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Engineered extracellular vesicles efficiently deliver CRISPR-Cas9 ribonucleoprotein(RNP)to inhibit herpes simplex virus1 infection in vitro and in vivo

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1362-1379页

作者： yuanda Wan Liren Li Ruilin Chen Jiajia Han Qiyun Lei Zhipeng Chen Xiaodong Tang Wenyu wu Shuwen Liu Xingang Yao NMPA Key Laboratory for Research and Evaluation of Drug Metabolism Guangdong Provincial Key Laboratory of New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Center of Clinical Pharmacy Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China Key Laboratory of Infectious Diseases Research in South China(Southern Medical University) Ministry of EducationGuangzhou 510515China

Extracellular vesicles(EVs)have recently emerged as a promising delivery platform for CRISPR/Cas9 ribonucleoproteins(RNPs),owing to their ability to minimize off-target effects and immune ***,enhancements are required to boost the efficiency and safety of Cas9 RNP enrichment within *** response,we employed the Fc/Spa interaction system,in which the human Fc domain was fused to the intracellular domain of PTGFRN-Δ687 and anchored to the EV ***,the B domain of the Spa protein was fused to the C domain of cargos such as Cre or *** to the robust interaction between Fc and Spa,this method enriched nearly twice the amount of cargo within the *** loaded with spCas9 RNP targeting the HSV1 genome exhibited significant inhibition of viral replication in vitro and in ***,following neuron-targeting peptide RVG modification,the in vivo dosage in neural tissues substantially increased,contributing to the clearance of the HSV1 virus in neural tissues and exhibiting a lower off-target *** findings establish a robust platform for efficient EV-based SpCas9 delivery,offering potential therapeutic advantages for HSV1 infections and other neurological disorders.

关键词： Extracellular vesicles CRISPR/Cas9 Ribonucleoproteins PTGFRN Fc/Spa HSV1 Neuron-targeting Delivery

Interference at the single-photon level based on silica photonics robust against channel disturbance

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Photonics Research 2021年第2期9卷 222-228页

作者： XIAO LI MEIZHEN REN JIASHUN ZHANG LIANGLIANG WANG WEI CHEN YUE WANG XIAOJIE YIN yuanda wu JUNMING AN State Key Laboratory on Integrated Optoelectronics Institute of SemiconductorsChinese Academy of SciencesBeijing 100083China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China Division of Quantum Materials and Devices Beijing Academy of Quantum Information SciencesBeijing 100193China Laboratory of Quantum Information CASUniversity of Science and Technology of ChinaHefei 230026China

Quantum key distribution(QKD) provides a solution for communication of unconditional security. However,the quantum channel disturbance in the field severely increases the quantum bit-error rate, degrading the performance of a QKD system. Here we present a setup comprising silica planar light wave circuits(PLCs), which is robust against the channel polarization disturbance. Our PLCs are based on the asymmetric Mach–Zehnder interferometer(AMZI), integrated with a tunable power splitter and thermo-optic phase modulators. The polarization characteristics of the AMZI PLC are investigated by a novel pulse self-interfering method to determine the operation temperature of implementing polarization insensitivity. Over a 20 km fiber channel with 30 Hz polarization scrambling, our time-bin phase-encoding QKD setup is characterized with an interference fringe visibility of 98.72%. The extinction ratio for the phase states is kept between 18 and 21 d B for 6 h without active phase correction.

关键词： polarization channel interferometer

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高线性波分复用模拟光链路的设计及实现

激光与光电子学进展 2023年第5期60卷 97-102页

作者：黄宁博吴远大郑州大学物理学院河南郑州450001 河南仕佳光子科技股份有限公司河南鹤壁458030

面向多路射频模拟信号的高线性传输需求,基于强度调制-直接探测的原理,提出了基于波分复用技术的模拟射频光传输方案;利用高线性度模拟直调半导体激光器、波分复用器、模拟光电探测器,设计了基于微波光子技术的波分复用射频光传输链路,... 详细信息

面向多路射频模拟信号的高线性传输需求,基于强度调制-直接探测的原理,提出了基于波分复用技术的模拟射频光传输方案;利用高线性度模拟直调半导体激光器、波分复用器、模拟光电探测器,设计了基于微波光子技术的波分复用射频光传输链路,该链路具有低串扰、低失真、链路增益可调等性能。利用该链路进行了直调激光器、驱动控制电路、射频光发射模块和光接收模块的样机研制。对所研制出的样机进行了实验测试。测试结果表明:通道增益可在-30~10 dB调谐,通道内基波与二次谐波抑制比高于50 dB,相邻及非相邻通道间射频串扰均低于60 dB,相位一致性在±5°以内。针对不同的信号输入功率,在线调整链路增益,改善链路的信噪比或非线性失真效应。设计和研制的样机可用于低频段射频信号的光纤传输。

