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The role of snapin in regulation of brain homeostasis

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Neural Regeneration Research 2024年第8期19卷 1696-1701页

作者： Jiawen Li Xinqi Huang Yumei An Xueshi Chen Yiyang Chen Mingyuan Xu Haiyan Shan mingyang zhang Shanghai Key Lab of Forensic Medicine Key Lab of Forensic ScienceMinistry of JusticeChina(Academy of Forensic Science)ShanghaiChina Institute of Forensic Sciences Suzhou Medical CollegeSoochow UniversitySuzhouJiangsu ProvinceChina Department of Obstetrics and Gynecology The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhouJiangsu ProvinceChina

Brain homeostasis refe rs to the normal working state of the brain in a certain period,which is impo rtant for overall health and normal life activities.Currently,there is a lack of effective treatment methods for the adverse consequences caused by brain homeostasis imbalance.Snapin is a protein that assists in the formation of neuronal synapses and plays a crucial role in the normal growth and development of synapses.Recently,many researchers have reported the association between snapin and neurologic and psychiatric disorders,demonstrating that snapin can improve brain homeostasis.Clinical manifestations of brain disease often involve imbalances in brain homeostasis and may lead to neurological and behavioral sequelae.This article aims to explo re the role of snapin in restoring brain homeostasis after injury or diseases,highlighting its significance in maintaining brain homeostasis and treating brain diseases.Additionally,it comprehensively discusses the implications of snapin in other extracerebral diseases such as diabetes and viral infections,with the objective of determining the clinical potential of snapin in maintaining brain homeostasis.

关键词： brain homeostasis diabetes neurological diseases snapin traumatic brain injury vesicle fusion

Mitophagy in intracerebral hemorrhage:a new target for therapeutic intervention

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Neural Regeneration Research 2024年第2期19卷 316-323页

作者： Yiyang Chen Wenxuan Tang Xinqi Huang Yumei An Jiawen Li Shengye Yuan Haiyan Shan mingyang zhang Institute of Forensic Sciences Suzhou Medical CollegeSoochow UniversitySuzhouJiangsu ProvinceChina Shanghai Key Lab of Forensic Medicine Key Lab of Forensic ScienceMinistry of Justice(Academy of Forensic Science)ShanghaiChina Department of Obstetrics and Gynecology The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhouJiangsu ProvinceChina

Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Recent studies have indicated that mitochondrial dysfunction and mitophagy likely relate to the pathophysiology of intracerebral hemorrhage.Mitophagy,or selective autophagy of mitochondria,is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria.Mitophagy markedly contributes to the reduction of secondary brain injury caused by mitochondrial dysfunction after intracerebral hemorrhage.This review provides an overview of the mitochondrial dysfunction that occurs after intracerebral hemorrhage and the underlying mechanisms regarding how mitophagy regulates it,and discusses the new direction of therapeutic strategies targeting mitophagy for intracerebral hemorrhage,aiming to determine the close connection between mitophagy and intracerebral hemorrhage and identify new therapies to modulate mitophagy after intracerebral hemorrhage.In conclusion,although only a small number of drugs modulating mitophagy in intracerebral hemorrhage have been found thus far,most of which are in the preclinical stage and require further investigation,mitophagy is still a very valid and promising therapeutic target for intracerebral hemorrhage in the long run.

关键词： intracerebral hemorrhage mitochondrial dysfunction mitophagy neuroinflammation neuroprotection reactive oxygen species secondary brain injury therapeutic target

Fine-tuning the activation behaviors of ternary modular cabazitaxel prodrugs for efficient and on-target oral anti-cancer therapy

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 188-203页

作者： mingyang zhang Yifan Miao Can Zhao Tong Liu Xiyan Wang Zixuan Wang Wenxin Zhong Zhonggui He Chutong Tian Jin Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province Hangzhou 310058China Joint International Research Laboratory of Intelligent Drug Delivery Systems Ministry of EducationShenyang 110016China Liaoning Provincial Institute of Drug Inspection and Testing Shenyang 110036China

