Introduction: Disaster damage to health systems is a human and health tragedy, results in huge economic losses, deals devastating blows to development goals, and shakes social confidence. Hospital disaster preparednes...Introduction: Disaster damage to health systems is a human and health tragedy, results in huge economic losses, deals devastating blows to development goals, and shakes social confidence. Hospital disaster preparedness presents complex clinical operation. It is difficult philosophical challenge. It is difficult to determine how much time, money, and effort should be spent in preparing for an event that may not occur. Health facilities whether hospitals or rural health clinics, should be a source of strength during emergencies and disasters. They should be ready to save lives and to continue providing essential emergencies and disasters. Jeddah has relatively a level of disaster risk which is attributable to its geographical location, climate variability, topography, etc. This study investigates the hospital disaster preparedness (HDP) in Jeddah. Methods: Questionnaire was designed according to five Likert scales. It was divided into eight fields of 33 indicators: structure, architectural and furnishings, lifeline facilities’ safety, hospital location, utilities maintenance, surge capacity, emergency and disaster plan, and control of communication and coordination. Sample of six hospitals participated in the study and rated to the extent of disaster preparedness for each hospital disaster preparedness indicators. Two hazard tools were used to find out the hazards for each hospital. An assessment tool was designed to monitor progress and effectiveness of the hospitals’ improvement. Weakness was found in HDP level in the surveyed hospitals. Disaster mitigation needs more action including: risk assessment, structural and non-structural prevention, and preparedness for contingency planning and warning and evacuation. Conclusion: The finding shows that hospitals included in this study have tools and indicators in hospital preparedness but with lack of training and management during disaster. So the research shed light on hospital disaster preparedness. Considering the importance of preparedness in disaster, it is necessary for hospitals to understand that most of hospital disaster preparedness is built in the hospital system.展开更多
Hydrogen peroxide(H_(2)O_(2)),as a green oxidant,plays a vital role in various applications,including environmental remediation,disinfection,and chemical synthesis[1].The conventional anthraquinone process,despite its...Hydrogen peroxide(H_(2)O_(2)),as a green oxidant,plays a vital role in various applications,including environmental remediation,disinfection,and chemical synthesis[1].The conventional anthraquinone process,despite its industrial maturity and high yield,suffers from high energy consumption,carbon emissions,safety risks,and reliance on precious metals[2].Despite ongoing optimizations,a more sustainable alternative is urgently needed.The direct synthesis of hydrogen peroxide from water and oxygen has long been considered as an ideal alternative due to its theoretical 100%atom efficiency and environmental sustainability.展开更多
Artificial photosynthesis presents a sustainable and cost-effective approach to harnessing solar energy to produce value-added chemicals[1,2].In particular,the simultaneous photocatalytic conversion of CO_(2)and H_(2)...Artificial photosynthesis presents a sustainable and cost-effective approach to harnessing solar energy to produce value-added chemicals[1,2].In particular,the simultaneous photocatalytic conversion of CO_(2)and H_(2)O into formic acid(HCOOH)and hydrogen peroxide(H2O2)has emerged as a promising strategy to mitigate global warming driven by CO_(2)emissions.HCOOH is a versatile chemical and hydrogen carrier,offering economic and practical advantages due to its compatibility with existing industrial processes and energy storage/conversion systems.Meanwhile,H_(2)O_(2)is among the world’s top 100 essential chemicals,with a global market valued at$4.0 billion in 2020 and projected to grow to$5.2 billion by 2026.展开更多
