:2019-02-28

The oldest human being outside Africa may be in the Loess Plateau of China? Is man suffering from depression because the neurons in the lateral nucleus of the brain are exploding at high frequencies? Mr. Newton, your universal gravitational constant has been accurately measured by Chinese comrades... In 2018, China’s basic research field shines. On February 27, 2019, the Basic Research Management Center of the Ministry of Science and Technology held the "2018 China Science Top Ten Experts Interpretation Meeting", and released the 20th China Science Top Ten Progress: Successfully cloned macaques based on somatic cell nuclear transfer technology, creating the first Artificial single-chromosome eukaryotic cells, revealing depression and rapid antidepressant mechanism of ketamine, developing intelligent DNA nano-robots for tumor treatment, measuring the highest precision gravitational constant G value to date, and directly detecting electron cosmic ray energy for the first time The inflection near the 1TeV, revealing the atomic structure and magical effects of hydrated ions, creating nano and millimeter-scale imaging techniques that detect intracellular structural interactions, regulating plant growth-metabolic balance for sustainable agricultural development, and humans Ten major scientific advances, including the history of the Loess Plateau and the 2.12 million years ago, were selected.
Ye Yujiang, Director of the Basic Research Department of the Ministry of Science and Technology, and Liu Min, Director of the High Technology Research and Development Center and the Basic Research Management Center of the Ministry of Science and Technology, issued certificates of honor for the top ten candidates. Experts have interpreted the top ten progress item by item.
1. Successfully cloned macaques based on somatic cell nuclear transfer technology. Non-human primates are the closest animals to humans. Somatic cell cloning technology is considered to be the best method for constructing non-human primate genetically modified animal models because of the short-term production of animal models with consistent genetic background and no chimerism. Since the 1997 report of the cloned sheep "Dolly", although many laboratories have tried somatic clonal monkey research, they have not succeeded. The Institute of Neuroscience of the Chinese Academy of Sciences/Center for Excellence in Brain Science and Intelligent Technology Sun Qiang and Liu Zhen's research team succeeded in obtaining two healthy and surviving somatic cloned monkeys after five years of research. They found that the combined use of histone H3K9me3 demethylase Kdm4d and TSA can significantly increase the in vitro blastocyst development rate of cloned embryos and the pregnancy rate of recipients after transplantation. On this basis, they used fetal fibroblasts as donor cells for nuclear transfer, and transplanted cloned embryos to surrogate recipients, successfully obtained two healthy surviving cloned monkeys; and using cumulus granule cells as donor nuclei In the nuclear transfer experiment, although two full-term individuals were also obtained, the two monkeys died very quickly. Genetic analysis confirmed that the nuclear DNA of the cloned monkeys produced in the above two cases was derived from the donor cells, and the mitochondrial DNA was derived from the oocyte donor monkey. The success of somatic cell cloning monkeys is a breakthrough in this field. This technology will provide more convenient and precise technical means for non-human primate gene editing operations, making non-human primates possible to be widely used. Animal models, in turn, promote the rapid development of primate reproductive development, biomedical science, and brain cognitive science and brain disease mechanisms. Nikos K. Logothetis, a member of the German Academy of Sciences, commented on the topic "Cloning NHP: A major milestone in basic and biomedical research" and concluded that this work demonstrates the use of somatic cell nuclear reproduction. The feasibility of cloning macaques has broken technical barriers and created a new era of using non-human primates as experimental models, a truly exciting milestone in biomedical research.
