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C/EBPβ/AEP Signaling Drives Alzheimer's Disease Pathogenesis

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Neuroscience Bulletin 2023年第7期39卷 1173-1185页

作者： Jing Xiong Zhentao Zhang keqiang ye Department of Neurology Renmin Hospital of Wuhan UniversityWuhan 430060China Faculty of Life and Health Sciences Shenzhen Institute of Advanced Technology(SIAT)Shenzhen 518034China

Alzheimer’s disease(AD)is the most common type of *** two-thirds of patients with AD are *** reason for the higher susceptibility to AD onset in women is ***,hormone changes during the menopausal transition are known to be associated with *** recently,we reported that follicle-stimulating hormone(FSH)promotes AD pathology and enhances cognitive dysfunctions via activating the CCAAT-enhancer-binding protein(C/EBPβ)/asparagine endopeptidase(AEP)*** review summarizes our current understanding of the crucial role of the C/EBPβ/AEP pathway in driving AD pathogenesis by cleaving multiple critical AD players,including APP and Tau,explaining the roles and the mechanisms of FSH in increasing the susceptibility to AD in postmenopausal *** FSH-C/EBPβ/AEP pathway may serve as a novel therapeutic target for the treatment of AD.

关键词： Alzheimer's disease C/EBPβ Asparagine endopeptidase Pathogenesis Follicle stimulating hormone

涎腺内镜联合口内小切口取出颌下腺导管腺门部结石53例分析

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口腔医学研究 2024年第4期40卷 325-329页

作者：叶克强吕继连裴飞张瑞乔翔鹤赵媛郑州大学附属郑州中心医院口腔颌面外科河南郑州450000 郑州大学第一附属医院口腔颌面外科河南郑州450052

目的:观察涎腺内镜联合口内小切口取出颌下腺导管腺门部结石的应用效果。方法:采用回顾性病例研究的方法,收集2020年1月~2023年12月于我院就诊的颌下腺导管腺门部结石患者临床资料。经过涎腺内镜联合口内小切口手术取石治疗病例纳入观察... 详细信息

目的:观察涎腺内镜联合口内小切口取出颌下腺导管腺门部结石的应用效果。方法:采用回顾性病例研究的方法,收集2020年1月~2023年12月于我院就诊的颌下腺导管腺门部结石患者临床资料。经过涎腺内镜联合口内小切口手术取石治疗病例纳入观察组(53例),采用传统口内入路切开取石病例纳入对照组(55例)。统计分析两组手术成功率、并发症发生率。统计分析观察组手术前后生活质量。结果:观察组中52例患者成功取出结石、保留腺体,手术成功率98.1%,术后均无舌神经损伤等并发症;1例未取出结石者术中同期行颌下腺切除术,术后出现暂时性舌神经损伤,并发症发生率1.89%。经随访,52例取出结石患者腺体不同程度恢复功能,术后生活质量较术前显著提升(P<0.05)。截至目前无二次手术摘除腺体病例。对照组中成功取出结石35例,成功率63.6%,其中10例患者出现暂时性舌体麻木,1例患者出现舌下腺囊肿,并发症发生率20%。结论:涎腺内镜联合口内小切口手术治疗颌下腺导管腺门部结石成功率高,创伤小,患者术后并发症少,有利于提升患者生活质量。

关键词：涎腺内镜口内切口涎腺导管结石生活质量

δ-secretase in neurodegenerative diseases: mechanisms, regulators and therapeutic opportunities

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Translational Neurodegeneration 2020年第1期9卷 1-9页

作者： Zhentao Zhang ye Tian keqiang ye Department of Neurology Renmin Hospital of Wuhan UniversityWuhan 430060People’s Republic of China Department of Pathology and Laboratory Medicine Emory University School of MedicineAtlantaGA 30322USA

Mammalian asparagine endopeptidase(AEP)is a cysteine protease that cleaves its protein substrates on the Cterminal side of asparagine *** lines of evidence indicate that AEP may be involved in the pathogenesis of several neurological diseases,including Alzheimer’s disease,Parkinson’s disease,and frontotemporal *** is activated in the aging brain,cleaves amyloid precursor protein(APP)and promotes the production of amyloid-β(Aβ).We renamed AEP to δ-secretase to emphasize its role in APP fragmentation and Aβ *** also cleaves other substrates,such as tau,α-synuclein,SET,and TAR DNA-binding protein 43,generating neurotoxic fragments and disturbing their physiological *** activity of δ-secretase is tightly regulated at both the transcriptional and posttranslational ***,we review the recent advances in the role of δ-secretase in neurodegenerative diseases,with a focus on its biochemical properties and the transcriptional and posttranslational regulation of its activity,and discuss the clinical implications of δ-secretase as a diagnostic biomarker and therapeutic target for neurodegenerative diseases.