At present,there is currently a lack of unified standard methods for the determination of antimony content in groundwater in China.The precision and trueness of related detection technologies have not yet been systema...At present,there is currently a lack of unified standard methods for the determination of antimony content in groundwater in China.The precision and trueness of related detection technologies have not yet been systematically and quantitatively evaluated,which limits the effective implementation of environmental monitoring.In response to this key technical gap,this study aimed to establish a standardized method for determining antimony in groundwater using Hydride Generation–Atomic Fluorescence Spectrometry(HG-AFS).Ten laboratories participated in inter-laboratory collaborative tests,and the statistical analysis of the test data was carried out in strict accordance with the technical specifications of GB/T 6379.2—2004 and GB/T 6379.4—2006.The consistency and outliers of the data were tested by Mandel's h and k statistics,the Grubbs test and the Cochran test,and the outliers were removed to optimize the data,thereby significantly improving the reliability and accuracy.Based on the optimized data,parameters such as the repeatability limit(r),reproducibility limit(R),and method bias value(δ)were determined,and the trueness of the method was statistically evaluated.At the same time,precision-function relationships were established,and all results met the requirements.The results show that the lower the antimony content,the lower the repeatability limit(r)and reproducibility limit(R),indicating that the measurement error mainly originates from the detection limit of the method and instrument sensitivity.Therefore,improving the instrument sensitivity and reducing the detection limit are the keys to controlling the analytical error and improving precision.This study provides reliable data support and a solid technical foundation for the establishment and evaluation of standardized methods for the determination of antimony content in groundwater.展开更多
Electron–hole(e–h)recombination is a fundamental process that governs energy dissipation and device efficiency in semiconductors.In two-dimensional(2D)materials,the formation of tightly bound excitons makes exciton-...Electron–hole(e–h)recombination is a fundamental process that governs energy dissipation and device efficiency in semiconductors.In two-dimensional(2D)materials,the formation of tightly bound excitons makes exciton-mediated e–h recombination the dominant decay pathway.In this work,nonradiative e–h recombination within excitons in monolayer MoS2 is investigated using first-principles simulations that combine nonadiabatic molecular dynamics with𝐺𝑊and real-time Bethe–Salpeter equation(BSE)propagation.A two-step process is identified:rapid intervalley redistribution induced by exchange interaction,followed by slower phonon-assisted recombination facilitated by exciton binding.By selectively removing the screened Coulomb and exchange terms from the BSE Hamiltonian,their respective contributions are disentangled—exchange interaction is found to increase the number of accessible recombination pathways,while binding reduces the excitation energy and enhances nonradiative decay.A reduction in recombination lifetime by over an order of magnitude is observed due to the excitonic many-body effects.These findings provide microscopic insights for understanding and tuning exciton lifetimes in 2D transition-metal dichalcogenides.展开更多
针对含光伏(photovoltaic,PV)、电动汽车(electric vehicle,EV)及家庭电器负荷的智能社区,以车入户(vehicle to home,V2H)的形式将EV纳入家庭需求响应框架,利用EV的双向输能特性并考虑EV充/放电带来的电池容量退化成本,协同PV、电网的...针对含光伏(photovoltaic,PV)、电动汽车(electric vehicle,EV)及家庭电器负荷的智能社区,以车入户(vehicle to home,V2H)的形式将EV纳入家庭需求响应框架,利用EV的双向输能特性并考虑EV充/放电带来的电池容量退化成本,协同PV、电网的实时电价和用户需求的可容忍时延,基于Lyapunov优化理论提出随机环境下V2H用户的EV充/放电调度策略和每户家庭的负荷响应策略,最小化家庭用户的长期平均购电成本。并提出一种智能社区在线能量交易方案,旨在最小化智能社区总的购电成本、最大限度提高社区能源利用率。理论分析和仿真结果表明,所提算法无需实时电价、PV出力、用户负荷需求的先验概率信息,仅基于当前系统状态就可使优化目标趋于最优值,实现家庭用户的能量调度和家庭用户之间的能量共享,减少家庭购电成本,提高用户之间能量交易的灵活性。展开更多
Nearly half of the global population are carriers of Helicobacter pylori(H. pylori),a Gram-negative bacterium that persists in the healthy human stomach. H. pylori can be a pathogen and causes development of peptic ul...Nearly half of the global population are carriers of Helicobacter pylori(H. pylori),a Gram-negative bacterium that persists in the healthy human stomach. H. pylori can be a pathogen and causes development of peptic ulcer disease in a certain state of the macroorganism. It is well established that H. pylori infection is the main cause of chronic gastritis and peptic ulcer disease(PUD). Decontamination of the gastric mucosa with various antibiotics leads to H. pylori elimination and longer remission in this disease. However,the reasons for repeated detection of H. pylori in recurrent PUD after its successful eradication remain unclear. The reason for the redetection of H. pylori in recurrent PUD can be either reinfection or ineffective anti-Helicobacter therapy. The administration of antibacterial drugs can lead not only to the emergence of resistant strains of microorganisms,but also contribute to the conversion of H. pylori into the resting(dormant) state. The dormant forms of H. pylori have been shown to play a potential role in the development of relapses of PUD. The paper discusses morphological H. pylori forms,such as S-shaped,C-shaped,U-shaped,and coccoid ones. The authors proposes the classification of H. pylori according to its morphological forms and viability.展开更多
