html
427. RaTG13 is fake. Nerd Has Power. Accessed September 28, 2021. https://nerdhaspower.weebly.com/ratg13-is-fake.html
428. RaTG13 – the Undeniable Evidence That the Wuhan Coronavirus Is Man-Made. GNEWS. Published May 2, 2020. Accessed September 28, 2021. https://gnews.org/192144
429. Scientific history of RaTG13. Peak Prosperity. Accessed September 28, 2021. https://www.peakprosperity.com/forum-topic/scientific-history-of-ratg13/
430. No one can find the animal that gave people covid-19. MIT Technology Review. Accessed September 28, 2021. https://www.technologyreview.com/2021/03/26/1021263/bat-covid-coronavirus- cause-origin-wuhan/
431. How WHO is working to track down the animal reservoir of the SARS-CoV-2 virus. Accessed September 28, 2021. https://www.who.int/news-room/feature-stories/detail/how-who-is-working-to- track-down-the-animal-reservoir-of-the-sars-cov-2-virus
432. Jewers C. More Lancet letter signatories found to have links to Wuhan. Mail Online. Published September 11, 2021. Accessed September 28, 2021. https://www.dailymail.co.uk/news/article- 9980015/26-Lancet-scientists-trashed-theory-Covid-leaked-Chinese-lab-links-Wuhan.html
433. Wang N, Li S-Y, Yang X-L, et al. Serological Evidence of Bat SARS-Related Coronavirus Infection in Humans, China. Virol Sin. 2018;33(1):104-107. doi:10.1007/s12250-018-0012-7
434. Daszak and scientists stand by Lancet letter condemning Wuhan lab “conspiracy theories.” MSN. Accessed September 28, 2021. https://www.msn.com/en-us/health/medical/daszak-and-scientists- stand-by-lancet-letter-condemning-wuhan-lab-conspiracy-theories/ar-AALT8w6
435. Albaugh G. Journal That Mocked COVID Lab-Leak As “Conspiracy” Recants. Citizens Journal. Published September 22, 2021. Accessed September 28, 2021. https://www.citizensjournal.us/journal- that-mocked-covid-lab-leak-as-conspiracy-recants/
436. Calisher C, Carroll D, Colwell R, et al. Statement in support of the scientists, public health professionals, and medical professionals of China combatting COVID-19. The Lancet. 2020;395(10226):e42-e43. doi:10.1016/S0140-6736(20)30418-9
437. Lancet’s COVID origins panel disbands over ties to Peter Daszak’s EcoHealth Alliance. swiftheadline. Published September 26, 2021. Accessed September 28, 2021. https://swiftheadline.com/lancets-covid-origins-panel-disbands-over-ties-to-peter-daszaks-ecohealth- alliance/
438. WHO Covid Expert Peter Daszak’s Alleged China Connection and CCP Money Trail: What’s the Truth? Published February 11, 2021. Accessed September 28, 2021. https://www.ibtimes.sg/who-covid- expert-peter-daszaks-alleged-china-connection-ccp-money-trail-whats-truth-55511
439. Rutz D. Media fact-checkers, Facebook cited Wuhan lab-linked scientist to knock down lab leak theory. Fox News. Published June 3, 2021. Accessed September 28, 2021. https://www.foxnews.com/media/daszak-fact-checks-coronavirus-wuhan-lab
440. Daszak P, Chmura A. A Fall From Grace To... Virulence? Ecohealth. 2008;5(1):96-97. doi:10.1007/s10393-008-0163-3
441. Bogich TL, Chunara R, Scales D, et al. Preventing pandemics via international development: a systems approach. PLoS Med. 2012;9(12):e1001354. doi:10.1371/journal.pmed.1001354
442. Daszak P, Howard SE, Chmura AA. Rock, paper, scissors; chicken, human, swine. EcoHealth. 2009;6(1):159-160. doi:10.1007/s10393-009-0245-x
443. Ge X-Y, Li J-L, Yang X-L, et al. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature. 2013;503(7477):535-538. doi:10.1038/nature12711
444. Latinne A, Hu B, Olival KJ, et al. Origin and cross-species transmission of bat coronaviruses in China. BioRxiv Prepr Serv Biol. Published online May 31, 2020:2020.05.31.116061. doi:10.1101/2020.05.31.116061
445. Li H-Y, Zhu G-J, Zhang Y-Z, et al. A qualitative study of zoonotic risk factors among rural communities in southern China. Int Health. 2020;12(2):77-85. doi:10.1093/inthealth/ihaa001
446. Li H, Chen Y, Machalaba CC, et al. Wild animal and zoonotic disease risk management and regulation in China: Examining gaps and One Health opportunities in scope, mandates, and monitoring systems. One Health Amst Neth. 2021;13:100301. doi:10.1016/j.onehlt.2021.100301
447. Nava A, Shimabukuro JS, Chmura AA, Luz SLB. The Impact of Global Environmental Changes on Infectious Disease Emergence with a Focus on Risks for Brazil. ILAR J. 2017;58(3):393-400. doi:10.1093/ilar/ilx034
448. Wang N, Li S-Y, Yang X-L, et al. Serological Evidence of Bat SARS-Related Coronavirus Infection in Humans, China. Virol Sin. 2018;33(1):104-107. doi:10.1007/s12250-018-0012-7
449. Zeng L-P, Gao Y-T, Ge X-Y, et al. Bat Severe Acute Respiratory Syndrome-Like Coronavirus WIV1 Encodes an Extra Accessory Protein, ORFX, Involved in Modulation of the Host Immune Response. J Virol. 2016;90(14):6573-6582. doi:10.1128/JVI.03079-15
450. David Martin. The Fauci COVID 19 Dossier.; 2021. Accessed September 28, 2021. http://archive.org/details/the-fauci-covid-19-dossier
451. 161385360554578. Coronavirus patients WELDED into homes in China as death toll spirals to 813. The US Sun. Published February 9, 2020. Accessed September 28, 2021. https://www.the- sun.com/news/378365/coronavirus-patients-welded-into-homes-in-china-as-death-toll-spirals-to-813/ 452. Archive VA, Author E the, Twitter F on, et al. COVID-19 deaths in NY nursing homes were 50 percent higher than claimed: probe. New York Post. Published January 28, 2021. Accessed September 28, 2021. https://nypost.com/2021/01/28/ny-nursing-home-covid-deaths-50-higher-than-stated-ag- probe/
453. Ciavaglia DR and J. Investigations into Northeast nursing homes ongoing as true COVID death toll rises by 16K. The Intelligencer. Accessed September 28, 2021. https://www.theintell.com/story/news/coronavirus/2021/09/14/covid-nursing-homes-deaths- investigation-pa-ny-nj/8280221002/
454. editor@palltimes.com A and SR. New York health chief, Cuomo defender, resigning. Oswego County News Now. Accessed September 28, 2021. http://www.oswegocountynewsnow.com/news/new- york-health-chief-cuomo-defender-resigning/article_4e6877f6-1d7a-11ec-b7fc-23eab87d9a8a.html
455. Care homes accused of using powerful sedatives to kill corona victims quickly. The Sun. Published July 12, 2020. Accessed September 28, 2021. https://www.thesun.co.uk/news/12100515/care-homes-accused-sedatives-coronavirus-die-quickly/ 456. Wayne Smith, The Man Exposing The Midazolam Mass Murder Care Home Scandal Found Dead - Plandemic. Accessed September 28, 2021. https://plandemic.co/2021/08/19/wayne-smith-the-man- exposing-the-midazolam-mass-murder-care-home-scandal-found-dead/
457. Did the ‘First Wave’ Mean the Mass Murder of the Elderly With Midazolam? – The White Rose. Accessed September 28, 2021. https://thewhiterose.uk/was-this-the-first-wave-mass-murder-of-the- elderly-with-midazolam/
458. News: Face mask shortage prompts CDC to... (The Washington Post) - Behind the headlines - NLM. NCBI. Accessed September 28, 2021. https://www.ncbi.nlm.nih.gov/search/research-news/8835 459. Evstatieva M. U.S. Companies Shifted To Make N95 Respirators During COVID. Now, They’re Struggling. NPR. https://www.npr.org/2021/06/25/1009858893/u-s-companies-shifted-to-make-n95- respirators-during-covid-now-theyre-struggling. Published June 25, 2021. Accessed September 28, 2021. 460. Pandemic Market Oddity: N95 Mask Shortage Despite Availability. Verisk. Accessed September 28, 2021. https://www.verisk.com/insurance/covid-19/iso-insights/pandemic-market-oddity-n95-mask- shortage-despite-availability/
461. In the early days of the pandemic, the U.S. government turned down an offer to manufacture millions of N95 masks in America. Washington Post. https://www.washingtonpost.com/investigations/in-the-early-days-of-the-pandemic-the-us- government-turned-down-an-offer-to-manufacture-millions-of-n95-masks-in- america/2020/05/09/f76a821e-908a-11ea-a9c0-73b93422d691_story.html. Accessed September 28, 2021.
462. Cheong W. The US government turned down an offer to manufacture up to 1.7 million N95 masks weekly in January: report. Business Insider. Accessed September 28, 2021. https://www.businessinsider.com/us-government-rejected-an-offer-to-manufacture-up-to-17-million- n95-masks-weekly-2020-5
463. Dugdale CM, Walensky RP. Filtration Efficiency, Effectiveness, and Availability of N95 Face Masks for COVID-19 Prevention. JAMA Intern Med. 2020;180(12):1612-1613. doi:10.1001/jamainternmed.2020.4218
464. What’s a PCR test cycle threshold and why it matters. Full Fact. Published 16:47:37.518768+00:00. Accessed September 28, 2021. https://fullfact.org/health/cycle-threshold- values/
465. Rajyalakshmi B, Samavedam S, Reddy PR, Aluru N. Prognostic Value of “Cycle Threshold” in Confirmed COVID-19 Patients. Indian J Crit Care Med Peer-Rev Off Publ Indian Soc Crit Care Med. 2021;25(3):322-326. doi:10.5005/jp-journals-10071-23765
466. Covid Mandates: Unscientific, Irrational And Fraudulent, Dozens Of Reasons To Stop Them Now | Covid Call To Humanity. Accessed September 28, 2021. https://covidcalltohumanity.org/2021/09/27/nicanor-perlas-covid-mandates-unscientific-irrational-and- fraudulent-dozens-of-reasons-to-stop-them-now/
467. The COVID-19 PCR Test Is Key to the Pandemic Fraud | Principia Scientific Intl. Principia Scientific Intl. | A science-based community. Published September 8, 2020. Accessed September 28, 2021. https://principia-scientific.com/the-covid-19-pcr-test-is-key-to-the-pandemic-fraud/
468. Mandavilli A. Your Coronavirus Test Is Positive. Maybe It Shouldn’t Be. The New York Times. https://www.nytimes.com/2020/08/29/health/coronavirus-testing.html. Published August 29, 2020. Accessed September 28, 2021.
469. The Fog of COVID-19 Data: How many cases aren’t even cases? John Locke Foundation. Accessed September 28, 2021. https://www.johnlocke.org/update/the-fog-of-covid-19-data-how-many- cases-arent-even-cases/
470. Caught Red-Handed: CDC Changes Test Thresholds To Virtually Eliminate New COVID Cases Among Vaxx’d. Rights and Freedoms. Published May 24, 2021. Accessed September 28, 2021. https://rightsfreedoms.wordpress.com/2021/05/24/caught-red-handed-cdc-changes-test-thresholds-to- virtually-eliminate-new-covid-cases-among-vaxxd/
471. Trabert D. CDC: maximum 28 CT for post-vaccine COVID PCR tests. The Sentinel. Published May 3, 2021. Accessed September 28, 2021. https://sentinelksmo.org/cdc-maximum-28-ct-for-post-vaccine- covid-pcr-tests/
472. FLCCC-Alliance-MATHplus-Protocol-ENGLISH.pdf. Accessed September 28, 2021. https://covid19criticalcare.com/wp-content/uploads/2021/01/FLCCC-Alliance-MATHplus-Protocol- ENGLISH.pdf
473. Kashiouris MG, L’Heureux M, Cable CA, Fisher BJ, Leichtle SW, Fowler AA. The Emerging Role of Vitamin C as a Treatment for Sepsis. Nutrients. 2020;12(2):E292. doi:10.3390/nu12020292
474. Obi J, Pastores SM, Ramanathan LV, Yang J, Halpern NA. Treating sepsis with vitamin C, thiamine, and hydrocortisone: Exploring the quest for the magic elixir. J Crit Care. 2020;57:231-239. doi:10.1016/j.jcrc.2019.12.011
475. Harris R. “Tantalizing” Results For A Test Of Vitamin C For Sepsis. NPR. https://www.npr.org/sections/health-shots/2019/10/01/766029397/mixed-results-for-a-test-of- vitamin-c-for-sepsis. Published October 1, 2019. Accessed September 28, 2021.
476. nutraingredients.com. “Ethically and morally unacceptable”: Reaction to vitamin C for sepsis trial. nutraingredients.com. Accessed September 28, 2021. https://www.nutraingredients.com/Article/2020/01/28/Ethically-and-morally-unacceptable-Reaction- to-vitamin-C-for-sepsis-trial
477. Research C for DE and. FDA Updates and Press Announcements on NDMA in Zantac (ranitidine). FDA. Published online July 1, 2021. Accessed September 28, 2021. https://www.fda.gov/drugs/drug- safety-and-availability/fda-updates-and-press-announcements-ndma-zantac-ranitidine
478. FDA studies: No post-ingestion NDMA from ranitidine. Accessed September 28, 2021. https://www.raps.org/news-and-articles/news-articles/2021/6/fda-studies-no-post-ingestion-ndma- from-ranitidine
479. Ahmadi A, Ebrahimzadeh MA, Ahmad-Ashrafi S, Karami M, Mahdavi MR, Saravi SSS. Hepatoprotective, antinociceptive and antioxidant activities of cimetidine, ranitidine and famotidine as histamine H2 receptor antagonists. Fundam Clin Pharmacol. 2011;25(1):72-79. doi:10.1111/j.1472- 8206.2009.00810.x
480. Nutrition C for FS and A. LES Labs - 593764 - 07/23/2020. Center for Food Safety and Applied Nutrition. Published July 29, 2020. Accessed September 28, 2021. https://www.fda.gov/inspections- compliance-enforcement-and-criminal-investigations/warning-letters/les-labs-593764-07232020
481. US senator, NPA press FDA on NAC supplements. Natural Products INSIDER. Published August 18, 2021. Accessed September 28, 2021. https://www.naturalproductsinsider.com/regulatory/us- senator-npa-press-fda-nac-supplements
482. nutraingredients-usa.com. CRN: ‘This is not the final word on NAC.’ nutraingredients-usa.com. Accessed September 28, 2021. https://www.nutraingredients-usa.com/Article/2021/05/11/CRN-This-is- not-the-final-word-on-NAC
483. Amazon confirms plans on removing NAC supplements. Natural Products INSIDER. Published May 6, 2021. Accessed September 28, 2021. https://www.naturalproductsinsider.com/regulatory/amazon-confirms-plans-removing-nac- supplements
484. Harvard University Professor and Two Chinese Nationals Charged in Three Separate China Related Cases. Published January 28, 2020. Accessed September 28, 2021. https://www.justice.gov/opa/pr/harvard-university-professor-and-two-chinese-nationals-charged- three-separate-china-related
485. Research Sponsors - Lieber Research GroupThe Lieber group is focused broadly on science and technology at the nanoscale - Lieber Research Group. Accessed September 28, 2021. http://cml.harvard.edu/resources/research-sponsors
486. Shaw J. Virus-Sized Transistors. Harvard Magazine. Published December 16, 2010. Accessed September 28, 2021. https://www.harvardmagazine.com/2011/01/virus-sized-transistors
487. Why did a Chinese university hire Charles Lieber to do battery research? Accessed September 28, 2021. https://www.science.org/content/article/why-did-chinese-university-hire-charles-lieber-do- battery-research
488. Writer PRHS. Reading life’s building blocks. Harvard Gazette. Published January 5, 2012. Accessed September 28, 2021. https://news.harvard.edu/gazette/story/2012/01/reading-lifes-building- blocks/
489. Correspondent CM-MH. Harvard researchers present nanowire devices update. Harvard Gazette. Published July 2, 2019. Accessed September 28, 2021. https://news.harvard.edu/gazette/story/2019/07/harvard-researchers-present-nanowire-devices- update/
490. Harvard University Professor Indicted on False Statement Charges. Published June 9, 2020. Accessed September 28, 2021. https://www.justice.gov/usao-ma/pr/harvard-university-professor- indicted-false-statement-charges
491. Barry E, Kolata G. China’s Lavish Funds Lured U.S. Scientists. What Did It Get in Return? The New York Times. https://www.nytimes.com/2020/02/06/us/chinas-lavish-funds-lured-us-scientists-what-did- it-get-in-return.html. Published February 6, 2020. Accessed September 28, 2021.
