Biological nitrogen fixation(BNF)and photosynthetic carbon fixation underpin food production and climate mitigation,yet natural systems are constrained by oxygen sensitivity,high energy demand,and inefficient catalyst...Biological nitrogen fixation(BNF)and photosynthetic carbon fixation underpin food production and climate mitigation,yet natural systems are constrained by oxygen sensitivity,high energy demand,and inefficient catalysts.This review synthesizes advances that recast these processes as engineering targets and proposes a conceptual roadmap that bridges synthetic symbioses with the synthetic biology of enzymes and pathways.For BNF,progress spans cross-kingdom strategies—from refactoring nif gene sets and targeting nitrogenase assembly to eukaryotic organelles,to engineering plant-associated diazotrophs,rhizosphere control circuits,and emerging nodule-like microenvironments.For carbon assimilation,new-to-nature CO_(2)-fixation modules and photorespiratory bypasses illustrate how pathway redesign and alternative carboxylases can circumvent key Calvin–Benson–Bassham limitations,and expanding photosynthetic light capture offers additional leverage.Across these domains,we extract common design principles:(i)nitrogenase output is increasingly governed by carbon/energy supply and electron delivery as much as by oxygen protection;(ii)robust function requires compartment-aware enzyme–chassis coordination,substrate channeling,and dynamic regulation using sensors and control circuits;and(iii)scalable implementation may benefit from distributing metabolic labor across engineered consortia rather than forcing all functions into a single host.We discuss enabling technologies—including AI-guided protein design and directed evolution,cell-free prototyping,chassis toolkits,and materials/bioelectrochemical interfaces—that can accelerate design–build–test–learn cycles and reduce barriers to deployment.Together,these insights define a path toward integrated nitrogen and carbon fixation systems for low-emission agriculture and biomanufacturing.展开更多
Optimizing the microchannel design of the next generation of chips requires an understanding of the in situ property evolution of the chip-based materials under fast cooling.This work overcomes the conventional relian...Optimizing the microchannel design of the next generation of chips requires an understanding of the in situ property evolution of the chip-based materials under fast cooling.This work overcomes the conventional reliance on reheating data of melt-quenched glasses by demonstrating direct observations of glass transition on cooling curves utilizing the most advanced fast differential scanning calorimetry.By leveraging an MEMS chip sensor that allows for rapid heat extraction from microgram-sized samples to a purged gas coolant,the device is able to reach ultra-fast cooling rates of up to 40,000 K·s^(−1).Four thermal regions are identified by examining the cooling behaviors of two metallic glasses.This is because the actual rate of the specimen can differ from the programmed rate,especially at high set rate when the actual rate decreases before the glass transition is completed.We define the operational window for reliable cooling curve analysis,build models with empirical and theoretical analyses to determine the maximum feasible cooling rate,and demonstrate how optimizing sample mass and environment temperature broaden this window.The method avoids deceptive structural relaxation effects verified by fictivetemperature analysis and permits the capture of full glass transition during cooling.展开更多
1.Introduction.Pancreaticoduodenectomy is an essential surgical procedure for the treatment of malignant tumors in the pancreatic head,distal common bile duct,and duodenal papilla,and is widely used in clinical practi...1.Introduction.Pancreaticoduodenectomy is an essential surgical procedure for the treatment of malignant tumors in the pancreatic head,distal common bile duct,and duodenal papilla,and is widely used in clinical practice.One of the primary determinants of surgical success is the durability of the pancreaticojejunal anastomosis.展开更多
High entropy alloys(HEAs)have recently attracted significant attention due to their exceptional mechanical properties and potential applications across various fields.Friction stir welding and processing(FSW/P),as not...High entropy alloys(HEAs)have recently attracted significant attention due to their exceptional mechanical properties and potential applications across various fields.Friction stir welding and processing(FSW/P),as notable solid-state welding and processing techniques,have been proved effectiveness in enhancing microstructures and mechanical properties of HEAs.This review article summarizes the current status of FSW/P of HEAs.The welding materials and conditions used for FSW/P in HEAs are reviewed and discussed.The effects of FSW/P on the evolutions of grain structure,texture,dislocation,and secondary phase for different HEAs are highlighted.Furthermore,the influences of FSW/P on the mechanical properties of various HEAs are analyzed.Finally,potential applications,challenges,and future directions of FSW/P in HEAs are forecasted.Overall,FSW/P enable to refine grains of HEAs through dynamic recrystallization and to activate diverse deformation mechanisms of HEAs through tailoring phase structures,thereby significantly improving the strength,hardness,and ductility of both single-and dual-phase HEAs.Future progress in this field will rely on comprehensive optimization of processing parameters and alloy composition,integration of multi-scale modeling with advanced characterization for in-depth exploration of microstructural mechanisms,systematic evaluation of functional properties,and effective bridging of the gap between laboratory research and industrial application.The review aims to provide an overview of recent advancements in the FSW/P of HEAs and encourage further research in this area.展开更多
