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Id2 epigenetically controls CD8^(+)T-cell exhaustion by disrupting the assembly of the Tcf3-LSD1 complex

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Cellular & Molecular Immunology 2024年第3期21卷 292-308页

作者： Yiming Li Mingwei Han Haolin Wei Wan Huang Zhinan Chen Tianjiao Zhang Meirui Qian Lin Jing Gang Nan Xiuxuan Sun Shuhui Dai kun wang Jianli Jiang Ping Zhu Liang Chen Department of Cell Biology of National Translational Science Center for Molecular Medicine and Department of Clinical Immunology of Xijing Hospital Fourth Military Medical UniversityXi’anShaanxi 710032China State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases GanzhouJiangxi341000Xi’anShaanxi 710032China School of Medicine Shanghai UniversityShanghai 200444China

CD8^(+)T-cell exhaustion is a state of dysfunction that promotes tumor progression and is marked by the generation of Slamf6^(+)progenitor exhausted(Tex^(prog))and Tim-^(3+)terminally exhausted(Tex^(term))*** of DNA binding protein 2(Id2)has been shown to play important roles in T-cell development and CD8^(+)T-cell ***,the role of Id2 in CD8^(+)T-cell exhaustion is ***,we found that Id2 transcriptionally and epigenetically regulates the generation of Texprog cells and their conversion to Texterm *** deletion of Id2 dampens CD8^(+)T-cell-mediated immune responses and the maintenance of stem-like CD8^(+)T-cell subpopulations,suppresses PD-1 blockade and increases tumor ***,through its HLH domain,Id2 binds and disrupts the assembly of the Tcf3-Tal1 transcriptional regulatory complex,and thus modulates chromatin accessibility at the Slamf6 promoter by preventing the interaction of Tcf3 with the histone lysine demethylase ***,Id2 increases the abundance of the permissive H3K4me2 mark on the Tcf3-occupied E-boxes in the Slamf6 promoter,modulates chromatin accessibility at the Slamf6 promoter and epigenetically regulates the generation of Slamf6+Texprog *** LSD1 inhibitor GSK2879552 can rescue the Id2 knockout phenotype in tumor-bearing *** of LSD1 increases the abundance of Slamf6^(+)Tim-3^(−)Tex^(prog) cells in tumors and the expression level of Tcf1 in Id2-deleted CD8+T *** study demonstrates that Id2-mediated transcriptional and epigenetic modification drives hierarchical CD8^(+)T-cell exhaustion,and the mechanistic insights gained may have implications for therapeutic intervention with tumor immune evasion.

关键词： Id2 T-cell exhaustion Epigenetic modification Immune evasion

锁定、调整与再生——国外都市区工业空间功能演化路径比较

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国际城市规划 2024年第1期39卷 100-107页

作者：王昆王秋杨中国城市规划设计研究院绿色城市研究所

国外都市区工业空间是城市实现转型、把握未来发展机遇的重要空间载体,对我国城市量大面广的工业空间转型升级具有借鉴意义。本文基于演化经济地理学的视角,结合国外工业空间转型实例,分析了都市区内既有工业用地转型升级过程中的功能... 详细信息

国外都市区工业空间是城市实现转型、把握未来发展机遇的重要空间载体,对我国城市量大面广的工业空间转型升级具有借鉴意义。本文基于演化经济地理学的视角,结合国外工业空间转型实例,分析了都市区内既有工业用地转型升级过程中的功能分化趋势、典型代表、影响因素以及具体的演化路径。笔者认为:(1)工业空间演化过程主要影响因素包括自身优势条件、拟解决的主要问题、外部发展诉求等,各方面因素合力下形成了不同的功能演化方向。(2)从功能演化的国际案例来看,工业空间的功能演化可以分为再生型(即实现功能突破)、调整型(即实现功能延伸)、锁定型(即功能被动锁定)三种典型路径。(3)具体而言,再生型演化路径以文化活力为路径核心,促使原有工业空间走向高活力城市区;调整型演化路径以科技创新为路径核心,促使原有工业空间转向高科技集聚区;锁定型演化路径以制造升级作为路径核心,促使原有工业空间走向更高质量的工业区。

关键词：都市区工业空间功能演化空间转型演化路径

体育非物质文化遗产智能化保护与传播的数字技术赋权策略研究

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武汉体育学院学报 2024年第9期58卷 59-65,96页

