In exploring persistent infections and malignancies, a distinctive subgroup of CD8^(+) T cells, progenitor exhausted CD8^(+) T(Tpex) cells, has been identified. These Tpex cells are notable for their remarkable self-r...In exploring persistent infections and malignancies, a distinctive subgroup of CD8^(+) T cells, progenitor exhausted CD8^(+) T(Tpex) cells, has been identified. These Tpex cells are notable for their remarkable self-renewal and rapid proliferation abilities. Recent strides in immunotherapy have demonstrated that Tpex cells expand and differentiate into responsive exhausted CD8^(+) T cells, thus underscoring their critical role in the immunotherapeutic retort. Clinical examinations have further clarified a robust positive correlation between the proportional abundance of Tpex cells and enhanced clinical prognosis. Tpex cells have found noteworthy applications in the formulation of inventive immunotherapeutic approaches against tumors. This review describes the functions of Tpex cells in the tumor milieu, particularly their potential utility in tumor immunotherapy. Precisely directing Tpex cells may be essential to achieving successful outcomes in immunotherapy against tumors.展开更多
The inverse relationship between the warm phase of the El Nino Southern Oscillation(ENSO)and the Indian Summer Monsoon Rainfall(ISMR)is well established.Yet,some El Nino events that occur in the early months of the ye...The inverse relationship between the warm phase of the El Nino Southern Oscillation(ENSO)and the Indian Summer Monsoon Rainfall(ISMR)is well established.Yet,some El Nino events that occur in the early months of the year(boreal spring)transform into a neutral phase before the start of summer,whereas others begin in the boreal summer and persist in a positive phase throughout the summer monsoon season.This study investigates the distinct influences of an exhausted spring El Nino(springtime)and emerging summer El Nino(summertime)on the regional variability of ISMR.The two ENSO categories were formulated based on the time of occurrence of positive SST anomalies over the Nino-3.4 region in the Pacific.The ISMR’s dynamical and thermodynamical responses to such events were investigated using standard metrics such as the Walker and Hadley circulations,vertically integrated moisture flux convergence(VIMFC),wind shear,and upper atmospheric circulation.The monsoon circulation features are remarkably different in response to the exhausted spring El Nino and emerging summer El Nino phases,which distinctly dictate regional rainfall variability.The dynamic and thermodynamic responses reveal that exhausted spring El Nino events favor excess monsoon rainfall over eastern peninsular India and deficit rainfall over the core monsoon regions of central India.In contrast,emerging summer El Nino events negatively impact the seasonal rainfall over the country,except for a few regions along the west coast and northeast India.展开更多
Firstly,the status quo of Pingxiang City as a resource-exhausted city was introduced firstly,and then the development situation of Anyuan Coal Mine,which is the representative of traditional coal industry in Pingxiang...Firstly,the status quo of Pingxiang City as a resource-exhausted city was introduced firstly,and then the development situation of Anyuan Coal Mine,which is the representative of traditional coal industry in Pingxiang,was summarized.Moreover,the classification and value of mining heritage were analyzed,and it is proposed that the development of mine heritage tourism and urban transformation should be combined.The planning of Anyuan National Mine Park under the background of urban transformation was analyzed to provides an idea for the protection and utilization of industrial heritage.展开更多
This paper establishes the evaluation index system of ecological environment and economic development in resource exhausted cities, and calculates the level of economic development and ecological environment during th...This paper establishes the evaluation index system of ecological environment and economic development in resource exhausted cities, and calculates the level of economic development and ecological environment during the year 2005-2012 by using the entropy method. Furthermore, this study analyzes the coordination degree and coordinated development degree by using the coordination model. The results show that the coordination relationship of economic development and ecological environment continues to improve from 2005 to 2012 in most of these resource exhausted cities. By 2012, other resource depletion cities are in all kinds of hierarchical coordination except Yichun and Hegang. From the standpoint of coordination development degree, although most of these resource exhausted cities have been increased continuously but the level is also lower except in Tongling and Xinyu. Finally, this paper puts forward the corresponding countermeasures and suggestions according to the results of the analysis.展开更多
In this study adsorptive removal of Pb(II) and Cu(II) from aqueous solution by using environmental friendly natural polymers present in exhausted tea leaves has been studied. The biosorbent was modified with dimethyla...In this study adsorptive removal of Pb(II) and Cu(II) from aqueous solution by using environmental friendly natural polymers present in exhausted tea leaves has been studied. The biosorbent was modified with dimethylamine to introduce N-functional groups on the surface of adsorbent. The modified adsorbent was characterized by elemental analysis, zeta potential analysis, SEM, DRFTIR, XRD and TG/DTA analysis to conform the modification. Adsorption capacity of the adsorbent was determined as the function of pH of the solution, initial concentration of the solution and contact time. The adsorption experiments were performed using batch experiments. The maximum adsorption capacities of the adsorbent were found to be 91.68 and 71.20 mg/g for Pb(II) and Cu(II), respectively. To minimize the process cost, regeneration of the biosorbent and recovery of metal ions was explored by desorption study. The results indicate that the adsorbent holds great potential for the sequestration of Pb(II) and Cu(II) from their aqueous solution. Hence the modified exhausted tea leaves (MTL) have been investigated as a new cost effective and efficient biosorbent for removal of Pb(II) and Cu(II) from their aqueous solution.展开更多
Exhausted T cells are a group of dysfunctional T cells,which are present in chronic infections or tumors.The most significant characteristics of exhausted T cells are attenuated effector cytotoxicity,reduced cytokine ...Exhausted T cells are a group of dysfunctional T cells,which are present in chronic infections or tumors.The most significant characteristics of exhausted T cells are attenuated effector cytotoxicity,reduced cytokine production,and upregulation of multiple inhibitory molecular receptors(e.g.,PD-1,TIM-3,and LAG-3).The intracellular metabolic changes,altered expression of transcription factors,and a unique epigenetic landscape constitute the exhaustion program.Recently,researchers have made progress in understanding exhausted T cells,with the definition and identification of exhausted T cells changing from phenotypebased to being classified at the transcriptional and epigenetic levels.Recent studies have revealed that exhausted T cells can be separated into two subgroups,namely TCF1^(+)PD-1^(+)progenitor-like precursor exhausted cells and TCF1-PD-1^(+)terminally differentiated exhausted T cells.Moreover,the progenitor-like precursor cell population may be a subset of T cells that can respond to immunotherapy.Studies have also found that TOX initiates and dominates the development of exhausted T cells at the transcriptional and epigenetic levels.TOX also maintains T cell survival and may affect decisions regarding treatment strategies.In this review,we discuss the latest developments in T cell exhaustion in regards to definitions,subpopulations,development mechanisms,differences in diverse diseases,and treatment prospects for exhausted T cells.Furthermore,we hypothesize that the epigenetic state regulated by TOX might be the key point,which can determine the reversibility of exhaustion and the efficacy of immunotherapy.展开更多
