Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidat...Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidative stress,and mitochondrial dysfunction.Regrettably,there is a paucity of clinically available therapeutics to address these issues.Emerging evidence underscores the pivotal roles of astrocytes,the most abundant glial cells in the brain,throughout the various stages of ischemic stroke.In this comprehensive review,we initially provide an overview of the fundamental physiological functions of astrocytes in the brain,emphasizing their critical role in modulating neuronal homeostasis,synaptic activity,and blood-brain barrier integrity.We then delve into the growing body of evidence that highlights the functional diversity and heterogeneity of astrocytes in the context of ischemic stroke.Their well-established contributions to energy provision,metabolic regulation,and neurotransmitter homeostasis,as well as their emerging roles in mitochondrial recovery,neuroinflammation regulation,and oxidative stress modulation following ischemic injury,are discussed in detail.We also explore the cellular and molecular mechanisms underpinning these functions,with particular emphasis on recently identified targets within astrocytes that offer promising prospects for therapeutic intervention.In the final section of this review,we offer a detailed overview of the current therapeutic strategies targeting astrocytes in the treatment of ischemic stroke.These astrocyte-targeting strategies are categorized into traditional small-molecule drugs,microRNAs(miRNAs),stem cell-based therapies,cellular reprogramming,hydrogels,and extracellular vesicles.By summarizing the current understanding of astrocyte functions and therapeutic targeting approaches,we aim to highlight the critical roles of astrocytes during and after stroke,particularly in the pathophysiological development in ischemic stroke.We also emphasize promising avenues for novel,astrocyte-targeted therapeutics that could become clinically available options,ultimately improving outcomes for patients with stroke.展开更多
Background:Coronavirus disease 2019(COVID-19)is now a global public threat.Given the pandemic of COVID-19,the economic impact of COVID-19 is essential to add value to the policy-making process.We retrospectively condu...Background:Coronavirus disease 2019(COVID-19)is now a global public threat.Given the pandemic of COVID-19,the economic impact of COVID-19 is essential to add value to the policy-making process.We retrospectively conducted a cost and affordability analysis to determine the medical costs of COVID-19 patients in China,and also assess the factors affecting their costs.Methods:This analysis was retrospectively conducted in Shandong Provincial Chest Hospital between 24 January and 16 March 2020.The total direct medical expenditures were analyzed by cost factors.We also assessed affordability by comparing the simulated out-of-pocket expenditure of COVID-19 cases relative to the per capita disposable income.Differences between groups were tested by student t test and Mann-Whitney test when appropriate.A multiple logistic regression model was built to determine the risk factors associated with high cost.Results:A total of 70 COVID-19 patients were included in the analysis.The overall mean cost was USD 6827 per treated episode.The highest mean cost was observed in drug acquisition,accounting for 45.1%of the overall cost.Total mean cost was significantly higher in patients with pre-existing diseases compared to those without preexisting diseases.Pre-existing diseases and the advanced disease severity were strongly associated with higher cost.Around USD 0.49 billion were expected for clinical manage of COVID-19 in China.Among rural households,the proportions of health insurance coverage should be increased to 70%for severe cases,and 80%for critically ill cases to avoid catastrophic health expenditure.Conclusions:Our data demonstrate that clinical management of COVID-19 patients incurs a great financial burden to national health insurance.The cost for drug acquisition is the major contributor to the medical cost,whereas the risk factors for higher cost are pre-existing diseases and severity of COVID-19.Improvement of insurance coverage will need to address the barriers of rural patients to avoid the occurrence of catastrophic health expenditure.展开更多
Autophagy is a universal cellular process in eukaryotes that plays a critical role in plant growth and stress response.However,the role of autophagy in fruit ripening is largely unknown.Here,we demonstrated that most ...Autophagy is a universal cellular process in eukaryotes that plays a critical role in plant growth and stress response.However,the role of autophagy in fruit ripening is largely unknown.Here,we demonstrated that most autophagy-related genes(ATGs)were up-regulated during tomato(Solanum lycopersicum L.)fruit ripening.By using mutants of different autophagy pathway genes(ATG6,ATG10,ATG18a),we revealed that the deficiency of autophagy delayed the ripening of fruit.Compared with wild-type(WT),the production of ethylene was significantly reduced and the accumulation of lycopene was delayed in atg mutants during fruit ripening.We also observed the contents of glucose and fructose were both significantly decreased in atg mutants compared with WT,while the content of organic acids showed the opposite trend.Additionally,the negative regulator of ethylene production,APETALA2a(AP2a),interacted with ATG8 through a specific ATG8-interacting motif(AIM)and could be degraded through the autophagy pathway.These results demonstrate that autophagy plays a critical role in fruit ripening by regulating ethylene production and the accumulation of pigments,sugars and organic acids in tomato.展开更多
