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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 junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This 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 treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The 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 function.We 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 vitro.After 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 saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neuro

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

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Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

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Neural Regeneration Research 2024年第6期19卷 1256-1261页

作者： Helen M.Knight Merve Demirbugen ?z adriana PerezGrovas-Saltijeral Division of Cells Organisms and Molecular Genetics School of Life Sciences University of Notingham Department of Pharmaceutical Toxicology Faculty of Pharmacy Ankara University

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms. Methylation of N6 adenosine(m6A) and C5 cytosine(m5C) bases occur on mRNAs, tRNA, mt-tRNA, and rRNA species as well as non-coding RNAs. With emerging knowledge of RNA binding proteins that act as writer, reader, and eraser effector proteins, comes a new understanding of physiological processes controlled by these systems. Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain, give rise to different forms of disease. In this review, we discuss accumulating evidence that changes in the m6A and m5C methylation systems contribute to neurocognitive disorders. Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m6A RNA reader protein. Subsequently, familial mutations within the m6A writer gene METTL5, m5C writer genes NSUN2, NSUN3, NSUN5, and NSUN6, as well as THOC2 and THOC6 that form a protein complex with the m5C reader protein ALYREF, were recognized to cause intellectual development disorders. Similarly, differences in expression of the m5C writer and reader effector proteins, NSUN6, NSUN7, and ALYREF in brain tissue are indicated in individuals with Alzheimer’s disease, individuals with a high neuropathological load or have suffered traumatic brain injury. Likewise, an abundance of m6A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases, Alzheimer’s disease, and individuals with high cognitive reserve. m6A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson’s disease tissue, whilst modified RNAs are misplaced within diseased cells, particularly where synapses are located. In parahippocampal brain tissue, m6A modification is enriched in transcripts associated with psychiatri

关键词： 5-methylcytosine methylation Alzheimer’s disease cognitive diseases epitranscriptomics intellectual disability Lewy body diseases N6 adenosine RNA modification

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How to fill the biodiversity data gap:Is it better to invest in fieldwork or curation?

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Plant Diversity 2024年第1期46卷 39-48页

作者： Carlos A.Vargas Marius Bottin Tiina Sarkinen James E.Richardson Marcela Celis Boris Villanueva adriana Sanchez Programa de Biología Facultad de Ciencias NaturalesUniversidad del RosarioBogotaD.C.Colombia Subdireccion Científica Jardín Botanico de Bogota“Jose Celestino Mutis”BogotaD.C.Colombia Independent Researcher BogotaD.C.Colombia Tropical Diversity Section Royal Botanic Garden EdinburghUK School of Biological Earth and Environmental SciencesUniversity College CorkCorkIreland Departamento de Química y Biología Universidad del NorteKm.5 Vía Puerto ColombiaArea Metropolitana de Barranquilla 081007Colombia

Data gaps and biases are two important issues that affect the quality of biodiversity information and downstream results.Understanding how best to fill existing gaps and account for biases is necessary to improve our current information most effectively.Two current main approaches for obtaining and improving data include(1)curation of biological collections,and(2)fieldwork.However,the comparative effectiveness of these approaches in improving biodiversity data remains little explored.We used the Flora de Bogota project to study the magnitude of change in species richness,spatial coverage,and sample coverage of plant records based on curation versus fieldwork.The process of curation resulted in a decrease in species richness(synonym and error removal),but it significantly increased the number of records per species.Fieldwork contributed to a slight increase in species richness,via accumulation of new records.Additionally,curation led to increases in spatial coverage,species observed by locality,the number of plant records by species,and localities by species compared to fieldwork.Overall,curationwas more efficient in producing new information compared to fieldwork,mainly because of the large number of records available in herbaria.We recommend intensive curatorial work as the first step in increasing biodiversity data quality and quantity,to identify bias and gaps at the regional scale that can then be targeted with fieldwork.The stepwise strategy would enable fieldwork to be planned more costeffectively given the limited resources for biodiversity exploration and characterization.

