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Single-cell RNA sequencing reveals the dynamics of hepatic non-parenchymal cells in autoprotection against acetaminophen-induced hepatotoxicity

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药物分析学报:英文版 2023年第8期13卷 926-941页

作者： Lingqi Yu Jun Yan yingqi zhan Anyao Li Lidan Zhu Jingyang Qian Fanfan Zhou Xiaoyan Lu Xiaohui Fan Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China Future Health Laboratory Innovation Center of Yangtze River DeltaZhejiang UniversityJiaxingZhejiang314100China Innovation Center in Zhejiang University State Key Laboratory of Component-Based Chinese MedicineHangzhou 310058China School of Pharmacy The University of SydneySydney2006Australia Jinhua Institute of Zhejiang University JinhuaZhejiang321016China Hangzhou Institute of Innovative Medicine Zhejiang UniversityHangzhou310058China Engineering Research Center of Innovative Anticancer Drugs Ministry of EducationHarbin150023China

Gaining a better understanding of autoprotection against drug-induced liver injury(DILI)may provide new strategies for its prevention and therapy.However,little is known about the underlying mechanisms of this phenomenon.We used single-cell RNA sequencing to characterize the dynamics and functions of hepatic non-parenchymal cells(NPCs)in autoprotection against DILI,using acetaminophen(APAP)as a model drug.Autoprotection was modeled through pretreatment with a mildly hepatotoxic dose of APAP in mice,followed by a higher dose in a secondary challenge.NPC subsets and dynamic changes were identified in the APAP(hepatotoxicity-sensitive)and APAP-resistant(hepatotoxicity-resistant)groups.A chemokine(C-C motif)ligand 2^(+)endothelial cell subset almost disappeared in the APAP-resistant group,and an R-spondin 3^(+)endothelial cell subset promoted hepatocyte proliferation and played an important role in APAP autoprotection.Moreover,the dendritic cell subset DC-3 may protect the liver from APAP hepatotoxicity by inducing low reactivity and suppressing the autoimmune response and occurrence of inflammation.DC-3 cells also promoted angiogenesis through crosstalk with endothelial cells via vascular endothelial growth factor-associated ligand-receptor pairs and facilitated liver tissue repair in the APAP-resistant group.In addition,the natural killer cell subsets NK-3 and NK-4 and the Sca-1^(-)CD62L^(+)natural killer T cell subset may promote autoprotection through interferon-γ-dependent pathways.Furthermore,macrophage and neutrophil subpopulations with anti-inflammatory phenotypes promoted tolerance to APAP hepatotoxicity.Overall,this study reveals the dynamics of NPCs in the resistance to APAP hepatotoxicity and provides novel insights into the mechanism of autoprotection against DILI at a high resolution.

关键词： Single-cell RNA sequencing Drug-induced liver injury Autoprotection against APAP hepatotoxicity Endothelial cells Dendritic cells

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Context‑dependent antioxidant defense system(ADS)‑based stress memory in response to recurrent environmental challenges in congeneric invasive species

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Marine Life Science & Technology 2024年第2期6卷 315-330页

作者： Hanxi Li Xuena Huang Aibin zhan Research Center for Eco-Environmental Sciences Chinese Academy of SciencesBeijing 100085China University of Chinese Academy of Sciences Beijing 100049China

Marine ecosystems are facing escalating environmental fluctuations owing to climate change and human activities,imposing pressures on marine species.To withstand recurring environmental challenges,marine organisms,especially benthic species lacking behavioral choices to select optimal habitats,have to utilize well-established strategies such as the antioxidant defense system(ADS)to ensure their survival.Therefore,understanding of the mechanisms governing the ADS-based response is essential for gaining insights into adaptive strategies for managing environmental challenges.Here we conducted a com-parative analysis of the physiological and transcriptional responses based on the ADS during two rounds of'hypersalinity-recovery'challenges in two model congeneric invasive ascidians,Ciona robusta and C.savignyi.Our results demonstrated that C.savignyi exhibited higher tolerance and resistance to salinity stresses at the physiological level,while C.robusta demonstrated heightened responses at the transcriptional level.We observed distinct transcriptional responses,particularly in the utilization of two superoxide dismutase(SOD)isoforms.Both Ciona species developed physiological stress memory with elevated total SOD(T-SOD)and glutathione(GSH)responses,while only C.robusta demonstrated transcriptional stress memory.The regulatory distinctions within the Nrf2-Keap1 signalling pathway likely explain the formation disparity of transcriptional stress memory between both Ciona species.These findings support the'context-dependent stress memory hypothesis',emphasizing the emergence of species-specific stress memory at diverse regulatory levels in response to recurrent environmental challenges.Our results enhance our understanding of the mechanisms of environmental challenge manage-ment in marine species,particularly those related to the ADS.

