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Super-enhancer receives signals from the extracellular matrix to induce PD-L1-mediated immune evasion via integrin/ BRAF/TAK1/ERK/ETV4 signaling

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Cancer Biology & Medicine 2022年第5期19卷 669-684页

作者： Panpan Ma Xinxin Jin Zhiwei Fan Zhou Wang Suhui Yue Changyue Wu Shiyin Chen Yuanyuan Wu Miaomiao chen Donghua Gu Siliang Zhang Renfang Mao Yihui Fan Laboratory of Medical Science School of MedicineNantong UniversityNantong 226001China Department of Pathogenic Biology School of MedicineNantong UniversityNantong 226001China Department of Clinical Laboratory Yancheng No.1 People’s HospitalYancheng 224005China School of Life Sciences Nantong UniversityNantong 226001China Department of Dermatology Affiliated Hospital of Nantong UniversityNantong UniversityNantong 226001China The Department of Urology the Second Affiliated Hospital of Nantong UniversityNantong UniversityNantong 226001China The Department of Radiotherapy Oncology Harbin Medical University Cancer HospitalHarbin 150086China Department of Pathophysiology School of MedicineNantong UniversityNantong 226001China

Objective:PD-L1 and PD-L2 expression levels determine immune evasion and the therapeutic efficacy of immune checkpoint blockade.The factors that drive inducible PD-L1 expression have been extensively studied,but mechanisms that result in constitutive PD-L1 expression in cancer cells are largely unknown.Methods:DNA elements were deleted in cells by CRISPR/Cas9-mediated knockout.Protein function was inhibited by chemical inhibitors.Protein levels were examined by Western blot,mRNA levels were examined by real-time RT-PCR,and surface protein expression was determined by cellular immunofluorescence and flow cytometry.Immune evasion was examined by in vitro T cell-mediated killing.Results:We determined the core regions(chr9:5,496,378–5,499,663)of a previously identified PD-L1L2-super-enhancer(SE).Through systematic analysis,we found that the E26 transformation-specific(ETS)variant transcription factor(ETV4)bound to this core DNA region but not to DNA surrounding PD-L1L2SE.Genetic knockout of ETV4 dramatically reduced the expressions of both PD-L1 and PD-L2.ETV4 transcription was dependent on ERK activation,and BRAF/TAK1-induced ERK activation was dependent on extracellular signaling fromαvβ3 integrin,which profoundly affected ETV4 transcription and PD-L1/L2 expression.Genetic silencing or pharmacological inhibition of components of the PD-L1L2-SE-associated pathway rendered cancer cells susceptible to T cell-mediated killing.Conclusions:We identified a pathway originating from the extracellular matrix that signaled via integrin/BRAF/TAK1/ERK/ETV4 to PD-L1L2-SE to induce PD-L1-mediated immune evasion.These results provided new insights into PD-L1L2-SE activation and pathways associated with immune checkpoint regulation in cancer.

关键词： PD-L1 super-enhancer ETV4 ERK αvβ3 integrin BRAF TAK1

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明代书信数字化研究的新尝试——以哈佛大学CSA明代书信计划为例

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图书馆论坛 2023年第12期43卷 186-192页

作者：陈士银扬州大学社会发展学院历史系哈佛大学

基于社会关系网络数据众包平台CSA以及中国历代人物传记资料库CBDB的明代书信计划是通过书信作者、收信人、书信名称及其所属文集进行检索的数据平台。自2020年成立以来,该平台已收录1,650位明代人物超过52,399封书信信息,另有约5万封... 详细信息

基于社会关系网络数据众包平台CSA以及中国历代人物传记资料库CBDB的明代书信计划是通过书信作者、收信人、书信名称及其所属文集进行检索的数据平台。自2020年成立以来,该平台已收录1,650位明代人物超过52,399封书信信息,另有约5万封书信信息待收录。通过整理书信往来人物,建立与CBDB数据库的关联,可以批量利用这些书信探索相关人物的身份信息,包括姓名、别名、籍贯、入仕、官名、著述、亲属关系与社交网络等,丰富对明代历史人物及其社会关系的研究。

关键词：明代书信数字化明代书信计划中国历代人物传记资料库

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The State of the Art of Data Science and Engineering in Structural Health Monitoring

