Dear Editor,Hepatitis B virus(HBV)is a small,enveloped DNA virus and a member of the Hepadnaviridae family(Zhao et al.,2020).It is a major human pathogen causing chronic liver disease,leading to significant morbidity ...Dear Editor,Hepatitis B virus(HBV)is a small,enveloped DNA virus and a member of the Hepadnaviridae family(Zhao et al.,2020).It is a major human pathogen causing chronic liver disease,leading to significant morbidity and mortality worldwide(Xia and Liang,2019).According to the World Health Organization(WHO),an estimated 296 million people live with chronic HBV infection,contributing to around 820,000 deaths annually due to complications such as liver cirrhosis and hepatocellular carcinoma(HCC)(Easterbrook et al.,2021).展开更多
The Southern Ocean is a critical component in the Earth system by dominating the global heat and anthropogenic carbon uptake and supplying heat to melt the largest ice sheet.Variability and changes in the water masses...The Southern Ocean is a critical component in the Earth system by dominating the global heat and anthropogenic carbon uptake and supplying heat to melt the largest ice sheet.Variability and changes in the water masses of the Southern Ocean are thus important to the global energy and water cycles,carbon cycling,and sea-level change.In this article,we review the recent progress on understanding the variability and changes in the four major water masses in the Southern Ocean,including Subantarctic Mode Water,Antarctic Intermediate Water,Circumpolar Deep Water and Antarctic Bottom Water.Subantarctic Mode Water and Antarctic Intermediate Water show statistically significant strong circumpolar shoaling,warming,and density reductions since 1970s,indicating that signals of global warming have entered the interior ocean.Meanwhile,strong regional variability of Subantarctic Mode Water and Antarctic Intermediate Water responding to surface buoyancy forcing and westerly winds is attracting more attention.Circumpolar Deep Water is an important modulator of heat content and nutrient concentrations on continental shelves around Antarctica and has made significant contributions to the basal melting of Antarctic ice shelves.Since the late 1950s,a long-term freshening trend in Antarctic Bottom Water in the Ross Sea and its downstream region has been observed and is mainly attributed to the accelerated basal melting of ice shelves in West Antarctica.The shrinking of Antarctic Bottom Water in the Weddell Sea during 1992–2020 has also been revealed and is attributed to reduced sea ice production over the southern Weddell continental shelf related to the Interdecadal Pacific Oscillation and the variability in the Amundsen Sea Low.Though significant advances have been achieved,there is an urgent need to enhance and improve both observations and model performances for better understandings and projections of the formation,transformation,and transport of the water masses in the Southern Ocean.展开更多
BACKGROUND Cholangiocarcinoma(CCA)is a highly aggressive malignancy with limited therapeutic options.Dysregulation of the Hippo-yes-associated protein(YAP)signaling pathway plays a key role in tumor progression,but th...BACKGROUND Cholangiocarcinoma(CCA)is a highly aggressive malignancy with limited therapeutic options.Dysregulation of the Hippo-yes-associated protein(YAP)signaling pathway plays a key role in tumor progression,but the effects of distinct bile acids on this pathway remain unclear.AIM To investigate the roles of glycochenodeoxycholic acid(GDCA)and deoxycholic acid(DCA)in CCA progression through Hippo-YAP signaling and to evaluate the effects of YAP-targeted interventions.METHODS The in vitro experiments were performed using HuCCT1 CCA cells treated with GDCA,DCA,and combinations with a YAP inhibitor(verteporfin)or agonist(GA-017).Key molecular changes in the Hippo-YAP pathway were assessed by western blot,immunofluorescence,and reverse transcription quantitative realtime polymerase chain reaction.Functional assays,including Cell Counting Kit-8,5-ethynyl-2’-deoxyuridine,Transwell,and terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate-nick end labelling,were conducted to evaluate cell proliferation,migration,invasion,and