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Neuroinflammation revisited through the microglial lens

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Neural Regeneration Research 2025年第7期20卷 1989-1990页

作者： Renato Socodato João B.Relvas Institute of Research and Innovation in Health(i3S)and Institute for Molecular and Cell Biology(IBMC) University of PortoPortoPortugal Department of Biomedicine Faculty of Medicine of the University of Porto(FMUP)PortoPortugal

Neuroimmunology is emerging as a pivotal field,shedding light on the intricate dialogues between the central nervous system(CNS)and the immune *** exploration is particularly significant in understanding microglia,the CNS’s innate immune cells,beyond the conventional conflation of“neuroinflammation”and“microglial activation.”This conflation has clouded the true complexity of these processes,potentially stalling scientific progress and the development of new *** challenge the long-standing perspectives that have oversimplified these interactions,advocating for a deeper exploration of the dynamic relationship between neuroinflammation and microglial *** dissecting specific molecular pathways,we aim to illuminate their elaborate roles in neuroinflammatory responses,especially in the context of Alzheimer’s disease(AD).Here,neuroinflammation is not merely a passive observer or a direct antagonist but a complex agent in the disease’s *** article calls for a significant paradigm shift towards an integrative,multi-omics approach to *** such a comprehensive framework is crucial for advancing our understanding of neuroinflammatory conditions and paving the way for targeted therapeutic strategies for brain diseases.

关键词： inflammation simplified activation

Contribution of mechanical forces to structural synaptic plasticity:insights from 3D cellular motility mechanisms

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Neural Regeneration Research 2025年第7期20卷 1995-1996页

作者： Rita o.Teodoro Mafalda Ribeiro Ramos Lara Carvalho iNoVA4Health NOVA Medical School|Faculdade de Ciências MédicasNMS|FCMUniversidade Nova de LisboaLisboaPortugal

Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no ***-intrinsic properties such as membrane lipid composition,abundance of mechanosensors,and cytoskeletal dynamics make cells more or less likely to sense these *** and extrinsic cues are integrated by cells and this combined information determines the rate and dynamics of membrane protrusion growth or retraction(Yamada and Sixt,2019).Cell protrusions are extensions of the plasma membrane that play crucial roles in diverse contexts such as cell migration and neuronal synapse *** the nervous system,neurons are highly dynamic cells that can change the size and number of their pre-and postsynaptic elements(called synaptic boutons and dendritic spines,respectively),in response to changes in the levels of synaptic activity through a process called *** plasticity is a hallmark of the nervous system and is present throughout our lives,being required for functions like memory formation or the learning of new motor skills(Minegishi et al.,2023;Pillai and Franze,2024).

关键词： plasticity structural mechanisms

Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： Christopher J.o’Connell Matthew J.Robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA James L.Winkle College of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic

Coarse to Fine: The Role of Severe Plastic Deformation in Advancing Titanium-Based Medical Implants - A Comprehensive Review

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Journal of Wuhan University of Technology(Materials Science) 2025年第1期40卷 295-306页

作者： Dragana R Mihajlović Bojan I Međo Ivana Lj Cvijović-Alagić Veljko R Djokić Faculty of Technology and Metallurgy University of BelgradeKarnegijeva 411120 BelgradeSerbia Vinča Institute of Nuclear Sci-ences-National Institute of the Republic of Serbia University of Belgrade11001BeogradSerbia Innovation Centre of the Faculty of Technology and Metallurgy Karnegijeva 411120 BelgradeSerbia

This paper describes severe plastic deformation(SPD)procedures,which are utilized to form an ultrafine-grained structure in metallic *** the SPD process,a solid material sample is subjected to very high loads without a significant change in sample *** the present work,the high-pressure torsion(HPT)process,as one of the SPD techniques,which achieves a high degree of deformation and ensures refinement of the microstructure,will be discussed in more *** that grain size control is accepted as a method to obtain materials with desired characteristics,an overview of the properties of ultrafine-grained titanium-based biomaterials to be used in medicine is ***,particular attention is dedicated to the influences of HPT process parameters,primarily hydrostatic pressure,and number of revolutions during torsion,on the grain size and physical and mechanical characteristics(modulus of elasticity,microhardness,and tensile properties),corrosion resistance,and biocompatibility of the titanium-based biomaterials.A review of the literature indicates that titanium-based materials obtained by the SPD process show improved mechanical and physical properties without losing biocompatibility and corrosion resistance,which suggests that these methods of obtaining implants are something that should be further developed in the future.

