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Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

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Neural Regeneration Research 2025年第5期20卷 1455-1466页

作者： Ju Zheng Yixin Li Ting Zhang Yanlin Fu Peiyan Long Xiao Gao Zhengwei Wang Zhizhong Guan Xiaolan Qi Wei Hong Yan Xiao Key Laboratory of Endemic and Ethnic diseases Ministry of Education&Key Laboratory of Medical Molecular Biology of Guizhou ProvinceGuizhou Medical UniversityGuiyangGuizhou ProvinceChina Guizhou center for Disease control and prevention GuiyangGuizhou ProvinceChina Department of Histology and Embryology Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Collaborative Innovation center for prevention and control of Endemic and Ethnic Regional diseases Co-constructed by the Province and Ministry GuiyangGuizhou ProvinceChina

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion *** occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains *** this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion *** found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced ***,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating *** autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion *** from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

关键词： apoptosis ATF4 autophagy C/EBP homologous protein cerebral ischemia/reperfusion injury eIF2α endoplasmic reticulum stress PERK

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

Unveiling phosphofructokinase as the key target: an innovative strategy combining pull-down assays with optical imaging for snail-killing mechanism exploration

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Science China Chemistry 2025年

作者： Yuxun Lu Weisi Wang Le Yu Yuqiang Zhao Ying Chen Yunhai Guo Bingrong Luo Yuhua Liu Shizhu Li Liping Duan Ying Zhou Yunnan Characteristic Plant Extraction Laboratory College of Chemical Science and Technology Yunnan University College of Biological and Chemical Engineering Guangxi University of Science and Technology National Institute of Parasitic diseases Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research)NHC Key Laboratory of Parasite and Vector Biology WHO Collaborating Centre for Tropical Diseases National Center for International Research on Tropical Diseases School of Chemistry and Environment Yunnan Minzu University Dali Institute of Schistosomiasis control

The Pomacea canaliculata, also known as apple snail, is an invasive species in China, posing a serious threat to agricultural production and public health. To prevent its rampant infestation, we developed a highly efficient snail-killing lead compound, 1-(4-chlorophenyl)-3-(pyridin-3-yl)urea (PBQ). However, the killing mechanism of PBQ remains unclear. To elucidate this, two novel compounds, B-PBQ and J-PBQ, were developed through structural modification of PBQ and were used, through both protein pull-down assay and confocal laser scanning microscopy imaging, to identify and confirm that phosphofructokinase(PFK) in the apple snail is the primary target protein of PBQ. Further studies revealed that PBQ successfully inhibits the activity,content, and expression of PFK in apple snail, disrupting the glycolysis pathway and leading to abnormal energy *** disruptions impair the snail’s tolerance to low oxygen, resulting in its efficient eradication. These findings offer a promising direction for developing next-generation PFK-targeted snail-killing pesticides. Furthermore, the strategy of combining pull-down assays with optical imaging used in this work provides a novel approach for the exploration of mechanisms of other pesticide candidates.

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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

Comparison of Xpert MTB/RIF, Real Amp, and CPA Tests in Detecting Mycobacterium tuberculosis

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Biomedical and Environmental Sciences 2019年第3期32卷 215-219页

作者： OU Xi Chao LI Hui LIU Dong Xin XIA Hui MA Xiao Guang WANG Shao Hua WANG Sheng Fen ZHU Yan Kun ZHAO Bing ZHAO Yan Lin National center for Tuberculosis control and prevention Chinese Center for Diseases Control and Prevention henan Provincial center for Disease control and prevention

Today, tuberculosis (TB) remains a global public health threat associated with significantly high rates of morbidity and mortality. The World Health Organization's (WHO) Global Tuberculosis Report 2018[1] has reported that in 2017, 10.0 million people across the world had developed TB diseases that resulted in an estimated 1.6 million deaths, and 889, 000 people developed TB in China that led to 39, 000 TB-related deaths. Therefore, rapid and accurate detection of Mycobacterium tuberculosis (MTB) is important for initiating early treatment and reducing mortality. Traditional diagnostic methods for pulmonary TB incorporate chest radiography and sputum smear microscopy;however, several cases of tuberculosis go undiagnosed because of the low sensitivity of smear microscopy[2].

关键词： Comparison Detecting Mycobacterium tuberculosis Xpert MTB/RIF

Measles Virus IgG Avidity Assay for Use in Identification of Measles Vaccine Failures in Tianjin, China

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Biomedical and Environmental Sciences 2019年第11期32卷 804-811页

作者： DING Ya Xing MAO Nai Ying ZHANG Yan LEI Yue GAO Zhi Gang XU Wen Bo ZHANG Ying Department of Expanded Program Immunization Tianjin Center for Diseases Control and PreventionTianjin 300011China National Institute for Viral Disease control and prevention Chinese Center for Diseases Control and PreventionBeijing 102206China Department of Viral Laboratory Tianjin Center for Diseases Control and PreventionTiannin 300011China Institute for Infectious diseases control and prevention Tianjin Center for Diseases Control and PreventionTianjin 300011China