492. Subbaraman N. Harvard chemistry chief’s arrest over China links shocks researchers. Nature. Published online February 3, 2020. doi:10.1038/d41586-020-00291-2
493. Portman R, Carper T. Threats to the U.S. Research Enterprise: China’s Talent Recruitment Plans. :109.
494. Krige J. Scholars or Spies? U.S.-China Tension in Academic Collaboration. China Research Center. Published October 12, 2020. Accessed September 28, 2021. https://www.chinacenter.net/2020/china_currents/19-3/scholars-or-spies-u-s-china-tension-in- academic-collaboration/
495. FBI_Risks_To_Academia.pdf. Accessed September 28, 2021. https://www.research.psu.edu/sites/default/files/FBI_Risks_To_Academia.pdf
496. Zweig D, Kang S. AMERICA CHALLENGES CHINA’S NATIONAL TALENT PROGRAMS. :20.
497. Zhang A, Zhao Y, You SS, Lieber CM. Nanowire probes could drive high-resolution brain-machine interfaces. Nano Today. 2020;31:100821. doi:10.1016/j.nantod.2019.100821
498. Hong G, Lieber CM. Novel electrode technologies for neural recordings. Nat Rev Neurosci. 2019;20(6):330-345. doi:10.1038/s41583-019-0140-6
499. Human Cells Eat Nanowires. IEEE Spectrum. Published December 19, 2016. Accessed September 28, 2021. https://spectrum.ieee.org/human-cells-eat-nanowires
500. They’ve got the beat. Boston Herald. Published August 29, 2012. Accessed September 28, 2021. https://www.bostonherald.com/2012/08/29/theyve-got-the-beat-2/
501. Tian B, Liu J, Dvir T, et al. Macroporous nanowire nanoelectronic scaffolds for synthetic tissues. Nat Mater. 2012;11(11):986-994. doi:10.1038/nmat3404
502. Board of Directors: Advancing mRNA Science - Moderna. Accessed September 28, 2021. https://www.modernatx.com/modernas-board-directors
503. Tognini G. MIT Scientist Bob Langer Becomes A Billionaire Thanks To Moderna Stock Rally. Forbes. Accessed September 28, 2021. https://www.forbes.com/sites/giacomotognini/2020/11/12/mit- scientist-bob-langer-becomes-a-billionaire-thanks-to-moderna-stock-rally/
504. Moderna’s Stock Rally Makes Bob Langer a Billionaire. Accessed September 28, 2021. https://www.ceotodaymagazine.com/2020/11/modernas-stock-rally-makes-bob-langer-a-billionaire/ 505. Langer Lab – MIT Department of Chemical Engineering. Accessed September 28, 2021. https://langerlab.mit.edu/
506. Nano-Bioelectronics. Lieber Research Group. Accessed September 28, 2021. http://cml.harvard.edu/research/nano-bioelectronics
507. Durden T. Klaus Schwab: Great Reset Will “Lead To Fusion Of Our Physical, Digital, & Biological Identity.” Invesbrain. Published November 17, 2020. Accessed September 28, 2021. https://invesbrain.com/klaus-schwab-great-reset-will-lead-to-fusion-of-our-physical-digital-biological- identity/
508. Shaping the Future of the Fourth Industrial Revolution by Klaus Schwab, Nicholas Davis: 9781984822611 | PenguinRandomHouse.com: Books. Accessed September 28, 2021. https://www.penguinrandomhouse.com/books/598250/shaping-the-future-of-the-fourth-industrial- revolution-by-klaus-schwab-founder-and-executive-chairman-world-economic-forum-with-nicholas- davis/
509. Love A. CONFIRMED! Graphene Oxide Main Ingredient In Covid Shots. Ariyana Love. Published August 9, 2021. Accessed September 28, 2021. https://ambassadorlove.wordpress.com/2021/08/09/confirmed-graphene-oxide-main-ingredient-in- covid-shots/
510. Graphene Oxide The Vector For Covid-19 Democide | The Liberty Beacon. Published July 30, 2021. Accessed September 28, 2021. https://www.thelibertybeacon.com/graphene-oxide-the-vector- for-covid-19-democide/
511. ORWELL CITY: Official interim report of Pfizer’s vaccination vial analysis explained by La Quinta Columna. ORWELL CITY. Accessed September 28, 2021. https://www.orwell.city/2021/06/vaccination- vial-analysis-explained.html
512. Yi J, Choe G, Park J, Lee JY. Graphene oxide-incorporated hydrogels for biomedical applications. Polym J. 2020;52(8):823-837. doi:10.1038/s41428-020-0350-9
513. Kim YH, Jo MS, Kim JK, et al. Short-term inhalation study of graphene oxide nanoplates. Nanotoxicology. 2018;12(3):224-238. doi:10.1080/17435390.2018.1431318
514. News · CBC. Potentially toxic masks distributed in schools and daycares in Quebec | CBC News. CBC. Published March 26, 2021. Accessed September 28, 2021. https://www.cbc.ca/news/canada/montreal/masks-early-pulmonary-toxicity-quebec-schools-daycares- 1.5966387
515. HAF. BOMBSHELL: Disposable Blue Face Masks Found to Contain Toxic, Asbestos-Like Substance that Destroys Lungs. https://humansarefree.com/. Accessed September 28, 2021. https://humansarefree.com/2021/04/bombshell-disposable-blue-face-masks-found-to-contain-toxic- asbestos-like-substance-that-destroys-lungs.html/
516. Reuters. Japan suspends 1.6M doses of Moderna shot after contamination reports. NBC News. Accessed September 28, 2021. https://www.nbcnews.com/news/world/japan-suspends-1-6m-doses- moderna-shot-after-contamination-reports-n1277669
517. Contaminant in Moderna COVID-19 vaccine vials found in Japan was metallic particles: report. FiercePharma. Accessed September 28, 2021. https://www.fiercepharma.com/pharma/contaminant- moderna-covid-19-vaccine-vials-found-japan-was-metallic-particles-report
518. Administrator A. Japan Suspects Contaminant In Moderna Vaccines Is Metallic, ‘Reacts To Magnets.’ The Burning Platform. Published August 27, 2021. Accessed September 28, 2021. https://www.theburningplatform.com/2021/08/27/japan-suspects-contaminant-in-moderna-vaccines- is-metallic-reacts-to-magnets/
519. Franceschi Biagioni A, Cellot G, Pati E, et al. Graphene oxide prevents lateral amygdala dysfunctional synaptic plasticity and reverts long lasting anxiety behavior in rats. Biomaterials. 2021;271:120749. doi:10.1016/j.biomaterials.2021.120749
520. Soothing the symptoms of anxiety with graphene oxide. Graphene Flagship. Accessed September 28, 2021. https://graphene-flagship.eu/graphene/news/soothing-the-symptoms-of-anxiety- with-graphene-oxide/
521. SARS-CoV-2 Spike Proteins Disrupt the Blood-Brain Barrier, Potentially Raising Risk of Neurological Damage in COVID-19 Patients. Temple Health. Accessed September 28, 2021. https://www.templehealth.org/about/news/sars-cov-2-spike-proteins-disrupt-the-blood-brain-barrier- potentially-raising-risk-of-neurological-damage-in-covid-19-patients
522. NEUROMODULATORY EFFECTS OF SARS-COV-2 ON THE BLOOD-BRAIN BARRIER. CROI Conference. Accessed September 28, 2021. https://www.croiconference.org/abstract/neuromodulatory-effects-of-sars-cov-2-on-the-blood-brain- barrier/
523. Ohta S, Kikuchi E, Ishijima A, Azuma T, Sakuma I, Ito T. Investigating the optimum size of nanoparticles for their delivery into the brain assisted by focused ultrasound-induced blood–brain barrier opening. Sci Rep. 2020;10(1):18220. doi:10.1038/s41598-020-75253-9
524. Vu MN, Rajasekhar P, Poole DP, et al. Rapid Assessment of Nanoparticle Extravasation in a Microfluidic Tumor Model. ACS Appl Nano Mater. 2019;2(4):1844-1856. doi:10.1021/acsanm.8b02056 525. Saraiva C, Praça C, Ferreira R, Santos T, Ferreira L, Bernardino L. Nanoparticle-mediated brain drug delivery: Overcoming blood–brain barrier to treat neurodegenerative diseases. J Controlled Release. 2016;235:34-47. doi:10.1016/j.jconrel.2016.05.044
526. Pappas S. Rare magnetism found in the world’s strongest material. livescience.com. Published October 14, 2020. Accessed September 28, 2021. https://www.livescience.com/graphene-hides-rare- magnetism.html
527. Augustyniak-Jabłokow MA, Tadyszak K, Strzelczyk R, Fedaruk R, Carmieli R. Slow spin relaxation of paramagnetic centers in graphene oxide. Carbon. 2019;152:98-105. doi:10.1016/j.carbon.2019.06.024
528. Sang M, Shin J, Kim K, Yu KJ. Electronic and Thermal Properties of Graphene and Recent Advances in Graphene Based Electronics Applications. Nanomaterials. 2019;9(3):374. doi:10.3390/nano9030374
529. INBRAIN Neuroelectronics Secures $17 Million in Series A Funding for First AI-Powered Graphene-Brain Interface. Published March 30, 2021. Accessed September 28, 2021. https://www.businesswire.com/news/home/20210330005388/en/INBRAIN-Neuroelectronics-Secures- 17-Million-in-Series-A-Funding-for-First-AI-Powered-Graphene-Brain-Interface
530. DARPA and the Brain Initiative. Accessed September 28, 2021. https://www.darpa.mil/program/our-research/darpa-and-the-brain-initiative
531. Six Paths to the Nonsurgical Future of Brain-Machine Interfaces. Accessed September 28, 2021. https://www.darpa.mil/news-events/2019-05-20
532. Neuralink and the Brain’s Magical Future. Wait But Why. Published April 20, 2017. Accessed September 28, 2021. https://waitbutwhy.com/2017/04/neuralink.html
533. Martins NRB, Angelica A, Chakravarthy K, et al. Human Brain/Cloud Interface. Front Neurosci. 2019;13:112. doi:10.3389/fnins.2019.00112
534. Lee S, Shin Y, Woo S, Lee KK and H-N. Review of Wireless Brain-Computer Interface Systems. IntechOpen; 2013. doi:10.5772/56436
535. Researchers demonstrate first human use of high-bandwidth wireless brain-computer interface. Brown University. Accessed September 28, 2021. https://www.brown.edu/news/2021-03-31/braingate- wireless
536. AI and VR Transform Thoughts to Action with Wireless BCI | Psychology Today. Accessed September 28, 2021. https://www.psychologytoday.com/us/blog/the-future-brain/202107/ai-and-vr- transform-thoughts-action-wireless-bci
537. Haselager P. Did I Do That? Brain–Computer Interfacing and the Sense of Agency. Minds Mach. 2013;23(3):405-418. doi:10.1007/s11023-012-9298-7
538. Mind reading and brain computer interface technology: the future is coming, fast. Privacy SOS. Accessed September 28, 2021. https://privacysos.org/technologies_of_controlmind_reading/
539. With Magnetic Nanoparticles, Scientists Remotely Control Neurons and Animal Behavior. Accessed September 28, 2021. http://www.buffalo.edu/news/releases/2010/07/11518.html
540. Brain-machine interfaces may be used to study and regulate mood - Science in the News. Accessed September 28, 2021. https://sitn.hms.harvard.edu/flash/2019/brain-machine-interfaces-may- used-study-regulate-mood/?web=1&wdLOR=c97F3B6A1-B18A-433D-96C4-477F88B46A83
541. Shanechi MM. Brain–machine interfaces from motor to mood. Nat Neurosci. 2019;22(10):1554- 1564. doi:10.1038/s41593-019-0488-y
542. Opinion / The Last Humans and the Next Brands - Critical Mass - Adforum.com. Accessed September 28, 2021. https://www.adforum.com/agency/6664937/press-releases/70226/opinion-the- last-humans-and-the-next-brands
543. Bonaci T, Herron J, Matlack C, Chizeck HJ. Securing the exocortex: A twenty-first century cybernetics challenge. In: 2014 IEEE Conference on Norbert Wiener in the 21st Century (21CW). ; 2014:1- 8. doi:10.1109/NORBERT.2014.6893912
544. Can dark triad leaders be a good choice for a leadership position? - Egon Zehnder. Can dark triad leaders be a good choice for a leadership position? - Egon Zehnder. Accessed September 28, 2021.
https://www.egonzehnder.com/insight/can-dark-triad-leaders-be-a-good-choice-for-a-leadership- position
545. Silver J. The Startling Accuracy of Referring to Politicians as “Psychopaths.” The Atlantic. Published July 31, 2012. Accessed September 28, 2021. https://www.theatlantic.com/health/archive/2012/07/the-startling-accuracy-of-referring-to-politicians- as-psychopaths/260517/
546. Schlesinger T. The Rise of the Psychopath and Sociopath to Political Power. World Issues — Politics, Economics, and More. Published December 1, 2020. Accessed September 28, 2021. https://medium.com/world-issues-politics-economics-and-more/the-rise-of-the-psychopath-and- sociopath-to-political-power-b67ef9073477
547. Commentary: 12% of corporate leaders are psychopaths. It’s time to take this problem seriously. Fortune. Accessed September 28, 2021. https://fortune.com/2021/06/06/corporate-psychopaths- business-leadership-csr/
548. 21 percent of CEOs are psychopaths. Only 21 percent? Washington Post. https://www.washingtonpost.com/news/on-small-business/wp/2016/09/16/gene-marks-21-percent-of- ceos-are-psychopaths-only-21-percent/. Accessed September 28, 2021.
549. McCullough J. The Psychopathic CEO. Forbes. Accessed September 28, 2021. https://www.forbes.com/sites/jackmccullough/2019/12/09/the-psychopathic-ceo/
550. The brain-computer interface: new rights or new threats to fundamental freedoms? Accessed September 28, 2021. https://pace.coe.int/en/files/28722
Copyright
The Spartacus Letter © 2021 by Spartacus is licensed under CC BY-SA 4.0. To view a copy of this
license, visit http://creativecommons.org/licenses/by-sa/4.0/
Point on the doll where the mechanic touched you. Jesus.
Ideology tops science every time for them !
All I have to say is if you look at the very bottom or those citation resources, ITS BEEN COPYRIGHTED! What now Bitches?
eightmillimeter
09-28-21, 22:50
Can we just lock this one before I lose my shit and get banned for a week
Can we just lock this one before I lose my shit and get banned for a week Well what's that mean? All I'm saying is someone put some work into that, Look at those resources!
I'm exhausted I have to go to bed.
Trolls are so predictable when they know they are under the target...lotsa 411 in the OP that touched a lotta different topics worthy of independent discussion that ultimately in turn went untouched due to the deliberate derail Because in no WAY can the jab be worse than the virus. No reason to continue reading what the OP posted & should immediately be dismissed, so let's take this train off the rails. Same tactic every thread by the same poster who clearly has superior thinking skills.
All I have to say is if you look at the very bottom or those citation resources, ITS BEEN COPYRIGHTED! What now Bitches?
The Handmaids Tale has been copyrighted. Means zip. And some of those sources are LOLworthy. Only thing missing is MK Ultra Mind Control experiments exposed.
The Handmaids Tale has been copyrighted. Means zip. And some of those sources are LOLworthy. Only thing missing is MK Ultra Mind Control experiments exposed.
Funny you should mention mind control. Have you seen any of that brain computer interface stuff mentioned in the citations?Thats what the Graphene oxide is for. And why do a whole lot of our politicians seem to be under someones control? As if they can't refuse. Take General Milley for example?. And why does Mark Zuckerberg look AND act like a freakin Robot?? https://www.darpa.mil/program/our-research/darpa-and-the-brain-initiative Also I just wanna say I always liked you back in your ARF.com days. And I mean that sincerely. When did you get the ban hammer again? Wasn't it around 2007...
I thought the graphene was to cause autism, now it’s mind control?
FromMyColdDeadHand
09-29-21, 01:53
This letter lost me at "nanoparticles". As for the political misuse of the pandemic...yeah, I can roll with that.
I’m with you on that. “Superradicals” I think was the other one that got my attention. Granted, it is almost 30 years since I took biochemistry, but some of that started sounding like word salad.
In general, Somethings made sense, others were opaque to me.
You’re right, he could be highly educated. If that was the case he wouldn’t be posting bullshit conspiracy theory letters riddled full of nonsense though. It’s obvious you think I think highly of myself. In a room full of tin foil hat wearing loons when it comes to basic science, yeah I do. When it comes to subjects I don’t know about I shut my mouth and listen to those that do. That’s why I read the firearms forums and hardly post, because I trust the wealth of firearms knowledge on this forum over my basic knowledge.
Maybe if you and others applied the same level of skepticism to the people posting ludicrous conspiracies this forum wouldn’t be dying and the old members who used to bring rational discussion would still be posting here.Now your assuming that I believe any of this.
