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.

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.

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.

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.

基于多元储能的分布式能源系统优化调度方法研究

为进一步构建清洁低碳、经济节能的供能系统,研究建立了含风、光以及多元储能的分布式能源系统,针对北京某办公园区,采用DeST预测用户负荷以及当地风、光条件。以经济性、节能性和环保性三方面的综合效益最大为目标,提出一种自适应优化运行策略,分别采用穷举搜索法和遗传算法对系统优化调度方案进行优化。同时,采用以电定热运行策略作为对照,对比分析几种不同运行策略下系统的综合效益。结果表明:传统以电定热运行模式下的综合效益平均值为0.41;而在自适应优化运行策略下,使用遗传算法得到的调度方案,其综合效益平均值可达0.5,穷举搜索法得到的运行方案,其综合效益平均值可达0.51。

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。

感知算法控制的双刃剑效应对零工工作者情绪耗竭的影响:基于合法性判断视角

基于279份来自零工工作者的问卷调查数据,以公平、隐私、自主合法性判断为中介变量,以人工智能风险观念为调节变量,探讨感知算法控制的双刃剑效应对零工工作者情绪耗竭的影响。研究结果表明:合法性判断负向影响零工工作者情绪耗竭且完全中介了感知算法控制对情绪耗竭的影响;感知算法规范指导通过公平合法性判断负向影响零工工作者情绪耗竭,感知算法追踪评估通过隐私合法性判断正向影响零工工作者情绪耗竭,感知算法行为约束通过自主合法性判断正向影响零工工作者情绪耗竭;人工智能风险观念强化了感知算法追踪评估对隐私合法性判断的负向影响。

石墨烯复合载体催化剂在柴油车尾气NO脱除中的应用

氨气选择性催化还原法有利于柴油车尾气中NO的脱除,为适合柴油车尾气条件和温度,制备一种石墨烯和TiO_(2)复合载体的脱硝催化剂,通过NH_(3)-SCR催化活性评价、X射线衍射(XRD)、扫描电子显微镜(SEM)、比表面积与孔隙度分析仪(BET)和程序升温还原(H_(2)-TPR)等表征得出以下结论:对于TiO_(2)载体催化剂,高含量的Ce有利于提高NH_(3)-SCR催化活性,并扩宽活性温度区间,活性组分Fe有利于其低温活性;对于石墨烯载体催化剂,活性组分Ce的催化活性更优越,但Fe更有利于高温活性;针对TiO_(2)和石墨烯复合载体脱硝催化剂,进一步扩宽了催化活性温度区间,改善催化剂反应过程中的粉化现象,但是催化活性略有下降,其中Fe0.1Ce0.4Ti/10%GR催化剂具有最优的NH_(3)-SCR活性,在220~450℃温度区间内NO转化率达到90%以上。

不同尾气热管理策略对当量天然气发动机WHTC循环排放的影响

国六天然气发动机采用等当量燃烧结合外部冷却EGR及TWC的排放控制技术路线,TWC的转化效率是保证发动机排放达标的重要因素,而催化器的入口温度是决定TWC转化效率高低的最重要影响参数之一。然而,在冷起动阶段及排气管路温降较大的情况下,存在TWC入口尾气温度难以满足发动机及整车排放高效转化需求的问题。针对该问题,在一台4.5 L排量的发动机和一辆搭载该发动机的城市环卫车上探究不同尾气热管理策略对发动机WHTC循环排放及整车作业循环排放的影响。研究结果表明:采用起动快速温升的尾气热管理策略,能有效提高冷起动阶段发动机尾气温度,WHTC循环的TWC入口温度达到300℃所需时间缩短了300 s,显著降低了NO_(x),CH 4和CO循环排放,降幅分别达到38.5%,38.5%和5.8%;采取在TWC上增加金属载体前级方案的尾气控制策略,WHTC循环的NO_(x),CH 4和CO循环排放分别降低了62.2%,42.8%和15.7%;采用对整车排气尾管包裹的尾气热管理策略,在整车作业循环工况下,TWC入口温度相比采用普通石棉包裹的方案提高了近200℃,使得NO_(x)瞬时排放值30 s平均值的最大值降低了60.9%,能更好地满足北京第六阶段的排放法规要求。

