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).

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.

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.

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.

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.

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.

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.

INVESTIGATION IN REDUCING EXHAUST EMISSIONS FROM TWO STROKE MOTORCYCLES

Test results of reducing two stroke motorcycle emissions with new type carburettors and electronic fuel injection systems are presented. Analyses and comparison between different systems are discussed. The adoption of electronically controlled injection and corresponding electronic control technique is an effective measure of prolonged vitality to improve emissions from two stroke motorcycles. Suggestions about the strategic steps of China′s motorcycle emission control are proposed.

Transitional Road of Resources-exhausted Cities to Low-carbon Economy:Tourism Resources Development——A Case Study of Gejiu City

Tourism is of vital practical significance to low-carbon economic transition of resources-exhausted cities.By taking Gejiu City of Yunnan Province for example,the paper discussed that Gejiu City as the resources-exhausted city should positively develop tourism,particularly industrial heritage tourism,treating tourism development as the breakthrough and motive power of low-carbon economic transition of resources-exhausted cities,so as to walk out a unique road of tourism promoting low-carbon economic development.

Computation of Electromagnetic Properties of Mildly Overexpanded and Underexpanded Rocket Exhaust Plume

An improved near far field divided coupled method was established to investigate the electromagnetic properties of mildly overexpanded and underexpanded rocket exhaust plumes. Firstly, axisymmetric Navier Stokes equations incorporated with k ε two equation turbulence models were solved using time dependent approach to calculate the pressure of the near filed. Secondly, parabolized axisymmetric Navier Stokes equations incorporated with finite rate chemical kinetics models were marching on the detailed pressure map of the near field. The termination of the near field would yield the initial line for the far field. In addition, in the far field, the spatial marching method was directly used under the constant pressure condition, but considering more complicated chemically reacting process. Finally, the electromagnetic parameters of the whole plume were calculated with the electron conductive model. The calculated results of the overexpanded and underexpanded rocket exhaust plume were discussed. The predicted microwave attenuation accorded with the experimental results. This improved method is feasible for calculating the microwave attenuation characteristics of mildly non fully expanded rocket exhaust plumes.

Influence of driving cycles on exhaust emissions and fuel consumption of gasoline passenger car in Bangkok

The influence of different driving cycles on their exhaust emissions and fuel consumption rate of gasoline passenger car was investigated in Bangkok based on the actual measurements obtained from a test vehicle driving on a standard chassis dynamometer. A newly established Bangkok driving cycle （BDC） and the European driving cycle （EDC） which is presently adopted as the legislative cycle for testing automobiles registered in Thailand were used. The newly developed BDC is constructed using the driving characteristic data obtained from the real on-road driving tests along selected traffic routes. A method for selecting appropriate road routes for real driving tests is also introduced. Variations of keyed driving parameters of BDC with different driving cycles were discussed. The results showed that the HC and CO emission factors of BDC are almost two and four times greater than those of EDC, respectively. Although the difference in the NOx emission factor is small, the value from BDC is still greater than that of EDC by 10%. Under BDC, the test vehicle consumes fuel about 25% more than it does under EDC. All these differences are mainly attributed to the greater proportion of idle periods and higher fluctuations of vehicle speed in the BDC cycle. This result indicated that the exhausted emissions and fuel consumption of vehicles obtained from tests under the legislative modal-type driving cycle （EDC） are significantly different from those actually produced under real traffic conditions especially during peak periods.

Late cardioprotection of exercise preconditioning against exhaustive exercise-induced myocardial injury by up-regulatation of connexin 43 expression in rat hearts

Objective: To investigate the expression of myocardium connexin 43(Cx43) in late exercise preconditioning(LEP) cardioprotection. Methods: Eight-week-old adult male Sprague Dawley rats were randomly assigned into four groups(n=8). Myocardial injury was judged in accordance with serum levels of c Tn and NT-pro BNP as well as hematoxylin basicfuchsin picric acid staining of myocardium. Cx43 m RNA was detected by in situ hybridization and qualified by real-time fluorescence quantitative PCR. Cx43 protein was localized by immunohistochemistry and its expression level was determined by western blotting. Results: The LEP obviously attenuated the myocardial ischemia/hypoxia injury caused by exhaustive exercise. There was no significant difference of Cx43 m RNA level between the four groups. Cx43 protein level was decreased significantly in group EE(P<0.05). However, LEP produced a significant increase in Cx43 protein level(P<0.05), and the decreased Cx43 protein level in exhaustive exercise was significantly up-regulated by LEP(P<0.05). Conclusions: LEP protects rat heart against exhaustive exercise-induced myocardial injury by up-regulating the expression of myocardial Cx43.