The activation of carbon-hydrogen(C-H)bonds is of great scientific importance and offers broad applications in modern organic chemistry[1].In recent years,strategies for C-H bond activation have made notable advances,...The activation of carbon-hydrogen(C-H)bonds is of great scientific importance and offers broad applications in modern organic chemistry[1].In recent years,strategies for C-H bond activation have made notable advances,particularly in the efficient construction of complex molecular architectures.However,most existing C-H activation systems rely on expensive noble metal catalysts,including palladium,rhodium,ruthenium,and iridium.These metals not only come at a high cost but are also often associated with significant toxicity,which further limits their viability and sustainability in industrial applications.展开更多
In eukaryotes, a cascade of events named DNA damage response (DDR) has evolved to handle DNA lesions. DDR engages the recruitment of signaling, checkpoint control, repair and chromatin remodeling protein complexes, al...In eukaryotes, a cascade of events named DNA damage response (DDR) has evolved to handle DNA lesions. DDR engages the recruitment of signaling, checkpoint control, repair and chromatin remodeling protein complexes, allowing cell cycle delay, DNA repair or induction of apoptosis. An early DDR event involves the phosphorylation of the histone variant γH2AX on serine 139 (H2AX139 phosphorylation) originating the so-called γH2AX. DDR-related H2AX139 phosphorylation have been extensively studied in interphase nuclei. More recently, γH2AX signals on mitotic chromosomes of asynchronously growing cell cultures were observed. We performed a quantitative analysis of γH2AX signals on γH2AX immunolabeled cytocentrifuged metaphase spreads, analyzing the γH2AX signal distributions of CHO9 chromosomes harboring homologous regions both in control and bleomycin (BLM)-treated cultures. We detected γH2AX signals in CHO9 chromosomes of controls which significantly increase after BLM-exposure. γH2AX signals were uniformly distributed in chromosomes of controls. However, the γH2AX signal distribution in BLM exposed cells was significantly different between chromosomes and among chromosome regions, with few signals near the centromeres and a tendency to increase towards the telomeres. Interestingly, both basal and BLM-induced γH2AX signal distribution were statistically equal between CHO9 homologous chromosome regions. Our results suggest that BLM exerts an effect on H2AX139 phosphorylation, prevailing towards acetylated and gene-rich distal chromosome segments. The comparable H2AX139 phosphorylation of homologous regions puts forward its dependence on chromatin structure or function and its independence of the position in the karyotype.展开更多
Oral squamous cell carcinoma(OSCC)is typified by extensive stromal fibrosis and an immunosuppressive microenvironment,both of which impede effective responses to immune checkpoint blockade.In this study,we identify pr...Oral squamous cell carcinoma(OSCC)is typified by extensive stromal fibrosis and an immunosuppressive microenvironment,both of which impede effective responses to immune checkpoint blockade.In this study,we identify prolyl 3-hydroxylase family member 4(P3H4)as a critical mediator of extracellular matrix(ECM)remodeling,epithelial-mesenchymal transition(EMT),and the exclusion of cytotoxic CD8+T lymphocytes.Elevated P3H4 expression correlates with unfavorable clinical outcomes and resistance to immunotherapy.Genetic ablation of P3H4 significantly attenuates tumor progression and promotes CD8^(+)T cell infiltration.To pharmacologically target P3H4,we engineered a liposomal formulation of 1,4-dihydrophenanthroline-2,5-dicarboxylic acid(1,4-DPCA),a small-molecule prolyl hydroxylase inhibitor.This nanomedicine,designated Lipo-1,4-DPCA,effectively downregulates P3H4 expression,mitigates tumor-associated fibrosis,reprograms the immune microenvironment,and elicits robust anti-tumor responses in vivo.Collectively,our findings establish P3H4 as a promising therapeutic target and highlight Lipo-1,4-DPCA as a dualfunctional nanotherapeutic candidate capable of enhancing the efficacy of immunotherapy in OSCC.展开更多
