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
This study was to optimize the exercise preconditioning(EP)intensity in protecting from exhaustive exercise-induced cardiac injury(EECI).A total of 98 male Sprague-Dawley rats were divided into 7 groups(n=14):the cont...This study was to optimize the exercise preconditioning(EP)intensity in protecting from exhaustive exercise-induced cardiac injury(EECI).A total of 98 male Sprague-Dawley rats were divided into 7 groups(n=14):the control group(C),the exhaustive exercise group(EE)and the EP+EE groups,which include the V10(53.0%VO_(2max)),V15(58.4%VO_(2max)),V20(67.0%VO_(2max)),V26(74.0%VO_(2max))and V30(80.0%VO_(2max))groups.Except the C group,the other groups were subjected to treadmill running.The serum contents of N terminal pro B type natriuretic peptide(NT-proBNP)and cardiac troponin I(cTn-I)were detected by the enzyme-linked immunosorbent assay method,ECG was recorded,heart function was detected by pressure volume catheter and the activities of mitochondrial electron transfer pathway(ET pathway)complexesⅠ,ⅡandⅣwere measured by high-resolution respiration instrument.Compared to the EE group,the EP groups have shown decrease of NT-proBNP and cTn-I,improvement of mitochondrial respiratory function and car-diac function.Compared to other EP groups,the V26 group has shown significant decrease of myocardial enzymes and improvement of mitochondrial function.The correlation analysis showed the EP effect was proportional to EP intensity in the range of 53.0%VO_(2max)-74.0%VO_(2max).High intensity and long duration of exhaustive exercise caused cardiac injury and EP could decrease serum level of NT-proBNP and cTn-I,improve electrical derangement and the left ventricular function,and raise the activities of ET pathway complexesⅠ,ⅡandⅣ.The protection of EP on EECI was improved as the EP intensity was increased from 53.0%VO_(2max)to 74.0%VO_(2max)and when EP intensity was 74.0%VO_(2max),the effect was the most obvious among all the setting EP groups.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
Extreme heat events contribute to high mortality[1,2]and overwhelm emergency medical services through increased ambulance calls and overcrowded emergency departments.[3]Because morbidity and mortality are directly rel...Extreme heat events contribute to high mortality[1,2]and overwhelm emergency medical services through increased ambulance calls and overcrowded emergency departments.[3]Because morbidity and mortality are directly related to both the degree and duration of hyperthermia,timely recognition and management of heat exhaustion and heat stroke are critical for preventing death and reducing healthcare burdens.展开更多
In recent years the crucial role of CD4^(+)T cells in tumor immunomodulation has garnered increasing recognition.While conventional cancer immunotherapy research has predominantly focused on the cytotoxic function of ...In recent years the crucial role of CD4^(+)T cells in tumor immunomodulation has garnered increasing recognition.While conventional cancer immunotherapy research has predominantly focused on the cytotoxic function of CD8+T cells,emerging evidence has now shown that CD4^(+)T cells enhance antitumor immunity by delivering co-stimulatory signals,secreting cytokines,and promoting cytotoxic T lymphocyte(CTL)activation and display unique immunoregulatory capabilities through direct tumor cell killing or remodeling of the tumor microenvironment.The high heterogeneity and functional plasticity of CD4^(+)T cell subsets significantly influence clinical responses to immunotherapy with underlying mechanisms involving multi-level regulatory networks,including epigenetic modulation and metabolic reprogramming.Deciphering the functional heterogeneity of CD4^(+)T cells and the interactions with the tumor microenvironment will provide essential mechanistic insights for next-generation immunotherapies,such as immune checkpoint inhibitors and chimeric antigen receptor T(CAR-T)therapies,thereby advancing personalized treatment paradigms.展开更多
Exercise produces a decrease in pain sensitivity via an effect called exercise-induced hypoalgesia(EIH).Transcranial direct current stimulation(tDCS),acting on similar analgesic mechanisms as EIH,represents a potentia...Exercise produces a decrease in pain sensitivity via an effect called exercise-induced hypoalgesia(EIH).Transcranial direct current stimulation(tDCS),acting on similar analgesic mechanisms as EIH,represents a potential complementary intervention that may amplify the effects of exercise on pain.This study aimed to explore if anodal tDCS could enhance the effect of exercise on pain compared to exercise alone.A total of 35 healthy participants aged 19–37 years completed a familiarisation session followed by two separate sessions where active and sham tDCS was applied in a randomised cross-over design.The familiarisation session involved familiarisation to the pain assessment and exercise tasks,while the