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A biomimetic spore nanoplatform for boosting chemodynamic therapy and bacteria-mediated antitumor immunity for synergistic cancer treatment

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Asian Journal of pharmaceutical sciences 2024年第3期19卷 106-118页

作者： Cuixia Zheng Lingling Sun Hongjuan Zhao Mengya Niu Dandan Zhang Xinxin Liu Qingling Song Weijie Zhong Baojin Wang Yun Zhang Lei Wang Huaihe Hospital of henan university Translational medicine Center Weihai Municipal Hospital Cheeloo College of Medicine Shandong University School of pharmaceutical sciences Zhengzhou University Pingyuan Lab Henan Normal University Gynecology the Third Affiliated Hospital of Zhengzhou University

Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting ***,the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial ***,monotherapy is ineffective in completely eliminating complex cancer with multiple contributing *** this study,based on our discovery that spore shell （SS） of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity,we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy,chemodynamic therapy and antitumor immunity for synergistic cancer *** detail,SS is separated from probiotic spores and then attached to the surface of liposome （Lipo） that was loaded with hemoglobin （Hb）,glucose oxidase （GOx） and JQ1to construct SS@Lipo/Hb/GOx/*** tumor tissue,highly toxic hydroxyl radicals （·OH）are generated via sequential catalytic reactions:GOx catalyzing glucose into H2O2and Fe2+in Hb decomposing H2O2into·*** combination of·OH and SS adjuvant can improve tumor immunogenicity and activate immune ***,JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune *** this manner,SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and *** summarize,the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.

关键词： Biomimetic spore shell Bacteria-mediated antitumor therapy Chemodynamic therapy Immunotherapy Tumor microenvironment

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Abundance and sources of particulate polycyclic aromatic hydrocarbons and aromatic acids at an urban site in central China

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Journal of Environmental sciences 2024年第8期142卷 155-168页

作者： Luqi Shang Zhe Dong Zihan Li Mingkai Wang Zihan Kong Xiao Li Ruiqin Zhang School of Ecology and Environment Zhengzhou UniversityZhengzhou 450001China College of Chemistry Zhengzhou UniversityZhengzhou 450001China institute of Environmental sciences Zhengzhou UniversityZhengzhou 450001China

We conducted a simultaneous field study of PM_(2.5)-bound particulate polycyclic aromatic hydrocarbons(PAHs)and aromatic acids(AAs)in a polluted city zhengzhou to explore the concentration,sources and potential conversion pathways between PAHs and AAs in different *** average concentrations of PM_(2.5),28PAHs and 8AAs during the sampling period were 77μg/m^(3),75 ng/m^(3),and 283 ng/m^(3),*** concentration of both28PAHs and 8AAs were highest in winter and lowest in summer with ratios of 6.3 and 2.3,*** with 5-7 rings were the main components of PAHs(52%),followed by 4rings PAHs(30%)and 2-3 rings PAHs(18%).According to the source appointment results obtained by positive matrix factorization,the main sources of PAHs were combustion and vehicle emissions,which account for 37%and 34%,respectively.8AAs were divided into three groups,including four benzene dicarboxylic acids(B2CAs),three benzene tricarboxylic acids(B3CAs)and one benzene tetracarboxylic acid(B4CA).And interspecies correlation analysis with PM_(2.5)source markers were used to investigate potential *** acid(o-Ph)was the most abundant specie of 8AAs(157 ng/m^(3),55%of 8AAs),which was well correlated with ***,B3CAs and B4CA were highly correlated with sulfate and weakly correlated with levoglucosan,suggesting that secondary formation was their main *** logical oxidation products of PAHs,o-Ph and B3CAs showed good correlations with a number of PAHs,indicating possible photochemical oxidation pathway by *** addition,O_(3),NO_(2),temperature and relative humidity have positive effects on the secondary formation of B3CAs.