关键词：光纤通信射频光传输直调半导体激光器模拟光链路

Ballistic performances of the hourglass lattice sandwich structures under high-velocity fragments

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Defence Technology（防务技术） 2024年第1期31卷 312-325页

作者： He-xiang wu Jia Qu Lin-zhi wu Key Laboratory of Advanced Ship Materials and Mechanics College of Aerospace and Civil EngineeringHarbin Engineering UniversityHarbin150001China School of Civil Engineering Northeast Forestry UniversityHarbin150040China

In this paper,the numerical simulation method is used to study the ballistic performances of hourglass lattice sandwich structures with the same mass under the vertical incidence of *** is paid to elucidating the influences of rod cross-section dimensions,structure height,structure layer,and rod inclination angle on the deformation mode,ballistic performances,and ability to change the ballistic direction of *** results show that the ballistic performances of hourglass lattice sandwich structures are mainly affected by their structural *** this respect,structural parameters optimization of the hourglass lattice sandwich structures enable one to effectively improve their ballistic limit velocity and,consequently,ballistic performances.

关键词： Hourglass lattice sandwich structures Ballistic performances high-velocity Finite element analysis

Resilience-incorporated seismic risk assessment of precast concrete frames with“dry”connections

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Earthquake Engineering and Engineering Vibration 2024年第2期23卷 403-425页

作者： wu Chenhao Tang Yuchuan Cao Xuyang wu Gang Key Laboratory of Concrete and Prestressed Concrete Structures of the Ministry of Education Nanjing 211102China Department of Civil and Environmental Engineering University of CaliforniaLos AngelesCA 90095USA School of Civil Engineering Southeast UniversityNanjing 211102China College of Civil and Transportation Engineering Hohai UniversityNanjing 210024China

A resilience-incorporated risk assessment framework is proposed and demonstrated in this study to manifest the advantageous seismic resilience of precast concrete frame(PCF)structures with“dry”connections in terms of their low damage and rapid *** framework integrates various uncertainties in the seismic hazard,fragility,capacity,demand,loss functions,and post-earthquake *** this study,the PCF structures are distinguished from ordinary reinforced concrete frame(RCF)structures by characterizing multiple limit states for the PCF based on its unique damage ***,probabilistic story-wise pushover analyses are performed to yield story-wise capacities for the predefined limit *** the seismic resilience analysis,a step-wise recovery model is proposed to idealize the functionality recovery process,with separate considerations of the repair and non-repair *** recovery model leverages the economic loss and downtime to delineate the stochastic post-earthquake recovery curves for the resilience loss *** such,contingencies in the probabilistic post-earthquake repairs are incorporated and the empirical judgments on the recovery parameters are largely *** proposed framework is demonstrated through a comparative study between two“dry”connected PCFs and one RCF designed as alternative structural systems for a prototype *** results from the risk quantification indicate that the PCFs show reduced loss hazards and lower expected losses relative to the ***,the PCF equipped with energy dissipation devices at the“dry”connections largely reduces the expected economic loss,downtime,and resilience loss by 29%,56%,and 60%,respectively,compared to the RCF.

关键词： precast concrete frame non-emulative precast system seismic resilience seismic risk functional recovery

New findings on the influence of El Ni?o events on tropical cyclone formation

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Science China Earth Sciences 2024年第3期67卷 892-893页

作者： Liguang wu Fudan University Department of Atmospheric and Oceanic Sciences Institute of Atmospheric Sciences

Tropical cyclones typically form over warm tropical and subtropical ocean surfaces, as their formation and intensification rely primarily on the energy provided by the ocean. Pioneering research by Gray (1968) revealed that the formation of tropical cyclones requires the sea surface temperature (SST) to be no less than 26.5°C. Consequently, SST is commonly recognized as a crucial parameter among the environmental factors influencing tropical cyclone formation(Gray, 1979; Emanuel and Nolan, 2004).