The dynamics of phase separation in H–He binary systems within gas giants such as Jupiter and Saturn exhibit remarkable complexity, yet lack systematic investigation. Through large-scale machine-learning-accelerated ...The dynamics of phase separation in H–He binary systems within gas giants such as Jupiter and Saturn exhibit remarkable complexity, yet lack systematic investigation. Through large-scale machine-learning-accelerated molecular dynamics simulations spanning broad temperature-pressure-composition(2000–10000 K, 1–7 Mbar,pure H to pure He) regimes, we systematically determine self and mutual diffusion coefficients in H–He systems and establish a six-dimensional framework correlating temperature, pressure, helium abundance, phase separation degree, diffusion coefficients, and anisotropy. Key findings reveal that hydrogen exhibits active directional migration with pronounced diffusion anisotropy, whereas helium passively aggregates in response. While the conventional mixing rule underestimates mutual diffusion coefficients by neglecting velocity cross-correlations,the assumption of an ideal thermodynamic factor(Q = 1) overestimates them due to unaccounted non-ideal thermodynamic effects—both particularly pronounced in strongly phase-separated regimes. Notably, hydrogen's dual role, anisotropic diffusion and bond stabilization via helium doping, modulates demixing kinetics. Large-scale simulations(216,000 atoms) propose novel phase-separation paradigms, such as “hydrogen bubble/wisp” formation, challenging the classical “helium rain” scenario, striving to bridge atomic-scale dynamics to planetary-scale phase evolution.展开更多
Objective:Cytotoxic T lymphocytes(CTLs)play a crucial role in the therapeutic approach to hepatocellular carcinoma(HCC).Recent research has indicated that junctional adhesion molecule-like protein(JAML)enhances the an...Objective:Cytotoxic T lymphocytes(CTLs)play a crucial role in the therapeutic approach to hepatocellular carcinoma(HCC).Recent research has indicated that junctional adhesion molecule-like protein(JAML)enhances the antitumor activity of CD8+T cells.Our study investigates the role of JAML+CD8+T cells in HCC.Methods:We utilized time-of-flight mass cytometry and an orthotopic mouse model of HCC to examine histone modifications in tumor-infiltrating immune cells undergoing immunotherapy.Flow cytometry was used to assess CD4+T cells differentiation and JAML expression in CD8+T cells infiltrating HCC.Correlation analysis revealed a strong positive correlation between lactate dehydrogenase A+(LDHA+)CD4+T cells and JAML+CD8+T cells.Subsequently,we evaluated the therapeutic effects of an agonistic anti-JAML antibody,both alone and combined with immunotherapy.Finally,RNA sequencing was conducted to identify potential regulatory mechanisms.Results:Immunotherapy significantly increased the percentage of CD8+T cells infiltrating HCC and induced histone modifications,such as H3K18 lactylation(H3K18la)in CD4+T cells.Flow cytometry analysis revealed that lactate promotes the differentiation of CD4+T cells into Th1 cells.LDHA,an enzyme that converts pyruvate to lactate,plays a key role in this process.Correlation analysis revealed a strong positive relationship between LDHA+CD4+T cells and JAML+CD8+T cells in patients who responded to immunotherapy.Moreover,high JAML expression in CD8+T cells was associated with a more favorable prognosis.In vivo experiments demonstrated that agonistic anti-JAML antibody therapy reduced tumor volume and significantly prolonged the survival of tumor-bearing mice,independent of the effects of anti-programmed cell death protein ligand-1 antibody(αPD-L1)-mediated immunotherapy.Pathway enrichment analysis further revealed that JAML enhances CTL responses through the oxidative phosphorylation pathway.Conclusions:Activation of JAML enhances CTL responses in HCC treatment,independent ofαPD-L1-mediated immunotherapy,providing a promising strategy for advanced HCC.展开更多
背景:H型血管(CD31hiEmcnhi)因独特的功能为深入理解血管介导的骨代谢调控机制提供了新的视角和切入点,引发了骨科学研究范式从“骨本位”向“骨-血管整合”的重要转变。目的:基于H型血管领域的文献数据进行可视化分析,探讨该领域的研...背景:H型血管(CD31hiEmcnhi)因独特的功能为深入理解血管介导的骨代谢调控机制提供了新的视角和切入点,引发了骨科学研究范式从“骨本位”向“骨-血管整合”的重要转变。目的:基于H型血管领域的文献数据进行可视化分析,探讨该领域的研究热点和前沿趋势。方法:系统检索CNKI和Web of Science核心合集中与H型血管相关的中英文文献,文献检索时限为2014-2024年。采用CiteSpace 6.2.R4信息可视化软件对文献的发表国家、作者、机构、关键词、时间线视图等进行可视化分析。结果与结论:①共纳入中文文献59篇、英文文献185篇。自2014年提出H型血管概念以来,相关研究文献数量逐年增加,中国在该领域的研究处于领先地位,主要研究机构包括南方医科大学、四川大学和上海交通大学等。关键词分析揭示,当前研究热点主要集中在H型血管的生成与调控机制、H型血管在骨生成和骨重塑过程中的作用以及H型血管与骨质代谢相关疾病的关系;此外,出现“诱导膜”“软骨修复”“中医药”等新兴关键词,表明研究正在向多样化和多学科交叉的方向发展。②H型血管在骨骼疾病的发生发展中发挥着关键作用,相关研究对深入理解骨组织的生理与病理过程具有重要意义。未来应进一步探讨H型血管在不同疾病背景下的具体作用机制,推动基础研究成果的临床转化,为骨骼疾病的预防和治疗提供新的思路与策略。展开更多