关键词： Polycyclic aromatic hydrocarbons Aromatic acids Source appointment Secondary formation

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Probing the Nucleation and Growth Kinetics of Bismuth Nanoparticles via In-situ Transmission Electron Microscopy

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Journal of Wuhan university of Technology(Materials Science) 2024年第4期39卷 877-887页

作者：王浪李超凡 RAN Maojin YUAN Manman 胡执一 LI Yu State Key Laboratory of Advanced Technology for Materials Synthesis and Processing Wuhan University of TechnologyWuhan 430070China Nanostructure Research Centre(NRC) Wuhan University of TechnologyWuhan 430070China institute of Chemistry Henan Academy of SciencesZhengzhou 450002China henan Academy of sciences Zhengzhou 450046China

The nucleation and growth mechanism of nanoparticles is an important theory,which can guide the preparation of ***,it is still lacking in direct observation on the details of the evolution of intermediate state structure during nucleation and *** this work,the evolution process of bismuth nanoparticles induced by electron beam was revealed by in-situ transmission electron microscopy(TEM)at atomic *** experimental results demonstrate that the size,stable surface and crystallographic defect have important influences on the growth of Bi *** non-classical growth paths including single crystal growth and polycrystalline combined growth,as well as,corresponding layer-by-layer growth mechanism along{012}stable crystal plane of Bi nanoparticles with dodecahedron structure were revealed by in-situ TEM *** results provide important guidance and a new approach for in-depth understanding of the nucleation and growth kinetics of nanoparticles.

关键词： bismuth nanoparticles crystal growth transmission electron microscopy in-situ electron microscopy

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Discovery of TK-642 as a highly potent,selective,orally bioavailable pyrazolopyrazine-based allosteric SHP2 inhibitor

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3624-3642页

作者： Kai Tang Shu Wang Siqi Feng Xinyu Yang Yueyang Guo Xiangli Ren Linyue Bai Bin Yu Hong-Min Liu Yihui Song School of pharmaceutical sciences&Key Laboratory of Advanced Drug Preparation Technologies Ministry of EducationZhengzhou UniversityZhengzhou 450001China College of Chemistry Pingyuan LaboratoryState Key Laboratory of Antiviral DrugsZhengzhou UniversityZhengzhou 450001China Tianjian Laboratory of Advanced Biomedical sciences Institute of Advanced Biomedical SciencesZhengzhou UniversityZhengzhou 450000China State Key Laboratory of pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Src homology-2-containing protein tyrosine phosphatase 2(SHP2)is a promising therapeutic target for cancer *** this work,we presented the structure-guided design of 5,6-fused bicyclic allosteric SHP2 inhibitors,leading to the identification of pyrazolopyrazine-based TK-642 as a highly potent,selective,orally bioavailable allosteric SHP2 inhibitor(SHP2WT IC_(50)=2.7 nmol/L)with favorable pharmacokinetic profiles(F=42.5%;t_(1/2)=2.47 h).Both dual inhibition biochemical assay and docking analysis indicated that TK-642 likely bound to the“tunnel”allosteric site of ***-642 could effectively suppress cell proliferation(KYSE-520 cells IC_(50)=5.73μmol/L)and induce apoptosis in esophageal cancer cells by targeting the SHP2-mediated AKT and ERK signaling ***,oral administration of TK-642 also demonstrated effective anti-tumor effects in the KYSE-520 xenograft mouse model,with a T/C value of 83.69%.Collectively,TK-642 may warrant further investigation as a promising lead compound for the treatment of esophageal cancer.

关键词： Protein tyrosine phosphatase Pyrazolopyrazine SHP2 inhibitor Esophageal cancer

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AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

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Neural Regeneration Research 2025年第1期20卷 253-264页

作者： Zhengwei Hu Jing Yang Shuo Zhang Mengjie Li Chunyan Zuo Chengyuan Mao Zhongxian Zhang Mibo Tang Changhe Shi Yuming Xu Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Academy of medical sciences of zhengzhou university ZhengzhouHenan ProvinceChina NHC Key Laboratory of Prevention and treatment of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina henan Key Laboratory of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina institute of Neuroscience Zhengzhou UniversityZhengzhouHenan ProvinceChina Sino-British Research Centre for Molecular Oncology National Centre for International Research in Cell and Gene TherapySchool of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Department of Gerontology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control *** this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s *** used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse *** overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated *** also alleviated the concentration of microglia and astrocytes around *** APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin *** of HSP70 and HSP40,which have functional relevance to CHIP,were also *** nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of *** research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 ***,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

关键词： adeno-associated virus Alzheimer’s disease APP/PS1 mice carboxyl terminus of Hsp70 interacting protein gene therapy

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Effect of wire diameter compression ratio on drawing deformation of micro copper wire

