China News Service, Beijing, January 13 (Reporter Sun Zifa) The Chinese Association of Science and Technology Association of Life Sciences released the results of the 2020 "Top Ten Progresses in Life Sciences in China" on the 13th, with a total of 8 knowledge innovation and 2 technological innovation projects The results were selected, including "the analysis of the first three-dimensional structure of the new coronavirus protein and the discovery of two clinical drug candidates" and "the construction of an animal model for new coronary pneumonia".
The contents of the latest China's top ten progress in life sciences in 2020 are as follows:
——The mystery of locust swarming: 4-vinyl anisole is the swarming pheromone of locusts.
A team of Kangle academicians from the Institute of Zoology, Chinese Academy of Sciences identified 4-vinylanisole (4VA), an odor molecule specifically volatilized by gregarious locusts, and identified it from chemical analysis, behavior verification, neuroelectrophysiological recording, and olfactory receptor identification , Gene knockout, field verification and other aspects prove that 4VA is a pheromone of migratory locust swarms.
The low-dose 4VA synthesized in the laboratory can attract a large number of wild locust populations.
This research not only reveals the mystery of locust swarms, it is also considered a major breakthrough in the fields of entomology and chemical ecology, and is of great significance to the control and prediction of locust plagues in the world.
The four control strategies based on insect chemosensory manipulation proposed in the study are considered to be new directions for future green pest control.
The results were published in "Nature" magazine, "Nature" issued editor's notes and special review articles, F1000Prime evaluation recommendation system gave the highest recommendation.
Progress 1: Migratory locust swarms and scattered locust bugs (larvae).
Photo courtesy of the Chinese Association of Science and Technology Life Sciences Association
——The analysis of the first three-dimensional structure of the new coronavirus protein and the discovery of two clinical drug candidates.
The main protease of the new coronavirus plays a key regulatory role in the virus life cycle and is a high-profile drug target.
The Shanghai University of Science and Technology and other units formed an anti-coronavirus joint research team, and took the lead in the world to analyze the high-resolution three-dimensional structure of the major protease and inhibitor complex of the key drug target of the new coronavirus. This is also the world's first analysis of the new coronavirus protein. Three-dimensional structure; clarified the mechanism of action of the inhibitor precisely targeting the main protease; found that ebselen and disulfiram and other old or clinical drugs are antiviral small molecules targeting the main protease, and both have been approved by the US FDA Entered into phase II clinical trial for the treatment of new coronary pneumonia.
The above results have laid an important foundation for the research and development of anti-coronavirus drugs.
The results were published in "Nature" magazine.
Progress 2: The complex structure of the new coronavirus main protease (red) and inhibitor (yellow).
Photo courtesy of the Chinese Association of Science and Technology Life Sciences Association
——The mechanism and regulation of organ aging.
Liu Guanghui's research group, Qu Jing's research group, Institute of Zoology, Chinese Academy of Sciences, Zhang Weiqi's research group, Beijing Institute of Genomics, Chinese Academy of Sciences, and Tang Fuchou's research group, Peking University collaborated to systematically analyze the aging markers and regulatory targets of important organs in primates; Revealed the molecular mechanism of elderly individuals susceptible to the new coronavirus; clarified the new mechanism of calorie restriction to delay aging by regulating the body's immune-inflammatory pathway at the system biology level; found that gene therapy based on the overexpression of core rhythm proteins can alleviate the bones of aging mice Joint degeneration and promote the regeneration of articular cartilage.
These research results have deepened people's understanding of the mechanism of organ aging and laid an important foundation for the establishment of early warning and scientific response strategies for aging and related diseases.
Related research results were published in journals such as Cell and Cell Research.
Progress 3: Systematic analysis of the markers and regulatory targets of primate organ aging.
Photo courtesy of the Chinese Association of Science and Technology Life Sciences Association
——Construction of animal model of new coronary pneumonia.
In the prevention and control of the new crown epidemic, animal models are one of the five main research directions for scientific research. It is the basic research work to clarify the pathogenic mechanism and transmission routes, screen drugs, and evaluate vaccines.
Discovering and identifying animals that are sensitive to the new coronavirus, developing reagents for detecting viruses in animals, and enabling animals to accurately simulate the clinical manifestations of diseases are the three key problems in modeling.
The research team of the Institute of Medical Laboratory Animals of the Chinese Academy of Medical Sciences cooperated with the Institute of Viral Disease Control and Prevention of the Chinese Center for Disease Control and Prevention and the Institute of Pathogenic Biology of the Chinese Academy of Medical Sciences. Through comparative medical analysis, they cultivated highly humanized animals with viral receptors. Established model-specific detection technology, confirmed the virus invasion receptor, confirmed the pathogenic pathogen according to Koch's law, revealed the immune and pathological characteristics of new coronary pneumonia, and reproduced the process of virus infection, replication, host immunity and pathogenesis. Simulated the different clinical characteristics of new coronary pneumonia, and constructed the first animal model in the world.
Using animal models, a series of disease mechanisms were clarified, a series of effective drugs were screened, and more than 80% of vaccine evaluations deployed by the country were completed. The model development methods and standards were provided to the World Health Organization (WHO) for international research.
