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Mitochondria-specific near-infrared photoactivation of peroxynitrite upconversion luminescent nanogenerator for precision cancer gas therapy

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Acta Pharmaceutica Sinica B 2024年第1期14卷 378-391页

作者： hui Yu Aliya Tiemuer Xufeng yao Mingyuan Zuo Hai-Yan Wang Yi Liu Xiaoyuan Chen Department of Biomedical Engineering School of EngineeringChina Pharmaceutical UniversityNanjing 211198China School of Mechanical Engineering Southeast UniversityNanjing 211189China Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingapore 119074Singapore Clinical Imaging Research Centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingapore 117599Singapore Nanomedicine Translational Research Program Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Institute of Molecular and Cell Biology Agency for ScienceTechnologyand Research(A*STAR)ProteosSingapore 138673Singapore

Gas therapy is emerging as a highly promising therapeutic strategy for cancer ***,there are limitations,including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision,associated with gas *** this study,we developed a series of photoactivatable nitric oxide(NO)donors NRh-R-NO(R=Me,Et,Bn,iPr,and Ph)based on an N-nitrosated upconversion luminescent rhodamine *** the irradiation of 808 nm light,only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion luminescence(FUCL)signal at 740 nm,ascribed to lower N-N bond dissociation *** also investigated the involved multistage near-infrared-controlled cascade release of gas therapy,including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation,the superoxide anion O_(2)^(⋅−)produced by the photodynamic therapy(PDT)effect of NRh-Ph,and highly toxic peroxynitrite anion(ONOO‒)generated from the co-existence of NO and O_(2)^(⋅−).After mild nano-modification,the nanogenerator(NRh-Ph-NO NPs)empowered with superior biocompatibility could target *** an 808 nm laser irradiation,NRh-Ph-NO NPs could induce NO/ROS to generate RNS,causing a decrease in the mitochondrial membrane potential and initiating apoptosis by caspase-3 activation,which further induced tumor immunogenic cell death(ICD).In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy,demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL ***,this versatile strategy defines the targeted RNS-mediated cancer therapy.

关键词： Near infrared Photo-triggered Mitochondrion Upconversion luminescent bioimaging Peroxynitrite Nanogenerator Gas therapy In vivo

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Effectiveness of cardioneuroablation in different subtypes of vasovagal syncope

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Journal of Geriatric Cardiology 2024年第6期21卷 651-657页

作者： Bin TU Zi-Hao LAI Ai-Yue CHEN Zhi-Yuan WENG Si-Min CAI Zhu-xin ZHANG Li-Kun ZHOU Li-hui ZHENG Yan yao Arrhythmia Center Fuwai HospitalNational Center for Cardiovascular DiseasesNational Key LaboratoryChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Cardiac Center Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina Cardiovascular Department The First Affiliated HospitalFujian Medical UniversityFujian Institute of HypertensionFujianChina Department of Cardiovascular The Second Affiliated Hospital of Zhejiang University School of MedicineZhejiangChina

BACKGROUND Cardioneuroablation(CNA)has shown encouraging results in patients with vasovagal syncope(VVS).However,data on different subtypes was *** This observational study retrospectively enrolled 141 patients[mean age:40±18 years,51 males(36.2%)]with the diagnosis of *** characteristics among different types of VVS and the outcomes after CNA were *** After a mean follow-up of 4.3±1.5 years,41 patients(29.1%)experienced syncope/pre-syncope events after ***/pre-syncope recurrence significantly differed in each subtype(P=0.04).The cardioinhibitory type of VVS had the lowest recurrence rate after the procedure(n=6,16.7%),followed by mixed(n=26,30.6%)and vasodepressive(n=9,45.0%).Additionally,a significant difference was observed in the analyses of the Kaplan-Meier survival curve(P=0.02).Syncope/pre-syncope burden was significantly reduced after CNA in the vasodepressive type(P<0.01).Vasodepressive types with recurrent syncope/pre-syncope after CNA have a lower baseline deceleration capacity(DC)level than those without(7.4±1.0 ms vs.9.0±1.6 ms,P=0.01).Patients with DC<8.4 ms had an 8.1(HR=8.1,95%CI:2.2-30.0,P=0.02)times risk of syncope/pre-syncope recurrence after CNA compared to patients with DC≥8.4 ms,and this association still existed after adjusting for age and sex(HR=8.1,95%CI:2.2-30.1,P=0.02).CONCLUSIONS Different subtypes exhibit different event-free *** vasodepressive type exhibited the lowest event-free rate,but those patients with DC≥8.4 ms might benefit from CNA.

