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Melittin analog p5RHH enhances recombinant adeno-associated virus transduction efficiency

Journal of Integrative Medicine 2024年第1期22卷 72-82页

作者： Jing-shun Meng Yun He Heng-bin Yang Li-ping Zhou si-yuan wang Xi-lin Feng Omar Yahya Al-shargi Xiao-min Yu Li-qing Zhu Chang-quan Ling Shanghai University of Traditional Chinese Medicine Shanghai 201203China Oncology Department of Traditional Chinese Medicine Changhai HospitalNaval Medical UniversityShanghai 200433China Faculty of Traditional Chinese Medicine Naval Medical UniversityShanghai 200043China State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology(Ministry of Education) School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200438China Yantai Fuheng Biological Technology Co. Ltd.YantaiShandong Province 264006China. Department of Clinical Laboratory the First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina

Objective Melittin and its derivatives have been characterized to establish effective gene delivery systems.Their capability of facilitating endosomal release enhances the nanoparticles-based gene delivery.Nevertheless,little investigation has been conducted to explore its potential application in the context of viral vectors.Methods Various melittin-derived peptides were inserted into the loop VIII of the capsid proteins of recombinant adeno-associated virus vectors.These vectors carrying either gfp or fluc genes were subjected to qPCR assays and transduction assays of HEK293T cells to investigate the efficiency of vector production and gene delivery.In addition,the ability of a specific p5RHH-rAAV vector to deliver genes was examined through in vitro transduction of different cultured cells and in vivo tail vein administration to C57BL/6 mice.Finally,the intricate details of the vector-mediated transduction mechanisms were revealed by specific pharmacological inhibitors of every stage of the rAAV2 intracellular life cycle.Results A total of 76 melittin-related peptides were compiled from existing literature.Among them,cMA2,Melt13,p5RHH and aAR3 were found to significantly enhance the gene delivery efficiency of rAAV2 vectors.The p5RHH-rAAV2 vectors efficiently transduced not only rAAV-potent cell lines but also cell lines previously considered resistant to rAAV.Mechanistically,bafilomycin A1,a vacuolar endosome acidification inhibitor,completely inhibited the transgene expression mediated by the p5RHH-rAAV2 vectors.Most importantly,p5RHH-rAAV8 vectors also demonstrated increased hepatic transduction in vivo in C57BL/6 mice.Conclusion The incorporation of melittin analogues into the rAAV capsids results in a significant improvement in rAAV-mediated transgene expression.While further modifications remain an area of interest,our studies have substantially broadened the pharmacological prospects of melittin in the context of viral vector-mediated gene delivery.

关键词： Melittin Recombinant adeno-associated virus Capsid engineering Transduction efficiency

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Rapid Unconscious Acquisition of Conditioned Fear with Low-Spatial-Frequency but Emotionally Neutral Stimuli

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Research 2024年第1期2023卷 753-762页

作者： Yujie Chen si Chen Zhongju Sun Xilei Zhang Xiangyong yuan Liang wang Yi Jiang State Key Laboratory of Brain and Cognitive Sciences CAS Center for Excellence in Brain Science and Intelligence TechnologyInstitute of PsychologyChinese Academy of SciencesBeijing 100101China Department of Psychology University of Chinese Academy of SciencesBeijing 100049China Chinese Institute for Brain Research Beijing 102206China CAS Key Laboratory of Mental Health Institute of PsychologyChinese Academy of SciencesBeijing 100101China

It has long been proposed that emotionally“prepared”(i.e.,fear-related)stimuli are privileged in the unconscious acquisition of conditioned fear.However,as fear processing is suggested to highly depend on the coarse,low-spatial-frequency(LSF)components of the fear-related stimuli,it is plausible that LSF may play a unique role in the unconscious fear conditioning even with emotionally neutral stimuli.Here,we provided empirical evidence that,following classical fear conditioning,an invisible,emotionally neutral conditioned stimulus(CS+)with LSF,but not with high spatial frequency(HSF),can rapidly elicit stronger skin conductance responses(SCRs)and larger pupil diameters than its CS−counterpart.In comparison,consciously perceived emotionally neutral CS+with LSF and HSF elicited comparable SCRs.Taken together,these results support that the unconscious fear conditioning does not necessarily entail emotionally prepared stimuli but prioritizes LSF information processing and highlight the crucial distinctions between the unconscious and the conscious fear learning.These findings not only coincide with the postulation that a rapid,spatial-frequency-dependent subcortical route is engaged in unconscious fear processing but also suggest the existence of multiple routes for conscious fear processing.