关键词： Colombia Flora de Bogota Sample coverage Species richness Tropical Andes

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SARS-CoV-2 variants are associated with different clinical courses in children with MIS-C

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World Journal of Pediatrics 2024年第2期20卷 143-152页

作者： Andres F.Moreno Rojas Emelia Bainto Helen Harvey adriana H.Tremoulet Jane C.Burns Kirsten B.Dummer Department of Pediatrics Division of Pediatric CardiologyUniversity of California San Diegoand Rady Children’s Hospital3020 Children’s Way MC 5004San DiegoCA 92123USA Kawasaki Disease Research Center La JollaCAUSA Department of Pediatrics Division of Pediatric Critical CareUniversity of California San Diegoand Rady Children’s HospitalSan DiegoCAUSA Department of Pediatrics University of California San Diegoand Rady Children’s HospitalSan DiegoCAUSA

Background Recent infection with SARS‑CoV-2 in children has been associated with multisystem inflammatory syndrome in children(MIS-C).SARS‑CoV-2 has undergone different mutations.Few publications exist about specific variants and their correlation with the severity of MIS-C.Methods This was a single-center,retrospective study including all patients admitted with MIS-C at Rady Children’s Hospital-San Diego between May 2020 and March 2022.Local epidemiologic data,including viral genomic information,were obtained from public records.Demographics,clinical presentation,laboratory values,and outcomes were obtained from electronic medical records.Results The analysis included 104 pediatric patients.Four MIS-C waves were identified.Circulating variants in San Diego during the first wave included clades 20A to C.During the second wave,there were variants from clades 20A to C,20G,21C(Epsilon),20I(Alpha),and 20J(Gamma).The third wave had Delta strains(clades 21A,21I,and 21J),and the fourth had Omicron variants(clades 21K,21L,and 22C).MIS-C presented with similar symptoms and laboratory findings across all waves.More patients were admitted to the pediatric intensive care unit(PICU)(74%)and required inotropic support(63%)during the second wave.None of the patients required mechanical circulatory support,and only two required invasive ventilatory support.There was no mortality.Conclusions The various strains of SARS-CoV-2 triggered MIS-C with differing severities,with the second wave having a more severe clinical course.Whether the differences in disease severity across variants were due to changes in the virus or other factors remains unknown.

关键词： Complications COVID-19 MIS-C SARS-CoV-2 variants

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Potential of GSHP coupled with PV systems for retrofitting urban areas in different European climates based on archetypes definition

Energy and Built Environment

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Energy and Built Environment 2024年第3期5卷 374-392页

作者： Laura Carnieletto Antonino Di Bella Davide Quaggiotto Giuseppe Emmi adriana Bernardi Michele De Carli Department of Industrial Engineering–DII University of Padovavia Venezia 1PadovaItaly University of Ferrara Italy CNR–National Research Council PadovaItaly

According to the recent policies regarding energy use in buildings and the need of retrofit strategies,the aim of this work is to support policies concerning the installation of ground source heat exchangers in urban and historical areas,raising the awareness on the potential energy saving achievable with optimal sizing and limited impact on the urban environment.Archetypes have been developed distinguishing among existing and historic buildings,focusing on single-family terrace houses,which are the typical residential buildings in European historic centres.A methodology for the optimal sizing of ground source heat pumps,eventually considering dual-source system or air system has been developed combining simulations of a photovoltaic system to estimate the self-sufficiency and the self-consumption for five orientations of the building.Extreme results have been obtained for warm cli-mates,with negligible heating energy demand and possibly free cooling systems rather than traditional cooling systems needed in wintertime.Penalty temperature was acceptable despite unbalanced energy demands.With proper inclination,photovoltaic systems could provide up to 40%of self-sufficiency share also in northern cli-mates.An energy-economic analysis was carried out obtaining a variety of cases representing a general overview of the European building stock and the potential benefits achievable in terms of renewable energy share,energy savings and economic investments needed to be extended to simulations at urban scale.

