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Novel phthalimides regulating PD-1/PD-L1 interaction as potential immunotherapy agents

Acta Pharmaceutica Sinica B 2022年第12期12卷 4446-4457页

作者： Chengliang Sun Yao Cheng Xiaojia Liu Gefei Wang Wenjian Min Xiao Wang Kai Yuan Yi Hou Jiaxing Li Haolin Zhang Haojie Dong Liping Wang chenguang lou Yanze Sun Xinmiao Yu Hongbin Deng Yibei Xiao Peng Yang State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization China Pharmaceutical UniversityNanjing 210009China Department of Medicinal Chemistry School of PharmacyChina Pharmaceutical UniversityNanjing 211198China Department of Pharmacology School of PharmacyChina Pharmaceutical UniversityNanjing 211198China Beijing Institute of Clinical Pharmacy Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of Physics Chemistry and PharmacyUniversity of Southern DenmarkCampusvej 555230 OdenseDenmark Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1)have emerged as one of the most promising immune checkpoint targets for cancer *** the inherent advantages of small-molecule inhibitors over antibodies,the discovery of small-molecule inhibitors has fallen behind that of antibody *** on docking studies between small molecule inhibitor and PD-L1 protein,changing the chemical linker of inhibitor from a flexible chain to an aromatic ring may improve its binding capacity to PD-L1 protein,which was not reported before.A series of novel phthalimide derivatives from structure-based rational design was synthesized.P39 was identified as the best inhibitor with promising activity,which not only inhibited PD-1/PD-L1 interaction(IC_(50)=8.9 nmol/L),but also enhanced killing efficacy of immune cells on cancer ***-crystal data demonstrated that P39 induced the dimerization of PD-L1 proteins,thereby blocking the binding of PD-1/***,P39 exhibited a favorable safety profile with a LD_(50)>5000 mg/kg and showed significant in vivo antitumor activity through promoting CD8^(+)T cell *** these data suggest that P39 acts as a promising small chemical inhibitor against the PD-1/PD-L1 axis and has the potential to improve the immunotherapy efficacy of T-cells.

关键词： PD-1/PD-L1 Small-molecule inhibitor Immunotherapy Co-crystal structure

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恩义文化传统的式微与重构——一道高三作文题引发的思考

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科教文汇 2013年第35期 166-166,169页

作者：楼晨光银川市唐徕回民中学宁夏银川750001

改革开放以后,人们的物质生活越来越丰裕了。但我们身边,一方面有不知孝顺父母,不知感恩老师,受了恩惠不知报答有了成就不懂回馈的人;另一方面也有一些功成名就之士乐意于公益慈善事业扶贫救危但却方法欠妥遭遇尴尬的现象。传统的恩义... 详细信息

改革开放以后,人们的物质生活越来越丰裕了。但我们身边,一方面有不知孝顺父母,不知感恩老师,受了恩惠不知报答有了成就不懂回馈的人;另一方面也有一些功成名就之士乐意于公益慈善事业扶贫救危但却方法欠妥遭遇尴尬的现象。传统的恩义文化链条本应能够传递正能量并承担积极的作用,但现实是它的确在日渐式微。幸好已经有越来越多的人在关注这个问题,并投身到具体的恩义文化传统的重构和传承的工作中去。家庭、学校、社会各界共同致力于感恩教育和责任教育中,以重构新型的恩义文化,全社会每一个人都有义务去主动重构并传承恩义文化。

关键词：感恩施恩报恩恩义文化伦理道德价值教育素质

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离心钢管混凝土长柱轴压性能分析

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安徽建筑大学学报 2019年第3期27卷 10-15页

作者：曹玉娟娄晨光赵锐戴良军陈刚合肥工业大学土木与水利工程学院安徽合肥230009 安徽建工集团有限公司安徽合肥230001

针对离心钢管混凝土长柱,运用ABAQUS有限元软件进行模拟,采用正交试验的分析方法,研究钢管壁厚、空心率及长细比对长柱轴压承载力的影响,结果表明,各因素影响能力顺序为:钢管壁厚>空心率>长细比。钢管壁厚每增加1mm,承载力增加约17%;空... 详细信息

