Top 10 Progress in China's Life Sciences in 2022 released

6. Discovery of metformin targets and elucidation of its mechanism of delaying aging

Metformin is not only the first-line drug for the treatment of type 2 diabetes, clinical studies have also found that metformin has anti-tumor, anti-aging and other magical effects. But metformin has been on the market for 65 years and its target has remained a mystery.

Xiamen University Lin Shengcai team after 7 years of scientific research, found a protein called PEN2 is the target protein of metformin. Importantly, this study not only identified the direct target of metformin, but also mapped out the road map of metformin's function from a molecular perspective. They also screened a chemical drug (commonly known as "Gu Jing") that can simulate the effect of Gu Gu (calorie restriction), which has the effect of lowering sugar, treating fatty liver, and extending life span. It was also found that "talisman" and metformin both use the glucose (calorie restriction) sensing pathway previously discovered by them, so as to couple to AMPK longevity related pathway, to treat major metabolic diseases such as diabetes and fatty liver and delay aging. Kei Sakamoto, an expert on metformin's mechanism of action, and Niels Jessen, a diabetes researcher, wrote that the discovery has important value in developing new alternative drugs to overcome metformin's defects. AMPK field expert David Carling has written that "talisman" is the magic bullet in the long-sought fight against metabolic diseases.

7. Precise treatment of ischemic cerebrovascular disease

High recurrence is a global problem in the prevention and treatment of ischemic cerebrovascular diseases. However, the effect of aspirin single antiplatelet therapy recommended by national guidelines is limited, and clinical studies of combined antiplatelet therapy with other drugs have failed due to ineffectiveness or increased risk of serious bleeding. Therefore, combined therapy has been banned for ischemic cerebrovascular diseases by international guidelines.

Wang Yongjun's team of Beijing Tiantan Hospital affiliated to Capital Medical University proposed for the first time in the world the short-range double-channel double-effect combination treatment program of aspirin plus clopidogrel, which rewrote the guidelines of many countries such as Europe and the United States. Based on this regimen, he found that ABCB1, CYP2C19 and F2R, the key genes of clopidogrel absorption and metabolic pathways, all significantly affect the efficacy of the drug, and proposed a "bypass gene" ticagrelor replacement therapy regimen for people carrying loss-function alleles of clopidogrel, which can reduce the risk of recurrence by 23%. It was evaluated by NEJM as opening a new era of gene-guided treatment of cerebrovascular diseases, and was evaluated by Nature Medicine and European Heart Journal as a new opportunity for genotyping to guide the treatment of cerebrovascular diseases.

The findings were published in the New England Journal of Medicine.

Efficacy of ticagrelor replacement therapy in persons carrying CYP2C19 function loss alleles

8. Developed subversive gene decoding technology to describe the world's first "disturbance map"

The human genome has long been sequenced, but its function is still poorly understood, which seriously hinders the diagnosis and treatment of diseases. The Chi Tian team of Shanghai University of Science and Technology has developed a unique path and fused the two underlying tools of "CRISPR gene editing" and "Cre gene recombination" into a subversive "high-throughput, pan-organization" gene function decoding technology iMAP, which can increase the decoding speed of mouse genes by at least 100 times. This work also uses iMAP to successfully describe the world's first "disturbance map", which shows the basic functions of 90 protein-coding genes in 39 kinds of tissue cells in mice, and will inevitably give birth to a "panoramic disturbance map" covering all genes and tissues and decoding the entire "book of life", which will become an indispensable "world map" for people to explore the mysteries of life in the future. iMAP is robust, easy to operate, easy to popularize, and has a wide range of uses (including mining disease drug targets and optimizing rice varieties), and has achieved technological breakthroughs in the field of gene decoding from 0 to 1.

How iMAP works and its uses. The image on the right (" Flying Flowers ") is a "Dunhuang version" of how iMAP works, showing the flying sky (Cre) releasing flowers (gRNA) from a vase (genetically modified), which produces chimeric mice (design: Li Zhuoshi, Chi Tian).

9. Molecular mechanism of initiation of autophagy in multicellular organisms

Autophagy acts as a "scavenger" in cells by wrapping misfolded proteins, damaged organelles and other "garbage" in a double-membrane structure called the autophagosome and transporting it to the lysosome for degradation and recycling. Autophagy is essential for resistance to many kinds of stress and maintenance of cell homeostasis. Finding the signal that determines the formation of autophagosomes is a long-standing problem in the field of autophagy.