关键词： Energy use database Ground source heat exchangers Urban context Energy retrofit Integrated renewables

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Prioritizing Strategies for Building the Resilience of Public Health Systems to Disasters Across Multiple Communities and Countries

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International Journal of Disaster Risk Science 2024年第1期15卷 1-17页

作者： Benjamin J.Ryan Mayumi Kako Shelby Garner Rok Fink Ismail Tayfur Jonathan Abrahams Sanjaya Bhatia adriana Campelo Matthew Fendt Alicia Fontenot Nahuel Arenas Garcia Tim Hatch Ryoma Kayano LaShonda Malrey‑Horne Makiko MacDermot Md Moshiur Rahman Chaverle Noel Shuhei Nomura Jeremy P.Novak Maria Opazo Kendell Oliver Luciana Peters Sohel Rahman PerihanŞimşek Andrew Stricklin Raymond Swienton Bryan W.brooks Frist College of Medicine Belmont UniversityNashvilleTN 37212USA Department of Environmental Science Environmental Health Science ProgramCollege of Arts and SciencesBaylor UniversityWacoTX 76798USA Division of Nursing Science School of Biomedical and Health SciencesHiroshima UniversityHiroshima 734-8553Japan Gordon E.Inman College of Health Sciences and Nursing Belmont UniversityNashvilleTN 37212USA Faculty of Health Sciences University of Ljubljana1000 LjubljanaSlovenia Department of Emergency Medicine University of Health Sciences34668 IstanbulTurkey Monash University Accident Research Center MelbourneVIC 3800Australia Global Education and Training Institute United Nations Ofce for Disaster Risk ReductionIncheon 22004Republic of Korea Regional Ofce for the Americas and Caribbean United Nations Ofce for Disaster Risk ReductionPanama City 0843-03441Panama Engineering and Computer Science Baylor UniversityWacoTX 76798USA Department of Public Health Robbins College of Health and Human SciencesBaylor UniversityWacoTX 76798USA Alabama Department of Public Health MontgomeryAL 36092USA World Health Organization Centre for Health Development(WHO Kobe Centre) Kobe 651-0073Japan Waco-McLennan County Public Health District WacoTX 76707USA Department of Health Policy and Management School of MedicineKeio UniversityTokyo 160-8582Japan Department of Global Health Policy Graduate School of MedicineThe University of TokyoTokyo 113-0033Japan Tokyo Foundation for Policy Research Tokyo 106-6234Japan Global Development College BrisbaneQLD 4000Australia Municipality of Pudahuel 13124 PudahuelChile City Hall of Porto Alegre Porto Alegre 90010-170Brazil Ministry of Health and Family Welfare Government of the People’s Republic of BangladeshDhaka 1000Bangladesh Department of Emergency Aid and Disaster Management Trabzon University61335 TrabzonTurkey Department of Emergency Medicine UT SouthwesternDallasTX 75390USA

The COVID-19 pandemic highlighted the urgent need to strengthen public health systems.In response,the United Nations Disaster Risk Reduction(UNDRR) Public Health System Resilience Scorecard(Scorecard) was applied in workshops across multiple countries.The aim of our research was to explore the workshop findings to develop priority strategies for strengthening public health system resilience.We conducted a workshop from 14 to 16 March 2023,at the UNDRR Global Education and Training Institute in Incheon,Republic of Korea.A sequential modified Delphi method was utilized to develop a set of prioritized resilience strategies.These were drawn from 70 strategies identified from 13 distinct workshops in eight countries.After two surveys,23 strategies were finalized.Ten received ratings of "High" or Very High" from89% of participants.These related to the inclusion of public health risks in emergency plans,integrating multidisciplinary teams into public health,enabling local transport mechanisms,and improving the ability to manage an influx of patients.The Scorecard provides an adaptable framework to identify and prioritize strategies for strengthening public health system resilience.By leveraging this methodology,our study demonstrated how resilience strategies could inform disaster risk reduction funding,policies,and actions.

