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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

Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

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Neural Regeneration Research 2025年第5期20卷 1483-1494页

作者： Xihang Chen Zhifeng Chen Menghua Li Weiwei Guo Shuolong Yuan Liangwei Xu Chang Lin Xi shi Wei Chen shiming yang Senior Department of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of Hearing and Balance Science BeijingChina National Clinical Research Center for Otolaryngologic Diseases BeijingChina Key Laboratory of Hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of Hearing Impairment Prevention and Treatment BeijingChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Otolaryngology Head and Neck Surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

Identification of a dual functional betulinic acid analog for the treatment of osteoarthritis by phenotypic screening

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Science China Life Sciences 2025年第1期68卷 300-302页

作者： Ze-Min Lin Mai Xiang Wen-Hui Wei Shu-Hui Fan Li Chen Jie Wang Xiao-Qian yang Chun-Hao yang shi-Jun He Jian-Ping Zuo Laboratory of Immunopharmacology State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of Sciences School of Pharmacy University of Chinese Academy of Sciences School of Pharmacy Nanjing University of Chinese Medicine State Key Laboratory of Drug Research Department of Medicinal ChemistryShanghai Institute of Materia MedicaChinese Academy of Sciences Innovation Research Institute of Traditional Chinese Medicine Shanghai University of Traditional Chinese Medicine Experiment Center for Science and Technology Shanghai University of Traditional Chinese Medicine

Dear Editor, Phenotypic drug discovery, which observes compound effects on physiology,has given way to targeting specific molecules, but has revived by using modern methods to find drugs based on therapeutic outcomes in disease models(Vincent et al., 2022). Osteoarthritis(OA) is a prevalent chronic joint disorder, primarily affecting knee joints, with osteoclast activation due to low-grade inflammation resulting in increased bone resorption and structural changes in the joint(Katz et al.,2021).

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Joint Feature Encoding and Task Alignment Mechanism for Emotion-Cause Pair Extraction

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Computers, Materials & Continua 2025年第1期82卷 1069-1086页

作者： shi Li Didi Sun College of Computer and Control Engineering Northeast Forestry UniversityHarbin150040China

With the rapid expansion of social media,analyzing emotions and their causes in texts has gained significant ***-cause pair extraction enables the identification of causal relationships between emotions and their triggers within a text,facilitating a deeper understanding of expressed sentiments and their underlying *** comprehension is crucial for making informed strategic decisions in various business and societal ***,recent research approaches employing multi-task learning frameworks for modeling often face challenges such as the inability to simultaneouslymodel extracted features and their interactions,or inconsistencies in label prediction between emotion-cause pair extraction and independent assistant tasks like emotion and cause *** address these issues,this study proposes an emotion-cause pair extraction methodology that incorporates joint feature encoding and task alignment *** model consists of two primary components:First,joint feature encoding simultaneously generates features for emotion-cause pairs and clauses,enhancing feature interactions between emotion clauses,cause clauses,and emotion-cause ***,the task alignment technique is applied to reduce the labeling distance between emotion-cause pair extraction and the two assistant tasks,capturing deep semantic information interactions among *** proposed method is evaluated on a Chinese benchmark corpus using 10-fold cross-validation,assessing key performance metrics such as precision,recall,and F1 *** results demonstrate that the model achieves an F1 score of 76.05%,surpassing the state-of-the-art by 1.03%.The proposed model exhibits significant improvements in emotion-cause pair extraction(ECPE)and cause extraction(CE)compared to existing methods,validating its *** research introduces a novel approach based on joint feature encoding and task alignment mechanisms,contributing to advancements in emotion-c

关键词： Emotion-cause pair extraction interactive information enhancement joint feature encoding label consistency task alignment mechanisms

Detection and Recognition of Spray Code Numbers on Can Surfaces Based on OCR

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Computers, Materials & Continua 2025年第1期82卷 1109-1128页

作者： Hailong Wang Junchao shi School of Computer Science Zhongyuan University of TechnologyZhengzhou450007China

A two-stage algorithm based on deep learning for the detection and recognition of can bottom spray codes and numbers is proposed to address the problems of small character areas and fast production line speeds in can bottom spray code number *** the coding number detection stage,Differentiable Binarization Network is used as the backbone network,combined with the Attention and Dilation Convolutions Path Aggregation Network feature fusion structure to enhance the model detection *** terms of text recognition,using the Scene Visual Text Recognition coding number recognition network for end-to-end training can alleviate the problem of coding recognition errors caused by image color distortion due to variations in lighting and background *** addition,model pruning and quantization are used to reduce the number ofmodel parameters to meet deployment requirements in resource-constrained environments.A comparative experiment was conducted using the dataset of tank bottom spray code numbers collected on-site,and a transfer experiment was conducted using the dataset of packaging box production *** experimental results show that the algorithm proposed in this study can effectively locate the coding of cans at different positions on the roller conveyor,and can accurately identify the coding numbers at high production line *** Hmean value of the coding number detection is 97.32%,and the accuracy of the coding number recognition is 98.21%.This verifies that the algorithm proposed in this paper has high accuracy in coding number detection and recognition.

关键词： Can coding recognition differentiable binarization network scene visual text recognition model pruning and quantification transport model

内外部经济政策不确定性与企业对外直接投资:风险规避还是出口抑制?