关键词： AEP Alzheimer’s disease Parkinson’s disease C/EBPβ TrkB TDP-43

7,8-dihydroxyflavone,a small molecular TrkB agonist,is useful for treating various BDNF-implicated human disorders

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Translational Neurodegeneration 2016年第1期5卷 9-17页

作者： Chaoyang Liu Chi Bun Chan keqiang ye School of Information and Safety Engineering Zhongnan University of Economics and LawWuhan 430073P.R.China Department of Physiology University of Oklahoma Health Sciences Center940 Stanton L.Young Blvd.Oklahoma CityOK 73104USA Department of Pathology and Laboratory Medicine Emory University School of Medicine615 Michael StreetAtlantaGA 30322USA

Brain-derived neurotrophic factor(BDNF)regulates a variety of biological processes predominantly via binding to the transmembrane receptor tyrosine kinase *** is a potential therapeutic target in numerous neurological,mental and metabolic ***,the lack of efficient means to deliver BDNF into the body imposes an insurmountable hurdle to its clinical *** address this challenge,we initiated a cell-based drug screening to search for small molecules that act as the TrkB agonist.7,8-Dihydroxyflavone(7,8-DHF)is our first reported small molecular TrkB agonist,which has now been extensively validated in various biochemical and cellular *** binding to the extracellular domain of TrkB,7,8-DHF triggers TrkB dimerization to induce the downstream ***,7,8-DHF is orally bioactive that can penetrate the brain blood barrier(BBB)to exert its neurotrophic activities in the central nervous *** reports suggest 7,8-DHF processes promising therapeutic efficacy in various animal disease models that are related to deficient BDNF *** this review,we summarize our current knowledge on the binding activity and specificity,structure-activity relationship,pharmacokinetic and metabolism,and the pre-clinical efficacy of 7,8-DHF against some human diseases.

关键词： Flavonoids Neurotrophin BDNF Mimetic compound Receptor agonistic activity

Fe65-engineered neuronal exosomes encapsulating corynoxine-B ameliorate cognition and pathology of Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5481-5494页

作者： Ashok Iyaswamy Abhimanyu Thakur Xin-Jie Guan Senthilkumar Krishnamoorthi Tsz Yan Fung Kejia Lu Isha Gaurav Zhijun Yang Cheng-Fu Su Kwok-Fai Lau Kui Zhang Roy Chun-Laam Ng Qizhou Lian King-Ho Cheung keqiang ye Huanhuan Joyce Chen Min Li Mr.&Mrs.Ko Chi-Ming Centre for Parkinson’s Disease Research School of Chinese MedicineHong Kong Baptist UniversityHong Kong SARChina Pritzker School of Molecular Engineering The University of ChicagoChicagoILUSA Ben May Department for Cancer Research The University of ChicagoChicagoILUSA School of Chinese Medicine Hong Kong Baptist UniversityHong Kong SARChina School of Life Sciences The Chinese University of Hong KongHong Kong SARChina Division of Neuroscience School of Biological SciencesFaculty of BiologyMedicine and HealthManchester Academic Health Science CentreUniversity of ManchesterManchesterUnited Kingdom Department of Medicine Li Ka Shing Faculty of MedicineThe University of Hong KongPok Fu LamHong Kong SARChina Prenatal Diagnostic Center and Cord Blood Bank Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhouChina HKUMed Laboratory of Cellular Therapeutics the University of Hong KongPok Fu LamHong Kong SARChina Faculty of Life and Health Sciences Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina

Alzheimer’s disease(AD)is a neurodegenerative disorder characterized by the predominant impairment of neurons in the hippocampus and the formation of amyloid plaques,hyperphosphorylated tau protein,and neurofibrillary tangles in the *** overexpression of amyloid-βprecursor protein(APP)in an AD brain results in the binding of APP intracellular domain(AICD)to Fe65 protein via the C-terminal Fe65-PTB2 interaction,which then triggers the secretion of amyloid-βand the consequent pathogenesis of ***,targeting the interaction between APP and Fe65 can offer a promising therapeutic approach for ***,exosome,a type of extracellular vesicle with diameter around 30–200 nm,has gained much attention as a potential delivery tool for brain diseases,including AD,due to their ability to cross the blood–brain barrier,their efficient uptake by autologous cells,and their ability to be surface-modified with target-specific receptor ***,the engineering of hippocampus neuron cell-derived exosomes to overexpress Fe65,enabled the development of a novel exosome-based targeted drug delivery system,which carried Corynoxine-B(Cory-B,an autophagy inducer)to the APP overexpressed-neuron cells in the brain of AD *** Fe65-engineered HT22 hippocampus neuron cell-derived exosomes(Fe65-EXO)loaded with Cory-B(Fe65-EXO-Cory-B)hijacked the signaling and blocked the natural interaction between Fe65 and APP,enabling APP-targeted delivery of ***,Fe65-EXO-Cory-B induced autophagy in APP-expressing neuronal cells,leading to amelioration of the cognitive decline and pathogenesis in AD mice,demonstrating the potential of Fe65-EXO-Cory-B as an effective therapeutic intervention for AD.

关键词： Alzheimer gained loaded

A modified stochastic model for LS+AR hybrid method and its application in polar motion short-term prediction

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Geodesy and Geodynamics 2024年第1期15卷 100-105页

作者： Fei ye Yunbin Yuan State Key Laboratory of Geodesy and Earth's Dynamics Innovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhan 430077China BeiDou High-precision Satellite Navigation and Location Service Hunan Engineering Research Center Hunan Institute of Geomatics Sciences and TechnologyChangsha 410007China Hunan Continuously Operating Reference Stations(HNCORS)Data Center Hunan Institute of Geomatics Sciences and TechnologyChangsha 410007China

Short-term(up to 30 days)predictions of Earth Rotation Parameters(ERPs)such as Polar Motion(PM:PMX and PMY)play an essential role in real-time applications related to high-precision reference frame ***,least squares(LS)+auto-regressive(AR)hybrid method is one of the main techniques of PM ***,the weighted LS+AR hybrid method performs well for PM short-term ***,the corresponding covariance information of LS fitting residuals deserves further exploration in the AR *** this study,we have derived a modified stochastic model for the LS+AR hybrid method,namely the weighted LS+weighted AR hybrid *** using the PM data products of IERS EOP 14 C04,the numerical results indicate that for PM short-term forecasting,the proposed weighted LS+weighted AR hybrid method shows an advantage over both the LS+AR hybrid method and the weighted LS+AR hybrid *** to the mean absolute errors(MAEs)of PMX/PMY sho rt-term prediction of the LS+AR hybrid method and the weighted LS+AR hybrid method,the weighted LS+weighted AR hybrid method shows average improvements of 6.61%/12.08%and 0.24%/11.65%,***,for the slopes of the linear regression lines fitted to the errors of each method,the growth of the prediction error of the proposed method is slower than that of the other two methods.

关键词： Stochastic model LS+AR Short-term prediction The earth rotation parameter(ERP) Observation model

A novel relationship between elastic modulus and void ratio associated with principal stress for coral calcareous sand

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第3期16卷 1033-1048页

作者： Ran Gao Jianhong ye State Key Laboratory of Geomechanics and Geotechnical Engineering Institute of Rock and Soil MechanicsChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing100049China

