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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 *** capability of facilitating endosomal release enhances the nanoparticles-based gene ***,little investigation has been conducted to explore its potential application in the context of viral *** Various melittin-derived peptides were inserted into the loop VIII of the capsid proteins of recombinant adeno-associated virus *** 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 *** 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 ***,the intricate details of the vector-mediated transduction mechanisms were revealed by specific pharmacological inhibitors of every stage of the rAAV2 intracellular life *** A total of 76 melittin-related peptides were compiled from existing *** them,cMA2,Melt13,p5RHH and aAR3 were found to significantly enhance the gene delivery efficiency of rAAV2 *** p5RHH-rAAV2 vectors efficiently transduced not only rAAV-potent cell lines but also cell lines previously considered resistant to ***,bafilomycin A1,a vacuolar endosome acidification inhibitor,completely inhibited the transgene expression mediated by the p5RHH-rAAV2 *** importantly,p5RHH-rAAV8 vectors also demonstrated increased hepatic transduction in vivo in C57BL/6 *** The incorporation of melittin analogues into the rAAV capsids results in a significant improvement in rAAV-mediated transgene *** 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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The Effect of Key Nodes on theMalware Dynamics in the Industrial Control Network

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Computers, Materials & Continua 2024年第4期79卷 329-349页

作者： Qiang Fu JunWang Changfu si Jiawei Liu College of Computer Science and Technology Shenyang University of Chemical TechnologyShenyang110142China College of Computer Science and Engineering Northeastern UniversityShenyang110169China

As industrialization and informatization becomemore deeply intertwined,industrial control networks have entered an era of *** connection between industrial control networks and the external internet is becoming increasingly close,which leads to frequent security *** paper proposes a model for the industrial control *** includes a malware containment strategy that integrates intrusion detection,quarantine,and ***,the role of keynodes in the spreadofmalware is studied,a comparisonexperiment is conducted to validate the impact of the containment *** addition,the dynamic behavior of the model is analyzed,the basic reproduction number is computed,and the disease-free and endemic equilibrium of the model is also obtained by the basic reproduction ***,through simulation experiments,the effectiveness of the containment strategy is validated,the influence of the relevant parameters is analyzed,and the containment strategy is *** otherwords,selective immunity to key nodes can effectively suppress the spread ofmalware andmaintain the stability of industrial control *** earlier the immunization of key nodes,the *** the time exceeds the threshold,immunizing key nodes is almost *** analysis provides a better way to contain the malware in the industrial control network.

关键词： Key nodes dynamic model industrial control network simulation

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Unraveling the biological link between diabetes mellitus and prostate cancer:Insights and implications

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World Journal of Diabetes 2024年第6期15卷 1367-1373页

作者： Jian Li Zhi-Peng Li si-si Xu Wei Wang Department of Interventional Oncology Municipal Hospital Affiliated to Taizhou UniversityTaizhou 318000Zhejiang ProvinceChina School of Medicine Taizhou UniversityTaizhou 318000Zhejiang ProvinceChina

This article is a comprehensive study based on research on the connection between diabetes mellitus(DM)and prostate cancer(PCa).It investigates the potential role of DM as an independent risk factor for PCa,delving into the biological links,including insulin resistance and hormonal *** paper critically analyzes previous studies that have shown varying results and introduces mendelian randomization as a method for establishing *** emphasizes the importance of early DM screening and lifestyle modifications in preventing PCa,and proposes future research directions for further understanding the DM-PCa relationship.

关键词： Biological mechanisms Diabetes mellitus Mendelian randomization Prevention prostatic cancer Treatment

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Switching,explosion,and chaos of multi-wavelength soliton states in ultrafast fiber lasers

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Science China(Physics,Mechanics & Astronomy) 2024年第7期67卷 82-90页

作者： Zhi-Zeng si Yue-Yue Wang Chao-Qing Dai College of Optical Mechanical and Electrical EngineeringZhejiang A&F UniversityLin’an 311300China

Because of the complexity and difficulty of realizing a multi-wavelength soliton state,reports on its internal dynamic characteristics are *** this study,the switching and periodic soliton explosion processes of the multi-wavelength soliton state in a negative dispersion passively mode-locked fiber laser are *** generation of the multi-wavelength soliton state undergoes the process of noise,oscillation,and stable mode-locking,and the splitting and annihilation of solitons with different group velocities directly impact the generation and disappearance of three *** and negative dispersion lead to different group velocities of *** presence and displacement of solitons with different group velocities cause soliton collisions,which lead to soliton explosions.A soliton experiences relative phase oscillation,chaos,and oscillation,as well as convergence and separation before and after an *** an increase in parameters related to pump power,single-soliton oscillation,multi-wavelength solitons,and chaos are found in experiments and simulations,proving the relevance and reliability between simulation and experimental *** work promotes the dynamical study of multi-soliton collisions in nonlinear science and the development of chaos theory in multi-comb lasers.