2. Create the first artificial single-chromosome eukaryotic cells. Eukaryotic cells usually contain multiple chromosomes, such as 46 humans, 40 mice, 8 fruit flies, and 24 rice. Whether the number of chromosomes of these naturally evolved eukaryotes can be artificially changed, whether a single-chromosome eukaryotic organism with normal functions can be artificially created is a frontier scientific problem in the field of life sciences. Institute of Plant and Plant Science Excellence in Innovation / Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Sui Zhongjun and Xue Xiaoli Research Group, Zhao Guoping Research Group, Institute of Biochemistry and Cell Biology Zhou Jinqiu Research Group, Wuhan Fraser Gene Information Co., Ltd. The eukaryotic Saccharomyces cerevisiae containing 16 chromosomes is a research material. It uses synthetic biology "engineering" method and high-efficiency enabling technology to artificially create a simple life that does not exist in nature for the first time in the world - only a single chromosome Eukaryotic cells. The study shows that natural complex life systems can be reduced to simple by human intervention, and even artificially create new life that does not exist in nature. Nature, The Scientist and others commented that this may be the largest genomic remodeling to date, and these genetically engineered yeast strains are powerful resources for studying important concepts of chromosomal biology, including chromosome replication, recombination and isolation.
3. Revealing the occurrence of depression and rapid antidepressant mechanism of ketamine Depression seriously impairs the physical and mental health of patients. It is an important cause of suicide in modern society, causing huge losses to society and families. However, traditional antidepressants have a slow onset of action (6-8 weeks) and only work in about 20% of patients, suggesting that the current understanding of the mechanism of depression has not touched its core. In recent years, it has been found clinically that the anesthetic ketamine has a rapid (within 1 hour) and high-efficiency (effective in 70% refractory patients) anti-depressant effect at low doses, and is considered to be the most in the field of mental diseases for nearly half a century. Important findings. However, ketamine is addictive and has a large side effect and cannot be used for a long time. Therefore, understanding the mechanism of rapid antidepressant of ketamine has become the "Holy Grail" in the field of depression research, because it will suggest the core brain mechanism of depression and provide a scientific basis for the development of fast, efficient and non-toxic antidepressants. In 2018, Hu Haiyan's research group of Zhejiang University School of Medicine made a breakthrough in research in this field: in the study of the neural circuit of depression, the team found that the brain's anti-reward center - the nerve in the lateral nucleus Meta-activity is the source of depression. Neurons in this region suppress the activity of the “reward center” in the brain through its special high-frequency dense “cluster discharge”. Through the technique of optogenetics, they directly proved that the cluster discharge in the nucleus of the nucleus is a sufficient condition for inducing behavioral manifestations such as despair and loss of pleasure in animals. In response to the molecular mechanism of depression, the team found that this cluster-like discharge is mediated by the NMDAR-type glutamate receptor. As a blocker of NMDAR, the pharmacological mechanism of ketamine is through inhibition of nucleus neurons. The cluster discharge discharges its suppression of the downstream “reward center” at a high speed and efficiently, thereby achieving the effect of improving mood in a very short time. At the same time, the research team made a more in-depth explanation of the cellular and molecular mechanisms that produce cluster discharges. Through high-throughput quantitative protein profiling techniques, they found that the formation of depression was accompanied by overexpression of the potassium channel Kir4.1 in glial cells. The regulation of depression in the Kir4.1 channel is rooted in the histological basis of dense packing of neurons by glial cells in the nucleus. In the narrow interface of neuronal-glial interactions, overexpression of Kir4.1 on glial cells triggers a decrease in the extracellular potassium concentration of neurons, which induces hyperpolarization of neuronal cells, T-VSCC calcium. Channel activation ultimately leads to NMDAR-mediated cluster discharge. The above studies systematically explained the mechanism of depression, a major disease, subverting the popular “monoamine hypothesis” on the core mechanism of depression, and providing side effects for the development of alternatives to ketamine and avoiding addiction. A new scientific basis. At the same time, the NMDAR, Kir4.1 potassium channel, T-VSCC calcium channel identified by the institute can be used as a molecular target for rapid anti-depression, providing a new and better way to develop more and better antidepressant drugs or intervention techniques. The idea is of great significance in the ultimate fight against depression. Journals such as Science and Scientific American reported on the work, saying "this is an amazing discovery."
