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miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1- containing AMPA receptors in a mouse model of Alzheimer’s disease

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Acta Pharmaceutica Sinica B 2024年第2期14卷 635-652页

作者： Man Luo yayan pang Junjie Li Lilin Yi Bin Wu Qiuyun Tian Yan He Maoju Wang Lei Xia Guiqiong He Weihong Song Yehong Du Zhifang Dong Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing 400014China Department of Anatomy Basic Medical CollegeChongqing Medical UniversityChongqing 400016China Townsend Family Laboratories Department of PsychiatryThe University of British ColumbiaVancouver BC V6T 1Z3Canada Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Institute of AgingKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceZhejiang Clinical Research Center for Mental DisordersSchool of Mental Health and the Affiliated Kangning HospitalWenzhou Medical UniversityWenzhou 325000China Institute for Brain Science and Disease of Chongqing Medical University Chongqing 400016China

Alzheimer ’s disease(AD) is a leading cause of dementia in the ***-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in ***,the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively ***(miRNAs) regulate gene expression at the post-transcriptional level,thereby repressing mRNA ***,we reported that the microRNA-429-3p(miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPPAD model *** further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3’-untranslated region(3’ UTR).Inhibition of miR-429-3p by its antagomir(A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ *** importantly,intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase(ERK1/2)-mediated GluAl hyperphosphorylation at Ser831 site,thereby increasing the surface expression of GluAl-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors(AMPARs).Together,these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice,suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

关键词： Alzheimer's disease MKP-1 miR-429-3p AMPAreceptor Learning and memory Long-term potentiation

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Lack of interferon regulatory factor 3 leads to anxiety/depression-like behaviors through disrupting the balance of neuronal excitation and inhibition in mice

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Genes & Diseases 2023年第3期10卷 1062-1074页

作者： Junjie Li yayan pang Yehong Du Lei Xia Mulan Chen Yepeng Fan Zhifang Dong Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China

Disrupting the balance of neuronal excitation and inhibition (E/I) is an important pathogenic mechanism of anxiety and depression. Interferon regulatory factor 3 (IRF3) plays a key role in the innate immune response, and activation of IRF3 triggers the expression of type I interferons and downstream interferon-stimulated genes, which are associated with anxiety and depression. However, whether IRF3 participates in the pathogenesis of anxiety/depression by regulating E/I balance remains poorly understood. Here, we reported that global knockout (KO) of IRF3 (IRF3^(−/−)) significantly increased anxiety/depression-like behaviors, but did not affect normal spatial learning and memory. Compared with wild type (WT) control mice, the E/I balance was disrupted, as reflected by enhanced glutamatergic transmission and decreased GABAergic transmission in the neurons of hippocampal CA1 and medial prefrontal cortex (mPFC) in IRF3-KO mice. Importantly, genetic rescue of IRF3 expression by adeno-associated virus (AAV) was sufficient to alleviate anxiety/depression-like behaviors and restore the neuronal E/I balance in IRF3-KO mice. Taken together, our results indicate that IRF3 is critical in maintaining neuronal E/I balance, thereby playing an essential role in ensuring emotional stability.

关键词： Anxiety Depression Hippocampus IRF3 Medial prefr ontal cortex Synaptic transmission

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MKP-1 reduces Aβ generation and alleviates cognitive impairments in Alzheimer’s disease models

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Signal Transduction and Targeted Therapy 2019年第1期4卷 149-160页

作者： Yehong Du Yexiang Du Yun Zhang Zhilin Huang Min Fu Junjie Li yayan pang Peng Lei Yu Tian Wang Weihong Song Guiqiong He Zhifang Dong Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing400014PR China Department of Anatomy Basic Medical CollegeChongqing Medical UniversityChongqing400016PR China Townsend Family Laboratories Department of PsychiatryThe University of British ColumbiaVancouverBCV6T 1Z3Canada West China School of Basic Medical Sciences and Forensic Medicine Sichuan UniversityChengdu610041SichuanChina Brain Research Centre The University of British ColumbiaVancouverBCV6T 2B5Canada