National parks as protected areas have been on the spotlight because they are essential in achieving ecological civilization in China.Despite the profound achievements of national parks to conserve nature,the benefits...National parks as protected areas have been on the spotlight because they are essential in achieving ecological civilization in China.Despite the profound achievements of national parks to conserve nature,the benefits of national parks for local residents remain lacking.Under the theory of harmonious coexistence between human and nature,this study focused on the development of local people’s livelihood in Qinghai’s national parks.We systematically explored the establishment of the national parks in Qinghai Province,analyzed the current prob-lems,and provided the main measures for developing people’s livelihood in protected areas in Qinghai.This study put forward the viewpoint that national parks should set a long-term goal,and gradually advance based on the environmental conditions and appropriately prioritize the improvement of local people’s wellbeing in the future.展开更多
为提升低空突防作战场景下分布式多输入多输出(Multiple Input and Multiple Output,MIMO)雷达系统的目标检测效能,提出一种合作博弈功率分配(Cooperative Game Power Allocation,CGPA)算法。基于带误差的支援信息建立了低空多径环境下...为提升低空突防作战场景下分布式多输入多输出(Multiple Input and Multiple Output,MIMO)雷达系统的目标检测效能,提出一种合作博弈功率分配(Cooperative Game Power Allocation,CGPA)算法。基于带误差的支援信息建立了低空多径环境下的分布式MIMO雷达信号模型,并推导了基于奈曼皮尔逊准则的检测模型。结合Max-Min准则以信干噪比(Signal to Interference plus Noise Ratio,SINR)为优化模型的效用函数。在此基础上,利用加权方法简化了联盟利益Shapley值的计算,得到满足帕累托最优性和公平性的合作资源分配方案。通过对发射功率资源的细致化管理,有效减小多径效应引起接收信号幅度的参差与衰落。在改善接收信号的稳定性的同时,挖掘并利用多径环境下丰富的散射特性,有效提升了雷达系统的探测效能。仿真实验验证了分布式MIMO雷达系统低空多径目标检测的出色性能,所提功率分配算法能够有效提升系统检测性能,并具有较好的实时性。展开更多
Cerebral ischemia/reperfusion(I/R)injury is an important pathophysiological condition of ischemic stroke that involves a variety of physiological and pathological cell death pathways,including autophagy,apoptosis,necr...Cerebral ischemia/reperfusion(I/R)injury is an important pathophysiological condition of ischemic stroke that involves a variety of physiological and pathological cell death pathways,including autophagy,apoptosis,necroptosis,and phagoptosis,among which autophagy is the most studied.We have reviewed studies published in the past 5 years regarding the association between autophagy and cerebral I/R injury.To the best of our knowledge,this is the first review article summarizing potential candidates targeting autophagic pathways in the treatment of I/R injury post ischemic stroke.The findings of this review may help to better understand the pathogenesis and mechanisms of I/R events and bridge the gap between basic and translational research that may lead to the development of novel therapeutic approaches for I/R injury.展开更多
Hepatocellular carcinoma(HCC)remains a leading cause of cancer-related mortality globally,with limited therapeutic progress for advanced stages.The aberrant fibroblast growth factor 19(FGF19)-fibroblast growth factor ...Hepatocellular carcinoma(HCC)remains a leading cause of cancer-related mortality globally,with limited therapeutic progress for advanced stages.The aberrant fibroblast growth factor 19(FGF19)-fibroblast growth factor receptor 4(FGFR4)axis promotes oncogenesis and is linked to targeted-immunotherapy of HCC.Multi-kinase inhibitors(MKIs)enhance anti-tumor effects by targeting this axis and FGF19 overexpression upregulates programmed cell death ligand 1 in tumor microenvironment.Clinical studies have demonstrated the efficacy of selective FGFR4 inhibitors in HCC treatment,with enhanced anti-tumor effects when combined with MKIs or immune checkpoint inhibitors.Phase I clinical trials of Irpagratinib(ABSK-011)demonstrated an objective response rate of 43.5%,which increased to 55.6%combined with atezolizumab.FGF19 also serves as a biomarker for HCC.This review systematically summarizes the literature retri-eved from PubMed and other databases using search terms“HCC”,“fibroblast growth factor 19”,“fibroblast growth factor receptor 4”,“FGFR4 inhibitor”,“targeted therapy”,“multi-kinase inhibitor”,“immunotherapy”,“immune checkpoint inhibitor”,and“biomarker”.It also firstly synthesizes combination strategies and underlying mechanisms between FGFR4 inhibitors and targeted-immunotherapy,addressing critical gaps in existing reviews.Additionally,we discuss the potential of FGF19 as a predictive biomarker,integrating mechanistic and clinical evidence to advance precision HCC therapeutics.展开更多
基金supported by the funds of the Ministry of Science and Technology of China(2019YFA0904700)the National Natural Science Foundation of China(32471477)to Cheng Qi.