4. The development of intelligent DNA nano-robots for cancer treatment using nanomedicine robots to achieve accurate diagnosis and treatment of major human diseases is a great dream pursued by scientists. National Nanoscience Center Nie Guangjun, Ding Baoquan and Zhao Yuliang Research Group and the Yanzhou Research Group of Arizona State University, etc., have made breakthroughs in the research of nano-robots that can transport drugs in vivo, realizing nano-robots in vivo (mouse and pig) The intravascular stable work and efficient completion of the fixed drug delivery function. The researchers built an automated DNA robot based on DNA nanotechnology, which was loaded with the thrombin, thrombin. The nano-robot is functionalized by a specific DNA aptamer and can bind to nucleolins specifically expressed on tumor-associated endothelial cells to precisely target tumor vascular endothelial cells; and as a responsive molecular switch, open DNA nano-robots Releases thrombin at the tumor site, activates its coagulation function, and induces tumor vascular embolization and tumor tissue necrosis. The therapeutic effects of this innovative approach have been validated in a variety of tumors including breast cancer, melanoma, ovarian cancer, and primary lung cancer. And experiments with mice and Bama miniature pigs show that this nano-robot has good safety and immune inertia. The above research shows that DNA nano-robot represents a new model for future accurate human drug design, providing a new intelligent strategy for the treatment of diseases such as malignant tumors. Nature Reviews Cancer, Nature Biotechnology and other comments believe that the work is a milestone; the United States Journal of the United States and the same sex breeding, liquid biopsy, artificial intelligence, together with the selection of the world's four major technological advances in 2018.
5. Measured the highest precision gravitational constant G value to date Newton's universal gravitational constant G is the first basic physical constant recognized by human beings, and plays a very important role in physics and even the entire natural sciences. For two centuries, experimental physicists have made tremendous and painstaking efforts to accurately measure g-values ​​of gravitational constants, but their measurement accuracy is still the lowest of all physics constants. According to Newton's law of universal gravitation, G should be a fixed constant, which does not change depending on the measurement location and measurement method. However, the current G values ​​measured by different research groups in different countries do not match. In order to study this problem in depth, the research groups of the Gravity Centers of the Physics Institute of Huazhong University of Science and Technology, Luo Jun, Yang Shanqing and Shao Chenggang, began to use two independent methods in 2009—the torsion balance cycle method and the torsion balance angle acceleration feedback method. G value. After years of hard work, both methods have achieved the highest international measurement accuracy in 2018 (G values ​​are 6.674184 × 10−11 and 6.674484 × 10−11m3/kg/s2, respectively, with relative standard deviations of 1 million points respectively). 11.64 and 11.61), more critically, the two results fit within the range of 3 standard deviations. Nature's journal, with the title "Gravity measured with record precision", commented that this work is the result of the least uncertainty of the gravitational constants measured by two independent methods to reveal The reason for the difference in the measurement of the gravitational constant provides a very good opportunity, and also provides an opportunity to further measure the true value of the gravitational constant; and evaluates this work as a "model of excellence in precision measurement."
6. For the first time, it is directly detected that the negative electrons and positrons in the high-energy cosmic ray near the 1 TeV of the electron cosmic ray spectrum will lose energy quickly during its travel, so its measurement data can be used as a probe for high-energy physical processes. It is even used to study the quenching or decay of dark matter particles. The electron cosmic ray energy spectrum obtained by indirect detection of the ground-based Cherenkov gamma-ray telescope array has signs of inflection near 1 TeV (1 TeV = 1000 GeV = 1 trillion electron volts), but its systematic error is large. The energy measurement range of the electronic astronomical ray of China's first astronomical satellite omnipotent (DAMPE) is significantly higher than that of foreign space exploration equipment (such as AMS-02, Fermi-LAT), expanding the window of human observation of the universe in space. Based on the in-orbit measurement data of the 530 days before the Goku, the DAMPE team accurately measured the electron cosmic ray spectrum of the 25GeV-4.6TeV energy range with unprecedented high energy resolution and low background. The energy spectrum obtained by the Wukong can be well fitted with a piecewise power law model rather than a single power law model, clearly indicating that there is an inflection near 0.9 TeV, confirming the results of ground indirect measurements. This inflection reflects the typical acceleration capability of high-energy electron radiation sources in the universe, and its precise descent behavior plays a key role in determining whether some of the electron cosmic rays are from dark matter. In addition, the energy spectrum obtained by the Goku shows signs of abnormal flow near 1.4 TeV, and further data is needed to confirm whether there is a fine structure. Professor Lars Bergstrom, a member of the Royal Swedish Academy of Sciences and secretary of the Nobel Prize in Physics, confirmed that this was the first direct measurement of this turning point. Professor Marc Kamionkowski of Johns Hopkins University in the United States commented that this is one of the most exciting scientific advances of the year.
