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

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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

dietary supplementation of valine,isoleucine,and tryptophan may overcome the negative effects of excess leucine in diets for weanling pigs containing corn fermented protein

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journal of Animal Science and Biotechnology 2025年第1期16卷 267-281页

作者： Andrea P.Mallea Charmaine d.Espinosa Su A Lee Minoy A.Cristobal Leidy j.Torrez‑Mendoza Hans H.Stein division of Nutritional Sciences University of IllinoisUrbanaIL 61801USA department of Animal Sciences University of IllinoisUrbanaIL 61801USA Present Address:EnviroFlight RaleighNCUSA.

Background diets with high inclusion of corn co-products such as corn fermented protein(CFP)may contain excess Leu,which has a negative impact on feed intake and growth performance of pigs due to increased catabolism of Val and Ile and reduced availability of Trp in the brain for serotonin ***,we hypothesized that the negative effect of using CFP in diets for weanling pigs may be overcome if diets are fortified with crystalline sources of Val,Trp,and(or)*** Three hundred and twenty weanling pigs were randomly allotted to one of 10 dietary treatments in a com-pletely randomized design,with 4 pigs per pen and 8 replicate pens per treatment.A corn-soybean meal diet and 2 basal diets based on corn and 10%CFP or corn and 20%CFP were *** additional diets were formu-lated by fortifying the basal diet with 20%CFP with Ile,Trp,Val,Ile and Val,Ile and Trp,Trp and Val,or Ile,Trp and Val.A two-phase feeding program was used,with d 1 to 14 being phase 1 and d 15 to 28 being phase *** scores were recorded every other *** samples were collected on d 14 and 28 from one pig per *** d 14,fecal samples were collected from one pig per pen in 3 of the 10 treatments to determine volatile fatty acids,ammonium concen-tration,and microbial *** pigs were also euthanized and ileal tissue was *** There were no effects of dietary treatments on any of the parameters evaluated in phase *** of 10%or 20%CFP in diets reduced(Pdy weight on d 28,and average daily gain(AdG)and average daily feed intake(AdFI)in phase 2 and for the entire experimental ***,pigs fed the CFP diet supplemented with Val,Ile,and Trp had final body weight,AdFI,AdG and gain to feed ratio in phase 2 and for the entire experiment that was not different from pigs fed the control *** scores in phase 2 were reduced(Pd protein may be included by up to 20%in diets for weanling pi

关键词： Branched-chain amino acids Corn fermented protein Leucine Tryptophan Valine Weanling pigs

Tailored design of novel Co0-Coδ+dual phase nanoparticles for selective CO2 hydrogenation to ethanol

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journal of Environmental Sciences 2025年第3期149卷 598-615页

作者： Subhasis das Ganapati d.Yadav department of Chemical Engineering Institute of Chemical TechnologyNathalal Parekh MargMatunga 400019MumbaiIndia

Catalytic hydrogenation of CO_(2)to ethanol is a promising solution to address the greenhouse gas(GHG)emissions,but many current catalysts face efficiency and cost *** based catalysts are frequently examined due to their abundance,cost-efficiency,and effectiveness in the reaction,where managing the Co^(0)to Co^(δ+)ratio is *** this study,we adjusted support nature(Al_(2)O_(3),MgO-MgAl_(2)O_(4),and MgO)and reduction conditions to optimize this balance of Co^(0)to Co^(δ+)sites on the catalyst surface,enhancing ethanol *** selectivity of ethanol reached 17.9%in a continuous flow fixed bed micro-reactor over 20 mol%Co@MgO-MgAl_(2)O_(4)(CoMgAl)catalyst at 270°C and 3.0 MPa,when reduced at 400°C for 8 *** results coupled with activity analysis confirmed that mild reduction condition(400°C,10%H_(2)balance N_(2),8 h)with intermediate metal support interaction favoured the generation of partially reduced Co sites(Co^(δ+)and Co^(0)sites in single atom)over MgO-MgAl_(2)O_(4)surface,which promoted ethanol synthesis by coupling of dissociative(CHx^(∗))/non-dissociative(CHxO^(∗))intermediates,as confirmed by density functional theory ***,the CoMgAl,affordably prepared through the coprecipitation method,offers a potential alternative for CO_(2)hydrogenation to yield valuable chemicals.

