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SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular Cl^(-)concentration

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1745-1759页

作者： Jian-Bang Xu Wei-Jie Guan Yi-Lin Zhang Zhuo-Er Qiu Lei Chen Xiao-Chun Hou Junqing yue yu-yun zhou Jie Sheng Lei Zhao yun-Xin Zhu Jing Sun Jincun Zhao Wen-Liang zhou Nan-Shan Zhong State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseNational Center for Respiratory MedicineDepartment of Respiratory and Critical Care MedicineGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Department of Thoracic Surgery Guangzhou Institute for Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Guangzhou National Laboratory GuangzhouP.R.China School of Life Sciences Sun Yat-sen UniversityGuangzhouP.R.China Guangdong Provincial Key Laboratory of Pharmaceutical Functional Genes School of Life SciencesSun Yat-sen UniversityGuangzhouP.R.China Department of Physiology School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhouP.R.China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection disrupts the epithelial barrier and triggers airway *** envelope(E)protein,a core virulence structural component of coronaviruses,may play a role in this *** could interfere with transepithelial Cl^(-)transport via impairment of the cystic fibrosis transmembrane conductance regulator(CFTR),which modulates nuclear factor kB(NF-kB)***,the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function,Cl^(-)transport and the robust inflammatory response remain to be ***,we have demonstrated that E protein down-regulated the expression of tight junctional proteins,leading to the disruption of the airway epithelial *** addition,E protein triggered the activation of Toll-like receptor(TLR)2/4 and downstream c-Jun N-terminal kinase(JNK)signaling,resulting in an increased intracellular Cl^(-)concentration([Cl^(-)]_(i))via up-regulating phosphodiesterase 4D(PDE4D)expression in airway epithelial *** elevated[Cl^(-)]_(i);contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1(SGK1).Moreover,blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E ***,these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.

关键词： airway inflammation elevated

靶向β-淀粉样蛋白的阿尔茨海默病免疫治疗研究进展

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国际药学研究杂志 2016年第2期43卷 216-223页

作者：余云舟徐青军事医学科学院生物工程研究所北京100071 北京交通大学生命科学与生物工程研究院北京100044

阿尔茨海默病是一种以认知功能障碍和记忆减退为主要特征的神经退行性疾病,主要神经病理学表现包括细胞外淀粉样蛋白堆积形成的老年斑、细胞内tau蛋白磷酸化形成的神经原纤维缠结,以及神经元的坏死。淀粉样蛋白级联假说认为,β-淀粉样... 详细信息

阿尔茨海默病是一种以认知功能障碍和记忆减退为主要特征的神经退行性疾病,主要神经病理学表现包括细胞外淀粉样蛋白堆积形成的老年斑、细胞内tau蛋白磷酸化形成的神经原纤维缠结,以及神经元的坏死。淀粉样蛋白级联假说认为,β-淀粉样蛋白的过量生成和积累是阿尔茨海默病致病的始发因素和中心环节。以β-淀粉样蛋白为靶标的主动免疫和被动免疫方法可能是最有希望治疗阿尔茨海默病的策略之一。本综述主要关注以β-淀粉样蛋白为靶标的阿尔茨海默病主动和被动免疫治疗方法,分析目前临床前研究和临床试验结果,探讨该领域的应用前景和发展方向,提出新一代有效疫苗的设计策略。

关键词：阿尔茨海默病 β-淀粉样蛋白免疫治疗疫苗抗体

Integration of Electrical Properties and Polarization Loss Modulation on Atomic Fe–N‑RGO for Boosting Electromagnetic Wave Absorption

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Nano-Micro Letters 2025年第2期17卷 517-532页

作者： Kaili Zhang yuefeng Yan Zhen Wang Guansheng Ma Dechang Jia Xiaoxiao Huang yu zhou State Key Laboratory of Precision Welding&Joining of Materials and Structures Harbin Institute of TechnologyHarbin 150001People’s Republic of China School of Materials Science and Engineering Harbin Institute of TechnologyHarbin 150001People’s Republic of China MIIT Key Laboratory of Advanced Structural‑Functional Integration Materials&Green Manufacturing Technology Harbin Institute of TechnologyHarbin 150001People’s Republic of China

