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Glycodiversification of gentamicins through in vivo glycosyltransferase swapping enabled the creation of novel hybrid aminoglycoside antibiotics with potent activity and low ototoxicity

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4149-4163页

作者： Xinyun Jian Cheng Wang Shijuan Wu Guo Sun Chuan Huang Chengbing Qiu Yuanzheng liu Peter FLeadlay Dong liu Zixin Deng Fuling Zhou yuhui Sun Department of Hematology Zhongnan Hospital of Wuhan UniversitySchool of Pharmaceutical SciencesWuhan UniversityWuhan 430071China Key Laboratory of Combinatorial Biosynthesis and Drug Discovery(Ministry of Education) Wuhan UniversityWuhan 430071China School of Pharmacy Huazhong University of Science and TechnologyWuhan 430030China School of Life Sciences Co-Innovation Center of NeuroregenerationNantong Laboratory of Development and DiseasesNantong UniversityNantong 226019China Department of Biochemistry University of CambridgeCambridge CB21GAUK Department of Biochemistry and Molecular Biology Biomedicine Discovery InstituteMonash UniversityClayton VIC 3800Australia ARC Centre of Excellence for Innovations in Protein and Peptide Science Monash UniversityClayton VIC 3800Australia

Aminoglycosides(AGs)are a class of antibiotics with a broad spectrum of ***,their use is limited by safety concerns associated with nephrotoxicity and ototoxicity,as well as drug *** address these issues,semi-synthetic approaches for modifying natural AGs have generated new generations of AGs,however,with limited types of modification due to significant challenges in *** study explores a novel approach that harness the bacterial biosynthetic machinery of gentamicins and kanamycins to create hybrid *** was achieved by glycodiversification of gentamicins via swapping the glycosyltransferase(GT)in their producer with the GT from kanamycins biosynthetic pathway and resulted in the creation of a series of novel AGs,therefore referred to as genkamicins(GKs).The manipulation of the hybrid biosynthetic pathway enabled the targeted accumulation of different GK species and the isolation and characterization of six GK *** compounds display retained antimicrobial activity against a panel of World Health Organization(WHO)critical priority pathogens,and GK-C2a,in particular,demonstrates low ototoxicity compared to clinical drugs in zebrafish *** study provides a new strategy for diversifying the structure of AGs and a potential avenue for developing less toxic AG drugs to combat infectious diseases.

关键词： Antibiotic Aminoglycoside biosynthesis Biosynthetic engineering Ototoxicity

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Precise nano-system-based drug delivery and synergistic therapy against androgen receptor-positive triple-negative breast cancer

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2685-2697页

作者： Fangyan Gao Yueyao Wu Runtian Wang yuhui Yao Yiqiu liu Lingling Fan Jingtong Xu Jian Zhang Xin Han Xiaoxiang Guan Department of Oncology the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization School of Medicine&Holistic Integrative MedicineNanjing University of Chinese MedicineNanjing 210023China Department of Oncology the Second Hospital of NanjingNanjing University of Chinese MedicineNanjing 210023China Department of Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 211166China

Targeting androgen receptor(AR)has shown great therapeutic potential in triple-negative breast cancer(TNBC),yet its efficacy remains ***,we aimed to identify promising targeted agents that synergize with enzalutamide,a second-generation AR inhibitor,in *** using a strategy for screening drug combinations based on the Sensitivity Index(SI),we found that MK-8776,a selective checkpoint kinase1(CHK1)inhibitor,showed favorable synergism with enzalutamide in AR-positive *** combination of enzalutamide and MK-8776 was found to exert more significant anti-tumor effects in TNBC than the single application of enzalutamide or MK-8776,***,a nanoparticle-based on hyaluronic acid(HA)-modified hollow-manganese dioxide(HMnO_(2)),named HMnE&M@H,was established to encapsulate and deliver enzalutamide and *** HA-modified nanosystem managed targeted activation via pH/glutathione ***&M@H repressed tumor growth more obviously than the simple addition of enzalutamide and MK-8776 without a ***,our study elucidated the synergy of enzalutamide and MK-8776 in TNBC and developed a novel tumor-targeted nano drug delivery system HMnE&M@H,providing a potential therapeutic approach for the treatment of TNBC.

