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Longitudinal assessment of peripheral organ metabolism and the gut microbiota in an APP/Ps1 transgenic mouse model of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2982-2997页

作者： Hongli Li Jianhua Huang di Zhao Lemei Zhu Zheyu Zhang Min Yi Weijun Peng Department of Integrated Traditional Chinese&Western Medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina National Clinical Research Center for Metabolic diseases ChangshaHunan ProvinceChina Hunan Academy of Chinese Medicine ChangshaHunan ProvinceChina Academician Workstation Changsha Medical UniversityChangshaHunan ProvinceChina

Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut *** aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease *** do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/Ps1)transgenic and control mice at 3,6,9,and 12 months of ***-month-old APP/Ps1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/Ps1 ***,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/Ps1 *** findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.

关键词： Alzheimer’s disease APP/Ps1 mice brain-kidney axis gut microbiota heart-brain axis liver-brain axis lung-brain axis microbiota-gut-brain axis peripheral organ metabolism spleen-brain axis

Creeping fat and gut microbiota in Crohn’s disease

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World Journal of Gastroenterology 2025年第1期31卷 16-23页

作者： Ana EV Quaglio Daniéla O Magro Marcello Imbrizi Ellen Cs De Oliveira Luiz C di stasi Ligia Y sassaki Verum Ingredients Botucatu Technology ParkBotucatu 18605-525São PauloBrazil Department of surgery Faculty of Medical SciencesState University of CampinasCampinas 13083-970São PauloBrazil Department of Gastroenterology Faculty of Medical SciencesUniversity of CampinasCampinas 13083-970São PauloBrazil Department of Internal Medicine Medical SchoolSão Paulo State UniversityBotucatu 18618-686São PauloBrazil Department of Biophysics and Pharmacology Institute of BiosciencesSão Paulo State UniversityBotucatu 18618-689São PauloBrazil

In this article,we explored the role of adipose tissue,especially mesenteric adipose tissue and creeping fat,and its association with the gut microbiota in the pathophysiology and progression of Crohn’s disease(CD).CD is a form of inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract,influenced by genetic predisposition,gut microbiota dysbiosis,and environmental *** microbiota plays a crucial role in modulating immune response and intestinal inflammation and is associated with the onset and progression of ***,visceral adipose tissue,particularly creeping fat,a mesenteric adipose tissue characterized by hypertrophy and fibrosis,has been implicated in CD pathogenesis,inflammation,and *** bacteria from the gut microbiota may translocate into mesenteric adipose tissue,contributing to the formation of creeping fat and influencing CD *** creeping fat may be a protective barrier against bacterial invasion,its expansion can damage adjacent tissues,leading to *** gut microbiota through interventions such as fecal microbiota transplantation,probiotics,and prebiotics has shown potential in managing ***,more research is needed to clarify the mechanisms linking gut dysbiosis,creeping fat,and CD progression and develop targeted therapies for microbiota modulation and fat-related complications in patients with CD.

关键词： Creeping fat Mesenteric adipose tissue Gut microbiota Crohn’s disease Inflammatory bowel disease

Revisiting cerebral endothelial cells in Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2911-2912页

作者： Amira s.Hanafy Department of Neurosurgery University Hospital BonnBonnGermany

Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory *** only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the *** amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.

关键词： Alzheimer Aβ cerebral

Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael s.Wolfe Computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-stay-Trim,”“sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria s.Aymerich Universidad de Navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Universidad de Navarra PamplonaSpain IdisNA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic *** has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

Multiple Tin Compounds Modified Carbon Fibers to Construct Heterogeneous Interfaces for Corrosion Prevention and Electromagnetic Wave Absorption

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Nano-Micro Letters 2025年第1期17卷 507-527页

作者： Zhiqiang Guo di Lan Zirui Jia Zhenguo Gao Xuetao shi Mukun He Hua Guo Guanglei Wu Pengfei Yin College of science Sichuan Agricultural UniversityYa’an 625014People’s Republic of China school of Materials science and Engineering Hubei University of Automotive TechnologyShiyan 442002People’s Republic of China Institute of Materials for Energy and Environment State Key Laboratory of Bio‑Fibers and Eco‑TextilesCollege of Materials Science and EngineeringQingdao UniversityQingdao 266071People’s Republic of China shaanxi Key Laboratory of Macromolecular science and Technology School of Chemistry and Chemical EngineeringNorthwestern Polytechnical UniversityXi’anShaanxi 710072People’s Republic of China

Currently,the demand for electromagnetic wave(EMW)absorbing materials with specific functions and capable of withstanding harsh environments is becoming increasingly ***-component interface engineering is considered an effective means to achieve high-efficiency EMW ***,interface modulation engineering has not been fully discussed and has great potential in the field of EMW *** this study,multi-component tin compound fiber composites based on carbon fiber(CF)substrate were prepared by electrospinning,hydrothermal synthesis,and high-temperature thermal *** utilizing the different properties of different substances,rich heterogeneous interfaces are *** effectively promotes charge transfer and enhances interfacial polarization and conduction *** prepared sns/sns_(2)/snO_(2)/CF composites with abundant heterogeneous interfaces have and exhibit excellent EMW absorption properties at a loading of 50 wt%in epoxy *** minimum reflection loss(RL)is−46.74 dB and the maximum effective absorption bandwidth is 5.28 ***,sns/sns_(2)/snO_(2)/CF epoxy composite coatings exhibited long-term corrosion resistance on Q235 steel ***,this study provides an effective strategy for the design of high-efficiency EMW absorbing materials in complex and harsh environments.