关键词： syncope subtypes diagnosis

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Single-cell transcriptomic atlas of goat ovarian aging

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Journal of Animal Science and Biotechnology 2024年第1期15卷 146-161页

作者： Dejun Xu Shuaifei Song Fuguo Wang Yawen Li Ziyuan Li hui yao Yongju Zhao Zhongquan Zhao Chongqing Key Laboratory of Herbivore Science College of Animal Science and TechnologySouthwest UniversityChongqing 400715China

Background The ovaries are one of the first organs that undergo degenerative changes earlier in the aging process,and ovarian aging is shown by a decrease in the number and quality of ***,little is known about the molecular mechanisms of female age-related fertility decline in different types of ovarian cells during aging,especially in ***,the aim of this study was to reveal the mechanisms driving ovarian aging in goats at single-cell *** For the first time,we surveyed the single-cell transcriptomic landscape of over 27,000 ovarian cells from newborn,young and aging goats,and identified nine ovarian cell types with distinct gene-expression *** enrichment analysis showed that ovarian cell types were involved in their own unique biological processes,such as Wnt beta-catenin signalling was enriched in germ cells,whereas ovarian steroidogenesis was enriched in granulosa cells(GCs).Further analysis showed that ovarian aging was linked to GCs-specific changes in the antioxidant system,oxidative phosphorylation,and ***,we identified a series of dynamic genes,such as AMH,CRABP2,THBS1 and TIMP1,which determined the fate of ***,FOXO1,SOX4,and HIF1A were identified as significant regulons that instructed the differentiation of GCs in a distinct manner during ovarian *** This study revealed a comprehensive aging-associated transcriptomic atlas characterizing the cell typespecific mechanisms during ovarian aging at the single-cell level and offers new diagnostic biomarkers and potential therapeutic targets for age-related goat ovarian diseases.

关键词： Goat Granulosa cells Ovarian aging Single-cell transcriptomic

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Comprehensive analysis of the potential pathogenesis of COVID-19 infection and liver cancer

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 436-457页

作者： yao Rong Ming-Zheng Tang Song-Hua Liu Xiao-Feng Li hui Cai First Clinical Medical College Gansu University of Chinese MedicineLanzhou 730000Gansu ProvinceChina General Surgery Clinical Medical Center Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

BACKGROUND A growing number of clinical examples suggest that coronavirus disease 2019(COVID-19)appears to have an impact on the treatment of patients with liver cancer compared to the normal population,and the prevalence of COVID-19 is significantly higher in patients with liver ***,this mechanism of action has not been *** sets for COVID-19(GSE180226)and liver cancer(GSE87630)were obtained from the Gene Expression Omnibus *** identifying the common differentially expressed genes(DEGs)of COVID-19 and liver cancer,functional enrichment analysis,protein-protein interaction network construction and scree-ning and analysis of hub genes were ***,the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was *** Of 518 common DEGs were obtained by screening for functional *** hub genes including aurora kinase B,cyclin B2,cell division cycle 20,cell division cycle associated 8,nucleolar and spindle associated protein 1,etc.,were further identified from DEGs using the“cytoHubba”*** enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation,cell cycle and other functions,and they may serve as potential molecular markers for COVID-19 and liver ***,we selected 10 of the hub genes for in vitro expression validation in liver cancer *** Our study reveals a common pathogenesis of liver cancer and *** common pathways and key genes may provide new ideas for further mechanistic studies.

