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Human neural stem cell-derived extracellular vesicles protect against ischemic stroke by activating the PI3K/AKT/mTOR pathway

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Neural Regeneration Research 2025年第11期20卷 3245-3258页

作者： Jiayi Wang Mengke Zhao Dong Fu Meina Wang Chao Han Zhongyue Lv Liang Wang Jing Liu Stem Cell Clinical Research Center The First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina dalian Innovation Institute of Stem Cell and Precision Medicine DalianLiaoning ProvinceChina Institute(college)of Integrative Medicine Dalian Medical UniversityDalianLiaoning ProvinceChina

Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived *** lays a foundation for the development of potentially potent new treatment modalities for ischemic ***,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical *** promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic *** found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal *** human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase *** findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling ***,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety ***,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.

关键词： behavior exosome extracellular vesicles ischemic stroke mammalian target of rapamycin(mTOR) middle cerebral artery occlusion neural stem cells neuronal apoptosis phosphoinositide 3-kinase(PI3K) protein kinase B(AKT)

Visible-light-responsive homologous heterostructure of oxynitrides constructed to boost charge separation and water splitting

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Science China Chemistry 2025年第1期68卷 186-191页

作者： Hai Zou Yunfeng Bao Xueshang Xin Yu Qi Tengfeng Xie Fuxiang Zhang State Key Laboratory of Catalysis Dalian National Laboratory for Clean Energy Dalian Institute of Chemical Physics Chinese Academy of Sciences School of Chemistry and Chemical Engineering Liaoning Normal University college of Chemistry Jilin University

Constructing type II heterostructures represents a widely recognized strategy for enhancing charge separation and photocatalytic efficiency,but it remains challenging to fabricate homologous heterostructures based on visible-light-responsive semiconductors,especially for popularly investigated （oxy）nitrides with low thermal ***,we synthesized a homologous heterostructure （denoted as YTON＿H） based on the oxynitrides of YTaO4-xNyand YTa *** heterostructure exhibits type II band structure alignment and intimate interface achieved through a magnesium （Mg） powder-assisted nitridation *** with widely reported heterologous heterostructures,the as-obtained YTON＿H homologous heterostructure could similarly exhibit enhanced charge separation as well as photocatalytic water splitting performance with respect to its counterparts(YTaO4-xNyand YTaON2).Meanwhile,detailed structural characterizations and spectroscopy analysis have been made to confirm the formation of heterostructure and promotion of spatial charge separation.

关键词： charge separation heterostructure oxynitride photocatalysis visible light

Gas-Solid Flow,Combustion Characteristics,and Gas Emissions in a 75 t/h CFB Boiler Based on the CPFD Method

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Journal of Thermal Science 2025年第1期34卷 323-336页

作者： HUANG Xiankun BAI Zhang ZHU Xiaoli WANG Shuoshuo MU Lin GONG Liang college of New Energy China University of Petroleum (East China) Key Laboratory of Ocean Energy Utilization and Energy Conservation of Ministry of Education School of Energy and Power EngineeringDalian University of Technology

A 3D simulation using Computational Particle Fluid Dynamics（CPFD） methods was used to calculate coal combustion in a 75 t/h industrial-scale circulating fluidized bed（CFB） *** characteristics,gas-solid flow characteristics,and gaseous pollutant emissions of CFB boilers from combustion ignition to stable operation were systematically evaluated in this *** show that the temperature distribution is relatively uniform throughout the *** the combustion process unfolds within the boiler,the gas composition curve strikingly portrays the inverse correlation between CO2and *** the combustion reaction progresses,it becomes evident that the concentration of CO2progressively increases,while the concentration of O2concurrently *** inverse relationship underscores the fundamental combustion reaction,where carbon-based fuels react with oxygen to produce carbon dioxide and release ***,a comprehensive analysis has revealed that,from ignition to stable combustion,both nitric oxide（NO） and sulfur dioxide（SO2） emissions exhibit a declining *** reduction in pollutant generation is attributed to the improvement in combustion *** complete combustion leads to lower levels of unburned hydrocarbons,which are prone to NO ***,the sulfur content in the fuel is more efficiently oxidized to sulfur trioxide（SO3） or bound in sulfates,reducing *** steady state in the simulation,the SO2mass flow rate varies significantly with the furnace height,gradually increasing from 0.07 kg·s-1at 4 m at the bottom of the furnace to a peak of 0.078 kg·s-1at 8 m in the center,and then decreasing to 0.06 kg·s-1at 20m at the top of the furnace.

