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Melittin analog p5RHH enhances recombinant adeno-associated virus transduction efficiency

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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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元素取代对Ge-As(Sb)-Se玻璃转变阈值行为的影响

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物理学报 2024年第5期73卷 297-303页

作者：许思维王训四沈祥湖南文理学院数理学院常德415000 宁波大学高等技术研究院浙江省光电探测材料及器件重点实验室宁波315211

本文针对Sb取代As元素对Ge_(x)As(Sb)_(20)Se_(80-x)玻璃阈值行为的影响进行研究.对理想共价网络玻璃GexAs20Se80-x的玻璃转变温度、密度和折射率等物理参数进行了系统测量,在其平均配位数为2.4和2.67处验证了转变阈值的存在,这两个转... 详细信息

本文针对Sb取代As元素对Ge_(x)As(Sb)_(20)Se_(80-x)玻璃阈值行为的影响进行研究.对理想共价网络玻璃GexAs20Se80-x的玻璃转变温度、密度和折射率等物理参数进行了系统测量,在其平均配位数为2.4和2.67处验证了转变阈值的存在,这两个转变分别代表玻璃内部的共价网络结构从欠限制的松散状态到过限制的紧致状态的转变和从二维到三维紧致状态的转变.但是,当金属性更强的Sb取代As时,得到的非理想共价网络玻璃Ge_(x)Sb_(20)Se_(80-x)则会引起转变阈值的变化,转变阈值改变为化学计量组成.进一步利用拉曼散射技术对其结构进行表征,并将拉曼光谱通过分峰拟合分解成不同的结构单元的特征峰,它们各自的强度变化表现出相同的行为,这归因于As和Sb的原子半径差异较大所引起的化学效应以及Sb元素具有较强的离子特性.

关键词：硫系玻璃玻璃转变拉曼散射

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Cardiac-Adaptive Conductive Hydrogel Patch Enabling Construction of Mechanical–Electrical Anisotropic Microenvironment for Heart Repair

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Research 2024年第1期2023卷 489-507页

作者： Xiaoping Song Jifeng Zhang si Shen Dan Liu Jie Zhang Wenming Yin Genlan Ye Leyu wang Liu Cai Honghao Hou Xiaozhong Qiu Central Laboratory The Fifth Affiliated HospitalSouthern Medical UniversityGuangzhouGuangdong 510910China Department of Anatomy Neuroscience Laboratory for Cognitive and Developmental DisordersMedical College of Jinan UniversityGuangzhou 510630China Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering School of Basic Medical ScienceBiomaterials Research CenterSchool of Biomedical EngineeringSouthern Medical UniversityGuangzhouGuangdong 510515China

The biomimetic construction of a microstructural–mechanical–electrical anisotropic microenvironment adaptive to the native cardiac tissue is essential to repair myocardial infarction(MI).Inspired by the 3D anisotropic characteristic of the natural fish swim bladder(FSB),a novel flexible,anisotropic,and conductive hydrogel was developed for tissue-specific adaptation to the anisotropic structural,conductive,and mechanical features of the native cardiac extracellular matrix.The results revealed that the originally stiff,homogeneous FSB film was tailored to a highly flexible anisotropic hydrogel,enabling its potential as a functional engineered cardiac patch(ECP).In vitro and in vivo experiments demonstrated the enhanced electrophysiological activity,maturation,elongation,and orientation of cardiomyocytes(CMs),and marked MI repair performance with reduced CM apoptosis and myocardial fibrosis,thereby promoting cell retention,myogenesis,and vascularization,as well as improving electrical integration.Our findings offer a potential strategy for functional ECP and provides a novel strategy to bionically simulate the complex cardiac repair environment.

