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Unlocking T cell exhaustion:Insights and implications for CAR-T cell therapy

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3416-3431页

作者： dian Xiong Haijun Yu Zhi-Jun Sun State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyFrontier Science Center for Immunology and MetabolismTaikang Center for Life and Medical ScienceWuhan UniversityWuhan 430079China Department of Radiation and Medical Oncology Hubei Province Cancer Clinical Study CenterHubei Key Laboratory of Tumor Biological BehaviorsZhongnan Hospital of Wuhan UniversityWuhan 430071China

Chimeric antigen receptor T(CAR-T)cell therapy as a form of adoptive cell therapy(ACT)has shown significant promise in cancer treatment,demonstrated by the FDA-approved CAR-T cell therapies targeting CD19 or B cell maturation antigen(BCMA)for hematological malignancies,albeit with moderate outcomes in solid ***,despite these advancements,the efficacy of CAR-T therapy is often compromised by T cell exhaustion,a phenomenon that impedes the persistence and effector function of CAR-T cells,leading to a relapse rate of up to 75%in patients treated with CD19 or CD22 CAR-T cells for hematological *** to overcome CAR-T exhaustion employ state-of-the-art genomic engineering tools and single-cell sequencing *** this review,we provide a comprehensive understanding of the latest mechanistic insights into T cell exhaustion and their implications for the current efforts to optimize CAR-T cell *** insights,combined with lessons learned from benchmarking CAR-T based products in recent clinical trials,aim to address the challenges posed by T cell exhaustion,potentially setting the stage for the development of tailored next-generation approaches to cancer treatment.

关键词： Cancer immunotherapy CAR-T therapy T cell exhaustion Tumor immune microenvironment Spatial immune contexture Single-cell technologies CAR-T engineering Combination therapy

PAPS: Progressive Attention-Based Pan-sharpening

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IEEE/CAA Journal of Automatica Sinica 2024年第2期11卷 391-404页

作者： Yanan Jia Qiming Hu Renwei dian Jiayi Ma Xiaojie Guo College of Intelligence and Computing Tianjin UniversityTianjin 300350 China IEEE School of Robotics Hunan UniversityChangsha 410082China Electronic Information School Wuhan UniversityWuhan 430072China

Pan-sharpening aims to seek high-resolution multispectral(HRMS) images from paired multispectral images of low resolution(LRMS) and panchromatic(PAN) images, the key to which is how to maximally integrate spatial and spectral information from PAN and LRMS images. Following the principle of gradual advance, this paper designs a novel network that contains two main logical functions, i.e., detail enhancement and progressive fusion, to solve the problem. More specifically, the detail enhancement module attempts to produce enhanced MS results with the same spatial sizes as corresponding PAN images, which are of higher quality than directly up-sampling LRMS *** a better MS base(enhanced MS) and its PAN, we progressively extract information from the PAN and enhanced MS images, expecting to capture pivotal and complementary information of the two modalities for the purpose of constructing the desired HRMS. Extensive experiments together with ablation studies on widely-used datasets are provided to verify the efficacy of our design, and demonstrate its superiority over other state-of-the-art methods both quantitatively and qualitatively. Our code has been released at https://***/JiaYN1/PAPS.

关键词： High-resolution multispectral image image fusion pan-sharpening progressive enhancement

Suspended particulate matter promotes epithelial-to-mesenchymal transition in alveolar epithelial cells via TGF-β1-mediated ROS/IL-8/SMAD3 axis

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Journal of Environmental Sciences 2024年第7期141卷 139-150页

作者： Shahrzad Molavinia.dian.Dayer Mohammad Javad Khodayar Gholamreza Goudarzi Maryam Salehcheh Cellular and Molecular Research Center Medical Basic Sciences Research InstituteAhvaz Jundishapur University of Medical SciencesAhvazIran Department of Toxicology School of PharmacyAhvaz Jundishapur University of Medical SciencesAhvazIran Student Research Committee Ahvaz Jundishapur University of Medical SciencesAhvazIran Toxicology Research Center Medical Basic Sciences Research InstituteAhvaz Jundishapur University of Medical SciencesAhvazIran Air Pollution and Respiratory Diseases Research Center Ahvaz Jundishapur University of Medical SciencesAhvazIran Iranian Scientific Association of Clean Air TehranIran

