For constructing next-generation lithium-ion batteries with advanced performances,pursuit of highcapacity Li-rich cathodes has caused considerable attention.So far,the low discharge specific capacity and serious capac...For constructing next-generation lithium-ion batteries with advanced performances,pursuit of highcapacity Li-rich cathodes has caused considerable attention.So far,the low discharge specific capacity and serious capacity fading are strangling the development of Fe-based Li-rich materials.To activate the extra-capacity of Fe-based Li-rich cathode materials,a facile molten salt method is exploited using an alkaline mixture of LiOH–LiNO3–Li2O2 in this work.The prepared Li1.09(Fe0.2Ni0.3Mn0.5)0.91O2 material yields high discharge specific capacity and good cycling stability.The discharge specific capacity shows an upward tendency at 0.1 C.After 60 cycles,a high reversible specific capacity of ~250 m Ah g-1is delivered.The redox of Fe3+/Fe4+and Mn3+/Mn4+are gradually activated during cycling.Notably,the redox reaction of Fe2+/Fe3+can be observed reversibly below 2 V,which is quite different from the material prepared by a traditional co-precipitation method.The stable morphology of fine nanoparticles(100–300 nm)is considered benefiting for the distinctive electrochemical performances of Li1.09(Fe0.2Ni0.3Mn0.5)0.91O2.This study demonstrates that molten salt method is an inexpensive and effective approach to activate the extra capacity of Fe-based Li-rich cathode material for high-performance lithium-ion batteries.展开更多
目的近年来,使用移动医疗应用程序为乳腺癌患者提供照护的实践数量日益增长。本研究旨在总结用于乳腺癌患者照护的移动医疗应用程序的现有证据,以便为后续研究提供发展方向。方法按照Arksey与O’Malley提出的范围综述方法框架,对PubMed...目的近年来,使用移动医疗应用程序为乳腺癌患者提供照护的实践数量日益增长。本研究旨在总结用于乳腺癌患者照护的移动医疗应用程序的现有证据,以便为后续研究提供发展方向。方法按照Arksey与O’Malley提出的范围综述方法框架,对PubMed、CINAHL和Web of Science数据库中发表于2010年1月至2020年12月的相关文献开展研究,并确定符合纳入标准的研究。由2名研究员独立进行文献的筛选、提取和分析。结果共检索出676篇文章,8篇文章符合纳入标准。研究结果呈现出4个主题:患者和卫生服务保健人员在设计和开发阶段的参与、患者的偏好、患者的特点、使用移动医疗应用程序的动机。研究显示,在乳腺癌患者的照护中采用移动医疗应用程序具有良好的前景,且一系列要素在相关应用程序的设计及开发过程中需要加以考虑。结论在为乳腺癌患者开发移动医疗应用程序时应考虑患者的特征、需求和患者自我报告的健康结果数据。此外,包括患者、护士和其他重要的卫生服务保健人员在内的合作将有助于乳腺癌患者移动医疗应用程序的开发。展开更多
Nanoplastics-induced developmental and reproductive toxicity,neurotoxicity and immunotoxicity are a focus of widespread attention.However,the effects of nanoplastics(NPs)on glycolipid metabolism and the precise underl...Nanoplastics-induced developmental and reproductive toxicity,neurotoxicity and immunotoxicity are a focus of widespread attention.However,the effects of nanoplastics(NPs)on glycolipid metabolism and the precise underlying mechanisms are unclear at present.Here,we showed that oral administration of polystyrene nanoparticles(PS-NPs)disrupts glycolipid metabolism,with reactive oxygen species(ROS)identified as a potential key signaling molecule.After PS-NPs treatment,excessive production of ROS induced the infammatory response and activated the antioxidant pathway through nuclear factor-erythroid factor 2-related factor 2.The activation of nuclear factor-κB(NFκB)signaling pathway induced the phosphorylation of the mitogen-activated protein kinases(MAPK)signaling pathway,which induced the activation of extracellular regulated kinases(ERK)and p38.Constitutive activation of the MAPK signaling proteins induced high continued phosphorylation of insulin receptor substrate-1,in turn,leading to decreased protein kinase B(Akt)activity,which weakened the sensitivity of liver cells to insulin signals and induced insulin resistance.In parallel,phosphorylation of Akt led to loss of control of Fo XO1,a key gene of gluconeogenesis,activating transcription of glucose-6-phosphatase(G6PC)and phosphoenolpyruvate carboxykinase(PEPCK)in a manner dependent on PGC1α.Moreover,the activated ERK promoted lipid accumulation through ERK-PPARγcascades.Therefore,sterol regulatory element-binding protein-1 and levels of its downstream lipogenic enzymes,ACC-1,were up-regulated.Upon treatment with the antioxidant resveratrol,PS-NPs-induced glucose and lipid metabolic disorders were improved by inhibiting ROS-induced activation of NFκB and MAPK signaling pathway in mice.Based on above,PS-NPs exposure disrupts glycolipid metabolism in mice,with ROS identified as a potential key signaling molecule.展开更多
High temperature warning indicators play a pivotal role in meteorological departments,serving as crucial criteria for issuing warnings that guide both social production and daily life.Despite their importance,limited ...High temperature warning indicators play a pivotal role in meteorological departments,serving as crucial criteria for issuing warnings that guide both social production and daily life.Despite their importance,limited studies have explored the relationship between different global warming levels and changes in high temperature warning indicators.In this study,we analyze data from 2,419 meteorological stations over China and utilize the Coupled Model Intercomparison Project Phase 6(CMIP6)models to examine historical changes in high temperature warning indicators used by the China Meteorological Administration.We evaluate model performance and estimate future changes in these indicators using an annual cycle bias correction method.The results indicate that since 1961,the number of high temperature days(TX35d and TX40d)and length of season(TX40d and TX40l)with daily maximum temperature reaching or exceeding 35℃ and 40℃ have increased over China.The intensity of high temperatures(TXx)has strengthened and the geographical extent affected by high temperatures has expanded.In 2022,the occurrence of 40℃ high temperatures surges,with Eastern China experiencing a two-day increase in TX40d and an extended seasonal length in TX40l by over five days.While CMIP6 models have underestimated the high temperature indictors associated with 35℃ during historical periods,notable difference is not observed between the models and observations for TX40d and TX40l,given their rare occurrence.However,future projections,after bias correction,indicate that the increasing trends for 35℃ and 40℃ high temperature days and length of season become more pronounced than the raw projection,suggesting a more severe increase than that anticipated originally.As global warming intensifies,the high temperature days and length of season are projected to increase non-linearly,while the intensity of high temperatures is expected to increase linearly.For every 1℃ increase in global temperature,the intensity is projected to rise by approximately 1.4℃.The impact of high temperatures is expanding,with the major hotspot for China located in the eastern and northwestern regions.Under 5℃ global warming,certain regions in China may experience prolonged extreme high temperatures.For instance,40℃ high temperature days in areas like North China and the Yangtze River Basin could increase by about 32 d,and the length of season could extend by approximately 100 d.展开更多
