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Fasudil-modified macrophages reduce inflammation and regulate the immune response in experimental autoimmune encephalomyelitis

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Neural Regeneration Research 2024年第3期19卷 671-679页

作者： Chunyun Liu Shangde Guo Rong Liu Minfang Guo Qing Wang Zhi Chai Baoguo Xiao Cungen Ma Institute of Brain Science Shanxi Datong UniversityDatongShanxi ProvinceChina The Key Research Laboratory of Benefiting Qi for Acting Blood Cireulation Method to Treat Multiple Sclerosis of State administration of Traditional Chinese Medicine/Research Center of Neurobiology Shanxi University of Chinese MedicineTaiyuanShanxi ProvinceChina Institute of Neurology Huashan HospitalInstitutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan UniversityShanghaiChina

Multiple sclerosis is characterized by demyelination and neuronal loss caused by inflammatory cell activation and infiltration into the central nervous *** polarization plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis,a traditional experimental model of multiple *** study investigated the effect of Fasudil on macrophages and examined the therapeutic potential of Fasudil-modified macrophages in experimental autoimmune *** found that Fasudil induced the conversion of macrophages from the pro-inflammatory M1 type to the anti-inflammatory M2 type,as shown by reduced expression of inducible nitric oxide synthase/nitric oxide,interleukin-12,and CD16/32 and increased expression of arginase-1,interleukin-10,CD14,and CD206,which was linked to inhibition of Rho kinase activity,decreased expression of toll-like receptors,nuclear factor-κB,and components of the mitogen-activated protein kinase signaling pathway,and generation of the pro-inflammatory cytokines tumor necrosis factor-α,interleukin-1β,and ***,Fasudil-modified macrophages effectively decreased the impact of experimental autoimmune encephalomyelitis,resulting in later onset of disease,lower symptom scores,less weight loss,and reduced demyelination compared with unmodified *** addition,Fasudil-modified macrophages decreased interleukin-17 expression on CD4^(+)T cells and CD16/32,inducible nitric oxide synthase,and interleukin-12 expression on F4/80^(+)macrophages,as well as increasing interleukin-10 expression on CD4^(+)T cells and arginase-1,CD206,and interleukin-10 expression on F4/80^(+)macrophages,which improved immune regulation and reduced *** findings suggest that Fasudil-modified macrophages may help treat experimental autoimmune encephalomyelitis by inducing M2 macrophage polarization and inhibiting the inflammatory response,thereby providing new insight into cell immunotherapy for m

关键词： anti-inflammatory experimental autoimmune encephalomyelitis Fasudil macrophage multiple sclerosis pro-inflammatory Rho kinase

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Character of Convective Systems Producing Short-Term Heavy Precipitation in Central China Revealed by Kilometer and Minute Interval Observations

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Journal of Meteorological Research 2024年第3期38卷 530-541页

作者： Zitong CHEN Yunying LI Zhiwei ZHANG Jing SUN Chengzhi YE Anyuan XIONG College of Meteorology and Oceanography National University of Defense TechnologyChangsha410073China High Impact Weather Key Laboratory of China Meteorological administration Changsha410073China Unit No.92192 of Chinese People’s Liberation Army Ningbo315000China Hubei Key Research Laboratory for Heavy Rain Monitoring and Warning Institute of Heavy RainChina Meteorological AdministrationWuhan430223China Institute of Meteorological Sciences of Hunan province Hunan Meteorological BureauChangsha410118China National Meteorological Information Centre China Meteorological AdministrationBeijing100081China

Accurate forecasting of heavy precipitation in central China is still a challenge,within which a key issue is our still incomplete understanding of the convective systems(CSs)responsible for such *** this study,through use of an iterative rain-cell tracking algorithm,the macroscale characteristics(scale,intensity,duration,etc.)of the CSs that produced 595 short-term heavy precipitation events in Hunan province,central China,are quantitatively analyzed,based on radar reflectivity,echo top,and rainfall observations at 1-km and 6-min intervals in April-September of *** results show that CSs present significant seasonal and diurnal *** CSs usually cover a larger echo area with stronger convective cores and thus generate more precipitation than summer CSs,though summer CSs develop more vigorously and *** initiated at 1400-1600 local time are characterized by the strongest convection and a smaller spatiotemporal scale,causing violent and transient showers with typical areal precipitation of 0.5-1 mm km^(−2),but less total *** analyses of the relationships among the scale,intensity,duration,and total precipitation of CSs reveal that the convective intensity is linearly correlated to the spatiotemporal scale of CSs,with the duration increasing on average by 0.0372 h dBZ^(−1);the echo area is significantly correlated to the total precipitation,and the duration and rainfall amount are connected with the area expansion rate(AER)of CSs:when the AER exceeds 50%,CSs expand rapidly with increasing total precipitation,but the duration is *** findings provide a helpful reference for the forecasting of short-term heavy precipitation induced by CSs in central China.

