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Gene therapy for monogenic disorders: challenges, strategies, and perspectives

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Journal of Genetics and Genomics 2024年第2期51卷 133-143页

作者： Yi zhang Zhi-Ying wu Department of Medical Genetics and Center for Rare Diseases Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Key Laboratory of Medical Neurobiology of Zhejiang Province HangzhouZhejiang 310009China

Monogenic disorders refer to a group of human diseases caused by mutations in single genes. While disease-modifying therapies have offered some relief from symptoms and delayed progression for some monogenic diseases, most of these diseases still lack effective treatments. In recent decades, gene therapy has emerged as a promising therapeutic strategy for genetic disorders. Researchers have developed various gene manipulation tools and gene delivery systems to treat monogenic diseases. Despite this progress, concerns about inefficient delivery, persistent expression, immunogenicity, toxicity, capacity limitation, genomic integration, and limited tissue specificity still need to be addressed. This review gives an overview of commonly used gene therapy and delivery tools, along with the challenges they face and potential strategies to counter them.

关键词： Gene therapy Monogenic diseases Geneediting Genedelivery Challenges

Balancing electron transfer and intermediate adsorption ability of metallic Ni-Fe-RE-P bifunctional catalysts via 4f-2p-3d electron interaction for enhanced water splitting

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Journal of Energy Chemistry 2024年第7期94卷 458-465页

作者： Hong-Rui Zhao cheng-Zong Yuan Chenliang Zhou Wenkai Zhao Lunliang zhang Cong-Hui Li Lei Xin Fuling wu Shufeng Ye Xiaomeng zhang Yunfa Chen School of Rare Earths University of Science and Technology of ChinaHefei 230026AnhuiChina Jiangxi Province Research Institute of Rare Earths Ganjiang Innovation AcademyChinese Academy of SciencesGanzhou 341119JiangxiChina State Key Laboratory of Multiphase Complex Systems Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China

Balancing electron transfer and intermediate adsorption ability of bifunctional catalysts via tailoring electronic structures is crucial for green hydrogen production,while it still remains challenging due to lacking efficient ***,one efficient and universal strategy is developed to greatly regulate electronic structures of the metallic Ni-Fe-P catalysts via in-situ introducing the rare earth(RE)atoms(Ni-Fe-RE-P,RE=La,Ce,Pr,and Nd).Accordingly,the as-prepared optimal Ni-Fe-Ce-P/CC self-supported bifunctional electrodes exhibited superior electrocatalytic activity and excellent stability with the low overpotentials of 247 and 331 mV at 100 mA cm^(-2) for HER and OER,*** the assembled electrolyzer,the Ni-Fe-Ce-P/CC as bifunctional electrodes displayed low operation potential of 1.49 V to achieve a current density of 10 mA cm^(-2),and the catalytic performance can be maintained for 100 *** results combined with density functional theory(DFT)calculation reveal that Ce doping leads to electron decentralization and crystal structure distortion,which can tailor the band structures and d-band center of Ni-Fe-P,further increasing conductivity and optimizing intermediate adsorption *** work not only proposes a valuable strategy to regulate the electron transfer and intermediate adsorption of electrocatalysts via RE atoms doping,but also provides a deep under-standing of regulation mechanism of metallic electrocatalysts for enhanced water splitting.

关键词： RE atoms Electron transfer Adsorption energy Oxygen evolution Hydrogen evolution

Tuina alleviates neuropathic pain through regulate the activation of microglia and the secretion of inflammatory cytokine in spinal cord

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Journal of Traditional Chinese Medicine 2024年第4期44卷 762-769页

作者： wu Zhiwei ZHU Qingguang KONG Lingjun SONG Pengfei ZHOU Xin GUO Guangxin zhang Shuaipan HE Tianxiang cheng Yanbin FANG Min Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Shanghai University of Traditional Chinese MedicineShanghai 200437China Institute of Tuina Shanghai Institute of Traditional Chinese MedicineShanghai 200437China Shuguang Hospital Shanghai University of Traditional Chinese MedicineShanghai 200021China Department of Acupuncture and Tuina Shanghai University of Traditional Chinese MedicineShanghai 201203China