Soli Deo Gloria
https://www.bitchute.com/video/8UDRbbJGfma6/
https://www.bitchute.com/video/5v9ijUCKDzgn/
https://www.bitchute.com/video/85ivTweidQ6h/
https://www.bitchute.com/video/bbzfQFMOi2az/
https://www.bitchute.com/video/UQqI5mVu8uAv/
https://www.bitchute.com/video/jzNhWC8psk9M/
https://www.bitchute.com/video/8UDRbbJGfma6/
https://www.bitchute.com/video/m0qljD8NghUm/
https://www.bitchute.com/video/8NKV6HBt1zSD/
So you posted up the ramblings of some unknown dude who make up a rant while he took a shit.
Very useful.
That can indicate BS or it can indicate someone who simply doesn't want to be identified. They did cite references so anyone can review versus the Jacinda Ardern "believe only us" approach.
Nah, I’m trying to say you aren’t capable of even discerning what is and isn’t misinformation, which your post is, because you’re an auto tech and don’t comprehend basic scientific literature
Ad Hominem much?
https://www.businesswire.com/news/home/20210330005388/en/INBRAIN-Neuroelectronics-Secures-
INBRAIN Neuroelectronics Secures $17 Million in Series A Funding for First AI-Powered Graphene-Brain Interface
Funding enables company to advance first-in-human studies for its flagship product, a less-invasive neuromodulation device for treating neurological conditions using artificial intelligence and graphene electrodes
March 30, 2021 07:00 AM Eastern Daylight Time
BARCELONA, Spain--(BUSINESS WIRE)--INBRAIN Neuroelectronics S.L., a company in the intersection between Medtech, Deeptech and Digital Health dedicated to developing the world’s first intelligent graphene-brain interface, today announced $16.8 million in Series A funding for its disruptive system for treating epilepsy and Parkinson’s disease.
“Led by an extraordinary team of professionals and investors with long-time expertise in the industry, INBRAIN represents a revolution in current neurological treatments, addressing a clear medical need and lowering costs for healthcare systems”
Tweet this
The investment, co-led by Asabys Partners and Alta Life Sciences, and joined by Vsquared Ventures and TruVenturo GmbH, includes the participation of the Spanish Ministry of Science’s CDTI and a follow-on investment by the Institut Catalŕ de Finances’ ICF Venture Tech II fund.
INBRAIN’s technology harnesses the power of graphene, a two-dimensional material first isolated in 2004 made of a lattice of carbon atoms only one atom thick. The strongest material ever tested, roughly 100 times stronger than the equivalent thickness of steel, graphene has unique electrical and thermal conduction properties that are still being explored.1,2
INBRAIN’s less-invasive graphene electrodes take advantage of some of these properties to enable ultra-high signal resolution at levels never seen before. The INBRAIN system’s machine learning software detects therapy-specific biomarkers to deliver highly focused, adaptive neuromodulation therapy that is personalized for each patient.
The funding will be used to advance INBRAIN’s first-in-human clinical program, aiming to establish the safety of graphene as the new standard of care for neurotechnology devices.
“At INBRAIN, our mission is to improve the lives of patients with brain-related diseases, who are forced to live alone with their conditions. Less invasive and more intelligent neuroelectronic technologies like ours could provide safer therapies that are upgradable and adaptive in real time, to empower these patients and improve the outcomes that matter to them,” said INBRAIN Neuroelectronics Co-founder & CEO Carolina Aguilar.
“Graphene technology has matured and is ready for the next challenge. This investment is an important stepping stone toward our goal of transforming the way neurological disorders are treated,” added Jose Garrido, Co-founder and Chief Scientific Officer of INBRAIN.
“At Asabys, we believe strongly in the promise of dedicated ecosystems in developing treatments to transform the lives of patients everywhere. This investment shows how applied science, international talent and specialized financial support can generate truly disruptive therapies addressing significant unmet needs,” noted Asabys Managing Partner Josep Sanfeliu, who is chairman of the board at INBRAIN.
“Led by an extraordinary team of professionals and investors with long-time expertise in the industry, INBRAIN represents a revolution in current neurological treatments, addressing a clear medical need and lowering costs for healthcare systems,” said Scott Moonly, managing partner at Alta Life Sciences.
About INBRAIN Neuroelectronics
INBRAIN Neuroelectronics S.L., founded in 2019, is a medical device company dedicated to developing the world’s first intelligent graphene-brain interface to treat a variety of conditions. INBRAIN’s first product is designed to read and modulate brain activity, using artificial intelligence to trigger adaptive responses for personalized neurological therapy for epilepsy and Parkinson’s disease. For more information, please visit www.inbrain-neuroelectronics.com.
About Asabys Partners
Asabys Partners is a venture capital manager firm specialized in the healthcare sector, founded by Josep Ll. Sanfeliu and Clara Campŕs and participated by Alantra. Its first investment vehicle, Sabadell Asabys Health Innovation Investments SCR, SA, was launched in 2019 and is backed by the Banc Sabadell as reference investor. The fund has a target size of more than €80M and invests in healthcare companies across three verticals: medtech, digital therapeutics and biotech, that have highly innovative and disruptive technologies. The fund’s investment in the company benefits from the financial backing of the European Union under the European Fund for Strategic Investments (“EFSI”) set up under the Investment Plan for Europe. The purpose of EFSI is to help support financing and implementing productive investments in the European Union and to ensure increased access to financing. www.asabys.com
About Alta Life Sciences
Alta Life Sciences Spain I FCR (ALSS I FCR) is a venture capital fund that invests in companies in all their stages of development: from financing through seed capital to business growth, and in all spheres of life sciences including biotechnology, medical devices, diagnosis, genomics and digital health. Altamar Private Equity SGIIC, a leading independent firm in the management of international private assets, is the managing company of ALSS I FCR and Alta Life Sciences, S.L., formed by leading professionals in the life sciences business, acting as an exclusive investment consultant. www.altals.com
About CDTI
CDTI is the body from the General State Administration that supports knowledge-based innovation, advising and offering public aid for innovation through subsidies or partially reimbursable aids. CDTI also internationalizes the R&D and innovation business projects of Spanish companies and entities and manages Spanish participation in international R&D organizations, such as Horizonte2020 and Eureka, as well as in the Science and Space industries. Additionally, through the Innvierte Economía Sostenible initiative, it supports and facilitates the capitalization of technology companies. www.cdti.es
About Vsquared Ventures
Vsquared Ventures is a VC firm based in Munich. Backed by leading European technology entrepreneurs and family offices, Vsquared Ventures embraces technology to advance society. Past founding investments include Isar Aerospace and IQM Quantum Computers among others. www.vsquared.vc
About TruVenturo
TruVenturo is one of the most successful early stage investors and company builders in Europe. For over a decade TruVenturo has been investing at the forefront of digitalization and life sciences, always focusing on identifying big future markets and disruptive business models. Therefore, the team is a strong believer in pharma to prevent age related disease and prolong healthy human lifespan as well as utilising neurostimulation technologies to create bi-directional Computer-Brain-Interfaces. TruVenturo’s current portfolio includes over 20 companies, among them several industry leaders and hidden champions. www.truventuro.com
About ICF Venture Tech II
ICF Venture Tech II FCRE is a €20M venture capital fund managed by ICF Capital SGEIC that invests in technology and innovative companies with high growth potential in early stage and Series A. It is one of the four venture capital funds directly managed by Institut Catalŕ de Finances. Investments are mainly in equity or debt/convertible debt, preferably in co-investment with other funds. The ticket size is between €500,000 and €2M. www.icf.cat
1Cao, K. (2020). "Elastic straining of free-standing monolayer graphene". Nature Communications. 11 (284): 284.
2 Novoselov, K. S.; Geim, A. K.; Morozov, S. V.; Jiang, D.; Zhang, Y.; Dubonos, S. V.; Grigorieva, I. V.; Firsov, A. A. (22 October 2004). "Electric Field Effect in Atomically Thin Carbon Films". Science. 306 (5696): 666–669.
I thought the graphene was to cause autism, now it’s mind control?
Thats aluminum I believe...
I’m with you on that. “Superradicals” I think was the other one that got my attention. Granted, it is almost 30 years since I took biochemistry, but some of that started sounding like word salad.
In general, Somethings made sense, others were opaque to me.
I think theres been some progress made since then... Mostly by the Chinese students!
https://particleandfibretoxicology.biomedcentral.com/articles/10.1186/s12989-016-0168-y
Review
Open Access
Published: 31 October 2016
Toxicity of graphene-family nanoparticles: a general review of the origins and mechanisms
Lingling Ou, Bin Song, Huimin Liang, Jia Liu, Xiaoli Feng, Bin Deng, Ting Sun & Longquan Shao
Particle and Fibre Toxicology volume 13, Article number: 57 (2016) Cite this article
319k Accesses
271 Citations
1912 Altmetric
Metrics details
Abstract
Due to their unique physicochemical properties, graphene-family nanomaterials (GFNs) are widely used in many fields, especially in biomedical applications. Currently, many studies have investigated the biocompatibility and toxicity of GFNs in vivo and in intro. Generally, GFNs may exert different degrees of toxicity in animals or cell models by following with different administration routes and penetrating through physiological barriers, subsequently being distributed in tissues or located in cells, eventually being excreted out of the bodies. This review collects studies on the toxic effects of GFNs in several organs and cell models. We also point out that various factors determine the toxicity of GFNs including the lateral size, surface structure, functionalization, charge, impurities, aggregations, and corona effect ect. In addition, several typical mechanisms underlying GFN toxicity have been revealed, for instance, physical destruction, oxidative stress, DNA damage, inflammatory response, apoptosis, autophagy, and necrosis. In these mechanisms, (toll-like receptors-) TLR-, transforming growth factor β- (TGF-β-) and tumor necrosis factor-alpha (TNF-α) dependent-pathways are involved in the signalling pathway network, and oxidative stress plays a crucial role in these pathways. In this review, we summarize the available information on regulating factors and the mechanisms of GFNs toxicity, and propose some challenges and suggestions for further investigations of GFNs, with the aim of completing the toxicology mechanisms, and providing suggestions to improve the biological safety of GFNs and facilitate their wide application.
Background
Graphene, which is isolated from crystalline graphite, is a flat monolayer composed of single-atom-thick, two-dimensional sheets of a hexagonally arranged honeycomb lattice [1]. Because of its unique structural, specific surface area and mechanical characteristics, the functions and applications of graphene have gained considerable attention since the discovery of the material in 2004 [2, 3]. Graphene and its derivatives include monolayer graphene, few-layer graphene (FLG), graphene oxide (GO), reduced graphene oxide (rGO), graphene nanosheets (GNS), and graphene nanoribbons, etc. [4–7]. GO is one of the most vital chemical graphene derivatives of the graphene-family nanomaterials (GFNs), which attracts increasing attention for its potential biomedical applications. Graphene-based materials usually have sizes ranging from several to hundreds of nanometer and are 1-10 nm thick [8, 9], which is also the definition of ‘nanoparticles’ or ‘nanomaterials’. Due to their exceptional physical and chemical properties, graphene materials have been widely used in various fields, including energy storage; nanoelectronic devices; batteries [10–12]; and biomedical applications, such as antibacterials [13, 14], biosensors [15–18], cell imaging [19, 20], drug delivery [8, 21, 22], and tissue engineering [23–25].
Along with the application and production of GFNs increasing, the risk of unintentional occupational or environmental exposure to GFNs is increasing [26]. And recently, there are some investigation on GFNs exposure in occupational settings and published data showed that the occupational exposure of GFNs had potential toxicity to the workers and researchers [27–29]. GFNs can be delivered into bodies by intratracheal instillation [30], oral administration [31], intravenous injection [32], intraperitoneal injection [33] and subcutaneous injection [34]. GFNs can induce acute and chronic injuries in tissues by penetrating through the blood-air barrier, blood-testis barrier, blood-brain barrier, and blood-placenta barrier etc. and accumulating in the lung, liver, and spleen etc. For example, some graphene nanomaterials aerosols can be inhaled and substantial deposition in the respiratory tract, and they can easily penetrate through the tracheobronchial airways and then transit down to the lower lung airways, resulting in the subsequent formation of granulomas, lung fibrosis and adverse health effects to exposed persons [2, 29]. Several reviews have outlined the unique properties [35, 36] and summarized the latest potential biological applications of GFNs for drug delivery, gene delivery, biosensors, tissue engineering, and neurosurgery [37–39]; assessed the biocompatibility of GFNs in cells (bacterial, mammalian and plant) [7, 40, 41] and animals (mice and zebrafish) [42]; collected information on the influence of GFNs in the soil and water environments [43]. Although these reviews discussed the related safety profiles and nanotoxicology of GFNs, the specific conclusions and detailed mechanisms of toxicity were insufficient, and the mechanisms of toxicity were not summarized completely. The toxicological mechanisms of GFNs demonstrated in recent studies mainly contain inflammatory response, DNA damage, apoptosis, autophagy and necrosis etc., and those mechanisms can be collected to further explore the complex signalling pathways network regulating the toxicity of GFNs. It needs to point out that there are several factors which largely influence the toxicity of GFNs, such as the concentration, lateral dimension, surface structure and functionalization etc. Herein, this review presents a comprehensive summary of the available information on the mechanisms and regulating factors of GFNs toxicity in vitro and in vivo via different experimental methods, with the goals of providing suggestions for further studies of GFNs and completing the toxicology mechanisms to improve the biological safety of GFNs and facilitate their wide application.
Toxicity of GFNs (in vivo and in vitro)
GFNs penetrate through the physiological barriers or cellular structures by different exposure ways or administration routes and entry the body or cells, eventually resulting in toxicity in vivo and in vitro. The varying administration routes and entry paths, different tissue distribution and excretion, even the various cell uptake patterns and locations, may determine the degree of the toxicity of GFNs [44–46]. So to make them clear may be helpful to better understand the laws of the occurrence and development of GFNs toxicity.
Administration route
The common administration routes in animal models include airway exposure (intranasal insufflation, intratracheal instillation, and inhalation), oral administration, intravenous injection, intraperitoneal injection and subcutaneous injection. The major exposure route for GFNs in the working environment is airway exposure, thus inhalation and intratracheal instillation are used mostly in mice to simulate human exposure to GFNs. Though the inhalation method provides the most realistic simulation to real life exposure, instillation is more effective and time-saving method, and GFNs was found that causing longer inflammation period using instillation (intratracheal instillation, intrapleural installation and pharyngeal aspiration) than inhalation [24, 30, 47, 48]. GFNs were investigated to deposit in the lungs and accumulate to a high level, which retained for more than 3 months in the lungs with slow clearing after intratracheal instillation [49]. Intravenous injection is also widely used to assess the toxicity of graphene nanomaterials, and graphene circulates through the body of mice in 30 min, accumulating at a working concentration in the liver and bladder [32, 50–52]. However, GO derivatives had rather finite intestinal adsorption and were rapidly excreted in adult mice via oral administration [31, 53]. Nano-sized GO (350 nm) caused less mononuclear cells to infiltrate subcutaneous adipose tissue after subcutaneous injection in the neck region compared to micron-sized GO (2 μm) [34]. GO agglomerated near the injection site after intraperitoneal injection, and numerous smaller aggregates settled in the proximity of the liver and spleen serosa [31, 33]. Experiments on skin contact with or skin permeation of GFNs were not found in the papers reviewed here, and there is insufficient evidence available to conclude that graphene can penetrate intact skin or skin lesions. The route of nasal drops, which has been widely used to test the neurotoxicity or brain injury potential of other nanomaterials, was not mentioned in the papers reviewed here.
GFNs entry paths
GFNs reach various locations through blood circulation or biological barriers after entering the body, which results in varying degrees of retention in different organs. Due to their nanosize, GFNs can reach deeper organs by passing through the normal physiological barriers, such as the blood-air barrier, blood-testis barrier, blood-brain barrier and blood-placental barrier.
Blood-air barrier
The lungs are a potential entrance for graphene nanoparticles into the human body through airway. The inhaled GO nanosheets can destroy the ultrastructure and biophysical properties of pulmonary surfactant (PS) film, which is the first line of host defense, and emerge their potential toxicity [54]. The agglomerated or dispersed particles deposit on the inner alveolar surface within the alveoli and then be engulfed by alveolar macrophages (AMs) [55]. Clearance in the lungs is facilitated by the mucociliary escalator, AMs, or epithelial layer [56–58]. However, some small, inhaled nanoparticles infiltrate the intact lung epithelial barrier and can then transiently enter the alveolar epithelium or the interstitium [59, 60]. Intratracheally instilled graphene can redistribute to the liver and spleen by passing through the air-blood barrier [61]. The study of blood-air barrier may draw an intensive attention, since the researchers and workers occupational exposure of GFNs usually through inhalation. To make clear how the blood-air barrier plays a role in the toxicity of GFNs may become a research hot topic.