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Engineering 2019年第2期5卷 234-242页

作者： Yuequan Bao Zhicheng chen shiyin Wei Yang Xu Zhiyi Tang Hui Li School of Civil Engineering Harbin Institute of Technology Harbin 150090 China

Structural health monitoring (SHM) is a multi-discipline field that involves the automatic sensing of structural loads and response by means of a large number of sensors and instruments, followed by a diagnosis of the structural health based on the collected data. Because an SHM system implemented into a structure automatically senses, evaluates, and warns about structural conditions in real time, massive data are a significant feature of SHM. The techniques related to massive data are referred to as data science and engineering, and include acquisition techniques, transition techniques, management techniques, and processing and mining algorithms for massive data. This paper provides a brief review of the state of the art of data science and engineering in SHM as investigated by these authors, and covers the compressive sampling-based data-acquisition algorithm, the anomaly data diagnosis approach using a deep learning algorithm, crack identification approaches using computer vision techniques, and condition assessment approaches for bridges using machine learning algorithms. Future trends are discussed in the conclusion.

关键词： Structural health monitoring Monitoring data Compressive sampling Machine learning Deep learning

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益气养阴通络汤联合贝那普利治疗糖尿病肾病疗效及对血清TGF-β1、VEGF指标影响

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中华中医药学刊 2024年第3期42卷 238-242页

作者：陈仕银胡朋海口市人民医院中医科海南海口570000

目的探讨益气养阴通络汤联合贝那普利治疗糖尿病肾病(diabetic nephropathy,DN)的疗效及对转化生长因子-β_(1)(transforming growth factor-β_(1),TGF-β_(1)),血管内皮生长因子(vascular endothelial growth factor,VEGF)影响。方法选取2019年10月—2021年10月医院收治的DN病人94例,随机分为对照组(n=48)和观察组(n=46)。入院后两组病人均实施生活方式相关的指导,包括体质量控制、运动、戒烟酒等,给予脂质的代谢紊乱相关纠正、血糖控制、血压等基础的治疗,对照组实施盐酸贝那普利片的口服治疗,观察组则在此基础上实施益气养阴通络汤治疗,两组持续治疗4周。对比两组临床疗效、尿微量白蛋白(microalbumin,mALB)、尿白蛋白肌酐比(urine albumin creatine ratio,UACR)、β_(2)微球蛋白(β_(2)-microglobulin,β_(2)-MG)水平、中医证候评分、血清同型半胱氨酸(homocysteine,Hcy)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(Interleukin-6,IL-6)、血清TGF-β_(1)和VEGF及空腹血糖(fasting plasma glucose/fasting blood glucose,FPG)、餐后2 h血糖(2 hour postprandial blood glucose,2 h PG)和糖化血红蛋白(glyeosylated hemoglobin,HbAlc)指标变化。结果治疗前两组mALB、UACR、β_(2)-MG指标间无统计学意义(P>0.05);治疗后两组mALB、UACR、β_(2)-MG指标较治疗前显著降低(P<0.05);并且观察组降低较明显(P<0.05);观察组治疗总有效率较对照组明显较高(P<0.05);治疗后两组主症评分、次症评分和中医证候总评分明显降低(P<0.05);且观察组降低较明显(P<0.05);治疗后两组血清Hcy、TNF-α、IL-6指标明显降低(P<0.05);且观察组降低较明显(P<0.05);治疗后两组血清TGF-β_(1)和VEGF指标较治疗前明显降低(P<0.05);且观察组降低较明显(P<0.05);治疗后两组FPG、2 h PG和HbAlc指标较治疗前明显降低(P<0.05);且观察组降低较明显(P<0.05)。结论采用益气养阴通络汤联合贝那普利治疗DN具有较好的临床疗效,可降低血清TGF-β_(1),VEGF指标,降低蛋白尿水平。

关键词：益气养阴通络汤贝那普利糖尿病肾病临床疗效血清TGF-β1 VEGF

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产业转移污染的法律应对

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中国政法大学学报 2020年第2期 51-62,207页

作者：陈世寅中国政法大学民商经济法学院

我国产业转移包括区际转移和城乡转移。腾格里沙漠污染的爆发使我们不得不再次审视产业转移带来的环境污染,其中表现的环境法律实施缺位问题,具体体现为环境影响评价环节的缺失、排污监测系统的失效以及行政权力的过度使用。深入分析我... 详细信息

