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Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity

Acta Pharmaceutica Sinica B 2024年第1期14卷 350-364页

作者： Yongshun Zhang Lan Yang Yangsen Ou Rui hu Guangsheng Du Shuang Luo Fuhua Wu Hairui Wang Zhiqiang Xie yu Zhang Chunting He Cheng Ma Tao Gong ling Zhang Zhirong Zhang Xun Sun Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China Med-X Center for Materials College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10(PTEN)gene in cancer cells may be associated with immunosuppressive tumor microenvironment(TME)and poor response to immune checkpoint blockade(ICB)***,efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB ***,we screened an adeno-associated virus(AAV)capsid for efficient PTEN gene delivery into B16F10 tumor *** demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death(ICD)and increasing immune cell ***,we developed an anti-PD-1 loaded phospholipid-based phase separation gel(PPSG),which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in *** order to effectively inhibit the recurrence of melanoma,we further applied a triple therapy based on AAV6-PTEN,PPSG^(@anti-PD-1)and CpG,and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory,which completely rejected tumor *** anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

关键词： Triple therapy Adeno-associated virus PTEN PPSG@anti-PD-1 CpG Immunogenic cell death Antitumor immune response Immune memory

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Comparative analysis of thermodynamic and mechanical responses between underground hydrogen storage and compressed air energy storage in lined rock caverns

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International Journal of Mining Science and Technology 2024年第4期34卷 531-543页

作者： Bowen hu Liyuan yu Xianzhen Mi Fei Xu Shuchen Li Wei Li Chao Wei Tao Zhang State Key Laboratory of Intelligent Construction and Healthy Operation and Maintenance of Deep Underground Engineering China University of Mining and TechnologyXuzhou 221116China Key Laboratory of Large Structure Health Monitoring and Control Shijiazhuang Tiedao UniversityShijiazhuang 050043China School of Mechanics and Civil Engineering China University of Mining and TechnologyXuzhou 221116China

Underground hydrogen storage(UHS)and compressed air energy storage(CAES)are two viable largescale energy storage technologies for mitigating the intermittency of wind and solar ***,it is meaningful to compare the properties of hydrogen and air with typical thermodynamic storage *** study employs a multi-physical coupling model to compare the operations of CAES and UHS,integrating gas thermodynamics within caverns,thermal conduction,and mechanical deformation around rock *** thermodynamic responses are validated using additional simulations and the field test *** and pressure variations of air and hydrogen within rock caverns exhibit similarities under both adiabatic and diabatic simulation *** reaches higher temperature and pressure following gas charging stage compared to air,and the ideal gas assumption may lead to overestimation of gas temperature and *** steel lining of CAES,the sealing layer(fibre-reinforced plastic FRP)in UHS is prone to deformation but can effectively mitigates stress in the sealing *** CAES,the first principal stress on the surface of the sealing layer and concrete lining is tensile stress,whereas UHS exhibits compressive stress in the same *** present research can provide references for the selection of energy storage methods.

关键词： Underground hydrogen storage Compressed air energy storage Mechanical response Thermodynamic response Lined rock caverns

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Potential therapeutic role of spermine via Rac1 in osteoporosis:Insights from zebrafish and mice

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Zoological Research 2024年第2期45卷 367-380页

作者： Rui-Xue Jiang Nan hu yu-Wei Deng Long-Wei hu Hao Gu Nan Luo Jin Wen Xin-Quan Jiang Department of Prosthodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China College of Stomatology Shanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai 200125China Department of Endodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200011China Department of Oral and Maxillofacial-Head and Neck Oncology Shanghai Ninth People’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200011China Department of Preventive Dentistry Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200011China

Osteoporosis(OP)is a prevalent metabolic bone *** drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted *** a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone *** showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone *** not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and ***,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and *** the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of *** findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening *** study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular *** their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

关键词： Osteoporosis Spermine Rac1 Zebrafish Mice

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Non-invasive Healthcare Analytical Platform Based on Organic Electrochemical Transistors

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CHEMICAL RESEARCH IN CHINESE UNIVERSITIES 2024年第5期40卷 824-841页