The cytokine granulocyte-macrophage-colony stimulating factor (GM-CSF) possesses the capacity to differentiate monocytes into macrophages (MØs) with opposing functions, namely, proinflammatory M1-like MØs an...The cytokine granulocyte-macrophage-colony stimulating factor (GM-CSF) possesses the capacity to differentiate monocytes into macrophages (MØs) with opposing functions, namely, proinflammatory M1-like MØs and immunosuppressive M2-like MØs. Despite the importance of these opposing biological outcomes, the intrinsic mechanism that regulates the functional polarization of MØs under GM-CSF signaling remains elusive. Here, we showed that GM-CSF-induced MØ polarization resulted in the expression of cytokine-inducible SH2-containing protein (CIS) and that CIS deficiency skewed the differentiation of monocytes toward immunosuppressive M2-like MØs. CIS deficiency resulted in hyperactivation of the JAK-STAT5 signaling pathway, consequently promoting downregulation of the transcription factor Interferon Regulatory Factor 8 (IRF8). Loss- and gain-of-function approaches highlighted IRF8 as a critical regulator of the M1-like polarization program. In vivo, CIS deficiency induced the differentiation of M2-like macrophages, which promoted strong Th2 immune responses characterized by the development of severe experimental asthma. Collectively, our results reveal a CIS-modulated mechanism that clarifies the opposing actions of GM-CSF in MØ differentiation and uncovers the role of GM-CSF in controlling allergic inflammation.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of coronavirus disease 2019(COVID-19),has had a significant impact on healthcare systems and economies worldwide.The continuous emergence...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of coronavirus disease 2019(COVID-19),has had a significant impact on healthcare systems and economies worldwide.The continuous emergence of new viral strains presents a major challenge in the development of effective antiviral agents.Strategies that possess broad-spectrum antiviral activities are desirable to control SARS-CoV-2 infection.ACE2,an angiotensin-containing enzyme that prevents the overactivation of the renin angiotensin system,is the receptor for SARS-CoV-2.ACE2 interacts with the spike protein and facilitates viral attachment and entry into host cells.Yet,SARS-CoV-2 infection also promotes ACE2 degradation.Whether restoring ACE2 surface expression has an impact on SARS-CoV-2 infection is yet to be determined.Here,we show that the ACE2-spike complex is endocytosed and degraded via autophagy in a manner that depends on clathrin-mediated endocytosis and PAK1-mediated cytoskeleton rearrangement.In contrast,free cellular spike protein is selectively cleaved into S1 and s2 subunits in a lysosomal-dependent manner.Importantly,we show that the pan-PAK inhibitor FRAX-486 restores ACE2 surface expression and suppresses infection by different SARS-CoV-2 strains.FRAX-486-treated Syrian hamsters exhibit significantly decreased lung viral load and alleviated pulmonary inflammation compared with untreated hamsters.In summary,our findings have identified novel pathways regulating viral entry,as well as therapeutic targets and candidate compounds for controlling the emerging strains of SARS-CoV-2 infection.展开更多
Domain of unknown function 1644 (DUF1644) is a highly conserved amino acid sequence motif present only in plants. Analysis of expression data of the family of DUF1644- containing genes indicated that they may regula...Domain of unknown function 1644 (DUF1644) is a highly conserved amino acid sequence motif present only in plants. Analysis of expression data of the family of DUF1644- containing genes indicated that they may regulate responses to abiotic stress in rice. Here we present our discovery of the role of Os.SIDP366, a member of the DUF1644 gene family, in response to drought and salinity stresses in rice. Transgenic rice plants overexpressing OsSIDP366 showed enhanced drought and salinity tolerance and reduced water loss as compared to that in the control, whereas plants with downregulated OsSIDP366 expression levels using RNA interference (RNAi) were more sensitive to salinity and drought treatments. The sensitivity to abscisic acid (ABA) treatment was not changed in OsStDP366-overexpressing plants, and OsSIDP366 expression was not affected in ABA- deficient mutants. Subcellular localization analysis revealed that OsSIDP366 is presented in the cytoplasmic foci that colocalized with protein markers for both processing bodies (PBs) and stress granules (SGs) in rice protoplasts. Digital gene expression (DGE) profile analysis indicated that stress-related genes such as SNACl, OsHAK5 and PRs were upregulated in OsSIDP366-overexpressing plants. These results suggest that OsSIDP366 may function as a regulator of the PBs/SGs and positively regulate salt and drought resistance in rice.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan dysfunction.Effective antivirals with safe clinical pro...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan dysfunction.Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis.In an analysis of a randomly collected cohort of 124 patients with COVID-19,we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity.By virtual screening of a U.S.FDA approved drug library,we identified an anticoagulation agent dipyridamole(DIP)in silico,which suppressed SARS-CoV-2 replication in vitro.In a proof-of-concept trial involving 31 patients with COVID-19,DIP supplementation was associated with significantly decreased concentrations of D-dimers(P<0.05),increased lymphocyte and platelet recovery in the circulation,and markedly improved clinical outcomes in comparison to the control patients.In particular,all 8 of the DIP-treated severely ill patients showed remarkable improvement:7 patients(87.5%)achieved clinical cure and were discharged from the hospitals while the remaining 1 patient(12.5%)was in clinical remission.展开更多
