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Late-stage modification of bioactive compounds:Improving druggability through efficient molecular editing

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1030-1076页

作者： Tongyu Huo Xinyi Zhao Zengrui Cheng Jialiang Wei Minghui Zhu xiaodong Dou ning Jiao State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Changping Laboratory Beijing 102206China Shanghai Key Laboratory of Green Chemistry and Chemical Processes East China Normal UniversityShanghai 200062China

Synthetic chemistry plays an indispensable role in drug discovery,contributing to hit compounds identification,lead compounds optimization,candidate drugs preparation,and so *** Nobel Prize laureate James Black emphasized,“the most fruitful basis for the discovery of a new drug is to start with an old drug”***-stage modification or functionalization of drugs,natural products and bioactive compounds have garnered significant interest due to its ability to introduce diverse elements into bioactive compounds *** modifications alter the chemical space and physiochemical properties of these compounds,ultimately influencing their potency and *** enrich a toolbox of chemical modification methods for drug discovery,this review focuses on the incorporation of halogen,oxygen,and nitrogen—the ubiquitous elements in pharmacophore components of the marketed drugs—through late-stage modification in recent two decades,and discusses the state and challenges faced in these *** also emphasize that increasing cooperation between chemists and pharmacists may be conducive to the rapid discovery of new activities of the functionalized ***,we hope this review would serve as a valuable resource,facilitating the application of late-stage modification in the construction of novel molecules and inspiring innovative concepts for designing and building new drugs.

关键词： Late-stage modification Drug space Halogenation Oxygenation Nitrogenation Synthetic chemistry

Targeted nanostrategies eliminate pre-metastatic niche of cancer

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Nano Research 2024年第6期17卷 5358-5373页

作者： Juan Wang ning Zhang Xiuping Ding Chengrui Fu xiaodong Li Baosheng Li Jianxun Ding Tianmeng Sun Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education Institute of ImmunologyThe First HospitalJilin University1 Xinmin StreetChangchun 130061China Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of Sciences5625 Renmin StreetChangchun 130022China Department of Radiation Oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical Sciences440 Jiyan RoadJinan 250117China Department of orthopaedics The Second Hospital of Shandong UniversityShandong University247 Beiyuan StreetJinan 250033China State Key Laboratory of Molecular Engineering of Polymers Fudan University220 Handan RoadShanghai 200433China

Establishing a pre-metastatic niche(PMN)in secondary organs is a prerequisite for cancer *** advances in cancer therapy,the efficient inhibition of PMN formation remains a clinical *** advances in understanding the specific characteristics of PMN and advances in nanotechnology have provided hope for manipulating their microenvironments.A series of nanostrategies have been designed to eliminate the PMN,including the removal of pro-metastatic exosomes from the bloodstream for excretion via the intestines,the targeting and scavenging of myeloid-derived suppressor cells,fibroblasts,and critical extracellular matrix components,and the elimination of circulating tumor cells prior to colonization in distant *** review summarizes the underlying mechanisms of PMN formation,highlights the anti-PMN efficacy of currently reported nanostrategies,and underlines the unresolved questions.

关键词： nanoparticle controlled drug delivery pre-metastatic niche elimination metastasis suppression cancer therapy

An effective strategy for dendrite free Li metal anodes:Nickel foam decorated with high lattice-matching CoN and CoF_(2) nanosheets for dense deposition

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Nano Research 2024年第5期17卷 4069-4078页

作者： Wenlong Liu Jianzong Man xiaodong Sun ning Zhang Yehong Du Kun Liu Zhongsheng Wen Song Li Juncai Sun Institute of Materials and Technology Dalian Maritime UniversityDalian 116026China Shandong Provinvial Key Laboratory of Chemical Energy Storage and Novel Cell Technology and School of Chemistry and Chemical enginneringLiaocheng UniversityLiaocheng 252000China Department of Public Security Management Liaoning Police CollegeDalian 116036China