文摘Biological nitrogen fixation(BNF)and photosynthetic carbon fixation underpin food production and climate mitigation,yet natural systems are constrained by oxygen sensitivity,high energy demand,and inefficient catalysts.This review synthesizes advances that recast these processes as engineering targets and proposes a conceptual roadmap that bridges synthetic symbioses with the synthetic biology of enzymes and pathways.For BNF,progress spans cross-kingdom strategies—from refactoring nif gene sets and targeting nitrogenase assembly to eukaryotic organelles,to engineering plant-associated diazotrophs,rhizosphere control circuits,and emerging nodule-like microenvironments.For carbon assimilation,new-to-nature CO_(2)-fixation modules and photorespiratory bypasses illustrate how pathway redesign and alternative carboxylases can circumvent key Calvin–Benson–Bassham limitations,and expanding photosynthetic light capture offers additional leverage.Across these domains,we extract common design principles:(i)nitrogenase output is increasingly governed by carbon/energy supply and electron delivery as much as by oxygen protection;(ii)robust function requires compartment-aware enzyme–chassis coordination,substrate channeling,and dynamic regulation using sensors and control circuits;and(iii)scalable implementation may benefit from distributing metabolic labor across engineered consortia rather than forcing all functions into a single host.We discuss enabling technologies—including AI-guided protein design and directed evolution,cell-free prototyping,chassis toolkits,and materials/bioelectrochemical interfaces—that can accelerate design–build–test–learn cycles and reduce barriers to deployment.Together,these insights define a path toward integrated nitrogen and carbon fixation systems for low-emission agriculture and biomanufacturing.
基金supported by the National Natural Science Foundation of China (Grant Nos.92580120 and 52471188)。
文摘Optimizing the microchannel design of the next generation of chips requires an understanding of the in situ property evolution of the chip-based materials under fast cooling.This work overcomes the conventional reliance on reheating data of melt-quenched glasses by demonstrating direct observations of glass transition on cooling curves utilizing the most advanced fast differential scanning calorimetry.By leveraging an MEMS chip sensor that allows for rapid heat extraction from microgram-sized samples to a purged gas coolant,the device is able to reach ultra-fast cooling rates of up to 40,000 K·s^(−1).Four thermal regions are identified by examining the cooling behaviors of two metallic glasses.This is because the actual rate of the specimen can differ from the programmed rate,especially at high set rate when the actual rate decreases before the glass transition is completed.We define the operational window for reliable cooling curve analysis,build models with empirical and theoretical analyses to determine the maximum feasible cooling rate,and demonstrate how optimizing sample mass and environment temperature broaden this window.The method avoids deceptive structural relaxation effects verified by fictivetemperature analysis and permits the capture of full glass transition during cooling.
文摘1.Introduction.Pancreaticoduodenectomy is an essential surgical procedure for the treatment of malignant tumors in the pancreatic head,distal common bile duct,and duodenal papilla,and is widely used in clinical practice.One of the primary determinants of surgical success is the durability of the pancreaticojejunal anastomosis.
基金supported by National Natural Science Foundation of China(Grant No.52171032)Hebei Natural Science Foundation(Grant No.E2023501002)Fundamental Research Funds for the Central Universities(Grant No.2024GFYD003)。
文摘High entropy alloys(HEAs)have recently attracted significant attention due to their exceptional mechanical properties and potential applications across various fields.Friction stir welding and processing(FSW/P),as notable solid-state welding and processing techniques,have been proved effectiveness in enhancing microstructures and mechanical properties of HEAs.This review article summarizes the current status of FSW/P of HEAs.The welding materials and conditions used for FSW/P in HEAs are reviewed and discussed.The effects of FSW/P on the evolutions of grain structure,texture,dislocation,and secondary phase for different HEAs are highlighted.Furthermore,the influences of FSW/P on the mechanical properties of various HEAs are analyzed.Finally,potential applications,challenges,and future directions of FSW/P in HEAs are forecasted.Overall,FSW/P enable to refine grains of HEAs through dynamic recrystallization and to activate diverse deformation mechanisms of HEAs through tailoring phase structures,thereby significantly improving the strength,hardness,and ductility of both single-and dual-phase HEAs.Future progress in this field will rely on comprehensive optimization of processing parameters and alloy composition,integration of multi-scale modeling with advanced characterization for in-depth exploration of microstructural mechanisms,systematic evaluation of functional properties,and effective bridging of the gap between laboratory research and industrial application.The review aims to provide an overview of recent advancements in the FSW/P of HEAs and encourage further research in this area.