Primary liver cancer(PLC)is a prevalent malignancy with high incidence and mortality rates globally.Hepatocellular carcinoma(HCC),primarily resulting from hepatitis B virus infections in Asia,constitutes most PLC case...Primary liver cancer(PLC)is a prevalent malignancy with high incidence and mortality rates globally.Hepatocellular carcinoma(HCC),primarily resulting from hepatitis B virus infections in Asia,constitutes most PLC cases.Despite advancements in targeted therapies and localized treatments,the 5-year survival rate remains low,indicating limited efficacy of current approaches.The advent of immunotherapy,particularly immune checkpoint inhibitors(ICIs),has brought new hope for patients with PLC.However,the liver's unique immune microenvironment presents significant challenges to the effectiveness of immunotherapy in HCC.This article reviews recent research developments in liver cancer immunotherapy,focusing on ICIs,combination therapies,emerging treatments,and prospective future directions.展开更多
To elucidate the cyclic creep mechanisms in China's impure salt rock after high-temperature damage,cyclic nanoindentation and uniaxial cyclic loading tests were conducted at 25℃,100℃,120℃,and 160℃in this study...To elucidate the cyclic creep mechanisms in China's impure salt rock after high-temperature damage,cyclic nanoindentation and uniaxial cyclic loading tests were conducted at 25℃,100℃,120℃,and 160℃in this study.The results revealed that under cyclic nanoindentation,gypsum mineral exhibited significantly lower indentation depths compared to halite and ankerite minerals,indicating superior resistance to deformation.Additionally,the results demonstrated that high temperature significantly enhances the creep behavior.The maximum indentation depth and creep displacement of minerals,as well as the maximum deformation and creep strain of rock cores,all followed an exponential increase with rising temperatures,with the rate of increase accelerating at higher temperatures.Importantly,it was found that mineral deformation is not the dominant factor in the overall deformation of rock cores;however,the behavior of the mineral phases fundamentally governs the salt rock's mechanical response under stress.Based on these findings,a new constitutive model for cyclic creep was established based on fractional derivatives to accurately characterize the nonlinear cyclic creep characteristics of impure salt rocks at different scales.This model was validated against test data,effectively representing the periodic fluctuations in indentation depth or strain,particularly during the accelerated creep stage.Furthermore,a temperature-dependent correction parameter was introduced,along with a modified Mori-Tanaka method,to upscale microscale results to the macroscale across varying temperatures.This study provides a theoretical foundation for predicting deformation and assessing the stability of salt cavern walls under high-temperature and cyclic loading conditions in deep geological settings.展开更多
As a pathfinder of the SiTian project,the Mini-SiTian(MST)Array,employed three commercial CMOS cameras,represents a next-generation,cost-effective optical time-domain survey project.This paper focuses primarily on the...As a pathfinder of the SiTian project,the Mini-SiTian(MST)Array,employed three commercial CMOS cameras,represents a next-generation,cost-effective optical time-domain survey project.This paper focuses primarily on the precise data processing pipeline designed for wide-field,CMOS-based devices,including the removal of instrumental effects,astrometry,photometry,and flux calibration.When applying this pipeline to approximately3000 observations taken in the Field 02(f02)region by MST,the results demonstrate a remarkable astrometric precision of approximately 70–80 mas(about 0.1 pixel),an impressive calibration accuracy of approximately1 mmag in the MST zero points,and a photometric accuracy of about 4 mmag for bright stars.Our studies demonstrate that MST CMOS can achieve photometric accuracy comparable to that of CCDs,highlighting the feasibility of large-scale CMOS-based optical time-domain surveys and their potential applications for cost optimization in future large-scale time-domain surveys,like the SiTian project.展开更多
基金supported by the National Natural Science Foundation of China,No.82001325Visiting Scholar Foundation of Shandong Province,No.20236-01(both to CS).
