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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal j.Goldschmidt-Clermont Aisha Khan George jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander j.P.Goldschmidt damien d.Pearse W.dalton dietrich Allan d.Levi james d.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FdA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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distilling physical origins of hardness in multi-principal element alloys directly from ensemble neural network models

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npj Computational Materials 2022年第1期8卷 1450-1460页

作者： d.Beniwal P.Singh S.Gupta M.j.kramer d.d.johnson P.K.Ray Metallurgical&Materials Engineering Indian Institute of Technology RoparRupnagar140001PunjabIndia Ames Laboratory US Department of EnergyAmesIA50011USA Materials Science&Engineering Iowa State UniversityAmesIA50011USA

despite a plethora of data being generated on the mechanical behavior of multi-principal element alloys,a systematic assessment remains inaccessible via Edisonian *** approach this challenge by considering the specific case of alloy hardness,and present a machine-learning framework that captures the essential physical features contributing to hardness and allows high-throughput exploration of multi-dimensional compositional *** model,tested on diverse datasets,was used to explore and successfully predict hardness in Al_(x)Ti_(y)(CrFeNi)_(1-x-y),Hf_(x)Co_(y)(CrFeNi)_(1-x-y)and Al_(x)(TiZrHf)_(1-x)systems supported by data from density-functional theory predicted phase stability and ordering *** experimental validation of hardness was done on *** selected systems pose diverse challenges due to the presence of ordering and clustering pairs,as well as vacancy-stabilized novel *** also present a detailed model analysis that integrates local partial-dependencies with a compositional-stimulus and model-response study to derive material-specific insights from the decision-making process.

关键词： alloys alloy element

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Preparation of stable colloidal suspensions of superdisintegrants via wet stirred media milling

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Particuology 2014年第3期12卷 76-82页

作者： Mohammad A.Azad Afolawemi Afolabi Nikita Patel Rajesh davé Ecevit Bilgili Otto H.York department of Chemical Biologicaland Pharmaceutical EngineeringNew Jersey Institute of TechnologyNewarkNJUSA

Superdisintegrants are cross-linked polymers that can be used as dispersants for fast release of drug nanoparticles from nanocomposite microparticles during in vitro and in vivo dissolution. Currently avail- able superdisintegrant particles have average sizes of approximately 5-130 μm, which are too big for drug nanocomposite applications. Hence, production of stable superdisintegrant suspensions with less than 5 μm particles is desirable. Here, we explore the preparation of colloidal suspensions of anionic and nonionic superdisintegrants using a wet stirred media mill and assess their physical stability. Sodium starch glycolate （SSG） and crospovidone （CP） were selected as representative anionic and nonionic superdisintegrants, and hydroxypropyl cellulose （HPC） and sodium dodecyl sulfate （SdS） were used as a steric stabilizer and a wetting agent/stabilizer, respectively. Particle sizing, scanning electron microscopy, and zeta potential measurements were used to characterize the suspensions. Colloidal superdisintegrant suspensions were prepared reproducibly. The extensive particle breakage was attributed to the swelling-induced softening in water. SSG suspensions were stable even in the absence of stabilizers, whereas CP suspensions required HPC-SdS for minimizing particle aggregation. These findings were explained by the higher absolute （negative） zeta potential of the suspensions of the anionic superdisintegrant （SSG） as compared with those of the nonionic superdisintegrant （CP）.

关键词： Colloidal suspensions dispersants Physical stability Superdisintegrants Swelling Wet stirred media milling

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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

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Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging

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Neural Regeneration Research 2025年第11期20卷 3144-3150页

作者： Holly Flyger Samantha j.Holdsworth Alistair j.Gunn Laura Bennet Hamid Abbasi Mātai Medical Research Institute Tairāwhiti GisborneNew Zealand department of Anatomy&Medical Imaging Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand Center for Brain Research The University of AucklandAucklandNew Zealand Auckland Bioengineering Institute The University of AucklandAucklandNew Zealand

Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental *** assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and *** present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic *** review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent *** review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic *** challenges limit the timing consistency,particularly the need for intensive care and clinical ***,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after *** suggests that in the future it will be important to explore a wider range of times after hypo

关键词： magnetic resonance imaging neonatal hypoxic-ischemic encephalopathy neurodevelopmental outcomes prognostic biomarkers in neuroimaging scan timing therapeutic hypothermia

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design of refractory multi-principal-element alloys for high-temperature applications

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npj Computational Materials 2023年第1期9卷 884-893页

