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Recent Advances in Deuteration Reactions

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Chinese Journal of Chemistry 2024年第10期42卷 1145-1156页

作者： Hao Li Muhammad Shabbir Wu Li Aiwen Lei Institutefor advanced Studies(IAS) Collegeof Chemistry and Molecular SciencesWuhan UniversityWuhanHubei 430072China

The deuteration of organic compounds has attracted more attentions in recent years for the potential applications in new drug discovery and synthetic *** this purpose,many efficient deuterium labeling methodologies have been developed,including hydrogen isotope exchange(HIE),reductive deuteration,and dehalogenative deuteration that allow for the synthesis of selectively deuterated *** the last few years,great breakthroughs in selective isotope labeling have been achieved and the interest in new methodologies for the deuteration of organic molecules is *** this review,we summarized the recent developments in the selective deuteration of organic molecules since *** types of key processes in deuterium incorporation reactions,including H/D exchange,reductive deuteration and dehalogenative deuteration,are introduced and discussed.

关键词： Deuterated compounds H/D exchange Reductive deuterations Dehalogenative deuterations Deuterium C-Hactivation Synthetic methods

MOF负载Weel抑制剂实现p53突变胆囊癌的合成致死靶向治疗

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Science Bulletin 2024年第9期69卷 1286-1301页

作者：郦仕杰 Sarun Juengpanich Win Topatana 谢天傲侯丽丹朱怡远陈佳东单煜凯韩依纳陆子毅陈天恩 Charlie Topatana 张斌曹佳胜胡家豪严加费陈迎鑫顾臻俞计成蔡秀军陈鸣宇 Department of General Surgery Sir Run-Run Shaw HospitalZhejiang UniversityHangzhou 310016China School of Medicine Zhejiang UniversityHangzhou 310058China National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments Sir Run-Run Shaw HospitalZhejiang UniversityHangzhou 310016China School of Materials Science and Engineering Zhejiang UniversityHangzhou 310058China Department of Chemistry Zhejiang UniversityHangzhou 310016China Department of Pathology Sir Run-Run Shaw HospitalZhejiang UniversityHangzhou 310016China International College Zhejiang UniversityHangzhou 310058China Institute of advanced Magnetic Materials and International Research Center for EM Metamaterials College of Materials&Environmental EngineeringHangzhou Dianzi UniversityHangzhou 310018China Zhejiang Provincial Key Laboratory for advanced drug delivery Systems College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China National Key Laboratory of advanced drug delivery and Release Systems Zhejiang UniversityHangzhou 310058China Liangzhu Laboratory Zhejiang UniversityHangzhou 311121China Jinhua Institute of Zhejiang University Jinhua 321299China MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China

Adavosertib(ADA)is a WEE1 inhibitor that exhibits a synthetic lethal effect on p53-mutated gallbladder cancer(GBC).However,drug resistance due to DNA damage response compensation pathways and high toxicity limits further ***,estrone-targeted ADA-encapsulated metal–organic frameworks(ADA@MOF-EPL)for GBC synthetic lethal treatment by inducing conditional factors are *** high expression of estrogen receptors in GBC enables ADA@MOF-EPL to quickly enter and accumulate near the cell nucleus through estrone-mediated endocytosis and release ADA to inhibit WEE1 upon entering the acidic tumor *** irradiation induces ADA@MOF-EPL to generate reactive oxygen species(ROS),which leads to a further increase in DNA damage,resulting in a higher sensitivity of p53-mutated cancer cells to WEE1 inhibitor and promoting cell death via conditional synthetic *** conditional factor induced by ADA@MOF-EPL further enhances the antitumor efficacy while significantly reducing systemic ***,ADA@MOF-EPL demonstrates similar antitumor abilities in other p53-mutated solid tumors,revealing its potential as a broad-spectrum antitumor drug.

