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

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

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Jun12682,a potent SARS-CoV-2 papain-like protease inhibitor with exceptional antiviral efficacy in mice

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4189-4192页

作者： Mianling Yang Meehyein Kim Peng zhan Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesShandong UniversityJi’nan 250012China Infectious Diseases Therapeutic Research Center Korea Research Institute of Chemical Technology(KRICT)Daejeon 34114Republic of Korea

Recently,a collaborative research study published in Science,led by Jun Wang,xufang Deng,Eddy Arnold,and Francesc xavier Ruiz1,identified a series of potent small molecule inhibitors that specifically target SARS-CoV-2 papain-like protease(Plpro).The study demonstrated nanomolar Plpro inhibitory potency with Ki values ranging from 13.2 to 88.2 nmol/*** employing a structure-based drug design strategy,the researchers discovered an exceptionally promising compound,named Jun12682,that effectively targets both the newly discovered ubiquitin Val70(Val70Ub)-binding site and the known blocking loop(Bl2)groove near the S4 subsite of ***,studies on the mechanism of action revealed that Jun12682 inhibits the deubiquitinating and deISGylating activities of Plpro,which are crucial for antagonizing the host’s innate immune response upon viral *** biology studies confirmed the“two-pronged”binding mode of Jun12682,aligning perfectly with their drug design ***,Jun12682 exhibited potent antiviral activity against SARS-CoV-2 and its variants,including nirmatrelvir-resistant mutants,in Caco-2 cells(EC50:0.44e2.02 mmol/l).It is noteworthy that its oral administration significantly improved survival rates and alleviated both lung virus loads and histopathological lesions in a lethal SARS-CoV-2 mouse *** conclusion。

关键词： SARS-CoV-2 Papain-like protease Broad-spectrum Anti-drug resistance Drug candidate

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On the Well-Posedness Problem of the Anisotropic Porous Medium Equation with a Variable Diffusion Coefficient

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Journal of Partial Differential Equations 2024年第2期37卷 135-149页

作者： zhan Huashui School of Mathematics and Statistics Xiamen University of TechnologyXiamen 361024China

The initial-boundary value problem of an anisotropic porous medium equation■is *** with the usual porous medium equation,there are two different characteristics in this *** lies in its anisotropic property,another one is that there is a nonnegative variable diffusion coefficient a(x,t)*** a(x,t)may be degenerate on the parabolic boundary∂Ω×(0,T),instead of the boundedness of the gradient|∇u|for the usual porous medium,we can only show that∇u∈l^(∞)(0,T;l^(2)_(loc)(Ω)).Based on this property,the partial boundary value conditions matching up with the anisotropic porous medium equation are discovered and two stability theorems of weak solutions can be proved naturally.

关键词： Anisotropic porous medium equation variable diffusion coefficient stability partial boundary condition

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Functional microfluidics:theory,microfabrication,and applications

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International Journal of Extreme Manufacturing 2024年第3期6卷 140-173页

作者： Mingzhu xie Ziheng zhan Yinfeng li Junkai Zhao Ce zhang Zhaolong Wang Zuankai Wang Interdisciplinary Research Center of low-carbon Technology and Equipment College of Mechanical and Vehicle EngineeringHunan UniversityChangsha 410082People’s Republic of China Energy Research Institute of Shandong Academy of Sciences Qilu University of Technology(Shandong Academy of Sciences)Jinan 250014People’s Republic of China Qian xuesen laboratory of Space Technology China Academy of Space Technology(CAST)Beijing 100094People’s Republic of China Department of Mechanical Engineering Hong Kong Polytechnic UniversityHong Kong Special Administrative Region of China 999077People’s Republic of China

Microfluidic devices are composed of microchannels with a diameter ranging from ten to a few hundred ***,quite a small(10-9–10-18l)amount of liquid can be manipulated by such a precise *** the past three decades,significant progress in materials science,microfabrication,and various applications has boosted the development of promising functional microfluidic *** this review,the recent progress on novel microfluidic devices with various functions and applications is ***,the theory and numerical methods for studying the performance of microfluidic devices are briefly ***,materials and fabrication methods of functional microfluidic devices are ***,the recent significant advances in applications of microfluidic devices are highlighted,including heat sinks,clean water production,chemical reactions,sensors,biomedicine,capillaric circuits,wearable electronic devices,and ***,perspectives on the challenges and future developments of functional microfluidic devices are *** review aims to inspire researchers from various fields engineering,materials,chemistry,mathematics,physics,and more—to collaborate and drive forward the development and applications of functional microfluidic devices,specifically for achieving carbon neutrality.