Blood-brain barrier
The intricate arrangement of the blood-brain barrier, consisting of numbers of membrane receptors and highly selective carriers, only exerts subtle influence on blood circulation and the brain microenvironment compared to the peripheral vascular endothelium [62]. The research on the mechanism of blood-brain barrier had made some progress involved in diseases and nanotoxicity. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) revealed that rGO, with an average diameter of 342 ± 23.5 nm, permeated through the paracellular pathway into the inter-endothelial cleft in a time-dependent manner by decreasing the blood-brain barrier paracellular tightness [63]. In addition, graphene quantum dots (GQDs), with a small size of less than 100 nm, can cross through the blood-brain barrier [64]. Studies on how graphene materials pass through the blood-brain barrier and cause neurotoxicity are very rare, and more data are needed to draw a conclusion.
Blood-testis barrier
The blood-testis and blood-epididymis barriers are well known for being some of the tightest blood-tissue barriers in the mammalian body [65]. GO particles with diameters of 54.9 ± 23.1 nm had difficulty penetrating the blood-testis and blood-epididymis barriers after intra-abdominal injection, and the sperm quality of the mice was not obviously affected even at 300 mg/kg dosage [66].
Blood-placenta barrier
The placental barrier is indispensable in maintaining pregnancy, as it mediates the exchange of nutrients and metabolic waste products, exerts vital metabolic functions and secretes hormones [67]. A recent review suggested that the placenta does not provide a tight barrier against the transfer of nanoparticles to foetuses, specifically against the distribution of carbonaceous nanoparticles to and in the foetus [42]. It was suggested that rGO and gold particles (diameter of 13 nm) are barely present or are absent in the placenta and foetus in late gestation after intravenous injection [44, 68]. However, other reports showed that transplacental transfer does occur in late gestational stages [69, 70]. Much attention had been paid to the developmental toxicity of nanomaterials, and reports showed that many nanoparticles did cross the placental barrier and strongly influenced the development of embryos [71–75]. But studies of the exposure to graphene materials through the placenta barrier are deficient, and how these particles transfer to embryos should be evaluated in detail in the future.
These four barriers were the most frequently mentioned barriers in the literature, and other barriers have not been evaluated in recent studies, such as skin barriers, which have not been mentioned in any of the hundreds of GFNs toxicity studies searched. Moreover, the mechanism by which GFNs pass through these barriers is not well understood, and more systematic investigations are urgently needed.
Distribution and excretion of GFNs in tissue
The absorption, distribution, and excretion of graphene nanoparticles may be affected by various factors including the administration routes, physicochemical properties, particle agglomeration and surface coating of GFNs.
The different administration routes influence the distribution of GFNs, for example, intratracheally instilled FLG passing through the air-blood barrier mainly accumulated and was retained in the lungs, with 47 % remaining after 4 weeks [61]. Intravenously administered GO entered the body through blood circulation and was highly retained in the lung, liver, spleen and bone marrow, and inflammatory cell infiltration, granuloma formation and pulmonary edema were observed in the lungs of mice after intravenous injection of 10 mg kg/body weight GO [49]. Similarly, high accumulation of PEGylated GO derivatives was observed in the reticuloendothelial (RES) system including liver and spleen after intraperitoneal injection. In contrast, GO-PEG and FLG did not show detectable gastrointestinal tract absorption or tissue uptake via oral administration [31].
The different properties of GFNs, such as their size, dose and functional groups, always lead to inconsistent results in the distribution profiles of graphene. For instance, Zhang et al. found that GO was mainly entrapped in mouse lungs [49]; however, Li et al. observed that GO accumulated in mouse liver [76]. Notably, small GO sheets, with diameters of 10–30 nm, were mainly distributed in the liver and spleen, whereas larger GO sheets (10–800 nm) mainly accumulated in the lungs [49, 52, 77]. If the size of GO is larger than the size of the vessels, GO usually becomes stuck in the arteries and capillaries in the proximity of the injection site. The accumulation of GO in the lungs was shown to increase with an increase in the injected dose and size, but that in the liver significantly decreased [78]. Coating biocompatible polymers onto GO also affects the biodistribution, for instance, the intravenous injection of GO-PEG and GO-dextran (GO-DEX) accumulate in the reticuloendothelial system (RES), including the liver and spleen, without short-term toxicity [31, 79]. Moreover, the charge of plasma proteins and adsorption of GO by plasma proteins also affects the biodistribution [34].
The excretion and clearance of GFNs vary in different organs. In the lungs, observations indicated that NGO is drawn into and cleared by AMs, which might be eliminated from the sputum through mucociliary clearance or other ways [57], and 46.2 % of the intratracheally instilled FLG was excreted through the faeces 28 d after exposure [61]. In the liver, nanoparticles can be eliminated thorough the hepato-biliary pathway following the biliary duct into the duodenum [80]. In addition, PEGylated GNS that mainly accumulates in the liver and spleen can be gradually cleared, likely by both renal and faecal excretion. As recently reviewed, GO sheets larger than 200 nm are trapped by splenic physical filtration, but small sizes (approximately 8 nm) can penetrate the renal tubules into the urine and be rapidly removed without obvious toxicity [81]. The excretion paths of GFNs have not yet been clearly explained, but renal and faecal routes appear to be the main elimination routes for graphene.
Recently, the distribution and excretion/toxicity strategy has become an important part of nano-toxicological studies. To date, several controversial results regarding the distribution and excretion of graphene in vivo have been reported in several papers, and a systematic evaluation of the toxicokinetics of GFNs is still needed. The metabolism and excretion of nanomaterials are long-period processes, however, the recent studies of GFNs had been limited to short-term toxicological assessments, and the long-term accumulation and toxicity of GFNs on different tissues remain unknown. Therefore, long-term studies on the deposition and excretion of GFNs need to be performed using different cells and animals to ensure the materials’ biosafety before utilization in human biomedical applications.
Uptake and location of GFNs in cells
The uptake and location of GFNs have also been observed to exert different effects in different cell lines. Graphene is taken up into cells via various routes [82, 83]. Basically, the physicochemical parameters such as the size, shape, coating, charge, hydrodynamic diameter, isoelectric point, and pH gradient are important to allow GO to pass through the cell membrane [84]. As stated previously, nanoparticles with diameters <100 nm can enter cells, and those with diameters <40 nm can enter the nucleus [85]. For example, GQDs possibly penetrate cell membranes directly, rather than through energy-dependent pathways [86, 87]. Larger protein-coated graphene oxide nanoparticles (PCGO) (~1 μm) enter cells mainly through phagocytosis, and smaller PCGO nanoparticles (~500 nm) enter cells primarily through clathrin-mediated endocytosis [88]. GO sheets could adhere and wrap around the cell membrane, insert in the lipid bilayer or be internalized into the cell as a consequence of interactions with cells [89]. Similarly, PEGylated reduced graphene oxide (PrGO) and rGO were shown to adhere onto the lipid bilayer cell membrane prominently due to the interaction of hydrophobic, unmodified graphitic domains with the cell membrane [90, 91]. Consequently, it was suggested that prolonged exposure to or a high concentration of graphene induces physical or biological damage to the cell membrane, along with destabilization of actin filaments and the cytoskeleton [92].
Current data demonstrates that GO sheets interact with the plasma membrane and are phagocytosed by macrophages. Three major receptors on macrophages take part in the phagocytosis of GNS: the Fcg receptor (FcgR), mannose receptor (MR), and complement receptor (CR). Furthermore, FcgR is a key receptor in the mediated phagocytic pathway [90, 93, 94]. The protein corona of GO promotes the recognition by macrophage receptors, especially the IgG contained within the protein corona. Macrophages were observed to undergo prodigious morphological changes upon contact with GO [34]. After internalization, graphene accumulated in the cell cytoplasm, perinuclear space, and nucleus, which induced cytotoxicity in murine macrophages by increasing intracellular ROS through depletion of the mitochondrial membrane potential and by triggering apoptosis through activation of the mitochondrial pathway [83]. The possible interactions and accumulation sites of GFNs are summarized in Fig. 1.
Fig. 1
figure1
Graphene materials and their biological interactions. (A) A parameter space for the most widely used graphene materials can be described by the dimensions and surface functionalization of the material, the latter defined as the percentage of the carbon atoms in sp3 hybridization. Green squares represent epitaxially grown graphene; yellow, mechanically exfoliated graphene; red, chemically exfoliated graphene; blue, graphene oxide. Note that a number of other graphene-related materials (such as graphene quantum dots and graphene nanoribbons) are also being used in experiments. (B) Possible interactions between graphene-related materials with cells (the graphene flakes are not to scale). (a) Adhesion onto the outer surface of the cell membrane. (b) Incorporation in between the monolayers of the plasma membrane lipid bilayer. (c) Translocation of membrane. (d) Cytoplasmic internalization. (e) Clathrin-mediated endocytosis. (f) Endosomal or phagosomal internalization. (g) Lysosomal or other perinuclear compartment localization. (h) Exosomal localization. The biological outcomes from such interactions can be considered to be either adverse or beneficial, depending on the context of the particular biomedical application. Different graphene-related materials will have different preferential mechanisms of interaction with cells and tissues that largely await discovery. [90] Copyright (2014), with permission from American Association for Advancement of Science
Full size image
Toxicity of GFNs in organs
The toxicity and biocompatibility of GFNs has been observed and assessed through theoretical and animal model studies. At present, there are a mass of data demonstrating the toxicity of GFNs in different organs or systems in animals, so that it is hard to list all the data in this review. Thus we summarized a certain number literature and chose some in vivo toxicological studies of GFNs listed in Table 1.
Table 1 Toxicity of GFNs in organs
Full size table
Toxicity in internal organs
GO can result in acute inflammation response and chronic injury by interfering with the normal physiological functions of important organs [32, 81]. Oral gavage experiments did not show detectable absorption of GO through the gastrointestinal tract [95]. Interesting, a low dose of GO caused serious damage to the gastrointestinal tract after maternal mice drank a GO suspension rather than a high-dose of GO because a low dose of GO without agglomeration can easily attach to the gastrointestinal surface and cause destruction through its abundant sharp edges [53]. GFNs caused inflammation and remained in the lung on day 90 after a single intratracheal instillation, and even translocated to lung lymph nodes by a nose-only inhalation [96, 97]. A high dose of GO that forms aggregations can block pulmonary blood vessels and result in dyspnea [50, 98], and platelet thrombi were observed at high concentrations of 1 and 2 mg/kg body weight via intravenous injection [89]. GO reportedly disrupted the alveolar-capillary barrier, allowing inflammatory cells to infiltrate into the lungs and stimulate the release of pro-inflammatory cytokines [99]. Fibrosis and inflammation could be verified by the increased levels of the protein markers collagen1, Gr1, CD68 and CD11b in the lungs. The use of Tween 80 to disperse FLG or a pluronic surfactant to disperse graphene was suggested to reduce the likelihood of lung fibrosis formation in cells or mice, whereas lung fibrosis was observed when graphene was suspended with bovine serum albumin (BSA) [100]. In addition, radioactive isotopes can be delivered into the lungs, accompanied by a depth distribution of 125I-NGO in the lungs, and the isotopes might deposit there and result in mutations and cancers [30]. However, recent publications claimed no obvious pathological changes in mice exposed to low dosages of GO and functionalized graphene by intravenous injection, including aminated GO (GO-NH2), poly(acrylamide)-functionalized GO (GO-PAM), poly(acrylic acid)-functionalized GO (GO-PAA) and GO-PEG; only GO-PEG and GO-PAA induced less toxicity than pristine GO in vivo [31, 79, 89]. So the functional groups of GFNs and the working concentration or aggregate state largely influence the toxicity of GFNs. Recently, the ways to modify the functional group of GFNs, decrease the working concentration or change the aggregate condition are usually used to decrease the toxicity of GFNs.
Toxicity in the central nervous system
Graphene has largely benefited neurosurgery with the application of drug/gene delivery for brain tumour treatment, intracranial and spinal biocompatible devices, biosensing and bioimaging techniques. Studies regarding the potentialities or risks of graphene in the brain have emerged. In the chicken embryo model, pristine graphene flakes decreased the ribonucleic acid level and the rate of deoxyribonucleic acid synthesis, leading to harmful effects on brain tissue development and the atypical ultrastructure was observed in the brain [101]. The recent researches of GFNs in the central nervous system are mostly involved in the application rather than the toxicity. The data of the toxic study on GFNs is underway.
Toxicity in reproduction and development system
Pristine graphene reduced the vascularization of the heart and the density of branched vessels after injection into fertilized chicken eggs followed by incubation for 19 d [101]. GO and rGO damage zebrafish embryos by influencing the embryo hatching rate and body length in a concentration-dependent manner. Although no obvious malformation or mortality was observed in exposed zebrafish embryos [102], GO adhered to and was wrapped in the chorion of the zebrafish embryos, causing remarkable hypoxia and hatching delay. GO aggregates were retained in many organelles, such as the eyes, heart, yolk sac, and tail of the embryos, and apoptosis and reactive oxygen species (ROS) generation were observed in these regions [103].
The GFNs exert different toxicological effects on male or female reproductive system. Data showed that GO exerted very low or nearly no toxic effects on male reproduction even at a high dose via intra-abdominal injection [66]. Additionally, rGO did not change the serum estrogen levels of non-pregnant female mice. The condition is different in the female mouse: mouse dams could give birth to healthy offspring after rGO injection before mating or during early gestation, and only a few abnormal foetuses were present among the rGO-injected dam litters. However, the pregnant mice had abortions at all dose, and most pregnant mice died when the high dose of rGO was injected during late gestation [44]. Notably, the development of offspring in the high dosage group was delayed during the lactation period. The high dose of GO decreased the maternal mice’s water consumption by oral exposure, which reduced milk production and thus postponed the growth of offspring [53]. Though the findings indicate that GFNs are potentially harmful to development, but data on reproductive and developmental toxicity are still deficient. Studies of the influence of GFNs on male and female reproduction and development are still required to elucidate the underlying toxicity mechanism.
Influence of haemocompatibility
GO release into the blood is ineluctable. The haemocompatibility of GO was found to be dependent on the functional coating and the exposure conditions. GO with submicron size resulted in the greatest haemolytic activity, while aggregated graphene induced the lowest haemolytic reaction. Pristine graphene and GO demonstrated haemolytic effect up to 75 μg/mL [104]. GO-polyethylenimine (GO-PEI) exhibited notable toxicity by binding to HSA, even at 1.6 μg/mL [105]. Carboxylated graphene oxide (GO-COOH) showed significant cytotoxicity toward T lymphocytes at concentrations above 50 μg/mL and had good biocompatibility below 25 μg/mL, whereas GO-chitosan nearly inhibited haemolytic activity [106]. Until now, the corresponding risk of haemocompatibility has remained largely unknown.
In conclusion, the lung injury induced by GFNs has been studied in several studies, the results of which have demonstrated inflammatory cell infiltration, pulmonary edema and granuloma formation in the lungs. However, only a few specific studies have evaluated in other organs, such as the liver, spleen, and kidney, and the injury symptoms, damage index and level of damage to these internal organs were not fully investigated. Moreover, studies on the neurotoxicity of GFNs are quite rare; no data has revealed which nerves or brain areas experience damage, nor have the related behavioural manifestations been studied. The developmental toxicity of GFNs may induce structural abnormalities, growth retardation, behavioural and functional abnormalities, and even death. A study on the reproductive and developmental toxicity of GFNs will be extremely significant and gain extensive attention in the future. Almost all the GFNs toxicity studies were short-period experiments, and no studies have investigated long-term chronic toxic injury. However, based on studies of other nanomaterials toxicity, long-term GFNs exposure may be an important factor harming health [107–109]. Therefore, the long-term study of GFNs is necessary.
Toxicity of GFNs in cell models
The cytotoxicity of GFNs in vitro has been verified in various cells to change the cell viability and morphology, destroy the membrane integrity, and induce DNA damage [110–112]. GO or rGO decrease cell adhesion; induce cell apoptosis; and enter lysosomes, mitochondria, cell nuclei, and endoplasm [113]. GQDs entered cells and induced DNA damage by the increased expression of p53, Rad 51, and OGG1 proteins in NIH-3 T3 cells [87]. However, GQDs did not pose significant toxicity to human breast cancer cell lines (at a dose of 50 μg/mL) or human neural stem cells (at a dose of 250 μg/mL) [114, 115]. GO derivatives dramatically decreased the expression of differential genes that are responsible for the structure and function of the cell membrane, such as regulation of the actin cytoskeleton, focal adhesion and endocytosis [89]. In rat pheochromocytoma cells (PC12 cells), graphene and rGO caused cytotoxic effects and mitochondrial injury, such as the release of lactate dehydrogenase (LDH), an increase in the activation of caspase-3, and the generation of ROS [82, 116].