关键词： bladder thereby patch

Alkaline sphingomyelinase deficiency impairs intestinal mucosal barrier integrity and reduces antioxidant capacity in dextran sulfate sodium-induced colitis

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World Journal of Gastroenterology 2024年第10期30卷 1405-1419页

作者： Ye Tian Xin Li Xu wang si-Ting Pei Hong-Xin Pan Yu-Qi Cheng Yi-Chen Li Wen-Ting Cao Jin-Dong Ding Petersen Ping Zhang International School of Public Health and One Health Hainan Medical UniversityHaikou 571199Hainan ProvinceChina Medical Laboratory Science and Technology College Harbin Medical University-Daqing CampusDaqing 163000Heilongjiang ProvinceChina Department of Laboratory Diagnosis Qiqihar Tuberculosis Control CenterQiqihar 161000Heilongjiang ProvinceChina Department of Public Health University of CopenhagenCopenhagen 1353Denmark Department of Public Health University of Southern DenmarkOdense 5000Denmark

BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported to play an anti-inflammatory role.However,the underlying mechanism is still unclear.AIM To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium(DSS)-induced colitis.METHODS Mice were administered 3%DSS drinking water,and disease activity index was determined to evaluate the status of colitis.Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran,and bacterial translocation was evaluated by measuring serum lipopolysaccharide.Intestinal epithelial cell ultrastructure was observed by electron microscopy.Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA,respectively.Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels.RESULTS Compared to wild-type(WT)mice,inflammation and intestinal permeability in alk-SMase knockout(KO)mice were more severe beginning 4 d after DSS induction.The mRNA and protein levels of intestinal barrier proteins,including zonula occludens-1,occludin,claudin-3,claudin-5,claudin-8,mucin 2,and secretory immunoglobulin A,were significantly reduced on 4 d after DSS treatment.Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells.Furthermore,by day 4,mitochondria appeared swollen and degenerated.Additionally,compared to WT mice,serum malondialdehyde levels in KO mice were higher,and the antioxidant capacity was significantly lower.The expression of the transcription factor nuclear factor erythroid 2-related factor 2(Nrf2)in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment.mRNA levels of Nrf2-re

关键词： Alkaline sphingomyelinase Intestinal mucosal barrier Antioxidant capacity Dextran sulfate sodium-induced colitis nuclear factor erythroid 2-related factor 2

A New Industrial Intrusion Detection Method Based on CNN-BiLSTM

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Computers, Materials & Continua 2024年第6期79卷 4297-4318页

作者： Jun wang Changfu si Zhen wang Qiang Fu College of Computer Science and Technology Shenyang University of Chemical TechnologyShenyang110142China

Nowadays,with the rapid development of industrial Internet technology,on the one hand,advanced industrial control systems(ICS)have improved industrial production efficiency.However,there are more and more cyber-attacks targeting industrial control systems.To ensure the security of industrial networks,intrusion detection systems have been widely used in industrial control systems,and deep neural networks have always been an effective method for identifying cyber attacks.Current intrusion detection methods still suffer from low accuracy and a high false alarm rate.Therefore,it is important to build a more efficient intrusion detection model.This paper proposes a hybrid deep learning intrusion detection method based on convolutional neural networks and bidirectional long short-term memory neural networks(CNN-BiLSTM).To address the issue of imbalanced data within the dataset and improve the model’s detection capabilities,the Synthetic Minority Over-sampling Technique-Edited Nearest Neighbors(SMOTE-ENN)algorithm is applied in the preprocessing phase.This algorithm is employed to generate synthetic instances for the minority class,simultaneously mitigating the impact of noise in the majority class.This approach aims to create a more equitable distribution of classes,thereby enhancing the model’s ability to effectively identify patterns in both minority and majority classes.In the experimental phase,the detection performance of the method is verified using two data sets.Experimental results show that the accuracy rate on the CICIDS-2017 data set reaches 97.7%.On the natural gas pipeline dataset collected by Lan Turnipseed from Mississippi State University in the United States,the accuracy rate also reaches 85.5%.