关键词： convective system radar reflectivity factor total precipitation iterative rain-cell tracking

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Necroptosis contributes to non-alcoholic fatty liver disease pathoetiology with promising diagnostic and therapeutic functions

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World Journal of Gastroenterology 2024年第14期30卷 1968-1981页

作者： Hong-Ju Sun Bo Jiao Yan Wang Yue-Hua Zhang Ge Chen Zi-Xuan Wang Hong Zhao Qing Xie Xiao-Hua Song Department of General Medicine Qingdao Central HospitalUniversity of Health and Rehabilitation Sciences(Qingdao Central Medical Group)Qingdao 266042Shandong ProvinceChina Department of Gastroenterology Qingdao Central HospitalUniversity of Health and Rehabilitation Sciences(Qingdao Central Medical Group)Qingdao 266042Shandong ProvinceChina Department of Medical administration Qingdao Central HospitalUniversity of Health and Rehabilitation Sciences(Qingdao Central Medical Group)Qingdao 266042Shandong ProvinceChina Qingdao Medical College Qingdao UniversityQingdao 266042Shandong ProvinceChina Department of Infectious Diseases Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Nonalcoholic fatty liver disease(NAFLD)is the most prevalent type of chronic liver ***,the disease is underappreciated as a remarkable chronic disorder as there are rare managing *** studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoe-tiology and suggest functional therapeutic and diagnostic ***,ferroptosis,and necroptosis are the main subtypes of non-apoptotic regulated cell deaths(RCDs),each of which represents particular *** the complexity of the findings,the present study aimed to review these types of RCDs and their contribution to NAFLD progression,and subsequently discuss in detail the role of necroptosis in the pathoetiology,diagnosis,and treatment of the *** study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer,hence it has potential in diagnostic and therapeutic ***,further studies are necessary.

关键词： Nonalcoholic fatty liver disease Apoptosis Necroptosis Cell death Diagnosis Treatment

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Spatial-Temporal Analysis of Drinking Water Type of Endemic Fluorosis—China,2009–2022

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China CDC weekly 2024年第2期6卷 25-29页

作者： Lijun Zhao Zhe Li Mang Li Hongna Sun Wei Wei Lin Gao Qiaoshi Zhao Yang Liu Xiaohong Ji Cheng Li Jian Wang Yanhui Gao Junrui Pei Center for Endemic Disease Control Chinese Center for Disease Control and PreventionHarbin Medical UniversityHarbin CityHeilongjiang ProvinceChina Key Lab of Etiology and Epidemiology Education Bureau of Heilongjiang Province(23618504)Ministry of Health of PRHarbin Medical UniversityHarbin CityHeilongjiang ProvinceChina

What is already known about this topic?Endemic fluorosis,caused by high fluoride levels in drinking water,has been a significant health issue in rural areas of China for many *** is added by this report?There has been a notable decline in the detection rate of dental fluorosis in children aged 8–12 years in drinking water fluorosis areas across the country from 2009 to *** 14 provincial-level administrative divisions are classified as low-probability clusters,Tianjin remains classified as a high-probability *** are the implications for public health practice?The current policy for preventing and controlling endemic fluorosis in China needs *** than focusing solely on regions with high incidence,there should be a shift towards monitoring and early warning of fluoride ***,local containment measures should be intensified.

关键词： intensified Spatial fluoride

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Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury

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Neural Regeneration Research 2024年第7期19卷 1608-1617页

作者： Yanan Dou Xiaowei Fei Xin He Yu Huan Jialiang Wei Xiuquan Wu Weihao Lyu Zhou Fei Xia Li Fei Fei Department of Neurosurgery Xijing HospitalAir Force Military Medical UniversityXi’anShaanxi ProvinceChina Department of Ophthalmology Xijing HospitalAir Force Military Medical UniversityXi’anShaanxi ProvinceChina

Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual *** is repo rted to play a protective role in neuroinflammation in the ***,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain *** our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion *** in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller *** found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion ***,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte *** opposite results we re observed with Homerla ove ***,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion *** together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.