Graphene can increase cell viability [117] or cause cell death [118] depending on the cell line, type of graphene material and the doseage. GO cytotoxicity was observed in human fibroblasts and lung epithelial cells at concentrations above 20 μg/mL after 24 h, but minimal toxicity was found in A549 cells at concentrations higher than 50 μg/mL [119]. The biological responses induced by GO such as ROS, malondialdehyde (MDA), and LDH increased, whereas superoxide dismutase (SOD) decreased dose-dependently in HeLa cells [120]. However, GO-molecular beacon (GO-MB) showed low cytotoxicity even at 20 μg/mL in HeLa cells [121]. GO decreased the viability of A549 cells, while the same concentration and time of exposure increased the cell viability of CaCo2 colorectal carcinoma cells [122]. Another study reported that GO dramatically enhanced the differentiation of SH-SY5Y, accompanied by increasing neurite length and the expression of neuronal marker MAP2 at low concentrations but that GO suppressed the viability of SH-SY5Y cells at high doses (≥80 mg/mL) [123]. Functionalized coatings on GO, such as GO-PEG [124] and GO-chitosan [125], can profoundly attenuate the particles’ cytotoxicity by inhibiting the interactions between cells.
The toxicity of GFNs in vitro is summarized in Table 2. Data on the cytotoxicity of graphene nanomaterials are contrasting, and varying characteristics influence the results. The mechanisms and influencing factors of toxicity need to be elucidated in detail.
Table 2 Toxicity of GFNs in cell models
Full size table
Origins of GFNs toxicity
Reportedly, the characteristics of graphene, including its concentration, lateral dimension, surface structure, functional groups, purity and protein corona, strongly influence its toxicity in biological systems [2, 7, 104, 126–129].
Concentration
Numerous results have shown that graphene materials cause dose-dependent toxicity in animals and cells, such as liver and kidney injury, lung granuloma formation, decreased cell viability and cell apoptosis [130–134]. In vivo studies, GO did not exhibit obvious toxicity in mice exposed to a low dose (0.1 mg) and middle dose (0.25 mg) but induced chronic toxicity at a high dose (0.4 mg). The high content of GO mainly deposited in the lungs, liver, spleen, and kidneys and was difficult to be cleaned by the kidneys via a single tail vein injection [135]. Intriguingly, increasing the dose resulted in a dramatic decrease in the hepatic uptake but an increase in the pulmonary uptake of s-GO by intravenous injection [31], because the high dose of GO potentially surpassed the uptake saturation or depleted the mass of plasma opsonins, which consequently suppressed the hepatic uptake. Moreover, an in vitro study reported that 20 μg/mL GO nanosheets exhibited no cytotoxicity in A549 within 2 h of incubation, but a higher concentration (85 μg/mL) decreased the cell viability to 50 % within 24 h [136, 137]. Lü et al. also demonstrated that GO had no obvious cytotoxicity at low concentrations for 96 h in a human neuroblastoma SH-SY5Y cell line, but the viability of cells sharply decreased to 20 % after treatment with 100 mg/mL GO for 96 h of incubation [123]. The results in HeLa cells, NIH-3 T3 cells, and breast cancer cells (SKBR3, MCF7) treated with graphene nanoribbons also showed a dose- (10–400 mg/ml) and time-dependent (12–48 h) decrease in cell viability [138]. Increasing concentrations of GO entered the lysosomes, mitochondria, endoplasm, and cell nucleus [119]. Several data indicated that rGO caused apoptosis-mediated cell death at a lower dose and early time point but that necrosis was prevalent with the increase in time/dose [110, 135].
Lateral dimension
Nanoparticles with sizes <100 nm can enter the cell, <40 nm can enter nucleus, and smaller than <35 nm can cross the blood brain barrier [85]. One study showed that GO (588, 556, 148 nm) did not enter A549 cells and had no obvious cytotoxicity [112]. When the diameter of graphene is between 100 ~ 500 nm, the smallest size may cause the most severe toxicity, and when the diameter is below 40 nm, the smallest sizes may be the safest. For instance, rGO with a diameter of 11 ± 4 nm could enter into the nucleus of the hMSCs and cause chromosomal aberrations and DNA fragmentation at very low concentrations of 0.1 and 1.0 mg/mL in 1 h. However, rGO sheets with diameters of 3.8 ± 0.4 nm exhibited no notable genotoxicity in hMSCs even at a high dose of 100 mg/mL after 24 h [118].
In an in vivo study, s-GO (100–500 nm) preferentially accumulated in the liver, whereas l-GO (1–5 μm) was mainly located in the lungs because l-GO formed larger GO-protein complexes that were filtered out by the pulmonary capillary vessels after intravenously injection [31]. Given the relative lateral sizes (205.8 nm, 146.8 nm and 33.78 nm) of the three GO nanosheets at the same concentration, smaller GO experiences much greater uptake than larger GO in Hela cells [139]. The high uptake of s-GO changed in the microenvironment of cells and consequently induced the greatest viability loss and most serious oxidative stress among three sizes of GO samples [119]. As a result, one study delineated that GO size-dependently induced the M1 polarization of macrophages and pro-inflammatory responses in vitro and in vivo. Larger GO showed stronger adsorption onto the plasma membrane with less phagocytosis, eliciting robust interactions with TLRs and activating NF-κB pathways, compared to smaller GO sheets, which were more likely taken up by cells [94]. To further uncover the detailed mechanism underlying these effects, more studies are needed to illustrate the vital mechanism of the lateral size of graphene materials.
Surface structure
GFNs possess widely varying surface chemistries. For example, the pristine graphene surface is hydrophobic, GO surface is partially hydrophobic with carboxylate groups [140–142], and rGO has intermediate hydrophilicity [143]. GFNs were observed to disrupt the function and structure of cell membranes and proteins probably by exceptionally strong molecular interactions with cells [2, 91]. For instance, rGO bonded to cell membranes, stimulated receptors and activated mitochondrial pathways, inducing apoptosis [110, 111, 144]. Limited evidence showed that GO is smaller and less toxic than rGO because of the high oxygen content, smoother edges, and hydrophilic properties of the former species [104, 145, 146]. Because of the different surface oxidation states of GO and rGO, GO possessing distinct hydrophilicity might be internalized and taken up by HepG2 cells easily. On the contrary, rGO with evident hydrophobicity, could be adsorbed and aggregated at cell surfaces without (or with lower) uptake [110]. Due to strong π-π stacking interactions, graphene is highly capability of breaking many residues of the protein, particularly the aromatic ones, such as the villin headpiece (HP), F10, W23, and F35. The protein’s secondary and tertiary structures are largely lying on the graphene surface, disrupting the structure and function of the protein [41] (Fig. 2). In addition, GO can insert between the base pairs of double-stranded DNA and disturb the flow of genetic information at the molecular level, which might be one of the main causes of the mutagenic effect of GO [7, 112, 146, 147].
Fig. 2
figure2
A representative trajectory of HP35 adsorbing onto the graphene. (a) Representative snapshots at various time points. The proteins are shown in cartoons with red helix and green loop, and the graphene is shown in wheat. The aromatic residues that form the π-π stacking interactions are shown in blue, others are shown in green. (b) The contacting surface area of HP35 with the graphene. (c) The RMSD of HP35 from its native structure and the number of residues in the α-helix structure. Here, the secondary structures are determined by the DSSP program. (d) The distance between the graphene and the aromatic residues, including F35, W23, F10, F17, and F06. To show the adsorbing process clearer, the χ-axis had been truncated and rescaled. [41] Copyright (2011), with permission from Journal of Physical of Chemistry
Full size image
Charge
A number of studies have highlighted the importance of the GO surface charge because of its ability to affect the internalization and uptake mechanism of cells [148–150]. GO internalization was negligible in non-phagocytes, which was likely due to the strong electrostatic repulsion between the negatively charged GO and the cell surface [34]. However, others have suggested that negatively charged nanoparticles can be internalized into non-phagocytic cells by binding to available cationic sites on the cell surface and be taken up by scavenger receptors [110, 146, 150]. GO/GS particles reportedly cause morphological changes and significant lysis, leading to high haemolysis in red blood cells (RBCs). RBC membrane disruption is probably attributed to the strong electrostatic interactions between the negatively charged oxygen groups on the GO/GS surface and positively charged phosphatidylcholine lipids on the RBC outer membrane [106].
Functionalization
Studies confirmed that functionalization with PEG [52], PEGylated poly-L-lysine (PLL) [151], poly(ε-caprolactone) [152], polyvinyl alcohol [3], Pluronic [153], amine [98], carboxyl, and dextran [79] groups largely decreases the toxicity and improves the biocompatibility of graphene. In vivo results revealed that only mild chronic inflammation emerged after the subcutaneous injection of GO-Pluronic hydrogel and no noticeable short-term toxicity was tested after the intravenous injection of GO-DEX [79, 154]. PEGylated GS did not induce appreciable toxicity in mice exposed to 20 mg/kg for 3 months, as evaluated by blood biochemistry and histological examinations, and showed relatively low retention in the RES [52, 155]. Coating GO with chitosan almost eliminated the haemolytic activity in blood [39]. Moreover, the PEG coating effectively alleviated GO-induced acute tissue injuries; decreased GO aggregation and retention in the liver, lungs, and spleen; and promoted the clearance of GO [81], GO-DEX [79], and fluorinated graphene oxide (FGO) [156].
In vitro, several cell function assays showed clear evidence that the surface functionalization of pristine graphene or GO was critical for reducing the strong toxicity effects [91]. PEG-GO, PEI-GO and LA-PEG-GO damaged human lung fibroblast cells less than GO [148]. PEG-GO exhibited no cytotoxicity toward several cell cultures, such as glioblastoma cells (U87MG), breast cancer cells (MCF-7), human ovarian carcinoma cells (OVCAR-3), colon cancer cells (HCT-116), and lymphoblastoid cells (RAJI), at concentrations up to 100 μg/mL [119, 157, 158]. GQDs-PEG exhibited very low or no toxicity against lung and cervical cancer cells even at very high concentrations (200 μg/mL) [159]. However, as a non-biodegradable material with great potential for cellular internalization, further investigation is needed to assess the possible long-term adverse effects of functionalized graphene.
Aggregations and sedimentation
Reportedly, nanomaterials have a propensity to form aggregates rather than individual units, particularly under physiological conditions. GS surfaces allowed fewer RBCs attach comparing to GO, and GS had the lower haemolytic activity for more aqueous aggregations formation. In contrast, the fast sedimentation and aggregate formation of GS greatly inhibited the nutrient availability of human skin fibroblast cells that were grown on the bottom of wells [106]. Therefore, the aggregations and sedimentation of graphene particles exert varying effects on different cells.
Impurities
Nanomaterial purity is an important consideration because residual, contaminating metals may be responsible for the observed toxicity, rather than the nanomaterial itself, which has resulted in conflicting data on GFNs cytotoxicity [35, 160]. Traditionally prepared GO often contains high levels of Mn2+ and Fe2+, which are highly mutagenic to cells. The nonspecific release of these ions from traditionally prepared GO might lead to unusually high levels of cytotoxicity and DNA fracturing [39]. In particular, Peng et al. [161] produced high-purity GO containing only 0.025 ppm Mn2+ and 0.13 ppm Fe2+, and Hanene et al. [162] invented a new method to prepare high-purity, single-layer GO sheets with good aqueous dispersibility and colloidal stability. GO produced by these new methods did not induce significant cytotoxic responses (at exposure doses up to 100 μg/mL) in vitro, and no obvious inflammatory response or granuloma formation (exposure doses up to 50 μg/animal) were observed in vivo. Therefore, the purity of GFNs deserves attention and is a vital step towards the determination of GFNs involved in bioapplications.
Protein corona effect
Because of the high free surface charge, nanomaterials can easily form “coronas” with proteins in biological systems [163, 164]. The protein corona is suggested to affect the circulation, distribution, clearance and toxicity of nanoparticles. Several papers reported that GO forms GO-protein coronas with adsorbed plasma proteins in serum and these GO-protein coronas play an important role in deciding the fate of the GO biokinetic behaviour in vivo. Such GO-protein coronas can regulate the adhesion of GO to endothelial and immune cells through both specific and nonspecific interactions [165]. Basically, immunoglobulin G and complement proteins in the protein corona help to reorganize nanoparticles in immune cells, causing the particles to be engulfed by the RES, and IgG-coated GO was taken up by either specific or nonspecific interactions with cell membrane receptors [31, 165]. However, another study found that GO could not adhere to mucosal epithelial cells directly in the intestinal tract after the filial mice drank an aqueous GO solution because abundant proteins in the milk had adsorbed on the surface of the GO and thus inhibited their direct interaction with the mucosal epithelial cells [53]. Protein corona mitigated the cytotoxicity of GO by limiting its physical interaction with the cell membrane and reducing the cellular morphological damage in HeLa, THP-1 and A549 cells [166–168]. The cytotoxic effect was largely reduced when GO was pre-coated with FBS and incubated with cells; nearly ∼ 90 % survival was observed with 100 μg/mL FBS-coated GO and 100 % survival with 20 μg/mL FBS-coated GO. Similar trends were observed for GO covered by BSA [166, 169]. Consistently, additional serum could neutralize the toxicity of pristine GO in J774.A1 cells at a dose of 4 μg/mL, which lead to a decrease in cell number of 52.5 % compared to untreated cells [89].
After reviewing many studies, it can be concluded that the toxicity of graphene is influenced by multiple factors. Those factors combined to largely change the toxicity of GFNs in many cases. Scientific studies often need the clear identification of cause and effect, which should keep only one factor different at a time, so that the effect of that single factor can be determined. But in some papers, several factors influencing GFNs toxicity were studied at the same time, which led to confused results.
Possible toxicity mechanisms of GFNs
Although some physicochemical properties and the toxicity of GFNs have been well studied by many scholars, the exact mechanisms underlying the toxicity of GFNs remain obscure. A schematic of the main mechanisms of GFNs cytotoxicity is illustrated in Fig. 3.
Fig. 3
figure3
Schematic diagram showed the possible mechanisms of GFNs cytotoxicity. GFNs get into cells through different ways, which induce in ROS generation, LDH and MDA increase, and Ca2+ release. Subsequently, GFNs cause kinds of cell injury, for instance, cell membrane damage, inflammation, DNA damage, mitochondrial disorders, apoptosis or necrosis
Full size image
Physical destruction
Graphene is a unique nanomaterial compared with other spherical or one-dimensional nanoparticles due to its two-dimensional structure with sp2-carbons. The physical interaction of graphene nanoparticles with cell membranes is one of the major causes of graphene cytotoxicity [7, 170, 171]. Graphene has high capability to bind with the α-helical structures of peptides because of its favourable surface curvature [172]. At concentration above 75 μg/mL, pristine graphene largely adhered to the surfaces of RAW 264.7 cells and resulted in abnormal stretching of the cell membrane [104]. The strong hydrophobic interactions of GFNs with the cell membrane lead to the morphological extension of F-actin filopodial and cytoskeletal dysfunction. Furthermore, the sharpened edges of GNS may act as ‘blades’, inserting and cutting through bacterial cell membranes [173]. Moreover, GO also damaged the outer membrane of E. coli bacteria directly, resulting in the release of intracellular components [173]. However, TEM imaging revealed that pre-coating GO with FBS eliminated the destruction of cell membranes [166].
ROS production leading to oxidative stress
Oxidative stress arises when increasing levels of ROS overwhelm the activity of antioxidant enzymes, including catalase, SOD, or glutathione peroxidase (GSH-PX) [174]. ROS act as second messengers in many intracellular signalling cascades and lead to cellular macromolecular damage, such as membrane lipid breakdown, DNA fragmentation, protein denaturation and mitochondrial dysfunction, which greatly influence cell metabolism and signalling [175–177]. The interactions of GO with cells can lead to excessive ROS generation, which is the first step in the mechanisms of carcinogenesis, ageing, and mutagenesis [83, 122]. Oxidative stress had a significant role in GO-induced acute lung injury [30], and the inflammatory responses caused by oxidative stress often emerged upon exposure to GFNs [133, 177, 178]. The activity of SOD and GSH-PX decreased after exposed to GO in a time- and dosage-dependent manner [82, 106, 119]. Similarly, oxidative stress was the key cause of apoptosis and DNA damage after HLF cells were exposed to GO [148]. Both the mitogen-activated protein kinase (MAPK) (JNK, ERK and p38) and TGF-beta-related signalling pathways were triggered by ROS generation in pristine graphene-treated cells, accompanied by the activation of Bim and Bax, which are two pro-apoptotic members of the Bcl-2 protein family. As a result, caspase-3 and its downstream effector proteins such as PARP were activated, and apoptosis was initiated [83, 179]. Detailed information regarding the MAPK-, TGF-β- and TNF-α-related signalling pathways, which induce inflammation, apoptosis and necrosis, are summarized in Fig. 4.
