Revolutionizing tumor immunotherapy:unleashing the power of progenitor exhausted T cells

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.

The Mechanisms of CD8+ T Cells Exhaustion in the Tumor Microenvironment and Immune Therapy

In the tumor immune microenvironment, CD8+ T cells differentiate towards functional failure. The exhaustion of CD8+ T cells (Tex) showed varying degrees of effect dysfunction, loss of proliferation ability, and sustained high expression of a variety of inhibitory receptors, with metabolic and epigenetic changes. Tex cells are heterogeneous, including several subsets with different characteristics at different stages of differentiation. Immune checkpoint inhibitors (ICIs) can restore the effect or function of Tex cells, indicating that this T cell subset plays a key role in tumor immunotherapy. The understanding of the mechanism of CD8+ T cell exhaustion will be helpful to the implementation of tumor immunotherapy. This article reviews the production, differentiation and functional characteristics of Tex cells and their relationship with tumor immunotherapy.

Fluid-Structure Coupled Analysis of the Transient Thermal Stress in an Exhaust Manifold

The development of thermal stress in the exhaust manifold of a gasoline engine is considered.The problem is addresses in the frame of a combined approach wherefluid and structure are coupled using the GT-POWER and STAR-CCM+software.First,the external characteristic curve of the engine is compared with a one-dimen-sional simulation model,then the parameters of the model are modified until the curve matches the available experimental values.GT-POWER is then used to transfer the inlet boundary data under transient conditions to STAR-CCM+in real-time.The temperature profiles of the inner and outer walls of the exhaust manifold are obtained in this way,together with the thermal stress and thermal deformation of the exhaust manifold itself.Using this information,the original model is improved through the addition of connections.Moreover,the local branch pipes are optimized,leading to significant improvements in terms of thermal stress and thermal deforma-tion of the exhaust manifold(a 7%reduction in the maximum thermal stress).

Effect of endurance training on the expression profile of circRNA-lncRNA-miRNA-mRNA in myocardial tissues of mice after exhaustive exercise

Objective:To clarify the effect of endurance training on the expression profile of circRNA-lncRNA-miRNA-mRNA in myocardial tissues of mice after exhaustive exercise.Methods:A total of 45 male C57BL/6 mice were randomly divided into control(C),low-strength endurance training(LSET)and high-strength endurance training(HSET)groups(n=15).The mice in the control group were not conducted to platform training.The mice in the LSET and HSET groups were conducted to platform training at 30%and 60%of exhaustive exercise once a day for 5 days a week,respectively.The exhaustion exercise was performed after 5 weeks of platform training.Total RNA was extracted from myocardial tissues,and the expression profile of circRNA-lncRNA-miRNA-mRNA in myocardial tissues was analyzed using Illimina transcriptome sequencing.Results:The distance and time of exhaustive exercise were longer in the LSET and HSET groups than in the control group,and the distance and time of exhaustive exercise were longer in the HSET group than in the LSET group(P<0.05).A total of 54 differentially expressed circRNAs(28 down-regulated and 26 up-regulated),7 differentially expressed lncRNAs(all down-regulated),3 differentially expressed miRNAs(1 down-regulated and 2 up-regulated)and 99 differentially expressed mRNAs(81 down-regulated and 18 up-regulated)were identified by transcriptome sequencing(P<0.05).Interaction network analysis revealed that ENSMUSG00000113041,MSTRG.79740,mmu-miR-374c-5p,18 down-regulated mRNAs and 3 up-regulated mRNAs formed a regulatory network.GO functional analysis revealed that the differentially expressed mRNAs were mainly enriched in primary metabolic processes and macromolecular synthesis and metabolic processes.KEGG pathway analysis revealed that the differentially expressed mRNAs were mainly enriched in complement and coagulation cascade pathways,estrogen signaling pathway and glucagon signaling pathway.Conclusion:Endurance training could alter the expression profile of circRNA-lncRNA-miRNA-mRNA in myocardial tissues of mice after exhaustive exercise,and these differentially expressed RNAs form a regulatory network that affects cardiomyocyte synthesis and metabolism and thus participates in the regulation of myocardial injury.