关键词： Antioxidant defense Ascidian Biological invasion Environmental stress Stress memory

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Gelfand-Kirillov Dimension and Reducibility of Scalar Generalized Verma Modules for Classical Lie Algebras

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Acta Mathematica Sinica,English Series 2024年第3期40卷 658-706页

作者： zhan Qiang BAI Jing JIANG School of Mathematical Sciences Soochow UniversitySuzhou 215006P.R.China E-mail:zqbai@*** jjsd6514@***

Let g be a classical complex simple Lie algebra and q be a parabolic subalgebra.Let M be a generalized Verma module induced from a one dimensional representation of q.Such M is called a scalar generalized Verma module.In this paper,we will determine the reducibility of scalar generalized Verma modules associated to maximal parabolic subalgebras by computing explicitly the Gelfand-Kirillov dimension of the corresponding highest weight modules.

关键词： Generalized Verma module Gelfand-Kirillov dimension Young tableau

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Research on the prognostic value of adjusting intraperitoneal threedimensional quality evaluation mode in laparoscopic cholecystectomy patients

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1078-1086页

作者： Yuan Zhou zhan-Qing Chen Operating Room Lianyungang Hospital of Traditional Chinese MedicineLianyungang 222000Jiangsu ProvinceChina Operating Room The Second People's Hospital of Lianyungang Affiliated to Kangda College of Nanjing Medical UniversityLianyungang 222000Jiangsu ProvinceChina

BACKGROUND Benign gallbladder diseases have become a high-prevalence condition not only in China but also worldwide.The main types of benign gallbladder diseases include gallbladder polyps,acute and chronic cholecystitis,and gallstones,with gallstones being the most common,accounting for over 70%of cases.Although the mortality rate of benign gallbladder diseases is low,they carry obvious potential risks.Studies have shown that an increased incidence of benign gallbladder diseases can increase the risk of cardiovascular diseases and gallbladder cancer,resulting in a substantial disease burden on patients and their families.AIM To assess the medical utility of the Configuration-Procedure-Consequence(CPC)three-dimensional quality evaluation model in modulating the prognosis of laparoscopic cholecystectomy patients.METHODS A total of 98 patients who underwent laparoscopic cholecystectomy in our hospital from February 2020 to January 2022 were selected as the subjects.According to the random number table method,they were divided into a study group and a control group,with 49 patients in each group.The control group received routine perioperative care,while the study group had the addition of the CPC three-dimensional quality evaluation.The postoperative recovery-related indicators(time to first flatus,time to oral intake,time to ambulation,hospital stay),stress indicators(cortisol and adrenaline levels),distinctions in anxiety and RESULTS The time to first flatus,time to oral intake,time to ambulation,and hospital stay of the study group patients were obviously lower than those of the control group patients,with statistical significance(P0.05).However,on the 3rd day after surgery,the cortisol and adrenaline levels,as well as SAS and SDS scores of the study gr

关键词： Configuration-Procedure-Consequence Three-dimensional quality evaluation Laparoscopic Cholecystectomy Recovery process Anxiety and depression Complications

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Mega-Constellations Based TT&C Resource Sharing: Keep Reliable Aeronautical Communication in an Emergency

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China Communications 2024年第2期21卷 1-16页

作者： Haoran Xie Yafeng zhan Jianhua Lu Department of Electronic Engineering Tsinghua UniversityBeijing 100084China Beijing National Research Center for Information Science and Technology Tsinghua UniversityBeijing 100084China

With the development of the transportation industry, the effective guidance of aircraft in an emergency to prevent catastrophic accidents remains one of the top safety concerns. Undoubtedly, operational status data of the aircraft play an important role in the judgment and command of the Operational Control Center(OCC). However, how to transmit various operational status data from abnormal aircraft back to the OCC in an emergency is still an open problem. In this paper, we propose a novel Telemetry, Tracking,and Command(TT&C) architecture named Collaborative TT&C(CoTT&C) based on mega-constellation to solve such a problem. CoTT&C allows each satellite to help the abnormal aircraft by sharing TT&C resources when needed, realizing real-time and reliable aeronautical communication in an emergency. Specifically, we design a dynamic resource sharing mechanism for CoTT&C and model the mechanism as a single-leader-multi-follower Stackelberg game. Further, we give an unique Nash Equilibrium(NE) of the game as a closed form. Simulation results demonstrate that the proposed resource sharing mechanism is effective, incentive compatible, fair, and reciprocal. We hope that our findings can shed some light for future research on aeronautical communications in an emergency.