Purpose：The aim of the present study was to investigate the impact of total soy saponins（TS） on the myocardial antioxidant capacity in rats exercised to exhaustion.Methods：The one-time exhausted treadmill model wa...Purpose：The aim of the present study was to investigate the impact of total soy saponins（TS） on the myocardial antioxidant capacity in rats exercised to exhaustion.Methods：The one-time exhausted treadmill model was used.All rats were divided into 4 groups：the control group,the TS group,the exhausted group,and the TS exhausted group.The TS and TS exhausted groups were fed TS at a dosage of 20 mg/kg body weight,once a day,for 2 weeks.The exhausted group was given a placebo,and the control group was not given any treatment.The treadmill speed was set at 30 m/min,and the rats（exhausted and TS exhausted groups） were trained at this speed until exhausted.The rats were decapitated and anatomized immediately after exhausted.A 10% homogenate of the myocardial tissue was prepared.Results：TS significant y increased the exercise time by 20.62%（p〈0.05）.As compared with the control group,the enzyme activities for catalase（CAT）,glutathione peroxidase（GSH-Px）,and glutathione reductase（GR） were significant y enhanced in the TS group（p〈0.01）;GR and GSH-Px activity was significant y enhanced in the TS exhausted group（p〈0.01）;malondialdehyde（MDA） levels were significant y decreased in the TS exhausted group（p〈0.05）.As compared with the exhausted group,the GSH-Px activity was significant y enhanced in the TS exhausted group（p〈0.01）;CAT,GSH-Px,and GR activities were significant y enhanced in the TS group（p〈0.01）.As compared with the TS group,the CAT and GR activity in the TS exhausted group was significant y decreased（p〈0.01）.Conclusion：TS can improve the exercised rats＇ antioxidant activity in their cardiac muscle to varying degrees,decrease MDA and serum AST and LDH levels,increase the exercise time,and delay the occurrence of sports fatigue.展开更多
Objective： To investigate the association between the T cell inhibitory receptor programmed death 1（PD-1）and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia（AML） and AML in c...Objective： To investigate the association between the T cell inhibitory receptor programmed death 1（PD-1）and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia（AML） and AML in complete remission（CR）.Methods：Surface expression of PD-1 and the exhaustion and immunosenescence markers CD244 and CD57 on CD3＋,CD4＋ and CD8＋ T cells from peripheral blood samples from 20 newly diagnosed,untreated AML patients and 10 cases with AML in CR was analyzed by flow cytometry.Twenty-three healthy individuals served as control.Results：A significantly higher percentage of PD-1＋ cells were found for CD3＋ T cells in the de novo AML group compared with healthy controls.In addition,an increased level of PD-1＋ CD8＋ T cells,but not PD-1＋ CD4＋,was found for CD3＋ T cells in the de novo AML and AML-CR samples.A higher percentage of CD244＋ CD4＋,CD244＋ CD8＋,CD57＋ CD4＋ and CD57＋ CD8＋ T cells was found in CD3＋ T cells in samples from those with de novo AML compared with those from healthy controls.Strong increased PD-1＋ CD244＋ and PD-1＋ CD57＋ coexpression was found for CD4＋ and CD8＋ T cells in the de novo AML group compared with healthy controls.Conclusions：We characterized the major T cell defects,including co-expression of PD-1 and CD244,CD57-exhausted T cells in patients with de novo AML,and found a particular influence on CD8＋ T cells,suggesting a poor anti-leukemia immune response in these patients.展开更多
Objective:To explore the difference in the anti-fatigue effect of moxibustion at different acupoints through observing the impacts of moxibustion at"Shènshù(肾俞BL23)","Zúsānlǐ(足三里ST...Objective:To explore the difference in the anti-fatigue effect of moxibustion at different acupoints through observing the impacts of moxibustion at"Shènshù(肾俞BL23)","Zúsānlǐ(足三里ST36)","Guānyuán(关元CV4)"and"Shénquè(神阙CV8)"on energy metabolic indexes in the one-off exhausted rats.Methods:A total of 56 SPF male rats were randomized into 7 groups,named a blank group,a model group,a non-acupoint group,a"BL23"group,a"ST36"group,a"CV4"group and a"CV8"group,8 rats in each group.The one-off exhaustion model was established by weight-bearing swimming experiment.Right after the exhaustive swimming of rats in each intervention group,the mild moxibustion was applied at the corresponding acupoints for 15 min immediately.4 h after the exhaustive swimming,the blood was collected from the femoral artery and the quadriceps femoris of the left hindlimb was stripped.The levels of blood lactate(BLD),lactate dehydrogenase(LDH),creatine kinase(CK)and blood urea nitrogen(BUN),the expressions of adenosine triphosphatease(ATP),fructose-6-phosphofructokinase(PFK)and malomdialdehyde(MDA)in the quadriceps femoris and the activity of superoxide dismutase(SOD)and catalase(CAT)were detected.Results:Compared with the model group and the non-acupoint group,the levels of serum BLD,LDH,CK and BUN were all lower those in the"BL23"group,the"ST36"group,the"CV4"group and the"CV8"group,indicating a statistical significance(all P<0.05).Compared with the model group and the nonacupoint group,PFK was higher in the"BL23"group,indicating a statistical significance(both P<0.05).Compared with the model group and the non-acupoint group,PFK was higher in the"ST36"group and the"CV4"group,indicating a statistical significance(all P<0.05).Conclusion:It was found in the research that moxibustion at"BL23""ST36""CV4"and"CV8"regulated the energy metabolism in the one-off exhausted rats so as to bring the anti-fatigue effect into play and the effect was different among the acupoints.Moxibustion at"CV8"may work on the prevention of the protein decomposition in the skeletal muscle and moxibustion at"BL23"may be against the oxidation in the skeletal muscle.展开更多
The gas and water flows during an underwater missile launch are numerically studied. For the gas flow, the explicit difference scheme of Non-oscillation and Non-free-parameter Dissipation (NND) is utilized to solve th...The gas and water flows during an underwater missile launch are numerically studied. For the gas flow, the explicit difference scheme of Non-oscillation and Non-free-parameter Dissipation (NND) is utilized to solve the Euler equations for compressible fluids in the body-fitted coordinates. For the water flow, the Hess-Smith method is employed to solve the Laplace equation for the velocity potential of irrotational water flows based on the potential theory and the boundary element method. The hybrid Eulerian-Lagrangian formulation for the free boundary conditions is used to compute the changes of the free surface of the exhausted gas bubble in time stepping. On the free surface of the exhausted gas bubble, the matched conditions of both the normal velocities and pressures are satisfied. From the numerical simulation, it is found that the exhausted gas bubble grows more rapidly in the axial direction than in the radial direction and the bubble will shrink at its "neck" finally. Numerical results of the movement of the shock wave and the distribution of the Mach number and the gas pressure within the bubble were presented, which reveals that at some time, the gas flow in the Laval nozzle is subsonic and the gas pressure in the nozzle is very high. Influences of various initial missile velocities and chamber total pressures and water depths on both the time interval when the gas flow in the nozzle is subsonic and the peak of the gas pressure at the nozzle end were discussed. It was suggested that a reasonable adjustment of the chamber total pressure can improve the performance of the engine during the underwater launch of missiles.展开更多