关键词： capillary theory functional devices functional microfluidics

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预处理技术--家庭生物废弃物处理过程中的微塑料制造者

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Engineering 2024年第1期32卷 116-126页

作者： Tian Hu Fan lü zhan Yang Zhenchao Shi Yicheng Yang Hua zhang Pinjing He Institute of Waste Treatment and Reclamation Tongji UniversityShanghai 200092China Shanghai Institute of Pollution Control and Ecological Security Shanghai 200092China Jiaxing-Tongji Environmental Research Institute jiaxing 314000China

Mechanical pretreatment is an indispensable process in biological treatment plants that remove plastics and other impurities from household biogenic waste(HBW).However,the imperfect separation of plastics in these pretreatment methods has raised concerns that they pose a secondary formation risk for microplastics(MPs).To validate this presumption,herein,quantities and properties of plastic debris and MPs larger than 50 μm were examined in the full chain of three different pretreatment methods in six *** facilities received HBW with or without prior depackaging at the *** key points in the secondary formation of MPs were ***,flux estimates of MPs were released,and an analysis of MPs sources was provided to develop an overview of their fate in HBW *** output can contain a maximum of(1673±279) to(3198±263) MP particles per kilogram of wet weight(particles·kg^(-1)ww) for those undepackaged at source,and secondary MPs formation is primarily attributed to biomass crushers,biohydrolysis reactors,and rough ***,HBW depackaged at the source can greatly reduce MPs by 8%-72%,regardless of pretreatment *** pretreatment,4.6-205.6 million MP particles were present in 100 tonnes of *** are produced at a rate of 741.11-33124.22 billion MP particles annually in anaerobic digester feedstock(ADF).This study demonstrated that HBW pretreatment is a competitive source of MPs and emphasized the importance of implementing municipal solid waste segregation at the ***,depackaging biogenic waste at the source is recommended to substantially alleviate the negative effect of pretreatment on MPs formation.

关键词： Microplastics Plastic debris Household biogenic waste Depackage Pretreatment

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Optimizing near-carbon-free nuclear energy systems:advances in reactor operation digital twin through hybrid machine learning algorithms for parameter identification and state estimation

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Nuclear Science and Techniques 2024年第8期35卷 177-203页

作者： li‑zhan Hong He‑lin Gong Hong‑Jun Ji Jia‑liang lu Han li Qing li Paris Elite Institute of Technology Shanghai Jiao Tong UniversityShanghai 200240China Science and Technology on Reactor System Design Technology laboratory Nuclear Power Institute of ChinaChengdu 610041China

Accurate and efficient online parameter identification and state estimation are crucial for leveraging digital twin simulations to optimize the operation of near-carbon-free nuclear energy *** previous studies,we developed a reactor operation digital twin(RODT).However,non-differentiabilities and discontinuities arise when employing machine learning-based surrogate forward models,challenging traditional gradient-based inverse methods and their *** study investigated deterministic and metaheuristic algorithms and developed hybrid algorithms to address these *** efficient modular RODT software framework that incorporates these methods into its post-evaluation module is presented for comprehensive *** methods were rigorously assessed based on convergence profiles,stability with respect to noise,and computational *** numerical results show that the hybrid KNNlHS algorithm excels in real-time online applications,balancing accuracy and efficiency with a prediction error rate of only 1%and processing times of less than 0.1 ***,algorithms such as FSA,DE,and ADE,although slightly slower(approximately 1 s),demonstrated higher accuracy with a 0.3%relative l_2 error,which advances RODT methodologies to harness machine learning and system modeling for improved reactor monitoring,systematic diagnosis of off-normal events,and lifetime management *** developed modular software and novel optimization methods presented offer pathways to realize the full potential of RODT for transforming energy engineering practices.