System analysis based on the T cell exhaustion‑related genes identifies CD38 as a novel therapy target for ovarian cancer

Ovarian cancer(OV)is highly heterogeneous tumor with a very poor prognosis.Studies increasingly show that T cell exhaustion is prognostically relevant in OV.The aim of this study was to dissect the heterogeneity of T cell subclusters in OV through single cell transcriptomic analysis.The single RNA-sequencing(scRNA-seq)data of five OV patients were analyzed,and six major cell clusters were identified after threshold screening.Further clustering of T cell-associated clusters revealed four subtypes.Pathways related to oxidative phosphorylation,G2M checkpoint,JAK-STAT and MAPK signaling were significantly activated,while the p53 pathway was inhibited in the CD8+exhausted T cells.The standard marker genes of CD8+T cell exhaustion were screened to develop a T-cell related gene score(TRS)based on random forest plots in TCGA cohort.The patients with low TRS have better prognosis compared to the patients with high TRS in both TCGA and GEO.In addition,most genes included in the TRS showed significant differences in expression levels between the high-and low-risk groups.Immune cell infiltration was analyzed using the MCPcounter and xCell algorithms,which revealed significant differences between the two risk groups,indicating that the different prognoses may stem from the respective immune landscapes.In addition,CD38 knockdown in OV cell lines increased apoptosis and inhibited invasion in vitro.Finally,we performed a drug sensitivity analysis and identified six potential drug candidates for OV.To summarize,we identified the heterogeneity and clinical significance of T cell exhaustion in OV and built a superior prognostic model based on T cell exhaustion genes,which can contribute to the development of more precise and effective therapies.

The Effects of Job Insecurity, Emotional Exhaustion, and Met Expectations on Hotel Employees’ Pro-Environmental Behaviors: Test of a Serial Mediation Model

There are a plethora of empirical pieces about employees’pro-environmental behaviors.However,the extant literature has either ignored or not fully examined various factors(e.g.,negative or positive non-green workplace factors)that might affect employees’pro-environmental behaviors.Realizing these voids,the present paper proposes and tests a serial mediation model that examines the interrelationships of job insecurity,emotional exhaustion,met expectations,and proactive pro-environmental behavior.We used data gathered from hotel customer-contact employees with a time lag of one week and their direct supervisors in China.After presenting support for the psychometric properties of the measures via confirmatory analysis in LISREL 8.30,the abovementioned linkages were gauged using the PROCESS plug-in for statistical package for social sciences.The findings delineated support for the hypothesized associations.Specifically,emotional exhaustion and met expectations partly mediated the effect of job insecurity on proactive pro-environmental behavior.More importantly,emotional exhaustion and met expectations serially mediated the influence of job insecurity on proactive pro-environmental behavior.These findings have important theoretical implications as well as significant implications for diminishing job insecurity,managing emotional exhaustion,increasing met expectations,and enhancing ecofriendly behaviors.

Propagation of Gaussian Schell-Model Array Beams through a Jet Engine Exhaust

Here a Gaussian Shell Model Array (GSMA) beam is used to investigate the propagation characteristics in the jet engine exhaust region. It has great significance to improve various optical systems for wide application in trapping cold atoms, creating gratings, and atmospheric optical communication. We calculate analytical formulas for the spectral density (SD) and the propagation factors Mx2 and My2 of a GSMA beam. The influence of inner scale of turbulence in the jet engine exhaust region on its power spectrum has been also analyzed. According to these results, the influence of turbulence in a jet engine exhaust on a GSMA beam has been reduced by changing the parameters of light source and turbulence. For example, it is an excellent tool for mitigation of the jet engine exhaust-induced anisotropy of turbulence to increase the source coherence length, the root-mean-squared (rms) beam width, the wavelength or reduce the outer scale of turbulence.