Objectives:Emotional exhaustion among healthcare professionals,particularly pharmacists,significantly impacts their well-being and efficacy in patient care.Understanding the psychological mechanisms contributing to em...Objectives:Emotional exhaustion among healthcare professionals,particularly pharmacists,significantly impacts their well-being and efficacy in patient care.Understanding the psychological mechanisms contributing to emotional exhaustion is essential for developing effective interventions.The present research sought to investigate the potential mediating roles of rumination and coping strategies(adaptive and maladaptive)in the relationship between perceived stress and emotional exhaustion among pharmacists.Methods:A cross-sectional survey was carried out between September 2023 and January 2024 involving 576 pharmacists working in public hospitals in Punjab who met the inclusion criteria and actively participated in the study.We employed the Perceived Stress Scale,the Ruminative Response Scale,the Brief Coping Orientation to Problems Experienced Inventory(COPE),and the Oldenburg Burnout Inventory(OLBI)to assess the hypothesized study model.Path analysis was employed to test the hypothesized mediation model,incorporating simple and chain mediation processes.Results:The findings provided empirical evidence supporting a positive association between perceived stress and emotional exhaustion.Rumination significantlymediated this relationship.Further,both adaptive andmaladaptive coping strategieswere found tomediate this relationship,withmaladaptive coping demonstrating amore substantial impact.Conclusion:The chainmediation model demonstrated that rumination and coping strategies(both maladaptive and adaptive)significantly mediate the relationship between perceived stress and emotional exhaustion among pharmacists.Specifically,rumination was found to be a key mediator,with maladaptive coping strategies having a more substantial impact.These findings provide a deeper understanding of the psychological mechanisms contributing to emotional exhaustion in the pharmacy profession.展开更多
The Brief Interactive Optimism Scale (BIOS-G), recently published, was developed to measure optimism based on the interactive personality styles theory in the general population of Mexican adults. It has been validate...The Brief Interactive Optimism Scale (BIOS-G), recently published, was developed to measure optimism based on the interactive personality styles theory in the general population of Mexican adults. It has been validated in both the general population in Mexico and other Latin American countries. This study aims to further consolidate the validity of the BIOS-G in a specific population. The objectives are to assess the psychometric properties of its items, validate its unidimensional structure, describe its distribution, verify its internal consistency, and examine its direct relationship with affective balance and positive affect, as well as its inverse relationship with emotional exhaustion and negative affect among Mexican university teachers. The BIOS-G, the CESQT emotional exhaustion subscale, and Scale of Positive and Negative Experience (SPANE) were administered to a non-probability sample of 213 Mexican university teachers. All items demonstrated discriminative power and internal consistency. The scale showed internal consistency (Green-Yang ordinal ω = 0.74 and McDonald ordinal ω = 0.88). The one-factor model presented good to acceptable fit to the data, with an average variance extracted of 0.65. Its distribution was negatively skewed and mesokurtic. The BIOS-G correlated directly with SPANE’s affective balance and positive emotional experiences and inversely with negative emotional experiences and emotional exhaustion, with moderate strengths of association. Its mean score was higher in men than in women and correlated positively with age. It is concluded that the BIOS-G demonstrates internal consistency and validity evidence among Mexican university teachers, and its use in this specific population is recommended.展开更多
This study investigated the relationship between AI anxiety and deviant behavior,as well as the roles of emotional exhaustion and leader support in this context.The sample comprised 381 Chinese e-commerce employees(72...This study investigated the relationship between AI anxiety and deviant behavior,as well as the roles of emotional exhaustion and leader support in this context.The sample comprised 381 Chinese e-commerce employees(72.7%female,age range 21–36 years).The results of the Process model analysis indicate that AI anxiety significantly is associated with higher deviant behaviour.Emotional exhaustion partially mediates this relationship between AI anxiety and employee deviant behavior exacerbating deviant behaviour.Leader support moderates the AI anxiety effect on emotional exhaustion such that when leader support is low.AI anxiety is associated with higher emotional exhaustion among employees.By implication,high levels of leader support can alleviate AI anxiety of employees.Employer organizations should provide appropriate guidance when introducing AI technology to prevent AI anxiety and associated emotional exhaustion and deviant behavior.展开更多
This paper presented a novel and environmentally friendly approach for recovering platinum group metals(PGMs)from spent automotive exhaust catalysts.The study employed lead slag and waste graphite electrodes as raw ma...This paper presented a novel and environmentally friendly approach for recovering platinum group metals(PGMs)from spent automotive exhaust catalysts.The study employed lead slag and waste graphite electrodes as raw materials,incorporating CaO as an additive to fine-tune the slag's viscosity and density.By reducing FeO in the lead slag using waste graphite electrodes,pure Fe was obtained,effectively trapping the PGMs from the exhausted catalysts.The study explored the effects of reductant addition,trapping duration,slag basicity,and trapping temperature on the recovery rate of PGMs.The results indicated that a maximum recovery rate of 97.86%was achieved when the reductant was added at 1.5 times the theoretical amount,with a trapping duration of 60 minutes,a slag basicity of 0.7,and a trapping temperature of 1600℃.This research offered a greener pathway for the recovery of PGMs from spent automotive exhaust catalysts.展开更多
The small punch test technique facilitates the convenient acquisition of the mechanical properties of in-service equipment materials and the assessment of their remaining service life through sampling.However,the weld...The small punch test technique facilitates the convenient acquisition of the mechanical properties of in-service equipment materials and the assessment of their remaining service life through sampling.However,the weldability of components with thin walls after small punch sampling,such as ethylene cracking furnace tubes,requires further investigation.Therefore,the weldability of in-service ethylene cracking furnace tubes following small punch sampling was investigated through nondestructive testing,microstructural characterization,and mechanical testing.Additionally,the impact of small punch sampling size and residual stress on the creep performance of the specimens was studied using an improved ductility exhaustion model.The results indicate that both the surface and interior of the weld repair areas on new furnace tubes and service-exposed furnace tubes after small-punch sampling are defect-free,exhibiting good weld quality.The strength of the specimens after weld repair was higher than that before sampling,whereas toughness decreased.Weld repair following small punch sampling of furnace tubes is both feasible and necessary.Furthermore,a linear relationship was observed between specimen thickness,diameter,and creep fracture time.The residual stress of welding affects the creep performance of the specimen under different stresses.展开更多
