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Adeno-associated virus as a delivery vector for gene therapy of human diseases

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1808-1840页

作者： Jiang-Hui Wang Dominic J.Gessler Wei Zhan Thomas l.Gallagher Guangping Gao Horae Gene Therapy Center University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Microbiology and Physiological Systems University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalEast MelbourneVIC3002Australia Ophthalmology Department of SurgeryUniversity of MelbourneEast MelbourneVIC3002Australia Department of Neurological Surgery University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Neurosurgery University of MinnesotaMinneapolisMN55455USA Department of Medicine University of Massachusetts Chan Medical SchoolWorcesterMA01605USA li Weibo Institute for Rare Diseases Research University of Massachusetts Chan Medical SchoolWorcesterMA01605USA

Adeno-associated virus(AAV)has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different *** AAV(rAAV)has been engineered for enhanced specificity and developed as a tool for treating various ***,as rAAV is being more widely used as a therapy,the increased demand has created challenges for the existing manufacturing *** rAAV-based gene therapy products have received regulatory approval,but there continue to be concerns about safely using high-dose viral therapies in humans,including immune responses and adverse effects such as genotoxicity,hepatotoxicity,thrombotic microangiopathy,and *** this review,we explore AAV biology with an emphasis on current vector engineering strategies and manufacturing *** discuss how rAAVs are being employed in ongoing clinical trials for ocular,neurological,metabolic,hematological,neuromuscular,and cardiovascular diseases as well as *** outline immune responses triggered by rAAV,address associated side effects,and discuss strategies to mitigate these *** hope that discussing recent advancements and current challenges in the field will be a helpful guide for researchers and clinicians navigating the ever-evolving landscape of rAAV-based gene therapy.

关键词： diseases specificity approval

Protection of steel hooks embedded in glass-fiber-reinforced concrete against macrocell corrosion

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Petrol.um Research 2024年第2期9卷 317-326页

作者： Husnu Gerengi Muhammed Maraşlı Marziya Rizvi Beni Kohen Ismail Taşkıran Corrosion Research laboratory Department of Mechanical EngineeringDuzce University81620DuzceTurkey Department of Engineering and Applied Sciences University of BergamoBGItaly Fibrobeton Company R&D Center DuzceTurkey Department of Chemistry Babasaheb Bhimrao Ambedkar UniversityLucknow226003U.PIndia

This study evaluated the corrosion behavior of steel hooks embedded in GFRC,which were protected by a zinc-rich(96%Zn)galvanizing *** coating provided the hooks with active cathodic protection and a passive physical *** corrosion may form when the anode is smaller than the total steel ***,the steel hooks at the embedment juncture were additionally sealed against water ingress and air exchange using a construction *** study was conducted in three phases in a salt-spray ***,the electrogalvanized steel hooks embedded in GFRC were allowed to freely corrode for 7 *** the second phase,the electrogalvanized steel hooks were painted with the zinc-rich coating and observed over 7 *** the third phase,the steel hooks were protected by the zinc-rich coating together with a primer and construction sealant,and observed over 7 *** evaluate the electrogalvanized hooks and the corrosion products formed,the thickness of the material was *** on the metal surface was inferred by studying the surface morphology of the hooks at various points of contact and after different periods of time.

关键词： Steel rebars Concrete corrosion GFRC Galvanization Sealant

Extremal Functions for Adams Inequalities in Dimension Four

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Journal of Partial Differential Equations 2020年第2期33卷 171-192页

作者： lI xiaomeng School of Information Huaibei Normal UniversityHuaibei 235000China Department of Mathematics Renmin University of ChinaBeijing 100872China

let Ω (∈) R4 be a smooth bounded domain,W2,20(Ω) be the usual Sobolev *** any positive integer e,λl(Ω) is the e-th eigenvalue of the bi-laplacian *** E(l)=Eλ1(Ω) ⊕ Eλ2(Ω)(⊕) … ⊕Eλe(Ω),where Eλi(Ω) is eigenfunction space associated with λi(Ω).E⊥e denotes the orthogonal complement of Ee in W2,20 (Ω).For 0 ≤ α ≤ λe+1 (Ω),we define a norm by ||u||22,α =||△u||22-α||u||22 for u ∈ E⊥*** this paper,using the blow-up analysis,we prove the following Adams inequalities supu∈E⊥e,||u||2,α≤1∫Ω e32π2u2 dx upremum can be attained by a function u0 ∈ E⊥e∩C4((Ω)) with || u0||2,α =*** result extends that of Yang (*** Equations,2015),and complements that of lu and Yang (***.2009) and Nguyen (arXiv: 1701.08249,2017).