Epidemiological evidence presents that dust storms are related to respiratory diseases,such as pulmonary fibrosis(PF).However,the precise underlying mechanisms of SPM-elicited adverse effects still need to be ***-mesenchymal transition(EMT)process is a characteristic of *** discussed whether suspended particulate matter(SPM)is involved in EMT induction via transforming growth factor-β1(TGF-β1).In this study,a detailed elemental analysis(55 elements),particle size,and morphology were *** investigate the toxicity of SPM,an MTT test was performed to detect cell ***,A549cells were exposed to selected concentrations of SPM(20 and 40μg/mL)for single and repeated *** DCFH-DA assay showed that exposure to SPM could produce reactive oxygen species(ROS).The ELISA assay demonstrated increased levels of interleukin-8(IL-8)and TGF-β1 in the *** blot was used to detect the expression of proteins associated with EMT and the SMAD3-dependent *** of western blot demonstrated that E-cadherin was reduced,whereas p-SMAD3,vimentin,andα-smooth muscle actin were *** findings indicated that SPM triggered EMT by induction of oxidative stress,inflammation,and the TGF-β1/SMAD3 pathway activation.

关键词： Particulate matter TGF-β1 Oxidative stress Epithelial-mesenchymal transition Pulmonary fibrosis Cells

Evolutionary Optimization Methods for High-Dimensional Expensive Problems:A Survey

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IEEE/CAA Journal of Automatica Sinica 2024年第5期11卷 1092-1105页

作者： MengChu Zhou Meiji Cui dian Xu Shuwei Zhu Ziyan Zhao Abdullah Abusorrah Department of Electrical and Computer Engineering New Jersey Institute of TechnologyNewarkNJ 07102 USA School of Information and Electronic Engineering Zhejiang Gongshang UniversityHangzhou 310018China School of Intelligent Manufacturing Nanjing University of Science and TechnologyNanjing 210094China Institute of Systems Engineering Macao University of Science and TechnologyMacao 999078China School of Artificial Intelligence and Computer Jiangnan UniversityWuxi 214122China School of Information Science and Engineering Northeastern UniversityShenyang 110819China Center of Research Excellence in Renewable Energy and Power Systems Department of Electrical and Computer EngineeringFaculty of EngineeringKing Abdulaziz UniversityJeddah 21589Saudi Arabia K.A.CARE Energy Research and Innovation Center King Abdulaziz UniversityJeddah 21589Saudi Arabia

Evolutionary computation is a rapidly evolving field and the related algorithms have been successfully used to solve various real-world optimization *** past decade has also witnessed their fast progress to solve a class of challenging optimization problems called high-dimensional expensive problems(HEPs).The evaluation of their objective fitness requires expensive resource due to their use of time-consuming physical experiments or computer ***,it is hard to traverse the huge search space within reasonable resource as problem dimension *** evolutionary algorithms(EAs)tend to fail to solve HEPs competently because they need to conduct many such expensive evaluations before achieving satisfactory *** reduce such evaluations,many novel surrogate-assisted algorithms emerge to cope with HEPs in recent *** there lacks a thorough review of the state of the art in this specific and important *** paper provides a comprehensive survey of these evolutionary algorithms for *** start with a brief introduction to the research status and the basic concepts of ***,we present surrogate-assisted evolutionary algorithms for HEPs from four main *** also give comparative results of some representative algorithms and application ***,we indicate open challenges and several promising directions to advance the progress in evolutionary optimization algorithms for HEPs.

关键词： computer optimization evolutionary

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Frontiers of Nursing 2024年第1期11卷 111-117页

作者： dian Hudiyawati Kartinah Afidatul Mujannidah Department of Medical Surgical Nursing School of NursingUniversitas Muhammadiyah SurakartaJawa Tengah 57169Indonesia Department of Geriatic Nursing School of NursingUniversitas Muhammadiyah SurakartaJawa Tengah 57169Indonesia Department of Nursing School of NursingUniversitas Muhammadiyah SurakartaJawa Tengah 57169Indonesia

Objective:To determine factors that affect the health-related quality of life(HRQOL)of congestive heart failure(CHF)patients with preserved and reduced ejection ***:A cross-sectional study design was used for this *** stratified random sampling was applied for each *** was measured with the Minnesota Living with Hear t Failure *** data were analyzed using chi-square,Spearman's correlation analysis,and independent ***:A number of 67 respondents participated in the recent *** total mean scores of HRQOL were significantly different(P=0.001)between heart failure(HF)patients with reduced and preserved ejection fractions,41.07±7.54 and 54.97±4.36,*** related with the physical(mean±standard deviation[SD]=10.4±2.14;t=-10.08,95%CI=-12.46 to-8.34;P-value=0.001)and psychological(mean±SD=3.5±0.5;t=-6.68,95%CI=-4.55 to-2.45;P-value=0.001)*** correlation was found between age(r=-0.898,P<0.05),NYHA functional classes(r=-0.858,P<0.01),duration of HF(r=-0.807,P<0.01),family support(r=0.927,P<0.01),and quality of life(Qo L).Conclusions:HRQOL in HF patients with reduced ejection fraction was higher than in those with preserved ejection *** suppor t is a fur ther determinant factor that has a positive correlation to the Qo L.