The results were published in the journals "Nature" and "Animal Model and Experimental Medicine".
Progress 4: Imaging and pathological changes in rhesus monkeys of different ages after being infected with the new coronavirus.
Photo courtesy of the Chinese Association of Science and Technology Life Sciences Association
——The key cells and regulatory network of human brain development.
The brain is the material carrier of human intelligence activities. The study of the establishment of brain structure and functions during development will reveal the cellular and molecular mechanisms of intelligence formation, and provide theoretical clues and technical solutions for related medical applications.
The Wang Xiaoqun group of the Institute of Biophysics, Chinese Academy of Sciences, the Wu Qian group of Beijing Normal University, and the Tang Fuchou group of Peking University collaborated to analyze the hippocampus, hypothalamus, and hypothalamus during the critical period of human embryonic development through high-throughput single-cell analysis. The multi-subregions of the cerebral cortex and the retina have been researched on cell constitution maps and gene regulatory networks. The functional development of key cell types has been tracked, the key time nodes and genes for the development of multiple brain regions have been revealed, and the dynamics of the human brain have been mapped in detail The development blueprint provides a solid foundation for the diagnosis and treatment of related diseases.
Many research results have been published in "Nature", "Nature-Communication" and other magazines.
Progress 5: Cell composition and gene regulatory network during the development of the human brain hippocampus.
Photo courtesy of the Chinese Association of Science and Technology Life Sciences Association
——Discover the brain-splenic nerve pathway of behavioral control antibody immunity.
People's life experience suggests that behaviors such as meditation to physical exercise may enhance immunity.
However, whether brain activity can directly control the immune response that occurs in lymphoid organs such as the spleen has not been supported by strict experimental evidence for a long time.
The Qi Hai research group of the Institute of Immunology of Tsinghua University, the Hu Ji research group of the Shanghai University of Science and Technology, and the Zhong Yi research group of the McGovern Institute of Brain Science of Tsinghua University have worked together to find in a mouse model that if the spleen loses its innervation, vaccination After that, the body cannot produce antibodies normally.
Further experiments show that this is because there is a type of CRH neurons in the brain called the central amygdala and paraventricular nucleus that are connected to the splenic nerve.
Activating CRH neurons will increase splenic nerve activity, which in turn can increase the antibodies produced by vaccination; conversely, inhibiting CRH neurons will reduce the effectiveness of the vaccine.
Furthermore, they also designed a behavioral paradigm for mice that can enhance antibody production by activating this newly discovered brain-splenic nerve pathway.
These findings establish for the first time a neural pathway through which brain activity can increase the production of antibodies, and point to the possibility of using exercises, meditation and other behaviors to enhance vaccine effects and strengthen human immunity in the future.
The results were published in "Nature" magazine.
Progress 6: "Diligence" and brain nuclei and pathways that enhance immunity.
Photo courtesy of the Chinese Association of Science and Technology Life Sciences Association
——The mechanism of eating-induced cholesterol synthesis and the discovery of new lipid-lowering drug targets.
Cholesterol is an essential lipid for life activities, but too much can cause cardiovascular and cerebrovascular diseases.
When people eat carbohydrates, cholesterol is mainly obtained by their own synthesis.
It takes a lot of energy to synthesize cholesterol, so mammals only up-regulate synthesis after eating, and inhibit it when they are hungry. The mechanism of this has been unclear for a long time.
The laboratory of Song Baoliang of Wuhan University has made a new breakthrough in the field of cholesterol. The team found that after eating carbohydrates, the elevated glucose and insulin in the blood prompt the phosphorylation of USP20 protein in the liver. USP20 stabilizes the rate-limiting enzyme HMGCR in the cholesterol synthesis pathway, thus Up-regulate cholesterol synthesis.
Inhibit USP20, reduce blood lipids, lose weight and increase insulin sensitivity.
This discovery not only reveals the human body's nutritional induction mechanism, but also proves that USP20 can be used as a target for the development of new lipid-lowering drugs.
This research result and its application will benefit the health of the whole people.
The results were published in "Nature" magazine.
Progress 7: The mechanism of cholesterol synthesis induced by eating.
Photo courtesy of the Chinese Association of Science and Technology Life Sciences Association
——A new mechanism to improve the nitrogen fertilizer use efficiency of green revolution crop varieties.
Facing the major strategic needs of national food security and sustainable agricultural development, Fu Xiangdong's research team from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences has achieved important breakthroughs in the field of high-yield rice and high-efficiency coordinated regulation of nitrogen.
The study found that NGR5, a new component of the gibberellin signal transduction pathway, regulates the response of plants to changes in soil nitrogen levels by mediating histone methylation modification, and at the same time it competes with the growth repressor DELLA protein to bind to the gibberellin receptor GID1 , Realize gibberellin to regulate plant growth and development.
Increasing the expression of NGR5 in high-yield rice varieties can still achieve high yields under the conditions of reduced nitrogen fertilizer.
The discovery found a new breeding strategy that can not only ensure high yield, but also reduce nitrogen fertilizer input and reduce environmental pollution. It lays a theoretical foundation for cultivating new green, high-yield and high-efficiency varieties with "less input, more output, and environmental protection". There are broad application prospects in production, which can produce huge economic and social benefits.