关键词： multi-wavelength fiber laser soliton explosion chaos state switching real-time dynamics

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The First Reported Case of Co-Infection with Neisseria Meningitidis and Bordetella Pertussis in the Cerebrospinal Fluid Specimen of a Normal Four-Year-Old Child

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Biomedical and Environmental Sciences 2024年第4期37卷 432-435页

作者： XIA Xian LI Guo Ming TANG Yi WANG si Quan HE Fei JIANG Yong Zhong YANG Hong Mei JIANG Hong Lin LYU Jing MAO ling Feng Hubei Key Laboratory of Edible Wild Plants Conservation&Utilization Hubei Normal UniversityHuangshi 430070HubeiChina Hubei Provincial Center for Disease Control and Prevention Wuhan 430079HubeiChina Joint Research Center for Molecular Diagnosis of Severe Infection in Children Binjiang Institute of Zhejiang UniversityHangzhou 310058ZhejiangChina

Pertussis is an acute and highly contagious respiratory disease caused by Bordetella pertussis(***),which occurs in people of all ages and is most dangerous for young children,especially *** introduction of whole-cell pertussis vaccines(wPVs)in the 1950s dramatically reduced the incidence of pertussis worldwide[1].However,over the past two decades,many studies have reported the resurgence of pertussis in different countries[2].Epidemiological surveillance in Hubei Province over the last 3 years revealed a clear increasing trend in the incidence of pertussis during the coronavirus disease 2019(COVID-19)epidemic.

关键词： Pertussis dangerous Hubei

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The noise spectral characteristics and noise reduction schemes of screw air-source heat pump:A case study

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Building simulation 2024年第1期17卷 53-70页

作者： Dongsheng Liu Yaohan Feng Jikang Jia Pengfei si Ya Feng China Southwest Architecture Design and Research Institute Co.Ltd. Chengdu 610041China CSCEC Green Construction Engineering Research Center Chengdu 610041China

The screw air-source heat pump can cause incessant high noise levels during operation,which might hinder adoption of this energy-efficient heat ***,acoustic measurements and comparison testing were performed in this *** measurements revealed that the compressor is the main noise source of the heat pump,and it shows a multipeak frequency distribution and a wide frequency spectrum under different work conditions,with multiple peaks at 63,250,and 1000 ***,a compressor sound insulation cover with broadband absorption was proposed,and it was experimentally proven that the insulation cover can reduce the maximum sound pressure level of one unit from 89.8 dBA to 79.1 ***,we proposed several noise reduction strategies and compared their noise reduction effects using computer *** results showed that the noise problem can be effectively improved through the rational design of the sound barrier and the layout and opening options of heat *** distance between the sound barrier and heat pump and the sound attenuation due to diffraction ALa exhibit a U-shaped *** buildings of different heights,the optimal heights of noise barrier are *** 5.5-meter is the optimal height of the sound barrier for single-story *** conclusions can be applied to other building projects for heat pump noise reduction.

关键词： acoustic simulation broadband noise noise reduction air-source heat pump sound barrier

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Structure and 2p decay mechanism of^(18)Mg

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Nuclear Science and Techniques 2024年第6期35卷 145-154页

作者： Long Zhou De-Qing Fang si-Min Wang Hui Hua Key Laboratory of Nuclear Physics and Ion-beam Application(MOE) Institute of Modern PhysicsFudan UniversityShanghai 200433China Shanghai Research Center for Theoretical Nuclear Physics NSFC and Fudan UniversityShanghai 200438China School of Physics and State Key Laboratory of Nuclear Physics and Technology Peking UniversityBeijing 100871China

The recently discovered,extremely proton-rich nuclide 18 Mg exhibits ground-state decay via two sequential two-proton(2p)emissions through the intermediate nucleus,*** study investigates the structure and the initial 2p decay mechanism of^(18)Mgby examining the density and correlations of the valence protons using a three-body Gamow coupled-channel *** results show that the ground state of^(18)Mgis significantly influenced by the continuum,resulting in a significant s-wave ***,based on the current framework,this does not lead to a significant deviation in mirror symmetry in either the structure or spectroscopy of the 18Mg-18C ***,the time evolution analysis of the^(18)Mgground state suggests a simultaneous 2p emission during the first step of *** observed nucleon-nucleon correlations align with those of the light-mass 2p emitters,indicating a consistent decay behavior within this nuclear region.