关键词： Adams inequality Trudinger-Moser inequality extremal function blow-up analysis

Radiation Spectral Analysis of 3D Dust Molecular Clusters(PAHs)and Peptoids under Ionization and Electric Field in ISM

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Research in Astronomy and Astrophysics 2024年第1期24卷 70-77页

作者： Ruiqing Wu Chunhua Zhu Guoliang lü Xiaojiao Zhang Xizhen lu Jinlong Yu Wujin Chen Mengqiu long School of Physics and Electronics Central South UniversityChangsha 410083China School of Physical Science and Technology Xinjiang UniversityUrumqi 830046China School of Microelectronics and Physics Hunan University of Technology and BusinessChangsha 410205China College of Mechanical and Electronic Engineering Tarim UniversityAlar 843300China School of Medicine Xinjiang Medical UniversityUrumqi 830011China

Polycyclic aromatic hydrocarbons(PAHs),PANHs,and peptoids dust spectral cal.ulations from the interstellar medium(ISM)are important for dust observations and *** goal is to cal.ulate the radiation spectrum of spherical PAHs dust clusters in a vacuum containing ionized and applied in the presence of an electric *** propose a new simple computational model to cal.ulate the size of three-dimensional spherical dust clusters formed by different initial dust *** the Vienna Ab-initio Simulation Package code,the density functional theory with the generalized approximation was used to cal.ulate the electron density gradient and obtain the radiation spectrum of *** the radius of spherical dust clusters is~[0.009-0.042]μm,the dust radiation spectrum agrees well with the Z=0.02 mMMP stellar spectra,and the PAHs radiation spectrum of NGC 4676 at wavelengths of(0-5]μm and(5-10]μm,*** the ionized state,the N-PAH,C_(10)H_(9)N,2(C_(4)H_(4))^(1+),and peptoids 4(CHON),(C_(8)H_(10)N_(2)O_(5))^(1+)dust clusters at 3.3μm,while the 2(C_(22)H_(21)N_(3)O_(2))^(1+),4(CHON)dust clusters at 5.2μm have obvious *** is a characteristic of part of PAHs and peptoids clusters radiation at the nearinfrared wavelength of 2μ***,especially after applying an electric field to the dust,the emission spectrum of the dust increases significantly in the radiation wavelength range[3-10]μ***,the dust clusters of PAHs,PANHs,and peptoids of the radius size~[0.009-0.042]μm are likely to exist in the ISM.

关键词： ISM:structure ISM:molecules radiation mechanisms:general (ISM:)dust extinction

基于非靶向代谢组学的怀珍珠菊和野菊花化学成分差异性分析

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中草药 2024年第19期55卷 6496-6507页

作者：杨晓萌赵楠刘欣欣张立新张晓哲张丽华沈阳化工大学化学工程学院沈阳化工大学功能分子研究所辽宁省绿色功能分子设计与开发重点实验室沈阳市靶向农药重点实验室中国科学院分离分析化学重点实验室中国科学院大连化学物理研究所

目的研究典型食用菊怀珍珠菊Chrysanthemum morifol.um与典型药用菊野菊花C. indicum的差异性成分。方法采用uPlC/Q-TOF-MS结合非靶向代谢组学方法，筛选怀珍珠菊与野菊花的差异性成分。结果从怀珍珠菊中共鉴定出包括黄酮类、萜类、... 详细信息

目的研究典型食用菊怀珍珠菊Chrysanthemum morifol.um与典型药用菊野菊花C. indicum的差异性成分。方法采用uPlC/Q-TOF-MS结合非靶向代谢组学方法，筛选怀珍珠菊与野菊花的差异性成分。结果从怀珍珠菊中共鉴定出包括黄酮类、萜类、苯丙素类、有机酸类等类化合物在内的80个代谢产物，其中木犀草苷、艾黄素、秦皮乙素等19个代谢产物是与野菊花具有显著差异性的分子。结论萜类化合物为怀珍珠菊和野菊花的主要差异性代谢物，这些代谢物与抗炎、抑菌和抗虫害密切相关，值得进一步研究。