关键词： high-pressure torsion process ultrafine-grained titanium-based materials electrochemical anodization physical properties mechanical properties

Dynamic stress concentration in an infinitely long cylindrical cavity due to a point spherical source embedded within a fluid-saturated poroelastic formation of infinite extent

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 139-156页

作者： H.HoSSEINI o.BALILASHAKI Department of Mechanical Engineering Faculty of EngineeringGolestan University

The effects of a harmonically exciting monopole source on an infinitely long cylindrical cavity embedded entirely within a fluid-saturated poroelastic formation of infinite extent are examined theoretically. It is assumed that the source is located outside the cavity at a specified distance from the borehole axis. The magnitudes of the hoop and radial stresses beside the pore pressures exerted on the interface and inside the porous medium surrounding the borehole are calculated and discussed. Biot's poroelastic modeling along with three types of boundary conditions for the cylindrical interface including the ideal fluid, empty borehole, and rigid inclusion with a hard boundary is employed for the analysis. Utilizing a proper translational addition theorem for expressing the incident spherical wave in terms of cylindrical wave expansions, the proposed boundary conditions at the interface are satisfied. Stresses are formulated by means of wave potential functions in a three-dimensional(3D) manner. The effects of the frequency and the radial distance between the source and borehole on the induced stresses are examined for the first cylindrical modes over frequency spectra. Two permeability conditions for the interface and three types of soils for the porous formation are considered throughout the analysis. To give an overall outline of the study, a numerical example is presented. The results clearly indicate that the distance is a key parameter and has considerable effects on the induced stress values. In addition, the interface permeability condition and soil characteristics play an important role in determining the dynamic response of the borehole. Finally,the obtained results are compared with the relevant analyses existing in the literature for some limit cases, and good agreement is achieved.

关键词： point source cylindrical cavity porous medium wave-field transformation stress concentration o353.4

The balance between efficient anti-inflammatory treatment and neuronal regeneration in the olfactory epithelium

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Neural Regeneration Research 2018年第10期13卷 1711-1714页

作者： Seo Young Chang isaias Glezer Department of Biochemistry Escola Paulista de MedicinaUniversidade Federal de SAo Paulo

The sense of smell is important for human quality of life. This sophisticated sensorial system relies on the detection of odorant molecules that engage receptors expressed in the cilia of dedicated neurons that constitute the olfactory epithelium（oE）. Importantly, the oE is a highly active site of adult neurogenesis where short-lived neurons are efficiently replenished, even after massive neuronal cell loss. It is suggested that the degree of olfactory function recovery after oE injury may depend on the nature of the lesion（traumatic, chemical, infectious or inflammatory）, as well on the velocity of cellular regeneration. Topical steroidal anti-inflammatory drugs, such as glucocorticoids, are routinely prescribed for treating upper airway inflammatory conditions, such as chronic rhinosinusitis. While the therapeutic strategy aims to minimize the inflammatory damage and dysfunction to nasal air conduction, new evidences raise concerns if such drugs may impair neuronal regeneration in the oE. In consequence, new directions are necessary in terms of drug development or prescription, in order to preserve olfactory function through lifelong repeated episodes of chronic inflammation in the upper respiratory tract. Here we discuss mechanisms involved in glucocorticoid deleterious effects to oE regeneration and possible therapeutic alternatives considering relevant side effects.

关键词： anti-inflammatory drugs corticosteroids hyposmia inflammation rhinosinusitis olfactory epithelium sensory neurons cell proliferation

Deep learning identification of novel autophagic protein-protein interactions and experimental validation of Beclin 2-Ubiquilin 1 axis in triple-negative breast cancer

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oncology research 2025年第1期33卷 67-81页

作者： Xiang Li Wenke Jin Lifeng Wu Huan Wang Xin Xie Wei Huang B o Liu State Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy and College of Medical Technology Chengdu University of Traditional Chinese Medicine Chengdu 611137 China. Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu 610041 China.