关键词： Structure of^(18)Mg Two-proton decay Proton-proton correlation

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Emergence of SARS and COVID-19 and preparedness for the next emerging disease X

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Frontiers of Medicine 2024年第1期18卷 1-18页

作者： Ben Hu Hua Guo Haorui si Zhengli Shi CAS Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing100049China

Severe acute respiratory syndrome(SARS)and Coronavirus disease 2019(COVID-19)are two human Coronavirus diseases emerging in this century,posing tremendous threats to public health and causing great loss to lives and *** this review,we retrospect the studies tracing the molecular evolution of SARS-CoV,and we sort out current research findings about the potential ancestor of *** knowledge about SARS-CoV-2-like viruses found in wildlife,the animal susceptibility to SARS-CoV-2,as well as the interspecies transmission risk of SARS-related coronaviruses(SARSr-CoVs)are gathered ***,we discuss the strategies of how to be prepared against future outbreaks of emerging or re-emerging coronaviruses.

关键词： SARS COVID-19 coronavirus

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Hydrophobic tag tethering degrader as a promising paradigm of protein degradation:Past,present and future perspectives

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Chinese Chemical Letters 2024年第8期35卷 187-200页

作者： si Ha Jiacheng Zhu Hua Xiang Guoshun Luo State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry China Pharmaceutical UniversityNanjing 211198China

Small molecule inhibitors have dominated the pharmaceutical landscape for a long time as the primary therapeutic paradigm targeting pathogenic ***,their efficacy heavily relies on the amino acid composition and spatial constitution of proteins,rendering them susceptible to drug resistance and failing to target undruggable *** recent years,the advent of targeted protein degradation(TPD)technology has captured substantial attention from both industry and *** an event-driven mode,TPD offers a novel approach to eliminate pathogenic proteins by promoting their degrada-tion,thus circumventing the limitations associated with traditional small molecule ***-bic tag tethering degrader(HyTTD)technology represents one such TPD approach that is currently in the burgeoning *** employ endogenous protein degradation systems to induce the degrada-tion of target proteins through the proteasome pathway,which displays significant potential for medical *** this review,we provide a comprehensive overview of the development history and the reported mechanism of action of ***,we delve into the physiological roles,structure-activity re-lationships,and medical implications of HyTTDs targeting various disease-associated ***,we propose insights into the challenges that necessitate resolution for the successful development of HyTTDs,with the ultimate goal of initiating a new age of clinical treatment leveraging the immense po-tential of HyTTDs.

关键词： Targeted protein degradation(TPD) Hydrophobic tag Degrader Hydrophobic tag tethering degrader(HyTTD) Targeted therapy

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Atomically Substitutional Engineering of Transition Metal Dichalcogenide Layers for Enhancing Tailored Properties and Superior Applications

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Nano-Micro Letters 2024年第5期16卷 248-284页

作者： Zhaosu Liu si Yin Tee Guijian Guan Ming‑Yong Han Institute of Molecular Plus Tianjin UniversityTianjin 300072People’s Republic of China Institute of Materials Research and Engineering A*STARSingapore 138634Singapore

Transition metal dichalcogenides(TMDs)are a promising class of layered materials in the post-graphene era,with extensive research attention due to their diverse alternative elements and fascinating semiconductor *** MX2 layers with different metal and/or chalcogen elements have similar structural parameters but varied optoelectronic properties,providing opportunities for atomically substitutional engineering via partial alteration of metal or/and chalcogenide atoms to produce ternary or quaternary *** resulting multinary TMD layers still maintain structural integrity and homogeneity while achieving tunable(opto)electronic properties across a full range of composition with arbitrary ratios of introduced metal or chalcogen to original counterparts(0–100%).Atomic substitution in TMD layers offers new adjustable degrees of freedom for tailoring crystal phase,band alignment/structure,carrier density,and surface reactive activity,enabling novel and promising *** review comprehensively elaborates on atomically substitutional engineering in TMD layers,including theoretical foundations,synthetic strategies,tailored properties,and superior *** emerging type of ternary TMDs,Janus TMDs,is presented specifically to highlight their typical compounds,fabrication methods,and potential ***,opportunities and challenges for further development of multinary TMDs are envisioned to expedite the evolution of this pivotal field.

关键词： Transition metal dichalcogenides Atomic substitution Tailored structure Tunable bandgap Enhanced applications

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