Praseodymium-ion-doped gain materials have the superiority of lasing at various visible wavelengths directly.Simple and compact visible lasers are booming with the development of blue laser diodes in recent years.In t...Praseodymium-ion-doped gain materials have the superiority of lasing at various visible wavelengths directly.Simple and compact visible lasers are booming with the development of blue laser diodes in recent years.In this Letter, we demonstrate the watt-level red laser with a single blue laser diode and Pr:YLiF4 crystal.On this basis,the passively Q-switched pulse lasers are obtained with monolayer graphene and Co:ZnO thin film as the Q-switchers in the visible range.展开更多
The 4th Chinese American Liver Society(CALS)/Society of Chinese Bioscientists in America(SCBA)Hepatology Division Annual Symposium was held virtually on October 29e30,2021.The goal of the CALS Symposium was to present...The 4th Chinese American Liver Society(CALS)/Society of Chinese Bioscientists in America(SCBA)Hepatology Division Annual Symposium was held virtually on October 29e30,2021.The goal of the CALS Symposium was to present and discuss the recent research data on the pathogenesis and therapeutic targets of liver diseases among the CALS members,trainees and invited speakers.Here we briefly introduce the history of the CALS/SCBA Hepatology Division and highlight the presentations that focus on the current progresses on basic and translational research in liver metabolism,bile acid biology,alcohol-related liver disease,drug-induced liver injury,cholestatic liver injury,non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and liver cancer.展开更多
The liver is an essential organ for nutrient and drug metabolism - possessing the remarkable ability to sense environmental and metabolic stimuli and provide an optimally adaptive response. Early growth response 1 (Eg...The liver is an essential organ for nutrient and drug metabolism - possessing the remarkable ability to sense environmental and metabolic stimuli and provide an optimally adaptive response. Early growth response 1 (Egr1), an immediate early transcriptional factor which acts as a coordinator of the complex response to stress, is induced during liver injury and controls the expression of a wide range of genes involved in metabolism, cell proliferation, and inflammation. In support of an important role of Egr1 in liver injury and repair, deficiency of Egr1 delays liver regeneration process. The known upstream regulators of Egr1 include, but are not limited to, growth factors (e.g. transforming growth factor β1, platelet-derived growth factor, epidermal growth factor, hepatocyte growth factor), nuclear receptors (e.g. hepatocyte nuclear factor 4α, small heterodimer partner, peroxisome proliferator-activated receptor-γ), and other transcription factors (e.g. Sp1, E2F transcription factor 1). Research efforts using various animal models such as fatty liver, liver injury, and liver fibrosis contribute greatly to the elucidation of Egr1 function in the liver. Hepatocellular carcinoma (HCC) represents the second leading cause of cancer mortality worldwide due to the heterogeneity and the late stage at which cancer is generally diagnosed. Recent studies highlight the involvement of Egr1 in HCC development. The purpose of this review is to summarize current studies pertaining to the role of Egr1 in liver metabolism and liver diseases including liver cancer.展开更多
Cell-to-cell communication is a fascinating process that is essential for maintaining tissue and wholebody homeostasis.Extracellular vesicles(EVs)are cell-derived membrane-bound nanoparticles that are a means of commu...Cell-to-cell communication is a fascinating process that is essential for maintaining tissue and wholebody homeostasis.Extracellular vesicles(EVs)are cell-derived membrane-bound nanoparticles that are a means of communication between cells.Accumulating evidence indicates that EVs can render either beneficial or harmful outcomes,depending on the specific cargos(e.g.,proteins,lipids,RNAs)transferred between cells.EVs also have great value as diagnostic and prognostic markers of disease because they are present in a variety of biological fluids and carry bioactive molecules from their cells or tissues of origin.Liver cells can both release and receive EVs derived from other cells and emerging evidence indicates that liver EVs play important roles in the pathogenesis of various liver diseases,including liver cancer,viral hepatitis,non-alcoholic fatty liver disease,and alcoholic liver disease.This review provides an overview of the biogenesis and secretion of EVs and summarizes the most recent advances in understanding the role of EVs in liver physiology and diseases.Additionally,we discuss potential applications of liver EVs as biomarkers and in therapeutic approaches to treat liver diseases.展开更多
Cytoplasmic processing bodies,termed P bodies,are involved in diverse post-transcriptional processes including mRNA decay,nonsense-mediated RNA decay(NMD),RNAi,miRNA-mediated translational repression and storage of tr...Cytoplasmic processing bodies,termed P bodies,are involved in diverse post-transcriptional processes including mRNA decay,nonsense-mediated RNA decay(NMD),RNAi,miRNA-mediated translational repression and storage of translationally silenced mRNAs.Regulation of the formation of P bodies in the context of multicellular organisms is poorly understood.Here we describe a systematic RNAi screen in C.elegans that identified 224 genes with diverse cellular functions whose inactivations result in a dramatic increase in the number of P bodies.83 of these genes form a complex functional interaction network regulating NMD.We demonstrate that NMD interfaces with many cellular processes including translation,ubiquitin-mediated protein degradation,intracellular trafficking and cytoskeleton structure.We also uncover an extensive link between translation and RNAi,with different steps in protein synthesis appearing to have distinct effects on RNAi efficiency.Moreover,the intracellular vesicular trafficking network plays an important role in the regulation of RNAi.A subset of genes enhancing P body formation also regulate the formation of stress granules in C.elegans.Our study offers insights into the cellular mechanisms that regulate the formation of P bodies and also provides a framework for system-level understanding of NMD and RNAi in the context of the development of multicellular organisms.展开更多