关键词： Sulfur dioxide

Electrochemical conversion of methane to bridge the gap in the artificial carbon cycle

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Journal of Energy Chemistry 2025年第1期100卷 286-308页

作者： Yuhao Peng Yuefeng Song Ihar Razanau Juanxiu Xiao Wei Xiao Di Hu Guoxiong Wang college of Chemistry and Molecular Sciences Hubei Key Laboratory of Electrochemical Power Sources Wuhan University State Key Laboratory of Catalysis Dalian National Laboratory for Clean Energy iChEM (Collaborative Innovation Center of Chemistry for Energy Materials) Dalian Institute of Chemical Physics Chinese Academy of Sciences Laboratory of Physical-Chemical Technologies SSPA Scientific and Practical Materials Research Centre of NAS of Belarus State Key Laboratory of Marine Resources Utilization in South China Sea Collaborative Innovation Center of Marine Science and Technology School of Marine Science and Engineering Hainan University Department of Chemical and Environmental Engineering University of Nottingham Ningbo China

Methane, an abundant one-carbon（C1） resource, is extensively used in the industrial production of vital fuels and value-added chemicals. However, current industrial methane conversion technologies are energy-and carbon-intensive, mainly due to the high activation energy required to break the inert C–H bond, low selectivity, and problematic side reactions, including CO2emissions and coke deposition. Electrochemical conversion of methane（ECM） using intermittent renewable energy offers an attractive solution, due to its modular reactor design and operational flexibility across a broad spectrum of temperatures and pressures. This review emphasizes conversion pathways of methane in various reaction systems, highlighting the significance and advantages of ECM in facilitating a sustainable artificial carbon cycle. This work provides a comprehensive overview of conventional methane activation mechanisms and delineates the complete pathways of methane conversion in electrolysis contexts. Based on surface/interface chemistry, this work systematically analyzes proposed reaction pathways and corresponding strategies to enhance ECM efficiency towards various target products, including syngas, hydrocarbons, oxygenates, and advanced carbon materials. The discussion also encompasses opportunities and challenges for the ECM process, including insights into ECM pathways, rational electrocatalyst design, establishment of benchmarking protocols, electrolyte engineering, enhancement of CH4conversion rates, and minimization of CO2emission.

关键词： Activation energy

In situ monitoring of the structural change of microemulsions in simulated gastrointestinal conditions by SAXS and FRET

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Acta Pharmaceutica Sinica B 2018年第4期8卷 655-665页

作者： Xia Lv Shuguang Zhang Huipeng Ma Peipei Dong Xiaodong Ma Ming Xu Yan Tian Zeyao Tang Jinyong Peng Haibo Chen Jianbin Zhang college of Pharmacy Dalian Medical University college of Life Science Dalian Minzu University Xinglin college Liaoning University of Traditional Chinese Medicine college of medical Laboratory Dalian Medical University

Microemulsions are promising drug delivery systems for the oral administration of poorly watersoluble drugs. However, the evolution of microemulsions in the gastrointestinal tract is still poorly characterized,especially the structural change of microemulsions under the effect of lipase and mucus. To better understand the fate of microemulsions in the gastrointestinal tract, we applied small-angle X-ray scattering(SAXS) and fluorescence resonance energy transfer(FRET) to monitor the structural change of microemulsions under the effect of lipolysis and mucus. First, the effect of lipolysis on microemulsions was studied by SAXS, which found the generation of liquid crystalline phases. Meanwhile, FRET spectra indicated micelles with smaller particle sizes were generated during lipolysis, which could be affected by CaCl_2, bile salts and lecithin. Then, the effect of mucus on the structural change of lipolysed microemulsions was studied. The results of SAXS and FRET indicated that the liquid crystalline phases disappeared, and more micelles were generated. In summary, we studied the structural change of microemulsions in simulated gastrointestinal conditions by SAXS and FRET, and successfully monitored the appearance and disappearance of the liquid crystalline phases and micelles.