Objective To identify measles vaccine failures in Tianjin, China using a measles virus Ig G avidity *** The China Information System for Disease control and prevention(CISDCP) was used to collect information about measles cases and blood specimens in Tianjin from 2013 to 2015. Measlesspecific Ig M and Ig G antibodies were detected using Enzyme-Linked Immunosorbent Assay(ELISA).Avidity testing for measles Ig G was performed using a commercial enzyme immunoassay(EIA).Results A total of 284 confirmed measles cases were identified. Of this total, 262(92.25%) were in patients aged ≥ 20 years. High avidity was exhibited in 172(60.56%) cases, while 80(28.17%) cases demonstrated low avidity. High avidity was detected in only 21.43% of cases in patients aged 0.05) in clinical severity between high avidity and low avidity cases. However, regardless of vaccination status, clinical severity was significantly lower in high avidity cases(P < 0.001) than in low avidity cases. The percentages of positive measles Ig M results in high avidity and low avidity cases were 66.28% and 91.25%, respectively. Geometric Mean Concentration(GMC) was significantly lower in high avidity cases at 33.73 U/m L, compared to 166.07 U/m L in low avidity *** Low clinical severity and inconclusive Ig M antibody results are more likely in high avidity measles cases. Measles cases were more common in adults. Therefore, a further dose of vaccines should be recommended for 30–39 years in Tianjin.

关键词： Measles IgG avidity China Primary vaccine failures Secondary vaccine failures

The frst avian infuenza A (H7N9) viral infection in humans in Zhejiang Province, China: a death report

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Frontiers of Medicine 2013年第3期7卷 333-344页

作者： Enfu Chen Fenjuan Wang Huakun Lv Yanjun Zhang Hua Ding Shelan Liu Jian Cai Li Xie Xiaoping Xu Chengliang Chai Haiyan Mao Jimin Sun Junfen Lin Zhao Yu Lianhong Li Zhiping Chen Shichang Xia Department of Infectious diseases Zhejiang Center for Disease Control and Prevention Department of Infectious diseases Xiaoshan District Center for Disease Control and Prevention Department of Infectious diseases Hangzhou Center for Disease Control and Prevention Department of Infectious diseases Jiande Center for Disease Control and Prevention

This study reports the frst death caused by a novel avian infuenza A(H7N9)virus in Zhejiang Province,*** patient had chronic hepatitis B and history of exposure to *** patient initially complained of diarrhea and infuenza-like symptoms on March 7 and 14 *** disease progressed to severe pneumonia,sustained hypoxia,and coagulation *** patient died on March 27 because of respiratory failure,multiple organ failure,and disseminated intravascular coagulation without oseltamivir *** H7N9 virus from Zhejiang is highly similar to isolates obtained from Shanghai,Jiangsu,Anhui,*** of hemagglutinin,neuramidinase,and matrix genes indicated that the isolates share the same avian origin,have low virulence,and are sensitive to oseltamivir,but are resistant to *** the isolate that caused the fatality exhibited substitution of Q226I in the HA gene,which indicates a potentially enhanced human *** secondary transmission rate was 1.6%(2/125).Only two health workers presented with infuenza-like symptoms,and they subsequently tested negative for H7N9 *** conclusion,underlying disease,late diagnosis,and untimely antiviral treatment are possible high-risk factors for infections and death caused by the lowpathogenicity avian infuenza A(H7N9).Person-to-person transmission of the H7N9 virus was not detected among close contacts,but such transmission should be investigated in the *** and enhancing surveillance will help in the early discovery and diagnosis of suspected cases,which will reduce the number of severe cases and deaths.

关键词： avian influenza A (H7N9) virus epidemiology contacts person-to-person transmission

Psychoactive Substance Use and the Impact on the AIDS Epidemic Among the MSM Population:a Meta-Analysis—Worldwide,2014-2023

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China CDC weekly 2024年第42期6卷 1086-1092,I0001-I0006页

作者： Donghang Luo Jie Xu Wei Luo National center for AIDS/STD control&prevention Chinese Center for Diseases Control and PreventionBeijingChina

What is already known about this topic?There is a correlation between psychoactive substance use and heightened human immunodeficiency virus(HIV)susceptibility in men who have sex with men(MSM)populations,although the precise impact on transmission risk remains *** is added by this report?In MSM populations,rush poppers and amphetamines are widely used,with rates of 10.91%and 9.97%.In China,rush poppers usage is notably higher at 47.26%.For other regions and coutries,amphetamines(12.86%),rush poppers(3.62%),and GHB(3.34%)are most ***,17%of MSM use psychoactive substances,with higher HIV risk from amphetamines[Odds ratio(OR)3.06]compared to rush poppers(OR 1.51)and general substances(OR 1.76).What are the implications for public health practice?This study supports the idea that targeting specific regions and types of psychoactive substances for reduction among MSM populations can help decrease HIV transmission as well as promote prevention strategies.

关键词： prevention precise Impact