关键词： COVID-19 Liver cancer Differentially expressed genes Hub genes Pathogenesis

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A DNA Force Circuit for Exploring Protein-Protein Interactions at the Single-Molecule Level

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Chinese Journal of Chemistry 2024年第13期42卷 1456-1464页

作者： Kangkang Ma Luoan Xiong Zhuofei Wang xin Hu Lihua Qu Xuetong Zhao yao Li Zhongbo Yu State Key Laboratory of Medicinal Chemical Biology Frontiers Science Center for Cell Responsesand College of PharmacyNankai University38 Tongyan RoadTianjin 300350China School of Physics and Key Laboratory of Functional Polymer Materials of Ministry of Education Nankai Universityand Collaborative Innovation Center of Chemical Science and EngineeringTianjin 300071China

Protein-protein interactions(PPls)play a crucial role in drug discovery and disease ***,the development of effective drugs targeting PPls remains challenging due to limited methodologies for probing their spatiotemporal ***,we propose a single-molecule approach using a unique force circuit to investigate Ppl dynamics and anisotropy under mechanical *** conventional techniques,this approach enables the manipulation and real-time monitoring of individual proteins at specific amino acids with defined geometry,offering insights into molecular mechanisms at the single-molecule *** DNA force circuit was constructed using click chemistry conjugation methods and genetic code expansion techniques,facilitating orthogonal conjugation between proteins and nucleic *** SET domain of the MLL1 protein and the tail of histone H3 were used as a model system to demonstrate the application of the DNA force *** the use of atomic force microscopy and magnetic tweezers,optimized assembly procedures were *** DNA force circuit provides an exceptional platform for studying the anisotropy of PPis and holds promise for advancing drug discovery research targeted at PPIs.

关键词： Single-molecule studies Protein-protein interactions Click chemistry Genetic code expansion Molecular dynamics

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Peroxidase-like active Cu-ZIF-8 with rich copper(I)-nitrogen sites for excellent antibacterial performances toward drug-resistant bacteria

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Nano Research 2024年第8期17卷 7427-7435页

作者： Xiaoze Wang hui Wang Jingkun Zhang Ning Han Wenjun Ma Donghai Zhang Mingshui yao Xianliang Wang Yunfa Chen State Key Laboratory of Mesoscience and Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China University of the Chinese Academy of Sciences Beijing 100049China Laboratory of Theoretical and Computational Nanoscience CAS Key Laboratory of Nanosystem and Hierarchial FabricationCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China China CDC Key Laboratory of Environment and Population Health National Institute of Environmental HealthChinese Center for Disease Control and PreventionBeijing 100021China

Bacterial pathogens pose a serious threat to human health,and there is an urgent need to develop highly effective antibacterial materials to eliminate the increasingly serious contamination of drug-resistant ***,a Cu-doped ZIF-8 particle with unsaturated copper exhibits high peroxidase-like activity.99.998%antibacterial efficiency against *** can be achieved for 30 min at a low concentration of 50μg·mL^(−1),as well as complete sterilization against ***(up to 8 log).99.999%antibacterial efficiency against Methicillin-resistant Staphylococcus aureus can be achieved,performing orders of magnitude higher than *** mechanism shows that the unsaturated Cu-Nx sites are enzyme-like active centers,which could promote the consumption of bacteria reducing substances by H_(2)O_(2),and the generated*OH further aggravates bacterial oxidative stress and membrane *** importantly,the oxidation activity of adsorbed oxygen species on Cu-ZIF-8 is enhanced by charge transfer and structural changes between the ligand and copper center like natural ***-doped ZIF-8 with peroxidase-like activity shows great potential in antibacterial application and the revealed catalytic mechanism is helpful for understanding the high antibacterial activity of nanoparticles with Cu-Nx sites.

