I.EXECUTIVE SUMMARY next-generation,high-intensity electron-positron collider"Higgs factory",such as the Circular Electron-Positron Collider(CEPC),is among the highest priorities for the global high-energy c...I.EXECUTIVE SUMMARY next-generation,high-intensity electron-positron collider"Higgs factory",such as the Circular Electron-Positron Collider(CEPC),is among the highest priorities for the global high-energy collider physics community.The CEPC can provide unprecedented opportunities for making fundamental discoveries and providing decisive insights in the quest for a"New Standard Model(SM)"of nature's fundamental interactions.The CEPC could:·Identify the origin of matter,especially the mechanism related to the first-order phase transition in the early Universe,which could produce a detectable gravitational wave signal.展开更多
Proprotein convertase subtilisin/kexin type 9(PCSK9)has evolved as a pivotal enzyme in lipid metabolism and a revolutionary therapeutic target for hypercholesterolemia and its related cardiovascular diseases(CVD).This...Proprotein convertase subtilisin/kexin type 9(PCSK9)has evolved as a pivotal enzyme in lipid metabolism and a revolutionary therapeutic target for hypercholesterolemia and its related cardiovascular diseases(CVD).This comprehensive review delineates the intricate roles and wide-ranging implications of PCSK9,extending beyond CVD to emphasize its significance in diverse physiological and pathological states,including liver diseases,infectious diseases,autoimmune disorders,and notably,cancer.Our exploration offers insights into the interaction between PCSK9 and low-density lipoprotein receptors(LDLRs),elucidating its substantial impact on cholesterol homeostasis and cardiovascular health.It also details the evolution of PCSK9-targeted therapies,translating foundational bench discoveries into bedside applications for optimized patient care.The advent and clinical approval of innovative PCSK9 inhibitory therapies(PCSK9-iTs),including three monoclonal antibodies(Evolocumab,Alirocumab,and Tafolecimab)and one small interfering RNA(siRNA,Inclisiran),have marked a significant breakthrough in cardiovascular medicine.These therapies have demonstrated unparalleled efficacy in mitigating hypercholesterolemia,reducing cardiovascular risks,and have showcased profound value in clinical applications,offering novel therapeutic avenues and a promising future in personalized medicine for cardiovascular disorders.Furthermore,emerging research,inclusive of our findings,unveils PCSK9’s potential role as a pivotal indicator for cancer prognosis and its prospective application as a transformative target for cancer treatment.This review also highlights PCSK9’s aberrant expression in various cancer forms,its association with cancer prognosis,and its crucial roles in carcinogenesis and cancer immunity.In conclusion,this synthesized review integrates existing knowledge and novel insights on PCSK9,providing a holistic perspective on its transformative impact in reshaping therapeutic paradigms across various disorders.It emphasizes the clinical value and effect of PCSK9-iT,underscoring its potential in advancing the landscape of biomedical research and its capabilities in heralding new eras in personalized medicine.展开更多
The past few decades have witnessed a global trend of population aging as a result of declines in fertility and improvements in health and longevity.While more elder people can live longer,aging has brought substantia...The past few decades have witnessed a global trend of population aging as a result of declines in fertility and improvements in health and longevity.While more elder people can live longer,aging has brought substantial impacts on healthcare and welfare systems at societal level,as well as changes on individual physical and psychological health and family ecosystems.Meanwhile,the Global Burden of Disease,a study conducted by the World Health Organization and World Bank,shows that large amount of increase of disabled elderly is predicable in almost all regions of the world.展开更多
基金the Natural Science Foundation of China(NSFC)(11905162,12035008,12075097,12075123,12090060,12090064,12105248,12135006,12175039,12205227,12205312,12205387,12205171,12235008,12321005,12235001,12305094,12305115,12335005,12375091,12375094,12375096,11975129,12375194,12447167,12475094,12475101,12475106,12475111,12425506,12375101,12405119,12405101,12505121,12135007,12175218,12075213,12335005,12175243,12533001,12125503,12305103,12505120,12575099,12505122,12342502,12575106,12147214,W2432006,W2441004)the National Key R&D Program of China(2024YFA1610603)+22 种基金the China Postdoctoral Science Foundation(2023M732255,2025M773403,GZC20231613)the Natural Science Foundation of Jiangsu Province(BK20210201)the Natural Science Foundation of Henan(Distinguished Young Scholars of Henan Province)(242300421046)the Natural Science Foundation of Sichuan Province(2025ZNSFSC0880)the Guangdong Major Project of Basic and Applied Basic Research(2020B0301030008)the Department of Science and Technology of Shandong province(tsqn202312052,2024HWYQ-005)the Startup Research Fund of Henan Academy of