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Asialoglycoprotein receptor 1 promotes SARS-CoV-2 infection of human normal hepatocytes

Signal Transduction and Targeted Therapy 2024年第3期9卷 1199-1208页

作者： Xinyi Yang Xu Zheng Yuqi Zhu Xiaying Zhao Jun Liu Jiangna xun Songhua Yuan Jun Chen Hanyu Pan Jinlong Yang Jing Wang Zhimin Liang Xiaoting Shen Yue Liang Qinru Lin Huitong Liang Min Li Fei Peng Daru Lu Jianqing xu Hongzhou Lu Shibo Jiang Ping Zhao Huanzhang Zhu State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology Ministry of EducationInstitute of GeneticsSchool of Life SciencesYiwu Research InstituteFudan UniversityShanghaiChina Department of Microbiology Faculty of Naval MedicineNaval Medical UniversityShanghai 200433China Scientific Research Center Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Department of Infectious Diseases and Immunology Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Changzheng Hospital Naval Medical UniversityShanghaiChina Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) Shanghai Institute of Infectious Disease and BiosecuritySchool of Basic Medical SciencesFudan UniversityShanghaiChina Department of Infectious Diseases and Nursing Research Institution National Clinical Research Center for Infectious DiseasesThe Third People’s Hospital of ShenzhenShenzhenGuangdongChina

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)causes multi-organ damage,which includes hepatic dysfunction,as observed in over 50%of COVID-19 patients.Angiotensin I converting enzyme(peptidyl-dipeptidase A)2(ACE2)is the primary receptor for SARS-CoV-2 entry into host cells,and studies have shown the presence of intracellular virus particles in human hepatocytes that express ACE2,but at extremely low levels.Consequently,we asked if hepatocytes might express receptors other than ACE2 capable of promoting the entry of SARS-CoV-2 into cells.To address this question,we performed a genome-wide CRISPR-Cas9 activation library screening and found that Asialoglycoprotein receptor 1(ASGR1)promoted SARS-CoV-2 pseudovirus infection of HeLa cells.In Huh-7 cells,simultaneous knockout of ACE2 and ASGR1 prevented SARS-CoV-2 pseudovirus infection.In the immortalized THLE-2 hepatocyte cell line and primary hepatic parenchymal cells,both of which barely expressed ACE2,SARSCoV-2 pseudovirus could successfully establish an infection.However,after treatment with ASGR1 antibody or siRNA targeting ASGR1,the infection rate significantly dropped,suggesting that SARS-CoV-2 pseudovirus infects hepatic parenchymal cells mainly through an ASGR1-dependent mechanism.We confirmed that ASGR1 could interact with Spike protein,which depends on receptor binding domain(RBD)and N-terminal domain(NTD).Finally,we also used Immunohistochemistry and electron microscopy to verify that SARS-CoV-2 could infect primary hepatic parenchymal cells.After inhibiting ASGR1 in primary hepatic parenchymal cells by siRNA,the infection efficiency of the live virus decreased significantly.Collectively,these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of hepatic parenchymal cells.

关键词： ACE2 infection glycoprotein

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Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

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Journal of Pharmaceutical Analysis 2024年第1期14卷 100-114页

作者： Sze Wan Hung Massimiliano Gaetani Yiran Li Zhouyurong Tan Xu Zheng Ruizhe Zhang Yang Ding Gene Chi Wai Man Tao Zhang Yi Song Yao Wang Jacqueline Pui Wah Chung Tak Hang Chan Roman A.Zubarev Chi Chiu Wang Department of Obstetrics&Gynaecology The Chinese University of Hong KongHong KongChina Division of Physiological Chemistry I Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Chemical Proteomics Core Facility Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Unit of Chemical Proteomics Science for Life Laboratory(SciLifeLab)StockholmSE 17177Sweden Center for Reproductive Medicine Henan Key Laboratory of Reproduction and GeneticsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450003China Department of Chemistry McGill UniversityMontrealH3A2K6Canada Department of Pharmacological&Technological Chemistry I.M.Sechenov First Moscow State Medical UniversityMoscow119146Russia Reproduction and Development Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine The Chinese University of Hong KongHong KongChina

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

关键词： Molecular targets ProEGCG EGCG Angiogenesis Treatment Endometriosis

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High-Order Decoupled and Bound Preserving Local Discontinuous Galerkin Methods for a Class of Chemotaxis Models

