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

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

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Low Selenium and Low Protein Exacerbate Myocardial Damage in Keshan Disease by Affecting the PINK1/Parkin-mediated Mitochondrial Autophagy Pathway

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Current Medical Science 2024年第1期44卷 93-101页

作者： Li-wei ZHANG Hong-qi FENG Song-bo FU dian-jun SUN Center for Endemic Disease Control Chinese Center for Disease Control and PreventionHarbin Medical UniversityNHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University)Key Lab of Etiology and EpidemiologyEducation Bureau of Heilongjiang ProvinceHarbin 150086China

Objective Keshan disease(KD)is a myocardial mitochondrial disease closely related to insufficient selenium(Se)and protein *** induced putative kinase 1(PINK1)/Parkin mediated mitochondrial autophagy regulates various physiological and pathological processes in the *** study aimed to elucidate the relationship between PINK1/Parkin-regulated mitochondrial autophagy and KD-related myocardial *** A low Se and low protein animal model was *** hundred Wistar rats were randomly divided into 5 groups(control group,low Se group,low protein group,low Se+low protein group,and corn from KD area group).The JC-1 method was used to detect the mitochondrial membrane potential(MMP).ELISA was used to detect serum creatine kinase MB(CK-MB),cardiac troponin I(cTnI),and mitochondrial-glutamicoxalacetic transaminase(M-GOT)***-PCR and Western blot analysis were used to detect the expression of PINK1,Parkin,sequestome 1(P62),and microtubule-associated proteins1A/1B light chain 3B(MAP1LC3B).Results The MMP was significantly decreased and the activity of CK-MB,cTnI,and M-GOT significantly increased in each experimental group(low Se group,low protein group,low Se+low protein group and corn from KD area group)compared with the control group(P<0.05 for all).The mRNA and protein expression levels of PINK1,Parkin and MAP1LC3B were profoundly increased,and those of P62 markedly decreased in the experimental groups compared with the control group(P<0.05 for all).Conclusion Low Se and low protein levels exacerbate myocardial damage in KD by affecting the PINK1/Parkin-mediated mitochondrial autophagy pathway.

关键词： Keshan disease low selenium and low protein myocardial mitochondrial injury PTEN induced putative kinase 1(PINK1)/Parkin mitochondrial autophagy

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Highly Thermally Conductive Polydimethylsiloxane Composites with Controllable 3D GO@f-CNTs Networks via Self-sacrificing Template Method

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Chinese Journal of Polymer Science 2024年第7期42卷 897-906,I0005页

作者： Shuang-Shuang Wang dian-Ying Feng Zhi-Ming Zhang Xia Liu Kun-Peng Ruan Yong-Qiang Guo jun-Wei Gu Shaanxi Key Laboratory of Macromolecular Science and Technology School of Chemistry and Chemical EngineeringNorthwestern Polytechnical UniversityXi’an710072China Shandong Institute of Nonmetallic Materials Jinan250031China Queen Mary University of London Engineering School Northwestern Polytechnical UniversityXi’an710072China

Constructing controllable thermal conduction networks is the key to efficiently improve thermal conductivities of polymer *** this work,graphite oxide(GO)and functionalized carbon nanotubes(f-CNTs)are combined to prepare“Line-Plane”-like hetero-structured thermally conductive GO@f-CNTs fillers,which are then performed to construct controllable 3D GO@f-CNTs thermal conduction networks via selfsacrificing template method based on oxalic ***,thermally conductive GO@f-CNTs/polydimethylsiloxane(PDMS)composites are fabricated via casting *** the size of oxalic acid is 0.24 mm and the volume fraction of GO@f-CNTs is 60 vol%,GO@f-CNTs/PDMS composites present the optimal thermal conductivity coefficient(λ,4.00 W·m^(-1)·K^(-1)),about 20 times that of theλof neat PDMS(0.20 W·m^(-1)·K^(-1)),also much higher than theλ(2.44 W·m^(-1)·K^(-1))of GO/f-CNTs/PDMS composites with the same amount of randomly dispersed ***,the obtained GO@f-CNTs/PDMS composites have excellent thermal stability,whoseλdeviation is only about 3%after 500 thermal cycles(20-200℃).