The effect of gradient exhaust strategy and blind plate installation on the inhibition of backflow and thermal stratification in data center cabinets is systematically investigated in this study through numericalmetho...The effect of gradient exhaust strategy and blind plate installation on the inhibition of backflow and thermal stratification in data center cabinets is systematically investigated in this study through numericalmethods.The validated Re-Normalization Group(RNG)k-ε turbulence model was used to analyze airflow patterns within cabinet structures equipped with backplane air conditioning.Key findings reveal that server-generated thermal plumes induce hot air accumulation at the cabinet apex,creating a 0.8℃ temperature elevation at the top server’s inlet compared to the ideal situation(23℃).Strategic increases in backplane fan exhaust airflow rates reduce server 1’s inlet temperature from 26.1℃(0%redundancy case)to 23.1℃(40%redundancy case).Gradient exhaust strategies achieve equivalent server temperature performance to uniform exhaust distributions while requiring 25%less redundant airflow.This approach decreases the recirculation ratio from1.52%(uniformexhaust at 15%redundancy)to 0.57%(gradient exhaust at equivalent redundancy).Comparative analyses demonstrate divergent thermal behaviors:in bottom-server-absent configurations,gradient exhaust reduces top server inlet temperatures by 1.6℃vs.uniformexhaust,whereas top-serverabsent configurations exhibit a 1.8℃ temperature increase under gradient conditions.The blind plate implementation achieves a 0.4℃ top server temperature reduction compared to 15%-redundancy uniform exhaust systems without requiring additional airflow redundancy.Partially installed server arrangements with blind plates maintain thermal characteristics comparable to fully populated cabinets.This study validates gradient exhaust and blind plate technologies as effective countermeasures against cabinet-scale thermal recirculation,providing actionable insights for optimizing backplane air conditioning systems in mission-critical data center environments.展开更多
Two environmentalists using bamboo bicycles to promote green transportation.THE exhaust emissions generated by transporting the world’s population on a daily basis are one of the main sources of greenhouse gases.Vehi...Two environmentalists using bamboo bicycles to promote green transportation.THE exhaust emissions generated by transporting the world’s population on a daily basis are one of the main sources of greenhouse gases.Vehicles such as cars,subways,and motorcycles,all produce carbon emissions.展开更多
Based on 5G and IoT technology,this study addresses the issues of manual control dependency,poor reliability,and high labor costs in traditional ceramic kiln exhaust cover operations.An intelligent control system for ...Based on 5G and IoT technology,this study addresses the issues of manual control dependency,poor reliability,and high labor costs in traditional ceramic kiln exhaust cover operations.An intelligent control system for kiln exhaust covers was designed in this paper.The system employs temperature measurement devices to monitor the internal temperature of the kiln in real time.A controller automatically operates the actuator to open or close the kiln exhaust cover based on temperature measurements.Additionally,the system integrates data transmission units and cloud services,enabling remote monitoring of kiln temperature and historical data storage.Experimental results demonstrate that the system effectively reduces labor costs and significantly enhances the IoT capabilities of kiln operations.展开更多
CAR-T cell therapy demonstrates tremendous potential for tumor treatment,yet faces challenges in solid tumor therapy due to immune suppression,T-cell exhaustion,and cytokine release syndrome(CRS)induced by the tumor m...CAR-T cell therapy demonstrates tremendous potential for tumor treatment,yet faces challenges in solid tumor therapy due to immune suppression,T-cell exhaustion,and cytokine release syndrome(CRS)induced by the tumor microenvironment(TME).Traditional Chinese medicine(TCM)holds substantial potential to enhance CAR-T efficacy and mitigate adverse reactions due to its multi-targeted advantages.TCM active ingredients and formulations can synergistically amplify CAR-T anti-tumor effects while reducing adverse events through multiple mechanisms,including reversing T-cell exhaustion,prolonging CAR-T cell persistence,improving TME hypoxia and fibrosis,modulating gut microbiota,and suppressing CRS.This benefits patient treatment and recovery.Combining TCM with CAR-T therapy can increase objective response rates,prolong cell persistence,and reduce CRS incidence.Future efforts will focus on exploring the precise mechanisms and standardized protocols for TCM-enhanced CAR-T treatment through high-quality clinical trials and multi-omics technologies,driving its clinical translation and application.展开更多
Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due...Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due to the complex pathogenesis.Although OA mechanisms have been investigated on a large scale over the past decade,the OA pathology correlated with aging-associated changes is still largely unrevealed.Therefore,in-depth analysis of the aging microenvironment and aging-related molecular mechanisms in OA may offer additional strategies for clinical prevention and treatment.In this review,we discuss the potential pathogenesis of OA in light of aging-associated changes and summarize three main components of the aging microenvironment of the OA joint:immune homeostatic imbalance,cellular senescence,and stem cell exhaustion,which could be induced by aging and further exacerbate OA progression.Additionally,it is emphasized that immune homeostatic imbalance appears before established OA,which occurs in the early stage and is the therapeutic window of opportunity for better clinical outcomes.Importantly,we evaluate recent therapeutic targets and promising interventions against these components,as well as the challenges and prospects for precise and individualized therapies of OA patients,which we believe would guide the construction of novel combined strategies targeting aging-related factors against OA for better treatments in the future.展开更多
基金supported by grants from the National Natural Science Foundation of China (Grant No. 32270955)the Jiangsu Provincial Medical Key Discipline (Grant No. YXZDXK202236)+1 种基金the Key Project of Jiangsu Provincial Health Commission (Grant No. K2023069)the Science and Technology Support Plan (Social Development) Project of Changzhou (Grant No. CE20235058)。
文摘In exploring persistent infections and malignancies, a distinctive subgroup of CD8^(+) T cells, progenitor exhausted CD8^(+) T(Tpex) cells, has been identified. These Tpex cells are notable for their remarkable self-renewal and rapid proliferation abilities. Recent strides in immunotherapy have demonstrated that Tpex cells expand and differentiate into responsive exhausted CD8^(+) T cells, thus underscoring their critical role in the immunotherapeutic retort. Clinical examinations have further clarified a robust positive correlation between the proportional abundance of Tpex cells and enhanced clinical prognosis. Tpex cells have found noteworthy applications in the formulation of inventive immunotherapeutic approaches against tumors. This review describes the functions of Tpex cells in the tumor milieu, particularly their potential utility in tumor immunotherapy. Precisely directing Tpex cells may be essential to achieving successful outcomes in immunotherapy against tumors.