关键词： aeronautical emergency communication mega-constellation networked TT&C resource allocation stackelberg game

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A Review on the Mullins Effect in Tough Elastomers and Gels

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Acta Mechanica Solida Sinica 2024年第2期37卷 181-214页

作者： Lin zhan Shaoxing Qu Rui Xiao MOE Key Lab of Disaster Forecast and Control in Engineering College of Mechanics and Construction EngineeringJinan UniversityGuangzhou510632China State Key Laboratory of Fluid Power and Mechatronic System Key Laboratory of Soft Machines and Smart Devices of Zhejiang ProvinceDepartment of Engineering MechanicsZhejiang UniversityHangzhou310027China

Tough elastomers and gels have garnered broad research interest due to their wide-ranging potential applications.However,during the loading and unloading cycles,a clear stress softening behavior can be observed in many material systems,which is also named as the Mullins effect.In this work,we aim to provide a complete review of the Mullins effect in soft yet tough materials,specifically focusing on nanocomposite gels,double-network hydrogels,and multi-network elastomers.We first revisit the experimental observations for these soft materials.We then discuss the recent developments of constitutive models,emphasizing novel developments in the damage mechanisms or network representations.Some phenomenological models will also be briefly introduced.Particular attention is then placed on the anisotropic and multiaxial modeling aspects.It is demonstrated that most of the existing models fail to accurately predict the multiaxial data,posing a significant challenge for developing future anisotropic models tailored for tough gels and elastomers.

关键词： Mullins effect Double-network hydrogels Nanocomposite gels Multi-network elastomers Anisotropic damage model Multiaxial model

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Recent Advances in Enantioselective Reactions of Terminal Unactivated Alkenes

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Chinese Journal of Chemistry 2024年第7期42卷 760-776页

作者： Qihang Guo Xbxuzhong She zhan Lu Centerof ChemistryforFrontier Technologies Departmentof ChemistryZhejiang UniversityHangzhouZhejiang 310058China ZJU-Hangzhou Global Scientific and Technological Innovation Center HangzhouZhejiang 311215China College of Chemistry Zhengzhou UniversityZhengzhouHenan 450001China

α-Olefins as aliphatic terminal alkenes could be obtained easily from numerous contemporary synthetic reactions as well as petro-chemical industry,and also found in natural products.Compared to the alkenes attaching the directing groups or activating group,the catalytic asymmetric reaction of unactivated terminal alkenes presents great challenges due to the weak electron effect and small steric hindrance effect.This review mainly summarizes the latest progress of the asymmetric reaction of unactivated terminal olefins since 2016.

关键词： Asymmetric catalysis Terminal unactivated alkenes Hydrofunctionalization Difunctionalization Metal-catalyzed

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Kinetic model of vibration screening for granular materials based on biological neural network

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Particuology 2024年第5期88卷 98-106页

作者： zhan Zhao Yan zhang Fang Qin Mingzhi Jin School of Agricultural Engineering Jiangsu UniversityZhenjiang212013China Shandong Academy of Agricultural Machinery Sciences Ji'nan250100China

The kinetic model is the theoretical basis for optimizing the structure and operation performance of vibration screening devices.In this paper,a biological neurodynamic equation and neural connections were established according to the motion and interaction properties of the material under vibration excitation.The material feeding to the screen and the material passing through apertures were considered as excitatory and inhibitory inputs,respectively,and the generated stable neural activity landscape was used to describe the material distribution on the 2D screen surface.The dynamic process of material vibration screening was simulated using discrete element method(DEM).By comparing the similarity between the material distribution established using biological neural network(BNN)and that obtained using DEM simulation,the optimum coefficients of BNN model under a certain screening parameter were determined,that is,one relationship between the BNN model coefficients and the screening operation parameters was established.Different screening parameters were randomly selected,and the corresponding relationships were established as a database.Then,with straw/grain ratio,aperture diameter,inclination angle,vibration strength in normal and tangential directions as inputs,five independent adaptive neuro-fuzzy inference systems(ANFIS)were established to predict the optimum BNN model coefficients,respectively.The training results indicated that ANFIS models had good stability and accuracy.The flexibility and adaptability of the proposed BNN method was demonstrated by modeling material distribution under complex feeding conditions such as multiple regions and non-uniform rate.

