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Antibody-drug conjugates:Recent advances in linker chemistry

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3889-3907页

作者： Zheng Su Dian Xiao Fei Xie Lianqi Liu Yanming Wang shiyong fan Xinbo Zhou Song Li School of Pharmaceutical Engineering Shenyang Pharmaceutical UniversityShenyang 110016China National Engineering Research Center for the Emergency Drug Beijing Institute of Pharmacology and ToxicologyBeijing 100850China

Antibody-drug conjugates(ADCs)are gradually revolutionizing clinical cancer *** antibody-drug conjugate linker molecule determines both the efficacy and the adverse effects,and so has a major influence on the fate of *** ideal linker should be stable in the circulatory system and release the cytotoxic payload specifically in the ***,existing linkers often release payloads nonspecifically and inevitably lead to off-target *** defect is becoming an increasingly important factor that restricts the development of *** pursuit of ADCs with optimal therapeutic windows has resulted in remarkable progress in the discovery and development of novel *** present review summarizes the advance of the chemical trigger,linker-antibody attachment and linker-payload attachment over the last 5 years,and describes the ADMET properties of *** work also helps clarify future developmental directions for the linkers.

关键词： Antibody-drug conjugate Linker Chemical trigger Linker-antibody attachment Linker-payload attachment

From prodrug to pro-prodrug:hypoxia-sensitive antibody–drug conjugates

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Signal Transduction and Targeted Therapy 2022年第2期7卷 369-371页

作者： Yanming Wang Dian Xiao Jiaguo Li shiyong fan Fei Xie Wu Zhong Xinbo Zhou Song Li National Engineering Research Center for the Emergency Drug Beijing Institute of Pharmacology and Toxicology100850 BeijingChina Institute of Basic Medicine and Cancer(IBMC) Chinese Academy of Sciences310022 HangzhouZhejiangChina

Dear Editor,Antibody‒drug conjugates(ADCs),famous as biological targeting prodrugs,are gradually revolutionizing clinical cancer ***,less than 1%of the dosed ADCs accumulate in the tumors.1 Therefore,the nonspecific release of the highly toxic payload(MMAE et al.,10−12–10−10 M)is a real threat,which could induce severe off-target toxicity.2 This danger necessitates strict requirements for the design of the *** date,the mainstream enzyme cleavable linkers,includingβ-glucuronidase cleavable linkers,sulfatase-cleavable linkers,and the most popular cathepsin cleavable linkers(valine-citrulline linker),all face this nonspecific release problem,3 because their cleaving enzymes are widely distributed with no significant difference in their quantities between tumor tissues and normal tissues.

关键词： drug clinical

Magnetic Properties of lT-TaS_(2)

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Chinese Physics Letters 1995年第10期12卷 629-632页

作者： DAI Shouyu YU Chengtao LI Donghong fan shiyong JIN Jiucheng CAI Fengxin Institute of Physics Academia SinicaBeijing 100080 also International Center for Material and Physics Academia SinicaShenyang 110015 Hunan University Changsha 4100822Henan UniversityKaifeng 475001

The magnetic properties of 1T-TaS_(2) and 1T-Fe_(0.07)Ta_(0.93)S_(2) have been *** results show that the phase transition temperature of IT-TaS_(2) is a function of the magnetic *** low temperatures,both compounds are in a mixed state of charge density wave-spin density wave due to the coherent superposition of antifer-romagnetic coupling.

关键词： magnetic coherent wave

THE PHASE DISCRIMINATION OF Pr-Fe-B TERNARY SYSTEM BY THEIR MAGNETIC CHARACTERISTICS

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Chinese Physics Letters 1986年第1期3卷 21-24页

作者： HUANG Yiying TIAN Jinghua fan shiyong Institute of Physics Academia SinicaBeijing

The induced magnetic ordering effect of polycrystalline dhcp Pr at low temperature was applied to discriminate the minute Pr phase in Pr-Fe-B alloys with high *** conclusion that the composition range of HM phase of P... 详细信息

关键词： alloys sensitivity narrow

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Signal Transduction and Targeted Therapy 2022年第7期7卷 2533-2544页

作者： Xi Shi Zihao Wang Wei Ren Long Chen Cong Xu Menghua Li shiyong fan Yuru Xu Mengbing Chen fanjun Zheng Wenyuan Zhang Xinbo Zhou Yue Zhang Shiwei Qiu Liyuan Wu Peng Zhou Xinze Lv Tianyu Cui Yuehua Qiao Hui Zhao Weiwei Guo Wei Chen Song Li Wu Zhong Jian Lin Shiming Yang Department of Pharmacy Peking University Third HospitalBeijingChina Artificial Auditory Laboratory of Jiangsu Province Xuzhou Medical UniversityXuzhouChina National Engineering Research Center for the Emergency Drug Beijing Institute of Pharmacology and ToxicologyBeijingChina College of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalBeijingChina National Clinical Research Center for Otolaryngologic Diseases BeijingChina Key Lab of Hearing Science Ministry of EducationBeijingChina Beijing Key Lab of Hearing Impairment for Prevention and Treatment BeijingChina Synthetic and Functional Biomolecules Center Beijing National Laboratory for Molecular SciencesKey Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of EducationCollege of Chemistry and Molecular EngineeringInnovation Center for GenomicsPeking UniversityBeijingChina