Let(M,g)be a Kähler surface andΣbe aβ-symplectic critical surface in M.If L_(q)(Σ)is bounded for some q>3,then we give a uniform upper bound for the Kähler angle onΣ.This bound only depends on M,q,βa...Let(M,g)be a Kähler surface andΣbe aβ-symplectic critical surface in M.If L_(q)(Σ)is bounded for some q>3,then we give a uniform upper bound for the Kähler angle onΣ.This bound only depends on M,q,βand the Lq functional ofΣ.For q>4,this estimate is known and we extend the scope of q.展开更多
Background and aim:Non-alcoholic fatty liver disease(NAFLD)is becoming a leading cause of chronic liver disease worldwide.The molecular events that influence disease progression from non-alcoholic fatty liver(NAFL)to ...Background and aim:Non-alcoholic fatty liver disease(NAFLD)is becoming a leading cause of chronic liver disease worldwide.The molecular events that influence disease progression from non-alcoholic fatty liver(NAFL)to aggressive non-alcoholic steatohepatitis(NASH)remain incompletely understood,leading to lack of mechanism-based targeted treatment options for NASH.This study aims to identify early signatures associated with disease progression from NAFL to NASH in mice and humans.Materials and methods:Male C57BL/6J mice were fed a high-fat,-cholesterol,and-fructose(HFCF)diet for up to 9 months.The extent of steatosis,inflammation,and fibrosis was evaluated in liver tissues.Total RNA sequencing(RNA-seq)was conducted to determine liver transcriptomic changes.Results:After being fed the HFCF diet,mice sequentially developed steatosis,early steatohepatitis,steatohepatitis with fibrosis,and eventually spontaneous liver tumor.Hepatic RNA-seq revealed that the key signatures during steatosis progression to early steatohepatitis were pathways related to extracel-lular matrix organization and immune responses such as T cell migration,arginine biosynthesis,C-type lectin receptor signaling,and cytokine-cytokine receptor interaction.Genes regulated by transcription factors forkhead box M1(FOXM1)and negative elongation factor complex member E(NELFE)were significantly altered during disease progression.This phenomenon was also observed in patients with NASH.展开更多
A wide array of chemokine receptors,including CCR2,are known to control Treg migration.Here,we report that CCR2 regulates Tregs beyond chemotaxis.We found that CCR2 deficiency reduced CD25 expression by FoxP3^(+) Treg...A wide array of chemokine receptors,including CCR2,are known to control Treg migration.Here,we report that CCR2 regulates Tregs beyond chemotaxis.We found that CCR2 deficiency reduced CD25 expression by FoxP3^(+) Treg cells.Such a change was also consistently present in irradiation chimeras reconstituted with mixed bone marrow from wild-type(WT)and CCR2−/−strains.Thus,CCR2 deficiency resulted in profound loss of CD25 ^(hi) FoxP3^(+) Tregs in secondary lymphoid organs as well as in peripheral tissues.CCR2−/−Treg cells were also functionally inferior to WT cells.Interestingly,these changes to Treg cells did not depend on CCR2+monocytes/moDCs(the cells where CCR2 receptors are most abundant).Rather,we demonstrated that CCR2 was required for TLR-stimulated,but not TCR-or IL-2-stimulated,CD25 upregulation on Treg cells.Thus,we propose that CCR2 signaling can increase the fitness of FoxP3^(+) Treg cells and provide negative feedback to counter the proinflammatory effects of CCR2 on myeloid cells.展开更多
Graphene and other extraordinary two-dimensional materials together with recent advances in optical modulators have set the foundations for the widespread applications of next-generation optoelectronic devices. In thi...Graphene and other extraordinary two-dimensional materials together with recent advances in optical modulators have set the foundations for the widespread applications of next-generation optoelectronic devices. In this work, we report on the high-performance fundamentally mode-locked waveguide laser modulated by chemicalvapor-deposition-grown WSe2 as a saturable absorber. By incorporating a WSe2 sample into a monolithic Nd:YVO4 waveguide platform, 6.526 GHz picosecond pulsed laser generation has been achieved at the wavelength of 1 μm with pulse duration of 47 ps.展开更多
基金supported by the Nature Science Foundations of Hebei Province (B2016210071, B2016210111)the Natural Science Foundation of Hebei Education Department (QN2016057, ZD2015082, ZC2016045)+3 种基金the National College Students’ Innovative Entrepreneurial Training Project of Chinasupported by the Chinese National 973 Program (2015CB251106)the Joint Funds of the National Natural Science Foundation of China (U1564206)Major achievements Transformation Project for Central University in Beijing
文摘For constructing next-generation lithium-ion batteries with advanced performances,pursuit of highcapacity Li-rich cathodes has caused considerable attention.So far,the low discharge specific capacity and serious capacity fading are strangling the development of Fe-based Li-rich materials.To activate the extra-capacity of Fe-based Li-rich cathode materials,a facile molten salt method is exploited using an alkaline mixture of LiOH–LiNO3–Li2O2 in this work.The prepared Li1.09(Fe0.2Ni0.3Mn0.5)0.91O2 material yields high discharge specific capacity and good cycling stability.The discharge specific capacity shows an upward tendency at 0.1 C.After 60 cycles,a high reversible specific capacity of ~250 m Ah g-1is delivered.The redox of Fe3+/Fe4+and Mn3+/Mn4+are gradually activated during cycling.Notably,the redox reaction of Fe2+/Fe3+can be observed reversibly below 2 V,which is quite different from the material prepared by a traditional co-precipitation method.The stable morphology of fine nanoparticles(100–300 nm)is considered benefiting for the distinctive electrochemical performances of Li1.09(Fe0.2Ni0.3Mn0.5)0.91O2.This study demonstrates that molten salt method is an inexpensive and effective approach to activate the extra capacity of Fe-based Li-rich cathode material for high-performance lithium-ion batteries.