作者：崔琪王坤乔治华盛顿大学哥伦比亚艺术与科学学院华盛顿20052 上海交通大学体育系上海200240

随着大数据的生成并快速渗透、运用于人们的社会生活,新兴的人工智能技术开始改变着体育非遗与广大受众之间的关系。随之而来的是体育非遗数字化建设以及智能化保护与传播日益受到广泛关注。针对体育非遗资源保护与传播的现实状况,全面... 详细信息

随着大数据的生成并快速渗透、运用于人们的社会生活,新兴的人工智能技术开始改变着体育非遗与广大受众之间的关系。随之而来的是体育非遗数字化建设以及智能化保护与传播日益受到广泛关注。针对体育非遗资源保护与传播的现实状况,全面认识其数字技术的执行特征,已经成为进行现代性保护与传播的关键。在对体育非遗资源数字技术智能化特征分析的基础上,由田野调查向智慧数据分析拓展、提升体育非遗资源档案处理效率、缩小体育非遗传承人对数字技术认知差距角度,对体育非遗信息数字化赋权的合理逻辑进行了分析。认为建立非遗数字化分类体系、融入非遗虚拟现实技术、建立非遗展示与传播平台、确立“参与式数字化保护”理念等,是体育非遗资源智能化保护与传播的主要赋权路径。而随着大数据、虚拟现实和视觉搜索等现代科技手段的不断融入,以及人工智能技术与体育非遗的高度融合,体育非遗资源的智能化数字保护与传播将成为必然。

关键词：体育非物质文化遗产智能化保护智能化传播数字技术赋权体育非遗资源

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Himalayas as a global hot spot of springtime stratospheric intrusions:Insight from isotopic signatures in sulfate aerosols

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Research in Cold and Arid Regions 2024年第1期16卷 5-13页

作者： kun wang ShiChang Kang Mang Lin PengFei Chen ChaoLiu Li XiuFeng Yin Shohei Hattori Teresa L.Jackson JunHua Yang YiXi Liu Naohiro Yoshida Mark HThiemens State Key Laboratory of Cryospheric Science Northwest Institute of Eco-Environment and ResourcesChinese Academy of Sciences(CAS)LanzhouGansu 730000China State Key Laboratory of Isotope Geochemistry Guangzhou Institute of GeochemistryCASGuangzhouGuangdong 510640China University of Chinese Academy of Sciences Beijing 100049China International Center for Isotope Effects Research(ICIER) School of Earth Sciences and EngineeringNanjing UniversityNanjingJiangsu 210023China Frontiers Science Center for Critical Earth Material Cycling State Key Laboratory for Mineral Deposits ResearchSchool of Earth Sciences and EngineeringNanjing UniversityNanjingJiangsu 210023China Department of Chemical Science and Engineering School of Materials and Chemical TechnologyTokyo Institute of Technology4259 Nagatsuta-choMidori-kuYokohamaKanagawa 226-8502Japan Department of Chemistry and Biochemistry University of California San DiegoLa JollaCA 92093-0021USA Earth-Life Science Institute Tokyo Institute of TechnologyMeguro-kuTokyo 152-8551Japan National Institute of Information and Communications Technology KoganeiTokyo 184-8795Japan

Downward transport of stratospheric air into the troposphere(identified as stratospheric intrusions)could potentially modify the radiation budget and chemical of the Earth's surface *** the highest and largest plateau on earth,the Tibetan Plateau including the Himalayas couples to global climate,and has attracted widespread attention due to rapid warming and cryospheric *** studies recognized strong stratospheric intrusions in the Himalayas but are poorly understood due to limited direct evidences and the complexity of the meteorological dynamics of the third ***^(35)S is a radioactive isotope predominately produced in the lower stratosphere and has been demonstrated as a sensitive chemical tracer to detect stratospherically sourced air mass in the planetary boundary ***,we report 6-month(April–September 2018)observation of^(35)S in atmospheric sulfate aerosols(^(35)SO_(4)^(2-))collected from a remote site in the Himalayas to reveal the stratospheric intrusion phenomenon as well as its potential impacts in this *** the sampling campaign,the^(35)SO_(4)^(2-)concentrations show an average of 1,070±980 atoms/m^(3).In springtime,the average is 1,620±730 atoms/m^(3),significantly higher than the global existing data measured so *** significant enrichments of^(35)SO_(4)^(2-)measured in this study verified the hypothesis that the Himalayas is a global hot spot of stratospheric intrusions,especially during the springtime as a consequence of its unique geology and atmospheric *** combined with the ancillary evidences,e.g.,oxygen-17 anomaly in sulfate and modeling results,we found that the stratospheric intrusions have a profound impact on the surface ozone concentrations over the study region,and potentially have the ability to constrain how the mechanisms of sulfate oxidation are affected by a change in plateau atmospheric properties and *** study provides new observational constraints on stra

