End point in 2019: heavyweight breakthrough research results of Nature magazine

By the end of the year, 2019 is coming to an end, and we will be greeted by a brand-new 2020 In 2019, the three famous international magazines cell, nature and Science (CNS) still published a lot of heavyweight research The small and medium-sized editors of this paper collate and share the highlights of the research published by nature in 2019! Photo source: Wikimedia [1] nature: drinking and smoking induce driver gene mutations, leading to esophageal cancer Yokoyama, A., kakiuchi, N., yoshizato, T et al Age related remodelling of oesophageal epichelia by mutated cancer drivers Nature 565312 – 317 (2019) doi: 10.1038/s41586-018-0811-x, January 2019, an international journal Nature In the previous study report, researchers from Kyoto University and other research institutions in Japan found that drinking and smoking may induce gene mutation to cause esophageal cancer; in this paper, the researchers used 682 kinds of micro scale PNE samples from human subjects with different ages and different lifestyles of esophageal squamous cell carcinoma risk to study early cloning events in the esophagus Then, the whole exome sequencing was used to detect the somatic mutation and abnormal copy number in these samples Through the unbiased detection of somatic mutations in PNE samples from a large number of subjects, these researchers showed the comprehensive landscape of clonal expansion in PNE samples, and revealed the ultrastructure and evolution history of proliferating clonal cells The researchers found that age-related progressive proliferation occurred in cloned cells with mutations in the driving gene (mainly Notch1) in the PNE samples, and that drinking and smoking significantly accelerated this progressive proliferation In almost all human bodies, cloned cells carrying driving gene mutations have appeared on multiple focal sites since early childhood Their number and size increase with age, and eventually thousands of cloned cells carrying driving gene mutations reshape almost the entire esophageal epithelium, which can occur without a lot of drinking and smoking, but , heavy drinking and smoking greatly accelerate the remodeling process 【2】 Nature: a new mechanism is expected to activate the immune system of the body to resist cancer Jeffrey J Ishizuka, Robert T Manguso, Collins K Cheruiyot, et al Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade, nature (2018) Doi: 10.1038/s41586-018-0768-9 in January 2019, an international journal Nature In the previous study, scientists from the University of Baylan in Israel found a new mechanism to activate the immune system to resist cancer cells, which may help promote immune cells to detect and destroy cancer cells In this paper, the researchers focus on a special mechanism, which can help cells to mark human virus like genes, so as to avoid the body's attack of recognizing them as viruses When the mechanism is inhibited, the immune system of the body can be regulated, so as to resist cancer cells in a very effective way, which is expected to effectively treat lung cancer and melanoma 。 If the mechanism is blocked, the immune system will become very sensitive, and when the mechanism is deactivated, the immune system will be able to target tumor cells more effectively, the researchers said The researchers hope that the results of this study can help effectively enhance the activity of the immune system of the body, so as to attack cancer cells; based on the findings of this study, many pharmaceutical companies have started to select new drugs that can effectively stimulate the immune system of the body to resist cancer 【3】 Nature: scientists found a new CRISPR gene editing tool: casx Jun Jie Liu, Natalia Orlova, Benjamin L Oakes, et al Casx enzymes compare a distinct family of RNA guided gene editors, nature (2019) Doi: 10.1038/s41586-019-0908-x in February 2019, an international journal Nature In the previous report, scientists from the University of California, Berkeley found a new small CRISPR gene editing tool: casx, which is similar to protein cas9, but much smaller than cas9 Casx can cut double stranded DNA, bind DNA and regulate gene expression, and target specific DNA sequences The researchers captured the snapshot image of casx protein in the gene editing process by using the frozen electron microscope Based on the special molecular composition and shape of the protein, the researchers said that the evolution of casx is independent of cas9, and they have no common ancestor The first thing to point out, the researchers say, is how these highly specific domains perform functions similar to those they see in other RNA guided DNA binding proteins The minimum size of casx helps to show the basic formula it uses in nature, while understanding this formula can help develop useful gene editing tools 【4】 Nature: heavyweight! Scientists have identified nearly 2000 unknown bacteria in human intestines: Alexandre Almeida, Alex L Mitchell, Miguel Boland, et al A new genetic blueprint of the human gut microbiota, nature (2019) doi: 10.1038/s41586-019-0965-1 in February 2019, an international journal Nature In the last report, scientists from the European Institute of bioinformatics and Sanger Institute identified nearly 2000 kinds of bacteria in the human intestine through their research At present, these bacteria Not cultivated in laboratory conditions, researchers use a series of calculation methods to analyze individual samples from all over the world Although researchers are expected to create a comprehensive