基金This study was supported by the Natural Science Foundation of China(71874032)the Natural Science Foundation of China(72074054).
文摘目的近年来,使用移动医疗应用程序为乳腺癌患者提供照护的实践数量日益增长。本研究旨在总结用于乳腺癌患者照护的移动医疗应用程序的现有证据,以便为后续研究提供发展方向。方法按照Arksey与O’Malley提出的范围综述方法框架,对PubMed、CINAHL和Web of Science数据库中发表于2010年1月至2020年12月的相关文献开展研究,并确定符合纳入标准的研究。由2名研究员独立进行文献的筛选、提取和分析。结果共检索出676篇文章,8篇文章符合纳入标准。研究结果呈现出4个主题:患者和卫生服务保健人员在设计和开发阶段的参与、患者的偏好、患者的特点、使用移动医疗应用程序的动机。研究显示,在乳腺癌患者的照护中采用移动医疗应用程序具有良好的前景,且一系列要素在相关应用程序的设计及开发过程中需要加以考虑。结论在为乳腺癌患者开发移动医疗应用程序时应考虑患者的特征、需求和患者自我报告的健康结果数据。此外,包括患者、护士和其他重要的卫生服务保健人员在内的合作将有助于乳腺癌患者移动医疗应用程序的开发。
基金supported by the State Key Laboratory of Urban Water Resource and Environment (Harbin Institute of Technology) (No.2022TS28)the Natural Science Foundation of Heilongjiang Province (No.LH2021B012)the Fundamental Research Funds for the Central Universities (No.HIT.NSRIF202209)。
文摘Nanoplastics-induced developmental and reproductive toxicity,neurotoxicity and immunotoxicity are a focus of widespread attention.However,the effects of nanoplastics(NPs)on glycolipid metabolism and the precise underlying mechanisms are unclear at present.Here,we showed that oral administration of polystyrene nanoparticles(PS-NPs)disrupts glycolipid metabolism,with reactive oxygen species(ROS)identified as a potential key signaling molecule.After PS-NPs treatment,excessive production of ROS induced the infammatory response and activated the antioxidant pathway through nuclear factor-erythroid factor 2-related factor 2.The activation of nuclear factor-κB(NFκB)signaling pathway induced the phosphorylation of the mitogen-activated protein kinases(MAPK)signaling pathway,which induced the activation of extracellular regulated kinases(ERK)and p38.Constitutive activation of the MAPK signaling proteins induced high continued phosphorylation of insulin receptor substrate-1,in turn,leading to decreased protein kinase B(Akt)activity,which weakened the sensitivity of liver cells to insulin signals and induced insulin resistance.In parallel,phosphorylation of Akt led to loss of control of Fo XO1,a key gene of gluconeogenesis,activating transcription of glucose-6-phosphatase(G6PC)and phosphoenolpyruvate carboxykinase(PEPCK)in a manner dependent on PGC1α.Moreover,the activated ERK promoted lipid accumulation through ERK-PPARγcascades.Therefore,sterol regulatory element-binding protein-1 and levels of its downstream lipogenic enzymes,ACC-1,were up-regulated.Upon treatment with the antioxidant resveratrol,PS-NPs-induced glucose and lipid metabolic disorders were improved by inhibiting ROS-induced activation of NFκB and MAPK signaling pathway in mice.Based on above,PS-NPs exposure disrupts glycolipid metabolism in mice,with ROS identified as a potential key signaling molecule.
基金supported by the National Natural Science Foundation of China(Grant Nos.42025503&U2342228)the Key Innovation Team of China Meteorological Administration Climate Change Detection and Response(Grant No.CMA2022ZD03)。
文摘High temperature warning indicators play a pivotal role in meteorological departments,serving as crucial criteria for issuing warnings that guide both social production and daily life.Despite their importance,limited studies have explored the relationship between different global warming levels and changes in high temperature warning indicators.In this study,we analyze data from 2,419 meteorological stations over China and utilize the Coupled Model Intercomparison Project Phase 6(CMIP6)models to examine historical changes in high temperature warning indicators used by the China Meteorological Administration.We evaluate model performance and estimate future changes in these indicators using an annual cycle bias correction method.The results indicate that since 1961,the number of high temperature days(TX35d and TX40d)and length of season(TX40d and TX40l)with daily maximum temperature reaching or exceeding 35℃ and 40℃ have increased over China.The intensity of high temperatures(TXx)has strengthened and the geographical extent affected by high temperatures has expanded.In 2022,the occurrence of 40℃ high temperatures surges,with Eastern China experiencing a two-day increase in TX40d and an extended seasonal length in TX40l by over five days.While CMIP6 models have underestimated the high temperature indictors associated with 35℃ during historical periods,notable difference is not observed between the models and observations for TX40d and TX40l,given their rare occurrence.However,future projections,after bias correction,indicate that the increasing trends for 35℃ and 40℃ high temperature days and length of season become more pronounced than the raw projection,suggesting a more severe increase than that anticipated originally.As global warming intensifies,the high temperature days and length of season are projected to increase non-linearly,while the intensity of high temperatures is expected to increase linearly.For every 1℃ increase in global temperature,the intensity is projected to rise by approximately 1.4℃.The impact of high temperatures is expanding,with the major hotspot for China located in the eastern and northwestern regions.Under 5℃ global warming,certain regions in China may experience prolonged extreme high temperatures.For instance,40℃ high temperature days in areas like North China and the Yangtze River Basin could increase by about 32 d,and the length of season could extend by approximately 100 d.