Mitogen-activated protein kinase(MAPK)phosphatase 1(MKP-1)is an essential negative regulator of MAPKs by dephosphorylating MAPKs at both tyrosine and threonine *** of the MAPK signaling pathway has been associated with Alzheimer’s disease(AD).However,the role of MKP-1 in AD pathogenesis remains ***,we report that MKP-1 levels were decreased in the brain tissues of patients with AD and an AD mouse *** reduction in MKP-1 gene expression appeared to be a result of transcriptional inhibition via transcription factor specificity protein 1(Sp1)cis-acting binding elements in the MKP-1 gene ***-β(Aβ)-induced Sp1 activation decreased MKP-1 ***,upregulation of MKP-1 inhibited the expression of both Aβprecursor protein(APP)andβ-site APP-cleaving enzyme 1 by inactivating the extracellular signal-regulated kinase 1/2(ERK)/MAPK signaling ***,upregulation of MKP-1 reduced Aβproduction and plaque formation and improved hippocampal long-term potentiation(LTP)and cognitive deficits in APP/PS1 transgenic *** results demonstrate that MKP-1 impairment facilitates the pathogenesis of AD,whereas upregulation of MKP-1 plays a neuroprotective role to reduce Alzheimer-related ***,this study suggests that MKP-1 is a novel molecule for AD treatment.

关键词： Alzheimer Aβ impairment

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An agent-based model of agricultural land expansion in the mountain forest of Timor Island,Indonesia

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Journal of Mountain Science 2024年第7期21卷 2263-2282页

作者： PUJIONO Eko SADONO Ronggo IMRON Muhammad Ali SUTOMO JANUAR Hedi Indra KUSWANDI Relawan KURNIAWAN Hery HADI Etik Erna Wati SAPUTRA Muhammad Hadi HIDAYAH Izhamil HUMAIDA Nida SUKMAWATI Jalma Giring HADIYAN yayan NUGROHO Agung Wahyu HANI Aditya Research Center for Ecology and Ethnobiology National Research and Innovation Agency Republic of Indonesia(BRIN)Jl.Raya Jakarta-Bogor KM.46CibinongBogor 16911Indonesia Faculty of Forestry Gadjah Mada UniversityJl.Agro No.1Yogyakarta 55281Indonesia

The Mutis-Timau Forest Complex,located on Timor Island,Indonesia,is a mountainous tropical forest area that gradually decreases due to deforestation and forest *** modelling studies based on patterns indicate that deforestation primarily occurs at lower elevations and near the boundaries of forests and settlements,often associated with shifting cultivation by local *** study adopts a process-based modelling approach,specifically the agent-based model,to simulate land changes,particularly farmers'expansion of agricultural land around the Mutis mountain *** underlying concept of this agent-based approach is the interaction between the human and environmental ***,representing the human system,interact with the land,which represents the environmental system,through land use decision-making *** research was conducted in the Community Forest of the Timor Tengah Utara District,one of the sites within the Mutis-Timau Forest Complex with the highest deforestation *** use change simulations were performed using agent-based modelling from 1999 to 2030,considering the socio-economic conditions of farmers,spatial preferences,land use decisions,and natural *** results revealed that the agricultural area increased by 14%under the Business as Usual scenario and 5%under the Reducing Emission from Deforestation and Forest Degradation scenario,compared to the initial agricultural area of 245 *** probability of farmers deciding to extend agricultural activities was positively associated with the number of livestock maintained by farmers and the size of the village ***,the likelihood of farmers opting for agricultural extensification decreased with an increase in the area of private land and the farmer's *** findings are crucial for the managers of the Mutis-Timau Forest Complex and other relevant stakeholders,as they aid in arranging actions to combat deforestation,designing proper fore

关键词： Agricultural land expansion Simulation Agent-based model Farmer Deforestation Mountainous tropical forest

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Prenatal ultrasonic characteristics and diagnosis of fetal Currarino syndrome:Report of 2 cases and review of literature

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中国医学影像技术 2024年第8期40卷 1212-1215页

