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Top 10 medical researches in August 2021 Highly Recommended!
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Top 10 medical researches in August 2021 Highly Recommended!
August passed quickly. What are the highlights of this month’s research worthy of our in-depth study? Based on the type, popularity and research field of this month’s news, the editor has selected the top 10 blockbuster studies of this month, and learn with everyone!
ELF4 may serve as a transcriptional regulator of inflammation in the human body.
Image source: Tyler, P.M., et al. Nat Immunol (2021). doi: 10.1038/s41590-021-00984-4
 Nat Immunol: A new discovery in the study of human own inflammatory diseases: ELF4 may be used as a transcriptional regulator of inflammation in the human body
Currently, researchers are not very aware of transcription factors that are specifically designed to limit the destruction potential of inflammatory immune cells. Recently, in a research report titled “Human autoinflammatory disease reveals ELF4 as a transcriptional regulator of inflammation” published in the international journal Nature Immunology, scientists from Yale University School of Medicine and other institutions have discovered a simulated inflammation through research.
The genetic causes behind the rare childhood disorders of bowel disease, related research results may be expected to help researchers uncover the root causes of a series of other inflammatory and autoimmune diseases.
In this study, the researchers investigated a very mysterious case, that is, a young boy was admitted to the hospital for treatment with abdominal pain, intermittent fever, multi-day diarrhea, and a cavity ulcer. Genome sequencing revealed that the boy’s body carried a genetic defect that could block the function of ELF4, which is a transcription factor on the X chromosome that can regulate the expression of a large number of other genes.
Later, after contacting researchers engaged in rare diseases, the researchers discovered two other male children with similar symptoms, carrying ELF4 gene mutations in their bodies. The researchers named this disorder “ELF4-deficient X-linked disorder” “(DEX, Deficiency in ELF4, X-linked), researchers have discovered more and more cases. Researcher Professor Carrie Lucas said that starting with patients, we discovered a new gene that plays a fundamental role in regulating inflammation in the body.
Inflammatory diseases induced by mutations in a single gene affect the health of about 1 child in every 5000 children. According to the researchers, the symptoms experienced by the children in this study are similar to those of other inflammatory bowel diseases, including ulcerative colitis and Crohn’s disease, which are considered to be excessive immunity that damages the host’s tissues. Caused by system reaction.
After the ELF4 gene mutation was identified, the researcher Lucas’ laboratory studied the effects of the mutation in cells cultured from the patient’s body, and at the same time introduced the ELF4 derived from the patient’s body using the CRISRP gene editing technology in the mouse body. Mutations, the results confirmed that mutations can interfere with the function of ELF4, and will cause the body’s multiple immune cells to increase the level of inflammatory response.
 Sci Transl Med: New discovery! IgA, the second largest antibody in the body, may be expected to help fight human malaria!
Immunoglobulin A (IgA) antibody plays a key role in defending against mucosal pathogens. However, although it is second only to IgG in the blood, it plays a role in the body’s immunity to non-mucosal pathogens (such as Plasmodium falciparum). The role has not yet been clearly clarified by researchers. Recently, in a research report titled “Functional human IgA targets a conserved site on malaria sporozoites” published in the international journal Science Translational Medicine, scientists from the National Institute of Allergy and Infectious Diseases and other institutions put forward a research report on The new insights of malaria and human antibody IgA, IgA can target and kill the malaria parasite; before that, researchers have not found a correlation between IgA antibodies and the body’s defenses against malaria parasite infection.
Researchers conducted studies on people from Mali, West Africa, and found that these people have the activity of IgA antibodies and can effectively resist the invasion of malaria. Malaria is a disease caused by four kinds of Plasmodium, namely Plasmodium vivax, Plasmodium falciparum, Plasmodium ovale and Plasmodium vivax. According to data from the World Health Organization, this Plasmodium can damage the body. Red blood cells, which in turn induce joint pain, fever, hemolytic anemia, and increased urine hemoglobin. Plasmodium is a kind of protozoan, which is transmitted by female Anopheles, that is, Anopheles transfers the plasmodium to the blood of the bitten person when biting an animal. The latest research focuses on malaria caused by Plasmodium falciparum because of its It is closely related to the increase in morbidity and mortality in the population.