关键词： neutral necessarily diameters

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Collective Molecular Machines: Multidimensionality and Reconfigurability

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Nano-Micro Letters 2024年第8期16卷 309-340页

作者： Bin wang yuan Lu Department of Chemical Engineering Tsinghua UniversityBeijing 100084People’s Republic of China Key Laboratory of Industrial Biocatalysis Ministry of EducationTsinghua UniversityBeijing 100084People’s Republic of China

Molecular machines are key to cellular activity where they are involved in converting chemical and light energy into efficient mechanical work.During the last 60 years,designing molecular structures capable of generating unidirectional mechanical motion at the nanoscale has been the topic of intense research.Effective progress has been made,attributed to advances in various fields such as supramolecular chemistry,biology and nanotechnology,and informatics.However,individual molecular machines are only capable of producing nanometer work and generally have only a single functionality.In order to address these problems,collective behaviors realized by integrating several or more of these individual mechanical units in space and time have become a new paradigm.In this review,we comprehensively discuss recent developments in the collective behaviors of molecular machines.In particular,collective behavior is divided into two paradigms.One is the appropriate integration of molecular machines to efficiently amplify molecular motions and deformations to construct novel functional materials.The other is the construction of swarming modes at the supramolecular level to perform nanoscale or microscale operations.We discuss design strategies for both modes and focus on the modulation of features and properties.Subsequently,in order to address existing challenges,the idea of transferring experience gained in the field of micro/nano robotics is presented,offering prospects for future developments in the collective behavior of molecular machines.

关键词： Molecular machines Collective control Collective behaviors DNA Biomolecular motors

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Adhesive Contact of Elastic Solids with Self-Affine Fractal Rough Surfaces

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Acta Mechanica Solida sinica 2024年第2期37卷 265-270页

作者： Xuan-Ming Liang Shi-Wen Chen si-He wang Zhen-yuan Gong Jun Feng Gang-Feng wang Department of Engineering Mechanics SVL and MMMLXi’an Jiaotong UniversityXi’an710049China OPPO Mobile Telecommunications Corporation Ltd. Dongguan523860China

The elastic adhesive contact of self-affine fractal rough surfaces against a rigid flat is simulated using the finite element method. An array of nonlinear springs, of which the force-separation law obeys the Lennard–Jones potential, is introduced to account for the interfacial adhesion. For fractal rough surfaces, the interfacial interaction is generally attractive for large mean gaps, but turns repulsive as the gap continuously shrinks. The interfacial interactions at the turning point corresponding to the spontaneous contact are shown for various surfaces. For relatively smooth surfaces, the probability density distributions of repulsion and attraction are nearly symmetric. However, for rougher surfaces, the simulation results suggest a uniform distribution for attraction but a monotonously decreasing distribution with a long tail for repulsion. The pull-off force rises with increasing ratio of the work of adhesion to the equilibrium distance, whereas decreases for solids with a higher elastic modulus and a larger surface roughness. The current study will be helpful for understanding the adhesion of various types of rough solids.

关键词： Fractal rough surfaces Adhesion Contact mechanics Lennard-Jones potential

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Biological Eagle-eye Inspired Target Detection for Unmanned Aerial Vehicles Equipped with a Manipulator

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Machine Intelligence Research 2023年第5期20卷 741-752页

作者： Yi-Min Deng si-yuan wang School of Automation Science and Electrical Engineering Beihang UniversityBeijing 100191China

Inspired by eagle eye mechanisms,the structure and information processing characteristics of the eagle′s visual system are used for the target capture task of an unmanned aerial vehicle(UAV)with a mechanical arm.In this paper,a novel eagle-eye inspired multi-camera sensor and a saliency detection method are proposed.A combined camera system is built by simulating the double fovea structure on the eagle retina.A saliency target detection method based on the eagle midbrain inhibition mechanism is proposed by measuring the static saliency information and dynamic features.Thus,salient targets can be accurately detected through the collaborative work between different cameras of the proposed multi-camera sensor.Experimental results show that the eagle-eye inspired visual system is able to continuously detect targets in outdoor scenes and that the proposed algorithm has a strong inhibitory effect on moving background interference.