subsequent tDCS sessions involved pain sensitivity assessment,exercise and either anodal tDCS or sham tDCS.tDCS doses were applied at 2 mA over the primary motor cortex for 10 min,with the reference electrode placed over the contralateral supraorbital area.The exercise task involved a sustained isometric grip strength contraction at 35%of maximal voluntary contraction(MVC)until volitional exhaustion.Pain sensitivity was evaluated as pressure pain threshold before tDCS,after tDCS,and after exercise.Across both tDCS conditions,pain threshold was higher after exercise when compared to pre-and post-tDCS measurement.This increase in pain threshold did not differ between active and sham tDCS conditions.Our findings suggest that the hypoalgesic effects of active anodal tDCS over the motor cortex prior to exercise are no greater than the effects of sham tDCS prior to exercise.展开更多
Unmanned combat aerial vehicles require lightweight,stealth-capable exhaust systems.However,traditional metallic nozzles increase radar detectability and reduce range,while advanced composites offer high performance b...Unmanned combat aerial vehicles require lightweight,stealth-capable exhaust systems.However,traditional metallic nozzles increase radar detectability and reduce range,while advanced composites offer high performance but are expensive.Therefore,to improve the operational range and survivability of unmanned combat aerial vehicles,a lightweight,high-temperature-resistant,oxidation-resistant,and low-observable composite exhaust nozzle is developed to replace conventional metallic straight-type nozzles.The nozzle features a double serpentine shape to reduce radar and infrared signatures and is manufactured as a monolithic structure using the filament winding process,accommodating the complex geometry and large size(length:1.8 m,width:0.8 m).The exhaust nozzle consists of a ceramic matrix composite made of silicon carbide fibers and a silicon oxycarbide matrix,which absorbs and scatters radio frequency signals while withstanding prolonged exposure to high-temperature(700℃)oxidizing environments typical of engine exhaust gases.The polysiloxane resin used to produce the silicon oxycarbide matrix poses significant challenges owing to its low tackiness and high viscosity variations depending on the presence of nanoparticles,making filament winding difficult.These challenges are addressed by optimizing resin viscosity and winding pattern design.As a result,the tensile strength of the composite specimens fabricated with the optimized viscosity increases by 228.03% before pyrolysis and 97.68%after pyrolysis,compared with that of the non-optimized specimens.In addition,the density and tensile strength of the composite processed via three cycles of polymer infiltration and pyrolysis increased by 13.08% and 80.37%,respectively,compared to those of the non-densified composite.High-temperature oxidation and flame tests demonstrate exceptional thermal and oxidative stability.Furthermore,when compared with carbon fiber-reinforced ceramic matrix composites,the developed composite exhibits a permittivity at least two levels lower and a reflection loss below7 dB within the frequency range of 9.3-10.9 GHz,underscoring its superior electromagnetic stealth performance.展开更多
Exhausted CD8^(+)T(Tex)cells are dysfunctional due to persistent antigen exposure in chronic viral infection and tumor contexts.A stem cell-like Tex(Tex-stem)subset can self-renew and differentiate into terminally exh...Exhausted CD8^(+)T(Tex)cells are dysfunctional due to persistent antigen exposure in chronic viral infection and tumor contexts.A stem cell-like Tex(Tex-stem)subset can self-renew and differentiate into terminally exhausted(Tex-term)cells.Here,we show that ectopic Tcf1 expression potently promoted the generation of Tex-stem cells in both a chronic viral infection and preclinical tumor models.Tcf1 overexpression diminished coinhibitory receptor expression and enhanced polycytokine-producing capacity while retaining a heightened responses to checkpoint blockade,leading to enhanced viral and tumor control.Mechanistically,ectopically expressed Tcf1 exploited existing and novel chromatin accessible sites as transcriptional enhancers or repressors and modulated the transcriptome by enforcing pre-existing expression patterns in Tex-stem cells,such as enhanced suppression of Blimp1 and Bim and acquisition of new downstream genes,including Mx1,Tox2,and Runx3.These findings reveal a pronounced impact of ectopic Tcf1 expression on Tex functional restoration and highlight the therapeutic potential of harnessing Tcf1-enforced transcriptional programs.展开更多