关键词：怀珍珠菊野菊花 uPlC/Q-TOF-MS 主成分分析差异性分析萜类化合物木犀草苷艾黄素秦皮乙素

Shape and Size Optimization of Truss Structures under Frequency Constraints Based on Hybrid Sine Cosine Firefly Algorithm

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Computer Modeling in Engineering & Sciences 2023年第1期134卷 405-428页

作者： Ran Tao xiaomeng Yang Huanlin Zhou Zeng Meng School of Civil Engineering Hefei University of TechnologyHefei230009China

Shape and size optimization with frequency constraints is a highly nonlinear problem withmixed design variables,non-convex search space,and multiple local ***,a hybrid sine cosine firefly algorithm(HSCFA)is proposed to acquire more accurate solutions with less finite element *** full attraction model of firefly algorithm(FA)is analyzed,and the factors that affect its computational efficiency and accuracy are revealed.A modified FA with simplified attraction model and adaptive parameter of sine cosine algorithm(SCA)is proposed to reduce the computational complexity and enhance the convergence ***,the population is classified,and different populations are updated by modified FA and SCA ***,the random search strategy based on lévy flight is adopted to update the stagnant or infeasible solutions to enhance the population *** selection technique is applied to save the promising solutions and further improve the convergence ***,the adaptive penalty function is employed to deal with the ***,the performance of HSCFA is demonstrated through the numerical examples with nonstructural masses and frequency *** results show that HSCFA is an efficient and competitive tool for shape and size optimization problems with frequency constraints.

关键词： Firefly algorithm sine cosine algorithm frequency constraints structural optimization

基于生物信息学和动物实验探讨泄浊解毒方调控铁死亡治疗溃疡性结肠炎的作用机制

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中国实验方剂学杂志 2024年第11期30卷 166-173页

作者：孙超迪刘建平杜明民康欣崔建从赵源贾苏杰郎晓猛河北中医药大学石家庄050091 河北省中西医结合胃肠病研究重点实验室石家庄050011 河北省中医院石家庄050011

目的:运用生物信息学的方法,筛选与溃疡性结肠炎(uC)密切相关的铁死亡差异基因(FRGs),通过动物实验验证泄浊解毒方治疗uC的作用机制是否与调控细胞铁死亡相关。方法:从GEO数据库中获取uC患者结肠黏膜组织差异表达基因,与铁死亡基因取交... 详细信息

目的:运用生物信息学的方法,筛选与溃疡性结肠炎(uC)密切相关的铁死亡差异基因(FRGs),通过动物实验验证泄浊解毒方治疗uC的作用机制是否与调控细胞铁死亡相关。方法:从GEO数据库中获取uC患者结肠黏膜组织差异表达基因,与铁死亡基因取交集,获取FRGs,通过聚类分析、最小绝对收缩和选取算子(lASSO)回归和接收者操作特征曲线(ROC)曲线分析获取核心FRGs。动物实验采用2.5%的葡聚糖硫酸钠(DSS)自由饮方式制备uC小鼠模型,泄浊解毒方及美沙拉嗪灌胃7 d,苏木素-伊红(HE)染色观察结肠黏膜炎性浸润情况,实时荧光定量聚合酶链式反应(Real-time PCR)方法检测结肠组织中E3泛素连接酶(FBXW7)、锌指蛋白(ZFP36)、溶质载体家族7成员11(SlC7A11)、Toll样受体4(TlR4)mRNA表达量;蛋白免疫印迹法(Western blot)检测结肠组织中FBXW7、ZFP36、SlC7A11、TlR4蛋白表达量。结果:从GEO数据库筛选出数据集GSE87466,与铁死亡基因取交集,得到21个FRGs,经过聚类分析及lASSO回归和ROC曲线分析后得到核心FRGs(FBXW7、ZFP36、SlC7A11、TlR4),免疫浸润分析结果显示初始B细胞、M1型巨噬细胞、浆细胞、M2型巨噬细胞在uC小鼠结肠黏膜组织中表达差异具有统计学意义,核心FRGs与此类免疫细胞同样存在显著相关性。进一步通过动物实验发现,模型组小鼠结肠黏膜组织结构紊乱,大量炎性细胞浸润,经泄浊解毒方及美沙拉嗪治疗后各组小鼠结肠黏膜组织炎症反应情况均出现不同程度的缓解,泄浊解毒方高剂量组小鼠结肠黏膜几乎无炎症改变。与正常组比较,模型组FBXW7、ZFP36、SlC7A11、TlR4蛋白和mRNA的表达量显著升高(PlC7A11、TlR4是与uC发病密切相关的铁死亡基因,泄浊解毒方可通过下调铁死亡核心基因明显缓解小鼠结肠黏膜炎症反应。

