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L1CAM overexpression promotes tumor progression through recruitment of regulatory T cells in esophageal carcinoma

Cancer Biology & Medicine 2021年第2期18卷 547-561页

作者： Xuan zhao Shasha Liu Xinfeng Chen Jianyi zhao Feng Li qitai zhao Tan Xie Lan Huang Zhen Zhang Yu Qi Yang Yang Song zhao Yi Zhang Biotherapy Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Cancer Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Thoracic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Pediatric Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China School of Life Sciences Zhengzhou UniversityZhengzhou 450052China Henan Key Laboratory for Tumor Immunology and Biotherapy Zhengzhou 450052China

Objective:L1 cell adhesion molecule(L1 CAM)exhibits oncogenic activity in ***,the link between L1 CAM and the tumor microenvironment remains poorly understood in patients with esophageal squamous cell carcinoma(ESCC).In this study,we investigated how L1 CAM expression in ESCC affects the oncogenic characteristics of tumor cells and the tumor ***:Human ESCC samples were collected,and the m RNA and protein levels of L1 CAM were examined by real-time PCR and *** and knockdown gene expression assays were used for mechanistic *** cell proliferation and cell cycle were measured with CCK-8 assays and flow *** migration and invasion ability were measured with Transwell *** bead-based assays were performed to identity the factors downstream of L1 *** studies were performed in nude mice to evaluate the effects of L1 CAM on tumor growth and regulatory T cell(Treg)***:L1 CAM expression was significantly elevated in ESCC tissues(P<0.001)and correlated with poorer prognosis(P<0.05).Ablation of L1 CAM in ESCC cells inhibited tumor growth and migration,and increased tumor cell apoptosis(P<0.05).In the tumor microenvironment,L1 CAM expression correlated with Treg infiltration in ESCC by affecting CCL22 ***,L1 CAM facilitated CCL22 expression by activating the PI3 K/Akt/NF-κB signaling ***,CCL22 promoted Treg recruitment to the tumor site;the Tregs then secreted TGF-β,which in turn promoted L1 CAM expression via Smad2/3 in a positive feedback ***:Our findings provide new insight into the mechanism of immune evasion mediated by L1 CAM,suggesting that targeting L1 CAM-CCL22-TGF-βcrosstalk between tumor cells and Tregs may offer a unique means to improve treatment of patients with ESCC.

关键词： L1CAM CCL22 Tregs TGF-β esophageal squamous cell carcinoma

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Overcoming resistance to immunotherapy by targeting GPR84 in myeloid-derived suppressor cells

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2408-2422页

作者： Guohui Qin Shasha Liu Jinyan Liu Hongwei Hu Li Yang qitai zhao Congcong Li Bin Zhang Yi Zhang Biotherapy Center and Cancer Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan450052China Department of Medicine-Division of Hematology/Oncology Feinberg School of Medicine Northwestern UniversityChicagoIL60611USA School of Life Sciences Zhengzhou UniversityZhengzhouHenan450001China Henan Key Laboratory for Tumor Immunology and Biotherapy ZhengzhouHenan450052China State Key Laboratory of Esophageal Cancer Prevention&Treatment Zhengzhou UniversityZhengzhouHenan450052China

Myeloid-derived suppressor cells(MDSCs)were found to gradually accumulate in the orthotopic esophageal cancer mouse model during tumor *** the roles of MDSCs in promoting tumor growth and inhibiting immune response have been extensively explored,currently,there are still no effective means for targeting MDSCs *** deficiency of specific markers of MDSCs was responsible for the limited strategy to eliminating in *** study identified that GPR84 was exclusively overexpressed on *** was further found that GPR84 was prominently expressed on MDSCs in clinical samples and tumor mouse models,which drives the immunosuppression on CD8^(+)T cells by inhibiting PD-L1 degradation in ***,G-CSF and GM-CSF were found to induce GPR84 expression through the STAT3/C/EBPβsignaling *** addition,GPR84+MDSCs and PD-L1^(+)MDSCs were highly accumulated in anti-PD-1 therapy-resistant patients with esophageal cancer,and high GPR84 signature risk was verified as a negative factor for the overall survival of patients with anti-PD-1 ***,GPR84 antagonism combined with an anti-PD-1 antibody enhanced the antitumor ***,targeting GPR84 enhanced anti-PD-1 efficacy in esophageal cancer and other malignant *** combination therapy has the potential for tumor therapy in clinics.

关键词： esophageal inhibiting suppressor

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Integrated characterization of CD8+T cells in solid tumors through single-cell RNA-sequencing analysis

Integrated characterization of CD8+T cells in solid tumors t...