文摘Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidative stress,and mitochondrial dysfunction.Regrettably,there is a paucity of clinically available therapeutics to address these issues.Emerging evidence underscores the pivotal roles of astrocytes,the most abundant glial cells in the brain,throughout the various stages of ischemic stroke.In this comprehensive review,we initially provide an overview of the fundamental physiological functions of astrocytes in the brain,emphasizing their critical role in modulating neuronal homeostasis,synaptic activity,and blood-brain barrier integrity.We then delve into the growing body of evidence that highlights the functional diversity and heterogeneity of astrocytes in the context of ischemic stroke.Their well-established contributions to energy provision,metabolic regulation,and neurotransmitter homeostasis,as well as their emerging roles in mitochondrial recovery,neuroinflammation regulation,and oxidative stress modulation following ischemic injury,are discussed in detail.We also explore the cellular and molecular mechanisms underpinning these functions,with particular emphasis on recently identified targets within astrocytes that offer promising prospects for therapeutic intervention.In the final section of this review,we offer a detailed overview of the current therapeutic strategies targeting astrocytes in the treatment of ischemic stroke.These astrocyte-targeting strategies are categorized into traditional small-molecule drugs,microRNAs(miRNAs),stem cell-based therapies,cellular reprogramming,hydrogels,and extracellular vesicles.By summarizing the current understanding of astrocyte functions and therapeutic targeting approaches,we aim to highlight the critical roles of astrocytes during and after stroke,particularly in the pathophysiological development in ischemic stroke.We also emphasize promising avenues for novel,astrocyte-targeted therapeutics that could become clinically available options,ultimately improving outcomes for patients with stroke.
基金The study was supported by the Shandong Taishan Scholar Program(TS201712099)the National Key Research Program of China(2018ZX10103–001)the Beijing Hospitals Authority’Ascent Plan(DFL20191601).
文摘Background:Coronavirus disease 2019(COVID-19)is now a global public threat.Given the pandemic of COVID-19,the economic impact of COVID-19 is essential to add value to the policy-making process.We retrospectively conducted a cost and affordability analysis to determine the medical costs of COVID-19 patients in China,and also assess the factors affecting their costs.Methods:This analysis was retrospectively conducted in Shandong Provincial Chest Hospital between 24 January and 16 March 2020.The total direct medical expenditures were analyzed by cost factors.We also assessed affordability by comparing the simulated out-of-pocket expenditure of COVID-19 cases relative to the per capita disposable income.Differences between groups were tested by student t test and Mann-Whitney test when appropriate.A multiple logistic regression model was built to determine the risk factors associated with high cost.Results:A total of 70 COVID-19 patients were included in the analysis.The overall mean cost was USD 6827 per treated episode.The highest mean cost was observed in drug acquisition,accounting for 45.1%of the overall cost.Total mean cost was significantly higher in patients with pre-existing diseases compared to those without preexisting diseases.Pre-existing diseases and the advanced disease severity were strongly associated with higher cost.Around USD 0.49 billion were expected for clinical manage of COVID-19 in China.Among rural households,the proportions of health insurance coverage should be increased to 70%for severe cases,and 80%for critically ill cases to avoid catastrophic health expenditure.Conclusions:Our data demonstrate that clinical management of COVID-19 patients incurs a great financial burden to national health insurance.The cost for drug acquisition is the major contributor to the medical cost,whereas the risk factors for higher cost are pre-existing diseases and severity of COVID-19.Improvement of insurance coverage will need to address the barriers of rural patients to avoid the occurrence of catastrophic health expenditure.
基金supported by the National Natural Science Foundation of China(Grant Nos.32302642,32272790)the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(Grant No.SN-ZJU-SIAS-0011)+1 种基金Collaborative Promotion Program of Zhejiang Provincial Agricultural Technology of China(Grant No.2023ZDXT05)the Fundamental Research Funds for the Central Universities(Grant No.226-2022-00122).