作者： WEI Yingni ZHANG Yuchen DENG Zongfeng WANG Yingqiu HUANG Qiaojie CHEN yayan Department of Ultrasound Shenzhen Longhua Maternity&Child Healthcare HospitalShenzhen 518110China

Objective To explore prenatal ultrasonic characteristics of fetal Currarino syndrome(CS)and methods for prenatal diagnosis of *** Two fetuses with CS confirmed by genetic examination were retrospectively analyzed,while 6 CS fetuses with complete prenatal ultrasonic data in literature were *** ultrasonic characteristics of CS fetuses and the method for prenatal diagnosis of CS were *** Among 8 CS fetuses diagnosed with prenatal ultrasound,4 were female singletons with a clear family history of CS,and MNX 1 gene mutation was found in 1 *** other 4 fetuses were 2 pairs of male monochorionic twins,all with MNX 1 gene *** 8 CS fetuses,complete triad(sacral agenesis abnormalities,anorectal malformation and presacral mass)were displayed only in 2 fetuses,while all 8 had sacral agenesis abnormalities and 6(6/8,75.00%)were detected with prenatal ultrasound,6 had low location of conus medullaris and 2(2/6,33.33%)detected with prenatal *** Prenatal ultrasound was the first choice for non-invasive diagnosis of fetal *** one of sacral agenesis abnormalities,anorectal malformation and presacral mass was found with prenatal ultrasound,the possibility of CS should be considered,and fetal MRI,genetic examination and prenatal genetic counselling should be recommended if necessary.

关键词： Currarino triad ultrasonography,prenatal amniocentesis genes

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数字艺术在开放大学课程资源建设中的应用

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河北开放大学学报 2024年第5期29卷 29-33页

作者：张亚艳唐山开放大学河北唐山063000

在教育数字化的大背景下,数字艺术为开放大学课程资源建设带来了前所未有的创新机遇,借助动画、视频、虚拟现实等数字艺术手段,教学内容得以更加生动、形象的展现,教学方式也变得更加多元化和个性化。数字艺术如何与开放大学课程资源建... 详细信息

在教育数字化的大背景下,数字艺术为开放大学课程资源建设带来了前所未有的创新机遇,借助动画、视频、虚拟现实等数字艺术手段,教学内容得以更加生动、形象的展现,教学方式也变得更加多元化和个性化。数字艺术如何与开放大学课程资源建设紧密结合,特别是在重塑教学内容、构建互动教学平台、实现教学数据可视化、赋能学习评估与反馈机制以及促进跨学科融合等方面的应用是需要研究的问题。通过具体案例和实践经验,结合开放大学课程特点,展示数字艺术在开放大学课程资源建设中的创新应用成果,可为相关领域的研究和实践提供有益的参考。

关键词：数字艺术开放大学课程资源建设创新应用

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Expert consensus on irrigation and intracanal medication in root canal therapy

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International Journal of Oral Science 2024年第1期16卷 26-35页

作者： Xiaoying Zou Xin Zheng Yuhong Liang Chengfei Zhang Bing Fan Jingping Liang Junqi Ling Zhuan Bian Qing Yu Benxiang Hou Zhi Chen Xi Wei Lihong Qiu Wenxia Chen Wenxi He Xin Xu Liuyan Meng Chen Zhang Liming Chen Shuli Deng yayan Lei Xiaoli Xie Xiaoyan Wang Jinhua Yu Jin Zhao Song Shen Xuedong Zhou Lin Yue Department of Cariology and Endodontology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental MaterialsBeijingChina Center of Stomatology Peking University HospitalBeijingChina State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina Department of Emergency Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental MaterialsBeijingChina Restorative Dental Sciences EndodonticsFaculty of DentistryThe University of Hong KongPok Fu LamHong Kong SARChina State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyWuhan UniversityWuhanChina Department of Endodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Clinical Research Center for Oral DiseasesNational Center for StomatologyShanghai Key Laboratory of StomatologyShanghaiChina Department of Operative Dentistry and Endodontics Hospital of StomatologyGuanghua School of StomatologySun Yat-Sen University&Guangdong Provincial Key Laboratory of StomatologyGuangzhouChina State Key Laboratory of Oral&Maxillofacial Reconstruction and R

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.

