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Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

Neural Regeneration Research 2025年第5期20卷 1324-1335页

作者： Hassan Saad Bachar El Baba Ali Tfaily Firas Kobeissy Juanmarco Gutierrez Gonzalez Daniel Refai Gerald R.Rodts Christian mustroph David Gimbel Jonathan Grossberg Daniel l.Barrow matthew F.Gary Ali m.Alawieh Department of Neurosurgery Emory University School of MedicineAtlantaGAUSA Department of Neurology Yale UniversityNew HavenCTUSA Center for Neurotrauma Multiomics&Biomarkers(CNMB)Morehouse School of MedicineAtlantaGAUSA

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this *** the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing *** this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the *** study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular *** effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord *** this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human *** review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

关键词： complement neuroinflammation neuroplasticity regeneration spinal cord injury targeted therapy

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Search for microglia-specific peptides:advances in the discovery toolbox

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Neural Regeneration Research 2025年第2期20卷 471-472页

作者： Ivan Sarabia Kyle m.Koss Department of Surgery University of ArizonaTucsonAZUSA

Uncontrolled and chronic inflammatory states in the central nervous system(CNS)are the hallmark of neurodegenerative pathology and every injury or stroke-related *** key mediators of these neuroinflammatory states are glial cells known as microglia,the resident immune cell at the core of the inflammatory event,and astroglia,which encapsulate inflammatory insults in proteoglycan-rich scar *** gliotic scar blocks significant portions of healthy axonal networking,preventing *** most neuroinflammation is exclusively based on the responses of said microglia,their phenotypes are suggested to follow those of macrophages;m1 and m2 are opposites of pro-and ***,microglial phenotypes have been identified to be on an inflammatory spectrum encompassing developmental,homeostatic,and reparative behaviors as opposed to their ability to affect devastating cell death cascades and scar tissue formation.

关键词： inflammation pathology death

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Non-existence of Shimura curves of mumford type generically in the non-hyperelliptic locus

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Science China mathematics 2025年

作者： Xin lü Shengli Tan Kang Zuo School of mathematical Sciences Key Laboratory of Mathematics and Engineering Applications(Ministry of Education) Shanghai Key Laboratory of Pure Mathematics and Mathematical PracticeEast China Normal University School of mathematics and Statistics Wuhan University Institut für mathematik Universit?t Mainz

We show that there does not exist any Shimura curve with a strictly maximal Higgs field generically in the Torelli locus of non-hyperelliptic curves of genus g≥4. In particular, Shimura curves of mumford type are not...

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SBl-JP-0004: A promising dual inhibitor of JAK2 and PI3KCD against gastric cancer

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Oncology research 2025年第1期33卷 235-243页

作者： Hassan m Otifi Department of Pathology College of Medicine King Khalid University Abha 62521 Saudi Arabia.

Background:Gastric cancer (GC) remains a global health burden and is often characterized by heterogeneous molecular profiles and resistance to conventional therapies. The phosphoinositide 3-kinase and PI3K and Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathways play pivotal roles in GC progression, making them attractive targets for therapeutic interventions.methods:This study applied a computational and molecular dynamics simulation approach to identify and characterize SBl-JP-0004 as a potential dual inhibitor of JAK2 and PI3KCD kinases. KATOIII and SNU-5 GC cells were used for evaluation.Results:SBl-JP-0004 exhibited a robust binding affinity for JAK2 and PI3KCD kinases, as evidenced by molecular docking scores and molecular dynamics simulations. Binding interactions and Gibbs binding free energy estimates confirmed stable and favorable interactions with target proteins. SBl-JP-0004 displayed an half-maximal inhibitory concentration (IC) value of 118.9 nm against JAK2 kinase and 200.9 nm against PI3KCD enzymes. SBl-JP-0004 exhibited potent inhibition of cell proliferation in KATOIII and SNU-5 cells, with half-maximal growth inhibitory concentration (GI) values of 250.8 and 516.3 nm, respectively. A significant elevation in the early phase apoptosis (28.53% in KATOIII cells and 26.85% in SNU-5 cells) and late phase apoptosis (17.37% in KATOIII cells and 10.05% in SNU-5 cells) were observed with SBl-JP-0004 treatment compared to 2.1% and 2.83% in their respective controls.Conclusion:The results highlight SBl-JP-0004 as a promising dual inhibitor targeting JAK2 and PI3KCD kinases for treating GC and warrant further preclinical and clinical investigations to validate its utility in clinical settings.

关键词： Dual inhibition Gastric cancer (GC) JAK2 molecular docking molecular dynamics simulation PI3KCD SBl-JP-0004

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Beginning from the end:the presynaptic terminal as a pathomechanism hub in frontotemporal dementia and amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第11期20卷 3217-3218页

作者： laura Huggon Emma l.Clayton UK Dementia Research Institute at King’s College london LondonUK Department of Basic and Clinical Neuroscience Institute of Psychiatry Psychology&NeuroscienceKing’s College LondonLondonUK

Frontotemporal dementia and amyotrophic lateral sclerosis:Frontotemporal dementia(F T D)and amyo t rophic lateral sclerosis(AlS)are neurodegenerative diseases with significant overlapping *** these neurodegenerative diseases affect different neuronal populations(with FTD affecting neurons of the frontal and temporal lobes,and AlS affecting upper and lower motor neurons),these two diseases are complexly *** and AlS exist on a disease spectrum,with shared genetic causes,clinical presentations,and pathologies.