基金funding support from the National Monsoon Mission program of the Ministry of Earth Sciences(MoES),New Delhi。
文摘The inverse relationship between the warm phase of the El Nino Southern Oscillation(ENSO)and the Indian Summer Monsoon Rainfall(ISMR)is well established.Yet,some El Nino events that occur in the early months of the year(boreal spring)transform into a neutral phase before the start of summer,whereas others begin in the boreal summer and persist in a positive phase throughout the summer monsoon season.This study investigates the distinct influences of an exhausted spring El Nino(springtime)and emerging summer El Nino(summertime)on the regional variability of ISMR.The two ENSO categories were formulated based on the time of occurrence of positive SST anomalies over the Nino-3.4 region in the Pacific.The ISMR’s dynamical and thermodynamical responses to such events were investigated using standard metrics such as the Walker and Hadley circulations,vertically integrated moisture flux convergence(VIMFC),wind shear,and upper atmospheric circulation.The monsoon circulation features are remarkably different in response to the exhausted spring El Nino and emerging summer El Nino phases,which distinctly dictate regional rainfall variability.The dynamic and thermodynamic responses reveal that exhausted spring El Nino events favor excess monsoon rainfall over eastern peninsular India and deficit rainfall over the core monsoon regions of central India.In contrast,emerging summer El Nino events negatively impact the seasonal rainfall over the country,except for a few regions along the west coast and northeast India.
文摘Firstly,the status quo of Pingxiang City as a resource-exhausted city was introduced firstly,and then the development situation of Anyuan Coal Mine,which is the representative of traditional coal industry in Pingxiang,was summarized.Moreover,the classification and value of mining heritage were analyzed,and it is proposed that the development of mine heritage tourism and urban transformation should be combined.The planning of Anyuan National Mine Park under the background of urban transformation was analyzed to provides an idea for the protection and utilization of industrial heritage.
文摘This paper establishes the evaluation index system of ecological environment and economic development in resource exhausted cities, and calculates the level of economic development and ecological environment during the year 2005-2012 by using the entropy method. Furthermore, this study analyzes the coordination degree and coordinated development degree by using the coordination model. The results show that the coordination relationship of economic development and ecological environment continues to improve from 2005 to 2012 in most of these resource exhausted cities. By 2012, other resource depletion cities are in all kinds of hierarchical coordination except Yichun and Hegang. From the standpoint of coordination development degree, although most of these resource exhausted cities have been increased continuously but the level is also lower except in Tongling and Xinyu. Finally, this paper puts forward the corresponding countermeasures and suggestions according to the results of the analysis.
文摘In this study adsorptive removal of Pb(II) and Cu(II) from aqueous solution by using environmental friendly natural polymers present in exhausted tea leaves has been studied. The biosorbent was modified with dimethylamine to introduce N-functional groups on the surface of adsorbent. The modified adsorbent was characterized by elemental analysis, zeta potential analysis, SEM, DRFTIR, XRD and TG/DTA analysis to conform the modification. Adsorption capacity of the adsorbent was determined as the function of pH of the solution, initial concentration of the solution and contact time. The adsorption experiments were performed using batch experiments. The maximum adsorption capacities of the adsorbent were found to be 91.68 and 71.20 mg/g for Pb(II) and Cu(II), respectively. To minimize the process cost, regeneration of the biosorbent and recovery of metal ions was explored by desorption study. The results indicate that the adsorbent holds great potential for the sequestration of Pb(II) and Cu(II) from their aqueous solution. Hence the modified exhausted tea leaves (MTL) have been investigated as a new cost effective and efficient biosorbent for removal of Pb(II) and Cu(II) from their aqueous solution.
基金supported by the National Key R&D Program of China(Grant No.2018YFC1313400)。
文摘Exhausted T cells are a group of dysfunctional T cells,which are present in chronic infections or tumors.The most significant characteristics of exhausted T cells are attenuated effector cytotoxicity,reduced cytokine production,and upregulation of multiple inhibitory molecular receptors(e.g.,PD-1,TIM-3,and LAG-3).The intracellular metabolic changes,altered expression of transcription factors,and a unique epigenetic landscape constitute the exhaustion program.Recently,researchers have made progress in understanding exhausted T cells,with the definition and identification of exhausted T cells changing from phenotypebased to being classified at the transcriptional and epigenetic levels.Recent studies have revealed that exhausted T cells can be separated into two subgroups,namely TCF1^(+)PD-1^(+)progenitor-like precursor exhausted cells and TCF1-PD-1^(+)terminally differentiated exhausted T cells.Moreover,the progenitor-like precursor cell population may be a subset of T cells that can respond to immunotherapy.Studies have also found that TOX initiates and dominates the development of exhausted T cells at the transcriptional and epigenetic levels.TOX also maintains T cell survival and may affect decisions regarding treatment strategies.In this review,we discuss the latest developments in T cell exhaustion in regards to definitions,subpopulations,development mechanisms,differences in diverse diseases,and treatment prospects for exhausted T cells.Furthermore,we hypothesize that the epigenetic state regulated by TOX might be the key point,which can determine the reversibility of exhaustion and the efficacy of immunotherapy.