apoptosis.In vivo,nude mice bearing subcutaneous HuCCT1 tumors were treated with GDCA,DCA,or combined YAP modulators.Tumor growth was monitored,and molecular analyses of tumor tissues were performed using western blot.RESULTS The GDCA significantly activated YAP by reducing mammalian STE20-like protein kinase 1 and large tumor suppressor 1 phosphorylation,promoting YAP nuclear translocation,and enhancing tumor cell proliferation,migration,and invasion.In contrast,DCA inhibited YAP activation,suppressed tumor cell functions,and increased apoptosis.GDCA combined with YAP inhibitors attenuated its tumor-promoting effects,while DCA combined with YAP agonists reversed its inhibitory effects.In vivo,GDCA accelerated tumor growth,while DCA reduced tumor size and weight,with molecular changes consistent with in vitro findings.CONCLUSION The GDCA and DCA exert opposing effects on CCA progression through Hippo-YAP signaling.GDCA promotes tumor growth via YAP activation,while DCA inhibits these processes.YAP-targeted interventions demonstrate therapeutic potential,providing insights into new treatment strategies for CCA.展开更多
NiTi alloy lattice structures are crucial for reusable energy absorption due to their shape memory effects.However,existing NiTi alloy lattice structures always suffer from localized deformation bands during loading,c...NiTi alloy lattice structures are crucial for reusable energy absorption due to their shape memory effects.However,existing NiTi alloy lattice structures always suffer from localized deformation bands during loading,causing local strains to exceed the recoverable strain limit of the alloy and significantly reducing their reusable energy-absorbing capacity.In this study,we developed a NiTi alloy helical lattice structure(HLS)to effectively prevent localized deformation bands.This is attributed to its struts distributing stress and strain uniformly through torsional deformation,thereby alleviating local stress concentrations and suppressing the formation of localized deformation bands.Additionally,its unit cells provide mutual support and reinforcement during deformation,effectively preventing the progression of localized deformation bands.The NiTi alloy HLS exhibits superior reusable energy absorption compared to previously reported reusable energy-absorbing materials/structures and enhanced damage tolerance under large compression strain.This study provides valuable insights for the development of high-performance reusable NiTi alloy energy-absorbing lattice structures.展开更多
As the development of new power systems progresses,the inherent inertia of power systems continues to diminish.Centralized frequency regulation,which relies on rapid communication and real-time control,can enable inve...As the development of new power systems progresses,the inherent inertia of power systems continues to diminish.Centralized frequency regulation,which relies on rapid communication and real-time control,can enable inverter-based thermostatically controlled load(ITCL)clusters to provide virtual inertia support to the power grid.However,ITCL clusters exhibit significant discrete response characteristics,which precludes the direct integration of load-side inertia support into the synchronous unit side.To address this issue,this paper elaborates on the existing technical framework and analyzes the underlying causes of the problem.It proposes a timestamp allocation mechanism for ITCL cluster control instructions,ensuring that many ITCL terminals can be triggered at staggered times,thereby allowing the load cluster power to adhere to the inertia analog control law at any moment.Building on this foundation,the paper further examines the impact of the inertia response delay of ITCL clusters,which is based on centralized frequency regulation,on the stability of the power system.A design scheme for inertia analog control parameters is proposed,taking into account dual constraints,frequency stability and load cluster regulation capacity.Finally,the feasibility and applicability of the proposed mechanism and parameter design scheme are investigated through simulations conducted via MATLAB/Simulink.展开更多