关键词： Kinetic model Material distribution Vibration screening Biological neural network DEM simulation Adaptive neuro-fuzzy inference systems

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Thymoquinone affects hypoxia-inducible factor-1αexpression in pancreatic cancer cells via HSP90 and PI3K/AKT/mTOR pathways

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World Journal of Gastroenterology 2024年第21期30卷 2793-2816页

作者： zhan-Xue Zhao Shuai Li Lin-Xun Liu Department of General Surgery Qinghai Provincial People's HospitalXining 810007Qinghai ProvinceChina Department of Clinical Pharmacy The Affiliated Hospital of Qinghai UniversityXining 810001Qinghai ProvinceChina

BACKGROUND Pancreatic cancer(PC)is associated with some of the worst prognoses of all major cancers.Thymoquinone(TQ)has a long history in traditional medical practice and is known for its anti-cancer,anti-inflammatory,anti-fibrosis and antioxidant pharmacological activities.Recent studies on hypoxia-inducible factor-1α(HIF-1α)and PC have shown that HIF-1αaffects the occurrence and development of PC in many aspects.In addition,TQ could inhibit the development of renal cancer by decreasing the expression of HIF-1α.Therefore,we speculate whether TQ affects HIF-1αexpression in PC cells and explore the mechanism.AIM To elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1αexpression.METHODS Cell counting kit-8 assay,Transwell assay and flow cytometry were performed to detect the effects of TQ on the proliferative activity,migration and invasion ability and apoptosis of PANC-1 cells and normal pancreatic duct epithelial(hTERTHPNE)cells.Quantitative real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1αmRNA and protein in PC cells.The effects of TQ on the HIF-1αprotein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and co-immunoprecipitation.RESULTS TQ significantly inhibited proliferative activity,migration,and invasion ability and promoted apoptosis of PANC-1 cells;however,no significant effects on hTERT-HPNE cells were observed.TQ significantly reduced the mRNA and protein expression levels of HIF-1αin PANC-1,AsPC-1,and BxPC-3 cells.TQ significantly inhibited the expression of the HIF-1αinitial expression pathway(PI3K/AKT/mTOR)related proteins,and promoted the ubiquitination degradation of the HIF-1αprotein in PANC-1 cells.TQ had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1αprotein but affected the stability of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90,thus promoting its ubiquitination

关键词： Thymoquinone Pancreatic cancer Hypoxia-inducible factor-1α PI3K/AKT/mTOR HSP90

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Enhanced memristor performance via coupling effect of oxygen vacancy and ferroelectric polarization

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Journal of Materials Science & Technology 2024年第4期171卷 139-146页

作者： Zhi Yun Yue Zhi Dong zhang zhan Jie Wang Shenyang National Laboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China School of Materials Science and Engineering University of Science and Technology of ChinaShenyang 110016China School of Materials Science and Engineering Shenyang University of TechnologyShenyang 110870China

As a new type of nonvolatile memory,the resistive memristor has broad application prospects in in-formation storage and neural computing based on its excellent resistive switching(RS)performance.At present,it is still a great challenge to improve both ferroelectric polarization and leakage current to achieve a high RS on/offratio of ferroelectric memristors.Herein,epitaxial Pb(Zr_(0.40)Ti_(0.60))O_(3)(PZT)thin films with low content Ca doping were deposited on the Nb:SrTiO_(3)substrate to prepare PCZT/NSTO het-erostructures and their RS behaviors were studied.The research findings show that compared with pure PZT film,the ferroelectric polarization of 1-mol%-Ca-doped PZT film is slightly improved,while the leak-age current is increased by three orders of magnitude.Therefore,the RS on/offratio reaches 2.5×10^(5),about three orders of magnitude higher than pure PZT films.The theoretical analysis reveals that the RS behavior of PCZT/NSTO heterostructures is controlled by the PCZT/NSTO interfacial barrier and the space charge-limited current mechanism.Our results demonstrate that the ferroelectricity and electricity of ferroelectric thin films can be improved simultaneously by doping low-content Ca ions to increase the RS performance,which provides a good reference for the development of high-performance ferroelectric memristor devices.

关键词： Ferroelectric memristor Ca-doped PZT Ferroelectric polarization Oxygen vacancies Resistive switching

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