基金This work was funded by the Second Tibetan Plateau Scientific Expe-dition and Research(STEP)program(Grant No.2019QZKK0501)the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDA2002030302)+1 种基金Joint Grant from Chinese Academy of Sciences-People’s Government of Qinghai Province on Sanjiangyuan Na-tional Park(Grant No.LHZX-2020-01)Construction Fund for Qing-hai Key Laboratories(Grant No.2017-ZJ-Y23).
文摘National parks as protected areas have been on the spotlight because they are essential in achieving ecological civilization in China.Despite the profound achievements of national parks to conserve nature,the benefits of national parks for local residents remain lacking.Under the theory of harmonious coexistence between human and nature,this study focused on the development of local people’s livelihood in Qinghai’s national parks.We systematically explored the establishment of the national parks in Qinghai Province,analyzed the current prob-lems,and provided the main measures for developing people’s livelihood in protected areas in Qinghai.This study put forward the viewpoint that national parks should set a long-term goal,and gradually advance based on the environmental conditions and appropriately prioritize the improvement of local people’s wellbeing in the future.
文摘为提升低空突防作战场景下分布式多输入多输出(Multiple Input and Multiple Output,MIMO)雷达系统的目标检测效能,提出一种合作博弈功率分配(Cooperative Game Power Allocation,CGPA)算法。基于带误差的支援信息建立了低空多径环境下的分布式MIMO雷达信号模型,并推导了基于奈曼皮尔逊准则的检测模型。结合Max-Min准则以信干噪比(Signal to Interference plus Noise Ratio,SINR)为优化模型的效用函数。在此基础上,利用加权方法简化了联盟利益Shapley值的计算,得到满足帕累托最优性和公平性的合作资源分配方案。通过对发射功率资源的细致化管理,有效减小多径效应引起接收信号幅度的参差与衰落。在改善接收信号的稳定性的同时,挖掘并利用多径环境下丰富的散射特性,有效提升了雷达系统的探测效能。仿真实验验证了分布式MIMO雷达系统低空多径目标检测的出色性能,所提功率分配算法能够有效提升系统检测性能,并具有较好的实时性。
基金Shanghai Rehabilitation Medical Association,Grant/Award Number:2023JGKT24China Rehabilitation Medical Association,Grant/Award Number:KFKT-2023Shanghai“14th Five-Year Plan”Traditional Chinese Medicine Specialty and Traditional Chinese Medicine Emergency Capacity Improvement Project,Grant/Award Number:ZYTSZK2-7。
文摘Cerebral ischemia/reperfusion(I/R)injury is an important pathophysiological condition of ischemic stroke that involves a variety of physiological and pathological cell death pathways,including autophagy,apoptosis,necroptosis,and phagoptosis,among which autophagy is the most studied.We have reviewed studies published in the past 5 years regarding the association between autophagy and cerebral I/R injury.To the best of our knowledge,this is the first review article summarizing potential candidates targeting autophagic pathways in the treatment of I/R injury post ischemic stroke.The findings of this review may help to better understand the pathogenesis and mechanisms of I/R events and bridge the gap between basic and translational research that may lead to the development of novel therapeutic approaches for I/R injury.
基金Supported by Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province,No.CXPJJH124001-2406National Natural Science Foundation of China,No.U23A20483.
文摘Hepatocellular carcinoma(HCC)remains a leading cause of cancer-related mortality globally,with limited therapeutic progress for advanced stages.The aberrant fibroblast growth factor 19(FGF19)-fibroblast growth factor receptor 4(FGFR4)axis promotes oncogenesis and is linked to targeted-immunotherapy of HCC.Multi-kinase inhibitors(MKIs)enhance anti-tumor effects by targeting this axis and FGF19 overexpression upregulates programmed cell death ligand 1 in tumor microenvironment.Clinical studies have demonstrated the efficacy of selective FGFR4 inhibitors in HCC treatment,with enhanced anti-tumor effects when combined with MKIs or immune checkpoint inhibitors.Phase I clinical trials of Irpagratinib(ABSK-011)demonstrated an objective response rate of 43.5%,which increased to 55.6%combined with atezolizumab.FGF19 also serves as a biomarker for HCC.This review systematically summarizes the literature retri-eved from PubMed and other databases using search terms“HCC”,“fibroblast growth factor 19”,“fibroblast growth factor receptor 4”,“FGFR4 inhibitor”,“targeted therapy”,“multi-kinase inhibitor”,“immunotherapy”,“immune checkpoint inhibitor”,and“biomarker”.It also firstly synthesizes combination strategies and underlying mechanisms between FGFR4 inhibitors and targeted-immunotherapy,addressing critical gaps in existing reviews.Additionally,we discuss the potential of FGF19 as a predictive biomarker,integrating mechanistic and clinical evidence to advance precision HCC therapeutics.