文摘Introduction: Disaster damage to health systems is a human and health tragedy, results in huge economic losses, deals devastating blows to development goals, and shakes social confidence. Hospital disaster preparedness presents complex clinical operation. It is difficult philosophical challenge. It is difficult to determine how much time, money, and effort should be spent in preparing for an event that may not occur. Health facilities whether hospitals or rural health clinics, should be a source of strength during emergencies and disasters. They should be ready to save lives and to continue providing essential emergencies and disasters. Jeddah has relatively a level of disaster risk which is attributable to its geographical location, climate variability, topography, etc. This study investigates the hospital disaster preparedness (HDP) in Jeddah. Methods: Questionnaire was designed according to five Likert scales. It was divided into eight fields of 33 indicators: structure, architectural and furnishings, lifeline facilities’ safety, hospital location, utilities maintenance, surge capacity, emergency and disaster plan, and control of communication and coordination. Sample of six hospitals participated in the study and rated to the extent of disaster preparedness for each hospital disaster preparedness indicators. Two hazard tools were used to find out the hazards for each hospital. An assessment tool was designed to monitor progress and effectiveness of the hospitals’ improvement. Weakness was found in HDP level in the surveyed hospitals. Disaster mitigation needs more action including: risk assessment, structural and non-structural prevention, and preparedness for contingency planning and warning and evacuation. Conclusion: The finding shows that hospitals included in this study have tools and indicators in hospital preparedness but with lack of training and management during disaster. So the research shed light on hospital disaster preparedness. Considering the importance of preparedness in disaster, it is necessary for hospitals to understand that most of hospital disaster preparedness is built in the hospital system.
文摘Hydrogen peroxide(H_(2)O_(2)),as a green oxidant,plays a vital role in various applications,including environmental remediation,disinfection,and chemical synthesis[1].The conventional anthraquinone process,despite its industrial maturity and high yield,suffers from high energy consumption,carbon emissions,safety risks,and reliance on precious metals[2].Despite ongoing optimizations,a more sustainable alternative is urgently needed.The direct synthesis of hydrogen peroxide from water and oxygen has long been considered as an ideal alternative due to its theoretical 100%atom efficiency and environmental sustainability.
文摘Artificial photosynthesis presents a sustainable and cost-effective approach to harnessing solar energy to produce value-added chemicals[1,2].In particular,the simultaneous photocatalytic conversion of CO_(2)and H_(2)O into formic acid(HCOOH)and hydrogen peroxide(H2O2)has emerged as a promising strategy to mitigate global warming driven by CO_(2)emissions.HCOOH is a versatile chemical and hydrogen carrier,offering economic and practical advantages due to its compatibility with existing industrial processes and energy storage/conversion systems.Meanwhile,H_(2)O_(2)is among the world’s top 100 essential chemicals,with a global market valued at$4.0 billion in 2020 and projected to grow to$5.2 billion by 2026.
基金supported by the National Natural Science Foundation of China(Project No.42307555).
文摘At present,there is currently a lack of unified standard methods for the determination of antimony content in groundwater in China.The precision and trueness of related detection technologies have not yet been systematically and quantitatively evaluated,which limits the effective implementation of environmental monitoring.In response to this key technical gap,this study aimed to establish a standardized method for determining antimony in groundwater using Hydride Generation–Atomic Fluorescence Spectrometry(HG-AFS).Ten laboratories participated in inter-laboratory collaborative tests,and the statistical analysis of the test data was carried out in strict accordance with the technical specifications of GB/T 6379.2—2004 and GB/T 6379.4—2006.The consistency and outliers of the data were tested by Mandel's h and k statistics,the Grubbs test and the Cochran test,and the outliers were removed to optimize the data,thereby significantly improving the reliability and accuracy.Based on the optimized data,parameters such as the repeatability limit(r),reproducibility limit(R),and method bias value(δ)were determined,and the trueness of the method was statistically evaluated.At the same time,precision-function relationships were established,and all results met the requirements.The results show that the lower the antimony content,the lower the repeatability limit(r)and reproducibility limit(R),indicating that the measurement error mainly originates from the detection limit of the method and instrument sensitivity.Therefore,improving the instrument sensitivity and reducing the detection limit are the keys to controlling the analytical error and improving precision.This study provides reliable data support and a solid technical foundation for the establishment and evaluation of standardized methods for the determination of antimony content in groundwater.