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Transactions of Nonferrous Metals Society of China 2024年第8期34卷 2605-2618页

作者： Tao HUANG Han-jiang WU Ke-xing SONG Yan-min ZHANG Yan-jun ZHOU Shao-lin LI School of Materials Science and Engineering Henan University of Science and TechnologyLuoyang 471023China henan Key Laboratory of Advanced Conductor Materials Institute of MaterialsHenan Academy of SciencesZhengzhou 450000China

A crystal plasticity finite element model was developed for the drawing deformation of pure copper micro wire,based on rate-dependent crystal plasticity *** impact of wire diameter compression ratio on the micro-mechanical deformation behavior during the wire drawing process was *** indicate that the internal deformation and slip of the drawn wire are unevenly distributed,forming distinct slip and non-slip ***,horizontal strain concentration bands develop within the drawn *** the wire diameter compression ratio increases,the strength of the slip systems and the extent of slip zones inside the deformation zone also ***,the fluctuating stress state,induced by contact pressure and frictional stress,results in a rough and uneven wire surface and diminishes the stability of the drawing process.

关键词： micro copper wire drawing deformation crystal plasticity finite element slip mode

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Triggering triplet excitons of carbon nanodots through nanospace domain confinement for multicolor phosphorescence in aqueous solution

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Nano Research 2024年第7期17卷 6534-6543页

作者： Ya-Chuan Liang Qing Cao Yuan Deng Yong Wang Kai-Kai Liu Chong-Xin Shan School of Electronics and Information Zhengzhou University of Light IndustryZhengzhou 450002China henan Key Laboratory of Diamond Optoelectronic Material and Devices Key Laboratory of Material PhysicsMinistry of EducationSchool of Physics and MicroelectronicsZhengzhou UniversityZhengzhou 450001China Academy for Quantum Science and Technology Zhengzhou University of Light IndustryZhengzhou 450002China institute of Quantum Materials and Physics Henan Academy of SciencesZhengzhou 450046China

Easy non-radiative decay property of long-lived triplet excitons in aqueous solution obstructs their applications in aquatic *** reported phosphorescence phenomena in aqueous solution have excited researchers enormously but achieving full-color water-soluble phosphorescent carbon nanodots(CNDs)is still a challenging ***,full-color phosphorescence of water-soluble CNDs has been demonstrated by triggering their triplet excitons through nanospace domain confinement,and Förster energy resonance transfer is used for further tuning phosphorescence *** phosphorescence spans across most of the visible spectrum,ranging from 400 to 700 *** an aqueous solution,the CNDs exhibits blue,green,and red phosphorescence,lasting for approximately 6,10,and 7 s,***,the phosphorescence quantum yields are 11.85%,8.6%and 3.56%,making them readily discernible to the naked eyes and laying a solid foundation for practical ***,phosphorescence flexible optical display and bioimaging have been demonstrated by using the multicolor CNDs-based nanomaterials,showing distinct superiority for accuracy and complete display and imaging in complex emission background.

关键词： carbon nanodots triplet excitons multicolor aqueous solution

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Hemin blocks TIGIT/PVR interaction and induces ferroptosis to elicit synergistic effects of cancer immunotherapy

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Science China(Life sciences) 2024年第5期67卷 996-1009页

作者： Xiaowen Zhou Yang Li Xiangrui Zhang Beibei Li Shengzhe Jin Menghan Wu Xiuman Zhou Qingyu Dong Jiangfeng Du Wenjie Zhai Yahong Wu Lu Qiu Guodong Li Yuanming Qi Wenshan Zhao Yanfeng Gao School of Life sciences Zhengzhou UniversityZhengzhou 450001China School of pharmaceutical sciences(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhen 518107China

The immune checkpoint TIGIT/PVR blockade exhibits significant antitumor effects through activation of NK and CD8^(+)T cell-mediated *** checkpoint blockade(ICB)could induce tumor ferroptosis through IFN-γreleased by immune cells,indicating the synergetic effects of ICB with ferroptosis in inhibiting tumor ***,the development of TIGIT/PVR inhibitors with ferroptosis-inducing effects has not been explored *** this study,the small molecule Hemin that could bind withTIGIT to block TIGIT/PVR interaction was screened by virtual molecular docking and cell-based blocking *** could effectively restore the IL-2 secretion from Jurkat-hTIGIT *** reinvigorated the function of CD8^(+)T cells to secrete IFN-γand the elevated IFN-γcould synergize with Hemin to induce ferroptosis in tumor *** inhibited tumor growth by boosting CD8^(+)T cell immune response and inducing ferroptosis in CT26 tumor *** importantly,Hemin in combination with PD-1/PD-L1 blockade exhibited more effective antitumor efficacy in anti-PD-1 resistant B16 tumor *** summary,our finding indicated that Hemin blocked TIGIT/PVR interaction and induced tumor cell ferroptosis,which provided a new therapeutic strategy to combine immunotherapy and ferroptosis for cancer treatment.

