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ncreasing the safety and efficacy of chimeric antigen receptor T cell therapy

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Protein & Cell 2017年第8期8卷 573-589页

作者： Hua Li yangbing zhao Center for Cellular Immunotherapies Perelman School of Medicine University of Pennsylvania PhiladelphiaPA 19104-5156 USA Cancer Center Chengdu Military General Hospital Chengdu 610083 China

Chimeric antigen receptor （CAR） T cell therapy is a promising cancer treatment that has recently been undergoing rapid development. However, there are still some major challenges, including precise tumor targeting to avoid off-target or ＂on-target/off-tumor＂ toxicity, adequate T cell infiltration and migration to solid tumors and T cell proliferation and persistence across the physical and biochemical barriers of solid tumors. In this review, we focus on the primary challenges and strafegies to design safe and effective CAR T cells, including using novel cutting-edge technologies for CAR and vecfor designs to increase both the safety and efficacy, further T cell modification to overcome the tumorassociated immune suppression, and using gene editing technologies to generate universal CAR T cells. All these efforts promote the development and evolution of CAR T cell therapy and move toward our ultimate goal--curing cancer with high safety, high efficacy, and low cost.

关键词： chimeric antigen receptors cancer adoptive immunotherapy T lymphocytes gene therapy,gene editing

Storage, form, and influencing factors of karst inorganic carbon in a carbonate area in China

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Science China Earth Sciences 2024年第3期67卷 725-739页

作者： Chaochao DU Xiaoyong BAI yangbing LI Qiu TAN Cuiwei zhao Guangjie LUO Luhua WU Fei CHEN Chaojun LI Chen RAN Sirui ZHANG Lian XIONG Fengjiao SONG Biqin XIAO Zilin LI Yingying XUE Mingkang LONG Qing LUO Xiaoyun ZHANG Minghui LI Xiaoqian SHEN Shu YANG State Key Laboratory of Environmental Geochemistry Institute of GeochemistryChinese Academy of SciencesGuiyang 550081China School of Geography and Environmental Sciences Guizhou Normal UniversityGuiyang 550001China CAS Center for Excellence in Quaternary Science and Global Change Xi'an 710061China Guizhou Provincial Key Laboratory of Geographic State Monitoring of Watershed Guizhou Normal CollegeGuiyang 550018China College of Resources and Environmental Engineering Guizhou UniversityGuiyang 550025China

Carbonate rock chemical weathering carbon sinks reduce the rate of increase of the atmospheric CO_(2) concentration and global warming. However, uncertainty still exists in the estimation results of carbonate rock chemical weathering carbon sink fluxes(CCSF), and the contributions of climate change and ecological restoration to the CCSF are not clear. To this end, we compiled published site data on ion concentrations in different watersheds in China and used a classical thermodynamic dissolution model to reassess the potential and spatial and temporal patterns of the CCSF in China from 1991 to 2020. We quantified the contributions of temperature(MAT), precipitation(MAP), evapotranspiration(ET), soil water(SM), and the normalized difference vegetation index(NDVI) to the CCSF. The results revealed that(1) China's CCSF was 22.76 t CO_(2)km^(-2)yr^(-1), which was higher than the global average(15.77 t CO_(2)km^(-2)yr^(-1)). The total carbonate rock chemical weathering carbon sink(CCS) was 4772.67×10^(4)t CO_(2), contributing 14.91% of the global CCS through a carbonate rock area of 252.98×10^(4)km^(-2).(2) China's CCSF decreased gradually from southeast to northwest, with values of 33.14, 12.93, and7.27 t CO_(2)km^(-2)yr^(-1)in the southern karst, Qinghai-Tibetan karst, and northern karst regions, respectively.(3) The overall CCSF in China exhibited an increasing trend from 1991 to 2020, with a rate of increase of 0.16 t CO_(2)km^(-2)yr^(-1).(4) The contributions of the MAP, MAT, ET, SM, and NDVI to the CCSF were 63.3%, 3.02%, 27.5%, 3.1%, and 3.05%, respectively. Among them, the increase in precipitation was the main contributor to the increase in the CCSF in China over the last 30 years, while the enhancement of ET offset part of the positive contribution of the increase in precipitation to the CCSF. In conclusion, the results of this study provide a systematic quantification of the magnitude, the patterns, and the influencing factors of CCS over a long time series in China. The results are of great significance an