基金supported by the National Key Research and Development Program of China (Grant Nos.2024YFA1409800 for J.Z.and2024YFA1408603 for Q.Z.)the National Natural Science Foundation of China (Grant Nos.12125408,12334004for J.Z.,and 12174363 for Q.Z.)+1 种基金the Innovation Program for Quantum Science and Technology (Grant No.2021ZD0303306 for J.Z.)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB0450101 for J.Z.)。
文摘Electron–hole(e–h)recombination is a fundamental process that governs energy dissipation and device efficiency in semiconductors.In two-dimensional(2D)materials,the formation of tightly bound excitons makes exciton-mediated e–h recombination the dominant decay pathway.In this work,nonradiative e–h recombination within excitons in monolayer MoS2 is investigated using first-principles simulations that combine nonadiabatic molecular dynamics with𝐺𝑊and real-time Bethe–Salpeter equation(BSE)propagation.A two-step process is identified:rapid intervalley redistribution induced by exchange interaction,followed by slower phonon-assisted recombination facilitated by exciton binding.By selectively removing the screened Coulomb and exchange terms from the BSE Hamiltonian,their respective contributions are disentangled—exchange interaction is found to increase the number of accessible recombination pathways,while binding reduces the excitation energy and enhances nonradiative decay.A reduction in recombination lifetime by over an order of magnitude is observed due to the excitonic many-body effects.These findings provide microscopic insights for understanding and tuning exciton lifetimes in 2D transition-metal dichalcogenides.
文摘针对含光伏(photovoltaic,PV)、电动汽车(electric vehicle,EV)及家庭电器负荷的智能社区,以车入户(vehicle to home,V2H)的形式将EV纳入家庭需求响应框架,利用EV的双向输能特性并考虑EV充/放电带来的电池容量退化成本,协同PV、电网的实时电价和用户需求的可容忍时延,基于Lyapunov优化理论提出随机环境下V2H用户的EV充/放电调度策略和每户家庭的负荷响应策略,最小化家庭用户的长期平均购电成本。并提出一种智能社区在线能量交易方案,旨在最小化智能社区总的购电成本、最大限度提高社区能源利用率。理论分析和仿真结果表明,所提算法无需实时电价、PV出力、用户负荷需求的先验概率信息,仅基于当前系统状态就可使优化目标趋于最优值,实现家庭用户的能量调度和家庭用户之间的能量共享,减少家庭购电成本,提高用户之间能量交易的灵活性。
文摘Nearly half of the global population are carriers of Helicobacter pylori(H. pylori),a Gram-negative bacterium that persists in the healthy human stomach. H. pylori can be a pathogen and causes development of peptic ulcer disease in a certain state of the macroorganism. It is well established that H. pylori infection is the main cause of chronic gastritis and peptic ulcer disease(PUD). Decontamination of the gastric mucosa with various antibiotics leads to H. pylori elimination and longer remission in this disease. However,the reasons for repeated detection of H. pylori in recurrent PUD after its successful eradication remain unclear. The reason for the redetection of H. pylori in recurrent PUD can be either reinfection or ineffective anti-Helicobacter therapy. The administration of antibacterial drugs can lead not only to the emergence of resistant strains of microorganisms,but also contribute to the conversion of H. pylori into the resting(dormant) state. The dormant forms of H. pylori have been shown to play a potential role in the development of relapses of PUD. The paper discusses morphological H. pylori forms,such as S-shaped,C-shaped,U-shaped,and coccoid ones. The authors proposes the classification of H. pylori according to its morphological forms and viability.
文摘The activation of carbon-hydrogen(C-H)bonds is of great scientific importance and offers broad applications in modern organic chemistry[1].In recent years,strategies for C-H bond activation have made notable advances,particularly in the efficient construction of complex molecular architectures.However,most existing C-H activation systems rely on expensive noble metal catalysts,including palladium,rhodium,ruthenium,and iridium.These metals not only come at a high cost but are also often associated with significant toxicity,which further limits their viability and sustainability in industrial applications.
