In August, a number of studies involving Chinese scholars were published in Nature and its important sub-Journals, including single-cell RNA sequencing and analysis of transcriptional regulatory networks. It was the first report that pathogens can directly act on death receptor complexes, as well as H7N9 influenza The latest progress in virus research.
First, researchers from Tongji University collaborated with the University of California, Los Angeles, using single-cell RNA sequencing (RNA-seq) technology, for the first time in the world to systematically analyze the transcriptional regulatory network of human and other mammalian embryos before implantation. Fully clarified the relevant important scientific issues in the early embryonic development process.
The researchers used the RNA-seq technology of single-cell expression profiling to break through the bottleneck of a small initial sample size. A systematic analysis of the whole-genome RNA transcription profile of each stage of early human embryonic development found that there existed various stages of early embryonic development Differences in expression of single alleles from father or mother. At the same time, using weighted gene co-expression network analysis (WGCNA) showed that the cell cycle, gene regulation, protein translation and transcriptional changes of metabolic pathways in each stage of early embryonic development occurred sequentially in a step-by-step manner, and it was clear that the mechanism is Conservation exists between species, only differing in development specificity and timing, which proves the evolutionary commonness of early embryonic development in mammals. In addition, the study also identified key candidate genes that drive various stages of early embryonic development.
The research results will have a profound impact on the purification, classification and clinical treatment of stem cells. The article systematically analyzed the differentiation process of mammalian early embryonic totipotent cells and obtained molecular markers at various cell stages Selection and clinical stem cell therapy provide guidance, especially in some refractory diseases, such as nerve cell injury and treatment. At the same time, the research results will also bring good news to human assisted reproductive technology, commonly known as "test tube baby" technology.
Secondly, researchers from NIBS reported for the first time that pathogenic bacteria can directly act on death receptor complexes, demonstrating a new mechanism of pathogenic virulence, and revealing how enteropathogenic Escherichia coli can be effectively determined in the host by suppressing natural immunity Molecular mechanism of colonization.
Researchers "inject" virulence effector proteins into eukaryotic cells through a type 3 secretion system, thereby blocking or regulating various signaling pathways in the host, which is an important mechanism for common Gram-negative pathogen infection and pathogenicity. The researchers first discovered that NleB can effectively inhibit the tumor necrosis factor (TNFα) activation of NF-κB inflammation, but has no effect on IL-1β activation of NF-κB. Then they combined yeast two-hybrid and co-immunoprecipitation and other biochemical methods to identify the linker molecule TRADD downstream of TNF receptor (TNFR1) as the host target protein of NleB, and found that NleB acts on the C-terminal death domain of TRADD Inhibit its oligomerization. Consistent with the biochemical results, they found that NleB not only inhibited TNFα activation of NF-κB inflammation, but also effectively blocked TNFα-induced apoptosis and necrosis. Through a series of mass spectrometry analysis and biochemical experiments in vitro and in vivo, they further revealed that NleB is a brand-new glycosyltransferase, N-acetylglucosamination modification of arginine at position 235 in the TRAD death domain, resulting in The domain loses oligomerization activity.
In addition, researchers from the Shantou University School of Medicine, the University of Hong Kong and others tracked the evolution of H7N9, a deadly avian influenza virus, and found evidence of the parallel evolution of H7N9 and a similar avian influenza virus that infects mammals.
Also in the Nature magazine on August 29, BGI Shenzhen BGI cooperated with the French Academy of Agricultural Sciences and the University of Copenhagen and found for the first time that there are significant differences in the types and numbers of intestinal flora in obese and non-obese people. And pointed out that the intestinal flora can be used as a new entry point to provide new prevention and treatment ideas for the obesity problem that increasingly disturbs the lives of modern people.
This study used a new analysis method-quantitative metagenomics (quantitative metagenomics) to analyze the intestinal flora of 292 Danes. It was found that the population can be divided into two groups according to the number of individual intestinal microbial genes, that is, the intestinal microbial abundance, low microbial abundance groups and high microbial abundance groups. The study found that a quarter of the samples were distributed in low-microbial richness groups, and the remaining samples were distributed in high-microbial richness groups. The proportion of obese individuals in the low-microbial-abundance group is significantly higher than that of the high-abundance group, and the individuals in them show more obese characteristics.
Through further research, it was found that individuals with low microbial richness often carried more pro-inflammatory bacteria, while individuals with high microbial richness contained more anti-inflammatory bacteria. Individuals with low microbial abundance also contain more body fat, most of which show insulin resistance, increased serum leptin, high serum insulin, high triglycerides and free fatty acids, low serum high density lipoprotein cholesterol and other phenomena. There are other signs of inflammation, so people with low microbial abundance are at higher risk of developing obesity-related diseases such as pre-diabetes, type 2 diabetes, and ischemic cardiovascular disease.
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