我国产业转移包括区际转移和城乡转移。腾格里沙漠污染的爆发使我们不得不再次审视产业转移带来的环境污染,其中表现的环境法律实施缺位问题,具体体现为环境影响评价环节的缺失、排污监测系统的失效以及行政权力的过度使用。深入分析我国近几十年的经济发展模式,发现产业转移是中西部地区和农村环境污染的重要原因。但作为全球经济发展通行模式,也作为我国经济发展战略决策,产业转移不可避免。因此,如何有序地引导产业转移成为决策者和执行者考虑的重要问题。宏观上国家发展战略应具有可持续,充分利用主体功能区划制度;微观上将环境法落到实处,相关环境行政管理机关和地方政府强化环境执法,合理、充分地利用环境司法工具作为最后一道屏障。

关键词：产业转移污染腾格里沙漠环境法实施司法工具

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Development of a fluorescent probe hydrolysis-insulated isothermal PCR for rapid and sensitive on-site detection of African swine fever virus

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Virologica Sinica 2022年第3期37卷 462-464页

作者： Tianli Zou Junhua Deng Xiangdong Li shiyin Zhang Lingyan chen Liying Hao Jinshan Zhuang Heng Wang Guihong Zhang Shengxiang Ge Kegong Tian Beijing Wantai Biopharmaceutical Co. LtdBeijing102206China Luoyang Putai Bio-Tech Co.Ltd Luoyang471003China National Research Center for Veterinary Medicine Luoyang471003China School of Public Health Xiamen UniversityXiamen361102China ASFV Regional Reference Laboratory in Guangzhou South China Agricultural UniversityGuangzhou510642China

Dear Editor,African swine fever virus(ASFV),the sole member of the family Asfarviridae,is the causative agent of African swine fever(ASF),a viral disease that leads to high mortality in domestic pigs.Since firstly identified in Kenya in the 1920s,ASFV has been prevalent in Africa,Europe,and Russian Federation(Sanchez et al.,2019).Recently,ASFV was introduced to Asian countries including China,Mongolia,Vietnam,Cambodia,Laos and South Korea,which lead to huge economic losses to local pig industries(Li and Tian,2018;Gaudreault and Richt,2019).The first case of ASFV in China was reported in August 2018(Zhou et al.,2018).

关键词： swine hydrolysis African

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SPOC模式在历史类教学课程中的引入和实践

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科技风 2022年第4期 108-110页

作者：陈士银扬州大学社会发展学院江苏扬州225000

历史类课程多以“传统”“保守”等著称。即便如此,历史类课程也可紧跟时代步伐,尝试采取SPOC混合教学等新型教学模式。实践证明,在一定程度上,SPOC教学模式有助于拓展教学空间,增强师生之间的互动,也有助于历史类课程实现从“教师本位... 详细信息

历史类课程多以“传统”“保守”等著称。即便如此,历史类课程也可紧跟时代步伐,尝试采取SPOC混合教学等新型教学模式。实践证明,在一定程度上,SPOC教学模式有助于拓展教学空间,增强师生之间的互动,也有助于历史类课程实现从“教师本位”到“学生本位”的转换,从而提升教学质量。

关键词： SPOC 历史类课程教学反馈学生本位

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Remodeling the tumor immune microenvironment via siRNA therapy for precision cancer treatment

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Asian Journal of Pharmaceutical Sciences 2023年第5期18卷 51-76页

作者： Lingxi Jiang Yao Qi Lei Yang Yangbao Miao Weiming Ren Hongmei Liu Yi Huang Shan Huang Shiyin Chen Yi Shi Lulu Cai Department of Pharmacy Personalized Drug Therapy Key Laboratory of Sichuan ProvinceSichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610072China Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072China Health Management Center Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072China Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences(2019RU026) Sichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalChengdu 610072China Department of Pharmacy Jianyang People’s Hospital of Sichuan ProvinceJianyang 641400China