关键词： Carbonate rocks Carbon sinks Patterns Influencing factors Thermodynamic dissolution modeling

山区乡村多功能发展与乡村聚落演变的耦合机理

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农业工程学报 2024年第11期40卷 259-270页

作者：赵雯欣李阳兵王清荣邵景安重庆师范大学地理与旅游学院重庆401331 重庆师范大学三峡库区地表过程与生态修复重庆市重点实验室重庆401331 三峡库区地表生态过程重庆市野外科学观测研究站重庆401331

探究山区乡村功能多元化与乡村聚落演变的耦合关系,对山区乡村振兴和乡村可持续发展具有重要意义。通过构建二者的耦合协调综合评价指标体系,利用耦合协调度模型和地理探测器等方法,以三峡库区腹地奉节县为研究区,定量探究了乡村功能多... 详细信息

探究山区乡村功能多元化与乡村聚落演变的耦合关系,对山区乡村振兴和乡村可持续发展具有重要意义。通过构建二者的耦合协调综合评价指标体系,利用耦合协调度模型和地理探测器等方法,以三峡库区腹地奉节县为研究区,定量探究了乡村功能多元化与乡村聚落演变的耦合关系及驱动机制,进而提出了相关建议。结果表明:1)研究区乡村功能多元化和乡村聚落演变综合指数呈上升趋势;两系统耦合协调度逐年增长,失调乡镇数量减少,在空间上呈现“西低东高,南低北高”的发展态势。2)乡村功能多元化与乡村聚落演变耦合协调度具有明显的空间集聚特征,高高集聚区域主要集中在永安街道等中心城镇的郊区。3)基于功能多元化综合指数与聚落演变综合指数的增减关系,该文将各乡镇归纳为活力型、衰退型、转型型和传统型4种耦合模式。4)人口密度、人均GDP、人类活动强度等社会经济因素是主要驱动因子,各因子间的交互作用大部分为非线性增强和双因子增强。该文的研究方法和研究结果可为其他地区进行相关研究以及制定差异化的村落振兴方案提供参考。

关键词：乡村功能聚落耦合关系三峡库区

Novel T cells with improved in vivo anti-tumor activity generated by RNA electroporation

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Protein & Cell 2017年第7期8卷 514-526页

作者： Xiaojun Liu Shuguang Jiang Chongyun Fang Hua Li Xuhua Zhang Fuqin Zhang Carl H. June yangbing zhao Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology School of Basic Medical Sciences Shandong University Jinan 250012 China Center for Cellular Immunotherapies University of Pennsylvania Cancer Center Philadelphia PA 19104 USA Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104-5156 USA

