End of 2019: Interpretation of Chinese scientists' heavyweight research results

Time is always fleeting, 2019 is coming to an end, and we will be greeted by a new 2020 In the coming 2019, Chinese scientists have made many significant and far-reaching research results in many research fields The small and medium-sized editors of this paper will sort out and interpret the important research results published by Chinese scientists in 2019 and share them with readers! Photo source: cell, DOI: 10.1016/j.cell.2018.12.030 [1] cell: revealing the mechanism of new antiviral factors inhibiting HIV-1 programmed-1 ribosome migration Xinlu Wang, Yifang Xuan, Yuling Han, et al Regulation of HIV-1 Gag pol expression by shiftless, an inhibitor of programmed-1 ribosome framing, cell 24 January 2019, DOI: 10.1016/j.cell.2018.12.030 virus genome size is usually relatively small In order to increase the information content of genome, many viruses use a translation and recording mechanism called programmed ribosome transcoding -In eukaryotes, - 1prf may also lead to the premature appearance of termination codons, which may lead to mRNA degradation The -1PRF mechanism plays an important role in the post transcriptional regulation of gene expression However, how the -1PRF mechanism is regulated by host factors is largely unknown In January 2019, in a research report published in the international journal Cell, scientists from China reported a new host antiviral factor inhibiting-1prf, which researchers call "shiftless" In order to explore the mechanism of shiftless, Gao Guangxia's research group analyzed the interaction between shiftless and - 1 PRF RNA and ribosome in translation, and the latter two are the two key factors in the process of - 1 PRF Shiftless and the latter two interact Based on this result, they speculated that the simultaneous binding of shiftless with ribosome and - 1 PRF RNA in translation might cause ribosome to fall into a nonproductive state, thus stagnating on - 1 PRF RNA Stagnant ribosomes should be rescued through quality control mechanisms, leading to premature translation termination 【2】 Nature: a new therapeutic target for early stage of HCC Nature 567257-261 (2019) doi: 10.1038/s41586-019-0987-8 In March 2019, in a research report published in the international journal Nature, scientists from China described 110 pairs of tumor tissue and non tumor tissues of early clinical HCC related to hepatitis B virus (HBV) infection through proteomic analysis and phosphoproteomic analysis Tissue, the quantitative proteomic data thus obtained highlight the heterogeneity of early HCC In this paper, the researchers used this heterogeneity to divide these early HCC into three different subtypes: S-I, S-II and s-iii, each with different clinical results Based on a mouse model of xenogeneic transplantation of HCC tumor derived from patients, the researchers found that treatment with a soas1 inhibitor called avasimibe significantly reduced the size of the tumor with high levels of soat1 expression The proteomic typing of early HCC proposed in this study provides new insights into the biological characteristics of this cancer and offers opportunities for personalized treatment targeting it 【3】 Cell Rep: discovery of intestinal microflora may help human beings resist cold, Baoguo Li, Li Li, Min Li, et al Microbiota completion improvements thermogenesis of brown adipse tissue and browning of white adipse tisssue, cell reports, 5 March 2019, DOI: 10.1016/j.cellep.2019.02.015 In March 2019, in a research report published in the international journal Cell reports, scientists from China revealed the key role of intestinal flora in the body's temperature regulation and the animal's response to the cold environment during the temperature regulation In cold exposure, animals can generate heat by activating brown adipose tissue (BAT), while maintaining body temperature by promoting "browning" of white adipose tissue; in order to analyze the function of intestinal flora in bat activation, researchers used different antibiotics After removing the intestinal flora from animals, they found that animals without intestinal flora would suffer from the damage of temperature regulation In addition, the researchers found that the removal of intestinal flora can inhibit the increase of UCP1 expression in bat, but also reduce the level of browning of white adipose tissue; the reason for this effect may be the lack of complete microbial group of the body, so that animals can not digest enough food to meet the increase of energy demand in cold state, and this effect on bat It is also a secondary effect 【4】 Nature: to reveal the mechanism of cancer cells regulating ammonia metabolism through p53 Li, L., Mao, Y., Zhao, L et al P53 regulation of ammonia metabolism through urea cycle controls polyamine biosynthesis Nature 567253 – 256 (2019) doi: 10.1038/s41586-019-0996-7 in March 2019, an international journal Nature In the previous report, scientists from China found that as the most frequently mutated tumor suppressor gene in human tumors, p53 regulates ammonia metabolism by inhibiting urea cycle By downregulating the transcription of CPS1, OTC and arg1, p53 can inhibit urea production and ammonia clearance in vitro and in vivo, thus inhibiting tumor growth In turn, the down-regulation of these