Elastic moduli,*** modulus G and bulk modulus K,are important parameters of geotechnical materials,which are not only the indices for the evaluation of the deformation ability of soils but also the important basic parameters for the development of the constitutive models of geotechnical *** this study,a series of triaxial loading-unloading-reloading shear tests and isotropic loading-unloadingreloading tests are conducted to study several typical mechanical properties of coral calcareous sand(CCS),and the void ratio evolution during loading,unloading and *** test results show that the stress-strain curves during multiple unloading processes are almost parallel,and their slopes are much greater than the deformation modulus at the initial stage of *** relationship between the confining pressure and the volumetric strain can be defined approximately by a hyperbolic equation under the condition of monotonic loading of confining *** the condition of confining pressure unloading,the evolution of void ratio is linear in the e-lnp0 plane,and these lines are a series of almost parallel lines if there are multiple processes of *** on the experimental results,it is found that the modified Hardin formulae for the elastic modulus estimation have a significant deviation from the tested values for *** on the experimental results,it is proposed that the elastic modulus of soils should be determined by the intersection line of two spatial surfaces in the G/K-e-p’/pa space(pa:atmosphere pressure).“ye formulation”is further proposed for the estimation of the elastic modulus of *** new estimation formulation for soil elastic modulus would provide a new method to accurately describe the mechanical behavior of granular soils.

关键词： Coral calcareous sand(CCS) Elastic shear modulus Elastic bulk modulus Triaxial test Estimation formulation ye formulation

Global precipitation change during the Holocene:a combination of records and simulations

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Frontiers of Earth Science 2024年第1期18卷 112-126页

作者： Wangting ye Yu LI Key Laboratory of Western China᾽s Environmental Systems(Ministry of Education) College of Earth and Environmental SciencesCenter for Hydrologic Cycle and Water Resources in Arid RegionLanzhou UniversityLanzhou 730000China

Precipitation can shape our climate both in the present and the *** though we have made significant advances in studying the mechanisms of millennial-scale climate changes through high-resolution records,we still cannot quantitatively characterize the global spatiotemporal precipitation variations within the ***,we developed a new approach to integrating data from 349 globally distributed records and climate models to reconstruct regional and global precipitation patterns over the last 12000 *** results reveal that precipitation reconstructions can be divided into monsoon-driven and westerly driven *** results suggest that an arid climate was experienced in the late glacial and early Holocene epoch(~12−7.4 cal ka BP),attaining a middle Holocene optimum(~7.4−3.5 cal ka BP),and drier after the middle *** to our reconstructions,the global precipitation reconstruction increased from the early Holocene until 3.8 cal ka BP and then subsequently *** addition,our reconstructions better reproduce the low-frequency events and extreme precipitation at the millennial scale in the hemispheres,but the performance of the reconstructions in the equatorial Pacific and the Southern Hemisphere of Africa and the Americas is *** resolution of the record and the simulation capability of the climate model remain important means to improve our understanding of past climate change.

关键词： Holocene equatorial glacial

Investigations of Water Flow Behaviors Induced by Local Temperature Variations through a Single Rough Fracture for the Enhanced Geothermal Systems

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Journal of Thermal Science 2024年第3期33卷 1055-1064页

作者： LI Jiawei ye Lin Department of Energy and Power Engineering Tsinghua UniversityBeijing100084China School of Power and Energy Northwestern Polytechnical UniversityXi’an710072China

In recent years,Enhanced Geothermal System(EGS)technologies have been applied to the geothermal resources production in the Hot Dry Rock(HDR).The core of EGS technologies is to adopt hydraulic fracturing in the reservoir to create a connected network of discrete fractures with the consideration of water as a working fluid for hydraulic fracturing and heat *** paper investigates the characteristics of water flow behaviors through a single rough fracture under different temperature and pressure conditions.A single fracture model with rough fracture surfaces is constructed and then characterized,and influences of the anisotropic factor on the average tortuosity and frictional resistance coefficient of water flow through a single fracture with rough surfaces have been compared and *** consideration of other impacting factors(temperature,pressure,fracture roughness),the impact of mass flow rate has also been *** simulation results present that changes of average tortuosity for water flow through a single rough facture are mainly affected by *** can be observed that higher temperature leads to larger average tortuosity but the frictional resistance coefficient shows an opposite *** for pressure conditions,it is found that effects of pressure on average tortuosity and frictional resistance coefficient is very small,which can be neglected under high pressure ***,the average tortuosity shows a progressively linear relationship with the mass flow *** the contrary,the frictional resistance coefficient has a negative relationship with the mass flow *** is revealed that when the mass flow rate reaches a critical point,the influences of temperature on the frictional resistance coefficient will be *** of single rough fractures with different anisotropic factors show that values of average tortuosity and frictional resistance coefficient have positive relationships with the increase

关键词： single rough fracture tortuosity frictional resistance enhanced geothermal system