Although cancer immunotherapy has taken center stage,exhaustion of T cells is undeniably one of the major problems preventing it from being fully successful[1].Certainly,reversal of T-cell exhaustion or dysfunction is...Although cancer immunotherapy has taken center stage,exhaustion of T cells is undeniably one of the major problems preventing it from being fully successful[1].Certainly,reversal of T-cell exhaustion or dysfunction is of great importance for developing new strategies and restoring immune function.Nevertheless,counterarguments about the adverse effect of reversing T-cell exhaustion(leading to overactivation of T cells and cytotoxicity)and even their irreversible properties have been quite common in scientific debates.With more to be discovered about the reasons for T-cell failure,a better understanding of the molecular factors/determinants[2,3]that shape/remodel“heterogeneous”dysfunctional T cells in cancer makes clear sense.Indeed,two recent publications in Nature immunology have described the intriguing perspective of T-cell exhaustion[4,5].Of interest,Vignali et al.focused on the hypoxia-driven CD39-dependent suppressor function of exhausted T cells,whereas Saadey et al.emphasized restoring the epigenetic balance of TGFβ1/BMP signaling in exhausted T cells to unlock responsiveness to immune checkpoint blockade therapy.展开更多
Background Overtraining Syndrome(OTS)is a condition resulting from excessive physical activity without adequate recovery,predominantly affecting elite athletes and military personnel.While overreaching can be a tempor...Background Overtraining Syndrome(OTS)is a condition resulting from excessive physical activity without adequate recovery,predominantly affecting elite athletes and military personnel.While overreaching can be a temporary state,non-functional overreaching may progress to chronic OTS.This review explores various hypotheses regarding the pathogenesis of OTS,including glycogen depletion,dysregulated cytokine response,oxidative stress,and alterations in the autonomic nervous system function.It also highlights the systemic impact of OTS on multiple organ systems,immune function,and overall health,linking the condition to chronic inflammation and an increased disease susceptibility.Additionally,it addresses the role of the gut microbiome in health modulation through physical activity.Methods This narrative review was conducted through a structured search of peer-reviewed journal articles in databases such as PubMed,Web of Science,and Google Scholar,focusing on studies involving human participants and published in English.Results OTS has systemic effects on multiple organ systems,immune function,and overall health,leading to chronic inflammation and increased disease susceptibility.Athletes with OTS exhibit higher morbidity rates,influenced by factors such as sleep deprivation and stress.The review also emphasizes the role of the gut microbiome as a significant modulator of health through physical activity.Conclusion Balanced training and recovery are crucial for preventing OTS and maintaining optimal health and quality of life in physically active individuals.Understanding the complex pathophysiology of OTS is essential for developing effective prevention and treatment strategies.展开更多
Objectives:This study aimed to establish the concept of overcoming exhaustion,providing a reference basis for nursing management and conducting related nursing research.Methods:Liehr and Smith’s three-phase,nine-step...Objectives:This study aimed to establish the concept of overcoming exhaustion,providing a reference basis for nursing management and conducting related nursing research.Methods:Liehr and Smith’s three-phase,nine-step concept-building process was used to create the concept of overcoming exhaustion.The nine steps were as follows:1)write a practice story;2)name the emerging concept;3)select a theoretical lens;4)link concept to literature;5)gather a concept story;6)identify final core qualities;7)formulate concept definition;8)create a concept model;and 9)specify the concept building synthesis.Results:The concept of overcoming exhaustion was identified based on the elements of a practice story,the life experiences of nurses who struggle with the demands of caring for their patients,their families,and themselves.The theory of self-transcendence was then recognized as the theoretical lens from which to ground the concept.The core qualities,despair and moments of calmness,were derived from the literature and confirmed through a concept story.A definition of the concept integrating the core qualities was formed:overcoming exhaustion involves realizing moments of calmness amidst despair.A model was created to demonstrate the relationship between core qualities,despair,and moments of calmness.Conclusions:The concept of overcoming exhaustion was developed and,through the concept-building process,was defined as realizing moments of calmness amidst despair.By identifying the complexities of overcoming exhaustion,this work lays the foundation for a future research program to develop understanding and interventions that support nurse well-being in the context of ongoing personal and professional demands.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
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.