Experimental Study of Thermoelectric Heat Pump Water Heater with Exhaust Heat Recovery from Kitchens

A new kind of thermoelectric heat pump water heater for kitchens exhaust heat recovery was presented,and its performances were investigated under different operating voltages.The experiment results show that the coefficient of performance decreases and the temperature difference between the hot and cold sides becomes larger with the increase of the operating voltage,but the heating time becomes short.The higher the temperature of water,the greater the temperature difference between the hot and cold sides,leading to a smaller coefficient of performance.Under an exhaust temperature of 36 ℃,the coefficient of performance decreases from 1.66 to 1.22 when the temperature of water increases from 28 ℃ to 46 ℃ with operating voltage 16 V.Performance tests illustrate that,compared with the conventional electrical water heaters,the new kind of thermoelectric heat pump water heater is more coefficient.

Stability of Cu-Mn bimetal catalysts based on different zeolites for NO_x removal from diesel engine exhaust

Cu–Mn bimetal catalysts were prepared to remove nitrogen oxides(NOx)from diesel engine exhaust at low temperatures.At a Cu/Mn ratio of 3:2,the NOx conversions at 200°C reached 65%and 90%on Cu–Mn/ZSM‐5 and Cu–Mn/SAPO‐34,respectively.After a hydrothermal treatment and reaction in the presence of C3H6,the activity of Cu–Mn/SAPO‐34 was more stable than that of Cu–Mn/ZSM‐5.No obvious variations in the crystal structure or dealumination were observed,whereas the physical structure was best maintained in Cu–Mn/SAPO‐34.The atomic concentration of Cu on the surface of Cu–Mn/SAPO‐34 was quite stable,and the consumption of octahedrally coordinated Cu2+could be recovered.Conversely,the proportion of octahedrally coordinated Cu2+on the surface of Cu–Mn/ZSM‐5 significantly decreased.Therefore,besides the structure,the redox cycle between Cu+and octahedrally coordinated Cu2+played an important role in the stability of the catalysts.

Optimum Tilt Angle of Flow Guide in Steam Turbine Exhaust Hood Considering the Effect of Last Stage Flow Field

Abstract Heat transfer and vacuum in condenser are influenced by the aerodynamic performance of steam tur- bine exhaust hood. The current research on exhaust hood is mainly focused on analyzing flow loss and optimal design of its structure without consideration of the wet steam condensing flow and the exhaust hood coupled with the front and rear parts. To better understand the aerodynamic performance influenced by the tilt angle of flow guide inside a diffuser, taking a 600 MW steam turbine as an example, a numerical simulator CFX is adopted to solve compressible three-dimensional （3D） Reynolds time-aver- aged N-S equations and standard k-e turbulence model. And the exhaust hood flow field influenced by different tilt angles of flow guide is investigated with consideration of the wet steam condensing flow and the exhaust hood coupled with the last stage blades and the condenser throat. The result shows that the total pressure loss coefficient and the static pressure recovery coefficient of exhaust hood change regularly and monotonously with the gradual increase of tilt angle of flow guide. When the tilt angle of flow guide is within the range of 30~ to 40~, the static pressure recovery coefficient is in the range of 15.27% to 17.03% and the total pressure loss coefficient drops to approximately 51%, the aerodynamic performance of exhaust hood is significantly improved. And the effectiveenthalpy drop in steam turbine increases by 0.228% to 0.274%. It is feasible to obtain a reasonable title angle of flow guide by the method of coupling the last stage and the condenser throat to exhaust hood in combination of the wet steam model, which provides a practical guidance to flow guide transformation and optimal design in exhaust hood.

Exhausted T cells and epigenetic status

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.

Optimization of gasoline hydrocarbon compositions for reducing exhaust emissions

Effects of hydrocarbon compositions on raw exhaust emissions and combustion processes were studied on an engine test bench. The optimization of gasoline hydrocarbon composition was discussed. As olefins content increased from 10.0% to 25.0% in volume, the combustion duration was shortened by about 2 degree crank angle （°CA）, and the engine-out THC emission was reduced by about 15%. On the other hand, as aromatics content changed from 35.0% to 45.0%, the engine-out NOx emissions increased by 4%. An increment in olefins content resulted in a slight increase in engine-out CO emission, while the aromatics content had little effect on engine-out total hydrocarbon （THC） and CO emissions. Over the new European driving cycle （NEDC）, the THC, NOx and CO emissions of fuel with 25.0% olefins and 35.0% aromatics were about 45%, 21% and 19% lower than those of fuel with 10.0% olefins and 40.0% aromatics, respectively. The optimized gasoline compositions for new engines and new vehicles have low aromatics and high olefins contents.