文摘In eukaryotes, a cascade of events named DNA damage response (DDR) has evolved to handle DNA lesions. DDR engages the recruitment of signaling, checkpoint control, repair and chromatin remodeling protein complexes, allowing cell cycle delay, DNA repair or induction of apoptosis. An early DDR event involves the phosphorylation of the histone variant γH2AX on serine 139 (H2AX139 phosphorylation) originating the so-called γH2AX. DDR-related H2AX139 phosphorylation have been extensively studied in interphase nuclei. More recently, γH2AX signals on mitotic chromosomes of asynchronously growing cell cultures were observed. We performed a quantitative analysis of γH2AX signals on γH2AX immunolabeled cytocentrifuged metaphase spreads, analyzing the γH2AX signal distributions of CHO9 chromosomes harboring homologous regions both in control and bleomycin (BLM)-treated cultures. We detected γH2AX signals in CHO9 chromosomes of controls which significantly increase after BLM-exposure. γH2AX signals were uniformly distributed in chromosomes of controls. However, the γH2AX signal distribution in BLM exposed cells was significantly different between chromosomes and among chromosome regions, with few signals near the centromeres and a tendency to increase towards the telomeres. Interestingly, both basal and BLM-induced γH2AX signal distribution were statistically equal between CHO9 homologous chromosome regions. Our results suggest that BLM exerts an effect on H2AX139 phosphorylation, prevailing towards acetylated and gene-rich distal chromosome segments. The comparable H2AX139 phosphorylation of homologous regions puts forward its dependence on chromatin structure or function and its independence of the position in the karyotype.
基金supported by grants from the National Natural Science Foundation of China(Nos.82501207,81700993,52403312,and 82571151)Postdoctoral Fellowship Program of CPSF(No.GZC20251219)+1 种基金the Beijing Nova Program(No.20250484855)the Beijing Natural Science Foundation(No.L252168).
文摘Oral squamous cell carcinoma(OSCC)is typified by extensive stromal fibrosis and an immunosuppressive microenvironment,both of which impede effective responses to immune checkpoint blockade.In this study,we identify prolyl 3-hydroxylase family member 4(P3H4)as a critical mediator of extracellular matrix(ECM)remodeling,epithelial-mesenchymal transition(EMT),and the exclusion of cytotoxic CD8+T lymphocytes.Elevated P3H4 expression correlates with unfavorable clinical outcomes and resistance to immunotherapy.Genetic ablation of P3H4 significantly attenuates tumor progression and promotes CD8^(+)T cell infiltration.To pharmacologically target P3H4,we engineered a liposomal formulation of 1,4-dihydrophenanthroline-2,5-dicarboxylic acid(1,4-DPCA),a small-molecule prolyl hydroxylase inhibitor.This nanomedicine,designated Lipo-1,4-DPCA,effectively downregulates P3H4 expression,mitigates tumor-associated fibrosis,reprograms the immune microenvironment,and elicits robust anti-tumor responses in vivo.Collectively,our findings establish P3H4 as a promising therapeutic target and highlight Lipo-1,4-DPCA as a dualfunctional nanotherapeutic candidate capable of enhancing the efficacy of immunotherapy in OSCC.
基金supported by the National University of Defense Technology Research Fund Projectthe National Natural Science Foundation of China under Grant Nos. 12047561 and 12104507+1 种基金the NSAF under Grant No. U1830206the Science and Technology Innovation Program of Hunan Province under Grant No. 2021RC4026。
文摘The dynamics of phase separation in H–He binary systems within gas giants such as Jupiter and Saturn exhibit remarkable complexity, yet lack systematic investigation. Through large-scale machine-learning-accelerated molecular dynamics simulations spanning broad temperature-pressure-composition(2000–10000 K, 1–7 Mbar,pure H to pure He) regimes, we systematically determine self and mutual diffusion coefficients in H–He systems and establish a six-dimensional framework correlating temperature, pressure, helium abundance, phase separation degree, diffusion coefficients, and anisotropy. Key findings reveal that hydrogen exhibits active directional migration with pronounced diffusion anisotropy, whereas helium passively aggregates in response. While the conventional mixing rule underestimates mutual diffusion coefficients by neglecting velocity cross-correlations,the assumption of an ideal thermodynamic factor(Q = 1) overestimates them due to unaccounted non-ideal thermodynamic effects—both particularly pronounced in strongly phase-separated regimes. Notably, hydrogen's dual role, anisotropic diffusion and bond stabilization via helium doping, modulates demixing kinetics. Large-scale simulations(216,000 atoms) propose novel phase-separation paradigms, such as “hydrogen bubble/wisp” formation, challenging the classical “helium rain” scenario, striving to bridge atomic-scale dynamics to planetary-scale phase evolution.