Fig. 4
figure4
Schematic diagram of MAPKs, TGF-beta and TNF-α dependent pathways involved in GFNs toxicity. ROS was the main factors activating the MAPKs and TGF-beta signaling pathways to lead to the activation of Bim and Bax, triggering the cascade of caspases and JNK pathway. The activation of caspase 3 and RIP1 resulted in apoptosis and necrosis finally
Full size image
Mitochondrial damage
Mitochondria are energy production centres involved in various signalling pathways in cells and are also a key point of apoptotic regulation [83]. After exposure to GO and carboxyl graphene (GXYG), the mitochondrial membrane was depolarized, and the amount of mitochondria decreased in HepG2 cells [180]. Exposure to GFNs resulted in significantly increased coupled and uncoupled mitochondrial oxygen consumption, dissipation of the mitochondrial membrane potential, and eventual triggering of apoptosis by activating the mitochondrial pathway [181]. For instance, GO increased the activity of mitochondrial electron transport complexes I/III and the supply of electrons to site I/II of the electron transport chain, accelerating the generation of ROS during mitochondrial respiration in MHS cells [99]. The formation of •OH mediated by GO and the cytochrome-c/H2O2 electron-transfer system could enhance oxidative and thermal stress to impair the mitochondrial respiration system and eventually result in dramatic toxicity [151]. Additionally, the oxygen moieties on GO might accept electrons from cellular redox proteins, supporting the redox cycling of cytochrome c and electron transport proteins, and cytochromes MtrA, MtrB, and MtrC/OmcA might be involved in transferring electrons to GO [182]. Therefore, except for the plasma membrane damage and oxidative stress induction, GFNs can cause apoptosis and/or cell necrosis by direct influencing cell mitochondrial activity [183, 184].
DNA damage
Due to its small size, high surface area and surface charge, GO may possess significant genotoxic properties and cause severe DNA damage, for example, chromosomal fragmentation, DNA strand breakages, point mutations, and oxidative DNA adducts and alterations [87, 122, 185, 186]. Mutagenesis was observed in mice after intravenous injection of GO at a dose of 20 mg/kg compared with cyclophosphamide (50 mg/kg), a classic mutagen [112]. Even if GO cannot enter into the nucleus of a cell, it may still interact with DNA during mitosis when the nuclear membrane breaks down, which increases the opportunity for DNA aberrations [87, 147, 187, 188]. The π stacking interaction between the graphene carbon rings and the hydrophobic DNA base pairs can make a DNA segment ‘stand up’ or ‘lay on’ the surface of graphene with its helical axis perpendicular or parallel, respectively. The intermolecular forces severely deform the end base pairs of DNA, which potentially increases the genotoxicity [189]. GO may also induce chromosomal fragmentation, DNA adducts and point mutations by promoting oxidative stress or triggering inflammation through the activation of intracellular signalling pathways such as MAPK, TGF-β and NF-κB [110, 112, 146]. Graphene and rGO can also elevate the expression of p53, Rad51, and MOGG1-1, which reflect chromosomal damage, and decrease the expression of CDK2 and CDK4 by arresting the cell cycle transition from the G1 to the S phase in various cell lines [112]. DNA damage can not only initiate cancer development but also possibly threaten the health of the next generation if the mutagenic potential of GO arises in reproductive cells, which impacts fertility and the health of offspring [112, 190].
Inflammatory response
GFNs can cause a significant inflammatory response including inflammatory cell infiltration, pulmonary edema and granuloma formation at high doses via intratracheally instillation or intravenous administration [30, 49]. Platelets are the important components in clot formation to attack pathogens and particulate matter during the inflammatory response, and GO could directly activate platelet-rich thrombi formation to occlude lung vessels after intravenous injection [98, 191]. A strong inflammatory response was induced by subcutaneously injection with GO for 21 days, along with the secretion of key cytokines, including IL-6, IL-12, TNF-α, MCP-1, and IFN-g [34, 192]. GFNs can trigger an inflammatory response and tissue injury by releasing cytokines and chemokines that lead to the recruitment of circulating monocytes and stimulating the secretion of Th1/Th2 cytokines and chemokines [124, 193]. Additionally, pristine graphene [193] and rGO [110] evoke an inflammatory response by binding to toll-like receptors (TLRs) and activating the NF-κB signalling pathway in cells. The NF-κB signalling cascade is triggered by TLRs and pro-inflammatory cytokines such as IL-1 and TNF-α. Upon activation, NF-κB shifts from the cytoplasm to the nucleus, facilitating the binding of degrading IκB and acting as a transcription factor to synthesize numerous pro-inflammatory cytokines [194]. A schematic of the signalling pathway of TLR4 and TLR9 activated by GFNs is shown in Fig. 5.
Fig. 5
figure5
A schematic diagram elucidating signalling pathway of TLR4 and TLR9 responsible for GFNs-induced cytotoxicity. GFNs can be recognized by TLRs, thus activate IKK and IκB by a MyD88-dependent mechanism, resulting in the release of NF-κB subunits and initiating the translocation into the nucleus. Thus, pro-inflammatory factors were transcribed and secreted out of nucleus, modulating the immune responses initiating programmed autophagy, apoptosis and necrosis
Full size image
Apoptosis
Apoptosis is defined as the self-destruction of a cell regulated by genes through complicated programmes [83, 195]. GO and rGO caused apoptosis and inflammation in mice lungs after inhalation [99], and GFNs also had pro-apoptotic effects in cells [111, 113, 124, 196]. Additionally, graphene and GO physically damaged cell membranes [166], increased the permeabilization of the outer mitochondrial membrane and changed the mitochondrial membrane potential; the increased ROS triggered the MAPK and TGF-β signalling pathways and activated caspase-3 via mitochondrial-dependent apoptotic cascades, prompting the execution of apoptosis [83, 99]. Similarly, rGO caused apoptosis at a low dose and an early time point, triggered by the death-receptor and canonical mitochondrial pathway [110]. Another study showed three different apoptosis pathways by GFNs: GO led to ROS-dependent apoptosis through direct interaction with protein receptors and subsequent activation of the B-cell lymphoma-2 (Bcl-2) pathway; GO-COOH transmitted a passive apoptosis signal to nuclear DNA by binding to protein receptors and activating a ROS-independent pathway; However, GO-PEI severely damaged the membranes of T lymphocytes to trigger apoptosis [105, 197].
Autophagy
Autophagy is the process of self-degradation of cellular components and recently recognized as non-apoptotic cell death [198–200]. Autophagy activation requires autophagosome formation containing Beclin 1, multiple autophagy-related proteins (ATG), microtubule-associated protein light chain 3 (LC3) and p62 [201]. Autophagosome accumulation is associated with exposure to various nanoparticles [202–205], and autophagy can remove extracellular organisms and destruct the organisms in the cytosol [206]. GO and GQDs was shown to induce autophagosome accumulation and the conversion of LC3-I to LC3-II; inhibit the degradation of the autophagic substrate p62 protein [207, 208]. Furthermore, GO can simultaneously trigger TLR4 and TLR9 responses in macrophages [34, 192] and colon cancer cells CT26 [206]. The autophagy pathway is linked to phagocytosis by TLR signalling in macrophages [206, 209].
Necrosis
Necrosis is an alternate form of cell death induced by inflammatory responses or cellular injury. The exposure of cells to pristine graphene causes apoptosis and necrosis at high doses (50 mg/mL) [83]. Reportedly, LDH leakage and the opening of the mitochondrial permeability transition pore, induced by elevated level of cytoplasmic Ca2+, lead to apoptosis/necrosis [210]. GO treatment was revealed to induce macrophagic necrosis by activating TLR4 signalling and subsequently partly triggering autocrine TNF-α production [93]. GO combined with CDDP (GO/CDDP) triggered necrosis by decreasing RIP1 and increasing RIP3 proteins, accompanied with the release of high mobility group B1 (HMGB1) into the cytosol from the nucleus and out of CT26 cells [205, 211, 212].
Epigenetic changes
Epigenetics involve DNA methylation, genomic imprinting, maternal effects, gene silencing, and RNA editing [213–215]. DNA methylation, which is one of the best-studied epigenetic modifications, includes phosphorylation, ubiquitination, and ATP-ribosylation and can lead to chromatin remodelling [197, 216, 217]. A recently paper reported that SL-GO/FL-GO exposure resulted in global DNA hypermethylation through upregulating DNMT3B and MBD1 genes; GNP treatment caused hypomethylation by decreasing the expression of DNMT3B and MBD1 genes [216]. GO could activate the miRNA-360 regulation pathway to suppress the DNA damage-apoptosis signalling cascade by affecting the component of CEP-1 [218]. Taken together, these data suggest that GFNs could cause subtle changes in gene expression programming by modulating epigenetic changes. However, studies of GFNs-induced epigenetic changes are few, and the epigenetic mechanism caused by GFNs exposure is not fully understood.
To conclude, many studies have discussed representative mechanisms of GFNs toxicity involving four signalling pathways: TLRs, TGF-β, TNF-α and MAPKs. These four signalling pathways are correlative and cross-modulatory, making the inflammatory response, autophagy, apoptosis and other mechanisms independent and yet connected to each other. Additionally, oxidative stress appears to play the most important role in activating these signalling pathways. It has been reported that there are intersections of apoptosis, autophagy and necrosis in the studies of other nanomaterials toxicity, they inhibit or promote mutually in some conditions. However, the signalling pathways of GFNs toxicity investigated in papers to date are only a small part of an intricate web, and the network of signalling pathways needs to be explored in detail in the future.
Data gaps and future studies
Currently, the literature is insufficient to draw conclusions about the potential hazards of GFNs. Two opposite opinions have begun to emerge: some researchers suggested that graphene materials are biocompatible in a number of studies focused on biomedical applications [119, 154, 162, 219], and other studies reported adverse biological responses and cytotoxicity [32, 118, 135, 138, 192]. These inconsistent results might have been caused by several factors, including the different research groups, various cellular or animal models, and varying physicochemical characterizations of GFNs. When GFNs are explored for in vivo applications in the human body or some other biomedical applications, biocompatibility must be considered, and more detailed and accurate studies of GFNs toxicity are needed.
First, detailed physicochemical characterization is imperative in all future studies of GFNs toxicity. In the experiments, feature descriptions of GFNs should include their size, morphology, surface area, charge, surface modifications, purity, and agglomeration [88, 141, 148, 162]. Because these physicochemical factors largely influence the toxicity and biocompatibility of GFNs, single-factor experimental designs and the exclusion of other interfering factors should be considered. Details of the fabrication process should also be provided because the formed oxidative debris could largely alter the surface structure of graphene and GO during functionalization [151]. Importantly, a single, universal method needs to be established in graphene technology, which will allow for better comparison of data from different studies or different laboratories.
Second, different observational criteria, parameters and selection of experimental methods might induce large inter-laboratory variations [220, 221]. For example, the MTT assay always fails to accurately predict graphene toxicity because the spontaneous reduction results in a false positive signal. Therefore, appropriate alternative assessments should be utilized, such as the water-soluble tetrazolium salt reagent (WST-8), ROS assay, and trypan blue exclusion test [106, 222]. Additionally, the comet assay often shows higher levels of DNA damage than the micronucleus assay because the former measures the repairable injury and the latter measures the gene damage that remains after cell division [159, 223]. Therefore, caution is required in choosing the most appropriate assay to evaluate the toxicity of graphene materials to avoid false-positive results.
Third, the selection of cell lines is of vital importance because cancer cell lines tend to be sensitive or resistant depending upon their genetic background. The same graphene nanoparticles can cause different reactions depending on their various cells origins. Suitable cell lines with good stability must be used to avoid false positive or negative results. Primary cells derived from humans or animals can better simulate the health conditions of humans. A large amount of primary cells have been utilized to test the toxicity of other nanomaterials [224–228], but the culturing of primary cells is extremely rare in the experiments with GFNs to date [210, 229]. Various cell experiments combined with primary cells should be performed to comprehensively evaluate the physicochemical properties and toxicity of GFNs.
Fourth, the administration route of GFNs plays a very important role in toxicity studies, and different delivery methods will result in different toxicological reactions [32, 53]. Thus, the route and period of exposure should be carefully chosen according to the aim of the study. Nasal drug delivery is often used to study the neurotoxicity of nanomaterials [230, 231], but this administration method has rarely been applied in the testing of GFNs toxicity. Toxicological studies of GFNs in the nervous system are rare, and the mechanism is unclear and needs to be studied further in the future. Recent toxicokinetic studies involving the absorption, distribution, metabolism, accumulation, and excretion of GFNs through different exposure routes have yielded some results but are far from sufficient to clarify the internal complex mechanisms. For instance, further studies are needed to understand the specific molecular mechanisms of GFNs passing through the physiological barriers and the amount of accumulation or the excretion period of GFNs in tissues. In addition, given the increased exposure of humans to GFNs, the assessment of systemic toxicity in the human body is indispensable in future studies.
Fifth, another important issue requiring attention is the long-term fate of GFNs after entering the body or being taken up by cells. Most recent studies have consisted of short-term toxicity assessments [89, 232], and long-term toxic injury has not received much attention since the widespread application of GFNs in 2008. Moreover, a functionalized graphene surface can improve its biocompatibility, but the long-term stability of the surface coatings should be considered [233]. If the surface coatings eventually break down, their toxicity may be significantly different from the short-term exposure results. Extended studies are needed to determine if longer treatment times influence the nanotoxic potential of GFNs.
Sixth, more specific signalling pathways in the mechanism of GFNs toxicity need to be discovered and elucidated. Currently, several typical toxicity mechanisms of GFNs have been illustrated and widely accepted, such as oxidative stress, apoptosis, and autophagy. However, these mechanisms have only been described in general terms, and the specific signalling pathways within these mechanisms need to be investigated in detail. The signalling pathways involved in the toxicity of other nanomaterials may also be relevant to the study of GFNs. Therefore, more signalling pathways should be detected in future research. For instance, nano-epigenetics has been considered in numerous studies of nanomaterials, which is also helpful in assessing the limited toxicity and side effects of GFNs. Recent studies have shown that GFNs could cause epigenetic and genomic changes that might stimulate physical toxicity and carcinogenicity [234]. GFNs have high surface areas, smooth continuous surfaces and bio-persistence, similar to the properties of tumorigenic solid-state implants. It is unknown whether GFNs have the potential to induce foreign body sarcomas, and definitive studies of tumour potentialities or risks of graphene should therefore be conducted as soon as possible.
Conclusions
In the past few years, GFNs have been widely utilized in a wide range of technological and biomedical fields. Currently, most experiments have focused on the toxicity of GFNs in the lungs and livers. Therefore, studies of brain injury or neurotoxicity deserve more attention in the future. Many experiments have shown that GFNs have toxic side effects in many biological applications, but the in-depth study of toxicity mechanisms is urgently needed. In addition, contrasting results regarding the toxicity of GFNs need to be addressed by effective experimental methods and systematic studies. This review provides an overview of the toxicity of GFNs by summarizing the toxicokinetics, toxicity mechanisms and influencing factors and aimed to provide information to facilitate thorough research on the in vitro and in vivo haemo- and biocompatibility of GFNs in the future. This review will help address safety concerns before the clinical and therapeutic applications of GFNs, which will be important for further development of GFNs in biological applications.
https://sitn.hms.harvard.edu/flash/2019/brain-machine-interfaces-may-used-study-regulate-mood/
NOVEMBER 6, 2019
BLOG
Brain-machine interfaces may be used to study and regulate mood
Brain-machine interfaces (BMIs) are devices that translate brain signals into information that can be used for various purposes. Much of the research with BMIs thus far has focused on using this information to control external devices, such as robotic limbs, that can restore lost motor function in paralyzed patients. Scientists are beginning to design BMIs that translate brain signals into emotion and mood states.
A group of scientists led by Maryam Shanechi, at University of Southern California, are interested in neuropsychiatric disorders such as depression and anxiety. One of their goals is to use machine learning to understand the brain signals that are associated with specific mood states. In one of their recent studies, electrodes were implanted directly onto the surface of the brain of patients, and brain activity was recorded over multiple days. Patients’ mood states were assessed using a self-report questionnaire that the researchers termed Immediate Mood Scaler (IMS). Shanechi and her colleagues then designed a computer algorithm that could predict IMS scores based on recorded brain activity. In this way, BMIs may be able to help us understand the neural mechanisms of how emotions arise, change, and dissipate.
Electrical stimulation could be used to regulate aberrant brain signal and restore emotional function in patients with treatment-resistant neuropsychiatric disorders. In theory, these devices would constantly monitor a patient’s brain activity and automatically apply stimulation to treat abnormal mood states. Such an invasive approach brings up concerns of safety, privacy, and identity. Altering our emotions would lead to a change in the way we perceive and experience the world, which poses the question of how much control we truly have over our thoughts and actions. With the potential emergence of these devices, extensive discussion of these ethical considerations will be of utmost importance.
Managing Correspondent: Jeremy Gungabeesoon
News Article: Maryam Shanechi designs machines to read minds. ScienceNews
Original Article: Brain–machine interfaces from motor to mood. Nature Neuroscience
http://www.buffalo.edu/news/releases/2010/07/11518.html
News Releases
News Topics
Media Advisories
University Statements
With Magnetic Nanoparticles, Scientists Remotely Control Neurons and Animal Behavior
By Ellen Goldbaum
Release Date: July 6, 2010
Share This Print
Related Multimedia
Research on magnetic nanoparticles by UB doctoral student Heng Huang (right) and UB physics professor Arnd Pralle could lead to disease treatments that remotely manipulate proteins or cells.
Download Hi-Res(198 KB)
BUFFALO, N.Y. -- Clusters of heated, magnetic nanoparticles targeted to cell membranes can remotely control ion channels, neurons and even animal behavior, according to a paper published by University at Buffalo physicists in Nature Nanotechnology.