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Communications on Applied Mathematics and Computation 2024年第1期6卷 372-398页

作者： Wei zheng Yan xu School of Mathematical Sciences University of Science and Technology of ChinaHefei230026AnhuiChina

In this paper,we explore bound preserving and high-order accurate local discontinuous Galerkin(LDG)schemes to solve a class of chemotaxis models,including the classical Keller-Segel(KS)model and two other density-dependent problems.We use the convex splitting method,the variant energy quadratization method,and the scalar auxiliary variable method coupled with the LDG method to construct first-order temporal accurate schemes based on the gradient flow structure of the models.These semi-implicit schemes are decoupled,energy stable,and can be extended to high accuracy schemes using the semi-implicit spectral deferred correction method.Many bound preserving DG discretizations are only worked on explicit time integration methods and are difficult to get high-order accuracy.To overcome these difficulties,we use the Lagrange multipliers to enforce the implicit or semi-implicit LDG schemes to satisfy the bound constraints at each time step.This bound preserving limiter results in the Karush-Kuhn-Tucker condition,which can be solved by an efficient active set semi-smooth Newton method.Various numerical experiments illustrate the high-order accuracy and the effect of bound preserving.

关键词： Chemotaxis models Local discontinuous Galerkin(LDG)scheme Convex splitting method Variant energy quadratization method Scalar auxiliary variable method Spectral deferred correction method

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Neural Circuitry Involving Substance P in Male Sexual Behavior

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Neuroscience Bulletin 2024年第4期40卷 544-546页

作者： Xinrong Wang Junqiang zheng Han xu Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of MedicineHangzhou310058China Nanhu Brain-Computer Interface Institute Hangzhou311100China Liangzhu Laboratory MOE Frontier Science Center for Brain Science and Brain-machine IntegrationState Key Laboratory of Brain-Machine IntelligenceZhejiang UniversityHangzhou311121China NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang UniversityHangzhou310058China Lingang Laboratory Shanghai200031China

Male sexual behavior is an innate social behavior crucial for reproduction[1].Previous studies have identified several brain regions crucial for the control of both sexual and aggressive behaviors in males.Yet,molecularly specified neural circuits that specifically control male sexual behavior remain elusive.Consistent with the inherently rewarding nature of sexual behavior,previous research has implicated the role of the dopamine system in regulating sexual desire[2].However,the interaction between reward and copulation at the circuit level remains largely unexplored.Besides,it is unclear if the associated neural pathways are specific in modulating sexual reward.

关键词： behavior neural specified

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A survey on facial image deblurring

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Computational Visual Media 2024年第1期10卷 3-25页

作者： Bingnan Wang Fanjiang xu Quan zheng Institute of Software Chinese Academy of SciencesBeijing100190China University of Chinese Academy of Sciences Beijing100049China

When a facial image is blurred,it significantly affects high-level vision tasks such as face recognition.The purpose of facial image deblurring is to recover a clear image from a blurry input image,which can improve the recognition accuracy,etc.However,general deblurring methods do not perform well on facial images.Therefore,some face deblurring methods have been proposed to improve performance by adding semantic or structural information as specific priors according to the characteristics of the facial images.In this paper,we survey and summarize recently published methods for facial image deblurring,most of which are based on deep learning.First,we provide a brief introduction to the modeling of image blurring.Next,we summarize face deblurring methods into two categories:model-based methods and deep learning-based methods.Furthermore,we summarize the datasets,loss functions,and performance evaluation metrics commonly used in the neural network training process.We show the performance of classical methods on these datasets and metrics and provide a brief discussion on the differences between model-based and learning-based methods.Finally,we discuss the current challenges and possible future research directions.