关键词： ejection fraction family support heart failure quality of life social support

Numerical study on ignition start-up process of an underwater solid rocket motor across a wide depth range

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Chinese Journal of Aeronautics 2024年第10期37卷 136-157页

作者： Deyou WANG Shipeng LI Ge JIN Ruyao WANG dian GUAN Ningfei WANG School of Aerospace Engineering Beijing Institute of TechnologyBeijing 100081China Beijing System Design Institute of Electro-mechanic Engineering Beijing 100854China

Solid rocket motors have important applications in the propulsion of trans-media vehicles and underwater launched *** this paper,the ignition start-up process of an underwater solid rocket motor across a wide depth range has been numerically studied.A novel multi-domain integrated model has been developed by combining the solid propellant ignition and combustion model with the volume of fluid multiphase *** integrated model enables the coupled simulation of the propellant combustion and gas flow inside the motor,along with the gas jet evolution in the external water *** detailed flow field developments in the combustion chamber,nozzle,and wake field are carefully *** variation rules of the internal ballistics and thrust performance are also *** effects of environmental medium and operating depth on the ignition start-up process are systematically *** results show that the influence of the operating environment on the internal ballistic characteristics is primarily reflected in the initial period after the nozzle closure *** development of the gas jet in water lags significantly compared with that in *** the water depth increases,the ignition delay time of the motor is shortened,and the morphology evolution of the gas jet is significantly compressed and ***,the necking and bulging of the jet boundary near the nozzle outlet and the consequent shock oscillations are intensified,resulting in stronger fluctuations in the wake pressure field and motor thrust.

关键词： Underwater propulsion Solid rocket motor Ignition start-up process Underwater gas jet Thrust oscillation

Effects of freeze-thaw cycles on sandstone in sunny and shady slopes

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第7期16卷 2503-2515页

作者： dian Xiao Xiaoyan Zhao Corrado Fidelibus Roberto Tomás Qiu Lu Hongwei Liu Academy of Railway Sciences Corporation Limited BeijingChina Faculty of Geosciences and Environmental Engineering Southwest Jiaotong UniversityChengduChina Department of Civil Engineering University of AlicanteAlicanteSpain Department of Innovation Engineering University of SalentoLecceItaly Department of Earth and Environmental Sciences University of Milano BicoccaMilanItaly

A growing rock engineering activity in cold regions is facing the threat of freeze-thaw(FT)weathering,especially in high mountains where the sunny-shady slope effects strongly control the difference in weathering behavior of *** this paper,an investigation of the degradation of petrophysical characteristics of sandstone specimens subjected to FT cycle tests to simulate the sunny-shady slope effects is *** this aim,non-destructive and repeatable testing techniques including weight,ultrasonic waves,and nuclear magnetic resonance methods on standard specimens were *** the sunny slope specimens,accompanied by the enlargement of small pores,100 FT cycles caused a significant decrease in P-wave velocity with an average of 23%,but a consistent rise of 0.18%in mass loss,34%in porosity,67%in pore geometrical mean radius,and a remarkable 14.5-fold increase in ***,slight changes with some abnormal trends in physical parameters of the shady slope specimens were observed during FT cycling,which can be attributed to superficial granular disaggregation and pore throat *** shocks enhance rock weathering on sunny slopes during FT cycles,while FT weathering on shady slopes is restricted to the small pores and the superficial *** two factors are primarily responsible for the differences in FT weathering intensity between sunny and shady *** conclusions derived from the interpretation of the experimental results may provide theoretical guidance for the design of slope-failure prevention measures and the selection of transportation routes in cold mountainous regions.