基金supported by the National Natural Science Foundation of China(No.11101354)
文摘Purpose：The aim of the present study was to investigate the impact of total soy saponins（TS） on the myocardial antioxidant capacity in rats exercised to exhaustion.Methods：The one-time exhausted treadmill model was used.All rats were divided into 4 groups：the control group,the TS group,the exhausted group,and the TS exhausted group.The TS and TS exhausted groups were fed TS at a dosage of 20 mg/kg body weight,once a day,for 2 weeks.The exhausted group was given a placebo,and the control group was not given any treatment.The treadmill speed was set at 30 m/min,and the rats（exhausted and TS exhausted groups） were trained at this speed until exhausted.The rats were decapitated and anatomized immediately after exhausted.A 10% homogenate of the myocardial tissue was prepared.Results：TS significant y increased the exercise time by 20.62%（p〈0.05）.As compared with the control group,the enzyme activities for catalase（CAT）,glutathione peroxidase（GSH-Px）,and glutathione reductase（GR） were significant y enhanced in the TS group（p〈0.01）;GR and GSH-Px activity was significant y enhanced in the TS exhausted group（p〈0.01）;malondialdehyde（MDA） levels were significant y decreased in the TS exhausted group（p〈0.05）.As compared with the exhausted group,the GSH-Px activity was significant y enhanced in the TS exhausted group（p〈0.01）;CAT,GSH-Px,and GR activities were significant y enhanced in the TS group（p〈0.01）.As compared with the TS group,the CAT and GR activity in the TS exhausted group was significant y decreased（p〈0.01）.Conclusion：TS can improve the exercised rats＇ antioxidant activity in their cardiac muscle to varying degrees,decrease MDA and serum AST and LDH levels,increase the exercise time,and delay the occurrence of sports fatigue.
基金supported by grants from the National Natural Science Foundation of China (No. 81570143 and 91642111)the Guangdong Provincial Basic Research Program (No. 2015B020227003)+3 种基金the Guangdong Provincial Applied Science and Technology Research & Development Program (No. 2016B020237006)the Guangzhou Science and Technology Project (No. 201510010211)the Fundamental Research Funds for the Central Universities (No. 21616108)the Medical Scientific Research Foundation of Guangdong Province, China (No. A2016045)
文摘Objective： To investigate the association between the T cell inhibitory receptor programmed death 1（PD-1）and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia（AML） and AML in complete remission（CR）.Methods：Surface expression of PD-1 and the exhaustion and immunosenescence markers CD244 and CD57 on CD3＋,CD4＋ and CD8＋ T cells from peripheral blood samples from 20 newly diagnosed,untreated AML patients and 10 cases with AML in CR was analyzed by flow cytometry.Twenty-three healthy individuals served as control.Results：A significantly higher percentage of PD-1＋ cells were found for CD3＋ T cells in the de novo AML group compared with healthy controls.In addition,an increased level of PD-1＋ CD8＋ T cells,but not PD-1＋ CD4＋,was found for CD3＋ T cells in the de novo AML and AML-CR samples.A higher percentage of CD244＋ CD4＋,CD244＋ CD8＋,CD57＋ CD4＋ and CD57＋ CD8＋ T cells was found in CD3＋ T cells in samples from those with de novo AML compared with those from healthy controls.Strong increased PD-1＋ CD244＋ and PD-1＋ CD57＋ coexpression was found for CD4＋ and CD8＋ T cells in the de novo AML group compared with healthy controls.Conclusions：We characterized the major T cell defects,including co-expression of PD-1 and CD244,CD57-exhausted T cells in patients with de novo AML,and found a particular influence on CD8＋ T cells,suggesting a poor anti-leukemia immune response in these patients.
基金Supported by Key Research Projects of Higher Education in Hebei Province:ZD2019061
文摘Objective:To explore the difference in the anti-fatigue effect of moxibustion at different acupoints through observing the impacts of moxibustion at"Shènshù(肾俞BL23)","Zúsānlǐ(足三里ST36)","Guānyuán(关元CV4)"and"Shénquè(神阙CV8)"on energy metabolic indexes in the one-off exhausted rats.Methods:A total of 56 SPF male rats were randomized into 7 groups,named a blank group,a model group,a non-acupoint group,a"BL23"group,a"ST36"group,a"CV4"group and a"CV8"group,8 rats in each group.The one-off exhaustion model was established by weight-bearing swimming experiment.Right after the exhaustive swimming of rats in each intervention group,the mild moxibustion was applied at the corresponding acupoints for 15 min immediately.4 h after the exhaustive swimming,the blood was collected from the femoral artery and the quadriceps femoris of the left hindlimb was stripped.The levels of blood lactate(BLD),lactate dehydrogenase(LDH),creatine kinase(CK)and blood urea nitrogen(BUN),the expressions of adenosine triphosphatease(ATP),fructose-6-phosphofructokinase(PFK)and malomdialdehyde(MDA)in the quadriceps femoris and the activity of superoxide dismutase(SOD)and catalase(CAT)were detected.Results:Compared with the model group and the non-acupoint group,the levels of serum BLD,LDH,CK and BUN were all lower those in the"BL23"group,the"ST36"group,the"CV4"group and the"CV8"group,indicating a statistical significance(all P<0.05).Compared with the model group and the nonacupoint group,PFK was higher in the"BL23"group,indicating a statistical significance(both P<0.05).Compared with the model group and the non-acupoint group,PFK was higher in the"ST36"group and the"CV4"group,indicating a statistical significance(all P<0.05).Conclusion:It was found in the research that moxibustion at"BL23""ST36""CV4"and"CV8"regulated the energy metabolism in the one-off exhausted rats so as to bring the anti-fatigue effect into play and the effect was different among the acupoints.Moxibustion at"CV8"may work on the prevention of the protein decomposition in the skeletal muscle and moxibustion at"BL23"may be against the oxidation in the skeletal muscle.