关键词： Intrusion detection convolutional neural network bidirectional long short-term memory neural network multi-head self-attention mechanism

A universal polymer-assisted route to fabricate Zr-doped TiO2 nanocomposite: boosting reactive desulfurization

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Tungsten 2024年第3期6卷 596-609页

作者： Yue Du Ping Li Zhi-Yi Zhong Wen-Xue Chen Yi-si Liu Yun-Long Xie Li-Na Zhou Kai wang Hubei Key Laboratory of Photoelectric Materials and Devices College of Material Science and Engineering Hubei Normal University National Laboratory of Solid State Microstructures Nanjing University College of Urban and Environmental Sciences Huangshi Key Laboratory of Prevention and Control of Soil Pollution Hubei Normal University School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University

A series of transition metal ion-doped TiO2composites were prepared by polyethyleneimine-assisted solvent-free selfassembly.Due to the similar electronegativity and ionic radius of Ti and Zr ions,the introduction of Zr element to TiO2can effectively improve its surface acidity and introduce more defect sites on the TiO2framework.As-fabricated Zr-doped TiO2nanocomposite exhibits the formation of Zr-Ti bond,strong surface acidity,connected mesoporous channels,and relatively high crystallinity.These remarkable properties contribute to its adsorption-oxidation-desulfurization capacity toward thiophene-type sulfides,which can remove 500 ×10-6dibenzothiophene from the model fuel within 100 min at low reaction temperatures.The polymer-induced self-assembly method can reduce organic solvent usage,pollutant emissions,and energy consumption,which provides an efficient and practical way to prepare porous metal oxide-based catalysts in future.

关键词： Oxidative desulfurization Transition metal ion-doped TiO 2 nanocomposite Dibenzothiophene Solvent-free self-assembly method

Four-Octyl itaconate ameliorates periodontal destruction via Nrf2-dependent antioxidant system

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International Journal of Oral Science 2022年第3期14卷 297-308页

作者： Liangjing Xin Fuyuan Zhou Chuangwei Zhang Wenjie Zhong Shihan Xu Xuan Jing Dong wang si wang Tao Chen Jinlin Song College of Stomatology Chongqing Medical UniversityChongqing Key Laboratory for Oral Diseases and Biomedical SciencesChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationChongqingChina Department of Ultrasound The First Affiliated HospitalChongqing Medical UniversityChongqingChina

Periodontitis is a widespread oral disease characterized by continuous inflammation of the periodontal tissue and an irreversible alveolar bone loss, which eventually leads to tooth loss. Four-octyl itaconate(4-OI) is a cell-permeable itaconate derivative and has been recognized as a promising therapeutic target for the treatment of inflammatory diseases. Here, we explored, for the first time,the protective effect of 4-OI on inhibiting periodontal destruction, ameliorating local inflammation, and the underlying mechanism in periodontitis. Here we showed that 4-OI treatment ameliorates inflammation induced by lipopolysaccharide in the periodontal microenvironment. 4-OI can also significantly alleviate inflammation and alveolar bone loss via Nrf2 activation as observed on samples from experimental periodontitis in the C57BL/6 mice. This was further confirmed as silencing Nrf2 blocked the antioxidant effect of 4-OI by downregulating the expression of downstream antioxidant enzymes. Additionally, molecular docking simulation indicated the possible mechanism under Nrf2 activation. Also, in Nrf2-/-mice, 4-OI treatment did not protect against alveolar bone dysfunction due to induced periodontitis, which underlined the importance of the Nrf2 in 4-OI mediated periodontitis treatment.Our results indicated that 4-OI attenuates inflammation and oxidative stress via disassociation of KEAP1-Nrf2 and activation of Nrf2 signaling cascade. Taken together, local administration of 4-OI offers clinical potential to inhibit periodontal destruction,ameliorate local inflammation for more predictable periodontitis.