AuCu bimetallic nanoclusters exhibit enhanced emission relative to structurally analogous Au nanoclusters,though their excited-state dynamics remains incompletely characterized.Here,we chose AuCu_(14)as a system to pr...AuCu bimetallic nanoclusters exhibit enhanced emission relative to structurally analogous Au nanoclusters,though their excited-state dynamics remains incompletely characterized.Here,we chose AuCu_(14)as a system to probe the excited-state behaviors and triplet energy transfer dynamics of bimetallic nanoclusters.The O_(2)sensitivity of both photoluminescence quantum yield and excited-state lifetime confirms triplet-origin emission,while the minimal spectral changes at low temperature suggest weak electron-vibration coupling.Notably,although O_(2)induces significant photoluminescence quenching,the addition of triplet-state acceptors(perylene and anthracene)shows no quenching effect due to steric hindrance from surface ligands.These results advance the mechanistic understanding of triplet-state dynamics in AuCu bimetallic nanoclusters.展开更多
In this paper, we investigate the downlink performance of cell-free massive multi-input multi-output non-orthogonal multiple access(CF-m MIMO-NOMA) system with conjugate beamforming precoder and compare against the or...In this paper, we investigate the downlink performance of cell-free massive multi-input multi-output non-orthogonal multiple access(CF-m MIMO-NOMA) system with conjugate beamforming precoder and compare against the orthogonal multiple access(OMA) counterpart. A novel achievable closed-form spectral efficiency(SE) expression is derived, which characterizes the effects of the channel estimation error, pilot contamination, imperfect successive interference cancellation(SIC) operation, and power optimization technique. Then, motivated by the closedform result, a sum-SE maximization algorithm with the sequential convex approximation(SCA) is proposed, subject to each AP power constraint and SIC power constraint. Numerical experiments indicate that the proposed sum-SE maximization algorithms have a fast converge rate, within about five iterations. In addition, compared with the full power control(FPC) scheme, our algorithms can significantly improve the achievable sum-SE. Moreover, NOMA outperforms OMA in many respects in the presence of the proposed algorithms.展开更多
基金supported by the National Key Research and Development Program of China(No.2023YFC2308500)the Fundamental Research Funds for the Central Universities(project no.2042024kf0026),the Open Grant from the Pingyuan Laboratory(2023PY-OP-0101)+3 种基金the National Natural Science Foundation of China(project no.81971936,32100125 and 32300131)Hubei Province's Outstanding Medical Academic Leader Program,East Lake Hi-tech Development Zone Unveiling and Commanding Project(No.2023KJB219)Science and Technology Talent Service Enterprise Project(No.2024DJC064)Basic and Clinical Medical Research Joint Fund of Zhongnan Hospital,Wuhan University.
文摘Dear Editor,Hepatitis B virus(HBV)is a small,enveloped DNA virus and a member of the Hepadnaviridae family(Zhao et al.,2020).It is a major human pathogen causing chronic liver disease,leading to significant morbidity and mortality worldwide(Xia and Liang,2019).According to the World Health Organization(WHO),an estimated 296 million people live with chronic HBV infection,contributing to around 820,000 deaths annually due to complications such as liver cirrhosis and hepatocellular carcinoma(HCC)(Easterbrook et al.,2021).
基金The Independent Research Foundation of Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)under contract Nos SML2023SP201 and SML2021SP306the Natural Science Foundation of Guangdong Province of China under contract No.2024A1515012717+5 种基金the Initial Research Foundation of Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)under contract Nos 313021004,313022009,and 313022001the National Natural Science Foundation of China under contract No.41706225the National Key R&D Program of China under contract No.2018YFA0605701the Impact and Response of Antarctic Seas to Climate Change under contract No.IRASCC 1-02-01Bthe Shenlan Program funded by Shanghai Jiao Tong University under contract No.SL2020MS021the fund from Shanghai Frontiers Science Center of Polar Research.
