In December 6, 2019, the essence of Science magazine published three HIV papers on Science.

December 19, 2019 / BIOON / - -- a new issue of Science Journal (December 6, 2019) will be published this week What are the highlights of its research? Let Xiaobian come together The picture is from science journal 1 Science: great progress! The new study found that the most common genetic origin of children's renal cancer doi: 10.1126/science.aax1323 children's renal cancer is very rare Wilms' tumour is the most common type of renal cancer in children, mainly affecting children under five years old It Diagnoses about 80 cases a year in the UK Nine out of ten cases can be cured by surgical removal of affected kidneys, chemotherapy, and sometimes radiotherapy In general, the cancer affects only one kidney, but in about 10% of cases, both kidneys are affected It is speculated that the cause of Wilms tumor is a "mistake" in one cell during the development of kidney in the first few weeks of life In a new study, British researchers found the earliest genetic cause of Wilms' tumors in children By comparing genomic sequences from normal kidney tissue and tumors, they identified what appeared to be normal renal tissue masses that actually carried DNA changes that led to Wilms' tumors The relevant research results were published in the Science Journal on December 5, 2019, and the title of the paper is "internal precursors of Wilms tutor" The study revealed a new pathway in which cancer can form in the first weeks of life, in which early cells acquire cancer-related modifications and proliferate as the kidneys develop Understanding the underlying causes of this cancer is expected to improve treatment and help prevent recurrence of Wilms's tumor The finding also raises the possibility that one day it might be possible to screen for the cancer before it can develop 2 Science: heavy weight! In a new study, researchers from Scripps Institute and other research institutions in the United States have successfully verified the principle of an advanced HIV vaccine strategy, which may also effectively protect people from other deadly infectious diseases The related research results were recently published in the Journal of science, and the title of the paper was "a generalized HIV vaccine design strategy for pricing of broad neutralizing antibody responses" The new vaccine strategy focuses on stimulating the immune system to produce broad neutralizing antibodies (bNAb) against HIV These special antibodies can bind to the important but inaccessible regions on the surface of HIV, and the differences between these regions are not significant among different HIV strains, so they can neutralize many different rapidly mutated HIV strains Vaccines that produce such antibodies can save millions of lives and billions of dollars, and may ultimately help eliminate the major public health problem of AIDS Based on a concept called germline targeting, the new strategy could block millions of different virus strains spreading around the world So far, it has been difficult to achieve this goal No candidate HIV vaccine has been found to induce protective bNAb responses in humans Schief and colleagues have previously demonstrated a reproductive targeting strategy in a particular case: bNAb captures HIV in an unusual way This new method is more powerful because it is suitable for antibodies that capture targets through a more common mechanism In addition, the analysis conducted in this study suggests that this method may also be suitable for the preparation of vaccines against many other refractory pathogens, such as influenza virus, dengue virus, Zika virus, hepatitis C virus and Plasmodium To confirm the feasibility of this strategy, Dr Jon Steichen, a senior scientist at schief laboratory and co-author of the paper, first selected an HIV bNAb known as bg18 as the test case By studying the structure of bg18 when combined with a target on HIV, the researchers identified key characteristics of the antibody's HIV capture capability Next, they searched a huge database of human antibody genes to find B cells that produced antibodies that naturally share the key characteristics of bg18 They then used a complex strategy to select and evolve a set of virus mimic proteins that may potentially activate a variety of bg18 like B cells These proteins will eventually act as "immunogens" to stimulate bg18 like B cells in vaccinated humans Tests on blood samples from HIV negative human donors confirmed that the immunogens designed by the researchers were well combined with B cells with the required bg18 like characteristics of normal circulation 3 Science: successfully induced the immune system to produce key antibodies to resist HIV infection doi: 10.1126/science.aay7199; Doi: 10.1126/science.aaz8647 recently, in a research report published in the international journal Science, scientists from Duke University Medical Center cleared the main obstacles encountered in the development of HIV vaccine through research, and also proved effective in animal models, that is, to induce short-term antibody proliferation to become the backbone of effective anti HIV Barton F Haynes, M.D., said that the reason why we don't have HIV vaccine now is that the immune system can't produce a special type of antibody that can neutralize HIV In this study, we engineered the immune system to produce a special environment to produce the appropriate antibody Based on