厚朴排气合剂联合经皮穴位电刺激对产后抑郁合并胃肠功能障碍患者胃肠功能及抑郁情绪的影响

目的:探讨厚朴排气合剂联合经皮穴位电刺激对产后抑郁合并胃肠功能障碍的临床效果。方法:将120例产后抑郁合并胃肠功能障碍患者随机分为观察组(n=60)和对照组(n=60)。对照组给予经皮穴位电刺激治疗,观察组给予厚朴排气合剂联合经皮穴位电刺激治疗,疗程均为7 d。比较两组患者胃肠功能恢复情况、胃肠道障碍症状评分、胃泌素(GAS)、胃动素(MTI)、腹胀发生率、腹胀程度、汉密尔顿抑郁量表评分以及不良反应发生情况。结果:与对照组相比,观察组患者的肠鸣音恢复、首次肛门排气、首次排便、总住院时间明显更短(P<0.05)。治疗后,两组患者胃肠道障碍症状评分均明显下降,观察组低于对照组(P<0.05)。治疗后,两组患者GAS、MTI水平和治疗前相比均明显升高,且观察组高于对照组(P<0.05)。治疗后,观察组患者腹胀发生率为11.7%,低于对照组的30.0%(P<0.05)。治疗后,观察组患者腹胀程度明显低于对照组(P<0.05)。治疗后,两组患者抑郁状态评分均明显下降,观察组低于对照组(P<0.05)。两组不良反应发生率(6.7%与5.0%)比较差异无统计学意义(P>0.05)。结论:厚朴排气合剂联合经皮穴位电刺激可有效促进产后抑郁合并胃肠功能障碍患者胃肠功能恢复,缓解腹胀和抑郁情绪,而且不会明显增加不良反应发生率。

岩巷综掘面抽尘参数影响粉尘污染扩散规律研究

抽尘系统是岩巷综掘面长压短抽通风方式中控除粉尘污染的重要组成部分,而确定适宜的抽尘参数是实现有效除尘的关键。利用Solidworks软件对某矿632岩巷综掘面进行了物理建模,并进行了ICEM-CFD网格划分,通过网格无关性检验确认了后续所用的网格模型,运用FLUENT计算流体力学软件对不同抽尘位置Dn(n分别为0、1/4、1/2、3/4、1)与抽风量(300~350 m^(3)/min)影响粉尘污染扩散状况进行了数值模拟,并通过仿真试验验证了数值模拟结果的准确性。结果表明:抽尘位置为D0、D1/4、D1/2、D3/4时,巷道内风流整体均处于较为紊乱的状态,粉尘污染经风流运载最终均扩散至整个巷道;抽尘位置为D1时,在抽风与压风协同作用下,距迎头4.6~6 m范围内形成了风向指向迎头、流动均匀且覆盖巷道全断面的有效控尘风幕,粉尘污染被风幕控制在掘进机司机与迎头之间的封闭空间内。抽风量在330 m^(3)/min及以上时,在司机处均形成了有效控尘风幕。为了在有效控尘的前提下尽可能降低能耗,最优抽风量选取最小值330 m^(3)/min。

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。

基于切削仿真的缸体进排气面铣削优化

针对缸体进排气面凸台铣削余量大、刀具耐用度低的技术问题,运用切削仿真技术对铣削参数进行分析。在确保切削负载、切削温度的前提下,通过优化加工程序提升加工效率和刀具耐用度。

泥蚶提取物抗氧化及抗运动性疲劳作用研究

为开发利用泥蚶资源,探究泥蚶水提物和醇提物的抗氧化及抗运动性疲劳作用效果,以1,1-二苯基-2-三硝基苯肼(1,1-diphenyl-2-picrylhydrazyl,DPPH)自由基清除能力、超氧阴离子(O_(2)^(-))自由基清除能力、抑制β-胡萝卜素褪色能力为指标评价泥蚶提取物的体外抗氧化作用。通过测定小鼠转棒停留时间、负重力竭游泳时间及小鼠运动后体内相关血清生化指标变化情况,分析泥蚶提取物的抗运动性疲劳作用效果。实验结果表明,泥蚶醇提物对DPPH、O_(2)^(-)自由基的清除能力及抑制β-胡萝卜素-亚油酸体系的褪色能力较强,其半抑制浓度(half maximal inhibitory concentration,IC_(50))分别为1.38、1.87、2.07 mg/mL。泥蚶水提物高剂量组对应的小鼠转棒停留时间为64.10±1.86 s、负重力竭游泳时间为102.55±2.49 min,并呈剂量-效应关系;另外,高剂量泥蚶水提物还可提高小鼠运动后体内肝糖原和肌糖原含量,降低尿素氮和血乳酸水平,其结果分别为16.36±0.42 mg/g、2.56±0.22 mg/g、7.84±0.31 mmol/L、3.44±0.25 mmol/L,与泥蚶醇提物各组差异显著(P<0.05)。该研究可为泥蚶的深度开发与利用提供理论依据。