关键词： Himalayas Stratospheric intrusions Cosmogenic^(35)SO_(4)^(2-) Ozone Atmospheric oxidation

Quality of life and survival analyses of breast cancer cases treated with integrated traditional Chinese and Western medicine

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World Journal of Clinical Cases 2024年第20期12卷 4074-4081页

作者： Yu-kun wang Rong-Wei Zhu Zhi-Peng Gao Yi Tao Thyroid and Breast Surgery Department the First Affiliated Hospital of Guangxi University of Traditional Chinese MedicineNanning 530000Guangxi Zhuang Autonomous RegionChina Clinical Integration of Traditional Chinese and Western Medicine Guangxi University of Chinese MedicineNanning 530000Guangxi Zhuang Autonomous RegionChina

BACKGROUND Breast cancer(BC)is the second leading cause of tumor-related mortality after lung *** resistance remains a major challenge to progress in BC treatment,warranting further exploration of feasible and effective alternative *** To analyzed the quality of life(QoL)and survival of patients with BC treated with integrated traditional Chinese and Western medicine(TCM-WM).METHODS This study included 226 patients with BC admitted to the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine between February 2018 and February 2023,including 100 who received conventional Western medicine treatment(control group)and 126 who received TCM-WM treatment(research group).The total effective rate,side effects(alopecia,nausea and vomiting,hepatorenal toxicity,and myelosuppression),QoL assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire(EORTC QLQ-C30),1-year overall survival(OS),recurrence and metastasis rates,and serum inflammatory factors[interleukin(IL)-6,IL-10,and tumor necrosis factor alpha]were comparatively *** The research group showed statistically better overall efficacy,EORTC QoL-C30 scores,and 1-year OS than the control group,with markedly lower side effects and 1-year recurrence and metastasis ***,the posttreatment levels of serum inflammatory in the research group were significantly lower than the baseline and those in the control *** Overall,TCM-WM demonstrated significantly improved therapeutic efficacy while ensuring drug safety in BC,which not only improved patients’QoL and prolonged survival,but also significantly inhibited the inflammatory response.

关键词： Integrated traditional Chinese and Western medicine Breast cancer Quality of life Survival Chemotherapy regimen

隐性成本:政府驻地迁移的民生性公共服务效应

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行政论坛 2024年第2期31卷 90-102页

作者：赵聚军王坤南开大学周恩来政府管理学院天津300071

中国的城市政府驻地通常具有强烈的资源聚集效应,政府驻地迁移对地方的经济和社会发展均具有深刻的影响。然而,无论是地方推动政府驻地迁移的主要政策目标,还是相关研究,均聚焦经济发展效应而对其民生性公共服务效应缺乏关注。为测度政... 详细信息

中国的城市政府驻地通常具有强烈的资源聚集效应,政府驻地迁移对地方的经济和社会发展均具有深刻的影响。然而,无论是地方推动政府驻地迁移的主要政策目标,还是相关研究,均聚焦经济发展效应而对其民生性公共服务效应缺乏关注。为测度政府驻地迁移对民生性公共服务的影响,在收集了2003—2019年266个地级及以上城市数据并借助因子分析法构建民生性公共服务指标体系的基础上,通过运用双重差分法进行检验,结果显示,政府驻地迁移会对民生性公共服务产生显著负面效应,存在隐性的社会成本;通过影响机制分析发现,政府驻地迁移通过支出偏向和财政压力,产生了民生性公共服务挤出效应;通过异质性分析则表明,在行政等级、所处地区、政策时点和迁移距离等不同条件下,其影响的强度会有所变化。将政府驻地迁移的政策效应从经济发展扩展至民生性公共服务,不仅拓宽了研究视域,也具有一定的政策价值,既可以为相关决策提供科学支持,也能够为抑制城市政府的“空间生产”冲动提供学理依据。

关键词：政府驻地迁移公共服务行政区划城市政府

带正同态算子的脉冲分数阶微分方程积分边值问题正解的多重性

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应用数学学报 2024年第1期47卷 29-44页

作者：龚平汪坤广东外语外贸大学数学与统计学院广州510006 广州大学数学与信息科学学院广州510006

本文关注带正同态算子的脉冲分数阶微分方程积分边值问题正解的多重性问题.利用经典的Guo-Krasnosel’skii不动点定理,给出了脉冲分数阶微分方程至少存在两个正解的充分条件.最后,用实例验证了理论结果的有效性.