关键词： Polydimethylsiloxane Hetero-structured thermally conductive fillers Self-sacrificing template Thermal conduction networks

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Decoding m^(6)A mRNA methylation by reader proteins in liver diseases

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Genes & Diseases 2024年第2期11卷 711-726页

作者： Lijiao Sun Xin Chen Sai Zhu Jianan Wang Shaoxi diao Jinyu Liu Jinjin Xu Xiaofeng Li Yingyin Sun Cheng Huang Xiaoming Meng Xiongwen Lv jun Li Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Anhui Institute of Innovative DrugsSchool of PharmacyAnhui Medical UniversityHefeiAnhui 230032China The Key Laboratory of Anti-inflammatory and Immune Medicines Anhui Medical UniversityMinistry of EducationHefeiAnhui 230032China Institute for Liver Diseases of Anhui Medical University ILD-AMUAnhui Medical UniversityHefeiAnhui 230032China Department of Nephropathy The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China Department of Oncology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230032China

N6-methyladenosine(m^(6)A)is a dynamic and reversible epigenetic *** the most prevalent internal post-transcriptional modification in eukaryotic RNA,it participates in the regulation of gene expression through various mechanisms,such as mRNA splicing,nuclear export,localization,translation efficiency,mRNA stability,and structural *** involvement of m^(6)A in the regulation of gene expression depends on the specific recognition of m^(6)A-modified RNA by reader *** the pathogenesis and treatment of liver disease,studies have found that the expression levels of key genes that promote or inhibit the development of liver disease are regulated by m^(6)A modification,in which abnormal expression of reader proteins determines the fate of these gene *** this review,we introduce m^(6)A readers,summarize the recognition and regulatory mechanisms of m^(6)A readers on mRNA,and focus on the biological functions and mechanisms of m^(6)A readers in liver cancer,viral hepatitis,non-alcoholic fatty liver disease(NAFLD),hepatic fibrosis(HF),acute liver injury(ALI),and other liver *** information is expected to be of high value to researchers deciphering the links between m^(6)A readers and human liver diseases.

关键词： IGF2BPs Liver diseases m^(6)A modification m^(6)A reader mRNA metabolism YTH domain protein

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Knowledge domain and emerging trends in the rupture risk of intracranial aneurysms research from 2004 to 2023

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World Journal of Clinical Cases 2024年第23期12卷 5382-5403页

作者： jun-Chen Chen Cheng Luo Yong Li dian-Hui Tan Department of Neurosurgery The First Affiliated Hospital of Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina

BACKGROUND Intracranial aneurysms(IAs)pose significant health risks,attributable to their potential for sudden rupture,which can result in severe outcomes such as stroke and *** extensive research,the variability of aneurysm behavior,with some remaining stable for years while others rupture unexpectedly,remains poorly *** To employ bibliometric analysis to map the research landscape concerning risk factors associated with IAs *** A systematic literature review of publications from 2004 to 2023 was conducted,analyzing 3804 documents from the Web of Science Core Collection database,with a focus on full-text articles and reviews in *** analysis encompassed citation and co-citation networks,keyword bursts,and temporal trends to delineate the evolution of research themes and collaboration *** software tools,CiteSpace and VOSviewer,were utilized for comprehensive data visualization and trend *** Analysis uncovered a total of 3804 publications on IA rupture risk factors between 2006 and *** interest surged after 2013,peaking in *** United States led with 28.97%of publications,garnering 37706 *** United States-China collaborations were *** Medical University produced 184 publications,while Utrecht University boasted a citation average of 69.62 per publication.“World Neurosurgery”published the most papers,contrasting with“Stroke”,the most cited *** PHASES score from“Lancet Neurology”emerged as a vital rupture risk prediction *** research favored endovascular therapy,transitioning to magnetic resonance imaging and flow *** This study assesses global IA research trends and highlights crucial gaps,guiding future investigations to improve preventive and therapeutic approaches.