genes activates p53 through the mechanism mediated by MDM2 The researchers pointed out that the accumulation of ammonia resulted in a significant decrease in the mRNA translation of ODC, the rate limiting enzyme of polyamine biosynthesis, thus inhibiting the biosynthesis of polyamine and cell proliferation Therefore, these studies found that p53 was associated with urea production and ammonia metabolism, and further revealed the role of ammonia in the control of polyamine biosynthesis and cell proliferation 【5】 Science: to analyze the three-dimensional structure of human parathyroid hormone receptor-1, Chinese Academy of Sciences, Medical College of Zhejiang University, Fudan University, University of Pittsburgh, van ander Institute, Massachusetts General Hospital, Li Hua Zhao, Shanshan Ma, Ieva sutkeviciute, et al Structure and dynamics of the active human paratyroid hormone receptor-1, Science 12 APR 2019: Vol 364, issue 6436, pp 148-153 doi: 10.1126/science.aav7942, April 2019, an international journal Science In the report above, scientists from China and the United States have built a three-dimensional picture of a molecular complex through research, which may help to develop drugs that better treat osteoporosis and cancer but have fewer side effects These near atomic resolution pictures describe the structure of human parathyroid hormone receptor-1 (PTH1R) PTH1R is a kind of molecule that transmits signals to cells, and can interact with two key messengers One of the messengers is a kind of molecule simulating parathyroid hormone (PTH), which can regulate the calcium level in vivo, and the other is a stimulating G protein, which can regulate bone turnover This molecular complex is composed of human PTH1R, PTH mimic and stimulating G protein The findings provide scientists with a better blueprint, or hope to develop drugs to treat osteoporosis and other diseases such as cachexia, which can cause severe weakness and weight loss, which can be fatal for cancer patients Photo source: Science Translational Medicine, 2019, Doi: 10.1126/scitranslmed.aau7116 [6] SCI transl Med: it is found that ntacapone is expected to treat obesity and diabetes by Chinese Academy of Sciences, the Fourth Military Medical University, Tsinghua University, shipping Peng, Wen Xiao, Dapeng Ju, et al Identification of entacapone as a chemical inhibitor of FTO medical metallic regulation through FoxO1, Science Translational Medicine 17 APR 2019: Vol 11, issue 488, eaau7116 doi: 10.1126/scitraslmed.aau7116 now researchers have found that gene FTO can participate in metabolic disorders such as obesity and diabetes However, the precise molecular mechanism of FTO regulating metabolism is still unknown In May 2019, in a research report published in the international journal Science Translational Medicine, scientists from China conducted a structure-based virtual screening of FDA approved drugs through research, and identified entacapone as a potential FTO inhibitor Through structural and biochemical studies, the researchers found that entacapone directly binds to FTO and inhibits FTO activity in vitro In addition, in diet induced obese mice, entacapone reduces weight and fasting blood glucose concentration The researchers identified the transcription factor FoxO1 MRNA is the direct substrate of FTO, and it is confirmed that entacapone has an effect on gluconeogenesis in liver and thermogenesis in adipose tissue by acting on fto-foxo1 regulatory axis 【7】 Nat Sci Rev: successfully inserted human brain gene into macaque genome Lei Shi, Xin Luo, Jin Jiang, et al Trans rhesus monkeys carrying the human MCPH1 gene copies show human like neuron of brain development, National Science Review (2019) Doi: 10.1093/nsr/nwz043 In May 2019, in a research report published in the international journal national science review, scientists from China created multiple transgenic macaques by inserting human genes involved in brain growth into the monkey's genome In this article, researchers described how they carried out relevant experiments on macaques after they were born In order to integrate the gene into the monkey genome, the researchers injected the virus carrying the gene into the monkey embryo, and promoted the natural development of the monkey Finally, 11 monkeys carrying the modified genome were born, but only 5 survived The researchers tested the 5 monkeys to clarify the impact of human genes on their development and body ability The researchers say that no macaque has ever had a larger brain than normal, but all monkeys perform better than average in memory testing and processing 【8】 PLoS Biol: develop drugs that can effectively inhibit hepatitis A virus, Tsinghua University, Sichuan University, CAS Cao L, Liu P, Yang P, Gao Q, Li h, sun y, et al (2019) structural basis for neutralization of hepatitis A virus information a rational design of high potency inhibitors PLoS Biology 17 (4): e3000229 Doi: 10.1371/journal.pbio.3000229 in May 2019, in a research report published in the international journal PLoS Biology, scientists from China found that in the past, a drug used to treat head and neck cancer could be used as a leading compound to help develop drugs for the treatment of hepatitis A virus infection In this new study, the authors report four powerful hepatitis A virus specific neutralizing antibodies