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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

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A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2025年第2期20卷 503-517页

作者： Qi liu Jianye Xie Runxue Zhou jin Deng Weihong Nie Shuwei Sun Haiping Wang Chunying Shi Department of Human Anatomy Histology and EmbryologySchool of Basic MedicineQingdao UniversityQingdaoShandong ProvinceChina Department of Neurology The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina Department of General Practice The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic ***,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in ***,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic *** metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ***,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel ***-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in *** results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor *** findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

关键词： angiogenesis biomaterial blood-brain barrier cerebral ischemia/reperfusion injury control release drug delivery inflammation QK peptides matrix metalloproteinase-2 neuroprotection self-assembling nanofiber hydrogel

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Propagating subduction initiation of the Caroline Plate at the Mussau Trench

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Science China Earth Sciences 2025年第1期68卷 253-269页

作者： Chun-feng LI Yongkang DENG Tao WU Dongdong DONG Guoliang ZHANG Jiazheng ZHANG Yutao liu Yaqing LI Fugui TANG Lulu ZHANG Department of Marine Sciences Zhejiang University Laboratory of Marine Mineral Resources Laoshan Laboratory Key Lab of Marine Geology and Environment Institute of Oceanology Chinese Academy of Sciences Key Lab of Ocean and Marginal Sea Geology South China Sea Institute of Oceanology Chinese Academy of Sciences Science & Technology on Integrated Information System Lab Institute of Software Chinese Academy of Sciences

New seismic imaging from the Mussau Trench confirms that, under horizontal compression on an oceanic plate boundary, it is within the young and weak oceanic plate that a trench will develop, and it is the young plate, not so long after its birth, that starts to subduct toward the old plate. The Mesozoic Pacific Plate cannot easily bend, under the joint horizontal compression and vertical gravity pull, even with a pre-existing weak zone in place and with a large age offset across the plate boundary. The bending of the Caroline Plate near the northern end of the Mussau Trench started only after a long-time span of trench migration, and/or after a prolonged transition from initial compression to trench development. Highly contrasting trench deformation and sedimentary accretion between two parallel seismic sections support an evident migration of underthrusting or significant longitudinal heterogeneity along the trench. The swift transition from underthrusting to non-thrusting can be explained by a counter-clockwise rotation of the Caroline Plate. That miniature accretionary wedges develop even before the subduction initiates imply strong compression and uplifting before the underthrusting can kick-start. Rotation of the Caroline Plate have been halted as the Mussau Trench is seismically rather quiet and the Lyra Trough to the east shows relaxational extension.

关键词： Mussau Trench Subduction initiation Seismic reflection Caroline Plate

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Effect of Ti Additions on Mechanical and Thermodynamic Properties of W-Ti Alloys: A First-principles Study

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Journal of Wuhan University of Technology(Materials Science) 2025年第1期40卷 246-257页

作者： ZHANG Jian NIE Wei HUANG jin ZHU Ke liu Ruxia ZHANG Ruizhi LUO Guoqiang SHEN Qiang State Key Laboratory of Advanced Technology for Materials Synthesis and Processing Wuhan University of TechnologyWuhan 430070China Institute for Carbon Neutrality University of Science and Technology BeijingBeijing 100083China

The mechanical and thermodynamic properties of W-Ti alloys(including W_(15)Ti_(1),W_(14)Ti_(2),W_(12)Ti_(4) and W_(8)Ti_(8) alloys)were investigated by the first-principles approach based on density functional *** results indicate that W-Ti alloys except W_(8)Ti_(8) are thermodynamically *** modulus and hardness of W-Ti alloys are smaller than those of pure tungsten and gradually decrease with increasing Ti ***,their B/G ratios and Poisson's ratios exceed those of pure tungsten,suggesting that the introduction of Ti decreases the mechanical strength while enhancing the ductility of W-Ti *** thermal expansion coefficients for W-Ti alloys all surpass those of pure tungsten,indicating that the introduction of titanium exacerbates the thermal expansion behavior of W-Ti ***,elevated pressure has the capacity to suppress the thermal expansion tendencies in titanium-doped tungsten *** study offers theoretical insights for the design of nuclear materials by exploring the mechanical and thermodynamic properties of W-Ti alloys.