关键词： Sunny-shady slope Freeze and thaw Pore structure Tight rocks Talus slope Cold regions

Superatom-assembled boranes,carboranes,and low-dimensional boron nanomaterials based on aromatic icosahedral B_(12)and C_(2)B_(10)

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Nano Research 2024年第7期17卷 6734-6740页

作者： Qiao-Qiao Yan Yan-Fang Wei Qiang Chen Yue-Wen Mu Si-dian Li Institute of Molecular Science Shanxi UniversityTaiyuan 030006China

Using the experimentally known aromatic icosahedral superatoms I_(h)B_(12)H_(12)2−and D_(5d)1,12-C_(2)B_(10)H_(12)as building blocks and based on extensive density functional theory calculations,we predict herein a series of core–shell superpolyhedral boranes and carboranes in a bottom-up approach,including the high-symmetry Th B_(12)@B_(152)H_(72)2−(2),C2h C_(2)B_(10)@B_(152)H_(72)(3),D_(3d)B_(12)@B_(144)H_(66)(4),I_(h)B_(12)@C_(24)B_(12)0H_(72)2−(6),and D_(5d)C_(2)B_(10)@C_(24)B_(12)0H_(72)(7).More interestingly,the superatom-assembled linear D2h B_(36)H_(32)^(2−)(8),close-packed planar D_(3d)B_(84)H_(60)^(2−)(10),and nearly close-packed core−shell D_(3d)B_(12)@B144H_(6)6(4)can be extended periodically to form the one-dimensional(1D)α-rhombohedral borane nanowire B_(12)H_(10)(Pmmm)(9),two-dimensional(2D)α-rhombohedral monolayer borophane B_(12)H_(6)(P m1)(11),and the experimentally known three-dimensional(3D)α-rhombohedral boron(R m)(12)which can be viewed as an assembly of the monolayer B_(12)H_(6)(11)staggered in vertical direction,setting up a bottom-up strategy to form low-dimensional boron-based nanomaterials from their borane“seeds”via partial or complete *** bonding analyses indicate that the high stability of these nanostructures originates from the spherical aromaticity of their icosahedral B_(12)or C_(2)B_(10)structural units which possess the universal skeleton electronic configuration of 1S21P61D101F8 following the Wade’s n+1 *** infrared(IR)and Raman spectra of the most-concerned neutral B_(12)@B144H_(6)6(4)and C_(2)B_(10)@C_(24)B_(12)0H_(72)(7)are computationally simulated to facilitate their experimental characterizations.

关键词： superatom-assembling bottom-up approach density functional theory superpolyhedral boranes superpolyhedral carboranes borophanes

Honokiol Prevents Intestinal Barrier Dysfunction in Mice with Severe Acute Pancreatitis and Inhibits JAK/STAT1 Pathway and Acetylation of HMGB1

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Chinese Journal of Integrative Medicine 2024年第6期30卷 534-542页

作者： LI Jie CHEN Ya-feng GAO Lei LI Yi-jie FENG dian-xu Department of General Surgery Putuo HospitalShanghai University of Traditional Chinese MedicineShanghai200062China

Objective To investigate the effect of honokiol(HON)and the role of high-mobility group protein B1(HMGB1)on the pathogenesis of severe acute pancreatitis(SAP).Methods Thirty mice were numbered according to weight,and randomly divided into 5 groups using a random number table,including control,SAP,SAP and normal saline(SAP+NS),SAP and ethyl pyruvate(SAP+EP),or SAP+HON groups,6 mice in each *** of pancreas,intestine,and blood were collected 12 h after SAP model induction for examination of pathologic changes,immune function alterations by enzyme linked immunosorbent assay(ELISA),and Western *** vitro experiments,macrophages were divided into 5 groups,the control,lipopolysaccharide(LPS),LPS+DMSO(DMSO),LPS+anti-HMGB1 monoclonal antibody(mAb),and LPS+HON *** tight connection level was determined by transmission electron microscopy and fluorescein *** location and acetylation of HMGB1 were measured by Western ***,pyridone 6 and silencing signal transducer and activator of the transcription 1(siSTAT1)combined with honokiol were added to determine whether the Janus kinase(JAK)/STAT1 participated in the regulation of honokiol on *** protein expression levels of HMGB1,JAK,and STAT1 were detected using Western *** Mice with SAP had inflammatory injury in the pancreas,bleeding of intestinal tissues,and cells with disrupted *** in the SAP+HON group had significantly fewer pathological *** with SAP also had significant increases in the serum levels of amylase,lipase,HMGB1,tumor necrosis factor-α,interleukin-6,diamine oxidase,endotoxin-1,and *** in the SAP+HON group did not show these abnormalities(P<0.01).Studies of Caco-2 cells indicated that LPS increased the levels of occludin and claudin-1 as well as tight junction permeability,decreased the levels of junctional adhesion molecule C,and elevated intercellular permeability(P<0.01).HON treatment blocked these *** of

关键词： severe acute pancreatitis intestinal barrier dysfunction honokiol high-mobility group protein B1 Januskinase signal transducerand activatorof transcription1