The generation of T cells with maximal anti-tumor activities will significantly impact the field of T-cell- based adoptive immunotherapy. In this report, we found that OKT3/IL-2-stimulated T cells were phenotypically more heterogeneous, with enhanced anti-tumor activity in vitro and when locally administered in a solid tumor mouse model. To further improve the OKT3/IL-2-based T cell manufacturing procedure, we developed a novel T cell stimulation and expansion method in which peripheral blood mononuclear cells were electroporated with mRNA encoding a chimeric membrane protein consisting of a single-chain variable fragment against CD3 and the intracellular domains of CD28 and 4-1BB （OKT3-28BB）. The expanded T cells were phenotypically and functionally similar to T cells expanded by OKT3/IL-2. Moreover, co-electroporation of CD86 and 4-1BBL could further change the phenotype and enhance the in vivo anti-tumor activity. Although T cells expanded by the co- electroporation of OKT3-28BB with CD86 and 4-1BBL showed an increased central memory phenotype, the T cells still maintained tumor lytic activities as potent as those of OKT3/IL-2 or OKT3-28BB-stimulated T cells. In different tumor mouse models, T cells expanded by OKT3-28BB RNA electroporation showed anti-tumor activities superior to those of OKT3/IL-2 T cells. Hence, T cells with both a less differentiated phenotype and potent tumor killing ability can be generated by RNA electroporation, and this T cell manufacturing procedure can be further optimized by simply co-delivering other splices of RNA, thus providing a simple and cost-effec- tive method for generating high-quality T cells for adop- tive immunotherapy.

关键词： T lymphocytes CAR manufacture genetransfer RNA electroporation

2000—2020年三峡库区腹地人地耦合土地系统演变机制

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农业工程学报 2024年第10期40卷 255-264,F0003页

作者：汪荣李阳兵邵景安郑骆珊陈艳王清荣赵雯欣重庆师范大学地理与旅游学院重庆401331 三峡库区地表过程与环境遥感重庆市重点实验室重庆401331

该研究基于人地耦合土地系统转型研究框架,采用耦合协调度模型、景观指数与二元Logistic回归模型等方法,探究人地耦合视角下三峡库区腹地土地系统演变规律,揭示其影响机制,从而归纳人地耦合土地系统数量—景观格局—功能转型模式。研究... 详细信息

该研究基于人地耦合土地系统转型研究框架,采用耦合协调度模型、景观指数与二元Logistic回归模型等方法,探究人地耦合视角下三峡库区腹地土地系统演变规律,揭示其影响机制,从而归纳人地耦合土地系统数量—景观格局—功能转型模式。研究结果表明:1)2000—2020年,三峡库区腹地人类活动强度由逐渐增强转变为逐渐减弱,人地耦合关系总体表现为向协调型平缓发展。在空间上,呈现出中部与东北部趋于协调型、北部趋于拮抗型、南部变化不明显的分异特征;2)人地耦合土地系统数量—景观格局—功能形态发生了明显的变化。拮抗区和失调区耕地总体减少,减少量分别为21263、40029 hm^(2)。其中,拮抗区林地恢复性增长,增长量为89648 hm^(2)。失调区林地呈先增加后减少的波动变化,总体增长16054 hm^(2)。协调区果园明显扩张,增长量为13856 hm^(2);斑块破碎化程度改善,趋于规则;土地系统由单功能主导向多功能转变;3)研究区人地耦合土地系统转型模式呈现多元化,可归纳为:拮抗区:林地恢复-斑块聚集不规则-生态;失调区:林地缩减-斑块聚集规则-生态主导;协调区:果园扩张-斑块聚集、整体规则-生态经济;4)距离与地形是影响土地系统演变的决定性因素,主导因子之间交互产生叠加效应,共同促进土地系统的变化。研究揭示了三峡库区人地耦合关系发展规律与土地系统转型模式,对促进山区土地资源合理利用与人地协调发展具有现实意义。

关键词：土地利用景观格局演变相关性三峡库区

三峡库区山区乡村功能多元化与坡耕地演变的耦合关系

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生态学报 2024年第7期44卷 2800-2816页

作者：赵雯欣李阳兵王清荣夏春华陈艳郑骆珊邵景安重庆师范大学地理与旅游学院重庆401331 三峡库区地表过程与环境遥感重庆市重点实验室重庆401331

探究快速城市化、工业化背景下,山区乡村功能多元化与坡耕地演变的耦合关系,对山区耕地保护和乡村可持续发展具有重要意义。从人地关系视角,构建了山区乡村功能多元化与坡耕地演变耦合关系测度模型,并以三峡库区奉节县为例,采用乡村功... 详细信息