Sciences(20251820001)the Excellent Young Talents Program of Wuhan University of Technology(40122102)the research program of the Wuhan University of Technology(3120625397,2020IB024)the Fundamental Research Funds for the Central Universities(JZ2023HGTB0222,WUT:2022IVA052)the Excellent Scholar Project of Southeast University(Class A)the Big Data Computing Center of Southeast University,National Science and Technology Council,the Ministry of Education(Higher Education Sprout Project NTU-114L104022-1)the Center for Theoretical Sciences of Taiwan,and Vietnam National Foundation for Science and Technology Development(NAFOSTED)(103.01-2023.50)the Research Office of the University of the Witwatersrand and South African Department of Science and Innovation through the SA-CERN programthe self-determined research funds of Central China Normal University from the colleges'basic research and operation of MOE(CCNU24AI003)SJTU Double First Class start-up fund(WF220442604)the Innovation Capability Support Program of Shaanxi(2021KJXX-47)the Slovenian Research Agency under the research core funding No.P1-0035,the research grants J1-3013,N1-0253,CONICET,ANPCyT under project(PICT-2021-00374)Higher Education Sprout Project(NTU-114L104022-1)KIAS Individual Grants(PG086002)at the Korea Institute for Advanced Study,FAPESP(2021/09547-9)the Slovenian Research Agency under the research core funding(P1-0035)research grants J1-3013,N1-0253the bilateral project Proteus PR-12696/Projet 50194VC。
文摘I.EXECUTIVE SUMMARY next-generation,high-intensity electron-positron collider"Higgs factory",such as the Circular Electron-Positron Collider(CEPC),is among the highest priorities for the global high-energy collider physics community.The CEPC can provide unprecedented opportunities for making fundamental discoveries and providing decisive insights in the quest for a"New Standard Model(SM)"of nature's fundamental interactions.The CEPC could:·Identify the origin of matter,especially the mechanism related to the first-order phase transition in the early Universe,which could produce a detectable gravitational wave signal.
基金supported by the National Natural Science Foundation of China(No.82272817,to X.B.)Shanghai Pujiang Program(No.22PJ1412400,to X.B.,and No.22PJ1402700,to Y.H.)Science and Technology Development Fund of Shanghai Pudong New Area(No.PKJ2022-Y50,to X.B.).
文摘Proprotein convertase subtilisin/kexin type 9(PCSK9)has evolved as a pivotal enzyme in lipid metabolism and a revolutionary therapeutic target for hypercholesterolemia and its related cardiovascular diseases(CVD).This comprehensive review delineates the intricate roles and wide-ranging implications of PCSK9,extending beyond CVD to emphasize its significance in diverse physiological and pathological states,including liver diseases,infectious diseases,autoimmune disorders,and notably,cancer.Our exploration offers insights into the interaction between PCSK9 and low-density lipoprotein receptors(LDLRs),elucidating its substantial impact on cholesterol homeostasis and cardiovascular health.It also details the evolution of PCSK9-targeted therapies,translating foundational bench discoveries into bedside applications for optimized patient care.The advent and clinical approval of innovative PCSK9 inhibitory therapies(PCSK9-iTs),including three monoclonal antibodies(Evolocumab,Alirocumab,and Tafolecimab)and one small interfering RNA(siRNA,Inclisiran),have marked a significant breakthrough in cardiovascular medicine.These therapies have demonstrated unparalleled efficacy in mitigating hypercholesterolemia,reducing cardiovascular risks,and have showcased profound value in clinical applications,offering novel therapeutic avenues and a promising future in personalized medicine for cardiovascular disorders.Furthermore,emerging research,inclusive of our findings,unveils PCSK9’s potential role as a pivotal indicator for cancer prognosis and its prospective application as a transformative target for cancer treatment.This review also highlights PCSK9’s aberrant expression in various cancer forms,its association with cancer prognosis,and its crucial roles in carcinogenesis and cancer immunity.In conclusion,this synthesized review integrates existing knowledge and novel insights on PCSK9,providing a holistic perspective on its transformative impact in reshaping therapeutic paradigms across various disorders.It emphasizes the clinical value and effect of PCSK9-iT,underscoring its potential in advancing the landscape of biomedical research and its capabilities in heralding new eras in personalized medicine.
文摘The past few decades have witnessed a global trend of population aging as a result of declines in fertility and improvements in health and longevity.While more elder people can live longer,aging has brought substantial impacts on healthcare and welfare systems at societal level,as well as changes on individual physical and psychological health and family ecosystems.Meanwhile,the Global Burden of Disease,a study conducted by the World Health Organization and World Bank,shows that large amount of increase of disabled elderly is predicable in almost all regions of the world.