关键词： Electrostatic spinning Component regulation Heterogeneous interfaces Electromagnetic wave absorption Corrosion protection

The Functional Redundancy of Neddylation E2s and E3s in Modulating the Fitness of Regulatory T Cells

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Research 2024年第2期2023卷 373-387页

作者： di Wu Yi sun Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China Cancer Center of Zhejiang University Hangzhou 310029China Zhejang Provincial Clinical Research Center for Cancer Zhejang ProvinceChina Key Laboratory of Molecular Biology in Medical sciences Zhejang ProvinceChina Research Center for Life science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China

Neddylation is necessary for activation of Cullin-RING ligases(CRLs),which degrade various immune regulatory *** recent study showed that while depletion of neddylation E2-E3 pair Ube2f-sag in regulatory T(T_(reg))cells had no obvious phenotype,the same depletion of either Ube2m or Rbx1 caused inflammation disorders with different *** these E2s or E3s compensate each other in functional regulations of T_(reg)cells is,however,previously *** this report,we generated Foxp3^(Cre);Ube2m^(fl/fl);Ube2f^(fl/fl)or Foxp3^(Cre);Rbx1^(fl/fl);sag^(fl/fl)double-null mice by simultaneous deletion of both neddylation E2s or E3s in T_(reg)cells,***,Ube2m&Ube2f double-null mice developed much severe autoimmune phenotypes than did Ube2m-null mice,indicating that Ube2m markedly compensates Ube2f in T_(reg)*** minor worsened autoimmune phenotypes seen at the very early stage in Rbx1&sag double-null than Rbx1-null mice is likely due to already severe phenotypes of the later,indicating a minor compensation of Rbx1 for *** RNA profiling-based analyses revealed that up-and down-regulations of few signaling pathways in T_(reg)cells are associated with the severity of autoimmune ***,severer inflammation phenotypes seen in mice with double E3-null than with double E2-null T_(reg)cells indicate a neddylation-independent mechanism of 2 E3s,also known to serve as the RING component of CRLs in regulation of T_(reg)cell fitness.

关键词： Foxp3 inflammation markedly

Actively tunable electromagnetically induced transparency in hybrid dirac-VO2 metamaterials

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Optoelectronics Letters 2025年第1期 13-20页

作者： di Ke XIE Meng XIA Huarong CHENG Anyu LIU Yu DU Jiajia Department of Optoelectronic Engineering Chongqing University of Post and Telecommunications Chongqing Key Laboratory of Autonomous Navigation and Microsystem Chongqing University of Posts and Telecommunications Department of Automation Chongqing University of Post and Telecommunications

In this paper, we present a metamaterial structure of dirac and vanadium dioxide（VO2） and investigate its optical properties using the finite-difference time-domain（FDTD） technique. Using the phase transition feature of VO2, the design can realize active tuning of the plasmon induced transparency（PIT） effect at terahertz frequency, thereby converting from a single PIT to a double-PIT. When VO2is in the insulating state, the structure is symmetric to obtain a single-band PIT effect. When VO2is in the metallic state, the structure turns asymmetric to realize a dual-band PIT effect. This design provides a reference direction for the design of actively tunable metamaterials. Additionally, it is discovered that the transparent window's resonant frequency and the Fermi level in this structure have a somewhat linear relationship. In addition, the structure achieves superior refractive index sensitivity in the terahertz band, surpassing 1 THz/RIU. Consequently, the design exhibits encouraging potential for application in refractive index sensors and optical switches.

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高校硕士研究生就业多重困境探析——以s高校为例

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江苏商论 2025年第1期 130-134页

作者：曹迪张浩哲沈阳化工大学人文与艺术学院辽宁沈阳110142

社会工作硕士毕业生严峻的就业形势与社会工作从业人员的巨大缺口这一矛盾,深刻地影响着社会的稳定。为了解决这一矛盾,本文由小看大,基于s大学社工硕士毕业生,利用问卷调查的方式,探究择业就业取向。再利用访谈法,分析得出取向形成的原... 详细信息

社会工作硕士毕业生严峻的就业形势与社会工作从业人员的巨大缺口这一矛盾,深刻地影响着社会的稳定。为了解决这一矛盾,本文由小看大,基于s大学社工硕士毕业生,利用问卷调查的方式,探究择业就业取向。再利用访谈法,分析得出取向形成的原因,进而提出相应对策,使其选择社会相关工作。建设社工人才队伍,弥补人才缺口,增加就业,解决就业矛盾,是促进社会稳定的一个重要的问题。

关键词：社工硕士毕业生择业就业取向问卷调查对策建议