关键词： Triple-negative breast cancer Androgen receptor Checkpoint kinase 1 Enzalutamide MK-8776 Synergy HMnO_(2) Nanodrug delivery system

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Analysis and suppression of operational overvoltage and inrush current for high-speed trains by automatic phase-switching technique

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HIGH VOLTAGE 2024年第3期9卷 733-748页

作者： Cao, Ye Xiao, Song Ye, Zhizong Wu, Guangning Guo, Yujun Gao, Guoqiang Sun, Chuanming liu, Jiancheng Chen, Zheng Hou, Hao Wang, Zijing liu, Puyang Zhang, yuhui Yu, Jie Southwest Jiaotong Univ Sch Elect Engn Chengdu Peoples R China Guangdong Power Grid LLC Co China Southern Power Grid Guangzhou Peoples R China CRRC Qingdao Sifang Co Ltd Qingdao Peoples R China State Grid Chongqing Elect Power Co Chongqing Peoples R China

When a high-speed train approaches the insulated phase-splitting section embedded between neighbouring power supply arms, the vacuum circuit breaker (VCB) installed on trains must be disconnected to maintain the traction power supply system as a no-load condition for completing phase-switching action, as the train passes through the phase-splitting section depending on its inertia. However, when operating VCBs, the arc is easily triggered between the mobile contacts inside, accompanied by an overvoltage impulse. Herein, to explore the generating mechanism of inrush current and operational overvoltage, a model describing the 'substation-catenary-train' traction power supply system is launched based on an equivalent circuit modelling technique. Through the analysis of the transient VCB operational process, the phase of catenary voltage is directly related to the characteristics of the VCB switching-on overvoltage, as the traction current's phase angle is relevant to the amplitude-frequency characteristics of the VCB switching-off overvoltage. Inrush current as a noteworthy element is related to the traction transformer's remanence. The automatic phase-switching technique is utilised to suppress both operational overvoltage and inrush current, as the optimal combination of VCB switching-on and switching-off phases considering the balance between overvoltage and inrush current is achieved based on the particle swarm algorithm.

关键词： IMPACT

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电针联合A型肉毒毒素肌肉注射治疗痉挛型脑瘫患儿的临床效果及对粗大运动功能的影响

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临床医学研究与实践 2024年第11期9卷 87-90页

作者：陆丽娜党举樵成万小雪李朋灰贺维郭鹏刘昱晖西安中医脑病医院脑病十五科陕西西安710032

目的观察电针联合A型肉毒毒素肌肉注射治疗痉挛型脑瘫患儿的临床效果及对粗大运动功能的影响。方法选取2021年7月至2023年11月本院收治的96例痉挛型脑瘫患儿为研究对象,按照随机数字表法将其分为对照组和观察组,每组48例。对照组采用A... 详细信息

目的观察电针联合A型肉毒毒素肌肉注射治疗痉挛型脑瘫患儿的临床效果及对粗大运动功能的影响。方法选取2021年7月至2023年11月本院收治的96例痉挛型脑瘫患儿为研究对象,按照随机数字表法将其分为对照组和观察组,每组48例。对照组采用A型肉毒毒素肌肉注射配合常规康复训练,观察组在对照组的基础上予以电针治疗。比较两组的治疗效果。结果治疗后,两组的改良Ashworth痉挛量表(MAS)评分、足背屈角、88项版本粗大运动功能测试量表(GMFM-88)评分均优于治疗前(P0.05),但观察组的GMFM-88评分明显高于对照组(P<0.05)。结论电针联合A型肉毒毒素肌肉注射治疗痉挛型脑瘫患儿效果显著,可以快速降低肢体肌张力,改善尖足,提高粗大运动功能,值得临床推广及应用。