针对离心钢管混凝土长柱,运用ABAQUS有限元软件进行模拟,采用正交试验的分析方法,研究钢管壁厚、空心率及长细比对长柱轴压承载力的影响,结果表明,各因素影响能力顺序为:钢管壁厚>空心率>长细比。钢管壁厚每增加1mm,承载力增加约17%;空心率每增加0.08,承载力减少约9%;长细比每增加10,承载力降低幅度均小于1%。将有限元计算结果与现有相关规范中的叠加理论和统一理论计算结果比较表明,理论计算值较有限元模拟值偏小7%~9%。工程运用中选用统一理论进行计算,更偏于安全。

关键词：离心钢管混凝土长柱有限元分析轴压承载力正交试验参数分析

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Rice SPL10 positively regulates trichome development through expression of HL6 and auxin-related genes

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Journal of Integrative Plant Biology 2021年第8期63卷 1521-1536页

作者： Jinjie Li Bo Tang Yingxiu Li chenguang Li Minjie Guo Haiyang Chen Shichen Han Jin Li Qijin lou Wenqiang Sun Peng Wang Haifeng Guo Wei Ye Zhanying Zhang Hongliang Zhang Sibin Yu Long Zhang Zichao Li State Key Laboratory of Agrobiotechnology/Beijing Key Laboratory of Crop Genetic Improvement College of Agronomy and BiotechnologyChina Agricultural UniversityBeijing100193 China National Key Laboratory of Crop Genetic Improvement Huazhong Agricultural UniversityWuhan430070 China College of Plant Protection China Agricultural UniversityBeijing100193 China

Trichomes function in plant defenses against biotic and abiotic stresses;examination of glabrous lines,which lack trichomes,has revealed key aspects of trichome development and *** of allelism in 51 glabrous rice(Oryza sativa)accessions collected worldwide identified OsSPL10 and OsWOX3B as regulators of trichome development in ***,we report that OsSPL10 acts as a transcriptional regulator controlling trichome *** and transient expression analyses revealed that variation in the approximately 700-bp OsSPL10 promoter region is the primary cause of the glabrous phenotype in the indica cultivar *** of OsSPL10 by genome editing decreased leaf trichome density and length in the NIL-HL6 *** with genotype OsSPL10^(WD-17993)/HL6 generated by crossing WD-17993 with NIL-HL6 also had fewer trichomes in the *** LEAF6(HL6)encodes another transcription factor that regulates trichome initiation and elongation,and OsSPL10 directly binds to the HL6 promoter to regulate its ***,the transcript levels of auxin-related genes,such as OsYUCCA5 and OsPIN-FORMED1b,were altered in OsSPL10 overexpression and RNAi transgenic *** tests using locusts(Locusta migratoria)demonstrated that non-glandular trichomes affect feeding by this *** findings provide a molecular framework for trichome development and an ecological perspective on trichome functions.

关键词： auxin complementary genes hairy leaves Oryza sativa OsWOX3B

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Causes of Recurrence of Rice Chilo suppressalis( Walker) in Longyou County and Prevention and Control Measures

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Asian Agricultural Research 2019年第2期11卷 111-113,116页

作者： Ying WANG Yong ZHANG chenguang ZHANG Runzhong lou Xinxin XU Xiaowei XU Longyou County Plant Protection and Quarantine Station of Zhejiang Province Quzhou City Plant Protection and Quarantine Station of Zhejiang Province

In recent years,the occurrence of rice Chilo suppressalis( Walker) in Longyou County of Zhejiang Province has increased year by year and has become aggravated. This poses a great threat to the safety of rice production. In order to curb the recurrence momentum of rice C. suppressalis,according to the dynamic monitoring and field system survey of rice C. suppressalis in Longyou County since 2015,the causes of the annual increase of rice C. suppressalis in recent years were analyzed,and the recurrence area of C. suppressalis was introduced,and finally some prevention and control measures were put forward.