关键词： facial image deblurring model-based deep learning-based semantic or structural prior

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Nanoforming of transferred metal contacts for enhanced twodimensional field effect transistors

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Nano Research 2024年第4期17卷 3210-3216页

作者： Shuoheng xu zheng Huang Jie Guan Yaowu Hu The Institute of Technological Sciences Wuhan UniversityWuhan 430072China School of Power and Mechanical Engineering Wuhan UniversityWuhan 430072China School of Physics Southeast UniversityNanjing 211189China

Two-dimensional transition metal chalcogenides(2D-TMDs)have attracted much attention because of their unique layered structure and physical properties for transistor applications.Mechanically transferred metal contacts on these low-dimensional materials or their homogeneous and heterogeneous multilayers have generated huge interest to avoid deposition damages.In this paper,we show that there are large physical gaps at both the edge contact and surface contact between the transferred electrodes and the 2D materials.A method called laser shock induced superplastic deformation(LSISD)is proposed to tackle this issue and enhance the performance of the transistors.The enhancement mechanism was investigated by molecular dynamics(MD)simulations of the nanoforming process,atomic force microscopy(AFM),scanning electron microscopy(SEM),transmission electron microscopy(TEM)characterizations of the interfaces,and density functional theory(DFT)modeling.The force effect of laser shock can reduce the contact gap between metals and semiconductors.The electrical performances of the transistors before and after LSISD,along with MD simulations,are used to find the optimal process parameters.In addition,this paper applies the LSISD method to the short-channel MoS_(2)/graphene vertical transistors to show potential improvement in interface contact and electrical properties.This paper demonstrates the first report on using mechanical force induced by laser shock to enhance metal–semiconductor interfaces and transistor performances.

关键词： laser shock nanoforming metal-semiconductor contact electronics two-dimensional transistors

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The Al_(2)O_(3)and Mn/Al_(2)O_(3)sorbents highly utilized in destructive sorption of NF_(3)

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Chinese Journal of Chemical Engineering 2024年第1期65卷 54-62页

作者： Yanfei Pan Hejian Li Li zheng Xiufeng xu School of Chemistry and Chemical Engineering Yantai UniversityYantai 264005China

NF_(3)is commonly used as an etching and cleaning gas in semiconductor industry,however it is a strongly greenhouse gas.Therefore,the destruction of disposal NF_(3)is an urgent task to migrate the greenhouse effect.Among the technologies for NF_(3)abatement,the destructive sorption of NF_(3)over metal oxides sorbents is an effective way.Thus,the search for a highly reactive and utilized sorbent for NF_(3)destruction is in great demand.In this work,AlOOH supported on carbon-sphere(AlOOH/CS)as precursors were synthesized hydrothermally and heat-treated to prepare the Al_(2)O_(3)sorbents.The influence of AlOOH/CS hydrothermal temperatures on the reactivity of derived Al_(2)O_(3)sorbents for NF_(3)destruction was investigated,and it is shown that the Al2O3 from AlOOH/CS hydro-thermalized at 120℃is superior to others.Subsequently,the optimized Al_(2)O_(3)was covered by Mn(OH)x to prepare Mn/Al_(2)O_(3)sorbents via changing hydrothermal temperatures and Mn loadings.The results show that the Mn/Al_(2)O_(3)sorbents are more utilized than bare Al_(2)O_(3)in NF_(3)destructive sorption due to the promotional effect of Mn_(2)O_(3)as surface layer on the fluorination of Al_(2)O_(3)as substrate,especially the optimal 5%Mn/Al2O3(160℃)exhibits a utilization percentage as high as 90.4%,and remarkably exceeds all the sorbents reported so far.These findings are beneficial to develop more efficient sorbents for the destruction of NF_(3).

关键词： Greenhouse gas NF_(3)destructive sorption Sorbents Al_(2)O_(3) Mn/Al_(2)O_(3) Reactivity

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Using Improved Particle Swarm Optimization Algorithm for Location Problem of Drone Logistics Hub

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Computers, Materials & Continua 2024年第1期78卷 935-957页

作者： Li zheng Gang xu Wenbin Chen School of Mathematics and Computer Sciences Nanchang UniversityNanchang330031China