The researchers found that when the IgA antibody from the Malian population was injected into the mouse body infected with Plasmodium in the laboratory, IgA reduced the number of Plasmodium proliferation in the animal body; from the individuals who resisted the Plasmodium infection, the study The researchers isolated an IgA monoclonal antibody that can reduce the burden of Plasmodium falciparum in the liver of mice; then they emphasized that an IgA antibody called MAD2-6 can adsorb itself to the surface protein of Plasmodium falciparum circumsporozoite (CSP). ) On a highly conserved epitope at the amino terminus, CSP protein is the main protein on the surface of Plasmodium, which can help neutralize protozoa.
 Nature: Heavy! Improving female fertility is expected! Scientists have identified nearly 300 new genes related to female fertility!
Reproductive lifespan is very necessary for fertility, and it also affects the healthy aging of women; but scientists know little about the biological mechanisms behind it and how to preserve women’s fertility. Recently, in a research report titled “Genetic insights into biological mechanisms governing human ovarian ageing” published in the international journal Nature, scientists from the University of Exeter School of Medicine and other institutions have identified nearly 300 Gene mutations may affect women’s reproductive lifespan. In addition, by studying mice, researchers have successfully manipulated multiple key genes related to mutations that extend their reproductive lifespan. Relevant research results are expected to help increase scientists’ understanding of the reproductive aging process and provide new methods to improve the prediction of which women may enter menopause earlier than other women.
Although people’s life expectancy has increased significantly in the past 150 years, the age at which most women enter natural menopause has been stable at about 50 years; women carry all their eggs at birth, and these eggs will follow As they age, they continue to age. Once most of the eggs disappear, women will have menopause, so their natural fertility ability will be significantly reduced. Researcher Eva Hoffmann said that it is clear that repairing damaged DNA in eggs is essential for establishing a female egg bank at birth and improving the rate of loss throughout life; and improving the understanding of the biological processes involved in reproductive aging or Can help improve human fertility therapy.
In this research report, the researchers identified new genetic mutations related to reproductive life span, which increased the number of known genetic mutations from 56 to 290; these findings are based on the analysis of hundreds of thousands from many studies. It is based on a dataset of women, including the British Biobank and 23andMe; 23andMe’s data is provided by customers who choose to participate in the study. Although most of the data comes from women of European descent, the researchers also analyzed Data from nearly 80,000 women of East Asian descent, and found roughly similar results.
Researchers have discovered that many related genes are directly related to the DNA repair process; in addition, many of these genes are already active before the body is born, and this is the case throughout the life of the body. It is worth noting that the genes CHEK1 and CHEK2 from the two cell cycle checkpoint pathways can help regulate a variety of DNA repair processes. Knock out a specific gene (CHEK2) so that it can no longer function and is overexpressed Another gene (CHEK1) can increase its activity, and both strategies can extend the reproductive life of mice by approximately 25%. The reproductive physiology of mice is also different from humans in key aspects. For example, mice do not have menopause; however, in this study, the researchers also analyzed women who have naturally deleted the active CHEK2 gene and found that compared to carrying normal active genes For women, women with this gene deletion will enter menopause 3.5 years later.
Schematic diagram of FIND-IT, picture source: Nature Chemical Biology, 2021, doi:10.1038/s41589-021-00842-2.
 Nat Chem Biol: Using two CRISPR enzymes, it can detect SARS-CoV-2 with high sensitivity within 20 minutes without amplification.
Frequent and rapid detection of COVID-19 is essential to control the spread of the epidemic, especially when new and more transmissible variants of the SARS-CoV-2 virus appear. Although the gold standard COVID-19 diagnostic test now uses qRT-PCR—quantitative reverse transcription polymerase chain reaction—very sensitive and can detect one copy of RNA per microliter, it requires specialized equipment and several Hours of running time and a centralized laboratory facility. Therefore, the test usually takes at least one to two days.
In a new study, a research team led by Jennifer Doudna, David Savage and Patrick Hsu of the University of California at Berkeley developed a diagnostic test method that is faster and easier to deploy than qRT-PCR. It now combines two different types of CRISPR enzymes to construct a test method that can detect small amounts of viral RNA in less than an hour. The relevant research results were published online in the journal Nature Chemical Biology on August 5, 2021, with the title of the paper “Accelerated RNA detection using tandem CRISPR nucleases”.
