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AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis

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Neural Regeneration Research 2025年第8期20卷 2408-2419页

作者： Ruiqi Qiu Mingzhu Yang Xiuxiu Jin Jingyang Liu Weiping Wang Xiaoli Zhang Jinfeng Han Bo Lei henan Eye Hospital Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Eye institute Henan Academy of Innovations in Medical ScienceZhengzhouHenan ProvinceChina Branch of National Clinical Research Center for Ocular Disease Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina Academy of Medical Science Zhengzhou UniversityZhengzhouHenan ProvinceChina

Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell ***,there is no effective treatment for retinitis pigmentosa caused by PDE6B ***-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis *** aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal *** do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and ***-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western ***2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 *** expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type *** Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction ***,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B ***,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B *** data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upr

关键词： apoptosis AAV2-PDE6B ERK1/2 gene therapy phototransduction proteomics rd10 retinitis pigmentosa

Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

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Neural Regeneration Research 2025年第9期20卷 2538-2555页

作者： Jie Jin Huajing Zhang Qianying Lu Linqiang Tian Sanqiao Yao Feng Lai Yangfan Liang Chuanchuan Liu Yujia Lu Sijia Tian Yanmei Zhao Wenjie Ren institute of Disaster and Emergency Medicine Tianjin UniversityTianjinChina Key Laboratory for Disaster Medicine Technology TianjinChina henan Medical Key Laboratory for Research of Trauma and Orthopedics The Third Affiliated Hospital of Xinxiang Medical UniversityXinxiangHenan ProvinceChina Clinical Medical Center of Tissue Engineering and Regeneration Xinxiang Medical UniversityXinxiangHenan ProvinceChina institutes of Health Central Plain Xinxiang Medical UniversityXinxiangHenan ProvinceChina School of Public Health Xinxiang Medical UniversityXinxiangHenan ProvinceChina

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive ***,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's *** offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug *** review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future *** principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various *** the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain *** have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain *** are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional *** use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective *** this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular tar

关键词： blood-brain barrier cognitive dysfunction exosomes gene silencing immunotherapy inorganic nanomaterials liposome nanoparticles neuroinflammation polymer nanoparticles stem cells

AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

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Neural Regeneration Research 2025年第1期20卷 253-264页

作者： Zhengwei Hu Jing Yang Shuo Zhang Mengjie Li Chunyan Zuo Chengyuan Mao Zhongxian Zhang Mibo Tang Changhe Shi Yuming Xu Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Academy of Medical Sciences of Zhengzhou University ZhengzhouHenan ProvinceChina NHC Key Laboratory of Prevention and treatment of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina henan Key Laboratory of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina institute of Neuroscience Zhengzhou UniversityZhengzhouHenan ProvinceChina Sino-British Research Centre for Molecular Oncology National Centre for International Research in Cell and Gene TherapySchool of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Department of Gerontology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control *** this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s *** used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse *** overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated *** also alleviated the concentration of microglia and astrocytes around *** APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin *** of HSP70 and HSP40,which have functional relevance to CHIP,were also *** nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of *** research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 ***,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

关键词： adeno-associated virus Alzheimer’s disease APP/PS1 mice carboxyl terminus of Hsp70 interacting protein gene therapy

Photoinduced radical sulfur dioxide insertion with asymmetric cyclization of alkenes: accessing β-chiral sulfones bearing S-stereocentric cyclic sulfinamides

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Science China Chemistry 2025年第01期 257-263页

作者： Jiapian Huang Chenxin Wang Xu Wang Xiaoyu Zhou Wei Xiao Jie Wu School of Pharmaceutical and Chemical Engineering & institute for Advanced Studies Taizhou University State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences School of Chemistry and Chemical Engineering Henan Normal University

The generation of various β-chiral sulfones bearing chiral cyclic sulfinamides through photoredox-catalyzed sulfur dioxide insertion with asymmetric radical cyclization is described. This method features a broad substrate scope and excellent stereospecificity. Computational studies reveal that the dispersion interaction between sulfinyl group and CH2SO2Ph group plays a crucial role in the stereoselectivity control.