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第十四届全国免疫学学术大会

作者： qitai zhao Lan Huang Yachang Huo Yi Zhang the First Affiliated Hospital of Zhengzhou University

CD8T cells are essential for cancer immunotherapy,but the heterogeneity and dynamics remain poorly *** characterize CD8T cells in solid tumors,we integrated 1 8 datasets containing 11 types of tumors,7 diffe rent tissues,and384 samples using canonical correlation analysis(CCA) and obtained more than 100000 CD8T cells at single-cell *** identified 16 clusters of CD8T cells with different characteristics and their specific gene signatures,***,a transition of CD8T cells from effector to exhausted are accompanied with alterations of LAG3 and *** uncovered two clusters of exhausted subsets,terminally and proliferating,those mainly exist in tumor tissues and have a high TCR clone *** set enrichment analysis(GSEA) revealed that MYC targets,G2 M checkpoint and fatty acid metabolism signaling were enriched in proliferating exhausted CD8T ***,an exhausted phenotype was correlated with the response of *** integrated analysis provides the insight into the diversity and transition of CD8T cells and its impact on immunotherapy.

关键词： CD8+T cells Single-cell RNA-sequencing analysis integrated analysis immunotherapy

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电解氟化在无机氟化物制备中的应用

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无机盐工业 2013年第3期45卷 1-4页

作者：赵启泰赵建轩核工业理化工程研究院天津300180 天津英伦研究开发中心

电解氟化是制备多种有机氟化物的重要方法之一,依据其工艺过程和机理,它也是制备某些无机氟化物的重要方法。介绍了电解氟化的工艺过程和反应机理,并提出电解氟化在无机氟化物制备中应用的方法。提出了机理的新概念——弱电场自由基反... 详细信息

电解氟化是制备多种有机氟化物的重要方法之一,依据其工艺过程和机理,它也是制备某些无机氟化物的重要方法。介绍了电解氟化的工艺过程和反应机理,并提出电解氟化在无机氟化物制备中应用的方法。提出了机理的新概念——弱电场自由基反应机理。

关键词：电解氟化电化学氟化无机氟化物反应机理

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二(三氟甲基磺酰)亚胺锂的应用与制备

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化工生产与技术 2008年第6期15卷 3-4,7页

作者：赵启泰核工业理化工程研究院天津300100

介绍了一种重要的有机氟化物——二(三氟甲基磺酰)亚胺锂的特性及其制法;叙述了它在有机合成和有机离子导体方面的应用;对近期国外报道的制备方法进行了工业生产的可行性分析。

关键词：二(三氟甲基磺酰)亚胺锂酸催化剂应用制备方法电化学氧化

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基于摩擦材料的摩擦摆隔震耗能试验探究

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四川建筑科学研究 2017年第5期43卷 90-93页

作者：李晓东王起台赵健兰州理工大学土木工程学院甘肃兰州730050

根据摩擦摆支座的基本构成和隔震原理,通过控制试验变量法探究了采用聚四氟乙烯和超高分子量聚乙烯两种不同摩擦材料时的支座力学性能,考察了竖向压力和滑移加载速率对摩擦摆支座滞回特性性能的影响规律。结果表明:摩擦摆支座的滞回特... 详细信息

根据摩擦摆支座的基本构成和隔震原理,通过控制试验变量法探究了采用聚四氟乙烯和超高分子量聚乙烯两种不同摩擦材料时的支座力学性能,考察了竖向压力和滑移加载速率对摩擦摆支座滞回特性性能的影响规律。结果表明:摩擦摆支座的滞回特性是由摩擦材料、竖向压力和滑移速率等因素共同影响的,且与润滑摩擦相比,干摩擦时的水平滞回曲线更加饱满,耗能能力更好。

关键词：摩擦摆支座摩擦材料滞回特性

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Immune molecular classification and characteristics of urothelial bladder cancer

Immune molecular classification and characteristics of uroth...

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第十四届全国免疫学学术大会

作者： Li Yang Aitian Li Fengsen Liu qitai zhao Shaofei Ji Wen Zhu Weina Yu Ru Zhang Yaqing Liu Wencai Li Yi Zhang The First Affiliated Hospital of Zhengzhou University 郑州市骨科医院

Objective:Urothelial bladder cancer(UBC) is the most common malignant tumor of the urinary system and is one of the ten most common *** patients with advanced cancer have shown durable remission,owing to the introduction of checkpoint inhibitors and other immunotherapies.H owever,not all patients with UBC can benefit from immune checkpoint *** in immune profiles have been linked to the subtypes,prognosis,and therapeutic responses of ***,the aim of this study was to further characterize the immune profile of UBC to identify subtypes that may be relevant for therapy ***:lmmune-related genes(IRGs) were analyzed using principal component analysis(PCA) and uniform manifold approximation and projection(UMAP) to identified the immune subtypes of *** different subtypes survival was estimated by Kaplan-Meier *** analysis evaluated the relationship between populations of the four subtypes and clinical pathological ***,the correlation between the expression of T cell signature genes and patient survival was *** and comparisons showed the immune cell infiltration in diffe rent ***,the relationship between immune cell infiltration and IRGs expression in the hot tumor subtype,and the relationship between immune cell infiltration and inhibitory molecules were explored using correlation ***,the enriched signaling pathways in each subtype,except cold tumor,were measured by GO and KEGG *** exhibited the correlation between these signaling pathways and immune cell infiltration or *** and immunofluorescence staining further confirmed using human UBC ***:The immune profile of UBC can be identified into four subtypes:immune ignorant,cold tumor,immune inactive,and hot *** survival in subtypes 2 and 4 was better than that of subtypes 1 and *** pathology and other clinical parameters of patients in cold tumor