关键词： Cu-doped ZIF-8 peroxidase-like reactive oxygen species(ROS) catalytic mechanism antibacterial activity

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Qubit Mapping Based on Tabu Search

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Journal of Computer Science & Technology 2024年第2期39卷 421-433页

作者：蒋慧邓玉欣徐鸣 Shanghai Key Laboratory of Trustworthy Computing East China Normal UniversityShanghai 200062China

The goal of qubit mapping is to map a logical circuit to a physical device by introducing additional gates as few as possible in an acceptable amount of *** present an effective approach called Tabu Search Based Adjustment(TSA)algorithm to construct the *** consists of two key steps:one is making use of a combined subgraph isomorphism and completion to initialize some candidate mappings,and the other is dynamically modifying the mappings by *** experiments show that,compared with state-of-the-art methods,TSA can generate mappings with a smaller number of additional gates and have better scalability for large-scale circuits.

关键词： quantum computing qubit mapping initial mapping tabu search logical circuit

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Retinoic acid alleviates rotavirus-induced intestinal damage by regulating redox homeostasis and autophagic flux in piglets

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Animal Nutrition 2024年第1期16卷 409-421页

作者： xin Lai Aimin Wu Bing Yu hui Yan Junqiu Luo Ping Zheng Jie Yu Daiwen Chen Institute of Animal Nutrition Sichuan Agricultural University Key Laboratory for Animal Disease-resistance Nutrition of China Ministry of Education Sichuan Agricultural University

Rotaviruses(RV) are a major cause of severe gastroenteritis, particularly in neonatal piglets. Despite the availability of effective vaccines, the development of antiviral therapies for RV remains an ongoing challenge. Retinoic acid(RA), a metabolite of vitamin A, has been shown to have anti-oxidative and antiviral properties. However, the mechanism by which RA exerts its intestinal-protective and antiviral effects on RV infection is not fully understood. The study investigates the effects of RA supplementation in Duroc × Landrace × Yorkshire(DLY) piglets challenged with RV. Thirty-six DLY piglets were assigned into six treatments, including a control group, RA treatment group with two concentration gradients(5and 15 mg/d), RV treatment group, and RV treatment group with the addition of different concentration gradients of RA(5 and 15 mg/d). Our study revealed that RV infection led to extensive intestinal architecture damage, which was mitigated by RA treatment at lower concentrations by increasing the villus height and villus height/crypt depth ratio(P < 0.05), enhancing intestinal stem cell signaling and promoting intestinal barrier functions. In addition, 15 mg/d RA supplementation significantly increased NRF2 and HO-1 protein expression(P < 0.05) and GSH content(P < 0.05), indicating that RA supplementation can enhance anti-oxidative signaling and redox homeostasis after RV challenge. Additionally,the research demonstrated that RA exerts a dual impact on the regulation of autophagy, both stimulating the initiation of autophagy and hindering the flow of autophagic flux. Through the modulation of autophagic flux, RA influence the progression of RV infection. These findings provide new insights into the regulation of redox hemostasis and autophagy by RA and its potential therapeutic application in RV infection.

关键词： Rotavirus Piglet Retinoic acid Intestinal barrier Redox hemostasis Autophagic flux

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Copper-induced formation of heterostructured Co_(3)O_(4)/CuO hollow nanospheres towards greatly enhanced lithium storage performance

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Chinese Chemical Letters 2024年第2期35卷 594-598页

作者： Junjun Zhang huiying Lu Tianhao yao xin Ji Qingmiao Zhang Lingjie Meng Jianmin Feng Hongkang Wang College of Geography & Environment Xianyang Normal UniversityXianyang 712000China State Key Lab of Electrical Insulation and Power Equipment Center of Nanomaterials for Renewable Energy (CNRE)School of Electrical EngineeringXi'an Jiaotong UniversityXi'an 710049China School of Chemistry Xi'an Key Laboratory of Sustainable Energy Material Chemistryand Instrumental Analysis CenterXi'an Jiaotong UniversityXi'an 710049China