The disulfide bond plays a crucial role in the design of anti-tumor prodrugs due to its exceptional tumor-specific redox responsiveness. However, premature breaking of disulfide bonds is triggered by small amounts of reducing substances (e.g., ascorbic acid, glutathione, uric acid and tea polyphenols) in the systemic circulation. This may lead to toxicity, particularly in oral prodrugs that require more frequent and high-dose treatments. Fine-tuning the activation kinetics of these prodrugs is a promising prospect for more efficient on-target cancer therapies. In this study, disulfide, steric disulfide, and ester bonds were used to bridge cabazitaxel (CTX) to an intestinal lymph vessel-directed triglyceride (TG) module. Then, synthetic prodrugs were efficiently incorporated into self-nanoemulsifying drug delivery system (corn oil and Maisine CC were used as the oil phase and Cremophor EL as the surfactant). All three prodrugs had excellent gastric stability and intestinal permeability. The oral bioavailability of the disulfide bond-based prodrugs (CTX-(C)S-(C)S-TG and CTX-S-S-TG) was 11.5- and 19.1-fold higher than that of the CTX solution, respectively, demonstrating good oral delivery efficiency. However, the excessive reduction sensitivity of the disulfide bond resulted in lower plasma stability and safety of CTX-S-S-TG than that of CTX-(C)S-(C)S-TG. Moreover, introducing steric hindrance into disulfide bonds could also modulate drug release and cytotoxicity, significantly improving the anti-tumor activity even compared to that of intravenous CTX solution at half dosage while minimizing off-target adverse effects. Our findings provide insights into the design and fine-tuning of different disulfide bond-based linkers, which may help identify oral prodrugs with more potent therapeutic efficacy and safety for cancer therapy.

关键词： Steric disulfide bond Triglyceride-like pr odrugs Cabazitaxel Lymphatic transport Oral chemotherapy

Corrigendum to“Bi-continuous Mg-Ti interpenetrating-phase composite as a partially degradable and bioactive implant material”[Journal of Materials Science&Technology 146(2023)211-220]

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Journal of Materials Science & Technology 2024年第3期170卷 255-257页

作者： Chenxi Dou mingyang zhang Dechun Ren Haibin Ji Zhe Yi Shaogang Wang Zengqian Liu Qiang Wang Yufeng Zheng Zhefeng zhang Rui Yang Liaoning Provincial Key Laboratory of Oral Diseases School and Hospital of StomatologyChina Medical UniversityShenyang 110001China Shi-Changxu Innovation Center for Advanced Materials Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China School of Materials Science and Engineering University of Science and Technology of ChinaHefei 230026China School of Materials Science and Engineering Peking UniversityBeijing 100871China Center for Adaptive System Engineering School of Creativity and ArtShanghaiTech UniversityShanghai 201210China

The authors are very sorry for their carelessness that there are some problems with Fig.3 in the original manuscript.

关键词： composite phase partially

Frontiers of collaborative intelligence systems

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Journal of Information and Intelligence

Journal of Information and Intelligence 2024年第1期2卷 14-27页

作者： Maoguo Gong Yajing He Hao Li Yue Wu mingyang zhang Shanfeng Wang Tianshi Luo School of Electronic Engineering Key Laboratory of Collaborative Intelligence SystemsMinistry of EducationXidian UniversityXi'an 710071China School of Computer Science and Technology Key Laboratory of Collaborative Intelligence SystemsMinistry of EducationXidian UniversityXi'an 710071China School of Cyber Engineering Key Laboratory of Collaborative Intelligence SystemsMinistry of EducationXidian UniversityXi'an 710071China