关键词： caspase-8 Homer1a interleukin-18 interleukin-1β intraocular pressure ischemia/reperfusion injury JSH-23 Müller cells NLRP3 nuclear factor-kB p65 retina

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Trimethylamine N-oxide aggravates vascular permeability and endothelial cell dysfunction under diabetic condition:in vitro and in vivo study

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 25-33页

作者： Jia-Yi Jiang Wei-Ming Liu Qiu-Ping Zhang Hang Ren Qing-Ying Yao Gao-Qin Liu Pei-Rong Lu Department of Ophthalmology the First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina Suzhou Center for Disease Prevention and Control Suzhou 215004Jiangsu ProvinceChina

AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic ***:The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells(HRMEC)under high glucose conditions was tested by a cell counting kit,wound healing,a transwell and a tube formation *** inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction(RT-PCR).The expression of the cell junction was measured by Western blotting(WB)and immunofluorescence *** addition,two groups of rat models,diabetic and non-diabetic,were fed with normal or 0.1%TMAO for 16wk,and their plasma levels of TMAO,vascular endothelial growth factor(VEGF),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere *** vascular permeability of rat retinas was measured using FITC-Dextran,and the expression of zonula occludens(ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence ***:TMAO administration significantly increased the cell proliferation,migration,and tube formation of primary HRMEC either in normal or high-glucose ***-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation,while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO *** rats showed higher plasma levels of TMAO as well as retinal vascular leakage,which were even higher in TMAO-feeding diabetic ***,TMAO administration increased the rat plasma levels of VEGF,IL-6 and TNF-αwhile decreasing the retinal expression levels of ZO-1 and ***:TMAO enhances the proliferation,migration,and tube formation of HRMEC,as well as destroys their vascular integrity and tight *** also regulates the expression of VEGF,IL-6,and TNF-α.

关键词： diabetic model trimethylamine N-oxide inflammation endothelial dysfunction rats retinal microvascular endothelial cells

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Variations in Column Concentration of Greenhouse Gases in China and Their Response to the 2015-2016 El Niño Event

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Journal of Meteorological Research 2024年第3期38卷 608-619页

作者： Ningwei LIU Lingjun XIA Youjun DOU Shaorou DONG Jing WEN Ying WANG Rui FENG Ruonan WANG Yuhe LI Institute of Atmospheric Environment China Meteorological AdministrationShenyang110166China Jiangxi Ecological Meteorology Centre Nanchang330096China Beijing Xiangyuan Academy of Meteorological Observing Technology Beijing100081China Climate Centre of Guangdong province Guangzhou510641China Guangdong Meteorological Service Guangzhou510062China Liaoning Provincial Meteorological Equipment Support Centre Shenyang110166China Meteorological Centre of Northeast Air Traffic administration of Civil Aviation of China Shenyang110161China

Since the industrial revolution,enhancement of atmospheric greenhouse gas concentrations as a result of human activities has been the primary cause of global *** monitoring and evaluation of greenhouse gases are significant prerequisites for carbon emission *** monthly data of global atmospheric carbon dioxide(CO_(2))and methane(CH4)column concentrations(hereinafter XCO_(2) and XCH_(4),respectively)retrieved by the Greenhouse Gas Observation Satellite(GOSAT),we analyzed the variations in XCO_(2)and XCH_(4)in China during 2010-2022 after confirming the reliability of the ***,the influence of a strong El Niño event in 2015-2016 on XCO_(2) and XCH_(4) variations in China was further *** results show that the retrieved XCO_(2) and XCH_(4) from GOSAT have similar temporal variation trends and significant correlations with the ground observation and emission inventory data of an atmospheric background station,which could be used to assess the variations in XCO_(2) and XCH_(4) in ***_(2) is high in spring and winter while XCH_(4) is high in *** XCO_(2) and XCH_(4) gradually declined from Southeast China to Northwest and Northeast China,with variation ranges of 401-406 and 1.81-1.88 ppmv,respectively;and the high value areas are located in the middle-lower Yangtze River ***_(2) and XCH_(4) in China increased as a whole during 2010-2022,with rapid enhancement and high levels of XCO_(2) and XCH_(4) in several *** significant increases in XCO_(2) and XCH_(4) over China in 2016 might be closely related to the strong El Niño-Southern Oscillation(ENSO)event during *** a global warming background in 2015,XCO_(2) and XCH_(4) increased by 0.768%and 0.657%in 2016 in *** analysis reveals that both the XCO_(2) and XCH_(4) variations might reflect the significant impact of the ENSO event on glacier melting in the Tibetan Plateau.