OBJECTIVE:To observe the analgesic effects of Tuina on neuropathic pain(NPP)and the underlying ***:Forty-eight Sprague-Dawley(SD)rats were assigned by random into three treatment groups:sham,chronic constriction injury(CCI),and *** group contained sixteen *** model was generated by ligating the right sciatic *** changes of CCI were assessed by the paw withdrawal threshold(PWT)and paw withdrawal latency(PWL).In addition,biochemical techniques such as immunofluorescence staining,enzyme-linked immunosorbent assay(ELISA)and Western blotting were used to profile levels of microglia activation and inflammatory factors in the spinal dorsal horn(SDH)of ***(clockwise pressing and rubbing)was performed at chengshan(BL57)to observe the analgesic effects on CCI rats and the underlying ***:Rats with CCI experienced significant reduction in the PWT and PWL of the right hind paw relative to CCI group at day *** treatment rescued this situation significantly on days 10 and ***,Iba-1,microglia M1 receptor CD68,tumor necrosis factor-α(TNF-α),and interleukin-1β(IL-1β)were higher in the right SDH for CCI group compared to the sham group on day *** expected,Tuina partially downregulated the CCI-induced overexpressed Iba-1,CD68,TNF-α,and IL-1βin the SDH of CCI ***:Tuina induces a time-dependent cumulative analgesic effect in CCI rats by inhibiting the activation of microglia and the secretion of IL-1βand TNF-αin SDH.

关键词： Tuina neuralgia microglia inflammatory cytokine spinal cord

Feeding prehistoric coastal community:A study of marine faunal remains at the Jingtoushan site

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Science China Earth Sciences 2024年第5期67卷 1574-1590页

作者： Endong wu Guoping SUN Ying zhang School of Culture History and LanguageAustralian National UniversityCanberra 2600Australia Zhejiang Provincial Institute of Cultural Relics and Archaeology Hangzhou 310012China National Centre for Archaeology Beijing 100013China

This article examines the abundant marine mollusc,and fish remains at the Jingtoushan shell midden(8,300 to7,800 cal a BP)in Zhejiang Province,China,to investigate the fishing economy,community development,the palaeoenvironment,and their interactions among the prehistoric populations in the lower Yangtze River Basin and southeastern coastal *** also attempts to explore the prosperity and decline of coastal settlements in China during the Neolithic Age and the potential reasons for their rise and fall,*** on the ecological and biological principles of marine animals,standard zooarchaeological methods and radiocarbon dating analysis are used for sampling,identification,measurement,and *** show that at least 11 mollusc taxa and 14 fish taxa can be identified from the Jingtoushan faunal *** ancient Jingtoushan residents possibly lived in a settlement close to the coast and engaged in inshore and offshore fishing,hunting,and gathering as their primary subsistence strategies,with low-level rice cultivation as a supplementary means of ***,the changes in the coastal environment could be one of the reasons why the Jingtoushan residents abandoned their *** research contributes to Chinese Neolithic archaeology with new evidence of the exploitation of marine resources around 8000 a BP in the eastern coastal areas and the relationship between Neolithic community development and environmental changes.