The results were published in the "Science" magazine as a cover paper.
Progress 8: A new mechanism for NGR5 to synergistically regulate rice yield and nitrogen use efficiency.
Photo courtesy of the Chinese Association of Science and Technology Life Sciences Association
——Cloning, mechanism analysis and breeding utilization of wheat Gibberella resistance gene Fhb7.
Wheat head blight caused by Fusarium is called a wheat "cancer". The source of resistance is scarce, and it is a major international problem threatening food security.
The research team of Kong Lingrang of Shandong Agricultural University lasted 20 years to clone the major scab resistance gene Fhb7 from the wheat related genus Elytrigia longiflora for the first time and clarify its function, disease resistance mechanism and horizontal transfer evolution mechanism.
At the same time, using distant hybridization to transfer Fhb7 to popular wheat varieties, the resistance to scab resistance was stable, and there was no significant negative impact on yield.
At present, several new wheat lines with scab resistance selected by the team have entered national and provincial regional trials or production trials, and have been included in the joint research plan of Chinese wheat varieties, providing a "golden key to solving the worldwide problem of wheat scab ".
In addition, the broad-spectrum detoxification function of Fhb7 on the trichothecene toxins secreted by Fusarium is expected to be applied to the genetic improvement of other crops against Fusarium disease, as well as to solve the problem of mycotoxin contamination in food and feed.
The results were published in "Science" magazine.
Progress Nine: Fusarium infects wheat grains, resulting in reduced yield and quality.
Photo courtesy of the Chinese Association of Science and Technology Life Sciences Association
——The mechanism of antigen receptor signal transduction and its application in CAR-T therapy.
CAR-T cell therapy has been successfully applied to the clinical treatment of tumors, but it faces challenges such as cytokine release syndrome and low cell persistence.
The signal elements of CAR come from the CD3 chain of the antigen receptor TCR and co-stimulatory molecules such as CD28.
At present, the modification of CAR mainly focuses on costimulatory signal elements, while ignoring antigen signal elements.
The Xu Chenqi research group of the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, the Huang Chaolan research group of Peking University Health Science Center, and the University of California, San Diego Huienfu research group cooperated and found that the CD3 chain of TCR has special characteristics through quantitative mass spectrometry and biochemical methods. The signal transduction function can simultaneously recruit inhibitory molecule Csk and activating molecule PI3K.
Adding the CD3? intracellular region to the clinically used CAR sequence can make CAR-T cells have better persistence, stronger anti-tumor function, and reduce the risk of cytokine release syndrome.
The results were published in "Cell" magazine.
Progress 10: Modification of the original signal of the chimeric antigen receptor (CAR).
Photo courtesy of the Chinese Association of Science and Technology Life Sciences Association
The Consortium of Life Sciences Associations of the Chinese Association for Science and Technology stated that the selection of the “Top Ten Progresses in Life Sciences in China” in 2020 continues the method of recommending and selecting project results in the knowledge innovation and technological innovation categories. Senior experts in the fields of, biotechnology and clinical medicine were selected and finalized by the presidency of the Life Science Society of the Chinese Association for Science and Technology.
In this selection, the number of projects recommended by the member societies of the consortium has increased significantly compared with previous years, reflecting that the selection of "Top Ten Progresses in Life Sciences in China" is becoming more and more perfect, and social influence and attention continue to expand; the proportion of the award-winning projects is the proportion of the projects led by African academicians It is larger than in previous years, reflecting the strong reserve force in the field of life science research in China.
More notably, this selected project has the characteristics of outstanding originality and great social significance. Among them, the knowledge innovation project "The mystery of locust swarms: 4-vinyl anisole is the swarming pheromone of locusts" , For the first time on a global scale, the mystery of locust swarms was revealed. It is of great significance to control and predict the world's locust plagues and solve the world's food problems.
The knowledge innovation project "Analysis of the first three-dimensional structure of the new coronavirus protein and the discovery of two clinical drug candidates" and the technological innovation project "Construction of an animal model for new coronary pneumonia" are of great significance to solving the current global epidemic of new coronary pneumonia.
Technological innovation projects "Cloning, mechanism analysis and breeding utilization of wheat gibberellin resistance gene Fhb7" and knowledge innovation projects "Mechanism of diet-induced cholesterol synthesis and discovery of new lipid-lowering drugs" focus on hot issues such as national economy, people's livelihood and national health.
The Consortium of Life Sciences Society of China Association for Science and Technology has carried out the annual selection of "Top Ten Progresses in China's Life Sciences" since 2015, aiming to promote life science research and technological innovation, and fully display and publicize major scientific and technological achievements in the field of life sciences in China.
At present, the selection activities have been carried out for 6 consecutive years. After the selection results are announced each year, selected project experts will be invited to write and publish popular science books, and exchange meetings and youth-oriented science reports will be held to reveal the new mysteries of life sciences to the public. The development of new science and technology, new breakthroughs in medicine, and the development of bio-economy provide new ideas and greatly enhance the social influence of life sciences.
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