关键词： Synthetic lethality Nanomedicine Sonodynamic therapy Gallbladder cancer Metal-organic frameworks DNA damage response

Vitamin D-binding protein in plasma microglia-derived extracellular vesicles as a potential biomarker for major depressive disorder

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Genes & Diseases 2024年第2期11卷 1009-1021页

作者： Gaojia Zhang Ling Li Yan Kong Dandan Xu Yu Bao Zhiting Zhang Zhixiang Liao Jiao Jiao Dandan Fan Xiaojing Long Ji Dai Chunming Xie Zhiqiang Meng Zhijun Zhang Department of Neurology Affiliated Zhongda HospitalResearch Institution of NeuropsychiatrySchool of MedicineSoutheast UniversityNanjingJiangsu 210009China Department of Biochemistry and Molecular Biology School of MedicineSoutheast UniversityNanjingJiangsu 210009China Shenzhen Key Laboratory of drug Addiction Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of Sciences (CAS)ShenzhenGuangdong 518000China CAS Key Laboratory of Brain Connectome and Manipulation The Brain Cognition and Brain Disease Institute (BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China Lauterbur Research Center for Biomedical Imaging Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China Shenzhen-Hong Kong Institute of Brain Sciences-Shenzhen Fundamental Research Institutions ShenzhenGuangdong 518000China Brain Cognition and Brain Disease Institute Department of Mental Health and Public HealthFaculty of Life and Health SciencesShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China

No well-established biomarkers are available for the clinical diagnosis of major depressive disorder(MDD).Vitamin D-binding protein(VDBP)is altered in plasma and postmortem dorsolateral prefrontal cortex(DLPFC)tissues of MDD ***,the role of VDBP as a potential biomarker of MDD diagnosis was further *** extracellular vesicles(EVs)and brain cell-derived EVs(BCDEVs)were isolated from the plasma of first-episode drug-naïve or drug-free MDD patients and well-matched healthy controls(HCs)in discovery(20 MDD patients and 20 HCs)and validation cohorts(88 MDD patients and 38 HCs).VDBP level in the cerebrospinal fluid(CSF)from chronic glucocorticoid-induced depressed rhesus macaques or prelimbic cortex from lipopolysaccharide(LPS)-induced depressed mice and wild control groups was measured to evaluate its relationship with VDBP in plasma microglia-derived extracellular vesicles(MDEVs).VDBP was significantly decreased in MDD plasma MDEVs compared to HCs,and negatively correlated with HAMD-24 score with the highest diagnostic accuracy among *** in plasma MDEVs was decreased both in depressed rhesus macaques and mice.A positive correlation of VDBP in MDEVs with that in CSF was detected in depressed rhesus *** levels in prelimbic cortex microglia were negatively correlated with those in plasma MDEVs in depressed *** main results suggested that VDBP in plasma MDEVs might serve as a prospective candidate biomarker for MDD diagnosis.

关键词： Biomarker Cerebrospinal fluid Major depressive disorder Microglia derived extracellular vesicles Vitamin-D binding protein

Structure-based design of pan-coronavirus inhibitors targeting host cathepsin L and calpain-1

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1651-1664页

作者： Xiong Xie Qiaoshuai Lan Jinyi Zhao Sulin Zhang Lu Liu Yumin Zhang Wei Xu Maolin Shao Jingjing Peng Shuai Xia Yan Zhu Keke Zhang Xianglei Zhang Ruxue Zhang jian Li Wenhao Dai Zhen Ge Shulei Hu Changyue Yu Jiang Wang Dakota Ma Mingyue Zheng Haitao Yang Gengfu Xiao Zihe Rao Lu Lu Leike Zhang Fang Bai Yao Zhao Shibo Jiang Hong Liu drug Discovery and Design Center State Key Laboratory of Drug ResearchCAS Key Laboratory of Receptor ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) School of Basic Medical SciencesShanghai Institute of Infectious Disease and BiosecurityFudan UniversityShanghai 200032China Shanghai Institute for advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China School of Chinese Materia Medica Nanjing University of Chinese Medicine138 Xian Lin RoadJiangsu 210023 NanjingChina School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUCASHangzhou 310024China National Clinical Research Center for Infectious Disease Shenzhen Third People's HospitalShenzhen 518112China

Respiratory disease caused by coronavirus infection remains a global health *** several SARS-CoV-2-specific vaccines and direct-acting antivirals are available,their effcacy on emerging coronaviruses in the future,including SARS-CoV-2 variants,might be ***-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging *** L(CTSL)and calpain-1(CAPN1)are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune ***,two peptidomimetic a-ketoamide compounds,14a and 14b,were identified as potent dual target inhibitors against CTSL and *** X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of a-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of *** showed potent and broad-spectrum anticoronaviral activities in vitro,and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern(VOCs)with ECso values ranging from 0.80 to 161.7 nM in various *** mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral ***,14a and 14b exhibited good oral pharmacokinetic properties in mice,rats and dogs,and favorable safety in *** addition,both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse *** 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%.Further evaluation showed that 14a and 14b exhibited excellent antiinflammatory effects in Raw 264.7 mouse macrophages and in mice with acute *** together,these results suggested that 14a and 14b are promising drug candidates,providing novel insight into developing pan-coronavirus inhibitors with anti