关键词： Neolithic Age Marine faunal remains Fishing economy Palaeoenvironment Community development

Experimental investigation on rockburst characteristics of highly stressed D-shape tunnel subjected to impact load

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Underground Space 2024年第6期19卷 153-168页

作者： wuxing wu Fengqiang Gong Zongxian zhang School of Civil Engineering Southeast UniversityNanjing 211189China State Key Laboratory of Geomechanics and Geotechnical Engineering Institute of Rock and Soil MechanicsChinese Academy of SciencesWuhan 430071China Oulu Mining School University of OuluOulu 90570Finland

Rockburst has always been a challenge for the safe construction of deep underground *** study investigated the rockburst characteristics in highly-stressed D-shape tunnels under impact loads from rock blasting and other mining-related dynamics *** biaxial Hopkinson pressure bar was utilized to apply varying biaxial prestress and the same impact loads to cube specimens with D-shape ***-speed camera and digital image correlation(DIC)were used to capture the failure process and strain field of *** test results demonstrate that the D-shape hole specimen experience rockburst under coupled static stress and impact *** this circumstance,the rockburst mechanism of the D-shaped hole specimens involves spalling in sidewall induced by impact load,indicating dynamic tensile *** high static prestress provides the initial stress field,while the impact load disrupts the stress equilibrium,result in the stress or strain concentration in the sidewall of the D-shape hole,inducing ***,the rockburst process can be divided into(1)calm stage,(2)crack initiation,propagation,and coalesce stage,(3)spalling stage and(4)rock fragments ejection *** load triggers rockburst occurrence,while vertical stress further determines the rockburst *** influence range and magnitude of strain concentration zone and displacement deformation of the tunnel surrounding rock increases with increasing vertical stress,thus inducing more severe rockburst.

关键词： Rockburst Spalling D-shape tunnel Impact load Biaxial prestresses Biaxial Hopkinson pressure bar

Root-derived long-distance signals trigger ABA synthesis and enhance drought resistance in Arabidopsis

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Journal of Genetics and Genomics 2024年第7期51卷 749-761页

作者： Qian-Qian Liu Jin-Qiu Xia Jie wu Yi Han Gui-Quan zhang Ping-Xia Zhao cheng-Bin Xiang Division of Life Sciences and Medicine Division of Molecular&Cell BiophysicsHefei National Science Center for Interdisciplinary Sciences at the MicroscaleUniversity of Science and Technology of ChinaThe Innovation Academy of Seed DesignChinese Academy of SciencesHefeiAnhui 230027China College of Life Sciences Anhui Agricultural UniversityHefeiAnhui 230036China College of Agronomy South China Agricultural UniversityGuangzhouGuangdong 510642China School of Biology and Basic Medical Sciences Soochow UniversitySuzhouJiangsu 215123China

Vascular plants have evolved intricate long-distance signaling mechanisms to cope with environmental stress,with reactive oxygen species(ROS)emerging as pivotal systemic signals in plant stress ***,the exact role of ROS as root-to-shoot signals in the drought response has not been *** this study,we reveal that compared with wild-type plants,ferric reductase defective 3(frd3)mutants exhibit enhanced drought resistance concomitant with elevated NINE-CIS-EPOXYCAROTENOID DIOXYGENASE 3(NCED3)transcript levels and abscisic acid(ABA)contents in leaves as well as increased hydrogen peroxide(H_(2)O_(2))levels in roots and *** experiments distinctly illustrate that drought resistance can be conferred by the frd3 rootstock regardless of the scion genotype,indicating that long-distance signals originating from frd3 roots promote an increase in ABA levels in ***,the drought resistance conferred by the frd3 mutant rootstock is weakened by the CAT2-overexpressing scion,suggesting that H_(2)O_(2)may be involved in long-distance ***,the results of comparative transcriptome and proteome analyses support the drought resistance phenotype of the frd3 *** together,our findings substantiate the notion that frd3 root-derived long-distance signals trigger ABA synthesis in leaves and enhance drought resistance,providing new evidence for root-to-shoot long-distance signaling in the drought response of plants.