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上海对外经贸大学学报 2021年第6期28卷 71-86页

作者：欧阳艳艳施养劲中山大学国际金融学院广州510275

本文以中国省级经济政策不确定性指数和关税不确定性指数分别作为内外部政策不确定性的代理变量,结合2005~2016年上市公司对外直接投资数据,实证检验内外部政策不确定性对企业对外直接投资的影响。结果发现:内部政策不确定性使企业提高... 详细信息

本文以中国省级经济政策不确定性指数和关税不确定性指数分别作为内外部政策不确定性的代理变量,结合2005~2016年上市公司对外直接投资数据,实证检验内外部政策不确定性对企业对外直接投资的影响。结果发现:内部政策不确定性使企业提高针对国内经济不确定性的风险规避水平,进而促使对外直接投资增加;而外部政策不确定性则显著减少出口贸易规模,进而抑制企业“走出去”。本文以自然灾害作为工具变量,克服内生性之后发现原有结果仍然保持稳健。在国内外复杂新形势下,相关部门应建立积极友好稳定的营商环境,企业进行决策时应充分考虑内外部风险,如此才能促进中国对外直接投资可持续健康发展。

关键词：经济政策贸易政策政策不确定性对外直接投资

混合学习五维评价模型的构建与应用——以“现代教育技术”公共课程为例

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现代教育技术 2016年第8期26卷 89-95页

作者：唐文秀石晋阳陈刚扬州大学新闻与传媒学院，江苏扬州 225002

在信息时代,混合学习是教学改革的重要方式之一。文献调研表明,混合学习的评价存在诸多问题,主要表现为评价方式单一、量规不科学、过程性评价缺位、情感体验评价缺乏等。文章在"现代教育技术"公共课程的混合学习实践中,从参与度、交互... 详细信息

在信息时代,混合学习是教学改革的重要方式之一。文献调研表明,混合学习的评价存在诸多问题,主要表现为评价方式单一、量规不科学、过程性评价缺位、情感体验评价缺乏等。文章在"现代教育技术"公共课程的混合学习实践中,从参与度、交互性、适应性、满意度和效果度五个方面构建了混合学习的五维评价模型。在此基础上,文章分析了五维学习评价结果并反思了其不足,最后针对该模型反映的问题提出了解决方案。

关键词：混合学习教学评价现代教育技术五维评价模型

Effect of order–disorder transition on thermodynamic and electronic properties of σ and χ phases in W–Re alloy: the first-principles calculation

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Tungsten 2025年第1期7卷 195-213页

作者： Zhi-Peng Zhu Dian Jia William Yi Wang Jun-Lei Yin Xing-Yu Gao Shu-Feng yang Hai-Feng Song jin-Shan Li State Key Laboratory of Solidification Processing Northwestern Polytechnical University Laboratory of Computational Physics Institute of Applied Physics and Computational Mathematics School of Metallurgical and Ecological Engineering University of Science and Technology Beijing

The Tungsten-Rhenium(W-Re) alloys,celebrated for their high melting point,strength at elevated temperatures,electrical resistivity,and radiation resistance,have been widely utilized in high-temperature components,aerospace,electronics,and nuclear *** constituents of the topologically close-packed(TCP) phases,the sigma phase(σ) and chi phase(χ) formed within W-Re alloys wield considerable influence on the mechanical properties and the stability of the *** calculations were utilized in the present work to explore the structural,thermodynamic,and electronic properties of both ordered and disordered configurations within the σ and χ phases,culminating in a systematic elucidation of the higher phase stability exhibited by the ordered *** is found that the bulk modulus of these two phases is directly proportional to the concentration of Re in the alloy,while the equilibrium volume is inversely *** thermodynamic parameters of the σ and χ phases are calculated via the mean-field potential *** similar trends observed in the isobaric heat capacity,enthalpy increment,and entropy change curves for these two phases suggest they possess comparable thermodynamic *** is noteworthy that the contribution of ionic vibrations predominantly affects the isobaric heat capacity,while the contribution of thermal electronic excitations increases linearly with *** the structure and thermodynamic properties of TCP phases in W-Re alloys at low temperatures has profound significance for optimizing material performance,microstructures features,establishing theoretical foundations,and predicting material behavior.

关键词： First-principles calculations Phase stability TCP phases Thermodynamic properties W–Re alloy

口服鲨烯对大鼠Leptin、体脂沉积和繁殖的影响

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华中农业大学学报 2009年第1期28卷 58-60页

作者：张庆德杨世锦杨利国张维民华中农业大学动物医学院武汉430070

将22日龄Wistar雄鼠32只,分对照组(饲料中不含鲨烯)和试验组(每千克饲料中含鲨烯1000mg),宰杀后测定血Leptin、血糖、胆固醇、甘油三酯和睾酮水平及体重脂肪指数和体重睾丸指数,同时,各组留6只与雌鼠交配,待观察产仔数。结果显示,对照... 详细信息

将22日龄Wistar雄鼠32只,分对照组(饲料中不含鲨烯)和试验组(每千克饲料中含鲨烯1000mg),宰杀后测定血Leptin、血糖、胆固醇、甘油三酯和睾酮水平及体重脂肪指数和体重睾丸指数,同时,各组留6只与雌鼠交配,待观察产仔数。结果显示,对照组和试验组饲料消耗没有差异,但试验组大鼠体重、体重脂肪指数、血Leptin、血糖、胆固醇和甘油三酯水平显著比对照组低,而试验组大鼠的体重睾丸指数、血睾酮水平和产仔数显著比对照组高。提示口服鲨烯可防止正常鼠体重和体脂肪增加并可降低肥胖鼠体重脂肪指数及降低血Leptin、血糖、胆固醇和甘油三酯的水平;同时,鲨烯可促进睾丸生长发育和睾酮分泌,增加产仔数。

关键词：鲨烯 Leptin 睾酮产仔数体重脂肪指数