关键词： Four-Octyl itaconate ameliorates periodontal destruction via Nrf2-dependent antioxidant system

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Inhibition of hepatitis B virus via selective apoptosis modulation by Chinese patent medicine Liuweiwuling Tablet

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World Journal of Gastroenterology 2024年第13期30卷 1911-1925页

作者： Fei-Lin Ge Yan Yang Lan-Lan si Yuan-Hua Li Meng-Zhen Cao Jun wang Zhao-Fang Bai Zhi-Gang Ren Xiao-He Xiao Yan Liu Department of Chinese Medicine State Key Laboratory of Antiviral DrugsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina The Fifth Medical Center of Chinese PLA General Hospital Beijing 100039China College of Traditional Chinese Medicine Chongqing Medical UniversityChongqing 400010China Beijing Key Laboratory of Emerging Infectious Diseases Peking University Ditan Teaching HospitalBeijing 100015China Department of Infectious Diseases State Key Laboratory of Antiviral Drugsthe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina

BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)infection.Previous studies have indicated an anti-HBV effect of LWWL,specifically in terms of antigen inhibition,but the underlying mechanism remains unclear.AIM To investigate the potential mechanism of action of LWWL against HBV.METHODS In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell lines.The in vivo experiment involved a hydrodynamic injectionmediated mouse model with HBV replication.Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL.RESULTS In HepG2.1403F cells,LWWL(0.8 mg/mL)exhibited inhibitory effects on HBV DNA,hepatitis B surface antigen and pregenomic RNA(pgRNA)at rates of 51.36%,24.74%and 50.74%,respectively.The inhibition rates of LWWL(0.8mg/mL)on pgRNA/covalently closed circular DNA in HepG2.1403F,HepG2.2.15 and HepG2.A64 cells were 47.78%,39.51%and 46.74%,respectively.Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis(PI3K-AKT,CASP8-CASP3 and P53 pathways).Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group(CG)among HBV-replicating cell lines,including HepG2.2.15(2.92%±1.01%vs 6.68%±2.04%,Psignificant differences in apoptosis rates between the non-HBV-replicating HepG2 cells(5.04%±0.74%vs 5.51%±1.57%,P>0.05),L02 cells(5.49%±0.80%vs 5.48%±1.01%,P>0.05)and LX2 cells(6.29%±1.54%vs 6.29%±0.88%,P>0.05).TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBVreplicating mouse model,while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replicating mouse m

关键词： Hepatitis B virus Chinese patent medicine Antiviral activity Antiviral mechanism Selective apoptosis

A Post-Quantum Cross-Domain Authentication Scheme Based on Multi-Chain Architecture

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Computers, Materials & Continua 2024年第2期78卷 2813-2827页

作者： Yi-Bo Cao Xiu-Bo Chen Yun-Feng He Lu-Xi Liu Yin-Mei Che Xiao wang Ke Xiao Gang Xu si-Yi Chen Information Security Center State Key Laboratory ofNetworking and Switching TechnologyBeijing University of Posts and TelecommunicationsBeijing100876China Information Center of China North Industries Group Corporation Beijing100089China School of Information Science and Technology North China University of TechnologyBeijing100144China

Due to the rapid advancements in network technology,blockchain is being employed for distributed data storage.In the Internet of Things(IoT)scenario,different participants manage multiple blockchains located in different trust domains,which has resulted in the extensive development of cross-domain authentication techniques.However,the emergence of many attackers equipped with quantum computers has the potential to launch quantum computing attacks against cross-domain authentication schemes based on traditional cryptography,posing a significant security threat.In response to the aforementioned challenges,our paper demonstrates a post-quantum cross-domain identity authentication scheme to negotiate the session key used in the cross-chain asset exchange process.Firstly,our paper designs the hiding and recovery process of user identity index based on lattice cryptography and introduces the identity-based signature from lattice to construct a post-quantum cross-domain authentication scheme.Secondly,our paper utilizes the hashed time-locked contract to achieves the cross-chain asset exchange of blockchain nodes in different trust domains.Furthermore,the security analysis reduces the security of the identity index and signature to Learning With Errors(LWE)and Short Integer Solution(siS)assumption,respectively,indicating that our scheme has post-quantum security.Last but not least,through comparison analysis,we display that our scheme is efficient compared with the cross-domain authentication scheme based on traditional cryptography.

关键词： Cross-domain identity authentication lattice-based cryptography blockchain hashed time-locked contract