list of common microorganisms in intestinal tract of North American and European people, they still lack data and information from other regions of the world Researchers say computational methods can help us understand bacteria that can't be cultured in the lab, using metagenomics It's a bit like mixing all the jigsaw pieces together to reconstruct hundreds of jigsaw pieces But researchers don't know what the final jigsaw image will look like Now researchers can use a series of computing tools to supplement and complete this work, so as to further explore the mystery of human intestine Now researchers have found a lot of the same bacteria when they analyze the population data of Europe and North America Species, and in the analysis of South American and African databases, they found that there may not be significant diversity in the previous populations, which shows that if we want to obtain complete picture information of human intestinal composition, we need to collect relevant data from the under representative populations Now scientists are expected to design a blueprint for human intestine, which will help scientists better study the pathogenesis of various human diseases, and develop new diagnosis technology and treatment methods for gastrointestinal diseases in the future Photo source: cc0 public domain [5] nature: heavyweight! Decoding the human immune system! Soto, C., bombardi, R.G., branchizio, A et al High frequency of shared clones in human B cell receptor repertoires Nature 566398 – 402 (2019) doi: 10.1038/s41586-019-0934-8, February 2019 In the previous report, researchers from Vanderbilt University in the United States sequenced for the first time the gene encoding the receptor Library of circulating B cells, a key part of the human immune system By sequencing these B-cell receptors in adults and infants, they found surprising overlaps in antibody sequences that may provide potential new antibody targets for developing vaccines and therapies that work in different populations In this study, researchers specifically studied part of the adaptive immune system, the circulating B-cell receptor, which is responsible for producing antibodies that are considered to be the main determinants of human immunity These B-cell receptors randomly select and link gene segments to form a unique nucleotide sequence called the "clonetype" of the receptor In this way, a small number of genes can lead to incredible receptor diversity, allowing the immune system to recognize almost any new pathogen By isolating white blood cells from three adults, the researchers cloned and sequenced up to 40 billion cells, specifically the combination of gene fragments that make up the circulating B cell receptor This kind of sequencing depth is unprecedented They also sequenced cord blood from three infants They do so with a view to collecting large amounts of data from a small number of individuals, rather than a small amount of data from a large number of people, as is the traditional practice 【6】 Nature: new research reveals why cancer most often spreads to the liver Lee, J.W., stone, M.L., porrett, p.m et al Hepatogenes direct the formation of a pro metastatic niche in the liver Nature 567249 – 252 (2019) doi: 10.1038/s41586-019-1004-y in March 2019, an international journal Nature In the previous research report, scientists from the University of Pennsylvania and other institutions revealed why cancer is most often spread to the liver through research In this paper, researchers found that liver parenchymal cells (the main functional cells of the liver) are at the center of a chain reaction, which makes the liver particularly sensitive to cancer cells These liver cells activate a kind of cell called stat 3 protein to respond to inflammation, which in turn increases the production of other proteins called SAA, which in turn reshapes the liver and creates the "soil" needed to "inoculate" cancer cells The researchers confirmed that blocking this process with antibodies that block IL-6, the inflammatory signal that drives this chain reaction, limits the potential for cancer to spread to the liver In addition, the researchers also found that IL-6 can promote liver changes whether there is tumor or not, which suggests that any disease (such as obesity or cardiovascular disease) related to the increase of IL-6 level may affect the liver's sensitivity to cancer These researchers say this provides evidence that therapies targeting hepatocytes may be able to prevent cancer from spreading to the liver, which is the main cause of cancer death 【7】 Nature: heavyweight! Scientists uncover the mystery of intestinal flora that human body can't cultivate! Stephen nayfash, Zhou Jason Shi, Rekha Seshadri, et al New insights from uncultured generations of the global human guide microorganism Nature, 2019; doi: 10.1038/s41586-019-1058-x, March 2019, an international journal Nature In the previous research report, scientists from Lawrence Berkeley National Laboratory and other institutions calculated and reconstructed 3810 open human intestinal macrogenomes, showing about 61000 microbial genomes, which are all the genes in the microbial samples The collection of materials, the macro genome assembly genome (MAGS) includes 2508 previously unknown species, which makes 4558 known species of human intestinal bacteria, and increases the phylogenetic diversity of sequenced intestinal flora by 50% The results of this study may help answer a number of questions, such as why specific microbial communities cannot be cultured in the laboratory, which scientists have previously used