基金supported by National Health and Medical Research Council of Australia(NHMRC)grants(1037321,1105209,1143976,1150425,1080321,1196335,5575500,1054925,and 1048278)an NHMRC Independent Research Institutes Infrastructure Support Scheme grant(361646)a Victorian State Government Operational Infrastructure Support grant.JB was supported by the Stafford Fox Medical Research Foundation.
文摘The cytokine granulocyte-macrophage-colony stimulating factor (GM-CSF) possesses the capacity to differentiate monocytes into macrophages (MØs) with opposing functions, namely, proinflammatory M1-like MØs and immunosuppressive M2-like MØs. Despite the importance of these opposing biological outcomes, the intrinsic mechanism that regulates the functional polarization of MØs under GM-CSF signaling remains elusive. Here, we showed that GM-CSF-induced MØ polarization resulted in the expression of cytokine-inducible SH2-containing protein (CIS) and that CIS deficiency skewed the differentiation of monocytes toward immunosuppressive M2-like MØs. CIS deficiency resulted in hyperactivation of the JAK-STAT5 signaling pathway, consequently promoting downregulation of the transcription factor Interferon Regulatory Factor 8 (IRF8). Loss- and gain-of-function approaches highlighted IRF8 as a critical regulator of the M1-like polarization program. In vivo, CIS deficiency induced the differentiation of M2-like macrophages, which promoted strong Th2 immune responses characterized by the development of severe experimental asthma. Collectively, our results reveal a CIS-modulated mechanism that clarifies the opposing actions of GM-CSF in MØ differentiation and uncovers the role of GM-CSF in controlling allergic inflammation.
基金the National Natural Science Foundation of China(NSFCNos.#82000007 toM.L.,#82001676 and#91842304 to B.T.L,#82125015 to Y.X.Z.#82272337 to J.F.W.C.)+7 种基金the GWCMC Postdoc Fund(Nos.#5001-3001061 to M.L.,#5001-3001060 to B.T.L.)Chongqing International Institute for Immunology(No.#2021YJC02 to Y.X.Z.)the Guangzhou Basic and Applied Basic Research Fund for Young Ph.D.scientists(No.#202102020194 to M.L.)Zhongnanshan Medical Foundation of Guangdong Province(No.#ZNSA-2020013 to J.C.Z.and Y.X.Z.)the General Research Fund(No.#17122322 to J.F.W.C.)Sanming Project of Medicine in Shenzhen,China(No.#SZSM201911014 to J.F.W.C.)the High Level-Hospital Program,Health Commission of Guangdong Province,China(to J.F.W.C.)and Emergency Collaborative Project(No.#EKPG22-01)of Guangzhou Laboratory(to J.F.W.C.).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of coronavirus disease 2019(COVID-19),has had a significant impact on healthcare systems and economies worldwide.The continuous emergence of new viral strains presents a major challenge in the development of effective antiviral agents.Strategies that possess broad-spectrum antiviral activities are desirable to control SARS-CoV-2 infection.ACE2,an angiotensin-containing enzyme that prevents the overactivation of the renin angiotensin system,is the receptor for SARS-CoV-2.ACE2 interacts with the spike protein and facilitates viral attachment and entry into host cells.Yet,SARS-CoV-2 infection also promotes ACE2 degradation.Whether restoring ACE2 surface expression has an impact on SARS-CoV-2 infection is yet to be determined.Here,we show that the ACE2-spike complex is endocytosed and degraded via autophagy in a manner that depends on clathrin-mediated endocytosis and PAK1-mediated cytoskeleton rearrangement.In contrast,free cellular spike protein is selectively cleaved into S1 and s2 subunits in a lysosomal-dependent manner.Importantly,we show that the pan-PAK inhibitor FRAX-486 restores ACE2 surface expression and suppresses infection by different SARS-CoV-2 strains.FRAX-486-treated Syrian hamsters exhibit significantly decreased lung viral load and alleviated pulmonary inflammation compared with untreated hamsters.In summary,our findings have identified novel pathways regulating viral entry,as well as therapeutic targets and candidate compounds for controlling the emerging strains of SARS-CoV-2 infection.
基金supported by Prophase Project of National Key Basic Research Program of China(2012CB126312)Science and Technology Foundation of Guizhou Province of China([2012]2277)
文摘Domain of unknown function 1644 (DUF1644) is a highly conserved amino acid sequence motif present only in plants. Analysis of expression data of the family of DUF1644- containing genes indicated that they may regulate responses to abiotic stress in rice. Here we present our discovery of the role of Os.SIDP366, a member of the DUF1644 gene family, in response to drought and salinity stresses in rice. Transgenic rice plants overexpressing OsSIDP366 showed enhanced drought and salinity tolerance and reduced water loss as compared to that in the control, whereas plants with downregulated OsSIDP366 expression levels using RNA interference (RNAi) were more sensitive to salinity and drought treatments. The sensitivity to abscisic acid (ABA) treatment was not changed in OsStDP366-overexpressing plants, and OsSIDP366 expression was not affected in ABA- deficient mutants. Subcellular localization analysis revealed that OsSIDP366 is presented in the cytoplasmic foci that colocalized with protein markers for both processing bodies (PBs) and stress granules (SGs) in rice protoplasts. Digital gene expression (DGE) profile analysis indicated that stress-related genes such as SNACl, OsHAK5 and PRs were upregulated in OsSIDP366-overexpressing plants. These results suggest that OsSIDP366 may function as a regulator of the PBs/SGs and positively regulate salt and drought resistance in rice.