文摘The Southern Ocean is a critical component in the Earth system by dominating the global heat and anthropogenic carbon uptake and supplying heat to melt the largest ice sheet.Variability and changes in the water masses of the Southern Ocean are thus important to the global energy and water cycles,carbon cycling,and sea-level change.In this article,we review the recent progress on understanding the variability and changes in the four major water masses in the Southern Ocean,including Subantarctic Mode Water,Antarctic Intermediate Water,Circumpolar Deep Water and Antarctic Bottom Water.Subantarctic Mode Water and Antarctic Intermediate Water show statistically significant strong circumpolar shoaling,warming,and density reductions since 1970s,indicating that signals of global warming have entered the interior ocean.Meanwhile,strong regional variability of Subantarctic Mode Water and Antarctic Intermediate Water responding to surface buoyancy forcing and westerly winds is attracting more attention.Circumpolar Deep Water is an important modulator of heat content and nutrient concentrations on continental shelves around Antarctica and has made significant contributions to the basal melting of Antarctic ice shelves.Since the late 1950s,a long-term freshening trend in Antarctic Bottom Water in the Ross Sea and its downstream region has been observed and is mainly attributed to the accelerated basal melting of ice shelves in West Antarctica.The shrinking of Antarctic Bottom Water in the Weddell Sea during 1992–2020 has also been revealed and is attributed to reduced sea ice production over the southern Weddell continental shelf related to the Interdecadal Pacific Oscillation and the variability in the Amundsen Sea Low.Though significant advances have been achieved,there is an urgent need to enhance and improve both observations and model performances for better understandings and projections of the formation,transformation,and transport of the water masses in the Southern Ocean.
文摘BACKGROUND Cholangiocarcinoma(CCA)is a highly aggressive malignancy with limited therapeutic options.Dysregulation of the Hippo-yes-associated protein(YAP)signaling pathway plays a key role in tumor progression,but the effects of distinct bile acids on this pathway remain unclear.AIM To investigate the roles of glycochenodeoxycholic acid(GDCA)and deoxycholic acid(DCA)in CCA progression through Hippo-YAP signaling and to evaluate the effects of YAP-targeted interventions.METHODS The in vitro experiments were performed using HuCCT1 CCA cells treated with GDCA,DCA,and combinations with a YAP inhibitor(verteporfin)or agonist(GA-017).Key molecular changes in the Hippo-YAP pathway were assessed by western blot,immunofluorescence,and reverse transcription quantitative realtime polymerase chain reaction.Functional assays,including Cell Counting Kit-8,5-ethynyl-2’-deoxyuridine,Transwell,and terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate-nick end labelling,were conducted to evaluate cell proliferation,migration,invasion,and apoptosis.In vivo,nude mice bearing subcutaneous HuCCT1 tumors were treated with GDCA,DCA,or combined YAP modulators.Tumor growth was monitored,and molecular analyses of tumor tissues were performed using western blot.RESULTS The GDCA significantly activated YAP by reducing mammalian STE20-like protein kinase 1 and large tumor suppressor 1 phosphorylation,promoting YAP nuclear translocation,and enhancing tumor cell proliferation,migration,and invasion.In contrast,DCA inhibited YAP activation,suppressed tumor cell functions,and increased apoptosis.GDCA combined with YAP inhibitors attenuated its tumor-promoting effects,while DCA combined with YAP agonists reversed its inhibitory effects.In vivo,GDCA accelerated tumor growth,while DCA reduced tumor size and weight,with molecular changes consistent with in vitro findings.CONCLUSION The GDCA and DCA exert opposing effects on CCA progression through Hippo-YAP signaling.GDCA promotes tumor growth via YAP activation,while DCA inhibits these processes.YAP-targeted interventions demonstrate therapeutic potential,providing insights into new treatment strategies for CCA.
基金financially supported by the National Key R&D Program of China(No.2022YFB4600500)the National Safety Academic Fund(Nos.U2130201 and U2330105).
文摘NiTi alloy lattice structures are crucial for reusable energy absorption due to their shape memory effects.However,existing NiTi alloy lattice structures always suffer from localized deformation bands during loading,causing local strains to exceed the recoverable strain limit of the alloy and significantly reducing their reusable energy-absorbing capacity.In this study,we developed a NiTi alloy helical lattice structure(HLS)to effectively prevent localized deformation bands.This is attributed to its struts distributing stress and strain uniformly through torsional deformation,thereby alleviating local stress concentrations and suppressing the formation of localized deformation bands.Additionally,its unit cells provide mutual support and reinforcement during deformation,effectively preventing the progression of localized deformation bands.The NiTi alloy HLS exhibits superior reusable energy absorption compared to previously reported reusable energy-absorbing materials/structures and enhanced damage tolerance under large compression strain.This study provides valuable insights for the development of high-performance reusable NiTi alloy energy-absorbing lattice structures.