Experiment Study on the Exhaust-Gas Heat Exchanger for Small and Medium-Sized Marine Diesel Engine

This paper aims to design a special exchanger to recover the exhaust gas heat of marine diesel engines used in small and medium-sized fishing vessels,which can then be used to heat water up to 55°C–85°C for membrane desalination devices to produce fresh water.A new exhaust-gas heat exchanger of fins and tube,with a reinforced heat transfer tube section,unequal spacing fins,a mixing zone between the fin groups and four routes tube bundle,was designed.Numerical simulations were also used to provide reference information for structural design.Experiments were carried out for exhaust gas waste heat recovery from a marine diesel engine in an engine test bench utilizing the heat exchanger.The experimental results show that the difference between heat absorption by water and heat reduction of exhaust gas is less than 6.5%.After the water flow rate was adjusted,the exhaust gas waste heat recovery efficiency was higher than 70%,and the exhaust-gas heat exchanger’s outlet water temperature was 55°C–85°C at different engine loads.This means that the heat recovery from the exhaust gas of a marine diesel engine meets the requirement to drive a membrane desalination device to produce fresh water for fishers working in small and medium-sized fishing vessels.

Contrasting Regional Responses of Indian Summer Monsoon Rainfall to Exhausted Spring and Concurrently Emerging Summer El Nino Events

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.

Design and Optimization of New Smoke Exhaust Pipe for Mining Trucks

In order to improve the maintenance efficiency,extend the use time,ensure that the exhaust emission meets the standard,forthe 830E truck heating bucket exhaust pipe design defects,the current single smoke exhaust system is transformed into atime period,convertible smoke exhaust system.After the transformation,it can not only realize the side row to prevent direct corrosion of the box bucket in summer,but also realize the heating of the box bucket at low temperature in winter to prevent snow and ice and frozen blocks from sticking to the box bucket and the materials transported.After the transformation can save a lot of manpower,material resources,financial resources,improve the service life.

基于进气节流耦合后喷策略的柴油机排气热管理

为研究柴油机颗粒物捕集器(diesel particulate filter,DPF)再生升温过程中排气热管理策略对柴油机氧化催化器(diesel oxidation catalyst,DOC)入口温度、发动机性能及污染物排放的影响,该研究分别选取低速低负荷、低速中负荷及中速低负荷工况,通过试验研究进气节流和喷油控制参数对DOC入口温度、燃油经济性及排放性能的影响。试验结果表明:通过进气节流、推迟后喷正时和增大后喷油量能够有效提高DOC入口温度,主喷正时和喷油压力对DOC入口温度的影响较小。基于Box-Behnken试验设计与响应曲面法对低速低负荷工况下进气节流耦合后喷策略的排气热管理策略进行多目标优化,以进气量、后喷正时和后喷油量为因子,DOC入口温度、有效燃油消耗率(brake specific fuel consumption,BSFC)、氮氧化合物(nitrogen oxides,NOx)和烟度排放为优化目标。响应曲面分析结果表明:各因素对DOC入口温度的影响程度从大到小为进气量、后喷油量、后喷正时;对BSFC和NOx排放的影响程度从大到小为后喷油量、后喷正时、进气量;对烟度排放的影响程度从大到小为进气量、后喷油量、后喷正时。当后喷正时为上止点后30℃A、进气量为87 kg/h、后喷油量为6 mg时,DOC入口温度达到最高,此时BSFC为275.4 g/(kW·h),NOx及烟度排放分别为7.38 g/(kW·h)和1.85 mg/m^(3)。优化后最佳进气量、后喷正时和后喷油量分别为87 kg/h、29℃A和5.4 mg,与优化前相比,DOC入口温度提升43.9℃,BSFC增加31.8 g/(kW·h),NOx和烟度排放分别降低18%和29%。研究结果可为DOC入口温度优化控制提供参考。