关键词：溃疡性结肠炎泄浊解毒方生物信息学铁死亡

Pumping-induced Well Hydraulics and Groundwater Budget in a leaky Aquifer System with Vertical Heterogeneity in Aquitard Hydraulic Properties

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Acta Geologica Sinica(English Edition) 2024年第2期98卷 477-490页

作者： ZHuANG Chao lÜChenyang YAN long lI Yabing ZHOu Zhifang WANG Jinguo DOu Zhi Walter A.IllMAN School of Earth Sciences and Engineering Hohai UniversityNanjing 211100China School of Geography Earth and Environmental SciencesUniversity of BirminghamBirmingham B152TTU.K. Department of Modern Mechanics University of Science and Technology of ChinaHefei 230027China Department of Earth and Environmental Sciences University of WaterlooOntario N2L 3G1Canada

In groundwater hydrology,aquitard heterogeneity is often less considered compared to aquifers,despite its significant impact on groundwater hydraulics and groundwater resources evaluation.A semi-analytical solution is derived for pumping-induced well hydraulics and groundwater budget with consideration of vertical heterogeneity in aquitard hydraulic conductivity(K)and specific storage(S_(s)).The proposed new solution is innovative in its partitioning of the aquitard into multiple homogeneous sub-layers to enable consideration of various forms of vertically heterogeneous K or S_(s).Two scenarios of analytical investigations are explored:one is the presence of aquitard interlayers with distinct K or S_(s) values,a common field-scale occurrence;another is an exponentially depth-decaying aquitard S_(s),a regional-scale phenomenon supported by statistical *** investigations reveal that a low-K interlayer can significantly increase aquifer drawdown and enhance aquifer/aquitard depletion;a high-S_(s) interlayer can noticeably reduce aquifer drawdown and increase aquitard *** of low-K or high-S_(s) interlayers also significantly impact well hydraulics and groundwater *** the context of an exponentially depth-decaying aquitard S_(s),a larger decay exponent can enhance aquifer *** using current models with a vertically homogeneous aquitard,half the sum of the geometric and harmonic means of exponentially depth-decaying aquitard S_(s) should be used to cal.ulate aquitard depletion and unconfined aquifer leakage.

关键词： hydrogeology aquitard vertical heterogeneity semi-analytical solution well hydraulics groundwater budget

Wear of semi-solid rheocast SiC_p/Al metal matrix composites

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中国有色金属学会会刊：英文版 2010年第S3期20卷 852-856页

作者： u.A.CuRlE l.IVANCHEV Materials Science and Manufacturing Council for Scientific and Industrial Research(South Africa)

Rheocasting of plates in Al alloy 359 reinforced with SiC at 11%,27% and 50%(volume fractions) exhibits the capability of the council for scientific and industrial research-rheocasting system(CSIR-RCS) in rheo-processing and high pressure die casting of SiC metal matrix *** metal matrix consisting of nearly spherical proeutectic α(Al) globules was *** of fibrous eutectic silicon took place upon heat treatment of the as-cast metal matrix composites(MMCs).Hardness increases as the volume fractions of SiC *** rates of the MMCs in the F and T6 heat treatment conditions were assessed with a metallographic preparation *** is found that the 11% SiC MMC wear rate is higher on SiC abrasives compared with the 50% SiC MMC wear rate due to wear of the aluminum *** trend is reversed on diamond abrasives due to pull-out of the irregular shaped composite *** 50% SiC MMC suffers from composite particle fracture porosity after high pressure die casting(HPDC).

关键词： CSIR-RCS HPDC SiC F condition T6 condition wear rate hardness porosity