基金funded by the Major Research Plan of the National Natural Science Foundation of China(No.92159202)the National Key Research and Development Program of China(No.2021YFA1100500)+1 种基金the Leading Innovation Team Project of Hangzhou Medical College(No.CXLJ202401)the Key Research and Development Plan of Zhejiang Provincial Department of Science and Technology(No.2024C03051)。
文摘Objective:Cytotoxic T lymphocytes(CTLs)play a crucial role in the therapeutic approach to hepatocellular carcinoma(HCC).Recent research has indicated that junctional adhesion molecule-like protein(JAML)enhances the antitumor activity of CD8+T cells.Our study investigates the role of JAML+CD8+T cells in HCC.Methods:We utilized time-of-flight mass cytometry and an orthotopic mouse model of HCC to examine histone modifications in tumor-infiltrating immune cells undergoing immunotherapy.Flow cytometry was used to assess CD4+T cells differentiation and JAML expression in CD8+T cells infiltrating HCC.Correlation analysis revealed a strong positive correlation between lactate dehydrogenase A+(LDHA+)CD4+T cells and JAML+CD8+T cells.Subsequently,we evaluated the therapeutic effects of an agonistic anti-JAML antibody,both alone and combined with immunotherapy.Finally,RNA sequencing was conducted to identify potential regulatory mechanisms.Results:Immunotherapy significantly increased the percentage of CD8+T cells infiltrating HCC and induced histone modifications,such as H3K18 lactylation(H3K18la)in CD4+T cells.Flow cytometry analysis revealed that lactate promotes the differentiation of CD4+T cells into Th1 cells.LDHA,an enzyme that converts pyruvate to lactate,plays a key role in this process.Correlation analysis revealed a strong positive relationship between LDHA+CD4+T cells and JAML+CD8+T cells in patients who responded to immunotherapy.Moreover,high JAML expression in CD8+T cells was associated with a more favorable prognosis.In vivo experiments demonstrated that agonistic anti-JAML antibody therapy reduced tumor volume and significantly prolonged the survival of tumor-bearing mice,independent of the effects of anti-programmed cell death protein ligand-1 antibody(αPD-L1)-mediated immunotherapy.Pathway enrichment analysis further revealed that JAML enhances CTL responses through the oxidative phosphorylation pathway.Conclusions:Activation of JAML enhances CTL responses in HCC treatment,independent ofαPD-L1-mediated immunotherapy,providing a promising strategy for advanced HCC.
文摘背景:H型血管(CD31hiEmcnhi)因独特的功能为深入理解血管介导的骨代谢调控机制提供了新的视角和切入点,引发了骨科学研究范式从“骨本位”向“骨-血管整合”的重要转变。目的:基于H型血管领域的文献数据进行可视化分析,探讨该领域的研究热点和前沿趋势。方法:系统检索CNKI和Web of Science核心合集中与H型血管相关的中英文文献,文献检索时限为2014-2024年。采用CiteSpace 6.2.R4信息可视化软件对文献的发表国家、作者、机构、关键词、时间线视图等进行可视化分析。结果与结论:①共纳入中文文献59篇、英文文献185篇。自2014年提出H型血管概念以来,相关研究文献数量逐年增加,中国在该领域的研究处于领先地位,主要研究机构包括南方医科大学、四川大学和上海交通大学等。关键词分析揭示,当前研究热点主要集中在H型血管的生成与调控机制、H型血管在骨生成和骨重塑过程中的作用以及H型血管与骨质代谢相关疾病的关系;此外,出现“诱导膜”“软骨修复”“中医药”等新兴关键词,表明研究正在向多样化和多学科交叉的方向发展。②H型血管在骨骼疾病的发生发展中发挥着关键作用,相关研究对深入理解骨组织的生理与病理过程具有重要意义。未来应进一步探讨H型血管在不同疾病背景下的具体作用机制,推动基础研究成果的临床转化,为骨骼疾病的预防和治疗提供新的思路与策略。