The development of information technology has propelled technological reform in artificial intelligence(AI).To address the needs of diversified and complex applications,AI has been increasingly trending towards intelligent,collaborative,and systematized development across different levels and tasks.Research on intelligent,collaborative and systematized AI can be divided into three levels:micro,meso,and macro.Firstly,the micro-level collaboration is illustrated through the introduction of swarm intelligence collaborative methods related to individuals collaboration and decision variables collaboration.Secondly,the meso-level collaboration is discussed in terms of multi-task collaboration and multi-party collaboration.Thirdly,the macro-level collaboration is primarily in the context of intelligent collaborative systems,such as terrestrial-satellite collaboration,space-air-ground collaboration,space-air-ground-air collaboration,vehicle-road-cloud collaboration and end-edge-cloud collaboration.Finally,this paper provides prospects on the future development of relevant fields from the perspectives of the micro,meso,and macro levels.

关键词： Artificial intelligence collaboration mechanism Micro,meso and macro collaboration Artificial intelligence mega application

Engineering the atomic interface of porous ceria nanorod with single palladium atoms for hydrodehalogenation reaction

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Nano Research 2022年第2期15卷 1338-1346页

作者： Zhijun Li mingyang zhang Lili zhang Xiuli Dong Leipeng Leng JHugh Horton Jun Wang Joint International Research Laboratory of Advanced Chemical Catalytic Materials&Surface Science College of Chemistry and Chemical EngineeringNortheast Petroleum UniversityDaqing 163318China Shenyang National Laboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China Department of Chemistry Queens UniversityKingstonK7L 3N6Canada

Tuning the electronic properties of single atom catalysts(SACs)between the central metal and the neighboring surface atoms has emerged as an efficient strategy to boost catalytic efficiency and metal utilization.Here we describe a simple and efficient approach to create atomically dispersed palladium atoms supported over defect-containing porous ceria nanorod containing palladium up to 0.26 wt.%.The existence of singly dispersed palladium atoms is confirmed by spherical aberration correction electron microscopy and extended X-ray absorption fine structure measurements.This catalyst shows excellent efficiency in hydrodehalogenation reactions at low H2 pressure under mild conditions,along with satisfactory recyclability and scalability.Density functional theory(DFT)calculations reveal that the high activity stems from the spatial isolation of palladium atoms and the modified electronic structure of palladium confined in defect-containing ceria nanorod.This work may lay the foundation for the facile creation of single atom catalysts within the synthetic community and shed light on the possibility for scale-up production.

关键词： heterogeneous catalysis palladium single atom catalyst porous ceria nanorod hydrodehalogenation catalytic activity

Disulfiram enhances the antitumor activity of cisplatin by inhibiting the Fanconi anemia repair pathway

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第3期24卷 207-220页

作者： Meng YUAN Qian WU mingyang zhang Minshan LAI Wenbo CHEN Jianfeng YANG Li JIANG Ji CAO Laboratory of Fruit Quality Biology/the State Agriculture Ministry Laboratory of Horticultural Plant Growth Development and Quality ImprovementFruit Science InstituteCollege of Agriculture and BiotechnologyZhejiang UniversityHangzhou 310058China Institute of Pharmacology and Toxicology Zhejiang Province Key Laboratory of Anti-Cancer Drug ResearchCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Polytechnic Institute Zhejiang UniversityHangzhou 310015China Department of Gastroenterology Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310006China Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province Hangzhou 310006China The Innovation Institute for Artificial Intelligence in Medicine Zhejiang UniversityHangzhou 310018China Cancer Center of Zhejiang University Hangzhou 310058China

A series of chemotherapeutic drugs that induce DNA damage,such as cisplatin(DDP),are standard clinical treatments for ovarian cancer,testicular cancer,and other diseases that lack effective targeted drug therapy.Drug resistance is one of the main factors limiting their application.Sensitizers can overcome the drug resistance of tumor cells,thereby enhancing the antitumor activity of chemotherapeutic drugs.In this study,we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms.We found that the alcohol withdrawal drug disulfiram(DSF)could significantly enhance the antitumor activity of DDP.JC-1 staining,propidium iodide(PI)staining,and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells.Subsequent RNA sequencing combined with Gene Set Enrichment Analysis(GSEA)pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism:DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia(FA)repair pathway,exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs.Thus,our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP.This might provide an effective and safe solution for combating DDP resistance in clinical treatment.