关键词：痉挛型脑瘫电针 A型肉毒毒素粗大运动功能

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刘半农与《教我如何不想她》

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人民音乐 2009年第10期 54-55页

作者：刘育辉

刘半农（1891—1934），江苏江阴人，在“五四”文学等众多领域均有建树，是我国现代语言学的奠基者。作为“五四”时期新诗园地中早春的一个拓荒者，他在新诗的语言、内容、形式和格律等方面亦做出了一系列的重要革新。

关键词：《教我如何不想她》刘半农现代语言学 “五四”文学 “五四”时期拓荒者新诗格律

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丹青泡椒的加工工艺及操作要点概述

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农产品加工 2024年第15期 88-90页

作者：吴光辉贾德翠雷艳刘昱卉高崇友杨廷李黎妮姚琼麻琼方湘西土家族苗族自治州农业科学研究院湖南吉首416000 湘西土家族苗族自治州农业农村局湖南吉首416000 吉首市农业农村局湖南吉首416000

丹青泡椒原产自湖南省湘西自治州丹青镇,通过天然发酵和苗家传统工艺加工而成,在保留了辣椒原汁原味的基础上,形成了清、香、脆、辣的独特口感,是具有鲜明地方特色的辣椒制品。通过介绍丹青泡椒的由来及特点、加工原理及加工技术要点,... 详细信息

丹青泡椒原产自湖南省湘西自治州丹青镇,通过天然发酵和苗家传统工艺加工而成,在保留了辣椒原汁原味的基础上,形成了清、香、脆、辣的独特口感,是具有鲜明地方特色的辣椒制品。通过介绍丹青泡椒的由来及特点、加工原理及加工技术要点,分析丹青泡椒产业的发展现状及发展前景。

关键词：丹青泡椒发酵加工工艺特色产业

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网络服务提供者内容审查义务的相关法律问题研究

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山东社会科学 2023年第5期 100-106页

作者：刘宇晖华北电力大学法政系华北电力大学区域法治与司法治理研究中心

技术进步与商业模式变化打破了“避风港原则”规范下网络服务提供者与著作权人之间的利益平衡。我国司法基于应知规则中“应知”的认定要求网络服务提供者负有对用户上传内容的注意义务,虽然较好地维护了著作权人的合法权益,但也造成了... 详细信息

技术进步与商业模式变化打破了“避风港原则”规范下网络服务提供者与著作权人之间的利益平衡。我国司法基于应知规则中“应知”的认定要求网络服务提供者负有对用户上传内容的注意义务,虽然较好地维护了著作权人的合法权益,但也造成了网络服务提供者面临的法律风险具有不确定性,并与网络服务提供者无内容审查义务相矛盾。在《信息网络传播权保护条例》和《民法典》中规定一定规模的网络服务提供者负有内容审查义务,应当对用户上传内容进行事前技术过滤,是我国顺应技术进步与商业发展趋势,重塑网络服务提供者与著作权人之间利益平衡的有效路径。

关键词：网络服务提供者内容审查义务过滤技术

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Unveiling non-radiative center control in CsPbBr_(3) nanocrystals:A comprehensive comparative analysis of hot injection and ligandassisted reprecipitation approaches

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Nano Research 2024年第5期17卷 4525-4534页

作者： Daocheng Hong Yuchen Zhang Shuhan Pan Hanyu liu Wei Mao Wanli Zhang yuhui Ye Zhihong Wei Xuxing Lu Xiaoyong Wang Zhenda Lu Yuxi Tian Key Laboratory for Advanced Technology in Environmental Protection of Jiangsu Province Yancheng Institute of TechnologyYancheng 224051China Laboratory of Mesoscopic Chemistry of MOE School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China College of Engineering and Applied Sciences Nanjing UniversityNanjing 210023China National Laboratory of Solid State Microstructures School of PhysicsCollaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093China School of Electronic Electrical Engineering and PhysicsFujian University of TechnologyFuzhou 350118China