基金National Key R&D Program of China(2017YFB0202600 and 2020YFC0841400)National Natural Science Foundation of China(91742109,8152204,31770978,81773674,and 21877134)+8 种基金National Health&Medical Research of Australia(1080321,1143976 and 1150425)Science Foundation of Guangzhou City(201904020023,China)Guangdong Province Higher Vocational Colleges and Schools Pearl River Scholar Funded Scheme(2016 and 2019,China)Guangdong Provincial Key Laboratory of Construction Foundation(2017B030314030,China)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y093,China)Zhejiang University special scientific research fund for COVID-19 prevention and control(China)National Health&Medical Research of Australia(1080321,1143976,and 1150425)Taikang Insurance Group Co.,Ltd.Beijing Taikang Yicai Foundation(Beijing,China)
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan dysfunction.Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis.In an analysis of a randomly collected cohort of 124 patients with COVID-19,we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity.By virtual screening of a U.S.FDA approved drug library,we identified an anticoagulation agent dipyridamole(DIP)in silico,which suppressed SARS-CoV-2 replication in vitro.In a proof-of-concept trial involving 31 patients with COVID-19,DIP supplementation was associated with significantly decreased concentrations of D-dimers(P<0.05),increased lymphocyte and platelet recovery in the circulation,and markedly improved clinical outcomes in comparison to the control patients.In particular,all 8 of the DIP-treated severely ill patients showed remarkable improvement:7 patients(87.5%)achieved clinical cure and were discharged from the hospitals while the remaining 1 patient(12.5%)was in clinical remission.
基金supported by the National Key Research and Development Program of China(Nos.2016YFB0701002and 2016YFB1102301)the National Natural Science Foundation of China(NSFC)(Nos.51772173,51632004,51472257,and 51872307)
文摘Praseodymium-ion-doped gain materials have the superiority of lasing at various visible wavelengths directly.Simple and compact visible lasers are booming with the development of blue laser diodes in recent years.In this Letter, we demonstrate the watt-level red laser with a single blue laser diode and Pr:YLiF4 crystal.On this basis,the passively Q-switched pulse lasers are obtained with monolayer graphene and Co:ZnO thin film as the Q-switchers in the visible range.
文摘The 4th Chinese American Liver Society(CALS)/Society of Chinese Bioscientists in America(SCBA)Hepatology Division Annual Symposium was held virtually on October 29e30,2021.The goal of the CALS Symposium was to present and discuss the recent research data on the pathogenesis and therapeutic targets of liver diseases among the CALS members,trainees and invited speakers.Here we briefly introduce the history of the CALS/SCBA Hepatology Division and highlight the presentations that focus on the current progresses on basic and translational research in liver metabolism,bile acid biology,alcohol-related liver disease,drug-induced liver injury,cholestatic liver injury,non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and liver cancer.
文摘The liver is an essential organ for nutrient and drug metabolism - possessing the remarkable ability to sense environmental and metabolic stimuli and provide an optimally adaptive response. Early growth response 1 (Egr1), an immediate early transcriptional factor which acts as a coordinator of the complex response to stress, is induced during liver injury and controls the expression of a wide range of genes involved in metabolism, cell proliferation, and inflammation. In support of an important role of Egr1 in liver injury and repair, deficiency of Egr1 delays liver regeneration process. The known upstream regulators of Egr1 include, but are not limited to, growth factors (e.g. transforming growth factor β1, platelet-derived growth factor, epidermal growth factor, hepatocyte growth factor), nuclear receptors (e.g. hepatocyte nuclear factor 4α, small heterodimer partner, peroxisome proliferator-activated receptor-γ), and other transcription factors (e.g. Sp1, E2F transcription factor 1). Research efforts using various animal models such as fatty liver, liver injury, and liver fibrosis contribute greatly to the elucidation of Egr1 function in the liver. Hepatocellular carcinoma (HCC) represents the second leading cause of cancer mortality worldwide due to the heterogeneity and the late stage at which cancer is generally diagnosed. Recent studies highlight the involvement of Egr1 in HCC development. The purpose of this review is to summarize current studies pertaining to the role of Egr1 in liver metabolism and liver diseases including liver cancer.
基金This work was supported by the USA National Institutes of Health grants NCI K22CA184146,P20 GM103549,P20GM103418,P30GM118247,and T32ES007079.
文摘Cell-to-cell communication is a fascinating process that is essential for maintaining tissue and wholebody homeostasis.Extracellular vesicles(EVs)are cell-derived membrane-bound nanoparticles that are a means of communication between cells.Accumulating evidence indicates that EVs can render either beneficial or harmful outcomes,depending on the specific cargos(e.g.,proteins,lipids,RNAs)transferred between cells.EVs also have great value as diagnostic and prognostic markers of disease because they are present in a variety of biological fluids and carry bioactive molecules from their cells or tissues of origin.Liver cells can both release and receive EVs derived from other cells and emerging evidence indicates that liver EVs play important roles in the pathogenesis of various liver diseases,including liver cancer,viral hepatitis,non-alcoholic fatty liver disease,and alcoholic liver disease.This review provides an overview of the biogenesis and secretion of EVs and summarizes the most recent advances in understanding the role of EVs in liver physiology and diseases.Additionally,we discuss potential applications of liver EVs as biomarkers and in therapeutic approaches to treat liver diseases.