作者： hu, Xingyu Mao, Ning Yan, Xinwen huang, ling Liu, Xu Yang, huige Sun, Qingqing Liu, Xuying Jia, Hanyu Zhengzhou Univ Sch Mat & Engn Zhengzhou 450001 Peoples R China Longmen Lab Sci & Technol Innovat Ctr Adv Mat Intelligent Equi Luoyang 471000 Peoples R China South Cent Univ Nationalities Hubei R&D Ctr Hyperbranched Polymers Synth & Appli Key Lab Catalysis & Energy Mat Chem Minist Educ Wuhan 430074 Peoples R China South Cent Univ Nationalities Hubei R&D Ctr Hyperbranched Polymers Synth & Appli Hubei Key Lab Catalysis & Mat Sci Wuhan 430074 Peoples R China

Non-invasive bioelectronics, especially organic electrochemical transistors (OECTs), have drawn extensive attentions of academical and medical communities by virtue of their efficient bio-electronic interfacing, water-involved ionic transport, excellent ionic-electronic coupling, ultralow power consumption, wide detectable range, and outstanding detection sensitivity. Designable structure diversity, low-temperature solution processability, facile bio/chemical functionalization, and excellent biocompatibility of organic mixed ionic-electronic conductors (OMIECs) render OECTs particularly suitable for non-invasive or minimally invasive healthcare analytical platform. Here, we comprehensively review recent advances of the non-invasive analytical healthcare applications based on OECTs, especially on the detection of biomarkers or metabolites in the excretory biofluids, as well as the recording of electrophysiological signals. A brief introduction of OECT and its comparison with other organic thin-film transistors upon device configuration and working mechanism are firstly discussed. State-of-the-art non-invasive OECT-based biosensors are summarized on their detection of ionic and molecular biomarkers, following with circuit design strategies of OECTs for real-time and in-situ electrophysiological recording from skin surface. In conclusion, remaining barriers and future challenges of non-invasive OECT-based bioelectronics towards lower detection limit, more accurate quantitative relationship between analyte concentrations and measured parameters, more intimate device-tissue interface, and long-term operation stability are deeply analyzed with a critical outlook.

关键词： Organic electrochemical transistor Non-invasive Bioelectronics Ion-selective Electrophysiological monitoring SENSITIVITY ION DETECTION

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Effect of temperature and reaction path interaction on fluidization reduction kinetics of iron ore powder

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Journal of Iron and Steel Research International 2024年第8期31卷 1840-1849页

作者： Guo-min Zhu Ming-wei hu An-nan Dou Jin-yu huang Jing Ding Qi-yan Xu School of Metallurgical Engineering Anhui University of TechnologyMa'anshan 243002AnhuiChina

Due to the instability of FeO at temperatures below 843 K,the fuidization reduction pathway of iron ore powder changes with the reduction ***,the effect of temperature and reaction pathway interaction on the kinetics of fuidization reduction of iron ore powder under low-temperature conditions ranging from 783 to 903 K was investigated to describe the fluidization reduction rate of iron ore powder from three aspects:microstructure change,reaction limiting link,and apparent activation energy of the reaction,exploring their internal *** experimental results revealed that in a temperature range of 783-813 K,the formation of a dense iron layer hindered the internal diffusion of reducing gas,resulting in relatively high gas diffusion *** addition,due to the differences in limiting links and reaction pathways in the intermediate stage of reduction,the apparent activation energy of the reaction *** apparent activation energy of the reaction ranged from 23.36 to 89.13 kJ/mol at temperature ranging from 783 to 813 K,while it ranged from 14.30 to 68.34 kJ/mol at temperature ranging from 873 to 903 K.

关键词： Reaction limiting link Gas internal diffusion Interface reaction Apparent activation energy Iron ore powder Reaction pathway Fluidization reduction

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Ergodicity of a Special Class of Markov Chains

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Acta Mathematicae Applicatae Sinica 2024年

作者： Xin-yu hu Ping HE School of Mathematics Shanghai University of Finance and Economics

The paper focuses on the ergodicity of a φ-irreducible Markov chain {X_n, n ≥ 0} that is generated iteratively through the expression Xn+1= f（X_n） + ?n+1. Here, {?_n, n ≥ 1} is a sequence of independent identically distributed centralized random variables, f（·） is an R-valued continuous function, and X0is arbitrary but independent of {?_n, n ≥ 1}. Our main contribution is to provide necessary and sufficient conditions for ergodicity of this special class of Markov chains. We also present a generalized approach for f（·） in the end.