关键词： first-principles mechanical properties thermodynamic properties tungsten-titanium alloys

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Studies on Mutagenicity and Teratogenicity of Sarafloxacin

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Agricultural Sciences in China 2002年第1期1卷 108-113页

作者： SHEN Jian-zhong, SHEN Chuan, XIAO Xi-long, LI Jun-suo liu jin-feng, ZHANG Su-xia, ZHOU Zong-can and FU Juan-ling( College of Veterinary Medicine, China. Agricultural University, Beijing 100094 Beijing Medical University, Beijing 100083) College of Veterinary Medicine China Agricultural University Beijing 100094 Beijing Medical University Beijing 100083

Wistar rats and closed Kunming strain mice were selected to study the genetic toxicity of sarafloxacin. The results indicated that sarafloxacin had no significant toxic effect of an excreted mutagen in S. typhimurium strains, and did not induce significantly higher percentages of polychromatic erythrocytes with micronuclei (MNPCE) in mice. No significant mutagenic activity was observed in dominant lethal assay. At 5 and 50mg/kg b.w. , sarafloxacin did not produce significant effects on the reproductive parameters of litters and fetal growth, and did not induce the teratogenic effects on fetuses. Sarafloxacin induced some toxic effects on body length and skeletal growth in fetuses of 500mg/kg b.w., but had no significant dose - response relationship among the administered dosages of sarafloxacin. The results of the genetic toxicology above indicated that no evidence showing sarafloxacin was mutagenic and potentially teratogenic for animals.

关键词： Sarafloxacin Rat Mouse Mutagenicity Teratogenicity Reproductive toxicity

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HLA-Cw位点低分辨基因分型“纯合子”的等位基因特性研究

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中华血液学杂志 2009年第2期30卷 92-96页

作者：梁飞刘楠金荔袁方刘金锋孙玉英奚永志军事医学科学院附属医院免疫学研究室及国家生物医学分析中心免疫实验室北京100071

目的研究HLA—Cw位点低分辨基因分型“纯合子”的等位基因特性，为临床移植配型提供精确资料。方法在43例血缘关系造血干细胞移植（HSCT）供受者中，对中国最常见的低分辨基因分型Cw＊03和Cw＊07的“纯合子”个体采用聚合酶链反应-序列... 详细信息

目的研究HLA—Cw位点低分辨基因分型“纯合子”的等位基因特性，为临床移植配型提供精确资料。方法在43例血缘关系造血干细胞移植（HSCT）供受者中，对中国最常见的低分辨基因分型Cw＊03和Cw＊07的“纯合子”个体采用聚合酶链反应-序列特异性引物（PCR—SSP）高分辨基因分型方法进行等位基因定型，并采用自主研制的三维结构匹配软件系统（HLA Stnic Markversion 1.0）对其等位基因产物进行三维结构匹配，以预测不同分辨率分型结果对移植物抗宿主病（GVHD）发生的影响。结果低分辨基因分型Cw＊03、Cw＊07“纯合子”个体的高分辨基闵分型结果显尔Cw＊03及Cw＊07的纯合子分别为14％和43％，其余均为Cw＊03及Cw＊07杂合子个体。可见其低分辨基因分型易造成供受者间等位基因的错配；在有家系校正的情况下，标本的低分辨模糊结果可以通过家系遗传分析来校正定型；在无家系校正的情况下，应通过高分辨基因分型来确定等位基因，三维结构差异分析则显示这些错配有可能造成HSCT后GVHD的发生。结论当低分辨基因分型结果只出现Cw位点“纯合子”时，有家系的标本应当以家系分型结果校正定型，无家系校正的标本应当用高分辨基因分型方法进行核实，从而为临床移植提供棒确的配型报告，以防止无关供-受者HSCT后因等位基因错配而引起的严重GVHD。