关键词： Unmanned aerial vehicle(UAV) eagle eye multi-camera sensor target detection saliency detection

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Stochastic Flexibility Evaluation for Virtual Power Plants by Aggregating Distributed Energy Resources

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CSEE Journal of Power and Energy Systems 2024年第3期10卷 988-999页

作者： siyuan wang Wenchuan Wu Qizhan Chen Junjie Yu Peng wang Department of Electrical Engineering Tsinghua UniversityBeijing 100084China Zhongshan Power Supply Bureau of the Guangdong Power Grid Corporation Zhongshan 528400China Beijing Qingda Gaoke System Control Company Beijing 102208China CSEE IEEE

To manage a large amount of flexible distributed energy resources(DERs)in the distribution networks,the virtual power plant(VPP)is introduced into the industry.The VPP can optimally dispatch these resources in a cluster manner and provide flexibility for the power system operation as a whole.Most existing studies formulate the equivalent power flexibility of the aggregating DERs as deterministic optimization models without considering their uncertainties.In this paper,we introduce the stochastic power flexibility range(PFR)and timecoupling flexibility(TCF)to describe the power flexibility of VPP.In this model,both operational constraints and the randomness of the DERs’output are incorporated,and a combined model and data-driven solution is proposed to obtain the stochastic PFR,TCF,and cost function of VPP.The aggregating model can be easily incorporated into the optimization model for the power system operator or market bidding,considering uncertainties.Finally,a numerical test is performed.The results show that the proposed model not only has higher computational efficiency than the scenario-based methods but also achieves more economic benefits.

关键词： Chance constrained optimization combined model and data-driven stochastic power flexibility virtual power plant

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Hepatocyte growth factor promotes retinal pigment epithelium cell activity through MET/AKT signaling pathway

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 806-814页

作者： si-Rui Zhou Yu-Sheng Zhu Wen-Ting yuan Xiao-Yan Pan Tong wang Xiao-Dong Chen Faculty of Life Sciences and Medicine Northwest UniversityXi’an 710069Shaanxi ProvinceChina First Affiliated Hospital of Northwest University Northwest UniversityXi’an 710069Shaanxi ProvinceChina Department of Ophthalmology Xi’an No.1 HospitalXi’an 710002Shaanxi ProvinceChina Shaanxi Institute of Ophthalmology Shaanxi Provincial Key Lab of OphthalmologyClinical Research Center for Ophthalmology Diseases of Shaanxi ProvinceXi’an 710002Shaanxi ProvinceChina

AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepithelial transition factor(MET)inhibitor SU11274 in vitro.Cell viability was detected by a Cell Counting Kit-8 assay.Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay,respectively.The expression levels of MET,phosphorylated MET,protein kinase B(AKT),and phosphorylated AKT proteins were determined by Western blot assay.The MET and phosphorylated MET proteins were also determined by immunofluorescence assay.RESULTS:HGF increased ARPE-19 cells’viability,proliferation and migration,and induced an increase of phosphorylated MET and phosphorylated AKT proteins.SU11274 significantly reduced cell viability,proliferation,and migration and decreased the expression of MET and AKT proteins.SU11274 suppressed HGF-induced increase of viability,proliferation,and migration in ARPE-19 cells.Additionally,SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins.CONCLUsiON:HGF enhances cellular viability,proliferation,and migration in RPE cells through the MET/AKT signaling pathway,whereas this enhancement is suppressed by the MET inhibitor SU11274.HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.