The research could have broad application, potentially resulting in innovative cancer treatments that remotely manipulate selected proteins or cells in specific tissues, or improved diabetes therapies that remotely stimulate pancreatic cells to release insulin.
The work also could be applied to the development of new therapies for some neurological disorders, which result from insufficient neuro-stimulation.
"By developing a method that allows us to use magnetic fields to stimulate cells both in vitro and in vivo, this research will help us unravel the signaling networks that control animal behavior," says Arnd Pralle, PhD, assistant professor of physics in the UB College of Arts and Sciences and senior/corresponding author on the paper.
The UB researchers demonstrated that their method could open calcium ion channels, activate neurons in cell culture and even manipulate the movements of the tiny nematode, C. elegans.
"We targeted the nanoparticles near what is the 'mouth' of the worms, called the amphid," explains Pralle. "You can see in the video that the worms are crawling around; once we turn on the magnetic field, which heats up the nanoparticles to 34 degrees Celsius, most of the worms reverse course. We could use this method to make them go back and forth. Now we need to find out which other behaviors can be controlled this way." [The video is available by clicking on the "watch video" link above.]
The worms reversed course once their temperature reached 34 degrees Celsius, Pralle says, the same threshold that in nature provokes an avoidance response. That's evidence, he says, that the approach could be adapted to whole-animal studies on innovative new pharmaceuticals.
The method the UB team developed involves heating nanoparticles in a cell membrane by exposing them to a radiofrequency magnetic field; the heat then results in stimulating the cell.
"We have developed a tool to heat nanoparticles and then measure their temperature," says Pralle, noting that not much is known about heat conduction in tissue at the nanoscale.
"Our method is important because it allows us to only heat up the cell membrane. We didn't want to kill the cell," he said. "While the membrane outside the cell heats up, there is no temperature change in the cell."
Measuring just six nanometers, the particles can easily diffuse between cells. The magnetic field is comparable to what is employed in magnetic resonance imaging. And the method's ability to activate cells uniformly across a large area indicates that it also will be feasible to use it in in vivo whole body applications, the scientists report.
In the same paper, the UB scientists also report their development of a fluorescent probe to measure that the nanoparticles were heated to 34 degrees Celsius.
"The fluorescence intensity indicates the change in temperature," says Pralle, "it's kind of a nanoscale thermometer and could allow scientists to more easily measure temperature changes at the nanoscale."
Pralle and his co-authors are active in the Molecular Recognition in Biological Systems and Bioinformatics and the Integrated Nanostructure Systems strategic strengths, identified by the UB 2020 strategic planning process.
In addition to Pralle, who has an adjunct position in the Department of Physiology and Biophysics in UB's School of Medicine and Biomedical Sciences, co-authors are Heng Huang and Savas Delikanli, both doctoral students in the UB Department of Physics, Hao Zeng, PhD, associate professor in the physics department, and Denise M. Ferkey, PhD, assistant professor in the UB Department of Biological Sciences.
The research was supported by the National Science Foundation and the UB 2020 Interdisciplinary Research Development Fund.
The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system and its largest and most comprehensive campus. UB's more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.
Media Contact Information
Ellen Goldbaum
News Content Manager
Medicine
Tel: 716-645-4605
goldbaum@buffalo.edu
Twitter: @UBmednews
I thought the graphene was to cause autism, now it’s mind control?
Thats aluminum I believe...
Never heard of graphene causing anything.
Autism was alleged to be caused by Thimerasol/mercury based preservatives in vaccines with one side claiming yes and another no.
Aluminum(IIRC) was alleged to play a roll in Alzheimer's with (also IIRC) the University of KY being the first to make the claim about 2 decades back. Don't recall seeing anything solid since then backing or debunking.
An interesting study mentioned on Dr. Dean Edell's radio show(used to also be on TV in the 80s at least) was a theory autism was based on parents being nerdy/dull personality types due to autism being prevalent in children of Silicon Valley employees. Can't recall seeing follow ups on that or if it was believed to be genetic or how the parents nurtured the child.
https://www.washingtonpost.com/nation/2020/05/06/bing-liu-university-of-pittsburgh-coronavirus-researcher-murder-suicide/
National
Coronavirus researcher killed in Pennsylvania murder-suicide, police say
Bing Liu, a coronavirus researcher, was killed in a murder-suicide, authorities say. (University of Pittsburgh School of Medicine)
By
Teo Armus
and
Lateshia Beachum
May 6, 2020
A University of Pittsburgh researcher on the cusp of making “very significant findings” about the novel coronavirus was killed over the weekend in what authorities say was a murder-suicide.
Bing Liu, 37, was shot multiple times in his townhouse around noon Saturday in Ross Township, Pa., police told WTAE, an ABC affiliate in Pittsburgh.
As a research assistant professor, Liu focused on using computational models to study biological processes. He was working from home during the pandemic and studying the virus, his supervisor said, according to the Pittsburgh Post-Gazette.
Officials told the newspaper Liu was shot by another man and suffered gunshot wounds to the head, neck, torso and extremities. The man, later identified as 46-year-old Hao Gu, then got into his car about 100 yards away and killed himself.
Neighbors told the paper they didn’t hear any gunshots the day Liu was killed.
The front and rear patio doors of Liu’s home were open at the time of his death because of the springtime weather, the Post-Gazette reported. His wife wasn’t home at that time.
No items were stolen from the home, according to the paper.
Ross Township Detective Brian Kohlhepp told WTAE that police don’t believe the relationship between the two men had anything to do with Liu’s research on the coronavirus.
It is unclear how the two men knew each other, and police are investigating whether there was any confrontation before the shooting. A possible motive for the murder also is unclear, the Post-Gazette reported.
In a statement, Liu’s department at the University of Pittsburgh School of Medicine called him a prolific researcher and generous mentor. Shortly before his death, he had begun researching the cellular mechanisms that underlie coronavirus infections and the cellular basis of ensuing complications.
Ivet Bahar, his supervisor and the head of his department, told the Post-Gazette Liu had just started to receive interesting results.
Bahar had sent several emails to Liu over the weekend about his work and was surprised that the normally prompt researcher wasn’t responding, according to the Post-Gazette.
After a conversation with a colleague about the crime, she confirmed Liu was the victim, the paper reported. He had not expressed any fear for his life to her, she told the paper.
“We will make an effort to complete what he started in an effort to pay homage to his scientific excellence,” the statement said.
Liu and his wife had no children and mostly kept to themselves, neighbors told the Post-Gazette.
Liu received his bachelor’s and doctoral degrees from the National University of Singapore, according to his professional website. He had previously worked as a postdoctoral fellow in the department of computer science at Carnegie Mellon University and with Bahar as a research associate in the department of computational and systems biology at the University of Pittsburgh School of Medicine.
Throughout his career, he published more than 30 academic papers and wrote a book.
Read more:
He was banned from performing autopsies. Then, he tried selling coronavirus tests to victims’ families.
Dallas hair salon owner, in act of civil disobedience, chooses to go to jail rather than close her doors.
https://www.youtube.com/watch?v=Zvb9y9gLJ0U
https://www.bitchute.com/video/v0NmIBbF8uyu/
There is a thread going over on ARF.com, but like a whole lotta guys I got the Ban hammer there long ago... https://www.ar15.com/forums/General/The-SPARTACUS-LETTER-on-CV19-STUNNING-/199-2491413/
SPEECH AT NYC MEDICAL FREEDOM RALLY [2021-09-23] - DR. LARRY PALEVSKY (VIDEO) https://www.bitchute.com/video/yZUaGOuyvspp/
FromMyColdDeadHand
09-29-21, 14:19
This letter lost me at "nanoparticles". As for the political misuse of the pandemic...yeah, I can roll with that.
Never heard of graphene causing anything.
Autism was alleged to be caused by Thimerasol/mercury based preservatives in vaccines with one side claiming yes and another no.
Aluminum(IIRC) was alleged to play a roll in Alzheimer's with (also IIRC) the University of KY being the first to make the claim about 2 decades back. Don't recall seeing anything solid since then backing or debunking.
An interesting study mentioned on Dr. Dean Edell's radio show(used to also be on TV in the 80s at least) was a theory autism was based on parents being nerdy/dull personality types due to autism being prevalent in children of Silicon Valley employees. Can't recall seeing follow ups on that or if it was believed to be genetic or how the parents nurtured the child.
My kids have a learning difference or whatever you call it. I think my son is just a boy, but my daughter definitely has language processing issues. I think that they have always been there, and maybe compensated for or hidden in the past when there was no advantage to them. But now, you get a special chair, and more time for tests. FUnny how it is the families with money who can get psych to diagnose something, and get an advantage on test. Like I said, learning difference and language processing issues and other things are real, but yuppie parents weaponized it.
There is a thread going over on ARF.com, but like a whole lotta guys I got the Ban hammer there long ago... https://www.ar15.com/forums/General/The-SPARTACUS-LETTER-on-CV19-STUNNING-/199-2491413/
I work with a guy with PhD in chemistry. Brilliant guy. His real skill though is taking huge amounts of complicated data and turn it into information that the rest of us can easily understand - so much so that you think that you knew the information all the time.
Just because you cut and paste esoteric articles doesn’t make your case. I read through one on the page before about graphene nanoparticles and control. Seems that they were able to influence a nematode and it takes the magentic field of an MRI machine. Maybe there is something there, but that’s going to get awkward.
Arguments are made on logic and relevant facts, not volume.
Inkslinger
09-29-21, 14:28
Also one must consider that going off on a graphene nanoparticle tangent does nothing to support the validity of the letter. In the letter they note “unexplained nanoparticles”. Not lipid nano, not graphene nano, but unexplained nanoparticles. So any speculation is a waste of time. I do find it curious that with the ability to correlate so much scientific information that there should be no difficulty in identifying the particles.
I work with a guy with PhD in chemistry. Brilliant guy. His real skill though is taking huge amounts of complicated data and turn it into information that the rest of us can easily understand - so much so that you think that you knew the information all the time.
Just because you cut and paste esoteric articles doesn’t make your case. I read through one on the page before about graphene nanoparticles and control. Seems that they were able to influence a nematode and it takes the magentic field of an MRI machine. Maybe there is something there, but that’s going to get awkward.
Arguments are made on logic and relevant facts, not volume.
Some one that actually knows what they are doing should be able to explain it to most people.
The issue I have with this is the groups(and many individuals within those) pushing the covid story line the hardest are the same groups(and individuals within those groups) that have pushed the anti-gun story line complete with fear, statistics, expert testimony, and the do as I say, not as I do lifestyle tossed in for good measure.
Also one must consider that going off on a graphene nanoparticle tangent does nothing to support the validity of the letter. In the letter they note “unexplained nanoparticles”. Not lipid nano, not graphene nano, but unexplained nanoparticles. So any speculation is a waste of time. I do find it curious that with the ability to correlate so much scientific information that there should be no difficulty in identifying the particles.
Well, the "unexplained Nanoparticles" where never disclosed on the "vaccine insert paper" that was never included with the "vaccines" when they were distributed, because apparently they don't have to disclose that information when the "vaccines" are being distributed under "emergency use authorization"... Hence them being, "unexplained"...
FromMyColdDeadHand
09-29-21, 14:56
Also one must consider that going off on a graphene nanoparticle tangent does nothing to support the validity of the letter. In the letter they note “unexplained nanoparticles”. Not lipid nano, not graphene nano, but unexplained nanoparticles. So any speculation is a waste of time. I do find it curious that with the ability to correlate so much scientific information that there should be no difficulty in identifying the particles.
I read that the mRNA vaccines are like a 80-90 step process, which I’m guessing has some kind of catalysis or sieving steps. That’s where I’d guess that nanoparticles are coming from.
You should be able to report in a day what the nanoparticles are. SEM them and just look at them. Then get the composition. Most engineering universities could run that.
Inkslinger
09-29-21, 15:32
Well, the "unexplained Nanoparticles" where never disclosed on the "vaccine insert paper" that was never included with the "vaccines" when they were distributed, because apparently they don't have to disclose that information when the "vaccines" are being distributed under "emergency use authorization"... Hence them being, "unexplained"...
Probably because like many products in many industries, they are not required to disclose every intricacy of their product. The wiki entry you posted states they use lipid nanoparticles. Lipids are fats, so I can’t imagine any way for them to be used for mind control…
Probably because like many products in many industries, they are not required to disclose every intricacy of their product. The wiki entry you posted states they use lipid nanoparticles. Lipids are fats, so I can’t imagine any way for them to be used for mind control… The lipids are the "delivery system" for the Graphene Oxide nanoparticles. Hence, Lipid Nanoparticles. Jesus, people, Reading is fundamental.
And the pharmaceutical industry is ABSOLUTELY required by federal law to disclose all ingredients in medications and the side affects. But that was all forgone and circumvented by way of the emergency use authorization! And now here we are, with millions of people around the world still not having full understanding of just what it is they are having injected into their bodies...
FromMyColdDeadHand
09-29-21, 16:31
The lipids are the "delivery system" for the Graphene Oxide nanoparticles. Hence, Lipid Nanoparticles. Jesus, people, Reading is fundamental.
And the pharmaceutical industry is ABSOLUTELY required by federal law to disclose all ingredients in medications and the side affects. But that was all forgone and circumvented by way of the emergency use authorization! And now here we are, with millions of people around the world still not having full understanding of just what it is they are having injected into their bodies...
Well, there is that theory and then there’s the theory that you are an AI bot that got loose from an MIT DARPA grant program.
We could vote on it.
Inkslinger
09-29-21, 16:33
The lipids are the "delivery system" for the Graphene Oxide nanoparticles. Hence, Lipid Nanoparticles. Jesus, people, Reading is fundamental.
And the pharmaceutical industry is ABSOLUTELY required by federal law to disclose all ingredients in medications and the side affects. But that was all forgone and circumvented by way of the emergency use authorization! And now here we are, with millions of people around the world still not having full understanding of just what it is they are having injected into their bodies...
Reading comprehension would imply I actually read all of those ridiculously long posts. I didn’t.
https://www.reuters.com/article/factcheck-graphene-lipidvaccines-idUSL1N2PI2XH
Reading comprehension would imply I actually read all of those ridiculously long posts. I didn’t. Then why comment at all?
Inkslinger
09-29-21, 16:42
Then why comment at all?
Well, if you read my first comment on it your reading comprehension must be on par with mine. No need to act like Hillary….
This was fun to read through. I can sum up why a lot of people are hesitant to jump on the “just do it man” train. Ready.
Covid was politicized.
Once that happen along with the early flip flops of said experts, people started tuning them out. Add in the coercion and people dug their feet in more.
It doesn’t have to be a vast conspiracy.
Sent from my iPhone using Tapatalk
Well, if you read my first comment on it your reading comprehension must be on par with mine? No need to act like Hillary…. Well your just a tattoo artist, WTF do you know. Listen, I will have you know I'm a bigly paid COLLISION REPAIR TECHNICIAN, damnit! With over 25 years experience, ain't none of you peons could carry my lunch box!
Inkslinger
09-29-21, 16:52
Well your just a tattoo artist, WTF do you know. Listen, I will have you know I'm a bigly paid COLLISION REPAIR TECHNICIAN, damnit! With over 25 years experience, ain't none of you peons could carry my lunch box!
And I’m sure you could articulate a complete bs statement about the inner workings of an automobile to a level that a layman would believe you’ll put their automobile on Mars before Elon Musk. That could easily be what’s happening in the letter…. You and I will never know.
And I’m sure you could articulate a complete bs statement about the inner workings of an automobile to a level that a layman would believe you’ll put their automobile on Mars before Elon Musk. That could easily be what’s happening in the letter…. You and I will never know. Duly noted and fair enough. And if you really knew me you would know that I'm your Huckleberry when spinning tails of automotive BS, to be sure...
This was fun to read through. I can sum up why a lot of people are hesitant to jump on the “just do it man” train. Ready.
Covid was politicized.
Once that happen along with the early flip flops of said experts, people started tuning them out. Add in the coercion and people dug their feet in more.
It doesn’t have to be a vast conspiracy.
Sent from my iPhone using Tapatalk
I going say that given the global aspect of this thing with seemingly locking down the entirety of the western world these last 18 months or so suggests that it most certainly is a vast conspiracy. And to suggest otherwise is being just plain obtuse. But don't take my saying that personal.
Well, there is that theory and then there’s the theory that you are an AI bot that got loose from an MIT DARPA grant program.
We could vote on it.
Na, I'm old school MK Ultra through and through...
Reading comprehension would imply I actually read all of those ridiculously long posts. I didn’t.
https://www.reuters.com/article/factcheck-graphene-lipidvaccines-idUSL1N2PI2XH
I didn't see this link the first time around FYI. Anytime you see the "factcheck" buzzword you can rest assured its bullshit. It is like how the CIA coined the term "conspiracy theory" to discredit anyone going against the narrative by thinking for themself's. And you guys can factcheck that. So again, all I can say is somebody is lying. We know Fauci lied about Wuhan and gain of function. And if you didn't read that stuff I posted, maybe you all should spend a little time trying to get your heads around it.