7. Revealing the atomic structure of hydrated ions and the combination of magic number effect ions and water molecules to form hydrated ions is one of the most common and important phenomena in nature, and plays an important role in many physical, chemical and biological processes. As early as the end of the 19th century, people realized the existence of ion hydration and began systematic research. The microstructure and dynamics of hydrated ions have been the focus of academic debate for more than a century, and there is still no conclusion. The reason is that there is a lack of atomic scale experimental characterization methods and accurate and reliable computational simulation methods. The research team of the Center for Quantum Materials Science, School of Physics, Peking University, Jiang Ying, Wang Enge and Xu Limei, and the Gao Yiqin Research Group of the School of Chemistry and Molecular Engineering, developed a new scanning probe technology based on high-order electrostatic force, which refreshed the scanning probe microscope. The world record of spatial resolution enables direct imaging and localization of hydrogen atoms. For the first time in the world, atomic-scale resolution images of individual sodium ion hydrates have been obtained, and it has been found that a specific number of water molecules can increase the mobility of hydrated ions. An order of magnitude, this is a new dynamic phantom effect. Combined with first-principles calculations and classical molecular dynamics simulations, they found that this magic number effect is derived from the degree of symmetry matching between ion hydrates and surface lattices, and still exists at room temperature and has a certain universality. . For the first time, this work clarified the atomic configuration of ion hydrates at the interface and established a direct correlation between the microstructure and transport properties of ion hydrates, subverting the traditional understanding of ion transport in restricted systems. This has important potential implications for many applications such as ion batteries, corrosion protection, electrochemical reactions, seawater desalination, and bioion channels. David Schilter, editor-in-chief of Nature Reviews Chemistry, commented that the study yielded "the perfect hydrated ion structure and kinetics information."
8. Create nano- and milli-scale imaging techniques that detect intracellular structural interactions Within eukaryotic cells, the organelles and cytoskeleton undergo highly dynamic and organized interactions to coordinate complex cellular functions. Observing these interactions requires non-invasive, long-term, high temporal and spatial resolution, low background noise imaging of the intracellular environment. In order to achieve these objectives in a normal situation, the Li Dong Research Group of the Institute of Biophysics of the Chinese Academy of Sciences and the Howard Hughes Medical Institute of the United States, Jennifer Lippincott-Schwartz and Eric Betzig, developed a grazing incidence structured light illumination microscope (GI- SIM) technology, which continuously images thousands of dynamic events near the cell basement membrane at 97 nanometer resolution and 266 frames per second. Using multicolor GI-SIM technology, the researchers revealed a variety of new interactions between organelles, organelles, and organelle-cytoskeleton, deepening the understanding of the complex behavior of these structures. Accurate measurements of microtubule growth and contraction events help distinguish different microtubule dynamic instability patterns. Analysis of the interaction between the endoplasmic reticulum (ER) and other organelles or microtubules reveals a new mechanism of remodeling of the endoplasmic reticulum, such as the endoplasmic reticulum on a mobile organelle. Moreover, studies have found that endoplasmic reticulum-mitochondrial contact points promote mitochondrial division and fusion. Professor Xiao-Fan Wang of the Chinese Academy of Sciences and Duke University of the United States commented that this work has developed a new technology that visualizes the dynamic interaction and movement of organelles and cytoskeleton in living cells, bringing cell biology into A new era helps to better understand the molecular events under living cell conditions, and also provides a window into the key biological processes from the mechanism, which can have a major impact on the entire discipline of life sciences.