关键词： Chilo suppressalis (Walker) Causes of recurrence Prevention and control measures

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中国职业技术教育的发展与挑战——基于全国32所职业院校的调查

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中国人口科学 2007年第2期 52-60页

作者：潘晨光李萌娄伟中国社会科学院中国社会科学院城市发展与环境研究中心

文章通过对全国32所职业技术院校的深入调研,分析、总结了中国职业技术教育的发展现状。研究表明,目前中国职业技术教育在发展中存在着社会歧视、资金“瓶颈”、教师素质欠缺、学生能力建设不足和就业服务不到位等问题与挑战。在此基础... 详细信息

文章通过对全国32所职业技术院校的深入调研,分析、总结了中国职业技术教育的发展现状。研究表明,目前中国职业技术教育在发展中存在着社会歧视、资金“瓶颈”、教师素质欠缺、学生能力建设不足和就业服务不到位等问题与挑战。在此基础上,作者进一步探讨了中国职业技术教育可持续发展的战略路径,并提出相应的政策建议。

关键词：职业教育发展挑战改革

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Indicating landfill stabilization state by using leachate property from Laogang Refuse Landfill

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Frontiers of Environmental Science & Engineering 2014年第3期8卷 405-410页

作者： Ziyang lou Xiaoli CHAI Youcai ZHAO Yu SONG Nanwen ZHU Jinping JIA School of Environmental Science and Engineering Shanghai Jiao Tong University Shanghai 200240 China The State Key Laboratory of Pollution Control and Resource Reuse School of Environmental Science and Engineering Tongii University Shanghai 200092 China

Variation and evolution process of leachate can be applied as a reference for landfill stabilization phase. In this work, leachates with different ages were collected from Laogang Refuse Landfill, and characterized with 14 key parameters. Simultaneously, principal component analysis （PCA） was applied to develop a synthetic parameter-F based on these 14 parameters, and a logarithm equation was simulated for the landfill stabilization process finally. It was predicted that leachates would meet Class I and Class II in standard for pollution control on the landfill site of municipal solid waste （GB 16889-1997） after 32 years and 22 years disposal under the natural attenuation in the humid and warm southern areas of China, respectively. The predication of landfill state would be more accurate and useful according to the synthetic parameter F of leachate from a working landfill.

关键词： landfill stabilization leachate evolution prin- cipal component analysis

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Greenhouse gas emission and its potential mitigation process from the waste sector in a large-scale exhibition

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Journal of Environmental Sciences 2015年第5期27卷 44-50页

作者： Ziyang lou Bernd Bilitewski Nanwen Zhu Xiaoli Chai Bing Li Youcai Zhao Peter Otieno School of Environmental Science and Engineering Shanghai Jiaotong University Institute for Waste Management and Contaminated Sites Treatment TU Dresden Faculty of Forestry Geo and Hydro SciencesPratzschwitzer Str.1501796 Pirna Germany State Key Laboratory of Pollution Control and Resource Reuse School of Environmental Science and Engineering Tongji University Institute of Ecological Chemistry Helmholtz Zentrum Müenchen German National Research Centre for Environmental HealthIngolst?dter Landstrasse 1D-85764 Neuherberg Germany Maseno University Department of Chemistry

As one of the largest human activities, World Expo is an important source of anthropogenic Greenhouse Gas emission（GHG）, and the GHG emission and other environmental impacts of the Expo Shanghai 2010, where around 59,397 tons of waste was generated during 184 Expo running days, were assessed by life cycle assessment（LCA）. Two scenarios, i.e., the actual and expected figures of the waste sector, were assessed and compared, and 124.01 kg CO2-equivalent（CO2-eq.）, 4.43 kg SO2-eq., 4.88 kg NO-3-eq., and 3509 m3 water per ton tourist waste were found to be released in terms of global warming（GW）, acidification（AC）,nutrient enrichment（NE） and spoiled groundwater resources（SGWR）, respectively. The total GHG emission was around 3499 ton CO2-eq. from the waste sector in Expo Park, among which 86.47% was generated during the waste landfilling at the rate of 107.24 kg CO2-eq.,and CH4, CO and other hydrocarbons（HC） were the main contributors. If the waste sorting process had been implemented according to the plan scenario, around 497 ton *** could have been attained. Unlike municipal solid waste, with more organic matter content, an incineration plant is more suitable for tourist waste disposal due to its high heating value, from the GHG reduction perspective.