The notorious dendrite and infinite volume change seriously restrict the advancement of lithium metal anodes(LMAs),during the long-term process of stripping/***,the nanosheets of metal fluoride(CoF_(2))and metal nitride(CoN)with magnificent lithiophilicity on the nickel(Ni)foam are designed as the“regulator”to uniform the Li plating and build stronger solid electrolyte interface(SEI)layer for dendrite free *** Ni foam offers abundant space to receive deposited Li *** CoN nanosheets can guarantee the fast transfer of electrons,which provides a stable interface of Li^(+)***,the nanosheet structure with lithiophilicity would accelerate the move of Li+and decrease the nucleation barrier,due to the high lattice-matching of Li and ***,the CoF_(2) could increase the content of F(LiF)in the SEI layer,which enhances the strength and avoids the destruction of SEI *** the cooperation of CoN and CoF_(2),the composited anode(Li/NF@CNCF)exhibits ultra-long cycle performance(more than 1200 h)and fantastic structure stability at 1 mA·cm^(-2) with 1 mAh·cm^(-2).Based on the LiFePO_(4) and Li/NF@CNCF,the full cells deliver excellent specifical capacity and steady coulombic *** strategy contributes an effective approach to alleviate the issues of lithium metal anodes in the field of LMAs.

关键词： CoN and CoF_(2) lattice-matching nanosheet lithiophilicity lithium metal anodes

Fabrication of Tβ4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralization

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Bioactive Materials 2022年第8期7卷 416-429页

作者： Peier Chen xiaodong ning Weirun Li Yuxuan Pan Ling Wang Hekai Li Xianglin Fan Jiexin Zhang Tiantian Luo Yaobin Wu Caiwen Ou Minsheng Chen Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease Department of Cardiology and Laboratory of Heart CenterSino-Japanese Cooperation Platform for Translational Research in Heart FailureZhujiang HospitalSouthern Medical UniversityGuangzhou510280China Biomaterials Research Center School of Biomedical EngineeringSouthern Medical UniversityGuangzhou510515China Guangdong Engineering Research Center for Translation of Medical 3D Printing Application Guangdong Provincial Key Laboratory of Medical BiomechanicsNational Key Discipline of Human AnatomySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou510515China

Currently,stem cell transplantations in cardiac repair are limited owing to disadvantages,such as immunological rejection and poor cell *** direct injection of exosomes can have a curative effect similar to that of stem cell transplantation,high clearance hinders its application in clinical *** reports suggested that induction of coronary collateralization can be a desired method of adjunctive therapy for someone who had missed the optimal operation time to attenuate myocardial *** this study,to mimic the paracrine and biological activity of stem cells,we developed artificial stem cells that can continuously release Tβ4-exosomes(Tβ4-ASCs)by encapsulating specific exosomes within microspheres using microfluidics *** results show that Tβ4-ASCs can greatly promote coronary collateralization in the periphery of the myocardial infarcted area,and its therapeutic effect is superior to that of directly injecting the *** addition,to better understand how it works,we demonstrated that the Tβ4-ASC-derived exosomes can enhance the angiogenic capacity of coronary endothelial cells(CAECs)via the miR-17-5p/PHD3/Hif-1α*** brief,as artificial stem cells,Tβ4-ASCs can constantly release functional exosomes and stimulate the formation of collateral circulation after myocardial infarction,providing a feasible and alternative method for clinical revascularization.

关键词： Artificial stem cells Exosomes Myocardial infarction Coronary collateralization

Multi-network-region traffic cooperative scheduling in large-scale LEO satellite networks

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Journal of Systems Engineering and Electronics 2024年第4期35卷 829-841页

作者： LI Chengxi WANG Fu YAN Wei CUI Yansong FAN xiaodong ZHU Guangyu XIE Yanxi YANG Lixin ZHOU Luming ZHAO Ran WANG ning School of Electronic Engineering Beijing University of Posts and TelecommunicationsBeijing 100876China The 6th Research Institute of China Electronics Corporation Beijing 102209China China Satellite Network Share Operation Co. LtdBeijing 100876China Weihai Electronic Information Technology Comprehensive Research Center of the Ministry of Industry and Information Technology Weihai 264200 China