基金supported by the Key Scientific and Technological Projects(2024KJGG27)of Tianfu Yongxing Laboratorythe Experimental Platform Open Innovation Funding(209042025003)of Sichuan Energy Internet Research Institute,Tsinghua University.
文摘As the development of new power systems progresses,the inherent inertia of power systems continues to diminish.Centralized frequency regulation,which relies on rapid communication and real-time control,can enable inverter-based thermostatically controlled load(ITCL)clusters to provide virtual inertia support to the power grid.However,ITCL clusters exhibit significant discrete response characteristics,which precludes the direct integration of load-side inertia support into the synchronous unit side.To address this issue,this paper elaborates on the existing technical framework and analyzes the underlying causes of the problem.It proposes a timestamp allocation mechanism for ITCL cluster control instructions,ensuring that many ITCL terminals can be triggered at staggered times,thereby allowing the load cluster power to adhere to the inertia analog control law at any moment.Building on this foundation,the paper further examines the impact of the inertia response delay of ITCL clusters,which is based on centralized frequency regulation,on the stability of the power system.A design scheme for inertia analog control parameters is proposed,taking into account dual constraints,frequency stability and load cluster regulation capacity.Finally,the feasibility and applicability of the proposed mechanism and parameter design scheme are investigated through simulations conducted via MATLAB/Simulink.
基金supported by the National Natural Science Foundation of China(No.22273095).
文摘AuCu bimetallic nanoclusters exhibit enhanced emission relative to structurally analogous Au nanoclusters,though their excited-state dynamics remains incompletely characterized.Here,we chose AuCu_(14)as a system to probe the excited-state behaviors and triplet energy transfer dynamics of bimetallic nanoclusters.The O_(2)sensitivity of both photoluminescence quantum yield and excited-state lifetime confirms triplet-origin emission,while the minimal spectral changes at low temperature suggest weak electron-vibration coupling.Notably,although O_(2)induces significant photoluminescence quenching,the addition of triplet-state acceptors(perylene and anthracene)shows no quenching effect due to steric hindrance from surface ligands.These results advance the mechanistic understanding of triplet-state dynamics in AuCu bimetallic nanoclusters.
基金supported in part by the National Key Research and Development Program of China under Grant 2018YFC1314903the National Natural Science Foundation of China under Grants 61861039,61372124,and 61427801+1 种基金the Science and Technology Project Foundation of Gansu Province under Grant 18YF1GA060the Postgraduate Research&Practice Innovation Program of Jiangsu Province under Grant SJKY19_0740 and KYCX20_0709。
文摘In this paper, we investigate the downlink performance of cell-free massive multi-input multi-output non-orthogonal multiple access(CF-m MIMO-NOMA) system with conjugate beamforming precoder and compare against the orthogonal multiple access(OMA) counterpart. A novel achievable closed-form spectral efficiency(SE) expression is derived, which characterizes the effects of the channel estimation error, pilot contamination, imperfect successive interference cancellation(SIC) operation, and power optimization technique. Then, motivated by the closedform result, a sum-SE maximization algorithm with the sequential convex approximation(SCA) is proposed, subject to each AP power constraint and SIC power constraint. Numerical experiments indicate that the proposed sum-SE maximization algorithms have a fast converge rate, within about five iterations. In addition, compared with the full power control(FPC) scheme, our algorithms can significantly improve the achievable sum-SE. Moreover, NOMA outperforms OMA in many respects in the presence of the proposed algorithms.