关键词： HLA-Cw位点“纯合子” 等位基因聚合酶链反应三维结构匹配

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天津宝坻县隐伏岩溶区地下水开发与地裂缝成生关系研究

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水文地质工程地质 2005年第6期32卷 38-41页

作者：刘金峰谢健邢罡石家庄经济学院工程学院石家庄050031 北京市地质勘察技术院北京102209

在调查分析地裂缝时空分布特征的基础上,研究地裂活动与区内水文地质条件、地下水开采过程的关系,认为过量开采奥灰水是产生地裂缝的主导因素。随着水位下降,盖层介质固结压密作用是导致地面压缩变形乃至地裂缝发生的直接原因。地下水... 详细信息

在调查分析地裂缝时空分布特征的基础上,研究地裂活动与区内水文地质条件、地下水开采过程的关系,认为过量开采奥灰水是产生地裂缝的主导因素。随着水位下降,盖层介质固结压密作用是导致地面压缩变形乃至地裂缝发生的直接原因。地下水系统结构特征以及固结压密作用的物质基础———松散盖层的厚度、岩性,是构成地面不均匀沉降的充要条件。当这种不均匀变形程度足以使土体连续性破坏时,则地裂缝便在沉降区应力集中的部位发生。

关键词：松散盖层岩溶水地裂缝固结压密地面沉降

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论企业的会计监督

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科技情报开发与经济 2008年第6期18卷 119-120页

作者：刘锦凤阳泉供电分公司山西阳泉045000

简述了会计监督的内涵与必要性,分析了会计监督弱化的原因,提出了有效解决会计监督弱化问题的对策。

关键词：企业管理会计监督会计监督弱化

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经济型轿车安全库存研究

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天津汽车 2006年第1期 7-8,25页

作者：刘凤金天津一汽夏利汽车股份有限公司销售分公司

建立安全合理的产品库存可以有效的为企业节约成本,满足需求的变化。文章介绍了国内企业通常对库存管理的一些规定,重点介绍了运用概率方法确定安全库存的方法,为轿车企业及其经销商确定安全库存提供了非常有效的方法。同时,考虑到实际... 详细信息

建立安全合理的产品库存可以有效的为企业节约成本,满足需求的变化。文章介绍了国内企业通常对库存管理的一些规定,重点介绍了运用概率方法确定安全库存的方法,为轿车企业及其经销商确定安全库存提供了非常有效的方法。同时,考虑到实际运作情况,结合实际运距因素,介绍了如何确定企业的最佳订货点,对轿车厂家及其经销商的库存管理有较高的参考价值。

关键词：轿车安全库存满意度

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磁敏感加权成像在出血性脑梗死中的诊断价值分析

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中国CT和MRI杂志 2015年第9期13卷 36-38页

作者：刘劲峰广东三九脑科医院影像诊断中心广东广州510510

目的探讨磁敏感加权成像在出血性脑梗死中的诊断价值。方法以我院放射科收治的25例缺血性脑卒中患者为研究对象,根据其临床资料进行回顾性分析,分别对其进行常规MRI、扩散加权成像以及磁敏感加权成像检查,根据图像分析结果比较不同扫描... 详细信息

目的探讨磁敏感加权成像在出血性脑梗死中的诊断价值。方法以我院放射科收治的25例缺血性脑卒中患者为研究对象,根据其临床资料进行回顾性分析,分别对其进行常规MRI、扩散加权成像以及磁敏感加权成像检查,根据图像分析结果比较不同扫描序列检出梗死灶内出血灶的情况。结果 25例患者发现47个出血灶,其中SWI序列显示出血灶46个,T1WI序列显示出血灶27个,DWI序列显示出血灶16个,T2WI显示出血灶11个,SWI序列对出血灶的检出率明显高于T1WI、T1W2、DWI,p<0.05,差异有统计学意义;SWI序列发现14例患者存在微出血灶的情况。结论磁敏感加权成像用于临床诊断出血性脑梗死,其影像具有一定的特征性,对病灶内出血情况的显示优于常规MRI和DWI序列,可以了解梗死灶内静脉血管的变化和微小出血灶的情况,能为患者临床治疗提供重要的参考依据,具有较高的临床使用价值。

关键词：出血性脑梗死磁敏感加权成像临床诊断

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