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Recent advances in construction of small molecule-based fluorophoredrug conjugates

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Journal of Pharmaceutical Analysis 2020年第5期10卷 434-443页

作者： Wenjie Lang Chaonan Yuan Liquan Zhu shubo du Linghui Qian Jingyan Ge Shao Q Yao Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and BioengineeringZhejiang University of TechnologyHangzhou310014PR China Department of Chemistry National University of Singapore3 Science Drive 3Singapore117543Singapore Institute of Drug Metabolism and Pharmaceutical Analysis College of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China

As a powerful tool to advance drug discovery,molecular imaging may provide new insights into the process of drug effect and therapy at cellular and molecular *** compared with other detection methods,fluorescence-based strategies are highly attractive and can be used to illuminate pathways of drugs’transport,with multi-color capacity,high specificity and good *** conjugates of fluorescent molecules and therapeutic agents create exciting avenues for real-time monitoring of drug delivery and distribution,both in vitro and in *** this short review,we discuss recent developments of small molecule-based fluorophore-drug conjugates,including non-cleavable and cleavable ones,that are capable of visualizing drug delivery.

关键词： Drug delivery Fluorescent monitoring Prodrug Cleavable linker

Intracellular effects of prodrug-like wortmannin probes

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Chinese Chemical Letters 2019年第1期30卷 67-70页

作者： Shasha Ying shubo du Jia Dong Bi Xuan Ng Chengwu Zhang Lin Li Jingyan Ge Qing Zhua Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering Zhejiang University of Technology Department of Chemistry National University of Singapore Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM) Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM) Nanjing Tech University (Nanjing Tech)

Wortmannin, a known inhibitor of phosphoinositide 3-kinases(PI3 Ks), their low selectivity and high toxicity is still problematic and less is known about their effects on PI3 Ks in cellular systems. Hence, we have synthesized a series of multifunctional wortmannin probes with the ability to self-activate, by installing a clickable handle at C11 site, and secondary amine and cancer-targeting moiety at C20 site respectively. MTT assay first confirmed that self-activating probes have better inhibition potency and biotin enhanced their cancer cell uptake. Further experiments showed most of probes can target PI3 K/Akt/mTOR pathway with prolonged turn-over time. Protein profiling and pull-down results were observed that the derivatives not only labelled four PI3 Ks with selectivity, but also engaged in covalent interactions with numerous cellular proteins which could be the major reason of their high toxicity.

关键词： Wortmannin P3IK Activity-based probe profiling Cancer-targeting Self-activating

Expanding puromycin based analogues capable of live cell and cell type-selective imaging

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Expanding puromycin based analogues capable of live cell and...

“Mix-and-Go” Cytosolic Delivery of Native Antibodies by Cell-Penetrating Poly（disulfide）s

第十届全国化学生物学学术会议

作者： Ge Jingyan du shubo Yao Shao Q. Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering Zhejiang University of Technology Department of Chemistry National University of Singapore

Global proteome analysis has provided important insights into diverse biological processes. Especially, newly synthesized proteins （NSP）, a subset of the proteome, are involved in every cellular process. However, existing chemical tools used to study them have shortcomings, including limited temporal resolution and incompatibility of live-cell imaging. Herein, we first reported a suite of cell-permeable puromycin analogues capable of being metabolically incorporated into newly synthesized proteins in both live cells and neurons. Furthermore, by taking advantage of"click-to-release" reaction, we developed a versatile puromycin-based strategy for imaging and profiling of newly synthesized proteomes in a cell-specific *** new methods making use of puromycin overcame major drawbacks of existing strategies, thus setting the stage to directly monitor NSP from specialized samples.

关键词： Newly synthesized protein Puromycin Live cell imaging Cell type-selective

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“Mix-and-Go” Cytosolic Delivery of Native Antibodies by Ce...

Enantio-divergent C–H borylation with two different ligands from a single chiral source

第十一届全国化学生物学学术会议

作者： shubo du Si Si Liew Shao Q.Yao Department of Chemistry National University of Singapore

Cytosolic delivery of functional antibodies is urgently required for live-cell imaging and protein-based therapeutics, but constantly plagued by the need of chemical/genetic modifications and endosomal trapping.[1-3] We report herein a Mix-and-Go strategy for convenient and highly efficient cytosolic delivery of native antibodies to different live mammalian cells, without any form of antibody modification. By simply mixing a cell-permeant bio-adapter（Protein A） with a desired antibody, the resulting non-covalent complex could be used for cytosolic delivery of native antibodies with immediate bioavailability and minimal endosomal trapping. Potential utilities of this novel antibody delivery approach was further illustrated by successful inhibition of endogenous PTP1 B activity with the corresponding cytosolically delivered antibodies.

关键词： native antibody intracellular delivery cell-penetrating poly(disulfide)s bioorthogonal chemistry

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Science China Chemistry 2025年第1期68卷 226-232页

作者： Rongrong du Senmiao Xu State Key Laboratory for Oxo Synthesis and Selective Oxidation Lanzhou Institute of Chemical Physics Chinese Academy of Sciences College of Material Chemistry and Chemical Engineering Key Laboratory of Organosilicon Chemistry and Material TechnologyMinistry of Education Hangzhou Normal University University of Chinese Academy of Sciences

Reported here is an iridium-catalyzed enantio-divergent C（sp3）–H borylation of α-gem-dimethyl groups of trifluoromethyl ketone-derived hydrazones to construct a series of acyclic all-carbon quaternary stereocenters with a high level of chiral induction. Two different chiral bidentate boryl ligands from a common chiral source not only can switch the enantioselectivity but also are complementary in terms of the substrate scope.