Duly noted and fair enough. And if you really knew me you would know that I'm your Huckleberry when spinning tails of automotive BS, to be sure...
Just remember to think in tenths and use a Flatliner to repair creases in panels..lol
But don't take my saying that personal.
It's the internet, I don't take anything personal. I'm not discounting that governments around the world have used this as a means to expand their powers. That kinda goes hand in hand with my statement that Covid was politicized though.
Seriously ,,, what has not been politicized ?
I'm not discounting that governments around the world have used this as a means to expand their powers. That kinda goes hand in hand with my statement that Covid was politicized though.
I agree. Tyrants are going to tyrant if given half a chance, but that doesn’t prove it’s some giant conspiracy.
Well your just a tattoo artist, WTF do you know. Listen, I will have you know I'm a bigly paid COLLISION REPAIR TECHNICIAN, damnit! With over 25 years experience, ain't none of you peons could carry my lunch box!
Don't care what any one else says dude. I like you.
If I was a girl I would give you some for sure. :)
(but i am not so forgetaboutit)
BangBang77
09-29-21, 20:32
I ain't got time to read a dissertation. Can I get the CliffsNotes version?
I ain't got time to read a dissertation. Can I get the CliffsNotes version?
In a word, Transhumanism.
https://www.bitchute.com/video/The3xkjMF5LQ/
https://www.bitchute.com/video/QVfP9XvDaHLw/
https://www.youtube.com/watch?v=8wx35QuLWCE
Funny you should mention mind control. Have you seen any of that brain computer interface stuff mentioned in the citations?Thats what the Graphene oxide is for. And why do a whole lot of our politicians seem to be under someones control? As if they can't refuse. Take General Milley for example?. And why does Mark Zuckerberg look AND act like a freakin Robot?? https://www.darpa.mil/program/our-research/darpa-and-the-brain-initiative Also I just wanna say I always liked you back in your ARF.com days. And I mean that sincerely. When did you get the ban hammer again? Wasn't it around 2007...
My God I finally understand. After reading everything it is now so clear and obvious.
I Should NOT Be Posting In This Thread...lol
Glad to have a long time fan, but I'm gonna politely hit eject on this one.
JFC, Toecutter - stop with the 5000 word posts.
Andy
JFC, Toecutter - stop with the 5000 word posts.
Andy
You smooth brain types are so very disappointing.
You smooth brain types are so very disappointing.
Thing is, we can agree this event has been used to expand the .govs power without going full Alex Jones.
Governments granting themselves emergency powers that they will most likely not relinquish is concerning enough without going full on rabbit hole conspiracy.
My line in the sand was crossed when the dementia riddled idiot granted himself the power to coerce people who made the decision not to get the jab, get jabbed or lose their livelihood. I don’t need to think there’s mind control material in the vaccine to see his actions are evil and allowing him to go through with his dictate is very bad for our country and our liberties now and down the road.
Sent from my iPhone using Tapatalk
My God I finally understand. After reading everything it is now so clear and obvious.
I Should NOT Be Posting In This Thread...lol
Glad to have a long time fan, but I'm gonna politely hit eject on this one.
HAHAHA, look I'm not a glowie, but my posting all this will probably attract them. And I just posting all this because after 18 months of doing my own research I have come to the same conclusions as whomever wrote that Spartacus letter. And the bitchute links I've posted should be more than enough to convince anyone. There have been so many Phd's from all areas of science and medicine that been actively trying to speak out against this thing and they are being censored and silenced. These are very accomplished people, NOT quacks. Dr. Peter McCullough, Dr Robert Malone, Dr Bret Winestein just to name a few, but there are many many others. And I would not be at all surprised if it was indeed one of them who wrote it!
Anyone still laboring under the delusion that this "vaccine" has anything to do with public heath is in for a very rude awakening. The Spartacus letter is dead on and it bears repeating, to those who are participating in the farce without any understanding of what they are doing, you are causing irreparable harm to country and fellow citizens!
And what's worse so many here don't want to take the conversation seriously and actively try to derail any productive discourse at every turn. Why? Is the knowledge that the reality they're living in has come into question a thought that is just too scary? Unplugging from the matrix too painful to bare. These people are dangerous to themselves and others and have to be awoken from they're slumber or we will all be put in bondage!
Thing is, we can agree this event has been used to expand the .govs power without going full Alex Jones.
Governments granting themselves emergency powers that they will most likely not relinquish is concerning enough without going full on rabbit hole conspiracy.
My line in the sand was crossed when the dementia riddled idiot granted himself the power to coerce people who made the decision not to get the jab, get jabbed or lose their livelihood. I donÂ’t need to think thereÂ’s mind control material in the vaccine to see his actions are evil and allowing him to go through with his dictate is very bad for our country and our liberties now and down the road.
Sent from my iPhone using Tapatalk
No you can't! The Fourth Industrial revolution and "transhumanism" are very very real...
You smooth brain types are so very disappointing.
Your unwillingness to provide a link and concise summary vice copying and pasting ridiculous blocks of text is disappointing.
Andy
Your unwillingness to provide a link and concise summary vice copying and pasting ridiculous blocks of text is disappointing.
Andy
Summary: The Fourth Industrial revolution and "transhumamism" are happening right now! Wether you are conscious of that fact or not. And if people don't want to wake up and take it seriously, well, then its their funeral! "vaccine" line forums there---->.
You can expect mandatory boosters every 3-6 months.
How do you know you are not the one being mind controlled?
What if the graphene is already in the fluoride in our water or maybe that’s what is in the chemtrails? So they can mind control you to mix the truth about mind control into a giant conspiracy so nobody will believe it.
How do you know you are not the one being mind controlled?
What if the graphene is already in the fluoride in our water or maybe that’s what is in the chemtrails? So they can mind control you to mix the truth about mind control into a giant conspiracy so nobody will believe it.
Look smart ass, everyone is being manipulated to some degree or another, Even you! Did you watch that Steven Colbert "vax-scene" shit on the last page? Those people in that audience are ****ing nuts! Seriously, they're already dead. So you can either heed Spartacus letters warning or continue on to your own slaughter with your head stuck up your ass...
Here’s the thing. I’ve already explained I think a dangerous precedent is being set using Covid as the backdrop. If you want to get people around to “wake up” to the continual .gov encroachment into our everyday lives; going off on transhumanism, mind control, and the like isn’t the way to do it. That will simply turn people off to your message.
Have you ever stopped to think that people like Alex Jones are simply grifters raking in millions off people’s paranoia? I don’t know if he is or not, but he’s been suspect on more than a few topics.
He’ll give out kernels of truth from time to time, but he usually goes off the deep end from there. In the end he’s in business dude and it’s the business of fear. He’s made millions off of it.
Sent from my iPhone using Tapatalk
Here’s the thing. I’ve already explained I think a dangerous precedent is being set using Covid as the backdrop. If you want to get people around to “wake up” to the continual .gov encroachment into our everyday lives; going off on transhumanism, mind control, and the like isn’t the way to do it. That will simply turn people off to your message.
Have you ever stopped to think that people like Alex Jones are simply grifters raking in millions off people’s paranoia? I don’t know if he is or not, but he’s been suspect on more than a few topics.
He’ll give out kernels of truth from time to time, but he usually goes off the deep end from there. In the end he’s in business dude and it’s the business of fear. He’s made millions off of it.
Sent from my iPhone using Tapatalk
Look when you start off by stating "here's the thing" and "I've already stated" it all sounds very obtuse. Is that intentional or is it just cognitive dissonance? Transhumanism is what these last 18 months have been all about. Our Western governments have be taken over by the Global elite to force their agenda of The Forth Industrial revolution and Transhumanism where by creating a utopia for themselfs and enslaving the common man.
As for Alex Jones, I wasn't the person who first brought him up in the discussion. And I've Never paid much attention to the guy. He was only brought into the conversation because you all have such a limited understanding of what exactly is taking place that when presented with the evidence of the Spartacus letter you all loose your minds and scream "conspiracy theory" and "Alex Jones" OMG-WTF-BBQ....But Honestly after what has transpired in the world for the last 18 months I would say it all ultimately lends to the validity of what he's been espousing for the last decade.
But again Transhumanism is what this Covid-19 business all about. And I think it would be a wise move and in everyones best interest for yourself's, your families and the world at large for you all to become aware of intricacies of just what this all means and where it will lead. I posted a lot of video links back there but didn't comment on them because, admittedly I am just a layperson and there is simple too much for me to comment on. You simply just have to watch. Thats about all I can say.
Start here.
https://www.bitchute.com/video/QVfP9XvDaHLw/
https://www.bitchute.com/video/The3xkjMF5LQ/
BangBang77
09-30-21, 10:24
Look when you start off by stating "here's the thing" and "I've already stated" it all sounds very obtuse. Is that intentional or is it just cognitive dissonance? Transhumanism is what these last 18 months have been all about. Our Western governments have be taken over by the Global elite to force their agenda of The Forth Industrial revolution and Transhumanism where by creating a utopia for themselfs and enslaving the common man.
As for Alex Jones, I wasn't the person who first brought him up in the discussion. And I've Never paid much attention to the guy. He was only brought into the conversation because you all have such a limited understanding of what exactly is taking place that when presented with the evidence of the Spartacus letter you all loose your minds and scream "conspiracy theory" and "Alex Jones" OMG-WTF-BBQ....But Honestly after what has transpired in the world for the last 18 months I would say it all ultimately lends to the validity of what he's been espousing for the last decade.
But again Transhumanism is what this Covid-19 business all about. And I think it would be a wise move and in everyones best interest for yourself's, your families and the world at large for you all to become aware of intricacies of just what this all means and where it will lead. I posted a lot of video links back there but didn't comment on them because, admittedly I am just a layperson and there is simple too much for me to comment on. You simply just have to watch. Thats about all I can say.
Start here.
https://www.bitchute.com/video/QVfP9XvDaHLw/
https://www.bitchute.com/video/The3xkjMF5LQ/
Dude, you talk pretty fancy for a auto technician. I'm impressed.
I think that Life's a Hillary guy was wrong about you. Then again, that seems to be a trend with him.
Guess i’m just writing as if we’re having a conversation face to face.
I’ll lay out my opinions and thoughts on this as clearly as I can while typing on my phone.
1. I think Covid has / is being used by governments around the world to expand their reach, power, and authority over their citizens. That’s very bad.
2. I don’t think the blanket vaccination campaign makes any sense at all. There are a whole host of factors not being taken into consideration with this approach.
3. I think there are a adverse side effects to these vaccines and the fact we’re not allowed to openly talk about them is concerning.
4. I’ve chosen not to get the vaccine. I also don’t think it’s full of things that are going to mind control me or whatever else though.
5. The situation as I see it is we can cede our liberties in the name of “safety” or choose not to.
6. I also think if people choose to get vaccinated i’ll leave that decision to them and not worry about it.
7. I’m firmly against forced vaccination as that flies in the face of individual liberty.
I’m willing to bet your thought process isn’t too far off from mine in regards to what I wrote above. You lost me (and others i’d assume) on the grand conspiracy stuff though.
With that, I’m out of this one.
Sent from my iPhone using Tapatalk
Business_Casual
09-30-21, 10:38
Wow, this is right in my wheelhouse, how did I miss this thread? I read the manifesto and tuned out.
Dude, you talk pretty fancy for a auto technician. I'm impressed.
I think that Life's a Hillary guy was wrong about you. Then again, that seems to be a trend with him.
You are very kind for saying so, Thank you.
Guess iÂ’m just writing as if weÂ’re having a conversation face to face.
IÂ’ll lay out my opinions and thoughts on this as clearly as I can while typing on my phone.
1. I think Covid has / is being used by governments around the world to expand their reach, power, and authority over their citizens. ThatÂ’s very bad.
2. I donÂ’t think the blanket vaccination campaign makes any sense at all. There are a whole host of factors not being taken into consideration with this approach.
3. I think there are a adverse side effects to these vaccines and the fact weÂ’re not allowed to openly talk about them is concerning.
4. IÂ’ve chosen not to get the vaccine. I also donÂ’t think itÂ’s full of things that are going to mind control me or whatever else though.
5. The situation as I see it is we can cede our liberties in the name of “safety” or choose not to.
6. I also think if people choose to get vaccinated iÂ’ll leave that decision to them and not worry about it.
7. IÂ’m firmly against forced vaccination as that flies in the face of individual liberty.
IÂ’m willing to bet your thought process isnÂ’t too far off from mine in regards to what I wrote above. You lost me (and others iÂ’d assume) on the grand conspiracy stuff though.
With that, IÂ’m out of this one.
Sent from my iPhone using Tapatalk
I agree with all but line 4. There is seemingly a tremendous amount of evidence that suggests otherwise. And 18 months ago I wouldn't have believed any of it myself. Thats said, I also have to tap out now, at least for a while, I've work to be done.
Best regards everyone.
I’m only being half smartass, if mind control exists then how would you know if you are being controlled?
Seriously though. There are even more vaccines worldwide, but why would “they” allow the J&J in the US if “they” were really controlling people with mRNA vaccines?
I’m only being half smartass, if mind control exists then how would you know if you are being controlled?
Seriously though. There are even more vaccines worldwide, but why would “they” allow the J&J in the US if “they” were really controlling people with mRNA vaccines?
Total mind control hasn't happened yet. But mankind as a species is on the precipice of being able to facilitate that reality. RIGHT NOW. This is all for real and no joke! And the global elite being lead by the likes of Bill Gates and Klaus Schwab of the world economic forum, and with the aid of the Chinese communist party, seem to have a clear and concise vision of how they are going to usher in their "great Reset" and their grand plain for enslaving all of humanity.
There are many hundreds of thousands of Chinese students at universities all around this country that are here feverishly studying things like Bio-nanoscience and nanotechnology and are all most assuredly also doubling as CCP operatives, they are most assuredly not here to meld with and become part of the western way of life. And they are laying the groundwork and developing, indeed mastering, the very things that are going too soon be used as means of total control over ALL of wester society. If you go back and look at all the over 500 references that where provided by whomever wrote the Spartacus letter. The names on the marquises of these scientific papers for nanotechnology and brain computer interface are by and large Chinese! And that should alarm you! All while the American students are F@*king around trying to figure out what their gender pronouns are and what sex they wanna be.
But again, I'm just a crazy "conspiracy theorist" auto mechanic, so WTF do I know... Get in line a get you shot, Do it for grandma.
https://www.youtube.com/watch?v=Zvb9y9gLJ0U&t=1s
Business_Casual
09-30-21, 13:27
No mind control? Everyone is walking around wearing a mask and calling an mRNA therapeutic a vaccine.
There is no corona virus vaccine, just as there is no cure for the common cold.
No mind control? Everyone is walking around wearing a mask and calling an mRNA therapeutic a vaccine.
There is no corona virus vaccine, just as there is no cure for the common cold.
You're right on target. And more precisely I think what we have witnessed with this indisputable Pys-op we all be subjected to over the course of the last year is something akin to MK Ultra. Honestly... I mean how else do you explain it. People are unable to even think rationally, put 2 and 2 together, and forum their own thoughts and opinions at this point. Its freaking scary.
Fear is all you need, not a mind control vaccine.
Guys, this Stew Peters show interview with Dr. Carrie Manej just published on Bitchute just 15 minutes ago. I've been following her on and off for months now. But it's going where she and the other PhD's have been saying it would for months. This is nuts. I don't even wanna think about this shit anymore. It's like the matrix movie, once you've taken the red pill there is no going back. I'm really starting to wish I wouldn't have started this thread now and I truly apologize for it. Pay attention to her body language at the end also, I see real concern.
https://www.bitchute.com/video/78St4NEySsbq/
FromMyColdDeadHand
09-30-21, 16:06
“Superconducting material… injectable computing system”
“Things moved to the edge and self assembled”- uhm evaporation on the edge draws material from the center and they clump together.
A self aware tentacled thing that seemed to be looking at them…..
Uhm, dirty slides….
She’s a DO also.
The only thing that makes colors like that is a nano super computer? You dumb f-ing twit, ever see a soap bubble??? Are those all nano super computers?????
OH MY GOD! ALL THE SEA SHELLS ARE ALIEN SUPERCOMPUTERS!!!!!!
YOUR WIFES MAKE-UP WITH PEARLESCENT PIGMENTS IS GOING TO MAKE HER LEAVE YOU!!!
YOUR TOOTHPASTE HAS THESE IN THEM TOO!!!!!!!!
Points for the hot doc. DEduct for absolute crap science. Seriously. Actually, the only conspiracy where her points make sense is that Bill Gates gave her these BOFO crazy talking points to throw people off the scent.
If that is a smoking gun, you are smoking something.
Mods, time to wrap it up and send ToeJam on his way.
Voodoochild
09-30-21, 16:11
Well once again another COVID thread bites the dust. I'm tired of getting reports from this.
Powered by vBulletin® Version 4.2.5 Copyright © 2024 vBulletin Solutions, Inc. All rights reserved.