关键词： treatment irrigation Expert

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籽粒玉米收获机配套简易烘干装置研究

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农业技术与装备 2024年第5期 3-5页

作者：赵雅燕晋城市农业农村局山西晋城048000

在一种小型籽粒玉米收获机方案的基础上,设计配套了一种简易烘干装置,利用籽粒玉米收获机所配套的柴油机排气管废气余热,对所收获的玉米籽粒进行一次简单烘干,降低玉米籽粒含水率。

关键词：籽粒玉米收获机烘干装置余热

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闽西文化融入地方基础教育课程调查与研究

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龙岩学院学报 2024年第2期42卷 104-109页

作者：刘亚燕杨丹龙岩学院龙岩第一中学福建龙岩364000

以文化强国战略和深化基础教育改革为背景,调查闽西文化融入基础教育课程的基本情况、主观实施态度和实施现状等,分析存在的问题和困境。闽西文化融入地方基础教育应依托多元主体共建,拓展和深化资源开发与建构的广度和深度。在资源转... 详细信息

以文化强国战略和深化基础教育改革为背景,调查闽西文化融入基础教育课程的基本情况、主观实施态度和实施现状等,分析存在的问题和困境。闽西文化融入地方基础教育应依托多元主体共建,拓展和深化资源开发与建构的广度和深度。在资源转化和利用过程中着眼于增强家国的共生关联,发挥独特的育人价值,遵循教育规律进行学科融合,开展亲和性的活化教学,在推动地方文化的传承和发展的同时,促进基础教育的改革和高质量发展。

关键词：基础教育闽西文化有效融入

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规范性急诊绿色救治护理模式对脑卒中患者救治及康复效果的影响

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中国基层医药 2024年第5期31卷 789-792页

作者：周雅燕刘科群马春花丽水市中心医院急诊医学科丽水323000

目的探讨脑卒中急诊救治中应用规范性急诊绿色救治护理的具体措施及效果。方法回顾性分析丽水市中心医院2021年2月至2022年4月收治的脑卒中患者80例的临床资料,按急诊救治护理模式不同分为对照组和观察组,各40例,观察组行规范性急诊绿... 详细信息

目的探讨脑卒中急诊救治中应用规范性急诊绿色救治护理的具体措施及效果。方法回顾性分析丽水市中心医院2021年2月至2022年4月收治的脑卒中患者80例的临床资料,按急诊救治护理模式不同分为对照组和观察组,各40例,观察组行规范性急诊绿色救治护理干预,未行该种护理干预的40例患者作为对照组。回顾性分析并比较患者救治期间耗时、救治效果、康复情况。结果观察组医师到位、静脉开通时间分别为(4.68±1.32)min、(9.60±2.28)min,均显著短于对照组的(7.67±2.42)min、(11.70±3.46)min,急诊至影像、影像、检验结果回报时间分别为(11.74±3.28)min、(10.26±3.00)min、(30.20±7.18)min,均显著短于对照组的(13.96±4.35)min、(13.78±5.31)min、(35.42±9.23)min,差异均有统计学意义(t=6.29、3.21、2.58、3.65、2.82,均P<0.05);对照组、观察组临床救治总有效率分别为72.50%(29/40)、92.50%(37/40),观察组高于对照组(χ^(2)=4.24,P<0.05);干预后2周观察组美国国立卫生院神经功能缺损评分(NIHSS)为(5.84±2.26)分,显著低于对照组的(7.76±3.25)分;Barthel指数为(52.56±15.48)分,显著高于对照组的(42.43±18.56)分,差异均有统计学意义(t=3.07、2.65,均P<0.05)。结论规范性急诊绿色救治护理模式应用于脑卒中患者,可明显缩短救治期间的耗时,提高总体救治效果,有助于患者康复。

关键词：卒中急诊处理护理时间预后康复

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