文摘Autophagy is a universal cellular process in eukaryotes that plays a critical role in plant growth and stress response.However,the role of autophagy in fruit ripening is largely unknown.Here,we demonstrated that most autophagy-related genes(ATGs)were up-regulated during tomato(Solanum lycopersicum L.)fruit ripening.By using mutants of different autophagy pathway genes(ATG6,ATG10,ATG18a),we revealed that the deficiency of autophagy delayed the ripening of fruit.Compared with wild-type(WT),the production of ethylene was significantly reduced and the accumulation of lycopene was delayed in atg mutants during fruit ripening.We also observed the contents of glucose and fructose were both significantly decreased in atg mutants compared with WT,while the content of organic acids showed the opposite trend.Additionally,the negative regulator of ethylene production,APETALA2a(AP2a),interacted with ATG8 through a specific ATG8-interacting motif(AIM)and could be degraded through the autophagy pathway.These results demonstrate that autophagy plays a critical role in fruit ripening by regulating ethylene production and the accumulation of pigments,sugars and organic acids in tomato.
文摘Primary liver cancer(PLC)is a prevalent malignancy with high incidence and mortality rates globally.Hepatocellular carcinoma(HCC),primarily resulting from hepatitis B virus infections in Asia,constitutes most PLC cases.Despite advancements in targeted therapies and localized treatments,the 5-year survival rate remains low,indicating limited efficacy of current approaches.The advent of immunotherapy,particularly immune checkpoint inhibitors(ICIs),has brought new hope for patients with PLC.However,the liver's unique immune microenvironment presents significant challenges to the effectiveness of immunotherapy in HCC.This article reviews recent research developments in liver cancer immunotherapy,focusing on ICIs,combination therapies,emerging treatments,and prospective future directions.
基金supported by the National Natural Science Foundation of China(Grant No.12402488)the China Postdoctoral Science Foundation(Grant No.2023M742898)the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(Grant No.GZC20232193).
文摘To elucidate the cyclic creep mechanisms in China's impure salt rock after high-temperature damage,cyclic nanoindentation and uniaxial cyclic loading tests were conducted at 25℃,100℃,120℃,and 160℃in this study.The results revealed that under cyclic nanoindentation,gypsum mineral exhibited significantly lower indentation depths compared to halite and ankerite minerals,indicating superior resistance to deformation.Additionally,the results demonstrated that high temperature significantly enhances the creep behavior.The maximum indentation depth and creep displacement of minerals,as well as the maximum deformation and creep strain of rock cores,all followed an exponential increase with rising temperatures,with the rate of increase accelerating at higher temperatures.Importantly,it was found that mineral deformation is not the dominant factor in the overall deformation of rock cores;however,the behavior of the mineral phases fundamentally governs the salt rock's mechanical response under stress.Based on these findings,a new constitutive model for cyclic creep was established based on fractional derivatives to accurately characterize the nonlinear cyclic creep characteristics of impure salt rocks at different scales.This model was validated against test data,effectively representing the periodic fluctuations in indentation depth or strain,particularly during the accelerated creep stage.Furthermore,a temperature-dependent correction parameter was introduced,along with a modified Mori-Tanaka method,to upscale microscale results to the macroscale across varying temperatures.This study provides a theoretical foundation for predicting deformation and assessing the stability of salt cavern walls under high-temperature and cyclic loading conditions in deep geological settings.
基金supported by the National Key Basic R&D Program of China via 2023YFA1608303the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0550103)+3 种基金the National Science Foundation of China 12422303,12403024,12222301,12173007,and 12261141690the Postdoctoral Fellowship Program of CPSF under grant Number GZB20240731the Young Data Scientist Project of the National Astronomical Data Center,and the China Post-doctoral Science Foundation No.2023M743447support from the NSFC through grant No.12303039 and No.12261141690.
文摘As a pathfinder of the SiTian project,the Mini-SiTian(MST)Array,employed three commercial CMOS cameras,represents a next-generation,cost-effective optical time-domain survey project.This paper focuses primarily on the precise data processing pipeline designed for wide-field,CMOS-based devices,including the removal of instrumental effects,astrometry,photometry,and flux calibration.When applying this pipeline to approximately3000 observations taken in the Field 02(f02)region by MST,the results demonstrate a remarkable astrometric precision of approximately 70–80 mas(about 0.1 pixel),an impressive calibration accuracy of approximately1 mmag in the MST zero points,and a photometric accuracy of about 4 mmag for bright stars.Our studies demonstrate that MST CMOS can achieve photometric accuracy comparable to that of CCDs,highlighting the feasibility of large-scale CMOS-based optical time-domain surveys and their potential applications for cost optimization in future large-scale time-domain surveys,like the SiTian project.