探究快速城市化、工业化背景下,山区乡村功能多元化与坡耕地演变的耦合关系,对山区耕地保护和乡村可持续发展具有重要意义。从人地关系视角,构建了山区乡村功能多元化与坡耕地演变耦合关系测度模型,并以三峡库区奉节县为例,采用乡村功能评价、耦合协调度模型等方法,揭示其耦合关系及其驱动机制。结果表明:(1)奉节县各乡村功能均呈现发展的趋势,其中社会保障功能的发展最为明显,乡村功能综合指数呈现南北部增加、中部减少的特征,且南部增加幅度大于北部;(2)奉节县坡耕地占比呈现下降趋势,缓坡耕地减少最少,急陡坡耕地减少最多,呈现南部减少幅度小、北部减少幅度大的特征;(3)乡村功能多元化与缓坡耕地演变的耦合协调度呈下降的趋势,与陡坡耕地和急陡坡耕地的耦合协调度呈先降后升的趋势,其耦合响应类型可以归纳为可持续型、转型型、一致型和衰退型4种类型;(4)乡村功能多元化与坡耕地演变耦合变化主要受到自然、社会经济、政策等要素驱动,今后应当从发展生态农业、推行环境治理等方面来提高乡村功能发展与坡耕地利用之间的协调性。研究方法和研究结果可为其他山区坡耕地资源的优化利用、生态保护以及乡村可持续发展提供借鉴价值。

关键词：乡村功能坡耕地耦合关系三峡库区

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临兴-神府区块深部煤层气地球化学特征及其影响因素

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煤田地质与勘探 2024年第5期52卷 56-66页

作者：吴鹏胡维强李洋冰马立涛李勇赵霏牛艳伟陈建奇李盼盼刘再振李晨晨曹地刘成中联煤层气有限责任公司北京100011 中海油能源发展股份有限公司工程技术分公司天津300452 中海油能源发展股份有限公司非常规勘探开发重点实验室天津300452 中国矿业大学(北京)地球科学与测绘工程学院北京100083

查明深部煤层气成因和地球化学特征对其勘探开发具有重要意义,以鄂尔多斯盆地东缘临兴-神府区块深部煤层参数井解吸气为研究对象,系统测试了二叠系下统太原组8+9号煤层气体成分、含量和碳同位素等,结合热演化程度、含气性、煤层埋深、... 详细信息

查明深部煤层气成因和地球化学特征对其勘探开发具有重要意义,以鄂尔多斯盆地东缘临兴-神府区块深部煤层参数井解吸气为研究对象,系统测试了二叠系下统太原组8+9号煤层气体成分、含量和碳同位素等,结合热演化程度、含气性、煤层埋深、地质构造和水文地质条件等,分析深部煤层气地球化学特征及影响因素。结果表明,煤层气主要成分包括CH4、CO_(2)、N_(2)、乙烷、丙烷、异丁烷、正丁烷、异戊烷和正戊烷,其中CH4含量最高,体积分数在75.98%~96.20%,平均86.49%;其他含量较高的为乙烷(平均5.97%)、CO_(2)(平均5.18%)及丙烷(平均1.24%),气体成分含量与浅部煤层气区块无明显差异。煤层气δ13C1(CH_(4))分布在-51.9‰~-38.2‰,平均-42.84‰;δ13CCO_(2)分布在-8.6‰~-0.63‰,平均-4.66‰;δ13C2分布在-27.36‰~-18.70‰,平均-25.27‰;δ13C3分布在-25.96‰~-14.69‰,平均-22.93‰,且煤层气主要为热成因气体;δ13C1(CH4)较浅部小,δ13CCO_(2)较浅部大。在平面上,从临兴地区东南向西北δ13C1呈增大趋势。从石炭纪起直到三叠纪末,研究区一直处于沉降状态;中侏罗世和早白垩世为主要生烃期,中侏罗世生烃持续时间较长,平均生烃速率较小,生烃产率一般;早白垩世生烃速率较大,生烃产率增加值较高,生气强度达到历史最大,是主要的生烃期。受气体分馏作用、储层孔裂隙发育特征、储层压力以及煤层顶底板密封性的控制,δ13C1随着镜质体最大反射率(Rmax)、含气量和埋深的增加而增加;在向斜核部区、断层应力集中区和褶皱两翼发育区的δ13C1值相对较大;在断层应力释放区和背斜核部δ13C1相对较大,这表明该区域的煤层气封存条件较差,不利于煤层气富集;受地下水溶解的影响,在水动力条件较强的地区δ13C1值较小;在弱流体动力学或滞流区δ13C1没有明显的变轻趋势。综合煤层气地球化学指标认为,临兴和神府地区东南部煤层气富集,且前者更有利,这对后期煤层气选区布井提供参考。