A low-Earth-orbit(LEO)satellite network can provide full-coverage access services worldwide and is an essential candidate for future 6G ***,the large variability of the geographic distribution of the Earth’s population leads to an uneven service volume distribution of access ***,the limitations on the resources of satellites are far from being able to serve the traffic in hotspot *** enhance the forwarding capability of satellite networks,we first assess how hotspot areas under different load cases and spatial scales significantly affect the network throughput of an LEO satellite network ***,we propose a multi-region cooperative traffic scheduling *** algorithm migrates low-grade traffic from hotspot areas to coldspot areas for forwarding,significantly increasing the overall throughput of the satellite network while sacrificing some latency of end-to-end *** algorithm can utilize all the global satellite resources and improve the utilization of network *** model the cooperative multi-region scheduling of large-scale LEO *** on the model,we build a system testbed using OMNET++to compare the proposed method with existing *** simulations show that our proposed method can reduce the packet loss probability by 30%and improve the resource utilization ratio by 3.69%.

关键词： low-Earth-orbit(LEO)satellite network satellite communication load balance multi-region scheduling latency optimization

Prediction of the short-term efficacy of anti-VEGF therapy for neovascular age-related macular degeneration using optical coherence tomography angiography

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Eye and Vision 2024年第3期10卷 21-30页

作者： Huixun Jia Bing Lu Zhi Zhao Yang Yu Fenghua Wang Minwen Zhou xiaodong Sun Department of Ophthalmology Shanghai General Hospital(Shanghai First People’s Hospital)Shanghai Jiao Tong University School of Medicine100 Hai Ning RoadShanghai200080People’s Republic of China Shanghai Key Laboratory of Ocular Fundus Diseases ShanghaiChina National Clinical Research Center for Eye Diseases ShanghaiChina Shanghai Engineering Center for Visual Science and Photomedicine ShanghaiChina Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases ShanghaiChina Clinical Research Institute Shanghai Jiao Tong University School of MedicineShanghaiChina

Background To evaluate whether the specific choroidal neovascularization(CNV)characteristics measured using optical coherence tomography angiography(OCTA)can predict the 6-month prognosis of neovascular age-related macular degeneration(nAMD)after anti-vascular endothelial growth factor(anti-VEGF)*** Patients with type 1,type 2,or mixed-type neovascularization(NV)were prospectively *** underwent an initial loading phase of three consecutive monthly intravitreal injections of Conbercept(0.5 mg)and were switched to a pro re nata(PRN)treatment *** images were evaluated for eyes that underwent follow-up assessments for more than 6 *** lesions were manually segmented,and the CNV area,vessel area,greatest vascular caliber(GVC),and greatest linear dimension(GLD)were compared between responders and *** masked graders independently measured the above-mentioned parameters using OCTA,and consistency was assessed using the intraclass correlation coefficient(ICC)*** logistic regression analysis was performed to evaluate the effect of a 3-month change in the CNV area,GLD,and GVC on the 6-month response to anti-VEGF *** Among the 60 eyes of 60 patients with nAMD,39 were responders and 21 were *** proportion of CNV types was significantly different between responders and non-responders(P=0.009).Patients with type 2 or mixed NV seemed more likely to respond to the treatment(28.2%vs.0.0%,and 30.8%vs.23.8%,respectively).The change in GVC showed a significant difference between responders(−4.98±17.17μm)and non-responders(11.01±14.10μm)after three monthly intravitreal anti-VEGF *** logistic regression analysis showed that only the change in GVC remained significant after controlling for baseline GVC,injection number,and CNV type(adjusted OR=1.083;P=0.008).Conclusions Type 2 and mixed-type NV were significantly associated with a better response to anti-VEGF *** i

关键词： Age-related macular degeneration Choroidal neovascularization Optical coherence tomography angiography Anti-VEGF

基于专利的我国制造业低碳技术创新产出分布规律及合作模式研究

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情报学报 2015年第7期34卷 701-710页

作者：毕克新黄平刘震宁晓东哈尔滨工程大学经济管理学院哈尔滨150001 哈尔滨理工大学管理学院哈尔滨150080 黑龙江省知识产权局哈尔滨150001

低碳技术创新作为实现碳减排目标与产业转型升级的重要手段已经得到全球各国的广泛认可和关注。对于旨在实现低碳绿色转型升级的我国制造业而言，低碳技术创新活动的有效开展及扩散至关重要。本文以低碳技术专利申请量作为测度低碳技术... 详细信息