Metal-halide perovskite nanocrystals(NCs)have gained significant attention in the field of optoelectronic and photonic devices due to their promising *** their exceptional optical properties,the impact of different synthetic strategies on the fundamental nature of NCs,such as nonradiative recombination centers,remains poorly *** this study,we investigated the photophysical properties of CsPbBr_(3) NCs synthesized using two distinct methods,hot injection and ligand-assisted reprecipitation,at the individual particle *** observed different blinking behaviors under specific photoexcitation power densities and proposed,through intensity-lifetime analysis and Monte-Carlo simulations,that these different synthetic strategies can fabricate NCs with similar crystal structures but distinct surface quenchers with varying energy levels,which significantly affected the photo-induced blinking-down and blinking-up behaviors in individual *** findings indicate a practical and feasible approach for controlling defect engineering in perovskite NCs,with significant implications for their use in optoelectronic and other technological applications.

关键词： metal-halide perovskite nanocrystals photophysical properties nonradiative recombination centers hot injection method ligand-assisted reprecipitation

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USE　OF　THE　DISCRETE　PSEUDO—WIGNER　DISTRIBUTION　FOR　FREQUENCY　ANALYSIS　OF　THE　FIRST　AND　THE　SECOND　HEART SOUNDS IN NORMAL MAN

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Chinese Journal of Biomedical Engineering(English Edition) 1995年第3期4卷 129-130页

作者： $$$$Wang jianqi liu yuhui Yang guosheng liu lijie(Department of Biomedical Engineering,The Fourth Military Medical CollegeXi’an 710032, China)

ＵＳＥＯＦＴＨＥＤＩＳＣＲＥＴＥＰＳＥＵＤＯ—ＷＩＧＮＥＲＤＩＳＴＲＩＢＵＴＩＯＮＦＯＲＦＲＥＱＵＥＮＣＹＡＮＡＬＹＳＩＳＯＦＴＨＥＦＩＲＳＴＡＮＤＴＨＥＳＥＣＯＮＤＨＥＡＲＴＳＯＵＮＤＳＩＮＮＯＲＭＡＬＭＡＮＵＳＥ... 详细信息

ＵＳＥＯＦＴＨＥＤＩＳＣＲＥＴＥＰＳＥＵＤＯ—ＷＩＧＮＥＲＤＩＳＴＲＩＢＵＴＩＯＮＦＯＲＦＲＥＱＵＥＮＣＹＡＮＡＬＹＳＩＳＯＦＴＨＥＦＩＲＳＴＡＮＤＴＨＥＳＥＣＯＮＤＨＥＡＲＴＳＯＵＮＤＳＩＮＮＯＲＭＡＬＭＡＮＵＳＥＯＦＴＨＥＤＩＳＣＲＥＴＥＰＳＥＵ...

关键词： FIRST

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用法治推动共治善治

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国家教育行政学院学报 2019年第1期 19-21页

作者：刘宇辉北京市教育委员会北京100031

教育需要法治保障,依法治教是依法治国在教育领域的具体体现。抓学习教育,增强法治理念;抓制度机制,夯实法治基础;抓机构队伍,做强法治力量;抓指导监督,提升执法效能,是实现教育治理能力和治理体系现代化的必由之路,也是实现教育共治善... 详细信息

教育需要法治保障,依法治教是依法治国在教育领域的具体体现。抓学习教育,增强法治理念;抓制度机制,夯实法治基础;抓机构队伍,做强法治力量;抓指导监督,提升执法效能,是实现教育治理能力和治理体系现代化的必由之路,也是实现教育共治善治的基本途径。

关键词：教育法治法治理念法治基础法治力量执法效能

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