作者： Gaoyuan Ouyang Prashant Singh Ranran Su duane d.johnson Matthew j.kramer john H.Perepezko Oleg N.Senkov daniel Miracle jun Cui division of Materials Science and Engineering Ames LaboratoryAmesIA 50011USA department of Materials Science and Engineering University of Wisconsin-MadisonMadisonWI 53706USA department of Materials Science and Engineering Iowa State UniversityAmesIA 50011USA Air Force Research Laboratory Materials and Manufacturing DirectorateWright-Patterson Air Force BaseDaytonOH 45433USA

Refractory multi-principal-element alloys(RMPEAs)exhibit high specific strength at elevated temperatures(T).However,current RMPEAs lack a balance of room-temperature(RT)ductility,high-T strength,and high-T creep *** density-functional theory methods,we scanned composition space using four criteria:(1)formation energies for operational stability:-150d via interstitial electron density with Young’s moduli E>250 GPa;(3)inverse Pugh ratio for ductility:G/Bd(4)high melting points:T_(m)>2500°*** rapid bulk alloy synthesis and characterization,we validated theory and down-selected promising alloy compositions and discovered Mo72.3W12.8Ta10.0Ti2.5Zr2.5 having well-balanced RT and high-T mechanical *** alloy has comparable high-T compressive strength to well-known MoNbTaW but is more ductile and more creep *** is also superior to a commercial Mo-based refractory alloy and a nickel-based superalloy(Haynes-282)with improved high-T tensile strength and creep resistance.

关键词： creep alloy alloys

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Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

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Neural Regeneration Research 2025年第7期20卷 2011-2012页

作者： Sharon j.Brown Rafael j.Yáñez-Muñoz Heidi R.Fuller School of Pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson Center for Inherited Neuromuscular disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice ***,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute

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Women in visual neural regeneration research

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Neural Regeneration Research 2025年第2期20卷 489-490页

作者： Tonia S.Rex dav.d j.Calkins Vanderbilt Eye Institute Vanderbilt University Medical CenterNashvilleTNUSA

The year 2024 marks the 60^(th)anniversary of Title IX and 25 years since the New York Times revealed bias against female faculty members at the Massachusetts Institute of *** take an opportunity here to examine the state of gender bias in a relatively new yet already prominent field,neural regeneration in the visual system,for which there is a well-defined context useful for this *** National Eye Institute(NEI)provided the first round of research funding for its Audacious Goals Initiative(AGI)on visual neural regeneration in 2013 and the last round in ***,we focus on this *** sources included PubMed,the National Science Foundation(NSF),the NEI,the Blue Ridge Institute for Medical Research and data from the major professional organization for eye and vision research,the Association for Research in Vision and Ophthalmology(ARVO).

关键词： neural visual Times

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Generation of brain vascular heterogeneity:recent advances from the perspective of angiogenesis

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Neural Regeneration Research 2025年第7期20卷 2013-2014页

作者： Nathanael j.Lee Ryota L.Matsuoka department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA department of Molecular Medicine Cleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOHUSA

Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose and oxygen through its vascular *** vasculature consists of highly divergent blood vessel branches,giving rise to a dense network of capillaries that supply blood to all cells across the *** elaborated vascular network is thought to develop via angiogenesis,a process in which new blood vessels grow from pre-existing *** capillaries exhibit organotypic features distinct from other tissues and are formed primarily by two major endothelial cell(EC)types:those that form the semi-permeable blood-brain barrier(BBB)and those that develop highly permeable pores known as fenestrae(Matsuoka et al.,2022).The structural and functional differences between BBB and fenestrated vascular ECs represent a fundamental feature of brain vasculature and form the foundation for both brain function and homeostasis.

关键词： angiogenesis homeostasis network

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Exploring effects of property variation on fragmentation of metal rings using a simple model

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defence Technology（防务技术） 2023年第5期23卷 1-7页

作者： j.d.Robson department of Materials The University of ManchesterManchesterM139PLUK

A simple finite element implementation of the Mott model for fragmentation of a thin walled ring has been implemented and used to explore the effect of local variations in fracture strain around the *** model has successfully reproduced the fragment size distributions previously reported,which follow a characteristic“Mott distribution”form,providing sufficient(1000)simulations are *** has been shown that this form is retained even when there are large differences in the random distribution of fracture strains or a different choice of function used to describe the fracture strain *** these cases,the strain rate has a much stronger effect than fracture strain distribution the on the average fragment size and fragment ***,for cases where there are a small number of local defects that strongly reduce the fracture strain at certain locations around the ring,the predicted fragment size distribution develops a bimodal *** is also the case for large but gradual variations in fracture strain with position around the *** results have implications for cases where a small number of large pre-existing defects exist,or processing has led to macrozones in the *** utility of a simple fast running model to study these cases is discussed.

关键词： Fragmentation Mott model Property variation

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