Background:Triple-negative breast cancer (TNBC), characterized by its lack of traditional hormone receptors and HER2, presents a significant challenge in oncology due to its poor response to conventional therapies. Autophagy is an important process for maintaining cellular homeostasis, and there are currently autophagy biomarkers that play an effective role in the clinical treatment of tumors. In contrast to targeting protein activity, intervention with protein-protein interaction (PPI) can avoid unrelated crosstalk and regulate the autophagy process with minimal interference pathways.Methods:Here, we employed Naive Bayes, Decision Tree, and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC, aiming to uncover novel therapeutic targets. Meanwhile, the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay, and the interaction relationship was verified by molecular docking and Co-IP experiments after intersection. Colony formation, cellular immunofluorescence, cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests were used to predict the clinical therapeutic effects of manipulating candidate PPI.Results:By developing three PPI classification models and analyzing over 13,000 datasets, we identified 3733 previously unknown autophagy-related PPIs. our network analysis revealed the central role of Beclin 2 in autophagy regulation, uncovering its interactions with 39 newly identified proteins. Notably, the Co-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1, which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay results. Subsequently, investigations showed that overexpressing Beclin 2 increased Ubiquilin 1, promoted autophagy-dependent cell death, and inhibited proliferation and metastasis in MDA-MB-231 cells.

关键词： Artificial intelligence (AI) Autophagy Beclin 2 Protein-protein interactions (PPI) Triple-negative breast cancer (TNBC) Ubiquilin 1

Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion

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Neural Regeneration Research 2025年第4期20卷 1192-1206页

作者： Tyler A.Smith Liwen Zhou Cameron L.Ghergherehchi Michelle Mikesh Cathy Z.Yang Haley o.Tucker JuliAnne Allgood Jared S.Bushman George D.Bittner Department of Molecular Biosciences University of Texas at AustinAustinTXUSA Department of Neuroscience University of Texas at AustinAustinTXUSA Division of Pharmaceutical Sciences University of WyomingLaramieWYUSA

Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal ***,such peripheral nerve allografts undergo immunological rejection by the host immune *** contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian *** relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this *** hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral *** examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal ***-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host *** to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days *** morphological signs of rejection,such as col

关键词： allograft rejection axotomy macrophage myelin nerve repair polyethylene glycol(PEG) sciatic nerve T cell transplantation Wallerian degeneration

Assistive techniques and their added value for tremor classification in multiple sclerosis

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Neural Regeneration Research 2024年第5期19卷 977-978页

作者： Nabin Koirala Abdulnasir Hossen Ioannis U.isaias Jens Volkmann Muthuraman Muthuraman Child Study Center School of MedicineYale UniversityNew HavenCTUSA Department of Electrical&Computer Engineering Sultan Qaboos UniversityAl-KhodMuscatOman Neural Engineering with Signal Analytics and Artificial Intelligence Department of NeurologyUniversity Hospital of WürzburgWürzburgGermany Centro Parkinson e Parkinsonism Azienda Socio Sanitaria Territoriale G.Pini-CTO20126 MilanItaly

Tremor occurs in about half of multiple sclerosis(MS)*** tremor has a broad frequency range of 2.5-7 Hz,with a higher prevalence of postural tremor(44%)compared to intentional tremor(6%)(Alusi et al.,2001).Tremor may affect the upper and lower extremities,head,and trunk,and may even affect the vocal cords in isolated cases of palatal *** tremor is classically attributed to lesions of the brain stem,cerebellum,or cerebellar peduncles,and tremor intensity has been shown to correlate with the number of lesions or their functional ***,recent work has demonstrated that inflammatory damage to the cerebello-thalamic and cortico-thalamic pathways might also play an important role in causing tremor,as it co-occurs with other signs and symptoms of MS such as dysarthria,dysmetria,dysdiadochokinesia,and dystonia(Alusi et al.,2001).

关键词： tremor sclerosis