关键词： frd3 Drought resistance Root-to-shoot long-distance signals Reactive oxygen species(ROS) H_(2)O_(2) Iron ABA

Recent Advances in C-F Bond Formation from Carbon-Centered Radicals

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Chinese Journal of Chemistry 2024年第9期42卷 1009-1031页

作者： Jihua zhang Juanjuan Wang Qiang cheng College of Chemistry and Molecular Sciences Wuhan UniversityWuhanHubei 430072China

Construction of C-F bonds is a direct and efficient method for introducing fluorine into pharmaceuticals,agrochemicals,and *** such as nucleophilic,electrophilic,radical,and transition-metal catalyzed fluorination have been developed to meet the demand of diverse C-F bond *** them,radical fluorination has been witnessed with substantial advancement in a recent ***,we reviewed methods for formation of C-F bonds with carbon-centered radicals as key intermediates,especially in recent five *** introduce in the paper with different fluorinating reagents,strategies for radical generation,and application in late-stage functionalization and synthesis of PET *** also indicate the current limitations and propose the direction of the field for the future development.

关键词： Fluorine Fluorinating reagents Late-stage fluorination [^(18)F]jfluorination Radical reactions Synthetic methods

Scene 3-D Reconstruction System in Scattering Medium

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Computers, Materials & Continua 2024年第8期80卷 3405-3420页

作者： Zhuoyifan zhang Lu zhang LiangWang Haoming wu School of Artificial Intelligence Beijing University of Posts and TelecommunicationsBeijing100876China School of Information and Communication Engineering Hainan UniversityHaikou570228China School of Computer Science and Technology Hainan UniversityHaikou570228China

Research on neural radiance fields for novel view synthesis has experienced explosive growth with the development of new models and *** NeRF(Neural Radiance Fields)algorithm,suitable for underwater scenes or scattering media,is also *** underwater 3D reconstruction systems still face challenges such as long training times and low rendering *** paper proposes an improved underwater 3D reconstruction system to achieve rapid and high-quality 3D ***,we enhance underwater videos captured by a monocular camera to correct the image quality degradation caused by the physical properties of the water medium and ensure consistency in enhancement across ***,we perform keyframe selection to optimize resource usage and reduce the impact of dynamic objects on the reconstruction *** pose estimation using COLMAP,the selected keyframes undergo 3D reconstruction using neural radiance fields(NeRF)based on multi-resolution hash encoding for model construction and *** terms of image enhancement,our method has been optimized in certain scenarios,demonstrating effectiveness in image enhancement and better continuity between consecutive frames of the same *** terms of 3D reconstruction,our method achieved a peak signal-to-noise ratio(PSNR)of 18.40 dB and a structural similarity(SSIM)of 0.6677,indicating a good balance between operational efficiency and reconstruction quality.

关键词： Underwater scene reconstruction image enhancement NeRF

A New Vehicle Detection Framework Based on Feature-Guided in the Road Scene

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Computers, Materials & Continua 2024年第1期78卷 533-549页

作者： Tianmin Deng Xiyue zhang Xinxin cheng School of Traffic and Transportation Chongqing Jiaotong UniversityChongqing400074China

Vehicle detection plays a crucial role in the field of autonomous driving ***,directly applying deep learning-based object detection algorithms to complex road scene images often leads to subpar performance and slow inference speeds in vehicle *** a balance between accuracy and detection speed is crucial for real-time object detection in real-world road *** paper proposes a high-precision and fast vehicle detector called the feature-guided bidirectional pyramid network(FBPN).Firstly,to tackle challenges like vehicle occlusion and significant background interference,the efficient feature filtering module(EFFM)is introduced into the deep network,which amplifies the disparities between the features of the vehicle and the ***,the proposed global attention localization module(GALM)in the model neck effectively perceives the detailed position information of the target,improving both the accuracy and inference speed of ***,the detection accuracy of small-scale vehicles is further enhanced through the utilization of a four-layer feature pyramid *** results show that FBPN achieves an average precision of 60.8% and 97.8% on the BDD100K and KITTI datasets,respectively,with inference speeds reaching 344.83 frames/s and 357.14 frames/*** demonstrates its effectiveness and superiority by striking a balance between detection accuracy and inference speed,outperforming several state-of-the-art methods.

关键词： Driverless car vehicle detection channel attention mechanism deep learning