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Characteristics of Breccias and C-O-Sr-S Isotope geochemistry of the Duocaima Pb-Zn Deposit in Tuotuohe, Qinghai Province: Implications for the Ore-forming Process

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Acta geologica Sinica(English Edition) 2015年第5期89卷 1568-1587页

作者： HAO Hongda SONG Yucai LI Liansong JIA Zongyong WANG Yuankui LIU Qun institute of geology Chinese Academy of Geological Sciences School of Earth Sciences and Resources China University of Geosciences no.5 institute of geology and Mineral Resources exploration

The Duocaima carbonate-hosted Pb-Zn deposit is a newly found large deposit in the southern area of Qinghai *** this paper, the characteristics, genesis, significance to Pb-Zn mineralization of the widely developed breccias, and the ore-forming process have been carefully studied based on geological documentation of drilling holes, microscopic observations of petrography and microstructure and some stable isotope *** on the compositions of the clast and matrix, the breccias can be classified into three types： limestone clasts cemented by marl; limestone clasts with fine-grained calcareous materials; and limestone clasts cemented by hydrothermal *** mineralization in the first type of breccia is weak, whereas it is strong in the latter two types of *** to the locations of occurrence and structural characteristics of the breccias along with the relationship between the breccias and mineralization, part of the limestone clasts that are cemented by marl and outcrop in the contact zone between the Wudaoliang Formation（Nw） and the underlying Jiushidaoban Formation（Pj） are attributed to synsedimentary fault-genetic breccia, whereas the last of the limestone clasts that are cemented by marl and developed in the Jiushidaoban Formation（Pj） are attributed to the breccia generated by karst cave collapse; the limestone clasts with fine-grained calcareous materials and the limestone clasts cemented by hydrothermal calcite are attributed to breccia formed by hydrothermal *** breccia formed by karst collapse had consistently evolved for a long period of time, while the breccias with other origins were formed around the period of mineralization（i.e., about or slightly later than 20–16 Ma）.The breccia generated by karst cave collapse and hydrothermal dissolution are somewhat related; the formation of the breccia from karst cave collapse provided open space for the later mineralization and reaction between hydrothermal fluids an

关键词： breccias hydrothermal dissolution karst cave Mississippi Valley Type Pb-Zn deposit Duocaima

Seismic Imaging of Complex Structures in the Tarim Basin

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Journal of Earth Science 2015年第4期26卷 586-591页

作者： Ning Guo Chao Wu Stuart Fagin geo Tech Groups LLC institute of exploration and Development CPNCKorla geo Image Resources LLC

Conventional time imaging techniques are not capable of producing accurate seismic imaging of the subsurface in the mountain front of the Tarim Basin, China. Their imaged structures have led to some major drilling failures before, bearing a disrepute that ＂their structural closures have wheels and their structural highs have springs＂. This article first lists the imaging challenges, and explains in a schematic why the time imaging techniques fail in this area. Then through a series of real data examples, it demonstrates that when there exist lateral velocity variations, depth imaging is the only solution to tackle the imaging challenges in this area. Depth imaging accounts for the complexity of the wavefield, therefore produces superior and geological plausible images. The core task in properly performing depth imaging is building the velocity model. This article stresses some the main aspects in this regard.

关键词： time migration depth migration seismic image quality velocity model building anisotropy.

geochemical significance of the Paleogene soda-deposits bearing strata in Biyang Depression,henan Province

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Science China Earth Sciences 2015年第10期58卷 129-137页

作者： YANG JiangHai YI ChengLong DU YuanSheng ZHANG ZongHeng YAN JiaXin State Key Laboratory of Biogeology and Environmental geology China University of Geosciences geological exploration institute of henan henan Provincial Bureau of geo-exploration and Mineral Development