previous years' research results, now researchers have clarified how and when broad-spectrum neutralizing antibodies (bnabs) appear in HIV infected people, and when they can effectively block the proliferation of antibodies to inhibit the virus One is the immune system, which sees bnabs as a danger and shuts down the production of bnabs; the other is that neutralizing antibodies require rare changes in their genetic makeup, which do not occur in important B cell diversification processes In this study, the researchers tracked the mutations and then engineered an HIV protein to target the V3 glycan region on the envelope of the virus, allowing it to preferentially bind to antibodies carrying the necessary mutations Using a mouse model expressing human neutralizing antibody precursors, the researchers found that immunogens can induce B cell lineages to undergo impossible mutations to produce broad-spectrum antibodies The researcher ALT said that we can create a mouse model expressing human broad-spectrum neutralizing antibody, which can provide us with a powerful new model system, in which we can repeatedly detect experimental HIV vaccine; the bnabs of the second pedigree will experience an impossible mutation, which will combine with different regions of the outer membrane called CD4 binding site, when After the researchers reconstructed the antibody history, they developed a second immunogen After testing in non-human primates, the researchers found that the immunogen also selects the necessary mutations, which can help develop potential neutralizing antibodies at CD4 binding sites 4 Science: the lymphatic system plays a key role in hair regeneration doi: 10.1126/science.aay4509; doi: 10.1126/science.aaz8780 considering the degree of daily wear, the skin has extraordinary self-healing ability Distributed in the skin are small stem cell banks, which are embedded in a supportive microenvironment called niches, so that the repair process is strictly controlled In repair, too much tissue may lead to cancer and other problems, while too little tissue may accelerate aging Until now, scientists were not sure whether these stem cells themselves could guide other stem cells to form new skin by reshaping their niches In a new study, Professor Elaine Fuchs of Rockefeller University and his team found that stem cells do affect tissue regeneration The study identified molecular coordination tools that stem cells use to transmit signals across niches The relevant research results were published online in the journal Science on October 31, 2019, and the title of the paper is "stem cell – driven repetitive coordinating ties tie region" The researchers also found a new component in the niches: a special type of blood vessel called lymphatic capillaries, which transports immune cells and expels excess fluid and toxins from tissues This new study shows that in the skin, these capillaries form a tight network around the stem cell niches within each follicle, connecting all their niches together The researchers found that hair follicle stem cells control the behavior of lymphatic capillaries by secreting molecules that act as drain switches, enabling them to control the fluid and cell composition of the surrounding environment, and ultimately keeping the regeneration of the entire tissue in sync 5 Science: scientists have successfully used the chain reaction of nine enzymes to produce the HIV drug islatravir doi: 10.1126/science.aay8484; Doi: 10.1126/science.aaz7376 recently, in a research report published in the international journal Science, researchers from Merck and kedicos successfully used a nine enzyme chain reaction method to manufacture HIV drug - islatravir; in the article, the researchers described the inspiration of their work and the effect of the final product The researchers pointed out that a variety of natural products are the result of many basic elements of biosynthesis Many organic experiences use the selectivity of enzymes to complete each step, which usually involves a multi-step chain reaction, the first of which will be used as the basis for the next step Based on this, researchers began to look for ways to make the experimental HIV drug islatravir First, they focused on the bacterial nucleoside salvage pathway (NSP) In pathway), this process is mainly involved in the recovery of bases and nucleosides from RNA degradation to DNA In this process, there are three main enzymes, namely, deoxyribose-5-phosphate aldolase (Dera), pentoxyribose-5-phosphate aldolase (PPM), and purine nucleoside phosphorylase (PNP) In order to use the same process to develop the drug islatravir, researchers need to take advantage of a special property of enzymes, that is, inverse property, which can make them different from traditional catalysts Researchers must find a way to make the above three enzymes accept unnatural substrates The solution is to borrow reverse NSP from RNP and ppm of E In order to make it work, researchers must also modify the enzymes to make them more active This work also involves optimizing the other two enzymes and using the other four enzymes in the natural state The final result is a cascade reaction involving nine enzymes, which can eventually produce the drug islatravir 6 Science: heavy weight! Scientists have identified special cells in the eyes that can help the brain distinguish between day and night! Doi: 10.1126/science.aaz0898 strong light at night will disturb the normal body