差异化授权型领导与知识型员工知识隐藏——基于跨层分析

基于团队和个体视角构建两个中介模型,探讨差异化授权型领导对知识型员工知识隐藏的内在作用机制。通过对67个团队的358位员工进行跨层检验,分析发现:在团队层面,差异化授权型领导通过降低团队信任,从而增强知识型员工知识隐藏动机;在个体层面,差异化授权型领导通过对知识型员工角色负荷、情绪耗竭的链式影响而诱发知识隐藏行为。上述结论丰富了差异化授权型领导影响后果研究,为促进团队成员知识分享与流动提供了重要的实践启示。

国Ⅵ直喷汽油机颗粒数量及微观形貌排气输运演变特性

开展了某一国Ⅵ直喷汽油机三元催化转化器(TWC)前、TWC后、汽油机颗粒捕集器(GPF)后3个位置的颗粒物采样及微观形貌研究,分析了发动机工况、TWC、GPF对国Ⅵ直喷汽油机尾气颗粒数量、粒径分布、微观形貌的影响。结果表明,该直喷汽油机尾气颗粒数量排放整体上呈单峰分布,低转速小负荷工况下,粒径<23nm的颗粒数量较高。随着发动机转速和负荷的增大,峰值粒径向大粒径方向移动。直喷汽油机尾气颗粒物由“核‒壳”结构基本碳粒子堆积形成,呈链状、枝状、簇状等结构;负荷增大,颗粒物尺寸略有增大,基本碳粒子重叠度增强,分形维数增大;转速增大,颗粒物尺寸减小,基本碳粒子重叠度减弱,分形维数减小。随着排气输运的进行,颗粒数量逐渐降低;TWC不影响颗粒的粒径分布形态,颗粒数量净化效率41.6%~94.2%,对<23 nm的小粒径颗粒净化效果较好,低转速小负荷工况的颗粒数量净化效率较高;GPF的颗粒数量净化效率约80%,23~100 nm颗粒数量净化效率较高,对粒径<10nm的颗粒净化作用不大。TWC和GPF不影响颗粒物结构形式,TWC和GPF后颗粒物基本碳粒子重叠度减弱,分形维数减小。

排烟口朝向与挡烟垂壁对地铁站台排烟效果的影响

为提高地铁站台的排烟效果,采用数值模拟方法,对地铁站不同排烟口朝向的机械排烟系统排烟效果进行分析,并进一步对比挡烟垂壁高度对排烟效果影响。研究结果表明:排烟口朝向不是影响烟气控制效果的主要因素,顶面排烟的排烟效果最佳,其总排热量是底面排烟的1.32倍,总排烟量是底面排烟的1.19倍;并通过分析3种排烟系统吸入烟气的方式和温度解释排烟效果产生差异的原因;增设挡烟垂壁可起到良好的控烟效果,当挡烟垂壁下沿高度分别降低至3.5,3.0,2.5 m时,顶面排烟,侧面排烟和底面排烟能够将烟气控制在起火防烟分区;挡烟垂壁与机械排烟系统具有协同作用,设置挡烟垂壁可以有效改善排烟效果,因此建议采用排烟管道顶面开口的排烟方式,并可通过设置一定高度的挡烟垂壁提高现有排烟系统的排烟效果。研究结果可为地铁站台排烟系统设计提供参考与借鉴。

助推段火箭发动机喷焰红外辐射特性数值计算

助推段火箭发动机尾喷焰具有显著的红外辐射特性,成为天基红外预警系统重点关注的对象。以三组元固体发动机为研究对象,建立连续流域和过渡流域的尾喷焰反应流场计算模型,采用两级助推段质心弹道法确定飞行弹道,通过反向寻优法完备发动机型谱参数,基于等效单喷管法简化流场计算,基于窄谱带法和视在光线法计算尾喷焰的红外辐射特性。研究结果表明:复燃效应使得尾喷焰红外辐射光谱强度升高约20倍,谱带积分强度升高约10倍;尾喷焰红外光谱存在2.7μm和4.3μm的特征峰值;低空流域的光谱强度较高,且不同谱带内积分强度随高度的升高呈现出波动规律和暗区现象;助推段尾喷焰辐射强度差值高达3个量级,尤其在4.3μm较为明显。所得成果可为火箭在助推段的探测和识别提供一定的理论参考。