Although this new technology has not yet reached a stage comparable to the sensitivity of qRT-PCR – it can detect only a few virus copies per microliter of liquid – it can detect the level of viral RNA – –About 30 copies of the virus per microliter of fluid —sufficient to monitor the population and limit the spread of infection. Savage said, “Given that this test method is convenient and fast enough, you don’t need the sensitivity of PCR to basically catch and diagnose COVID-19 in the community. We hope to advance biochemistry as much as you can imagine. In a convenient format, in an environment, you can be tested every day, for example, at the entrance to work.”
Several CRISPR-based test methods have been authorized by the U.S. Food and Drug Administration (FDA) for emergency use, but all these test methods require an initial step. In this step, viral RNA is amplified in order to detect the signal. It involves a fluorescent molecule that emits light that is bright enough under blue light so that it can be observed. Although this initial amplification step increases the sensitivity of the test to a level similar to that of qRT-PCR, it also introduces some steps that make the test more difficult to perform outside the laboratory. These authors tried to achieve useful sensitivity and speed without sacrificing the simplicity of detection. Tina Liu, the first author of the paper and a research scientist in Doudna’s laboratory, said, “For instant testing applications, you want a quick response so that people can quickly know if they are infected, for example, before you fly or visit relatives.”
 Science: Subvert the convention! The human metabolic rate reaches its peak early in life and only begins to decline after the age of 60.
Most of us remember that for a while, we could eat whatever we wanted without getting fat. However, in a new study, from the United States, China, Japan, the United Kingdom, Norway, Morocco, Ghana, the Netherlands, France, Switzerland, Norway, Germany, Mauritius, Jamaica, South Africa, Kenya, Rwanda, Finland, Denmark and Austria Researchers from, found that the human body’s metabolism—the rate at which calories burned—in fact reached its peak early in life, and its inevitable decline began later than people thought. The relevant research results were published in the Science Journal on August 13, 2021, with the title of the paper “Daily energy expenditure through the human life course”.
Herman Pontzer, co-corresponding author of the paper and associate professor of evolutionary anthropology at Duke University, said, “As we grow and get older, there are many physiological changes. Think about puberty, menopause, and other stages of life. Strangely, our The timing of the’metabolic life stage’ does not seem to match these typical milestones.” These authors analyzed the average calories consumed by more than 6,600 people from one year old to 95 years old in daily routines in 29 countries around the world.
In the past, most large-scale studies measured the energy used by the body to perform basic vital functions such as breathing, digestion, and pumping blood, in other words, the calories you need to sustain life. But this only accounts for 50% to 70% of the calories we burn every day.
This is not yet consider the energy we spend doing other things: washing dishes, walking the dog, sweating in the gym, or even just thinking or fidgeting. In order to arrive at total daily energy consumption figures, these authors rely on the “doubly labeled water” method. This is a urine test that involves letting a person drink water. The hydrogen and oxygen in the water molecules have been replaced with naturally occurring forms of “heavy elements”, and then the rate at which they are washed out is measured.
Since the 1980s, scientists have been using this technology—considered the gold standard for measuring daily energy consumption in normal daily life outside of the laboratory–to measure human energy consumption, but Due to cost reasons, the scale and scope of the research are very limited. Therefore, multiple laboratories decided to share their data and collect their measurement results into a single database to see if they could find the truth that was not revealed or only hinted at in previous research work.
 Cell Metabol: Heavy! Scientists have identified a subtype of human adipocytes that respond to insulin stimulation—AdipoPLIN cells
At present, researchers are not very clear about the contribution of cell structure heterogeneity and architecture to the function of white adipose tissue (WAT), and it is well known that fat cells can affect the body’s sensitivity to insulin. Recently, in a research report titled “Spatial mapping reveals human adipocyte subpopulations with distinct sensitivities to insulin” published in the international journal Cell Metabolism, scientists from Sweden’s Caroline College and other institutions found through research that white adipose tissue There are three different subtypes of mature adipocytes, and only mature adipocytes called AdipoPLIN will respond to insulin. The results of related research may help scientists develop new types of human metabolic diseases such as type 2 diabetes in the future. therapy.
Researcher Niklas Mejhert said that these findings have increased our understanding of the function of adipose tissue. The results of the study indicate that the overall ability of adipose tissue to respond to insulin is determined by the proportion and function of specific adipocyte subtypes. Obesity, insulin resistance and type 2 diabetes have certain significance and influence. In the article, the researchers identified 18 cell types that form clusters of white adipose tissue in the human body. Among them, three mature adipocytes have different phenotypes.