Developing effective strategies to regulate graphene’s conduction loss and polarization has become a key to expanding its application in the electromagnetic wave absorption(EMWA)*** on the unique energy band structure of graphene,regulating its bandgap and electrical properties by introducing heteroatoms is considered a feasible ***,metal-nitrogen doping reduced graphene oxide(M–N-RGO)was prepared by embedding a series of single metal atoms M–N_(4) sites(M=Mn,Fe,Co,Ni,Cu,Zn,Nb,Cd,and Sn)in RGO using an N-coordination atom-assisted *** composites had adjustable conductivity and polarization to optimize dielectric loss and impedance matching for efficient EMWA *** results showed that the minimum reflection loss(RL_(min))of Fe–N-RGO reaches−74.05 dB(2.0 mm)and the maximum effective absorption bandwidth(EAB_(max))is 7.05 GHz(1.89 mm)even with a low filler loading of only 1 wt%.Combined with X-ray absorption spectra(XAFS),atomic force microscopy,and density functional theory calculation analysis,the Fe–N_(4) can be used as the polarization center to increase dipole polarization,interface polarization and defect-induced polarization due to d-p orbital hybridization and structural ***,electron migration within the Fe further leads to conduction loss,thereby synergistically promoting energy *** study demonstrates the effectiveness of metal-nitrogen doping in regulating the graphene′s dielectric properties,which provides an important basis for further investigation of the loss mechanism.

关键词： Electromagnetic wave absorption Fe-N-RGO Dipole polarization Conduction loss Impedance matching

基于DNA和RNA的双功能Semliki森林病毒复制子载体的构建

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生物工程学报 2005年第5期21卷 713-718页

作者：余云舟孙志伟俞炜源军事医学科学院生物工程研究所北京100071

以semliki森林病毒衍生的复制子载体pSFV1和辅助载体pSFVhelper2为骨架,用CMVIE和T7启动子替换SP6启动子并在3′UTR下游插入BGH转录终止子,构建了基于DNA和RNA的复制子表达载体pSMCTA和辅助载体pSHCTA。在DNA和RNA二种递送方式上证实该... 详细信息

以semliki森林病毒衍生的复制子载体pSFV1和辅助载体pSFVhelper2为骨架,用CMVIE和T7启动子替换SP6启动子并在3′UTR下游插入BGH转录终止子,构建了基于DNA和RNA的复制子表达载体pSMCTA和辅助载体pSHCTA。在DNA和RNA二种递送方式上证实该表达载体可高水平表达外源基因,与辅助载体共转染可制备具有感染能力并能表达外源基因的重组病毒颗粒。构建的基于DNA和RNA的双功能复制子载体显著地提高SFV载体应用范围,在体外可用于高水平表达外源基因及大规模制备重组病毒颗粒,在体内也可用于研制复制子疫苗和基因治疗载体。

关键词： semliki森林病毒 RNA复制子双功能复制子载体

基于DNA的Semliki森林病毒复制子载体体内外高水平表达外源基因

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生物化学与生物物理进展 2006年第1期33卷 87-94页

作者：余云舟孙志伟刘志刚俞炜源军事医学科学院生物工程研究所北京100071

基于DNA的复制子载体显著地提高了复制子载体的应用范围,在体外可用于高水平表达外源基因,大规模制备重组病毒颗粒,在体内可用于复制子疫苗和基因治疗载体研究.将复制子RNA的cDNA置于RNA聚合酶Ⅱ启动子和转录终止子控制下时,基于RNA的... 详细信息

基于DNA的复制子载体显著地提高了复制子载体的应用范围,在体外可用于高水平表达外源基因,大规模制备重组病毒颗粒,在体内可用于复制子疫苗和基因治疗载体研究.将复制子RNA的cDNA置于RNA聚合酶Ⅱ启动子和转录终止子控制下时,基于RNA的复制子载体可转变为基于DNA的复制子载体.当DNA载体转染细胞后,第一阶段,RNA聚合酶Ⅱ启动子在核内起始合成RNA,经过加工和修饰后运输到细胞质中,相当于复制子RNA,第二阶段,该RNA自我复制及表达外源基因,相当于病毒RNA复制循环.在成功地构建了基于DNA和RNA的双功能复制子表达载体pSCTA和辅助载体pSHCTA的基础上,为了获得高效的基于DNA的复制子载体,对其进行改进而构建了共4种不同的基于DNA的semliki森林病毒复制子,通过对表达载体和相应的辅助载体表达报告基因及对制备重组病毒颗粒的能力进行比较,获得了复制能力提高的复制子载体pSCAR和pSHCAR.该表达载体pSCAR可高水平表达外源基因,与辅助载体pSHCAR共转染可制备高滴度的重组病毒颗粒,并且也能表达抗原基因.另外,报告基因在DNA复制子载体注射的小鼠体内得到了高水平表达,并且DNA免疫小鼠后也诱导产生高滴度特异性抗体以及细胞免疫反应.结果表明,经过改造SFV复制子载体,获得了高效的基于DNA的SFV复制子载体.该复制子载体增强了原复制子载体应用能力,并有潜力作为复制子疫苗和基因治疗载体.