基金supported by grants from the Hebei Province Natural Science Foundation of China(no.H2019104017)and Special Fund for Team of Sports Induced Heart Injury Prevention and Treatment in Military.
文摘This study was to optimize the exercise preconditioning(EP)intensity in protecting from exhaustive exercise-induced cardiac injury(EECI).A total of 98 male Sprague-Dawley rats were divided into 7 groups(n=14):the control group(C),the exhaustive exercise group(EE)and the EP+EE groups,which include the V10(53.0%VO_(2max)),V15(58.4%VO_(2max)),V20(67.0%VO_(2max)),V26(74.0%VO_(2max))and V30(80.0%VO_(2max))groups.Except the C group,the other groups were subjected to treadmill running.The serum contents of N terminal pro B type natriuretic peptide(NT-proBNP)and cardiac troponin I(cTn-I)were detected by the enzyme-linked immunosorbent assay method,ECG was recorded,heart function was detected by pressure volume catheter and the activities of mitochondrial electron transfer pathway(ET pathway)complexesⅠ,ⅡandⅣwere measured by high-resolution respiration instrument.Compared to the EE group,the EP groups have shown decrease of NT-proBNP and cTn-I,improvement of mitochondrial respiratory function and car-diac function.Compared to other EP groups,the V26 group has shown significant decrease of myocardial enzymes and improvement of mitochondrial function.The correlation analysis showed the EP effect was proportional to EP intensity in the range of 53.0%VO_(2max)-74.0%VO_(2max).High intensity and long duration of exhaustive exercise caused cardiac injury and EP could decrease serum level of NT-proBNP and cTn-I,improve electrical derangement and the left ventricular function,and raise the activities of ET pathway complexesⅠ,ⅡandⅣ.The protection of EP on EECI was improved as the EP intensity was increased from 53.0%VO_(2max)to 74.0%VO_(2max)and when EP intensity was 74.0%VO_(2max),the effect was the most obvious among all the setting EP groups.
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.
文摘Extreme heat events contribute to high mortality[1,2]and overwhelm emergency medical services through increased ambulance calls and overcrowded emergency departments.[3]Because morbidity and mortality are directly related to both the degree and duration of hyperthermia,timely recognition and management of heat exhaustion and heat stroke are critical for preventing death and reducing healthcare burdens.
基金supported by The National Key Research and Development Program of China(Grant No.2021YFA0910100)Healthy Zhejiang One Million People Cohort(Grant No.K-20230085)+6 种基金supported by National Natural Science Foundation of China(Grant Nos.82304946 and 82573745)Post-doctoral Innovative Talent Support Program(Grant No.BX2023375)567 Foundation of Zhejiang Province(Grant No.LMS25H160006)supported by the National Natural Science Foundation of China(Grant No.82473489)the Medical Science and Technology Project of Zhejiang Province(Grant No.WKJ-ZJ-2202)the Natural Science Foundation of Zhejiang Province(Grant No.LBD24H290001)supported by the National Natural Science Foundation of China(Grant No.82403546).
文摘In recent years the crucial role of CD4^(+)T cells in tumor immunomodulation has garnered increasing recognition.While conventional cancer immunotherapy research has predominantly focused on the cytotoxic function of CD8+T cells,emerging evidence has now shown that CD4^(+)T cells enhance antitumor immunity by delivering co-stimulatory signals,secreting cytokines,and promoting cytotoxic T lymphocyte(CTL)activation and display unique immunoregulatory capabilities through direct tumor cell killing or remodeling of the tumor microenvironment.The high heterogeneity and functional plasticity of CD4^(+)T cell subsets significantly influence clinical responses to immunotherapy with underlying mechanisms involving multi-level regulatory networks,including epigenetic modulation and metabolic reprogramming.Deciphering the functional heterogeneity of CD4^(+)T cells and the interactions with the tumor microenvironment will provide essential mechanistic insights for next-generation immunotherapies,such as immune checkpoint inhibitors and chimeric antigen receptor T(CAR-T)therapies,thereby advancing personalized treatment paradigms.