关键词： Parameter identification State estimation Reactor operation digital twin Reduced order model Inverse problem

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轻质铝基熵合金:概述与未来趋势

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Science China Materials 2024年第1期67卷 31-46页

作者：崔立莹张展陈晓光 Department of Applied Science University of Quebec at Chicoutimi555boulevard de l’UniversiteSaguenay G7H 2B1QCCanada

新一代合金——高熵合金的出现,揭示了熵效应在合金设计中的重要意义.受这一概念的启发,轻质铝基熵合金这一概念被提出.随着对低密度结构材料的需求不断增加,这些新型合金在各种应用中具有巨大的潜力.本文综述了轻质铝基熵合金的发展背... 详细信息

新一代合金——高熵合金的出现,揭示了熵效应在合金设计中的重要意义.受这一概念的启发,轻质铝基熵合金这一概念被提出.随着对低密度结构材料的需求不断增加,这些新型合金在各种应用中具有巨大的潜力.本文综述了轻质铝基熵合金的发展背景、设计原理、制造方法、微观结构和力学性能、高温应用,及其发展前景.通过对当前研究的全面调查,本文重点研究分析了122种密度低于4.0 g cm-3的铝基熵合金.轻质铝基熵合金可以弥补传统铝和钛合金在机械性能和密度方面的差距.轻质铝基熵合金优异的热稳定性使其有望成为在高温下使用的结构材料.此外,本文还讨论了轻质铝基熵合金领域的未来发展趋势.机器学习作为有效计算工具,可以极大地提高合金的开发效率.

关键词：高温应用合金设计新型合金机器学习铝基计算工具高熵合金微观结构

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Dynamic Control of Multiple Optical Patterns of Cholesteric liquid Crystal Microdroplets by light-Driven Molecular Motors

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CCS Chemistry 2024年第2期6卷 427-438页

作者： Jiaqin li Shuting xie Jiahui Meng Yuying liu Qi zhan Yang zhang lingling Shui Guofu Zhou Ben l.Feringa Jiawen Chen SCNU-UG International Joint laboratory of Molecular Science and Displays National Center for International Research on Green OptoelectronicsSouth China Normal UniversityGuangzhou 510006 Joint laboratory of Optofluidic Technology and Systems Guangdong Provincial Key Laboratory of Nanophotonic Functional Materials and DevicesSchool of Information and Optoelectronic Science and EngineeringSouth China Normal UniversityGuangzhou 510006 Stratingh Institute for Chemistry University of Groningen9747AG Groningen

The key to high-level encryption and anti-counterfeiting techniques is the storage of multiple levels of distinct information that can be individually and precisely addressed by certain *** continues to be a formidable challenge as the concealed images or codes must be read with fast response and high resolution without cross-talk to the first layer of ***,we report a non-fluorescencebased strategy to establish responsive encryption labels taking advantage of solely tuning multiple optical patterns of cholesteric liquid crystal(ClC)microdroplets doped with light-driven molecular *** photo-triggered unidirectional rotation of the motor induced not only changes in the helical twist power value but the opposite helical orientation of the superstructure in ClCs as well,resulting in changes in both the structural color and the selective reflection of circularly polar *** designed labels,which featured highly selective addressability of dual-level distinct information,good reversibility,and viewing angle-independence,were applied to build devices for daily practical use,demonstrating great potential in anti-counterfeiting technology and provide a versatile platform for enhanced data protection and encryption of authentic information.