关键词： semliki森林病毒 RNA复制子 DNA 重组病毒颗粒疫苗

Mechanistic insight into the synergy between nickel single atoms and nanoparticles on N-doped carbon for electroreduction of CO2

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Journal of Energy Chemistry 2025年第1期100卷 327-336页

作者： Mingdong Sun Wenwen Guan Cailing Chen Chao Wu Xiaoling Liu Biao Meng Tao Chen yu Han Jun Wang Shibo Xi yu zhou State Key Laboratory of Materials-Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University Advanced Membranes and Porous Materials Center Physical Sciences and Engineering Division King Abdullah University of Science and Technology Institute of Sustainability for Chemicals Energy and Environment A*STAR (Agency for Science Technology and Research) College of Materials Science and Engineering Sichuan University

The synergy of single atoms （SAs） and nanoparticles （NPs） has demonstrated great potential in promoting the electrocatalytic carbon dioxide reduction reaction （CO2RR）;however,the rationalization of the SAs/NPs proportion remains one challenge for the catalyst ***,a Ni2+-loaded porous poly（ionic liquids）(PIL) precursor synthesized through the free radical self-polymerization of the ionic liquid monomer,1-allyl-3-vinylimidazolium chloride,was pyrolyzed to prepare the Ni,N co-doped carbon materials,in which the proportion of Ni SAs and NPs could be facilely modulated by controlling the annealing *** catalyst Ni-NC-1000 with a moderate proportion of Ni SAs and NPs exhibited high efficiency in the electrocatalytic conversion of CO2into *** Ni K-edge X-ray absorption near-edge structure （XANES） spectra and theoretical calculations were conducted to gain insight into the synergy of Ni SAs and *** charge transfer from Ni NPs to the surrounding carbon layer and then to the Ni SAs resulted in the electron-enriched Ni SAs active *** the electroreduction of CO2,the coexistence of Ni SAs and NPs strengthened the CO2activation and the affinity towards the key intermediate of*COOH,lowering the free energy for the potential-determining*CO2→*COOH step,and therefore promoted the catalysis efficiency.

关键词： Activation energy

A型肉毒毒素轻链抑制剂CPI-1衍生物的合成及活性评价

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军事医学 2018年第11期42卷 856-860页

作者：沈锦涛余硕周良燚余云舟戴秋云军事科学院军事医学研究院生物工程研究所北京100071

目的在A型肉毒毒素轻链多肽抑制剂CPI-1引入穿膜序列,提高其抑制活性。方法基于CPI-1序列,在N端或C端增加穿膜序列Angiopep-2(Ang)或多聚精氨酸(R8),固相合成线性肽,空气氧化折叠形成目标产物,经RP-HPLC纯化得纯肽。表达A型肉毒毒素轻... 详细信息

目的在A型肉毒毒素轻链多肽抑制剂CPI-1引入穿膜序列,提高其抑制活性。方法基于CPI-1序列,在N端或C端增加穿膜序列Angiopep-2(Ang)或多聚精氨酸(R8),固相合成线性肽,空气氧化折叠形成目标产物,经RP-HPLC纯化得纯肽。表达A型肉毒毒素轻链截短体LC424,合成含荧光基团与淬灭基团的肉毒毒素轻链水解底物SNAPtide,采用荧光共振能量转移法(FRET)测定各多肽对肉毒毒素轻链的抑制活性,小鼠攻毒测定各肽体内活性。结果将Ang连接于CPI-1的N端或C端后,Ang-CPI-1、Ang-GG-CPI-1、CPI-1-Ang以及CPI-1-GG-Ang的IC_(50)值分别为148. 2、251. 9、88. 1、90. 9 nmol/L,相比于CPI-1(IC_(50)=411. 9 nmol/L)活性提升1～3倍;多聚精氨酸接入CPI-1的N端后导致抑制活性丧失。结论在CPI-1的N端和C端增加Ang肽能提升其对A型肉毒毒素轻链抑制活性,但不能增加体内活性。