关键词： diseases amyotrophic sclerosis

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Validity of Amontons's law for run-in short-cut aramid fiber reinforced elastomers:The effect of epoxy coated fibers

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Friction 2020年第3期8卷 613-625页

作者： m.KHAFIDH D.J.schipper m.A.mASEN N.VlEUGElS W.K.DIERKES J.W.m.NOORDERmEER Faculty of Engineering Technology University of TwenteEnschede 7500AEThe Netherlands Dutch Polymer Institute Eindhoven 5600AXThe Netherlands Department of mechanical Engineering Universitas Islam IndonesiaYogyakarta 55584Indonesia Department of mechanical Engineering Imperial College LondonLondon SW72AZUnited Kingdom

Friction between two contacting surfaces is studied *** of the k n o w n friction theories is Amontons,law which states that the friction force is proportional to the normal ***,Amontons7 law has been found to be invalid for *** the present study,the validity of Amontons7 law for short-cut aramid fiber reinforced elastomers is *** types of fillers are used to reinforce the elastomers,namely highly dispersible silica and short-cut aramid ***-cut aramid fibers with two different surface treatments are used,namely non-reactive fibers with standard oily finish(SF-fibers)and fibers treated with an epoxy coating(EF-fibers).A pin-on-disc tribometer is used to investigate the frictional behavior of the composites in sliding contact with a granite counter *** results show that,after the run-in phase,Amontons,law is valid for those composites that are reinforced by short-cut aramid fibers(without reinforcing filler,i.e.,silica)if the contact pressure is below a threshold ***,once the contact pressure exceeds this threshold value,Amontons'law will be *** threshold contact pressure of the composites containing EF-fibers is higher than of the composites containing *** composites that are reinforced by silica and short-cut aramid fibers do not follow Amontons7 law.

关键词： Amontons's law elastomer epoxy coated fiber short-cut aramid fiber

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Nonlinear forced vibration in a subcritical regime of a porous functionally graded pipe conveying fluid with a retaining clip

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Applied mathematics and mechanics(English Edition) 2025年第1期46卷 101-122页

作者： m.GHOlAmI m.EFTEKHARI Department of mechanical Engineering Shahid Bahonar University of Kerman

This study examines the nonlinear behaviors of a clamped-clamped porous pipe made of a functionally graded material(FGm) that conveys fluids and is equipped with a retaining clip, focusing on primary resonance and subcritical dynamics. The nonlinear governing equations for the FGm pipe are derived by the extended Hamilton's principle, and subsequently discretized through the application of the Galerkin *** direct method of multi-scales is then used to solve the derived equations. A thorough analysis of various parameters, including the clip stiffness, the power-law index, the porosity, and the clip location, is conducted to gain a comprehensive understanding of the system's nonlinear dynamics. Through the analysis of the first natural frequency, the study highlights the influence of the flow velocity and the clip stiffness, while the comparisons with metallic pipes emphasize the role of FGm composition. The examination of the forced response curves reveals saddle-node bifurcations and their dependence on parameters such as the detuning parameter and the power-law index, offering valuable insights into the system's nonlinear resonant behavior. Furthermore, the frequency-response curves illustrate the hardening nonlinearities influenced by factors such as the porosity and the clip stiffness, revealing nuanced effects on the system response and resonance characteristics. This comprehensive analysis enhances the understanding of nonlinear behaviors in FGm porous pipes with a retaining clip, providing key insights for practical engineering applications in system design and optimization.

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Anti-amyloid antibodies in Alzheimer’s disease: what did clinical trials teach us?

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Neural Regeneration Research 2025年第4期20卷 1092-1093页

作者： Danko Jeremic lydia Jiménez-Díaz Juan D.Navarro-lópez NeuroPhysiology&Behavior lab University of Castilla-La ManchaBiomedical Research Center(CRIB)School of Medicine of Ciudad RealCiudad RealSpain

Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the ***,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one *** researchers argue that these proteins are mere executors rather than primary causes of ***,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early ***,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).

关键词： amyloid Alzheimer additive

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Is glial heme oxygenase-1 suppression in neurodegenerative disorders permissive for neural repair?

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Neural Regeneration Research 2015年第2期10卷 208-210页

作者： Hyman m. schipper Bloomfield Centre for Research in Aging Lady Davis Institute for Medical Research Jewish General Hospital Department of Neurology &Neurosurgery and Department. of Medicine Mc Gill University

＇Core＇ neuropathology of degenerative central nervous system （CNS） disorders The common human neurodegenerative disorders （Alzheimer＇s disease （AD）, Parkinson＇s disease （PD）, amyotrophic lateral sclerosis, etc.） vary with respect to risk factors, ages of onset, sex predilections, neuraxial regions affected, hallmark cellular inclusions, behavioral and neurological symptoms, and responses to treatment. Despite these differences, there appears to be a set of ＇core＇ neuropathological features shared among these and related entities. Common to these conditions are 1） pathological deposition of non-transferrin bound iron, 2） oxidative stress and associated protein, lipid and nucleic acid modifications, 3） mitochondrial membrane damage and bioenergetic failure, and 4） macroautophagy in the affected neural tissues.

关键词： gene HO Is glial heme oxygenase-1 suppression in neurodegenerative disorders permissive for neural repair GFAP

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Glia-to-neuron reprogramming to the rescue?

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Neural Regeneration Research 2025年第5期20卷 1395-1396页

作者： Jack W.Hickmott Cindi m.morshead Department of Surgery University of TorontoTorontoONCanada Donnelly Centre for Cellular and Biomolecular Research TorontoONCanada Institute of Biomedical Engineering University of TorontoTorontoONCanada The KITE Research Institute Toronto Rehabilitation InstituteUniversity Health NetworkTorontoONCanada

Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative *** brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be *** exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.

关键词： programming passing proof

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