关键词： cancer immunotherapy TIGIT/PVR small molecule Hemin ferroptosis

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Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer

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Chinese Journal of Cancer Research 2024年第3期36卷 306-321页

作者： Zhifei Li Huan Zhao Huihui Hu Haili Shang Yongjing Ren Wenhui Qiu Hao Su Huifang Lyu Xiaobing Chen Department of Oncology the Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Engineering Research Center of Precision Therapy of Gastrointestinal CancerZhengzhou Key Laboratory for Precision Therapy of Gastrointestinal CancerZhengzhou 450008China henan university of Traditional Chinese Medicine Zhengzhou 450046China State Key Laboratory of Esophageal Cancer Prevention&Treatment Key Laboratory of Advanced Drug Preparation TechnologiesMinistry of EducationSchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450001China The First Affiliated Hospital of Xinxiang medical university Xinxiang 453000China Department of Oncology the Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhou 450008China

Gastric cancer is one of the most prevalent cancers worldwide,and human epidermal growth factor receptor 2(HER2)-positive cases account for approximately 20%of the total ***,trastuzumab+chemotherapy is the recommended first-line treatment for patients with HER2-positive advanced gastric cancer,and the combination has exhibited definite efficacy in HER2-targeted ***,the emergence of drug resistance during treatment considerably reduces its effectiveness;thus,it is imperative to investigate the potential mechanisms underlying *** the present review article,we comprehensively introduce multiple mechanisms underlying resistance to trastuzumab in HER2-positive gastric cancer cases,aiming to provide insights for rectifying issues associated with resistance to trastuzumab and devising subsequent treatment strategies.

关键词： HER2 gastric cancer trastuzumab drug resistance

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Interfacial assembly of 2D polydopamine/graphene heterostructures with well-defined mesopore and tunable thickness for high-energy planar micro-supercapacitors

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Chinese Chemical Letters 2024年第7期35卷 439-444页

作者： Jieqiong Qin Zhi Yang Jiaxin Ma Liangzhu Zhang Feifei Xing Hongtao Zhang Shuxia Tian Shuanghao Zheng Zhong-Shuai Wu College of Science Henan Agricultural UniversityZhengzhou 450002China State Key Laboratory of Catalysis Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China university of Chinese Academy of sciences Beijing 100049China Mechanical and Electrical Engineering institute Zhengzhou University of Light IndustryZhengzhou 450002China

Two-dimensional(2D)mesoporous pseudocapacitive polymer/graphene heterostructures combine the advanced merits of 2D materials and mesoporous materials,possessing unique nanosheet structure,large specific surface area(SSA),abundant oxygen/nitrogen-containing groups,desirable electrical conductivity and admirable electrochemical redox activity,and hold great potential for constructing high-performance planar micro-supercapacitors(MSCs).Herein,we demonstrate the interfacial assembly of 2D mesoporous polydopamine/graphene(mPDG)heterostructures with well-defined mesopore structure(12 nm)and adjustable thickness(7.5–14.1 nm)for planar high-energy pseudocapacitive *** to medium thickness,exposed mesopore of 12 nm and large SSA of 108 m^(2)/g,the m PDG with 10.8 nm thickness reveals prominent mass capacitance of 419 F/g and impressive cycling stability with~96%capacitance retention after 5000 ***,the symmetric mPDG-based MSCs with“water-in-salt”gel electrolyte present wide voltage window of 1.6 V,superior volumetric energy density of 11.5 mWh/cm^(3),outstanding flexibility and self-integration ***,this work offers a new platform of controllably synthesizing 2D mesoporous heterostructures for high-performance MSCs.

关键词： 2D materials Mesopores Heterostructures Polydopamine High energy density Micro-supercapacitors

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