关键词： calpain overcome entrance

Nucleus-targeting orange-emissive carbon dots delivery adriamycin for enhanced anti-liver cancer therapy

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Chinese Chemical Letters 2024年第6期35卷 421-426页

作者： Qiang Li Jiangbo Fan Hongkai Mu Lin Chen Yongzhen Yang Shiping Yu The Second Hospital of Shanxi Medical University Taiyuan 030001China Shanxi Medical University Taiyuan 030001China Key Laboratory of Interface Science and Engineering in advanced Materials Ministry of EducationTaiyuan University of TechnologyTaiyuan 030024China Shanxi-Zheda Institute of advanced Materials and Chemical Engineering Taiyuan 030032China

Carbon dots(CDs)with precise targeting function show great potential in the field of drug delivery *** this study,the functionalized nucleus-targeting orange-emissive CDs with nuclear localization sequence(NLS)were loaded with adriamycin(DOX)to obtain a nucleus-targeting orange-emissive CDs drug delivery system(CDs-NLS-DOX),which delivered DOX to tumor cell nuclei to enhance its anti-tumor *** drug carrier orange-emissive CDs showed excitation-independent behavior,stable and enhanced imaging capability and good biocompatibility in vitro and in ***,the CDs-NLS could target the nuclei efficiently,and the CDs-NLS-DOX complexes had a high drug loading rate(59.4%)after loading DOX,exhibiting p H-dependent DOX release behavior through breaking acylhydrazone bond in a weak acidic *** addition,the CDs-NLS-DOX complexes exhibited an enhanced killing activity against human hepatoma cells(HepG2).The in vivo therapeutic effects on HepG2 nude mice transplanted tumors indicated the CDs-NLS-DOX had a stronger ability to inhibit tumor growth compared to free *** short,CDs-NLS-DOX is expected to be a precise and efficient nucleus-targeting nano-drug delivery system for tumor treatment.

关键词： Carbon dots Nucleus-targeting Adriamycin drug delivery system Liver cancer therapy

Recent progresses of exosome-liposome fusions in drug delivery

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Chinese Chemical Letters 2024年第2期35卷 107-117页

作者： Lulu Zheng Bo Hu Deyao Zhao Wenjing Liu Qing Liu Yuanyu Huang Shaobo Ruan School of Life Science Advanced Research Institute of Multidisciplinary ScienceSchool of Medical TechnologyKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China Department of Radiation Oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China Beijing Key Laboratory of drug Resistance Tuberculosis Research Beijing Tuberculosis and Thoracic Tumor Research Instituteand Beijing Chest HospitalCapital Medical UniversityBeijing 101149China

Exosomes are membrane-bound nanoscale extracellular vesicles,which produced by almost all *** to the excellent biocompatibility,long circulation time as well as low immunogenicity,exosomes as naturally-derived drug delivery carriers have experienced explosive growth over the past ***,issues such as insufficient loading efficiency,heterogeneous delivery efficiency,uncontrollable targeting ability,and low production limit their wide ***,the emerging exosome-liposome fusion strategy has become a potential approach to solve such ***,this review mainly focuses on the currently developed exosome-liposome fusion strategy and their application in drug delivery as well as disease *** review aims to shed light on the advantages of fusion strategy in drug delivery and provides a better understanding for more rational *** current challenge and future perspective regarding their clinical translation and application will also be discussed.

关键词： Exosome Liposome Membrane fusion drug delivery Disease treatment

Probing the dynamic thermodynamic resolution and biological activity of Cu(Ⅱ) and Pd(Ⅱ) complexes with Schiff base ligand derived from proline

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Chinese Chemical Letters 2024年第4期35卷 99-105页

作者： Tao Yu Vadim A.Soloshonok Zhekai Xiao Hong Liu Jiang Wang State Key Laboratory of drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Pharmacy University of Chinese Academy of SciencesBeijing 100049China Department of Organic Chemistry Ⅰ Faculty of ChemistryUniversity of the Basque Country UPV/EHUSan Sebastian 20018Spain IKERBASQUE Basque Foundation for ScienceBilbao 48013Spain School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUCASHangzhou 310024China Lingang Laboratory Shanghai 200031China

Schiff base metal complexes are of great importance in pharmaceutical science owing to their unique chemical properties, which enable them to exhibit diverse biological activities such as anti-bacterial,anti-oxidant, anti-inflammatory, and anti-tumor properties. Furthermore, Schiff base metal complexes can serve as reagents and catalysts in chemical reactions. This review aims to provide an overview of our recently published studies on Cu(Ⅱ) and Pd(Ⅱ) complexes derived from proline Schiff base ligands. We also discuss the potential applications of these metal complexes in the fields of antibacterial and chiral resolution.