Inner ear disorders are a cluster of diseases that cause hearing loss in more than 1.5 billion people ***,the presence of the blood-labyrinth barrier(BLB)on the surface of the inner ear capillaries greatly hinders the effectiveness of systemic drugs for prevention and intervention due to the low permeability,which restricts the entry of most drug compounds from the bloodstream into the inner ear ***,we report the finding of a novel receptor,low-density lipoprotein receptor-related protein 1(LRP1),that is expressed on the BLB,as a potential target for shuttling therapeutics across this *** a proof-ofconcept,we developed an LRP1-binding peptide,IETP2,and covalently conjugated a series of model small-molecule compounds to it,including potential drugs and imaging *** compounds were successfully delivered into the inner ear and inner ear lymph,indicating that targeting the receptor LRP1 is a promising strategy to enhance the permeability of the *** discovery of the receptor LRP1 will illuminate developing strategies for crossing the BLB and for improving systemic drug delivery for inner ear disorders.

关键词： drugs prevention barrier

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发电厂输煤系统设备的管理与检修分析

集成电路应用 2023年第6期40卷 283-285页

作者：范士勇山西鲁晋王曲发电有限责任公司山西047500

阐述发电厂输煤系统设备的特点,设备运行和检修过程中的问题,造成输煤系统设备故障检修困难的因素,探讨输煤系统设备检修的应对措施。

关键词：控制技术输煤系统设备检修应对措施

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京广线木道沟大桥架梁施工技术

铁道建筑 2006年第11期46卷 65-66页

作者：梁秀海赵风岭范世勇河北铁建工程有限公司石家庄050057

木道沟大桥(7孔双线32 m预应力混凝土T形梁)架梁,属京广线提速改造工程。文章结合现场情况确定了出岔位置、道岔选择、站线利用等方案,并介绍了架梁便线设计、进梁、架梁等技术问题。

关键词：桥梁施工架桥机架梁架梁便线

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矿山地质环境问题特点及其治理对策

智能城市应用 2019年第6期2卷 101-102页

作者：范仕勇安徽省地质矿产勘查局327地质队安徽合肥230011

中国国土面积很大,幅员辽阔,天然矿产资源是非常丰富的,但由于传统的先污染后治理的落后发展观念,在对矿产资源进行开采的过程中没有做好矿藏区域内周边环境保护,此外,矿产资源被过度开采,矿业的可持续使用也没有被矿业企业所重视。由... 详细信息

中国国土面积很大,幅员辽阔,天然矿产资源是非常丰富的,但由于传统的先污染后治理的落后发展观念,在对矿产资源进行开采的过程中没有做好矿藏区域内周边环境保护,此外,矿产资源被过度开采,矿业的可持续使用也没有被矿业企业所重视。由于过度开采和不到位的开采保护,使得矿井周围常常会发生较为严重的地质灾害,一些资源采矿的企业在没有经过严格的污水处理的情况下,肆意的向自然环境中排放重污染的污水,从而导致了非常严重的水土污染。与矿山地质环境和自然资源以及生态的破坏有关的一些问题主要是由于采矿领域的人为因素造成的,因此,有必要按照生态、绿色、节能的环境保护理念预防和控制矿山开采所引发的地质灾害和生态污染,并将其作为矿山开采行业需要长期坚持的一个工作。基于此,将着重分析探讨矿山地质环境问题特点及治理措施,以期能为以后的实际工作起到一定的借鉴作用。

关键词：矿山地质环境特点处理

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虚拟仿真技术在现代通信网实验教学中的应用

实验技术与管理 2015年第4期32卷 133-135页

作者：陈丽霞范士勇刘鑫河北大学电子信息工程学院河北保定071002 河北省数字医疗工程重点实验室河北保定071002 河北大学计算中心河北保定071002

改变传统的实验箱教学模式,引进了中兴公司的程控交换设备、TD-SCDMA移动通信等现网设备,将虚拟仿真技术应用到实验教学中。通过程控交换虚拟仿真软件、TD-SCDMA虚拟仿真软件的使用,使学生能够更加直观地掌握主流通信设备的具体结构,提... 详细信息

改变传统的实验箱教学模式,引进了中兴公司的程控交换设备、TD-SCDMA移动通信等现网设备,将虚拟仿真技术应用到实验教学中。通过程控交换虚拟仿真软件、TD-SCDMA虚拟仿真软件的使用,使学生能够更加直观地掌握主流通信设备的具体结构,提高工科学生的动手能力和工程实践能力。

关键词：虚拟仿真技术程控交换软件 TD-SCDMA软件