关键词： GHG emission Mitigation process Waste sector Expo 2010 Shanghai Life cycle assessment

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Enhanced monopole transition strength from the cluster decay of ^(13)C

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Science China(Physics,Mechanics & Astronomy) 2019年第1期62卷 49-55页

作者： Jun Feng YanLin Ye Biao Yang ChengJian Lin HuiMin Jia DanYang Pang ZhiHuan Li JianLing lou QiTe Li XiaoFei Yang Jing Li HongLiang Zang Qiang Liu Wei Jiang chenguang Li Yang Liu ZhiQiang Chen HongYi Wu ChunGuang Wang Wei Liu Xiang Wang JingJing Li DiWen Luo Ying Jiang ShiWei Bai JinYan Xu NanRu Ma LiJie Sun DongXi Wang School of Physics and State Key Laboratory of Nuclear Physics and Technology Peking University China Institute of Atomic Energy School of Physics and Nuclear Energy Engineering Beihang University Beijing Key Laboratory of Advanced Nuclear Materials and Physics Beihang University

The inelastic excitations and cluster decay of ^(13)C have been measured using the reaction,9Be(^(13)C, ^(13)C* →~9Be + α)~9Be. We observe strong excitation to the 14.3-MeV(1/2-) resonant state from the cluster-decay channel, leading to an enhanced monopole matrix element of(6.3 ± 0.6) fm^2. This large cluster-related monopole strength is a clear indication of the cluster-structure domination of this state and is consistent with the recent prediction of the orthogonality condition model(OCM). It would be interesting to further explore the three-center molecular rotational band that is initiated from the observed band-head.

关键词： inelastic excitation monopole transition cluster decay

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局部进展期直肠癌新辅助放化疗后延长等待时间对肿瘤退缩的影响

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中华外科杂志 2023年第9期61卷 775-781页

作者：郑阔金路沈浮高显华朱晓明于冠宇郝立强楼征王颢于恩达白辰光张卫海军军医大学第一附属医院肛肠外科、上海长海医院遗传性结直肠癌筛查防治中心和遗传性肿瘤家庭阻断中心上海200433 海军军医大学第一附属医院影像科上海200433 海军军医大学第一附属医院病理科上海200433

目的探讨延长等待时间对局部进展期直肠癌新辅助放化疗后肿瘤退缩的影响。方法回顾性收集2012年1月至2021年12月在海军军医大学第一附属医院完成新辅助放化疗的728例局部进展期直肠癌患者的临床和病理学资料,主要研究终点为持续完全缓... 详细信息

目的探讨延长等待时间对局部进展期直肠癌新辅助放化疗后肿瘤退缩的影响。方法回顾性收集2012年1月至2021年12月在海军军医大学第一附属医院完成新辅助放化疗的728例局部进展期直肠癌患者的临床和病理学资料,主要研究终点为持续完全缓解。男性498例,女性230例,年龄[M(IQR)]58(15)岁(范围:22~89岁)。使用Logistic回归分析等待时间是否为持续完全缓解的独立影响因素,采用曲线拟合的方法描绘累计持续完全缓解率与等待时间的关系;根据等待时间将患者分为传统组(4~<12周)581例和延长组(12~<20周)147例,采用t检验、Wilcoxon秩和检验或χ^(2)检验比较两组患者肿瘤退缩情况、器官保留情况、手术情况等,采用Log-rank检验比较两组患者生存曲线差异。结果全组患者持续完全缓解比例为21.6%(157/728)。等待时间是患者达到持续完全缓解的独立影响因素,每延长1 d的OR值为1.010(95%CI:1.001~1.020,P=0.031)。累计持续完全缓解率随等待时间的延长而增加,在第10周时,累计持续完全缓解率的增速最大。延长组患者的持续完全缓解比例更高[27.9%(41/147)比20.0%(116/581),χ^(2)=3.901,P=0.048],在随访期内,延长组的患者器官保留比例更高[21.1%(31/147)比10.7%(62/581),χ^(2)=10.510,P=0.001]。传统组和延长组患者3年无局部复发/再生生存率分别为94.0%和91.1%,3年无病生存率分别为76.6%和75.4%,3年总体生存率分别为95.6%和92.2%,两组患者无局部复发/再生生存、无病生存和总体生存的差异均无统计学意义(χ^(2)=1.878,P=0.171;χ^(2)=0.078,P=0.780;χ^(2)=1.265,P=0.261)。结论延长等待时间有利于肿瘤退缩,等待时间延长为新辅助放化疗后12~<20周有可能提高患者的持续完全缓解率和器官保留率,且不增加手术难度,并对患者的肿瘤学结局影响较小。

关键词：结直肠肿瘤队列研究新辅助放化疗肿瘤退缩预后

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