关键词： Schiff bases Biological activity Tailor-made amino acids Asymmetric synthesis Chiral tridentate ligands Square-planar Cu(Ⅱ)-complexes Square-planar Pd(Ⅱ)-complexes

Timp1 Deletion Induces Anxiety-like Behavior in Mice

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Neuroscience Bulletin 2024年第6期40卷 732-742页

作者： Xiaotong Wang Wei Zheng Ziyi Zhu Biyu Xing Weijie Yan Ke Zhu Lingli Xiao Chaojuan Yang Mengping Wei Lei Yang Zi-Bing Jin Xueyun Bi Chen Zhang State Key Laboratory of Neurology and Oncology drug Development Nanjing210000China School of Basic Medical Sciences Wenzhou Medical UniversityWenzhou325035China School of Basic Medical Sciences Beijing Key Laboratory of Neural Regeneration and RepairAdvanced Innovation Center for Human Brain ProtectionBeijing Laboratory of Oral HealthCapital Medical UniversityBeijing100069China Beijing Institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing100005China Chinese Institute for Brain Research Beijing102206China Key Laboratory for Biomechanics and Mechanobiology of the Ministry of Education Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Engineering MedicineBeihang UniversityBeijing100191China

The hippocampus is essential for learning and memory,but it also plays an important role in regulating emotional behavior,as hippocampal excitability and plasticity affect anxiety and *** synaptic plasticity may be regulated by tissue inhibitor of matrix metalloproteinase 1(TIMP1),a known protein inhibitor of extracellular matrix(ECM),and the expression of TIMP1 in the hippocampus can be induced by neuronal excitation and various ***,the involvement of Timp1 in fear learning,anxiety,and hippocampal synaptic function remains to be *** study of Timp1 function in vivo revealed that Timp1 knockout mice exhibit anxiety-like behavior but normal fear *** results suggested that Timp1 knockout mice showed hyperactivity in the ventral CA1 region,but the basic synaptic transmission and plasticity were normal in the Schaffer collateral *** together,our results suggest that deletion of Timp1 in vivo leads to the occurrence of anxiety behaviors,but that Timp1 is not crucial for fear learning.

关键词： Timp1 Anxiety Fear Synaptic transmission Synaptic plasticity

Genome engineering of the human gut microbiome

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Journal of Genetics and Genomics 2024年第5期51卷 479-491页

作者： Linggang Zheng Juntao Shen Ruiyue Chen Yucan Hu Wei Zhao Elaine Lai-Han Leung Lei Dai Dr Neher's Biophysics Laboratory for Innovative drug Discovery/State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyTaipaMacao 999078China CAS Key Laboratory of Quantitative Engineering Biology Shenzhen Institute of Synthetic BiologyShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China University of Chinese Academy of Sciences Beijing 100049China Cancer Center Faculty of Health ScienceUniversity of MacaoMacao 999078China MOE Frontiers Science Center for Precision Oncology University of MacaoMacao 999078China

The human gut microbiome,a complex ecosystem,significantly influences host health,impacting crucial aspects such as metabolism and *** enhance our comprehension and control of the molecular mechanisms orchestrating the intricate interplay between gut commensal bacteria and human health,the exploration of genome engineering for gut microbes is a promising ***,the complexities and diversities inherent in the gut microbiome pose substantial challenges to the development of effective genome engineering tools for human gut *** this comprehensive review,we provide an overview of the current progress and challenges in genome engineering of human gut commensal bacteria,whether executed in vitro or in situ.A specific focus is directed towards the advancements and prospects in cargo DNA delivery and high-throughput ***,we elucidate the immense potential of genome engineering methods to enhance our understanding of the human gut microbiome and engineer the microorganisms to enhance human health.

关键词： Non-model gut commensals Genomeediting reagents Cargo delivery High-throughput genome engineering