How to effectively transform the pro-oncogenic tumor microenvironments(TME)surrounding a tumor into an anti-tumoral never fails to attract people to study.Small interfering RNA(siRNA)is considered one of the most noteworthy research directions that can regulate gene expression following a process known as RNA interference(RNAi).The research about siRNA delivery targeting tumor cells and TME has been on the rise in recent years.Using siRNA drugs to silence critical proteins in TME was one of the most efficient solutions.However,the manufacture of a siRNA delivery system faces three major obstacles,i.e.,appropriate cargo protection,accurately targeted delivery,and site-specific cargo release.In the following review,we summarized the pharmacological actions of siRNA drugs in remolding TME.In addition,the delivery strategies of siRNA drugs and combination therapy with siRNA drugs to remodel TME are thoroughly discussed.In the meanwhile,the most recent advancements in the development of all clinically investigated and commercialized siRNA delivery technologies are also presented.Ultimately,we propose that nanoparticle drug delivery siRNA may be the future research focus of oncogene therapy.This summary offers a thorough analysis and roadmap for general readers working in the field.

关键词： Small interfering RNA Tumor microenvironment siRNA delivery Cancer therapy Co-delivery

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Influencing Factors of Rural Land Internal Circulation Market in Guangdong Province

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Asian Agricultural Research 2020年第4期12卷 28-33页

作者： Shiyin Chen Zhiyu MA Management College of Guangdong Ocean University Zhanjiang 524088 China

The circulation of rural land is helpful to improving the allocation efficiency of land resources,increasing farmers'income and promoting the development of modern agriculture.In this paper,we used the social economy,the main participants and the market environment of rural land circulation to make a qualitative analysis for the factor of rural land internal circulation.With the aid of principal component analysis,grey correlation model,and other methods to make a quantitative analysis for the factor of rural land internal circulation.The results show that the grey correlation degrees of the output value of secondary and tertiary industries as a proportion of GDP,the expenditure on science and education per capita,the expenditure on financial support for agriculture,the proportion of non-agricultural population and the standardization of rural land circulation contracts are 0.8988,0.8382,0.7632 and 0.7576 respectively,indicating that these factors are significantly related to the rural internal land circulation market.

关键词： Rural land Internal circulation market Influencing factors Guangdong Province

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滋阴养阴汤联合吡格列酮在2 型糖尿病中的价值研究

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辽宁中医杂志 2023年第12期50卷 77-80页

作者：陈仕银胡朋海口市人民医院中医科海南海口570000

目的评价滋阴养阴汤联合吡格列酮在2型糖尿病治疗中的价值研究及对胰岛功能的改善作用。方法将2019年10月—2021年1月来海口市人民医院治疗的糖尿病患者128例以随机数字表法分为研究组(64例)和参照组(64例)。参照组患者口服吡格列酮,30 ... 详细信息

目的评价滋阴养阴汤联合吡格列酮在2型糖尿病治疗中的价值研究及对胰岛功能的改善作用。方法将2019年10月—2021年1月来海口市人民医院治疗的糖尿病患者128例以随机数字表法分为研究组(64例)和参照组(64例)。参照组患者口服吡格列酮,30 mg/次,1次/d,并结合盐酸二甲双胍片治疗;研究组采用在参照组患者治疗基础上结合滋阴养阴汤治疗。两组分别治疗3个月。比较两组治疗前后气阴两虚证相关中医证候积分变化和疗效;比较两组治疗前后血糖指标和胰岛素功能指标。结果研究组治疗总有效率高于参照组(P<0.05);治疗后研究组口渴多饮、气短懒言、五心烦热、神疲乏力、腰膝酸软和口干咽燥等中医证候积分降低幅度优于参照组(P<0.05);治疗后研究组胰岛素功能指标胰岛素分泌功能指数(homeostatic model assessment ofβ-cell funtion,HOMA-β)高于参照组,胰岛素抵抗指数(homeostaic model assessment insulin resistance index,HOMA-IR)低于参照组(P<0.05);治疗后研究组血糖指标降低幅度优于参照组(P<0.05)。结论滋阴养阴汤联合吡格列酮可显著改善糖尿病患者的中医证候,降低血糖,促进胰岛素的改善,提高胰岛素敏感性,降低胰岛素抵抗,提高治疗疗效,值得临床进一步研究探讨。

关键词：滋阴养阴汤吡格列酮糖尿病胰岛素抵抗影响

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