We report a facile template-free fabrication of heterostructured Co_(3)O_(4)/CuO hollow nanospheres using pre-synthesized Co/Cu-glycerate as conformal *** introduction of copper nitrate in the solvothermal reaction system of glycerol/isopropanol/cobalt nitrate readily induces the conversion from solid Co-glycerate to hollow Co/Cu-glycerate nanospheres,and the effect of the Co/Cu atomic ratio on the structure evolution of the metal glycerates as well as their corresponding oxides were *** examined as anode materials for lithium-ion batteries,the well-defined Co_(3)O_(4)/CuO hollow nanospheres with Co/Cu molar ratio of 2.0 demonstrate excellent lithium storage performance,delivering a high reversible capacity of 930 mAh/g after 300 cycles at a current density of 0.5 A/g and a stable capacity of 650 mAh/g after 500 cycles even at a higher current density of 2.0 A/g,which are much better than their counterparts of bare CuO and Co_(3)O_(4).The enhanced lithium storage performance can be attributed to the synergistic effect of the CuO and Co_(3)O_(4)heterostructure with hollow spherical morphology,which greatly enhances the charge/electrolyte transfer and effectively buffers the volume changes upon lithiation/delithiation cycling.

关键词： Lithium-ion batteries Co/Cu-glycerate Hollow nanospheres Co_(3)O_(4)/CuO heterostructure Electrochemical properties

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Cell division cyclin 25C knockdown inhibits hepatocellular carcinoma development by inducing endoplasmic reticulum stress

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World Journal of Gastroenterology 2024年第19期30卷 2564-2574页

作者： Yan-Fei Li Fang-Yuan Zheng xin-Yu Miao Hai-Long Liu yao-yao Zhang Nai-Xia Chao Fa-Rong Mo School of Basic Medical Sciences Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Key Laboratory of Biological Molecular Medicine Research(Guangxi Medical University) Education Department of Guangxi Zhuang Autonomous RegionNanning 530021Guangxi Zhuang Autonomous RegionChina Key Laboratory of Human Development and Disease Research(Guangxi Medical University) Education Department of Guangxi Zhuang Autonomous RegionNanning 530021Guangxi Zhuang Autonomous RegionChina

BACKGROUND Cell division cyclin 25C(CDC25C)is a protein that plays a critical role in the cell cycle,specifically in the transition from the G2 phase to the M *** research has shown that CDC25C could be a potential therapeutic target for cancers,particularly for hepatocellular carcinoma(HCC).However,the specific regulatory mechanisms underlying the role of CDC25C in HCC tumorigenesis and development remain incompletely *** To explore the impact of CDC25C on cell proliferation and apoptosis,as well as its regulatory mechanisms in HCC *** Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences(LV-CDC25C shRNA)to knock down ***,a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into C57BL/6 mice to assess the effects of CDC25C knockdown on HCC development in *** proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays,*** expression of endoplasmic reticulum(ER)stress-related molecules(glucose-regulated protein 78,X-box binding protein-1,and C/EBP homologous protein)was measured in both cells and subcutaneous xenografts using quantitative real-time PCR(qRT-PCR)and western ***,apoptosis was investigated using flow cytometry,qRT-PCR,and western *** CDC25C was stably suppressed in Hepa1-6 and B16 cells through LV-CDC25C shRNA transduction.A xenograft model with CDC25C knockdown was successfully established and that downregulation of CDC25C expression significantly inhibited HCC growth in ***25C knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response,ultimately promoting ER stress-induced apoptosis in HCC *** The regulatory mechanism of CDC25C in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signali

关键词： Cell division cyclin 25C Hepatocellular carcinoma Endoplasmic reticulum stress Proliferation Apoptosis

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