Drone logistics is a novel method of distribution that will become prevalent.The advantageous location of the logistics hub enables quicker customer deliveries and lower fuel consumption,resulting in cost savings for the company’s transportation operations.Logistics firms must discern the ideal location for establishing a logistics hub,which is challenging due to the simplicity of existing models and the intricate delivery factors.To simulate the drone logistics environment,this study presents a new mathematical model.The model not only retains the aspects of the current models,but also considers the degree of transportation difficulty from the logistics hub to the village,the capacity of drones for transportation,and the distribution of logistics hub locations.Moreover,this paper proposes an improved particle swarm optimization(PSO)algorithm which is a diversity-based hybrid PSO(DHPSO)algorithm to solve this model.In DHPSO,the Gaussian random walk can enhance global search in the model space,while the bubble-net attacking strategy can speed convergence.Besides,Archimedes spiral strategy is employed to overcome the local optima trap in the model and improve the exploitation of the algorithm.DHPSO maintains a balance between exploration and exploitation while better defining the distribution of logistics hub locations Numerical experiments show that the newly proposed model always achieves better locations than the current model.Comparing DHPSO with other state-of-the-art intelligent algorithms,the efficiency of the scheme can be improved by 42.58%.This means that logistics companies can reduce distribution costs and consumers can enjoy a more enjoyable shopping experience by using DHPSO’s location selection.All the results show the location of the drone logistics hub is solved by DHPSO effectively.

关键词： Drone logistics location problem mathematical model diversity particle swarm optimization

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Reliability ensemble averaging reduces surface wind speed projection uncertainties in the 21st century over China

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Advances in Climate Change Research 2024年第2期15卷 222-229页

作者： zheng-Tai ZHANG Chang-Ai xu Key Laboratory for Semi-Arid Climate Change of the Ministry of Education College of Atmospheric SciencesLanzhou UniversityLanzhou 730000China

Accurate prediction of future surface wind speed(SWS)changes is the basis of scientific planning for wind turbines.Most studies have projected SWS changes in the 21st century over China on the basis of the multi-model ensemble(MME)of the 6th Coupled Model Intercomparison Project(CMIP6).However,the simulation capability for SWS varies greatly in CMIP6 multi-models,so the MME results still have large uncertainties.In this study,we used the reliability ensemble averaging(REA)method to assign each model different weights according to their performances in simulating historical SWS changes and project the SWS under different shared socioeconomic pathways(SSPs)in 2015-2099.The results indicate that REA considerably improves the SWS simulation capacity of CMIP6,eliminating the overestimation of SWS by the MME and increasing the simulation capacity of spatial distribution.The spatial correlations with observations increased from 0.56 for the MME to 0.85 for REA.Generally,REA could eliminate the overestimation of the SWS by 33%in 2015-2099.Except for southeastern China,the SWS generally decreases over China in the near term(2020-2049)and later term(2070-2099),particularly under high-emission scenarios.The SWS reduction projected by REA is twice as high as that by the MME in the near term,reaching-4%to-3%.REA predicts a larger area of increased SWS in the later term,which expands from southeastern China to eastern China.This study helps to reduce the projected SWS uncertainties.

关键词： Surface wind speed Uncertainty Multi-model ensemble Reliability ensemble averaging CMIP6

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Can whole steps of grain production be outsourced? Empirical analysis based on the three provinces of Jiangsu,Jilin,and Sichuan in China

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Journal of Integrative Agriculture 2024年第1期23卷 336-347页

作者： Jiacheng Liu Shengzhi Mao Qiufen zheng Zhigang xu School of Finance and Taxation Nanjing University of Finance and EconomicsJiangsu 210023China School of Economics Southwestern University of Finance and EconomicsSichuan 611130China School of Economics and Management Nanjing Agricultural UniversityJiangsu 210095China

Certain outsourcing services for agricultural management in China,such as pest control in grain production,have experienced prolonged sluggishness,contrasting with the relatively high level of outsourcing services observed in harvesting,land preparation,and sowing.This study examines the feasibility of implementing whole-step outsourcing in grain production by conducting a case study of rice and maize production in Jiangsu,Jilin,and Sichuan provinces in China.The provision of outsourcing services hinges on two essential conditions:technological advancements fostering specialized production and economies of scale,coupled with a market size sufficient to realize the aforementioned potential economies of scale.The results showed that outsourcing pest control or harvesting services had varying economies of scale.The outsourcing services in pest control were less common than in harvesting services,and their marginal growth space of the economies of scale with technological change was also smaller.Determined by the operational characteristics of pest control itself,the market scale of its professional services is small.Therefore,achieving the whole-step outsourcing of grain production necessitates not only technological innovation but also effective policy interventions to overcome the constraints of market scale.Such interventions include(1)optimizing crop layouts between planning regions and reducing land fragmentation and(2)supplying timely and effective inter-regional agricultural information for service providers aided by information technology.

关键词： outsourcing services economy of scale technical conditions market scale

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