关键词： urothelial bladder cancer immune profiling immune cell infiltration tumor-intrinsic signaling pathway prognosis

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定向编辑CTLA4基因的向导RNA体外合成体系的构建及其编辑效率

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中国肿瘤生物治疗杂志 2017年第12期24卷 1362-1369页

作者：任飞飞李峰李砺锋赵启泰黄岚张毅郑州大学第一附属医院生物细胞治疗中心河南郑州450052 郑州大学生命科学学院河南郑州450052 郑州大学第一附属医院肿瘤科河南郑州450052

目的:基于CRISPR/Cas9基因编辑技术原理体外合成定向编辑细胞毒性T淋巴细胞相关抗原4(cytotoxic T-lymphocyte-associated protein 4,CTLA4)基因的向导RNA(small guide RNA,sgRNA)。方法:(1)使用Crispr网站对CTLA4位点的sgRNA进行预测并设计出3个sgRNA(sgRNA1、sgRNA2、sgRNA3),构建sgRNA重组质粒,将其转染293T细胞,48 h后提取基因组DNA,利用T7EN1核酸内切酶筛选活性较高的sgRNA序列;(2)以筛选到的sgRNA重组质粒为模板,设计引物并用PCR扩增体外合成sgRNA的DNA模板片段,进一步优化体外转录条件,转录出sgRNA,并利用Cas9核酸酶体外检测转录纯化sgRNA的切割效率;(3)将sgRNA与转录得到的Cas9 mRNA电转化入肺癌患者CD3^+T细胞,实现靶基因敲除。结果:T7EN1核酸内切酶实验证实了sgRNA2序列靶向敲除效率最高,效率达到66%;优化体外合成体系后,转录得到的CTLA4 sgRNA2产量高,具有较高的活性,在靶点上成功切开了DNA双链,Cas9核酸酶检测出其切割效率达到了65%;最终可在肺癌患者CD3^+T细胞中有效敲除CTLA4基因,CTLA4分子的表达从46%降低到22%,T7E1核酸内切酶实验进一步证实了其编辑效率为56%。结论:体外成功构建了具有较高编辑效率的定向编辑CTLA4基因的sgRNA,为后续针对该基因制定相应的免疫治疗策略奠定了基础。

关键词：肺癌免疫检查点 CTLA4 CRISPR/Cas9 向导RNA 体外转录

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贵州冬季层状云的观测研究

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气象 1988年第5期 9-14页

作者：李启泰卢成孝赵彩贵州省气象科学研究所

本文使用贵阳地区的探空、飞机探测、地面降水以及飞机撒播干冰人工增雨试验的初步结果等资料,对贵州冬季层状云的宏、微观结构,降水性质,降水的区域相关,云层对太阳辐射的影响以及人工催化增雨的可能性及实施作业的实际增雨效果等进行... 详细信息

本文使用贵阳地区的探空、飞机探测、地面降水以及飞机撒播干冰人工增雨试验的初步结果等资料,对贵州冬季层状云的宏、微观结构,降水性质,降水的区域相关,云层对太阳辐射的影响以及人工催化增雨的可能性及实施作业的实际增雨效果等进行了综合的研究分析。研究和试验结果表明,冬季层状云在贵州国民经济生产中,既是一种不利因素,又是一种可供实际开发的空中水资源。

关键词：层状云平均云层贵阳雨淞云底冻雨人工催化增雨飞机探测贵州

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水驱特征曲线应用中的问题研究

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石油勘探与开发 1986年第5期 37-44页

作者：林志芳俞启泰赵明石油工业部石油勘探开发科学研究院

应用油田生产和油水相对渗透率资料,分析了水驱特征曲线的形态,指出了直线段出现的条件。我国油田在开发过程中大多采用了细分开发层系、钻加密井、完善注采方式、提高排液量以及分层注水、堵水、压裂、酸化等调整措施。文中分析了这些... 详细信息

应用油田生产和油水相对渗透率资料,分析了水驱特征曲线的形态,指出了直线段出现的条件。我国油田在开发过程中大多采用了细分开发层系、钻加密井、完善注采方式、提高排液量以及分层注水、堵水、压裂、酸化等调整措施。文中分析了这些措施对水驱特征曲线的影响,以及在预测可采储量时需注意的问题和方法。文章强调指出,预测油田可采储量必须与开发分析相结合,要认识直线段所表达的物理意义,从而确定预测结果的取舍。在通常情况下,水油比-累积产油量、累积产水量-累积产油量这两条相关曲线的直线段应保持平行,预测时并用这两条曲线有助于提高预测效果。

关键词：水驱特征油田直线段矿物燃料矿床累积产油

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