关键词： Health system resilience Public policy Resilience scorecard Workshops

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Ecosystem Services of Grazed Grasslands in the Flooding Pampa

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Phyton-International Journal of Experimental Botany 2024年第6期93卷 1179-1202页

作者： Elizabeth J.Jacobo adriana M.Rodríguez Facultad de Agronomía Área de AgroecologíaUniversidad de Buenos AiresBuenos Aires1417Argentina Facultad de Agronomía Departamento de Producción AnimalUniversidad de Buenos AiresBuenos Aires1417Argentina

The Flooding Pampa grasslands are the last remnant of the Rio de la Plata grasslands in Argentina.Anthropo-genic interventions have led to severe degradation and,as a result,the ecosystem services provided by the grass-lands are declining,in terms of provisioning,regulating,and supporting services.We synthesized the existing literature on the ecosystem goods and services provided by these grasslands under grazing in different conditions and conservation status.We found that plant and animal diversity and primary production are the most studied ecosystem services,while climate regulation,water supply,nutrient cycling,meat production and erosion control,in that order,are less studied.Cultural services are under-researched.Continuous grazing and glyphosate spraying are the main drivers of grassland degradation.Controlled grazing and conservative stocking rates have been shown to reverse degradation and demonstrate that livestock production is compatible with ecosystem conserva-tion by maintaining regulating and provisioning services.As these management strategies are poorly integrated,improving their implementation will require important changes in farmers’decisions and the development of policies that create the economic conditions for this to happen.Research is needed to understand the conditions that prevent the knowledge generated from being transferred to producers and translated into practices that would improve the provision of ecosystem services.

关键词： Salado basin sustainability biodiversity rangelands meat production adaptative multi paddock grazing process technologies agroecology

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Bone-targeting engineered small extracellular vesicles carrying anti-miR-6359-CGGGAGC prevent valproic acid-induced bone loss

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Signal Transduction and Targeted Therapy 2024年第2期9卷 751-765页

作者： Xudong Xie Peng Cheng Liangcong Hu Wu Zhou Detai Zhang Samuel Knoedler Guodong Liu Yuan Xiong Hang Xue Yiqiang Hu Barbara Kern Doha Obed adriana CPanayi Lang Chen Chenchen Yan Ze Lin Guandong Dai Bobin Mi Yingze Zhang Guohui Liu Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration Wuhan 430022China Department of Clinical Laboratory Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022P.R.China Division of Plastic Surgery Brigham and Women’s HospitalHarvard Medical SchoolBostonMA 02152USA Department of Plastic Surgery and Hand Surgery Klinikum Rechts der IsarTechnical University of MunichMunichGermany Medical Center of Trauma and War Injuries Daping HospitalArmy Medical UniversityChonqing 400042China Department of Plastic Surgery Campus CharitéMitte|Campus Virchow-KlinikumCharité-Universitätsmedizin Berlincorporate member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany Berlin Institute of Health Charité-Universitätsmedizin BerlinBerlinGermany Department of Plastic AestheticHand and Reconstructive SurgeryHannover Medical SchoolHannoverGermany Department of Hand Plastic and Reconstructive SurgeryMicrosurgeryBurn CenterBG Trauma Center LudwigshafenUniversity of HeidelbergLudwig-Guttmann-Strasse 1367071 Ludwigshafen/RhineGermany Pingshan District People’s Hospital of Shenzhen Pingshan General Hospital of Southern Medical UniversityShenzhenGuangdong 518118China Department of Orthopaedic Surgery The Third Hospital of Hebei Medical UniversityNO.139 Ziqiang RoadShijiazhuang 050051China