关键词： hepatocyte growth factor mesenchymal epithelial transition factor SU11274 retinal pigment epithelial cells

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Research progress on venous thrombosis development in patients with malignant tumors

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World Journal of Clinical Cases 2024年第11期12卷 1900-1908页

作者： Teng-Fei wang Qian Chen Jie Deng Shi-Liang Li yuan Xu si-Xing Ma Department of Vascular Surgery The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550000Guizhou ProvinceChina Department of Organ Transplantation The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550000Guizhou ProvinceChina

The coexistence of venous thromboembolism(VTE)within patients with cancer,known as cancer-associated thrombosis(CAT),stands as a prominent cause of mortality in this population.Over recent years,the incidence of VTE has demonstrated a steady increase across diverse tumor types,influenced by several factors such as patient management,tumor-specific risks,and treatment-related aspects.Furthermore,mutations in specific genes have been identified as potential contributors to increased CAT occurrence in particular cancer subtypes.We conducted an extensive review encompassing pivotal historical and ongoing studies on CAT.This review elucidates the risks,mechanisms,reliable markers,and risk assessment methodologies that can significantly guide effective interventions in clinical practice.

关键词： Malignant tumor Venous thromboembolism Cancer-associated thrombosis Research progress

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Epidemiological features of seasonal influenza transmission among 11 climate zones in Chinese mainland

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Infectious Diseases of Poverty 2024年第1期13卷 27-41页

作者： Xiaohan si Liping wang Kerrie Mengersen Wenbiao Hu Ecosystem Change and Population Health Research Group School of Public Health and Social WorkQueensland University of TechnologyBrisbaneQLD 4059Australia Information Center Chinese Center for Disease Control and PreventionBeijing 102206China School of Mathematical Sciences Queensland University of TechnologyBrisbaneQLD 4000Australia

Background Previous studies provided some evidence of meteorological factors influence seasonal influenza transmission patterns varying across regions and latitudes.However,research on seasonal influenza activities based on climate zones are still in lack.This study aims to utilize the ecological-based Koppen Geiger climate zones classif-cation system to compare the spatial and temporal epidemiological characteristics of seasonal influenza in Chinese mainland and assess the feasibility of developing an early warning system.Methods Weekly influenza cases number from 2014 to 2019 at the county and city level were sourced from China National Notifiable Infectious Disease Report Information System.Epidemic temporal indices,time series seasonality decomposition,spatial modelling theories including Moran's/and local indicators of spatial association were applied to identify the spatial and temporal patterns of influenza transmission.Results All climate zones had peaks in Winter-Spring season.Arid,desert,cold(BWk)showed up the first peak.Only Tropical,savannah(Aw)and Temperate,dry winter with hot summer(Cwa)zones had unique summer peak.Temper-ate,no dry season and hot summer(Cfa)zone had highest average incidence rate(IR)at 1.047/100,000.The Global Moran's/showed that average IR had significant clustered trend(z=53.69,Psition.Conclusions Seasonal influenza exhibited distinct spatial and temporal patterns in different climate zones.Seasonal influenza primarily emerged in BWk,subsequently in Cfa and Cwa.Cfa,Cwa and BSk pose high risk for seasonal influ-enza epidemics.The research finds will provide scientific evidence for developing seasonal infl

关键词： Seasonal influenza Koppen Geiger climate zones classification system Chinese mainland Seasonality decomposition Local indicators of spatial association

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Effects of vitamin family members on insulin resistance and diabetes complications

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World Journal of Diabetes 2024年第3期15卷 568-571页

作者： Hong-Jin Chen Min wang Ding-Min Zou Gui-You Liang si-yuan Yang Division of Cardiac Surgery Guizhou Institute of Precision MedicineThe Affiliated Hospital of Guizhou Medical UniversityGuiyang 550009Guizhou ProvinceChina Translational Medicine Research Center Guizhou Medical UniversityGuiyang 550025Guizhou ProvinceChina School of Basic Medical Sciences/School of Biology and Engineering Guizhou Medical UniversityGuiyang 550025Guizhou ProvinceChina

The following letter to the editor highlights the article“Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance”in World J Diabetes 2023 Oct 15;14(10):1514-1523.It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.

关键词： Vitamin Insulin resistance Diabetes complications Letter

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