关键词： Microemulsions SAXS FRET Lipolysis Mucus Liquid crystalline phase

Adenine: an important drug scaffold for the design of antiviral agents

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Acta Pharmaceutica Sinica B 2015年第5期5卷 431-441页

作者： Changyuan Wang Zhendong Song Haiqing Yu Kexin Liu Xiaodong Ma college of Pharmacy Dalian Medical University

Adenine derivatives, in particular the scaffold bearing the acyclic nucleoside phosphonates (ANPS), possess significant antiviral and cytostatic now, several effective adenine derivatives have been marketed for the treatment of HIV, HBV, CMV and other virus-infected diseases. These compounds are represented by tenofovir (PMPA) a medicine for both HIV and HBV, and adefovir as an anti-HBV agent. More than this, other analogs, such as GS9148, GS9131, and GS7340, are also wellknown anti-viral agents that have been progressed to the clinical studies for their excellent activity. in general, the structures of these compounds include an adenine nueleobase linked to a phosphonate side ehain. Considerable structural modifications on the scaffold itself and the peripheral sections were made. The structure-activity relationships (SARs) of this skeleton will provide valuable clues to identify more effective adenine derivatives as antiviral drugs. Here, we systematically summarized the SARs of the adenine derivatives, and gave important information for further optimizing this template. (c) 2015 Chinese Pharmaceutical Association and Institute of Materia Medial., Chinese Academy of medical Sciences. Production and hosting by Elsevier B.V.

关键词： Antiviral Structureactivity relationship Adenine Aeyclic necleoside phosphonate Scaffold

Synthesis, Structural Features and Evaluation of Antibacterial Activities of Two Schiff Bases Derived from 3,4-Dihydroxybenzhydrazide

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Chinese Journal of Structural Chemistry 2010年第11期29卷 1684-1688页

作者：刁云鹏钟民涛张厚利黄珊珊刘欣李传勋郑泽宝林原黄敏 college of Pharmacy Dalian Medical University college of Microbiology Dalian Medical University Department of Chemistry Taishan University

A new Schiff base compound （I）, （E）-N＇-（2-hydroxy-3-methoxybenzylidene）-3,4-dihydroxybenzohydrazide-ethanol-water （1/1/1）, has been synthesized and characterized by elemental analysis, IR spectra, and single-crystal X-ray diffraction. The crystal belongs to monoclinic, space group P21/n with a = 7.459（4）, b = 18.316（10）, c = 13.638（7）, β = 101.585（9）o, V = 1825.2（17）3, Z = 4, μ = 0.104 mm-1, Dc = 1.333 g/cm3, F（000） = 776, the final R = 0.0635 and wR = 0.1302 for 3216 observed reflections with I 〉 2σ（I）. Another compound （Ⅱ）, （E）-N＇-（2,5-dimethoxybenzylidene）-3,4-dihydroxybenzohydrazide-ethanol-water （1/1/1）, has been synthesized and reported before. The antibacterial activities of these two compounds against seven bacteria were first evaluated, and one compound showed considerable antibacterial activity against S. aureus.