关键词：肉毒杆菌毒素,A型多肽抑制剂荧光共振能量转移

Effects of ultrasonic-assisted extraction on bioactive compounds,volatile flavors and antioxidant activities of vine tea water extracts

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Traditional Medicine Research 2025年第1期10卷 73-81页

作者： Xiao-Long zhou Wei-Jin Jiang Ji yu Mao-Jun Yao yun-Tong Li Hunan Provincial Key Laboratory of Research Resource Mining and High-valued Utilization on Edible&Medicinal PlantCollege of Chemistry and Chemical EngineeringJishou UniversityJishou 416000China Hunan Gaoge Dairy Co. Ltd.Changsha 410000China

Background:Ampelopsis grossedentata,vine tea,which is the tea alternative beverages in *** vine tea processing,a large amount of broken tea is produced,which has low commercial ***:This study investigates the influence of different extraction methods(room temperature water extraction,boiling water extraction,ultrasonic-assisted room temperature water extraction,and ultrasonic-assisted boiling water extraction,referred to as room temperature water extraction(RE),boiling water extraction(BE),ultrasonic assistance at room temperature water extraction(URE),and ultrasonic assistance in boiling water extraction(UBE))on the yield,dihydromyricetin(DMY)content,free amino acid composition,volatile aroma components,and antioxidant properties of vine tea ***:A notable influence of extraction temperature on the yield of vine tea extracts(P<0.05),with BE yielding the highest at 43.13±0.26%,higher than that of RE(34.29±0.81%).Ultrasound-assisted extraction significantly increased the DMY content of the extracts(P<0.05),whereas DMY content in the RE extracts was 59.94±1.70%,that of URE reached 66.14±2.78%.Analysis revealed 17 amino acids,with L-serine and aspartic acid being the most abundant in the extracts,nevertheless ultrasound-assisted extraction reduced total free amino acid *** chromatography-mass spectrometry analysis demonstrated an increase in the diversity and quantity of compounds in the vine tea water extracts obtained through ultrasonic-assisted ***,69 and 68 volatile compounds were found in URE and UBE extracts,which were higher than the number found in RE and BE *** vitro,antioxidant activity assessments revealed varying antioxidant capacities among different extraction methods,with RE exhibiting the highest DPPH scavenging rate,URE leading in ABTS•+free radical scavenging,and BE demonstrating superior ferric ion reducing antioxidant ***:The findings suggest that extraction methods signi

关键词： vine tea dihydromyricetin ultrasonic-assisted extraction volatile aroma components

E型肉毒神经毒素重组Hc-C亚单位疫苗免疫原性研究

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军事医学 2019年第5期43卷 346-351页

作者：李珍徐青余云舟北京交通大学生命科学与生物工程研究院北京100044 军事科学院军事医学研究院生物工程研究所北京100071

目的利用大肠杆菌高效表达并纯化E型肉毒神经毒素(BoNT/E)受体结合区Hc的亚结构域EHc C蛋白,并进行免疫原性研究。方法利用PCR技术扩增出EHc C基因,克隆于载体pTIG Trx His tag中得到重组质粒pTIG Trx EHc C,转入表达菌株BL21(DE3),经I... 详细信息

目的利用大肠杆菌高效表达并纯化E型肉毒神经毒素(BoNT/E)受体结合区Hc的亚结构域EHc C蛋白,并进行免疫原性研究。方法利用PCR技术扩增出EHc C基因,克隆于载体pTIG Trx His tag中得到重组质粒pTIG Trx EHc C,转入表达菌株BL21(DE3),经IPTG诱导表达后,超声破碎菌体,收集上清,经镍柱亲和纯化获得重组抗原EHc C蛋白,通过SDS PAGE和Western印迹检测纯化效果,之后免疫BALB/c小鼠,评价其免疫原性。结果通过原核表达纯化获得了纯度>90%的重组抗原EHc C蛋白,该重组抗原作为亚单位疫苗免疫小鼠产生了特异性抗体反应,10μg剂量抗原蛋白3次免疫小鼠即可抵抗104 LD50E型肉毒毒素攻击,血清中和抗体效价可达1.00 U/ml。结论获得的重组EHc C抗原免疫原性良好,免疫小鼠后能抵抗E型肉毒毒素的攻击,产生强烈保护作用,可作为亚单位候选疫苗预防E型肉毒毒素中毒或用于研究肉毒毒素疫苗和抗体的功能表位。

关键词：肉毒毒素类免疫原性原核表达亲和纯化疫苗,亚单位重组抗原EHc C蛋白