文摘The gas and water flows during an underwater missile launch are numerically studied. For the gas flow, the explicit difference scheme of Non-oscillation and Non-free-parameter Dissipation (NND) is utilized to solve the Euler equations for compressible fluids in the body-fitted coordinates. For the water flow, the Hess-Smith method is employed to solve the Laplace equation for the velocity potential of irrotational water flows based on the potential theory and the boundary element method. The hybrid Eulerian-Lagrangian formulation for the free boundary conditions is used to compute the changes of the free surface of the exhausted gas bubble in time stepping. On the free surface of the exhausted gas bubble, the matched conditions of both the normal velocities and pressures are satisfied. From the numerical simulation, it is found that the exhausted gas bubble grows more rapidly in the axial direction than in the radial direction and the bubble will shrink at its "neck" finally. Numerical results of the movement of the shock wave and the distribution of the Mach number and the gas pressure within the bubble were presented, which reveals that at some time, the gas flow in the Laval nozzle is subsonic and the gas pressure in the nozzle is very high. Influences of various initial missile velocities and chamber total pressures and water depths on both the time interval when the gas flow in the nozzle is subsonic and the peak of the gas pressure at the nozzle end were discussed. It was suggested that a reasonable adjustment of the chamber total pressure can improve the performance of the engine during the underwater launch of missiles.
基金supported by Social Policy Grant through Nazarbayev University,Kazakhstan.
文摘Objectives:Emotional exhaustion among healthcare professionals,particularly pharmacists,significantly impacts their well-being and efficacy in patient care.Understanding the psychological mechanisms contributing to emotional exhaustion is essential for developing effective interventions.The present research sought to investigate the potential mediating roles of rumination and coping strategies(adaptive and maladaptive)in the relationship between perceived stress and emotional exhaustion among pharmacists.Methods:A cross-sectional survey was carried out between September 2023 and January 2024 involving 576 pharmacists working in public hospitals in Punjab who met the inclusion criteria and actively participated in the study.We employed the Perceived Stress Scale,the Ruminative Response Scale,the Brief Coping Orientation to Problems Experienced Inventory(COPE),and the Oldenburg Burnout Inventory(OLBI)to assess the hypothesized study model.Path analysis was employed to test the hypothesized mediation model,incorporating simple and chain mediation processes.Results:The findings provided empirical evidence supporting a positive association between perceived stress and emotional exhaustion.Rumination significantlymediated this relationship.Further,both adaptive andmaladaptive coping strategieswere found tomediate this relationship,withmaladaptive coping demonstrating amore substantial impact.Conclusion:The chainmediation model demonstrated that rumination and coping strategies(both maladaptive and adaptive)significantly mediate the relationship between perceived stress and emotional exhaustion among pharmacists.Specifically,rumination was found to be a key mediator,with maladaptive coping strategies having a more substantial impact.These findings provide a deeper understanding of the psychological mechanisms contributing to emotional exhaustion in the pharmacy profession.
文摘The Brief Interactive Optimism Scale (BIOS-G), recently published, was developed to measure optimism based on the interactive personality styles theory in the general population of Mexican adults. It has been validated in both the general population in Mexico and other Latin American countries. This study aims to further consolidate the validity of the BIOS-G in a specific population. The objectives are to assess the psychometric properties of its items, validate its unidimensional structure, describe its distribution, verify its internal consistency, and examine its direct relationship with affective balance and positive affect, as well as its inverse relationship with emotional exhaustion and negative affect among Mexican university teachers. The BIOS-G, the CESQT emotional exhaustion subscale, and Scale of Positive and Negative Experience (SPANE) were administered to a non-probability sample of 213 Mexican university teachers. All items demonstrated discriminative power and internal consistency. The scale showed internal consistency (Green-Yang ordinal ω = 0.74 and McDonald ordinal ω = 0.88). The one-factor model presented good to acceptable fit to the data, with an average variance extracted of 0.65. Its distribution was negatively skewed and mesokurtic. The BIOS-G correlated directly with SPANE’s affective balance and positive emotional experiences and inversely with negative emotional experiences and emotional exhaustion, with moderate strengths of association. Its mean score was higher in men than in women and correlated positively with age. It is concluded that the BIOS-G demonstrates internal consistency and validity evidence among Mexican university teachers, and its use in this specific population is recommended.
基金funded by Guangxi Eco-Engineering Vocational&Technical College Talent Introduction Research Project and 2024 Guangxi Vocational Education Teaching Reform Research Project grant number[GXSTKYZX20240603]and[GXGZJG2024B125]and the APC was funded by GEVT College.
文摘This study investigated the relationship between AI anxiety and deviant behavior,as well as the roles of emotional exhaustion and leader support in this context.The sample comprised 381 Chinese e-commerce employees(72.7%female,age range 21–36 years).The results of the Process model analysis indicate that AI anxiety significantly is associated with higher deviant behaviour.Emotional exhaustion partially mediates this relationship between AI anxiety and employee deviant behavior exacerbating deviant behaviour.Leader support moderates the AI anxiety effect on emotional exhaustion such that when leader support is low.AI anxiety is associated with higher emotional exhaustion among employees.By implication,high levels of leader support can alleviate AI anxiety of employees.Employer organizations should provide appropriate guidance when introducing AI technology to prevent AI anxiety and associated emotional exhaustion and deviant behavior.
基金Funded by the Natural Science Foundation of Henan(No.252300421563)the Key Research Projects of Henan Provincial Colleges and Universities(No.25B450001)+3 种基金the Basic and Frontier Research Project of Nanyang(No.24JCQY032)National Natural Science Foundation of China(No.52201044)the Key Specialized Research&Development and Promotion Project(Scientific and Technological Project)of Henan Province(No.232102221022)the Basic and Frontier Technology Research Project of Nanyang(No.23JCQY1001)。
文摘This paper presented a novel and environmentally friendly approach for recovering platinum group metals(PGMs)from spent automotive exhaust catalysts.The study employed lead slag and waste graphite electrodes as raw materials,incorporating CaO as an additive to fine-tune the slag's viscosity and density.By reducing FeO in the lead slag using waste graphite electrodes,pure Fe was obtained,effectively trapping the PGMs from the exhausted catalysts.The study explored the effects of reductant addition,trapping duration,slag basicity,and trapping temperature on the recovery rate of PGMs.The results indicated that a maximum recovery rate of 97.86%was achieved when the reductant was added at 1.5 times the theoretical amount,with a trapping duration of 60 minutes,a slag basicity of 0.7,and a trapping temperature of 1600℃.This research offered a greener pathway for the recovery of PGMs from spent automotive exhaust catalysts.