关键词： molecular motor chirality amplification cholesteric liquid crystal anti-counterfeiting label data encryption

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Construction of Z-scheme Cu-CeO_(2)/BiOBr heterojunction for enhanced photocatalytic degradation of sulfathiazole

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Chinese Chemical letters 2024年第7期35卷 167-172页

作者： xingmin Chen Yunyun Wu Yao Tang Peishen li Shuai Gao Qiang Wang Wen liu Sihui zhan College of Environmental Sciences and Engineering Nankai UniversityTianjin 300350China laboratory for Micro-Sized Functional Materials&College of Elementary Education and Department of Chemistry Capital Normal UniversityBeijing 100048China College of Environmental Sciences and Engineering The Key Laboratory of Water and Sediment Sciences(MOE)Peking UniversityBeijing 100871China

The utilization of an efficient photocatalyst is crucial for the photocatalytic degradation of antibiotics in water through visible light,which is an imperative requirement for the remediation of water *** this study,a novel Cu-CeO_(2)/BiOBr Z-type heterojunction was synthesized by calcination and hydrothermal methods,and the degradation rate of sulfathiazole(STZ)antibiotic solution was studied using simulated illumination(300 W xenon lamp).The results indicated that 3%Cu-CeO_(2)/BiOBr achieved a degradation rate of 92.3%within 90 min when treating 20 mg/l STZ solution,demonstrating its potential for practical water treatment *** using various chemical instruments revealed that 3%Cu-CeO_(2)/Bi OBr exhibited the lowest electron-hole recombination rate and electron transfer ***,the utilization of ESR data and quenching experiments has substantiated the involvement of hydroxyl radicals(·OH)and superoxide radicals(·O_(2)^(-))as the primary active ***,a plausible degradation mechanism has been *** findings offer a prospective approach for the development of heterojunction materials with appropriate band matching.

关键词： Cu-CeO_(2)/BiOBr nanoheterojunction Photocatalytic degradation Sulfathiazole Z-scheme

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A bulk extraction method to determine the stable isotope ratios of iron,nickel,copper,zinc,and cadmium in seawater using multi-collector inductively coupled plasma mass spectrometry

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Acta Oceanologica Sinica 2024年第7期43卷 125-137页

作者： zhan Shen Yuncong Ge Jiahui liu Wenkai Guan Wenfeng Hu Ruifeng zhang School of Oceanography Shanghai Jiao Tong UniversityShanghai 200030China Southern Marine Science and Engineering Guangdong laboratory(Zhuhai) Zhuhai 519015China Shanghai Key laboratory of Polar life and Environment Sciences Shanghai Jiao Tong UniversityShanghai 200030China Key laboratory of Polar Ecosystem and Climate Change of Ministry of Education Shanghai Jiao Tong UniversityShanghai 200030China laboratory for Polar Science Polar Research Institute of ChinaMinistry of Natural ResourcesShanghai 200136China

The oceanic trace metals iron(Fe),nickel(Ni),copper(Cu),zinc(Zn),and cadmium(Cd)are crucial to marine phytoplankton growth and global carbon cycle,and the analysis of their stable isotopes can provide valuable insights into their biogeochemical cycles within the ***,the simultaneous isotopic analysis of multiple elements present in seawater is challenging because of their low concentrations,limited volumes of the test samples,and high salt *** this study,we present the novel method developed for the simultaneous analysis of five isotope systems by 1 l seawater *** the developed method,the NOBIAS Chelate-PA1 resin was used to extract metals from seawater,the AG MP-1M anion-exchange resin to purify Cu,Fe,Zn,Cd,and the NOBIAS Chelate-PA1 resin to further extract Ni from the matrix ***,a multi-collector inductively coupled plasma mass spectroscope(MC-ICPMS)was employed for the isotopic measurements using a doublespike technique or sample-standard bracketing combined with internal *** method exhibited low total procedural blanks(0.04 pg,0.04 pg,0.21 pg,0.15 pg,and 3 pg for Ni,Cu,Fe,Zn,and Cd,respectively)and high extraction efficiencies(100.5%±0.3%,100.2%±0.5%,97.8%±1.4%,99.9%±0.8%,and 100.1%±0.2%for Ni,Cu,Fe,Zn,and Cd,respectively).The external errors and external precisions of this method could be considered *** proposed method was further tested on the seawater samples obtained from the whole vertical profile of a water column during the Chinese GEOTRACES GP09 cruise in the Northwest Pacific,and the results showed good agreement with previous related *** innovative method will contribute to the advancement of isotope research and enhance our understanding of the marine biogeochemical cycling of Fe,Ni,Cu,Zn,and Cd.

关键词： trace metal stable isotopes seawater bulk extraction

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