关键词： asymmetric catalysis C–H borylation all-carbon quaternary stereocenters synthetic methods

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县级开放大学教学质量提升路径研究

大学（研究与管理） 2024年第8期 62-65页

作者：都书博凤城开放大学辽宁丹东118100

县级开放大学作为县域内终身教育的主要提供者,承担着满足广大学习者学习需求、促进社会发展的重要使命。然而,县级开放大学在定位、体系和质量方面存在诸如教学课程质量不高、学生支持服务不足、师资队伍建设滞后、信息化建设水平较低... 详细信息

县级开放大学作为县域内终身教育的主要提供者,承担着满足广大学习者学习需求、促进社会发展的重要使命。然而,县级开放大学在定位、体系和质量方面存在诸如教学课程质量不高、学生支持服务不足、师资队伍建设滞后、信息化建设水平较低等问题,对开放教育事业的健康发展产生了不利影响。基于此,文章以县级开放大学教学质量问题为关注点,结合县级开放大学的角色定位,总结当前县级开放大学教学质量问题,探索县级开放大学教学质量提升路径,旨在为县级开放大学提供可行的改进方案和战略措施,推动教学质量不断提升,为学习者提供更好的教育服务。

关键词：县级开放大学教学质量继续教育

From text to image:challenges in integrating vision into ChatGPT for medical image interpretation

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Neural Regeneration Research 2025年第2期20卷 487-488页

作者： Shunsuke Koga Wei du Department of Pathology and Laboratory Medicine Hospital of the University of PennsylvaniaPhiladelphiaPAUSA

Large language models(LLMs),such as ChatGPT developed by OpenAI,represent a significant advancement in artificial intelligence(AI),designed to understand,generate,and interpret human language by analyzing extensive text *** potential integration into clinical settings offers a promising avenue that could transform clinical diagnosis and decision-making processes in the future(Thirunavukarasu et al.,2023).This article aims to provide an in-depth analysis of LLMs’current and potential impact on clinical *** ability to generate differential diagnosis lists underscores their potential as invaluable tools in medical practice and education(Hirosawa et al.,2023;Koga et al.,2023).

关键词： image diagnosis text

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城轨交通非牵引能耗系统性节能研究

建筑科学 2021年第2期37卷 174-184页

作者：杜书波杨丽赵庆双刘晓东同济大学建筑与城市规划学院高密度人居环境生态与节能教育部重点实验室上海200092 聊城大学建筑工程学院山东聊城252000

随着我国轨道交通的快速发展,城轨交通在给人们带来便利的同时也带来耗能巨大的问题.本研究旨在对目前非牵引能效的研究状况以及策略进行全面的总结.数据显示目前我国轨交非牵引能耗占比高达总能耗的50%以上,节能潜力巨大.本文利用文献... 详细信息

随着我国轨道交通的快速发展,城轨交通在给人们带来便利的同时也带来耗能巨大的问题.本研究旨在对目前非牵引能效的研究状况以及策略进行全面的总结.数据显示目前我国轨交非牵引能耗占比高达总能耗的50%以上,节能潜力巨大.本文利用文献研究的方法对目前适用的非牵引能效提升策略、技术进行了全面评估和分类,提出了降低城轨交通非牵引总体能耗策略的筛选方法和技术路线.结果表明,通过实施低成本的综合能源优化策略,在不降低运营效率及舒适度的前提下,可在现有能耗基础上实现10%~25%的非牵引能耗节能空间挖掘.因此,采取低成本的优化策略,可以有效的实现深绿出行.

关键词：城轨交通非牵引能耗节能策略数据挖掘

基于功率信息的航空发动机叶片铣削刀具监测试验研究

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航空制造技术 2021年第16期64卷 87-92,110页

作者：乔石刘阔都书博王鹏飞王永青大连理工大学大连116024 中国航发贵州黎阳航空动力有限公司贵阳550000

针对航空发动机叶片铣削加工过程中刀具加工状态不易实时监控、更换刀具依赖加工经验等问题,利用基于功率信息的刀具状态监测方法,开发了刀具状态监测系统。通过三相功率传感器实时采集加工过程中机床主轴的功率信号,并对信号数据进行... 详细信息

针对航空发动机叶片铣削加工过程中刀具加工状态不易实时监控、更换刀具依赖加工经验等问题,利用基于功率信息的刀具状态监测方法,开发了刀具状态监测系统。通过三相功率传感器实时采集加工过程中机床主轴的功率信号,并对信号数据进行数据筛选、数据分析、离线学习,计算出功率阈值区间,以功率阈值区间为监测标准,实现了对刀具加工过程的监测以及对刀具寿命的预测。以航空发动机压气机叶片的铣削加工过程为研究对象,进行了刀具状态监测试验。结果表明,基于功率信息的刀具状态监测方法可以实现对航空发动机叶片铣刀加工状态的实时监测及对刀具剩余寿命的预测。

关键词：航空发动机叶片主轴功率离线学习刀具状态监测刀具寿命预测