文摘Exercise produces a decrease in pain sensitivity via an effect called exercise-induced hypoalgesia(EIH).Transcranial direct current stimulation(tDCS),acting on similar analgesic mechanisms as EIH,represents a potential complementary intervention that may amplify the effects of exercise on pain.This study aimed to explore if anodal tDCS could enhance the effect of exercise on pain compared to exercise alone.A total of 35 healthy participants aged 19–37 years completed a familiarisation session followed by two separate sessions where active and sham tDCS was applied in a randomised cross-over design.The familiarisation session involved familiarisation to the pain assessment and exercise tasks,while the subsequent tDCS sessions involved pain sensitivity assessment,exercise and either anodal tDCS or sham tDCS.tDCS doses were applied at 2 mA over the primary motor cortex for 10 min,with the reference electrode placed over the contralateral supraorbital area.The exercise task involved a sustained isometric grip strength contraction at 35%of maximal voluntary contraction(MVC)until volitional exhaustion.Pain sensitivity was evaluated as pressure pain threshold before tDCS,after tDCS,and after exercise.Across both tDCS conditions,pain threshold was higher after exercise when compared to pre-and post-tDCS measurement.This increase in pain threshold did not differ between active and sham tDCS conditions.Our findings suggest that the hypoalgesic effects of active anodal tDCS over the motor cortex prior to exercise are no greater than the effects of sham tDCS prior to exercise.
基金supported by the Agency for Defense Development Grant Funded by the Korean Government(Grant No.912822501).
文摘Unmanned combat aerial vehicles require lightweight,stealth-capable exhaust systems.However,traditional metallic nozzles increase radar detectability and reduce range,while advanced composites offer high performance but are expensive.Therefore,to improve the operational range and survivability of unmanned combat aerial vehicles,a lightweight,high-temperature-resistant,oxidation-resistant,and low-observable composite exhaust nozzle is developed to replace conventional metallic straight-type nozzles.The nozzle features a double serpentine shape to reduce radar and infrared signatures and is manufactured as a monolithic structure using the filament winding process,accommodating the complex geometry and large size(length:1.8 m,width:0.8 m).The exhaust nozzle consists of a ceramic matrix composite made of silicon carbide fibers and a silicon oxycarbide matrix,which absorbs and scatters radio frequency signals while withstanding prolonged exposure to high-temperature(700℃)oxidizing environments typical of engine exhaust gases.The polysiloxane resin used to produce the silicon oxycarbide matrix poses significant challenges owing to its low tackiness and high viscosity variations depending on the presence of nanoparticles,making filament winding difficult.These challenges are addressed by optimizing resin viscosity and winding pattern design.As a result,the tensile strength of the composite specimens fabricated with the optimized viscosity increases by 228.03% before pyrolysis and 97.68%after pyrolysis,compared with that of the non-optimized specimens.In addition,the density and tensile strength of the composite processed via three cycles of polymer infiltration and pyrolysis increased by 13.08% and 80.37%,respectively,compared to those of the non-densified composite.High-temperature oxidation and flame tests demonstrate exceptional thermal and oxidative stability.Furthermore,when compared with carbon fiber-reinforced ceramic matrix composites,the developed composite exhibits a permittivity at least two levels lower and a reflection loss below7 dB within the frequency range of 9.3-10.9 GHz,underscoring its superior electromagnetic stealth performance.
基金supported by grants from the NIH(AI112579,AI121080 and AI139874 to H.-H.X.,GM133712 to C.Z.,and GM113961,AI147064 and AI114543 to V.P.B.)the Veteran Affairs BLR&D Merit Review Program(BX002903)to H.-H.X.
文摘Exhausted CD8^(+)T(Tex)cells are dysfunctional due to persistent antigen exposure in chronic viral infection and tumor contexts.A stem cell-like Tex(Tex-stem)subset can self-renew and differentiate into terminally exhausted(Tex-term)cells.Here,we show that ectopic Tcf1 expression potently promoted the generation of Tex-stem cells in both a chronic viral infection and preclinical tumor models.Tcf1 overexpression diminished coinhibitory receptor expression and enhanced polycytokine-producing capacity while retaining a heightened responses to checkpoint blockade,leading to enhanced viral and tumor control.Mechanistically,ectopically expressed Tcf1 exploited existing and novel chromatin accessible sites as transcriptional enhancers or repressors and modulated the transcriptome by enforcing pre-existing expression patterns in Tex-stem cells,such as enhanced suppression of Blimp1 and Bim and acquisition of new downstream genes,including Mx1,Tox2,and Runx3.These findings reveal a pronounced impact of ectopic Tcf1 expression on Tex functional restoration and highlight the therapeutic potential of harnessing Tcf1-enforced transcriptional programs.