关键词： greenhouse gases column concentration CO_(2) CH4 El Niño-Southern Oscillation(ENSO) El Niño

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A Systematic Analysis of Early Life Exposure to the Chinese Famine(1959-1961)and the Health of Older Adults-China,2008-2023

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China CDC weekly 2024年第11期6卷 203-207,I0001-I0003页

作者： Chi Shen Xi Chen School of Public Policy and administration Xi’an Jiaotong UniversityXi’an CityShaanxi ProvinceChina Department of Health Policy and Management Yale School of Public HealthNew HavenCTU.S Department of Economics Yale UniversityNew HavenCTU.S

What is already known about this topic?There is mounting evidence indicating that the aging process initiates during early life stages,with in utero the individual’s environment playing a significant ***,it is crucial to comprehend the enduring effects of early life circumstances on health in old *** is added by this report?In this study,we conducted a meta-analysis to examine the effects of the Chinese Famine(1959–1961)on the health of older *** also explored potential mechanisms underlying these *** are the implications for public health practice?The complex interplay between early life circumstances,multiple health-related sectors,and healthy aging necessitates a comprehensive life-course approach and strategic interventions to enhance public health in an aging society.

关键词： life aging mount

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Sensitivity Simulations of the 30 March 2020 Xichang Wildfire in Southwest China Based on the WRF-Fire Model

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Journal of Meteorological Research 2024年第4期38卷 826-843页

作者： Yujue LIU Shiguang MIAO Hanbin ZHANG Institute of Urban Meteorology China Meteorological AdministrationBeijing 100089 Key Laboratory of Urban Meteorology China Meteorological AdministrationBeijing 100089

This paper describes a fire forecast system—Weather Research and Forecasting-Fire(WRF-Fire)—that is employed to simulate a real wildfire case in Xichang,Sichuan province,Southwest China on 30 March 2020 at a 100-m resolution over the fire area,in order to provide a fine representation of the terrain and fuel heterogeneities and explicitly resolve the atmospheric *** sensitivity experiments were conducted to analyze the impacts of atmospheric model grid spacing and fire–atmosphere interaction on simulated meteorological fields and fire *** results indicate that finer horizontal grid spacing in the atmospheric model improves the accuracy of wind,temperature,and moisture simulations in the near surface ***,it can better describe local wind field characteristics,capture microscale wind speed fluctuations,and produce more significant effect from fire–atmosphere *** mass and energy released by the fire model and its feedback to the atmospheric model exhibit enhanced heterogeneous *** simulated fire area aligns well with the observation,with KAPPA coefficient(KC)of 0.56–0.59 and spatial correlation coefficient(SC) of 0.52–*** this real case,the influence of heterogeneous land surface on the fire behavior is much greater than the atmosphere–fire *** study suggests that WRFFire holds high potential as a real wildfire simulation tool,offering a new and feasible approach for fire prediction.

关键词： Weather Research and Forecasting-Fire wildfire coupled fire–atmosphere modeling fire behavior large-eddy simulation(LES)

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From Control to Empowerment:A Paradigm Shift in the Discourse of Educational Supervision

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Journal of Contemporary Educational Research 2024年第9期8卷 176-180页

作者： Jinhua Zhou Kai Zhang Liupanshui Second Experimental Middle School Liupanshui 553001Guizhou ProvinceChina School of Public administration Sichuan UniversityChengdu 610065Sichuan ProvinceChina

As educational reforms intensify and societal emphasis shifts towards empowerment,the traditional discourse paradigm of management and control in educational supervision faces growing *** paper explores the transformation of this discourse paradigm through the lens of empowerment,analyzing its distinct characteristics,potential pathways,and effective *** paper begins by reviewing the concept of empowerment and examining the current research landscape surrounding the discourse paradigm in educational ***,we conduct a comparative analysis of the“control”and“empowerment”paradigms,highlighting their essential *** analysis illuminates the key characteristics of an empowerment-oriented approach to educational supervision,particularly its emphasis on dialogue,collaboration,participation,and,crucially,empowerment ***,this research advocates for a shift in educational supervision towards an empowerment-oriented discourse *** entails a multi-pronged approach:transforming ingrained beliefs,embracing renewed pedagogical concepts,fostering methodological innovation,and optimizing existing mechanisms and strategies within educational *** changes are proposed to facilitate the more effective alignment of educational supervision with the pursuit of high-quality education.

关键词： Educational supervision Paradigm shift Control Empowerment

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