关键词： INDEX

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Two-dimensional semiconductor heterostructures for photocatalytic CO_(2)conversion

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Science China Chemistry 2024年第8期67卷 2434-2447页

作者： Yang wu Mingyu wu Yongfu Sun Yi Xie Hefei National Research Center for Physical Sciences at Microscale University of Science and Technology of ChinaHefei 230026China

The CO_(2)reduction into carbon-contained fuel via solar energy offers the powerful tools to realize the zero-emission carbon *** to the intriguing features of the two-dimensional(2D)heterostructures,it is susceptible to modulate the electronic structure as well as the surface geometry for optimizing the photocatalytic CO_(2)*** this perspective,we surveyed the fundamental insights of 2D semiconductor heterostructures,involving the fabrication strategies and classification of the 2D semiconductor ***,we have detailly discussed the overview of 2D semiconductor heterostructure for optimizing CO_(2)photocatalytic influenced factors,including the solar energy utilization,photogenerated carriers separation,and redox reaction ***,we showed the significant advantages of 2D heterostructures in elevating CO_(2)photoreduction performance,focusing on activity,selectivity and *** analyzing the limitations and developments,we ended by putting forward insights into the further researches about the CO_(2)photocatalysts and reactor design,even industrial applications.

关键词： two-dimensional semiconductor heterostructures photocatalysis CO_(2)conversion

The Functional Redundancy of Neddylation E2s and E3s in Modulating the Fitness of Regulatory T Cells

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Research 2024年第2期2023卷 373-387页

作者： Di wu Yi Sun Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China Cancer Center of Zhejiang University Hangzhou 310029China Zhejang Provincial Clinical Research Center for Cancer Zhejang ProvinceChina Key Laboratory of Molecular Biology in Medical Sciences Zhejang ProvinceChina Research Center for Life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China

Neddylation is necessary for activation of Cullin-RING ligases(CRLs),which degrade various immune regulatory *** recent study showed that while depletion of neddylation E2-E3 pair Ube2f-Sag in regulatory T(T_(reg))cells had no obvious phenotype,the same depletion of either Ube2m or Rbx1 caused inflammation disorders with different *** these E2s or E3s compensate each other in functional regulations of T_(reg)cells is,however,previously *** this report,we generated Foxp3^(Cre);Ube2m^(fl/fl);Ube2f^(fl/fl)or Foxp3^(Cre);Rbx1^(fl/fl);Sag^(fl/fl)double-null mice by simultaneous deletion of both neddylation E2s or E3s in T_(reg)cells,***,Ube2m&Ube2f double-null mice developed much severe autoimmune phenotypes than did Ube2m-null mice,indicating that Ube2m markedly compensates Ube2f in T_(reg)*** minor worsened autoimmune phenotypes seen at the very early stage in Rbx1&Sag double-null than Rbx1-null mice is likely due to already severe phenotypes of the later,indicating a minor compensation of Rbx1 for *** RNA profiling-based analyses revealed that up-and down-regulations of few signaling pathways in T_(reg)cells are associated with the severity of autoimmune ***,severer inflammation phenotypes seen in mice with double E3-null than with double E2-null T_(reg)cells indicate a neddylation-independent mechanism of 2 E3s,also known to serve as the RING component of CRLs in regulation of T_(reg)cell fitness.

关键词： Foxp3 inflammation markedly

Rational surface charge engineering of haloalkane dehalogenase for boosting the enzymatic performance in organic solvent solutions

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Chinese Journal of Chemical Engineering 2024年第1期65卷 276-285页

作者： Yin wu Yan Sun Department of Biochemical Engineering School of Chemical Engineering and Technology and Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology(Ministry of Education)Tianjin UniversityTianjin 300350China

Biocatalysis in organic solvents(OSs)has numerous important applications,but native enzymes in OSs often exhibit limited catalytic ***,we proposed a computation-aided surface charge engineering strategy to improve the catalytic performance of haloalkane dehalogenase DhaA in OSs based on the energetic analysis of substrate binding to the DhaA *** variants with enhanced OS resistance were obtained by replacing negative charged residues on the surface with positive charged residue(Arg).Particularly,a four-substitution variant E16R/E93R/E121R/E257R exhibited the best catalytic performance(five-fold improvement in OS resistance and seven-fold half-life increase in 40%(vol)dimethylsulfoxide).As a result,the overall catalytic performance of the variant could be at least 26 times higher than the wild-type *** spectroscopy and molecular dynamics simulation studies revealed that the residue substitution mainly enhanced OS resistance from four aspects:(a)improved the overall structural stability,(b)increased the hydrophobicity of the local microenvironment around the catalytic triad,(c)enriched the hydrophobic substrate around the enzyme molecule,and(d)lowered the contact frequency between OS molecules and the catalytic *** findings validate that computationaided surface charge engineering is an effective and ingenious rational strategy for tailoring enzyme performance in OSs.

关键词： Surface charge engineering Organic solvent resistance Molecular dynamics simulation Haloalkane dehalogenase