文摘Although cancer immunotherapy has taken center stage,exhaustion of T cells is undeniably one of the major problems preventing it from being fully successful[1].Certainly,reversal of T-cell exhaustion or dysfunction is of great importance for developing new strategies and restoring immune function.Nevertheless,counterarguments about the adverse effect of reversing T-cell exhaustion(leading to overactivation of T cells and cytotoxicity)and even their irreversible properties have been quite common in scientific debates.With more to be discovered about the reasons for T-cell failure,a better understanding of the molecular factors/determinants[2,3]that shape/remodel“heterogeneous”dysfunctional T cells in cancer makes clear sense.Indeed,two recent publications in Nature immunology have described the intriguing perspective of T-cell exhaustion[4,5].Of interest,Vignali et al.focused on the hypoxia-driven CD39-dependent suppressor function of exhausted T cells,whereas Saadey et al.emphasized restoring the epigenetic balance of TGFβ1/BMP signaling in exhausted T cells to unlock responsiveness to immune checkpoint blockade therapy.
基金supported by the project SVV-2023-260656 and the Cooperatio Program,research area HEAS.
文摘Background Overtraining Syndrome(OTS)is a condition resulting from excessive physical activity without adequate recovery,predominantly affecting elite athletes and military personnel.While overreaching can be a temporary state,non-functional overreaching may progress to chronic OTS.This review explores various hypotheses regarding the pathogenesis of OTS,including glycogen depletion,dysregulated cytokine response,oxidative stress,and alterations in the autonomic nervous system function.It also highlights the systemic impact of OTS on multiple organ systems,immune function,and overall health,linking the condition to chronic inflammation and an increased disease susceptibility.Additionally,it addresses the role of the gut microbiome in health modulation through physical activity.Methods This narrative review was conducted through a structured search of peer-reviewed journal articles in databases such as PubMed,Web of Science,and Google Scholar,focusing on studies involving human participants and published in English.Results OTS has systemic effects on multiple organ systems,immune function,and overall health,leading to chronic inflammation and increased disease susceptibility.Athletes with OTS exhibit higher morbidity rates,influenced by factors such as sleep deprivation and stress.The review also emphasizes the role of the gut microbiome as a significant modulator of health through physical activity.Conclusion Balanced training and recovery are crucial for preventing OTS and maintaining optimal health and quality of life in physically active individuals.Understanding the complex pathophysiology of OTS is essential for developing effective prevention and treatment strategies.
文摘Objectives:This study aimed to establish the concept of overcoming exhaustion,providing a reference basis for nursing management and conducting related nursing research.Methods:Liehr and Smith’s three-phase,nine-step concept-building process was used to create the concept of overcoming exhaustion.The nine steps were as follows:1)write a practice story;2)name the emerging concept;3)select a theoretical lens;4)link concept to literature;5)gather a concept story;6)identify final core qualities;7)formulate concept definition;8)create a concept model;and 9)specify the concept building synthesis.Results:The concept of overcoming exhaustion was identified based on the elements of a practice story,the life experiences of nurses who struggle with the demands of caring for their patients,their families,and themselves.The theory of self-transcendence was then recognized as the theoretical lens from which to ground the concept.The core qualities,despair and moments of calmness,were derived from the literature and confirmed through a concept story.A definition of the concept integrating the core qualities was formed:overcoming exhaustion involves realizing moments of calmness amidst despair.A model was created to demonstrate the relationship between core qualities,despair,and moments of calmness.Conclusions:The concept of overcoming exhaustion was developed and,through the concept-building process,was defined as realizing moments of calmness amidst despair.By identifying the complexities of overcoming exhaustion,this work lays the foundation for a future research program to develop understanding and interventions that support nurse well-being in the context of ongoing personal and professional demands.
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.