The clinical role and underlying mechanisms of valproic acid(VPA)on bone homeostasis remain controversial.Herein,we confirmed that VPA treatment was associated with decreased bone mass and bone mineral density(BMD)in both patients and mice.This effect was attributed to VPA-induced elevation in osteoclast formation and activity.Through RNA-sequencing,we observed a significant rise in precursor miR-6359 expression in VPA-treated osteoclast precursors in vitro,and further,a marked upregulation of mature miR-6359(miR-6359)in vivo was demonstrated using quantitative real-time PCR(qRT-PCR)and miR-6359 fluorescent in situ hybridization(miR-6359-FISH).Specifically,the miR-6359 was predominantly increased in osteoclast precursors and macrophages but not in neutrophils,T lymphocytes,monocytes and bone marrow-derived mesenchymal stem cells(BMSCs)following VPA stimulation,which influenced osteoclast differentiation and bone-resorptive activity.Additionally,VPA-induced miR-6359 enrichment in osteoclast precursors enhanced reactive oxygen species(ROS)production by silencing the SIRT3 protein expression,followed by activation of the MAPK signaling pathway,which enhanced osteoclast formation and activity,thereby accelerating bone loss.Currently,there are no medications that can effectively treat VPA-induced bone loss.Therefore,we constructed engineered small extracellular vesicles(E-sEVs)targeting osteoclast precursors in bone and naturally carrying anti-miR-6359 by introducing of EXOmotif(CGGGAGC)in the 3’-end of the anti-miR-6359 sequence.We confirmed that the E-sEVs exhibited decent bone/osteoclast precursor targeting and exerted protective therapeutic effects on VPA-induced bone loss,but not on ovariectomy(OVX)and glucocorticoid-induced osteoporotic models,deepening our understanding of the underlying mechanism and treatment strategies for VPA-induced bone loss.

关键词： miR protective stimulation

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Is gastric cancer after bariatric surgery on the rise?Will history repeat itself?

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Chinese Journal of Cancer Research 2023年第1期35卷 11-14页

作者： adriana Vaz Safatle-Ribeiro Ulysses Ribeiro Jr Department of Gastroenterology Instituto do Cancer do Estado de Sao PauloHospital das ClinicasFaculdade de MedicinaUniversidade de Sao Paulo(ICESP-HCFMUSP)Sao PauloSP 01246-000Brazil

Gastric cancer is the fifth most common cancer and the fourth leading cause of cancer-related death worldwide(1).Despite its decreasing incidence during the last decades,a major concern has been raised in patients submitted to bariatric surgery(2).Morbid obesity incidence has increased worldwide leading to low quality of life expectancy in children。

关键词： surgery Gastric death

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A study of process-induced grain structures during steady state and non-steady state electron-beam welding of a titanium alloy

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Journal of Materials Science & Technology 2022年第18期113卷 117-127页

作者： Yu Lu Richard Turner Jeffery brooks Hector Basoalto School of Metallurgy and Materials University of BirminghamBirminghamB152TTUnited Kingdom Department of Materials Science and Engineering The University of SheffieldMappin StreetSheffieldS13JDUnited Kingdom

A detailed microstructural characterisation of the emerging weld-line grain structure,for bead-upon-plate welds in Ti-6Al-4V(Ti64)of differing plate thickness,was performed.The microstructure studied was formed during both steady state and non-steady state sections within the weld path,with the non-steady state portion being taken from the end of the plate as the weld bead and heat source overhang the edge of the plate.This allows for the effects of welding process conditions on the microstructural evolution to be determined.The weld pool geometry and 3D tomography of the weld-induced defects have been investigated.Detailed characterisation of microstructure and texture for different welding parameters and for steady and non-steady states have been used to identify physical parameters for the microstructure predictions that are difficult to obtain otherwise.The different states significantly affect the weld crown shape and formation,weld toe,weld bead depth and width.However,the heat affected zone(HAZ)re-mains unchanged.Regarding the microstructural evolution,both the steady and non-steady states have similar microstructure and texture.No defects were observed in the steady state section of welds,but sub-surface spherical pores have been observed in the non-steady state section of a weld.Finite element modelling to simulate the thermal-metallurgical-mechanical fields within the steady and non-steady state sections of the welds was considered,and the cooling rates predicted within steady state and non-steady sections were interrogated to improve the theoretical understanding of the microstructure and defect formation differences in these Ti64 EB weld regions.

关键词： Electron-beam fusion welding Processing Microstructure Ti-6Al-4V

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