低碳技术创新作为实现碳减排目标与产业转型升级的重要手段已经得到全球各国的广泛认可和关注。对于旨在实现低碳绿色转型升级的我国制造业而言，低碳技术创新活动的有效开展及扩散至关重要。本文以低碳技术专利申请量作为测度低碳技术创新产出的指标，采用专利计量分析方法和社会网络分析方法，以国家知识产权局专利数据库为数据来源，分别对我国制造业低碳技术创新产出的历时变化规律、空间分布规律、技术领域分布规律和行业分布规律进行了分析，并进一步探究了我国制造业低碳技术创新的合作模式及其变化规律。研究表明，我国制造业低碳技术创新呈现积极发展的态势，地域差异明显，技术领域相对集中，且各行业具有显著的低碳技术创新导向差异；另外，低碳技术创新合作活动自2004年起呈现明显的上升趋势，并逐步形成围绕高产发明组织或个人的，由结构较松散的小团体向相对紧密的大团体演变的发展态势。

关键词：低碳技术创新低碳技术专利分布规律合作模式

家庭尊严干预在老年轻度认知障碍患者主要照顾者中的应用

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中华护理杂志 2019年第4期54卷 543-548页

作者：陈丹宁晓东潘慧杨春万恩桂荆门市第一人民医院神经内科 448000 荆门市第一人民医院护理部 448000 荆门市第一人民医院肾脏内科 448000

目的探讨家庭尊严干预对老年轻度认知障碍患者主要照顾者照顾负担及负性情绪的影响。方法便利选取80对老年轻度认知障碍患者及其主要照顾者,按出院单双日分为实验组和对照组各40对。实验组在实施常规心理护理的基础上增加家庭尊严干预,... 详细信息

目的探讨家庭尊严干预对老年轻度认知障碍患者主要照顾者照顾负担及负性情绪的影响。方法便利选取80对老年轻度认知障碍患者及其主要照顾者,按出院单双日分为实验组和对照组各40对。实验组在实施常规心理护理的基础上增加家庭尊严干预,对照组实施常规心理护理。应用照顾者负担量表、医院焦虑抑郁量表、Herth希望指数量表评价干预效果。结果干预后实验组主要照顾者的照顾负担评分和焦虑抑郁评分明显低于对照组,希望指数评分明显高于对照组,差异有统计学意义(P<0.05)。结论家庭尊严干预能够明显减轻老年轻度认知障碍患者主要照顾者的照顾负担,有效缓解其负性情绪,提高其希望水平。

关键词：家庭尊严干预老年人认知障碍照顾者负担焦虑抑郁

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临床护士分级岗位培训的实施与效果评价

中华现代护理杂志 2015年第32期21卷 3935-3938页

作者：徐霞宁晓东湖北省荆门市第一人民医院护理部 448000

目的：探讨临床护士分级岗位培训的实施方法及效果。方法2012年1月起,对某三级甲等医院36个护理单元实施护士分级岗位培训。比较实施前后护士考核情况,护理缺陷、投诉和意外事件发生情况的差异。结果实施后与实施前比较,护士理论考试合... 详细信息

目的：探讨临床护士分级岗位培训的实施方法及效果。方法2012年1月起,对某三级甲等医院36个护理单元实施护士分级岗位培训。比较实施前后护士考核情况,护理缺陷、投诉和意外事件发生情况的差异。结果实施后与实施前比较,护士理论考试合格率由87.35%上升到94.13%,护理技能考核合格率由89.71%上升到96.13%,严重护理缺陷由0.04%下降至0.01%,护理意外事件由0.06%下降至0.03%,护理投诉由0.04%下降至0.01%,差异均有统计学意义（χ2值分别为18.06,20.86,3.86,5.16,4.84；P〈0.05）。结论实施临床护士分级岗位培训后护士主动培训意识增强,学习效率提高,患者满意度提高。

关键词：护理管理岗位培训分级效果评价