The Biyang Depression, lying in the eastern Nanxiang Basin, has a dustpan-shape with faults developed to the southwest and southeast. The Paleogene Hetaoyuan Formation in this depression hosts one of the oldest soda-deposits, the Anpeng deposit. These sodium carbonate-bearing strata consist of lutites, muddy dolomites, and bedded soda-deposits, which are dominated by nahcolite with little trona, mirabilite, and halite. In the top Unit 3 and lower Unit 2 of Hetaoyuan Formation where the sodium carbonates are concentrated, dolomitic shale, muddy carbonate, and sodium carbonate can be separated based on their distinct A1203, TiO〉 Na20, MgO＋CaO, and LOI （loss on ignition） contents. By using Na20/（MgO＋CaO） ratio as an indicator for the relative concentration of Na carbonates to Mg-Ca carbonates, the muddy dolomites can be classified into two groups. One group with Na20/（MgO＋CaO）〈0.6 exhibits a positive correlation between this ratio and AI203＋TiO2 content, an proxy for ter- rigenous clastic input and the other group with Na20/（MgO＋CaO）〉0.6 presents a negative correlation. As the clastic propor- tion decreases, the former indicates that it tends to form pure Mg-Ca carbonates reflecting evaporation less than or equal to re- plenishment for the lake water in a relative humid climate, and the latter reveals a trend to form sodium carbonates with lake water＇s evaporation more than replenishment in a relatively dry climate. From muddy dolomite to sodium carbonate samples, with Na20/（MgO＋CaO） ratio increasing, the A1 normalized Zr, Ti, La, K, Rb, and Ba tend to be enriched and the post-Archean Average Shale （PAAS） normalized positive Eu anomaly becomes more obvious. Integrated with the high B contents and the report of searlesite in the bedded sodium carbonates and the regional extensional tectonic regime, the above geochemical characteristics were interpreted to signify hydrothermal contribution to forming these soda-deposits through the deep fault systems of basin margins.

关键词： sodium carbonate-bearing strata nahcolite evaporation and concentration hydrothermal activity

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Alignment error modeling and control of a double-sided microlens array during precision glass molding

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Microsystems & Nanoengineering 2024年第2期10卷 311-322页

作者： Zihao Zeng Tianfeng Zhou Qian Yu Jia Zhou Gang Wang Qiuchen Xie Zifan Wang Xiaoqiang Yao Yubing Guo School of Medical Technology Beijing Institute of TechnologyNo.5 Zhongguancun South StreetHaidian DistrictBeijing100081China School of Mechanical Engineering Beijing Institute of TechnologyNo.5 Zhongguancun South StreetHaidian DistrictBeijing100081China

Double-sided microlens arrays(DSMLAs)include combinations of two single-sided MLAs to overcome positioning errors and greatly improve light transmissivity compared to other types of *** glass molding(PGM)is used to fabricate DSMLAs,but controlling alignment errors during this process is *** this paper,a mold assembly was manufactured with a novel combination of materials to improve the alignment accuracy of mold cores during PGM by using the nonlinear thermal expansion characteristics of the various materials to improve the DSMLA alignment *** establishing a mathematical model of the DSMLA alignment error and a thermal expansion model of the mold-sleeve pair,the relationship between the maximum alignment error of the DSMLA and the mold-sleeve gap was *** research provides a method to optimize the mold-sleeve gap and minimize the alignment error of the *** measured DSMLA alignment error was 10.56μm,which is similar to the predicted maximum alignment *** measurements showed that the uniformity of the homogenized beam spot was 97.81%,and the effective homogeneous area accounted for 91.66%of the total *** proposed method provides a novel strategy to improve the performance of DSMLAs.

关键词： sided alignment error

Magnetic Coupler Robust Optimization Design for Electric Vehicle Wireless Charger Based on Improved Simulated Annealing Algorithm

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Automotive Innovation 2022年第1期5卷 29-42页

作者： Zhenpo Wang Lantian Li Junjun Deng Baokun Zhang Shuo Wang School of Mechanical Engineering Beijing Institute of TechnologyNO.5 Zhongguancun StreetBeijingChina Collaborative Innovation Center of Electric Vehicles in Beijing NO.5 Zhongguancun StreetBeijingChina

Fleets of autonomous vehicles including shuttle buses,freight trucks,and road sweepers will be deployed in the Olympic Vil-lage during Beijing 2022 Winter *** requires intelligent charging infrastructure based on wireless power transfer technology to be *** increase the misalignment tolerance of a high-power wireless charger,the robustness of the magnetic coupler should be *** paper presents a new type of unipolar coupler,which is composed of three con-nected coils in *** dimensional configuration of the coils is analyzed by the finite element *** characteristic parameters of the coil are identified with their influence on the self-inductance and coupling *** expert model is built,whose feasibility can be verified in the aimed design *** with the expert model,an improved simulated annealing algorithm with a backtracking mechanism is *** primary coil can reach the expected characteristics from any starting parameter combination through the proposed optimization *** the same conditions in terms of external circuit parameters,ferrite usage,and aluminum shielding,the offset sensitivity of the magnetic coupler can be reduced from 58.79%to 18.89%.A prototype is established,validating the feasibility of the proposed coil structure with the optimized parameter algorithm.

关键词： Wireless power transfer Magnetic coupler Simulated annealing algorithm Robust optimization