关键词：深部煤层气地球化学碳同位素煤层气组分煤层气成因热演化

Polar plumes observed at the total solar eclipse in 2009

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Science China(Physics,Mechanics & Astronomy) 2011年第10期54卷 1906-1910页

作者： YANG ShuHong ZHANG Jun ZHANG ZhiYong zhao zhaoWang LIU yangbing SONG Qian YANG ShangBin BAO XingMing LI LePing CHU Zhe LI Ting Key Laboratory of Solar Activity National Astronomical Observatories Chinese Academy of Sciences Beijing 100012 China Graduate University of Chinese Academy of Sciences Beijing 100049 China

During the total solar eclipse of July 22, 2009, we carried out a white-light observation in Anji, Zhejiang, China. The aim wasto observe the polar plumes (PPs) with high spatial and temporal resolutions in white-light. With the observational data, weinvestigate the properties and evolution of the PPs and compare them with those of the low-latitude plumes (LPs). We find thatboth the PPs and the LPs have comparable lengths and widths, and the mean length and width are 300 Mm and 16 Mm, re-spectively. The average inclination angle (13 degree) of the PPs is smaller than that (32 degree) of the LPs. Generally, theplumes which are closer to the coronal hole center are more vertical. We trace the PPs and the LPs in the sequence of imagesand find that none of them disappears and no new one is created. Additionally, neither plasma outflow nor transverse oscilla-tion is observed. These imply that the evolution process of plumes is much longer than the timescale of eclipse.

关键词：观测数据极地日全食 PPS LPS 等离子流安吉县浙江省

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基因治疗在肿瘤过继性免疫治疗中的应用

生物医学工程学杂志 2008年第2期25卷 482-486页

作者：王纯(综述) 赵阳兵(审校) 成都体育学院运动医学系成都610041 Surgery Branch National Cancer Institute National Institutes of Health Bethesda Maryland 20892 USA

过继性输注肿瘤浸润性淋巴细胞(TILs)能可靠地治疗转移性黑色素瘤,并使其有效率稳定在50%左右。但由于受TIL来源的限制,大多数非黑色素瘤病人无法使用过继性免疫治疗。使用抗肿瘤抗原TCR修饰的T淋巴细胞成功用于黑色素瘤病人的治疗为非... 详细信息

过继性输注肿瘤浸润性淋巴细胞(TILs)能可靠地治疗转移性黑色素瘤,并使其有效率稳定在50%左右。但由于受TIL来源的限制,大多数非黑色素瘤病人无法使用过继性免疫治疗。使用抗肿瘤抗原TCR修饰的T淋巴细胞成功用于黑色素瘤病人的治疗为非黑色素瘤癌症病人的过继性免疫治疗提供了方向。本综述介绍了近几年来肿瘤特异性过继免疫治疗的进展,重点介绍基因修饰的T淋巴细胞的应用及存在的问题,并展望了发展前景。

关键词：过继性免疫治疗肿瘤基因治疗 T细胞受体