In order to test whether these adipocyte subtypes are related to any specific function, the researchers partially examined how these cell subtypes in four individual bodies responded to short-term increases in insulin levels in their bodies. The results showed that insulin can activate AdipoPLIN subtypes. The gene expression in type cells has no substantial effect on the other two adipocyte subtypes. In addition, the response to insulin stimulation is also proportional to the body’s insulin sensitivity. The findings of this article challenge the current view that insulin resistance is generally reduced in fat cells’ response to insulin. On the contrary, the findings of this article suggest that insulin resistance (and possibly type 2 diabetes) may be due to changes in specific subtypes of fat cells. ; This shows that adipose tissue is like a more complex tissue than we previously imagined, just like muscle tissue. There are also many subtypes of fat cells with different functions in the human body. This may be the future for different types of The development of fat cell interventions provides new ideas and clues.
 Science: Significant progress! CRISPR pioneer Zhang Feng uses human proteins to develop a new mRNA delivery platform to boost the development of gene therapy
In a new study, researchers from the Massachusetts Institute of Technology, McGovern Institute for Brain Science, Howard-Hughes Medical Institute, and Broad Institute have developed a platform for delivering molecular drugs to cells . The platform is called SEND, which can be programmed to package and deliver different RNA cargoes. SEND uses natural proteins in the body to form virus-like particles and bind RNA, and it may cause fewer immune responses than other delivery methods. The relevant research results were published in the Science Journal on August 20, 2021. The title of the paper is “Mammalian retrovirus-like protein PEG10 packages its own mRNA and can be pseudotyped for mRNA delivery”.
This new delivery platform works effectively in cell models and, with further development, may open up a new class of molecular drugs including those used for gene editing and gene replacement. Delivery method. Existing delivery tools for molecular drugs may be inefficient and randomly integrated into the genome of the host cell, and some may stimulate unnecessary immune responses. SEND is expected to overcome these limitations, which may open up new opportunities for the deployment of molecular drugs.
The corresponding author of the paper, a pioneer of CRISPR, a member of the Broad Institute’s Core Institute, a researcher at the McGovern Institute for Brain Science, and a professor of neuroscience at MIT, Dr. Feng Zhang, said, “The biomedical community has been developing Powerful molecular therapies, but delivering them to cells in a precise and effective manner is a challenge. SEND has the potential to overcome these challenges.”
In this new paper, Feng Zhang and his research team describe how SEND (Selective Endogenous eNcapsidation for cellular Delivery) uses molecules made by human cells. At the center of SEND is a protein called PEG10, which usually binds to its own mRNA and forms a spherical protective capsule around it. In their research, they designed PEG10 to selectively package and deliver other RNA. They used SEND to deliver the CRISPR-Cas9 gene editing system to mouse cells and human cells to edit target genes.
The spatial distribution of participants and air pollution in Taiwan.
Image source: Cui Guo, et al., Canadian Medical Association Journal (2021). DOI: 10.1503/cmaj.202729
 CMAJ: Even if you live in an air-polluted area, regular exercise can reduce the risk of death due to natural causes.
Exercise may increase the body’s inhalation of air pollution and aggravate the adverse effects of air pollution on health. Recently, an article was published in the international journal CMAJ entitled “Effects of air pollution and habitual exercise on the risk of death: a longitudinal cohort In the “study” report, scientists from the University of Hong Kong and other institutions found that regular exercise (even in places with air pollution) can reduce the risk of death due to natural causes.
Researcher Dr. Xiang Qian Lao said that regular exercise will reduce the risk of death regardless of exposure to air pollution, while air pollution generally increases the risk of death for people (regardless of whether they exercise regularly). Therefore, even for people living in Relative to people in polluted areas, habitual exercise can also be promoted as a strategy to improve health. In this research report, researchers conducted a large-scale study of 384,130 adults from Taiwan during the 15 years from 2001 to 2016, aiming to understand the effects of regular exercise and long-term exposure to fine-particle species on the population The impact of the risk of death from natural causes; researchers have found that high levels of regular exercise (even in polluted areas) are beneficial compared to inactivity, although exposure to less air pollution may be better .
The researchers pointed out that we found that high levels of habitual exercise and low levels of air pollution exposure are associated with a lower risk of death from natural causes, while low levels of habitual exercise and high levels of air pollution exposure are associated with higher population exposures. The risk is associated with an increased risk of death from natural causes. The research in this article complements several other smaller studies conducted by scientists in the United States, Denmark, and Hong Kong, which found that even in contaminated areas, regular exercise is beneficial to the body’s health. Later researchers need to conduct more in-depth research in areas with more severe air pollution to analyze whether the results of this article are also applicable to people living in areas with more severe air pollution. This research strengthens the importance of improving air pollution, such as reducing the harmful effects of air pollution on the health of the body, and maximizing the beneficial effects of regular exercise.