关键词：脉冲积分边值问题正同态算子多重性

羧甲司坦片联合沙丁胺醇气雾剂治疗慢性阻塞性肺疾病患者的临床研究

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中国临床药理学杂志 2024年第2期40卷 155-159页

作者：李敬王坤青岛市市立医院西院区、青岛市老年病医院急诊科山东青岛266300 青岛市胶州中心医院胸外科山东青岛266300

目的研究羧甲司坦片联合沙丁胺醇气雾剂治疗慢性阻塞性肺疾病(COPD)患者的临床疗效,以及对患者肺功能、氧化应激指标的影响。方法将COPD患者分为试验组和对照组。对照组接受沙丁胺醇气雾剂治疗,试验组在对照组的基础上给予羧甲司坦片,每... 详细信息

目的研究羧甲司坦片联合沙丁胺醇气雾剂治疗慢性阻塞性肺疾病(COPD)患者的临床疗效,以及对患者肺功能、氧化应激指标的影响。方法将COPD患者分为试验组和对照组。对照组接受沙丁胺醇气雾剂治疗,试验组在对照组的基础上给予羧甲司坦片,每次0.5 g,每天3次,口服治疗3个月。比较2组患者的肺功能情况、氧化应激指标、慢性阻塞性肺疾病自我评估测试情况(CAT)及血清炎症因子水平。结果治疗后,试验组和对照组的第1秒用力呼气量占用力肺活量百分比(FEV1/FVC)分别为(83.26±3.88)%和(75.12±3.87)%,用力肺活量(FVC)分别为(3.67±0.31)和(3.11±0.22)L,FEV1分别为(1.65±0.17)和(1.43±0.11)L·s^(-1),总抗氧化能力(T-AOC)分别为(36.81±3.09)和(23.25±2.10)U·mL^(-1),谷胱甘肽过氧化物酶(GPX)分别为(73.49±3.45)和(53.13±3.55)nmol·L^(-1),丙二醛(MDA)分别为(12.74±1.14)和(10.09±1.10)nmol·mL^(-1),超氧化物歧化酶(SOD)水平分别为(328.30±16.96)和(462.44±17.73)U·mL^(-1),CAT主观指标分别为(11.04±2.00)和(18.03±3.23)分,运动指标分数分别为(4.16±1.80)和(6.66±1.76)分,血清白细胞介素-17(IL-17)分别为(29.39±2.38)和(40.90±2.80)pg·mL^(-1),肿瘤坏死因子-α(TNF-α)分别为(31.96±2.04)和(40.04±2.57)pg·mL^(-1),高迁移率族蛋白1(HMGB1)水平分别为(41.50±3.03)和(72.23±4.63)pg·mL^(-1),在统计学上差异均有统计学意义(均P0.05)。结论在COPD临床治疗中联合应用羧甲司坦片、沙丁胺醇气雾剂能有效提高临床疗效,降低炎症反应,改善患者肺功能通气情况,减轻氧化应激反应。

关键词：沙丁胺醇气雾剂羧甲司坦片慢性阻塞性肺疾病氧化应激反应

Interphase migration and enrichment of lead and zinc during copper slag depletion

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Transactions of Nonferrous Metals Society of China 2024年第9期34卷 3029-3041页

作者： Jun HAO Zhi-he DOU Xing-yuan WAN Ting-an ZHANG kun wang Key Laboratory of Ecological Metallurgy of Multi-metal Intergrown Ores of Education Northeastern UniversityShenyang 110819China School of Metallurgy Northeastern UniversityShenyang 110819China

An interphase migration and enrichment model of lead and zinc during molten copper slag depletion was *** occurrence of various components in copper slag was predicted using sulfur-oxygen potential calculations and confirmed through high-temperature *** recovery rate of copper can reach 90.13%under the optimal conditions of 1200°C,an iron to silicon mass ratio of 1.0,3 wt.%ferrous sulfide,and a duration of 45 ***(54.07 wt.%)and zinc(17.42 wt.%)are found in the flue dust as lead sulfate,lead sulfide,and zinc oxide,while copper matte contains lead(14.44 wt.%)and zinc sulfide(1.29 wt.%).The remaining lead and zinc are encapsulated as oxides within the fayalite phase.

关键词： depletion lead copper slag stirring zinc