关键词： Schiff base crystal structure antibacterial

Inhibition of Escherichia coli nitroreductase by the constituents in Syzygium aromaticum

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Chinese Journal of Natural Medicines 2022年第7期20卷 506-517页

作者： CHEN Lu CHEN Xi BAI Yue ZHAO Zi-Nan CAO Yun-Feng LIU Li-Kun JIANG Tao HOU Jie college of Basic medical Sciences Dalian Medical UniversityDalian 116044China dalian Runsheng Kangtai medical Laboratory Co. Ltd.Dalian 116000China

Gut bacterial nitroreductases play an important role in reduction of various nitroaromatic compounds to the corresponding N-nitroso compounds,hydroxylamines or aromatic amines,most of which are carcinogenic and mutagenic *** of gut nitroreductases has been recognized as an attractive approach for reducing mutagen metabolites in the colon,so as to prevent colon *** this study,the inhibitory effects of 55 herbal medicines against Escherichia coli(***)nitroreductase(EcNfsA)were *** with other herbal extracts,Syzygium aromaticum extract showed superior inhibitory potency toward EcNf-sA mediated nitrofurazone ***,the inhibitory effects of 22 major constituents in Syzygium aromaticum against EcNfsA were *** with other tested natural compounds,ellagic acid,corilagin,betulinic acid,oleanic acid,ursolic acid,urolith-in M5 and isorhamnetin were found with strong to moderate inhibitory effect against EcNfsA,with IC50 values ranging from 0.67 to 28.98 mol·L^(−1).Furthermore,the inhibition kinetic analysis and docking simulation demonstrated that ellagic acid and betulinic acid potently inhibited EcNfsA(Ki<2μmol·L−1)in a competitively inhibitory manner,which created strong interactions with the catalytic triad of *** summary,our findings provide new scientific basis for explaining the anti-mutagenic activity of Syzygium aromaticum,where some newly identified EcNfsA inhibitors can be used for developing novel agents to reduce the toxicity induced by bacteri-al nitroreductase.

关键词： Gut bacterial nitroreductase EcNfsA inhibitor Syzygium aromaticum Anti-mutagenic activity

Cilastatin protects against imipenem-induced nephrotoxicity via inhibition of renal organic anion transporters(OATs)

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Acta Pharmaceutica Sinica B 2019年第5期9卷 986-996页

作者： Xiaokui Huo Qiang Meng Changyuan Wang Yanna Zhu Zhihao Liu Xiaodong Ma Xiaochi Ma Jinyong Peng Huijun Sun Kexin Liu Department of Clinical Pharmacology College of PharmacyDalian Medical UniversityDalian116044China college(Institute)of Integrative Medicine Dalian Medical UniversityDalian116044China Provincial Key Laboratory for Pharmacokinetics and Transport Dalian Medical UniversityDalian116044China

Imipenem is a carbapenem antibiotic. However, Imipenem could not be marketed owing to its instability and nephrotoxicity until cilastatin, an inhibitor of renal dehydropeptidase-I(DHP-I),was developed. In present study, the potential roles of renal organic anion transporters(OATs) in alleviating the nephrotoxicity of imipenem by cilastatin were investigated in vitro and in rabbits. Our results indicated that imipenem and cilastatin were substrates of h OAT1 and h OAT3. Cilastatin inhibited h OAT1/3-mediated transport of imipenem with IC50 values comparable to the clinical concentration, suggesting the potential to cause a clinical drug–drug interaction(DDI). Moreover,imipenem exhibited h OAT1/3-dependent cytotoxicity, which was alleviated by cilastatin and probenecid. Furthermore, cilastatin and probenecid ameliorated imipenem-induced rabbit acute kidney injury, and reduced the renal secretion of imipenem. Cilastatin and probenecid inhibited intracellular accumulation of imipenem and sequentially decreased the nephrocyte toxicity in rabbit primary proximal tubule cells. Renal OATs, besides DHP-I, was also the target of interaction between imipenem and cilastatin, and contributed to the nephrotoxicity of imipenem. This therefore gives in part the explanation about the mechanism by which cilastatin protected against imipenem-induced nephrotoxicity. Thus, OATs can potentially be used as a therapeutic target to avoid the renal adverse reaction of imipenem in clinic.

关键词： Imipenem Cilastatin Probenecid OATs h OAT1 h OAT3 Nephrotoxicity