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Synergistically constructed lamination-like network of redox-active polyimide and MXene via π-π interactions for aqueous NH_(4)^(+) storage

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Chinese Journal of Chemical Engineering 2024年第7期71卷 217-224页

作者： Jing He Hongye Xuan Jing Jin Ke yu Changyao Liyang Lintong hu Minjie Shi Chao Yan School of Materials Science and Engineering Jiangsu University of Science and TechnologyZhenjiang 212003China Jiangsu New Yangzi Shipbuilding Co. LtdJingjiang 214532China

As a nonmetallic charge carrier,ammonium ion(NH_(4)^(+))has garnered significant attention in the construction of aqueous batteries due to its advantages of low molar mass,small hydration size and rapid diffusion in aqueous *** are a kind of potential electro-active materials for aqueous NH_(4)^(+)***,traditional polymer electrodes are typically created by covering the bulky collectors with excessive additives,which could lead to low volume capacity and unsatisfactory ***,a nanoparticle-like polyimide(PI)was synthesized and then combined with MXene nanosheets to synergistically construct an additive-free and self-standing PI@MXene composite ***,the redox-active PI nanoparticles are enclosed between conductive MXene flakes to create a 3D lamination-like network that promotes electron transmission,while theπ-πinteractions existing between PI and MXene contribute to the enhanced structural integrity and stability within the composite *** such,it delivers superior aqueous NH_(4)^(+)storage behaviors in terms of a notable specific capacity of 110.7 mA·h·cm^(–3) and a long lifespan with only 0.0064%drop each ***,in-situ Raman and UV–Vis examinations provide evidence of reversible and stable redox mechanism of the PI@MXene composite electrode during NH_(4)^(+)uptake/removal,highlighting its significance in the area of electrochemical energy storage.

关键词： Synergetic coupling Composite materials Polyimide Energy storage Aqueous ammonium ion batteries

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Quasi-in-situ Observation and SKPFM Studies on Phosphate Protective Film and Surface Micro-Galvanic Corrosion in Biological Mg-3Zn-xNd Alloys

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Acta Metallurgica Sinica(English Letters) 2024年第4期37卷 648-664页

作者： Zhaochen yu Kaixuan Feng Shuyun Deng Yang Chen Hong Yan Honggun Song Chao Luo Zhi hu School of Advanced Manufacturing Nanchang UniversityNanchang330031China Institute for Advanced Study Nanchang UniversityNanchang330031China

The phosphate protective film and micro-galvanic corrosion of biological Mg-3Zn-xNd (x = 0, 0.6, 1.2) alloys were investigated by scanning and transmission electron microscopy, quasi-in-situ observation, scanning Kelvin probe force microscopy (SKPFM) and electrochemical tests. The results revealed the Mg-Zn-Nd phases formed in Mg-3Zn alloy contained with Nd. Adding Nd resulted in a significant decline in the cracks of the phosphate protective film and micro-galvanic corrosion of alloys, which were recorded by quasi-in-situ observation. In addition, the Volta potential difference of Mg-Zn-Nd/α-Mg (~ 188 mV) was lower than MgZn/α-Mg (~ 419 mV) and Zn-rich/α-Mg (~ 260 mV), and the corrosion rates of alloys markedly decreased after the addition of 0.6 wt% Nd. The improvement in corrosion resistance of Nd-containing alloys was mainly attributed to the following: (i) the addition of Nd reduced the Volta potential difference (second phases/α-Mg);(ii) the phosphate protective film containing Nd_(2)O_(3) deposited on the surface of the alloys, effectively preventing the penetration of harmful anions.

关键词： Magnesium alloys Quasi-in-situ observation Phosphate protective film Scanning Kelvin probe force microscopy(SKPFM) Micro-galvanic corrosion

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Effect of comprehensive nursing on the quality of life and swallowing function in individuals diagnosed with ischemic stroke

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World Journal of Clinical Cases 2024年第8期12卷 1406-1415页

作者： Heng-Fen hu yu-Fei Sang Yan-Qing Xiao Medical School Hunan Vocational and Technical College of Environmental BiologyHengyang 421005Hunan ProvinceChina Medical Team The Unit 95246 Of Chinese People’s Liberation ArmyNanning 530007Guangxi Zhuang Autonomous RegionChin Department of Gynecology and Obstetrics Hengyang Maternal and Child Health HospitalHengyang 421001Hunan ProvinceChina