关键词： CO_(2)hydrogenation Ethanol Co-based catalysts Metal support ineraction dFT analysis

Finding the balance: Modifying the cholesterol and steroidal glycoalkaloid synthesis pathway in tomato(Solanum lycopersicum L.) for human health, fruit flavor, and plant defense

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Horticultural Plant journal 2025年第1期11卷 42-56页

作者： Vincenzo Averello IV Adrian d.Hegeman Changbin Chen department of Horticultural Science University of Minnesota1970 Folwell AvenueSt.PaulMN 55108USA School of Life Sciences Arizona State University427 E Tyler MalTempeAZ 85287USA

Unlike most plants, members of the genus Solanum produce cholesterol and use this as a precursor for steroidal glycoalkaloids. The production of the compounds begins as a branch from brassinosteroid biosynthesis, which produces cholesterol that is further modified to produce steroidal glycoalkaloids. during the cholesterol biosynthesis pathway, genetic engineering could alter the formation of cholesterol from provitamin d3(7-dehydrocholesterol) and produce vitamin d3. Cholesterol is a precursor for many steroidal glycoalkaloids, including a-tomatine and esculeoside A. Alpha-tomatine is consumed by mammals and it can reduce cholesterol content and improve LdL:HdL ratio. When there is a high a-tomatine content, the fruit will have a bitter flavor, which together with other steroidal glycoalkaloids serving as protective and defensive compounds for tomato against insect, fungal, and bacterial pests. These compounds also affect the rhizosphere bacteria by recruiting beneficial bacteria. One of the steroidal glycoalkaloids, esculeoside A increases while fruit ripening. This review focuses on recent studies that uncovered key reactions of the production of cholesterol and steroidal glycoalkaloids in tomato connecting to human health, fruit flavor, and plant defense and the potential application for tomato crop improvement.

关键词： Cholesterol Steroidal glycoalkaloids Tomato Biosynthesis a-tomatine Sterols Terpenoids Plant defense

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

Effect of 5.25% Sodium Hypochlorite on Shear Bond Strength of Orthodontic Brackets Bonded with OBA-MCP

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Open journal of Orthopedics 2025年第1期15卷 1-14页

作者： Nhi Le Hoda Rahimi Richard d. Bloomstein Thomas j. Cangialosi Western dental and Orthodontics San Jose USA Orthodontic department Rutgers School of Dental Medicine Newark USA

Introduction: Bracket debonding is a frequent issue that clinicians encounter, leading to increased chair time, lost revenue, and material usage. In addition to patient compliance with their diet recommendations, the preparation and conditioning of teeth for bonding significantly influence bond strength and consequently impact orthodontic treatment success and efficiency. Because of OBA-MCP’s (orthodontic bonding adhesive with modified calcium phosphate) decreased shear bond strength (SBS), the purpose of this study was to evaluate the effects of conditioning with 5.25% sodium hypochlorite (NaOCl) before etching in the bonding protocol. Materials and Methods: 90 extracted teeth were divided into 3 groups to be bonded with orthodontic brackets with different bonding protocols: 1) Transbond XT with regular bonding protocol (etch + prime + adhesive);2) OBA-MCP with regular bonding protocol;and 3) OBA-MCP with NaOCl prior to acid etching in the regular bonding protocol. SBS (in Newtons) were measured using an MTS universal testing machine with a custom jig to apply a vertical force onto the bracket and ARI (adhesive remnant index) scores were recorded for each sample after de-bond to rate the amount of adhesive remaining. Results: The addition of NaOCl to the bonding protocol statistically significantly increased the SBS of OBA-MCP to comparable levels to Transbond XT. The ARI scores showed that when NaOCl was added, more adhesive remained. Conclusion: The addition of NaOCl to the bonding protocol can increase the SBS of adhesives with historically weaker bond strengths. However, the increased amount of adhesive remaining and the increased time spent during bonding must be considered. Further testing can be done in vivo to demonstrate the practicality of this new procedure.

关键词： Shear Bond Strength Sodium Hypochlorite Orthodontic Brackets

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

Emerging therapeutic options for the management of hepatitis C infection

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World journal of Gastroenterology 2014年第23期20卷 7079-7088页

作者： j Richard thompson department of Pharmacy Practice One University Park DriveLipscomb University College of PharmacyNashvilleTN 37204United States

Until recently the traditional treatment for hepatitis C infection included pegylated interferon and ribavirin combination *** sustained virological response(SVR)seen with this combination is poor and requires lengthy treatment to ***,significant side effects and numerous contraindications prevented many patients from being successfully treated with this *** 2011,two new protease inhibitors,telaprevir and boceprevir,were approved for use with pegylated interferon and ribavirin in the United States by the United States Food and drug *** agents have significantly improved SVR rates;however significant problems with toxicity remain including severe skin rash and *** are a wide range of compounds in late stage development for the future treatment of hepatitis C that exploit many different mechanisms of viral *** of these compounds include additional protease inhibitors,like telaprevir and boceprevir,as well as inhibitors of other nonstructural proteins in the viral genome such as NS5A and NS5B,and compounds that target host proteins within the *** of these agents are being developed for oral administration once daily and various combinations are being assessed for use without the need for pegylated interferon and *** paper reviews agents in late phase development that may be commercially available within 1-2 years.

关键词： Hepatitis C Pharmacotherapy Interferon Ribavirin Protease inhibitors Polymerase inhibitors Cyclophilin inhibitors

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