 Nat Biomed Eng: Heavy! Scientists have successfully developed a new type of whole brain genome editing technology that is expected to treat Alzheimer’s disease!
Familial Alzheimer’s disease is caused by a dominant mutation in the gene encoding amyloid beta precursor protein (app) and the genes encoding presenilin 1 (presenilin 1) and presenilin 2 (presenilin 2). Its pathology It is characterized by the appearance of extracellular amyloid plaques and intracellular neurofibrillary tangles in multiple brain regions. Recently, a research report titled “Brain-wide Cas9-mediated cleavage of a gene causing familial Alzheimer’s disease alleviates amyloid-related pathologies in mice” was published in the international journal Nature Biomedical Engineering. Scientists have developed a new technology through research and use of whole-brain genome editing technology, which may reduce the Alzheimer’s disease pathological manifestations of genetically modified Alzheimer’s disease mouse models. This advanced technology may It also has great potential to be transformed into a new type of long-acting strategy to treat patients with Alzheimer’s disease.
In China alone, it is estimated that more than 500,000 patients have inherited Alzheimer’s disease, which is a familial Alzheimer’s disease, that is, a congenital Alzheimer’s disease that is highly related to family history The form of the disease, although familial Alzheimer’s disease has a clear genetic cause and can be diagnosed before the patient’s cognitive problems occur, there is currently no effective treatment. The use of genome editing technology as a strategy to treat diseases caused by genetic mutations (such as familial Alzheimer’s disease, etc.) has great application prospects. It is very useful for correcting pathogenic gene mutations before disease symptoms appear. In this case, this strategy is considered to be a once-and-for-all therapeutic method, because its effects can last a lifetime. However, there are often multiple obstacles that hinder the clinical application and prospects of this technology. The most important thing is the lack of effective, efficient and non-invasive means to transport gene editing agents to the body’s brain; in addition, the current genome editing Technology also cannot produce beneficial therapeutic results in the entire brain.
In this research report, the researchers developed a new type of genome editing technology, which can not only cross the blood-brain chapter, but also transport optimized genome editing tools to the entire brain, using this newly designed genome editing transport Tool, this new technology can achieve efficient whole-brain genome editing through a single non-invasive intravenous injection, and it can effectively destroy the mutations that cause familial Alzheimer’s disease in Alzheimer’s disease mouse models. It can also improve the symptoms of Alzheimer’s disease in the entire brain, and at the same time provide ideas for the later development of new therapeutic strategies.
 Sci Robot: Developed an implantable pump that can be filled with absorbable capsules, which is expected to transport insulin to the body to treat diabetes
Creating a fully implantable robot to replace or restore the physiological process of the body is a huge challenge in the development of medical robots. In this sense, it is particularly interesting to restore the blood glucose balance of the body of type 1 diabetic patients. Intra-abdominal insulin transport can be thorough. Change type 1 diabetes therapy. At present, the intra-abdominal approach is rarely used, because it mainly relies on the access port connecting the intraperitoneal catheter and the external reservoir, and the drug-loaded pills will be transported through the digestive system and refilled in a minimally invasive manner. In this way, it can provide new possibilities for intraperitoneal drug delivery.
Recently, in a research report entitled “A fully implantable device for intraperitoneal drug delivery refilled by ingestible capsules” published in the international journal Science Robotics, scientists from the University of Hong Kong, China and other institutions have developed an implantable device through research The insulin delivery device can be filled with edible capsules. In the article, the researchers describe the development process of the device and the results of testing in pigs.
Patients with type 1 diabetes usually cannot produce insulin to regulate the body’s blood sugar. Therefore, in order to survive, the patient must inject insulin into the body through an exogenous method. There are currently three main options, namely injection, external pump and internal pump; however, These options may not be the best choice. The injection will cause pain to the patient, and the skin will become stiff, making long-term injections difficult; and the external pump will inject insulin through a port on the skin, which It may cause pain and patient infection; the internal pump must be replenished with a tube through a port on the skin. In this research report, researchers have developed an implantable insulin pump that can be filled with small swallowable capsules.
(source:internet, reference only)