Copper,an essential micronutrient,plays significant roles in numerous biological functions.Recent studies have identified imbalances in copper homeostasis across various cancers,along with the emergence of cuproptosis...Copper,an essential micronutrient,plays significant roles in numerous biological functions.Recent studies have identified imbalances in copper homeostasis across various cancers,along with the emergence of cuproptosis,a novel copper-dependent form of cell death that is crucial for tumor suppression and therapeutic resistance.As a result,manipulating copper levels has garnered increasing interest as an innovative approach to cancer therapy.In this review,we frst delineate copper homeostasis at both cellular and systemic levels,clarifying copper's protumorigenic and antitumorigenic functions in cancer.We then outline the key milestones and molecular mechanisms of cuproptosis,including both mitochondria-dependent and independent pathways.Next,we explore the roles of cuproptosis in cancer biology,as well as the interactions mediated by cuproptosis between cancer cells and the immune system.We also summarize emerging therapeutic opportunities targeting copper and discuss the clinical associations of cuproptosis-related genes.Finally,we examine potential biomarkers for cuproptosis and put forward the existing challenges and future prospects for leveraging cuproptosis in cancer therapy.Overall,this review enhances our understanding of the molecular mechanisms and therapeutic landscape of copper and cuproptosis in cancer,highlighting the potential of copper-or cuproptosis-based therapies for cancer treatment.展开更多
Understanding the responses of precipitation extremes to global climate change remains limited owing to their poor representations in models and complicated interactions with multi-scale systems.Here we take the recor...Understanding the responses of precipitation extremes to global climate change remains limited owing to their poor representations in models and complicated interactions with multi-scale systems.Here we take the record-breaking precipitation over China in 2021 as an example,and study its changes under three different climate scenarios through a developed pseudo-global-warming(PGW)experimental framework with 60-3 km variable-resolution global ensemble modeling.Compared to the present climate,the precipitation extreme under a warmer(cooler)climate increased(decreased)in intensity,coverage,and total amount at a range of 24.3%-37.8%(18.7%-56.1%).With the help of the proposed PGW experimental framework,we further reveal the impacts of the multi-scale system interactions in climate change on the precipitation extreme.Under the warmer climate,large-scale water vapor transport converged from double typhoons and the subtropical high marched into central China,enhancing the convective energy and instability on the leading edge of the transport belt.As a result,the mesoscale convective system(Mcs)that directly contributed to the precipitation extreme became stronger than that in the present climate.On the contrary,the cooler climate displayed opposite changing characteristics relative to the warmer climate,ranging from the large-scale systems to local environments and to the Mcs.In summary,our study provides a promising approach to scientifically assess the response of precipitation extremes to climate change,making it feasible to perform ensemble simulations while investigating the multi-scale system interactions over the globe.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.82272849 to G.D.,82403139 to L.Y.)Huxiang Youth Talent Program(Grant Nos.2023RC3072 to G.D.,2024RC3043 to F.Z.)+3 种基金Natural Science Fund for Outstanding Youths in Hunan Province(Grant No.2023JJ20093 to G.D.)Postdoctoral Fellowship Program of CPSF(Grant No.GZC20242053 to L.Y.)Changsha Municipal Natural Science Foundation(Grant No.kq243010 to L.Y.)Xiangya Hospital Youth Fund(Grant No.2023Q17 to L.Y.).
文摘Copper,an essential micronutrient,plays significant roles in numerous biological functions.Recent studies have identified imbalances in copper homeostasis across various cancers,along with the emergence of cuproptosis,a novel copper-dependent form of cell death that is crucial for tumor suppression and therapeutic resistance.As a result,manipulating copper levels has garnered increasing interest as an innovative approach to cancer therapy.In this review,we frst delineate copper homeostasis at both cellular and systemic levels,clarifying copper's protumorigenic and antitumorigenic functions in cancer.We then outline the key milestones and molecular mechanisms of cuproptosis,including both mitochondria-dependent and independent pathways.Next,we explore the roles of cuproptosis in cancer biology,as well as the interactions mediated by cuproptosis between cancer cells and the immune system.We also summarize emerging therapeutic opportunities targeting copper and discuss the clinical associations of cuproptosis-related genes.Finally,we examine potential biomarkers for cuproptosis and put forward the existing challenges and future prospects for leveraging cuproptosis in cancer therapy.Overall,this review enhances our understanding of the molecular mechanisms and therapeutic landscape of copper and cuproptosis in cancer,highlighting the potential of copper-or cuproptosis-based therapies for cancer treatment.
基金supported by the National Natural Science Foundation of China(42225505)the Beijing Nova Program(Z211100002121100)+2 种基金the National Key Research and Development Program of China(2021YFC3000805)the National Natural Science Foundation of China(U2142204)the Science&Technology Development Fund of Chinese Academy of Meteorological Sciences(CAMS)(2022KJ007)。
文摘Understanding the responses of precipitation extremes to global climate change remains limited owing to their poor representations in models and complicated interactions with multi-scale systems.Here we take the record-breaking precipitation over China in 2021 as an example,and study its changes under three different climate scenarios through a developed pseudo-global-warming(PGW)experimental framework with 60-3 km variable-resolution global ensemble modeling.Compared to the present climate,the precipitation extreme under a warmer(cooler)climate increased(decreased)in intensity,coverage,and total amount at a range of 24.3%-37.8%(18.7%-56.1%).With the help of the proposed PGW experimental framework,we further reveal the impacts of the multi-scale system interactions in climate change on the precipitation extreme.Under the warmer climate,large-scale water vapor transport converged from double typhoons and the subtropical high marched into central China,enhancing the convective energy and instability on the leading edge of the transport belt.As a result,the mesoscale convective system(Mcs)that directly contributed to the precipitation extreme became stronger than that in the present climate.On the contrary,the cooler climate displayed opposite changing characteristics relative to the warmer climate,ranging from the large-scale systems to local environments and to the Mcs.In summary,our study provides a promising approach to scientifically assess the response of precipitation extremes to climate change,making it feasible to perform ensemble simulations while investigating the multi-scale system interactions over the globe.