基金supports provided by the National Natural Science Foundation of China(No.52372330).
文摘The small punch test technique facilitates the convenient acquisition of the mechanical properties of in-service equipment materials and the assessment of their remaining service life through sampling.However,the weldability of components with thin walls after small punch sampling,such as ethylene cracking furnace tubes,requires further investigation.Therefore,the weldability of in-service ethylene cracking furnace tubes following small punch sampling was investigated through nondestructive testing,microstructural characterization,and mechanical testing.Additionally,the impact of small punch sampling size and residual stress on the creep performance of the specimens was studied using an improved ductility exhaustion model.The results indicate that both the surface and interior of the weld repair areas on new furnace tubes and service-exposed furnace tubes after small-punch sampling are defect-free,exhibiting good weld quality.The strength of the specimens after weld repair was higher than that before sampling,whereas toughness decreased.Weld repair following small punch sampling of furnace tubes is both feasible and necessary.Furthermore,a linear relationship was observed between specimen thickness,diameter,and creep fracture time.The residual stress of welding affects the creep performance of the specimen under different stresses.
基金financially supported by the Basic Research Funds for the Central Government“Innovative Team of Zhejiang University”under contract number(2022FZZX01-09).
文摘The effect of gradient exhaust strategy and blind plate installation on the inhibition of backflow and thermal stratification in data center cabinets is systematically investigated in this study through numericalmethods.The validated Re-Normalization Group(RNG)k-ε turbulence model was used to analyze airflow patterns within cabinet structures equipped with backplane air conditioning.Key findings reveal that server-generated thermal plumes induce hot air accumulation at the cabinet apex,creating a 0.8℃ temperature elevation at the top server’s inlet compared to the ideal situation(23℃).Strategic increases in backplane fan exhaust airflow rates reduce server 1’s inlet temperature from 26.1℃(0%redundancy case)to 23.1℃(40%redundancy case).Gradient exhaust strategies achieve equivalent server temperature performance to uniform exhaust distributions while requiring 25%less redundant airflow.This approach decreases the recirculation ratio from1.52%(uniformexhaust at 15%redundancy)to 0.57%(gradient exhaust at equivalent redundancy).Comparative analyses demonstrate divergent thermal behaviors:in bottom-server-absent configurations,gradient exhaust reduces top server inlet temperatures by 1.6℃vs.uniformexhaust,whereas top-serverabsent configurations exhibit a 1.8℃ temperature increase under gradient conditions.The blind plate implementation achieves a 0.4℃ top server temperature reduction compared to 15%-redundancy uniform exhaust systems without requiring additional airflow redundancy.Partially installed server arrangements with blind plates maintain thermal characteristics comparable to fully populated cabinets.This study validates gradient exhaust and blind plate technologies as effective countermeasures against cabinet-scale thermal recirculation,providing actionable insights for optimizing backplane air conditioning systems in mission-critical data center environments.
文摘Two environmentalists using bamboo bicycles to promote green transportation.THE exhaust emissions generated by transporting the world’s population on a daily basis are one of the main sources of greenhouse gases.Vehicles such as cars,subways,and motorcycles,all produce carbon emissions.
基金supported by Jiangxi 03 Special and 5G Project(20232ABC03A33)Ganpo Talent Support Program(20232BCJ23106)。
文摘Based on 5G and IoT technology,this study addresses the issues of manual control dependency,poor reliability,and high labor costs in traditional ceramic kiln exhaust cover operations.An intelligent control system for kiln exhaust covers was designed in this paper.The system employs temperature measurement devices to monitor the internal temperature of the kiln in real time.A controller automatically operates the actuator to open or close the kiln exhaust cover based on temperature measurements.Additionally,the system integrates data transmission units and cloud services,enabling remote monitoring of kiln temperature and historical data storage.Experimental results demonstrate that the system effectively reduces labor costs and significantly enhances the IoT capabilities of kiln operations.
文摘CAR-T cell therapy demonstrates tremendous potential for tumor treatment,yet faces challenges in solid tumor therapy due to immune suppression,T-cell exhaustion,and cytokine release syndrome(CRS)induced by the tumor microenvironment(TME).Traditional Chinese medicine(TCM)holds substantial potential to enhance CAR-T efficacy and mitigate adverse reactions due to its multi-targeted advantages.TCM active ingredients and formulations can synergistically amplify CAR-T anti-tumor effects while reducing adverse events through multiple mechanisms,including reversing T-cell exhaustion,prolonging CAR-T cell persistence,improving TME hypoxia and fibrosis,modulating gut microbiota,and suppressing CRS.This benefits patient treatment and recovery.Combining TCM with CAR-T therapy can increase objective response rates,prolong cell persistence,and reduce CRS incidence.Future efforts will focus on exploring the precise mechanisms and standardized protocols for TCM-enhanced CAR-T treatment through high-quality clinical trials and multi-omics technologies,driving its clinical translation and application.
基金supported by grants from National Natural Science Foundation of China(32370892)Science and Technology Commission of Shanghai Municipality(23141901200)+3 种基金Shanghai Natural Science Foundation(24ZR1450100)Health Commission of Shanghai Municipality(2022JC029)Biomaterials and Regenerative Medicine Institute Cooperative Research Project,Shanghai Jiaotong University School of Medicine(2022LHA11)Talent-Introduction Program of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine(2022YJRC05).
文摘Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due to the complex pathogenesis.Although OA mechanisms have been investigated on a large scale over the past decade,the OA pathology correlated with aging-associated changes is still largely unrevealed.Therefore,in-depth analysis of the aging microenvironment and aging-related molecular mechanisms in OA may offer additional strategies for clinical prevention and treatment.In this review,we discuss the potential pathogenesis of OA in light of aging-associated changes and summarize three main components of the aging microenvironment of the OA joint:immune homeostatic imbalance,cellular senescence,and stem cell exhaustion,which could be induced by aging and further exacerbate OA progression.Additionally,it is emphasized that immune homeostatic imbalance appears before established OA,which occurs in the early stage and is the therapeutic window of opportunity for better clinical outcomes.Importantly,we evaluate recent therapeutic targets and promising interventions against these components,as well as the challenges and prospects for precise and individualized therapies of OA patients,which we believe would guide the construction of novel combined strategies targeting aging-related factors against OA for better treatments in the future.