关键词： Disulfiram(DSF) Cisplatin(DDP) DNA damage Fanconi anemia(FA)repair Chemotherapy

Single palladium atoms stabilized byβ-FeOOH nanorod with superior performance for selective hydrogenation of cinnamaldehyde

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Nano Research 2022年第4期15卷 3114-3121页

作者： Zhijun Li Leipeng Leng Xiaowen Lu mingyang zhang Qian Xu J.Hugh Horton Junfa Zhu Joint International Research Laboratory of Advanced Chemical Catalytic Materials&Surface Science College of Chemistry and Chemical EngineeringNortheast Petroleum UniversityDaqing 163318China National Synchrotron Radiation Laboratory University of Science and Technology of ChinaHefei 230029China Department of Chemistry Queen′s UniversityKingstonK7L 3N6Canada

Atomically dispersed single atom catalysts represent an ideal means of converting less valuable organics into value-added chemicals of interest with high efficiency.Herein,we describe a facile synthetic approach to create defect-containingβ-FeOOH doped with isolated palladium atoms that bond covalently to the nearby oxygen and iron atoms.The presence of singly dispersed palladium atoms is confirmed by spherical aberration correction electron microscopy and extended X-ray absorption fine structure measurements.This single palladium atom catalyst manifests outstanding catalytic efficiency(conversion:99%;selectivity 99%;turnover frequency:2,440 h^(-1))in the selective hydrogenation of cinnamaldehyde to afford hydrocinnamaldehyde.Experimental measurements and density functional theory(DFT)calculations elucidate the high catalytic activity and the strong metal-support interaction stem from the unique coordination environment of the isolated palladium atoms.These findings may pave the way for the facile construction of single atom catalysts in a defect-mediated strategy for efficient organic transformations in heterogeneous catalysis.

关键词： heterogeneous catalysis palladium single atom catalyst β-FeOOH nanorod coordination environment hydrogenation of cinnamaldehyde

Boosting SN38-based oral chemotherapy to combine reductionbioactivated structured lipid-mimetic prodrug with ascorbic acid

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Nano Research 2022年第10期15卷 9092-9104页

作者： Helin Wang Qi Lu Yifan Miao Jiaxuan Song mingyang zhang Zixuan Wang Haotian zhang Zhonggui He Chutong Tian Jin Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China

The reduction-responsive disulfide bonds have been widely used as bioactive linkages to facilitate a rapid release of anticancer drugs into tumor cells.However,the activation can be hindered by the kinetics of the thiol-disulfide exchange reactions.Supplementing with an additional reductant is a promising strategy to further boost drug release.Herein,inspired by the specific absorption mechanism of triglyceride fat,structured lipid-mimetic oral prodrugs of 7-ethyl-10-hydroxycamptothecin(SN38)were designed to improve intestinal permeability and bypass the first-pass effect.SN38 prodrugs were prepared into lipid formulations that could self-emulsify into nano-sized particles after entering the gastrointestinal tract.Surprisingly,we found that the oral bioavailability of the prodrug lipid formulation could be up to 2.69-fold higher than that of the parent SN38,indicating an effective oral delivery.In addition,the reduction-responsive disulfide bond was used as a linker,and ascorbic acid(ASC)was coadministrated to further promote the efficient release of SN38 from the prodrug.ASC enhanced the oral antitumor effect of the reduction-responsive oral prodrug and exhibited good safety.In summary,the combination of a structured lipid-mimetic prodrug and ASC was firstly demonstrated to boost the oral chemotherapy effect of the difficult-for-oral chemotherapeutics.

关键词： oral chemotherapy structured lipid-mimetic prodrug 7-ethyl-10-hydroxycamptothecin(SN38) ascorbic acid