关键词： Bibliometric VOSviewer CiteSpace Intracranial aneurysm Risk factor

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A complete reference genome assembly for foxtail millet and Setaria-db, a comprehensive database for Setaria

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Molecular Plant 2024年第2期17卷 219-222页

作者： Qiang He Chunchao Wang Qiang He jun Zhang Hongkai Liang Zefu Lui Kun Xie Sha Tang Yuhan Zhou Bin Liu Hui Zhi Guanqing Jia Ganggang Guo Huilong Du Xianmin diao State Key Laboratory of Crop Gene Resources and Breeding Institute of Crop SciencesChinese Academy of Agricultural SciencesBeijing 100081China School of Life Sciences Institute of Life Sciences and Green DevelopmentHebei UniversityBaoding 071000China State Key Laboratory of Rice Biology&Breeding Zhejang Provincial Key Laboratory of Crop GermplasmThe Advanced Seed InstituteZhejiang UniversityHangzhouChina

Dear Editor,,Foxtail millet(Setaria italica)and its wild ancestor green foxtail(***),are two C4 genetic model plants known for their desirable traits,such as small size,short life cycle,ease of transformation,and a compact genome size(~420 Mb)(He et al.,2023).Foxtail millet stands out as the only cultivated species within the Setaria *** a foundational crop for ancient east Asian agriculture civilization,it possesses remarkable drought and soil-nutrient deficiency tolerance.

关键词： comprehensive soil cultivated

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Digital generation of super-Gaussian perfect vortex beams via wavefront shaping with globally adaptive feedback

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High Power Laser Science and Engineering 2024年第1期12卷 42-51页

作者： Rui Ma Ke Hai Luo Jing Song He Wei Li Zhang dian Yuan Fan Anderson S.L.Gomes jun Liu International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of Education Institute of Microscale OptoelectronicsShenzhen UniversityShenzhenChina Institute for Advanced Study Shenzhen UniversityShenzhenChina Fiber Optics Research Centre School of Information and Communication EngineeringUniversity of Electronic Science and Technology of ChinaChengduChina Departamento de Física Universidade Federal de PernambucoRecife-PEBrazil

High-intensity vortex beams with tunable topological charges and low coherence are highly demanded in applications such as inertial confinement fusion(ICF) and optical communication. However, traditional optical vortices featuring nonuniform intensity distributions are dramatically restricted in application scenarios that require a high-intensity vortex beam owing to their ineffective amplification resulting from the intensity-dependent nonlinear effect. Here, a low-coherence perfect vortex beam(PVB) with a topological charge as high as 140 is realized based on the super-pixel wavefront-shaping technique. More importantly, a globally adaptive feedback algorithm(GAFA) is proposed to efficiently suppress the original intensity fluctuation and achieve a flat-top PVB with dramatically reduced beam speckle contrast. The GAFA-based flat-top PVB generation method can pave the way for high-intensity vortex beam generation,which is crucial for potential applications in ICF, laser processing, optical communication and optical trapping.