9. Regulating Plant Growth - Metabolic Balance to Achieve Sustainable Agricultural Development Increasing crop productivity by increasing the amount of inorganic nitrogen fertilizer applied, while ensuring global food security, but also exacerbating damage to the ecological environment, thus improving crop nitrogen use efficiency important. This requires a deeper understanding of the synergistic regulation mechanisms such as plant growth and development, nitrogen uptake and utilization, and photosynthetic carbon fixation. Studies by Fu Xiangdong, a research group and collaborator of the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, showed that the reverse balance regulation between rice growth regulator GRF4 and growth inhibitor DELLA confers stability between plant growth and carbon-nitrogen metabolism. State adjustment. GRF4 promotes and integrates plant nitrogen metabolism, photosynthesis, and growth, while DELLA inhibits these processes. The high level of accumulation of DELLA protein, which is a typical feature of the “Green Revolution” variety, resulted in a semi-dwarf agronomic trait, but with a decrease in nitrogen use efficiency. By tilting the GRF4-DELLA balance to the increase in GRF4 abundance, it is possible to improve the nitrogen use efficiency of the "Green Revolution" variety and increase grain yield while maintaining the semi-dwarf traits. Therefore, the coordinated regulation of plant growth and metabolism is a new breeding strategy for sustainable agriculture and food security in the future. The Nature Journal published a review article that the breeding strategy declared "a new green revolution is coming."
10. Pushing the history of human life on the Loess Plateau to 2.12 million years ago The origin and evolution of human beings is a major world frontier scientific issue. The most recognized ancient stone place outside Africa is the Demanisi site in Georgia. The age is 1.85 million years ago. A 13-year study led by Zhu Zhaoyu from the Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Huang Weiwen and the University of Exeter, Robin Dennell, found a new Paleolithic site in Lantian County, Shaanxi Province. - Shang Chen site. The researchers used a multidisciplinary cross-technical approach such as loess-paleostratigraphy, sedimentology, mineralogy, geochemistry, paleontology, rock magnetism, and high-resolution paleomagnetic dating to test thousands of samples and establish new ones. The loess-paleozoic chronostratigraphic sequence, and 96 pieces of Paleolithic burial in the 17-story loess or paleosol layer of the Early Pleistocene, including stone cores, stone fragments, scrapers, drills, and sharpeners , stone hammer, etc., its age is about 1.26 million years to 2.12 million years. Together with the team’s early re-establishment of the Lantian Gongwangling Homo erectus from the original fixed date of 1.15 million years to 1.63 million years, the discovery of the oldest stone artifacts at the Chen’s site 2.12 million years ago pushed the Lantian ancient human activity era. About 1 million years old, this age is 270,000 years older than the Demanisi site, making Shang Chen one of the oldest remains of ancient humans outside Africa. This will prompt scientists to revisit major issues such as early human origin, migration, proliferation, and path. In addition, the discovery of a continuous loess-paleosol profile containing more than 20 layers of Paleolithic cultural layers in the world will open a new research direction for the Chinese loess research, which is already in the world's leading position, and will also serve the ancient human living environment and stone culture techniques. The evolution gives the chronograph scale and environmental markers. Professor Andrew P. Roberts of the Australian National University commented that this sensational work established the age and climatic environment of the oldest known ancient human-related sites outside Africa, which has a tremendous impact on our understanding of human evolution. It is a major achievement of Chinese science and a highlight of global science in 2018.

Source: China Science and Technology Network

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