BACKGROUND Ischemic stroke(IS)is a widely recognized disease characterized by high preva-lence,mortality,morbidity,disability,and recurrence *** ranks prominently in terms of mortality,constituting 60%-80%of stroke *** To explore the impact of comprehensive nursing care on the quality of life and swallowing function in individuals diagnosed with *** This study comprised 172 patients with IS admitted to our hospital between February 2018 to March *** participants were divided into two groups,namely the control group(n=80)receiving routine care and the research group(n=92)receiving comprehensive *** assessment scales,including the standard swallowing function assessment scale(SSA),National Institutes of Health Stroke scale(NIHSS),European stroke scale(ESS),self-rating anxiety scale(SAS),self-rating depression scale(SDS),Barthel index(BI),and the motor func-tion assessment scale(MAS),were employed to evaluate the improvement in swallowing function,neurological deficits,clinical outcomes,anxiety,depression,daily living activities,and motor function before and after ***,the study compared the occurrence of adverse reactions during the nursing period,life quality before and after the intervention,rehabilitation compliance,and nursing satisfaction between the two *** After the nursing intervention,the research group exhibited significantly improved SSA and NIHSS scores compared to the control group(P<0.05).Moreover,both groups demonstrated significant reductions in SAS and SDS scores(P<0.05),with the research group showing more obvious advantages(P<0.05).Compared to the control group,the research group displayed significantly better ESS,BI,and MAS scores(P<0.05),coupled with a lower incidence of adverse reactions(P<0.05).Additionally,the research group demonstrated markedly higher levels of life quality,rehabilitation compliance,and nursing satisfaction compared to the control group(P<0.05).CONCLUSION Comprehensive nu

关键词： Comprehensive nursing Stroke Swallowing function Quality of life Patient satisfaction

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Phosphorylation of PB2 at serine 181 restricts viral replication and virulence of the highly pathogenic H5N1 avian influenza virus in mice

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Virologica Sinica 2024年第1期39卷 97-112页

作者： Jiao hu Zixiong Zeng Xia Chen Manyu Zhang Zenglei hu Min Gu Xiaoquan Wang Ruyi Gao Shunlin hu yu Chen Xiaowen Liu Daxin Peng Xiufan Liu Animal Infectious Disease Laboratory School of Veterinary MedicineYangzhou UniversityYangzhou225009China Joint International Research Laboratory of Agriculture and Agri-Product Safety The Ministry of Education of ChinaYangzhou University225009China Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis Yangzhou UniversityYangzhou225009China Key Laboratory of Prevention and Control of Biological Hazard Factors(Animal Origin)for Agri-food Safety and Quality Ministry of Agriculture of China(26116120)Yangzhou UniversityYangzhou225009China

Influenza A virus(IAV)continues to pose a pandemic threat to public health,resulting a high mortality rate annually and during pandemic *** modification of viral protein plays a substantial role in regulating IAV ***,based on immunoprecipitation(IP)-based mass spectrometry(MS)and purified virus-coupled MS,a total of 89 phosphorylation sites distributed among 10 encoded viral proteins of IAV were identified,including 60 novel phosphorylation ***,for the first time,we provide evidence that PB2 can also be acetylated at site ***,the PB2 S181 phosphorylation site was consistently identified in both IP-based MS and purified virus-based *** S181 and K187 are exposed on the surface of the PB2 protein and are highly conserved in various IAV strains,suggesting their fundamental importance in the IAV life *** analysis results demonstrated that S181E/A and K187Q/R mimic mutations do not significantly alter the PB2 protein *** continuous phosphorylation mimicked by the PB2 S181E mutation substantially decreases viral fitness in mice,PB2 K187Q mimetic acetylation slightly enhances viral virulence in ***,PB2 S181E substantially impairs viral polymerase activity and viral replication,remarkably dampens protein stability and nuclear accumulation of PB2,and significantly weakens IAV-induced inflammatory ***,our study further enriches the database of phosphorylation and acetylation sites of influenza viral proteins,laying a foundation for subsequent mechanistic ***,the unraveled antiviral effect of PB2 S181E mimetic phosphorylation may provide a new target for the subsequent study of antiviral drugs.

关键词： H5N1 influenza virus PB2 Phosphorylation Acetylation Viral fitness Mice

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