关键词： digital micromirror device flat-top beam orbital angular momentum perfect vortex beam random fiber laser

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城市生活垃圾焚烧过程二次风量智能优化设定方法

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控制与决策 2024年第1期39卷 49-58页

作者：丁晨曦严爱军王殿辉北京工业大学信息学部北京100124 数字社区教育部工程研究中心北京100124 城市轨道交通北京实验室北京100124 中国矿业大学人工智能研究院江苏徐州221116 东北大学流程工业综合自动化国家重点实验室沈阳110004 拉筹伯大学计算机科学与信息技术系墨尔本VIC 3086

垃圾焚烧过程二次风量通常是依据人工经验设定,具有主观随意性,使污染物排放浓度不达标.针对此问题,提出一种二次风量智能优化设定方法.首先,建立二次风量的案例推理预设定模型、设定值的评价与学习模型;其次,建立工艺指标的随机配置网... 详细信息

垃圾焚烧过程二次风量通常是依据人工经验设定,具有主观随意性,使污染物排放浓度不达标.针对此问题,提出一种二次风量智能优化设定方法.首先,建立二次风量的案例推理预设定模型、设定值的评价与学习模型;其次,建立工艺指标的随机配置网络预测模型;接着,建立基于径向基神经网络自学习模糊推理的智能补偿模型;最后,将二次风量预设定模型、工艺指标预测模型、智能补偿模型以及设定值的评价与学习模型有机集成,设计二次风量智能优化设定方法的结构与功能,并给出算法实现.采用某垃圾焚烧厂历史数据进行实验,结果表明,所提方法获得的二次风量设定值波动程度更小,按此设定值运行的控制系统可以减少污染物排放浓度,促进垃圾焚烧过程运行优化目标的实现.

关键词：垃圾焚烧优化设定案例推理随机配置网络智能补偿评价与学习

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国图藏《雍正二年陕西甘肃两河武举乡试录》所载宁夏武举事

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兰台世界 2024年第4期 148-151页

作者：刁俊宁夏大学

明清两朝,随着中央政府对宁夏的经略,宁夏文教事业有了较快发展,涌现出一大批文武科举人才。两朝有30余种地方旧志流传至今,为我们溯源宁夏文教事业,特别是科举发展提供了重要的文献支撑。但地方旧志中关于文举记述较为翔实,武举内容则... 详细信息

明清两朝,随着中央政府对宁夏的经略,宁夏文教事业有了较快发展,涌现出一大批文武科举人才。两朝有30余种地方旧志流传至今,为我们溯源宁夏文教事业,特别是科举发展提供了重要的文献支撑。但地方旧志中关于文举记述较为翔实,武举内容则相对匮乏。国图现藏《雍正二年陕西甘肃两河武举乡试录》,详细记录了雍正二年甲辰科宁夏武举的相关情况,可对传世宁夏旧志相关内容进行补充。更难得的是,是书保存了宁夏武举人梁从直的策问试卷,这对宁夏乡贤研究提供了更加全面的文献基础。

关键词：雍正二年武乡试宁夏

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LuxS/AI-2群体感应系统在乳酸菌细菌素合成中的作用

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中国调味品 2024年第3期49卷 214-220页

作者：满丽莉向殿军内蒙古民族大学生命科学与食品学院内蒙古通辽028042 内蒙古民族大学农学院内蒙古通辽028042

乳酸菌细菌素具有抑菌谱广、稳定性高、安全性高等优势,作为新型生物防腐剂备受青睐,但目前工业化应用的细菌素数量有限,合成量低是其应用受限的重要原因。国内外研究显示与特定的微生物共培养是提高乳酸菌细菌素合成量的有效方法,该过... 详细信息

乳酸菌细菌素具有抑菌谱广、稳定性高、安全性高等优势,作为新型生物防腐剂备受青睐,但目前工业化应用的细菌素数量有限,合成量低是其应用受限的重要原因。国内外研究显示与特定的微生物共培养是提高乳酸菌细菌素合成量的有效方法,该过程受到LuxS/AI-2群体感应系统的调控。文章从乳酸菌LuxS/AI-2群体感应系统的组成及LuxS/AI-2群体感应系统在乳酸菌细菌素合成中的作用两个方面进行论述,为乳酸菌细菌素合成量的提高和工业化应用的实现提供了一定的理论依据。

关键词： LuxS/AI-2群体感应系统乳酸菌细菌素合成

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