基于不同能量回收模式的燃料电池系统性能增益研究

为减小燃料电池进气增压寄生功、提高系统效率,建立了以径流涡轮回收阴极排气能量的高功率燃料电池电化学、动力学与热力学系统模型,修正了基于NTU-ε法的中冷器性能预测方法,研究了单级增压−能量回收与顺序增压−能量回收模式下径流涡轮回收燃料电池阴极废气能量的效能.结果表明,整体能量回收效率随着电堆负载电流增加呈降低趋势;相比于单级增压−能量回收模式,在额定工况点与非额定工况点下顺序增压−能量回收模式的能量利用率增益显著.优化后的运行方案阴极排气能量利用率最高可提升28.9%,系统效率提升幅值达2.79%.

乏汽供热用大型蒸汽射汽器性能试验与研究

对乏汽供热用大型射汽器的性能进行了全面分析和研究。结合射汽器的固有特性,在300 MW等级机组的乏汽供热系统中对射汽器变工况性能进行了试验研究,得到了不同机组背压、动力蒸汽压力和出口压力下射汽器的性能曲线。建立了一种射汽器全工况特性的性能参数求解方法。结果表明:性能参数求解结果与试验数据吻合度高。

侧部双点排烟模式排热效率研究

为探究隧道火灾侧部排烟口排热效率的表达公式,采用理论分析推导出排热效率与火灾热释放速率、排烟风速、排烟口距地面高度、排烟口间距4个影响参数的量纲一关系式,通过FDS数值模拟研究不同因素影响下的烟流特征并对数据进行拟合,确定了排热效率与这4个影响参数的关系。结果表明,在侧部双点排烟模式下,排热效率随火灾热释放速率增大呈-0.33次方减小关系,与排烟口排烟风速呈0.23次方增长关系,与排烟口距地面高度呈1.25次方增长关系,与排烟口间距呈-0.57次方减小关系,最终通过线性拟合建立了考虑吸穿影响的侧部双点排烟模式下排烟口处排热效率的模型。研究结果可为隧道侧部排烟系统的设计提供参考。

电控放气阀涡轮增压器在柴油机上的试验研究

在一台满足国六b阶段排放标准的柴油机上,开展电控放气阀涡轮增压器对发动机性能、排放影响的试验研究。试验验证表明:发动机匹配电控放气阀涡轮增压器在发动机中高转速工况对油耗有一定改善,在中低负荷工况能降低油耗、提高排气温度。通过电控放气阀开度特性优化并确定最优的控制参数,在WHTC循环SCR催化器平均温度从226℃提升到246℃,冷态WHTC循环NOx排放降低25%,冷热加权NOx排放降低8.6%。

医护协作性、心理韧性对医务人员情绪衰竭的影响

目的:调查医务人员的情绪衰竭、心理韧性和医护协作性情况,探索三者间关联性。方法:采用一般资料问卷、Maslash职业倦怠量表通用版(MBI-GS)中情绪衰竭维度、简式心理韧性量表(BRS),以及医护合作量表(NPCS)中医护协作性维度对浙江省281名医务人员进行问卷调查,收集有效样本230份。建立结构方程模型,分析医护协作性、心理韧性和情绪衰竭的关联性。结果:医务人员情绪衰竭得分(1.62±0.64),心理韧性得分(3.22±0.63),医护协作性得分(22.53±5.27);心理韧性和医护协作性对情绪衰竭的标准化路径系数分别为-0.627(P<0.01)和-0.118(P<0.05),心理韧性与医护协作性的相关性不显著。结论:心理韧性、医护协作性对医务人员情绪衰竭都有负向影响,其中心理韧性的影响更显著。建议通过叙事医学赋能医院管理,通过社会支持和自我赋能促进医护协作和员工心理韧性,进而缓减情绪衰竭。