基金supported by the National Key Research and Development Program of China(2020YFA0908700)the National Natural Science Foundation of China(31870862,31700760,31770978,and 91742109)+4 种基金China Postdoctoral Science Foundation(2019M663225)Science and Technology Planning Project of GuangzhouChina(201804010385)Fundamental Research Funds for the Central Universities(18lgpy49)Guangdong Basic and Applied Basic Research Foundation(2019A1515110508)。
基金by the National High Technology Research and Development Program of China(863 Program)(Grant No.2005AA210910).
文摘Cytoplasmic processing bodies,termed P bodies,are involved in diverse post-transcriptional processes including mRNA decay,nonsense-mediated RNA decay(NMD),RNAi,miRNA-mediated translational repression and storage of translationally silenced mRNAs.Regulation of the formation of P bodies in the context of multicellular organisms is poorly understood.Here we describe a systematic RNAi screen in C.elegans that identified 224 genes with diverse cellular functions whose inactivations result in a dramatic increase in the number of P bodies.83 of these genes form a complex functional interaction network regulating NMD.We demonstrate that NMD interfaces with many cellular processes including translation,ubiquitin-mediated protein degradation,intracellular trafficking and cytoskeleton structure.We also uncover an extensive link between translation and RNAi,with different steps in protein synthesis appearing to have distinct effects on RNAi efficiency.Moreover,the intracellular vesicular trafficking network plays an important role in the regulation of RNAi.A subset of genes enhancing P body formation also regulate the formation of stress granules in C.elegans.Our study offers insights into the cellular mechanisms that regulate the formation of P bodies and also provides a framework for system-level understanding of NMD and RNAi in the context of the development of multicellular organisms.
基金supported by the National Natural Science Foundation of China(Grant No.11871436).
文摘Let(M,g)be a Kähler surface andΣbe aβ-symplectic critical surface in M.If L_(q)(Σ)is bounded for some q>3,then we give a uniform upper bound for the Kähler angle onΣ.This bound only depends on M,q,βand the Lq functional ofΣ.For q>4,this estimate is known and we extend the scope of q.
基金This work was supported by the National Institutes of Health grants R01DK119131,K22CA184146,P20 GM103549,P30GM118247,P20GM103418,T32ES007079,UL1 TR002366KUMC Enhancement Award,American Association for the Study of Liver Diseases(AASLD)Bridging Award,and American Cancer Society(ACS)Institutional Research Grant(IRG)16-194-07 to Y.Zhang.
文摘Background and aim:Non-alcoholic fatty liver disease(NAFLD)is becoming a leading cause of chronic liver disease worldwide.The molecular events that influence disease progression from non-alcoholic fatty liver(NAFL)to aggressive non-alcoholic steatohepatitis(NASH)remain incompletely understood,leading to lack of mechanism-based targeted treatment options for NASH.This study aims to identify early signatures associated with disease progression from NAFL to NASH in mice and humans.Materials and methods:Male C57BL/6J mice were fed a high-fat,-cholesterol,and-fructose(HFCF)diet for up to 9 months.The extent of steatosis,inflammation,and fibrosis was evaluated in liver tissues.Total RNA sequencing(RNA-seq)was conducted to determine liver transcriptomic changes.Results:After being fed the HFCF diet,mice sequentially developed steatosis,early steatohepatitis,steatohepatitis with fibrosis,and eventually spontaneous liver tumor.Hepatic RNA-seq revealed that the key signatures during steatosis progression to early steatohepatitis were pathways related to extracel-lular matrix organization and immune responses such as T cell migration,arginine biosynthesis,C-type lectin receptor signaling,and cytokine-cytokine receptor interaction.Genes regulated by transcription factors forkhead box M1(FOXM1)and negative elongation factor complex member E(NELFE)were significantly altered during disease progression.This phenomenon was also observed in patients with NASH.
基金We thank M.Dayton,Li Sun,and Lisa Reid for technical assistanceThis work was supported by the Rebecca L.Cooper Foundation,National Health and Medical Research Council of Australia(NHMRC)grants(1037321,1080321,1105209,1143976)+1 种基金an NHMRC Independent Research Institutes Infrastructure Support Scheme grant(361646)a Victorian State Government Operational Infrastructure Support grant.
文摘A wide array of chemokine receptors,including CCR2,are known to control Treg migration.Here,we report that CCR2 regulates Tregs beyond chemotaxis.We found that CCR2 deficiency reduced CD25 expression by FoxP3^(+) Treg cells.Such a change was also consistently present in irradiation chimeras reconstituted with mixed bone marrow from wild-type(WT)and CCR2−/−strains.Thus,CCR2 deficiency resulted in profound loss of CD25 ^(hi) FoxP3^(+) Tregs in secondary lymphoid organs as well as in peripheral tissues.CCR2−/−Treg cells were also functionally inferior to WT cells.Interestingly,these changes to Treg cells did not depend on CCR2+monocytes/moDCs(the cells where CCR2 receptors are most abundant).Rather,we demonstrated that CCR2 was required for TLR-stimulated,but not TCR-or IL-2-stimulated,CD25 upregulation on Treg cells.Thus,we propose that CCR2 signaling can increase the fitness of FoxP3^(+) Treg cells and provide negative feedback to counter the proinflammatory effects of CCR2 on myeloid cells.
基金supported by the National Natural Science Foundation of China(No.61775120)
文摘Graphene and other extraordinary two-dimensional materials together with recent advances in optical modulators have set the foundations for the widespread applications of next-generation optoelectronic devices. In this work, we report on the high-performance fundamentally mode-locked waveguide laser modulated by chemicalvapor-deposition-grown WSe2 as a saturable absorber. By incorporating a WSe2 sample into a monolithic Nd:YVO4 waveguide platform, 6.526 GHz picosecond pulsed laser generation has been achieved at the wavelength of 1 μm with pulse duration of 47 ps.