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The dorsal root ganglion as a target for neurorestoration in neuropathic pain

Neural Regeneration Research 2024年第2期19卷 296-301页

作者： Guillermo Estivill-Torrús Ana Belen Martínez-Padilla Lourdes Sánchez-Salido Anne Baron-Van Evercooren Beatriz García-Díaz Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina(IBIMA Plataforma BIONAND) MálagaSpain Unidad Clínica de Neurociencias Hospital Regional Universitario de MálagaMálagaSpain departamento de Biología Molecular y Bioquímica Universidad de MálagaSpain Sorbonne Université Institut du Cerveau-Paris Brain Institute-ICMINSERMCNRSAP-HPHôpital Pitié-SalpêtrièreParisFrance

Neuropathic pain is a severe and chronic condition widely found in the general population.The reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in patients.During the processing of pain,the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical stimulation.Furthermore,the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative therapies.Here,we will review the complex interplay between cells(satellite glial cells and inflammatory cells)and factors(cytokines,neurotrophic factors and genetic factors)that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic pain.More importantly,we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.

关键词： cytokines dorsal root ganglia genetic factors neuropathic pain neurotrophic factors pharmacologic and nonpharmacologic therapies satellite glial cells sensory neurons

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Positive solutions for some almost critical Brezis-Nirenberg type problems in bounded and exterior domains

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Acta Mathematica Sinica,English Series 2024年

作者： Salomón ALARCóN Pablo QUIJADA departamento de Matemática Universidad Técnica Federico Santa María

We study the equation-Δu=|x|~αu(p_α~*+ε)+λ_ε|x|~βu in Ω,under the condition u=0 on ?Ω,where Ω is a smooth bounded domain in RN,N≥ 5,which is symmetric respect to x1,x2,…,xNand contains the origin,α>-2,-2 0 is a small parameter and λ_ε> 0 depends on ε,with λ_ε→ 0 as ε→ 0.Our main focus lies in finding positive solutions that take the form of a tower of bubbles of order α,exhibiting concentration at the origin as ε tends to zero.Furthermore,we extend our study to the equation-Δu=|x|~αup_α~*-ε+λ_ε|x|~βu in RN\ B1,where B1is the unit ball centered at the origin,under Dirichlet zero boundary condition and an additional vanishing condition at infinity.In this context,we discover positive solutions that take the form of a tower of bubbles of order α,progressively flattening as ε tends to zero.

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Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies

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Neural Regeneration Research 2024年第4期19卷 895-899页

作者： Andrés Berardo Cristian R.Bacaglio Bárbara B.Báez Rubén Sambuelli Kazim A.Sheikh Pablo H.H.Lopez Laboratorio de Neurobiología Instituto de Investigación Médica Mercedes y Martin Ferreyra(INIMEC)-Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET)Universidad Nacional de Córdoba departamento de Química Biológica-Centro de Investigaciones en Química Biológica de Córdoba(CIQUIBIC)-Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET) Facultad de Cs.QuímicasUniversidad Nacional de Córdoba Servicio de Anatomía Patológica Clínica Universitaria Reina FabiolaUniversidad Católica de Córdoba department of Neurology University of Texas Medical School at Houston

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated wi

关键词： anti-ganglioside antibodies anti-glycan antibodies axon regeneration ganglioside Guillain-Barrésyndrome nerve repair ROCK Y-27632

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Kentish Plover(Charadrius alexandrinus) and Little Tern(Sternula albifrons) prefer shells for nesting:A field experiment

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Avian Research 2024年第1期15卷 55-59页

作者： Macarena Castro Andrés de la Cruz Nuria Martin-Sanjuan Alejandro Pérez-Hurtado Instituto Universitario de Investigacion Marina(INMAR) Campus de Excelencia Internacional del Mar(CEIMAR)Departamento de BiologíaUniversidad de CadizPuerto RealSpain Servicios centrales de Investigacion Salinas de la Esperanza Universidad de CadizPuerto RealSpain

Shorebird populations are declining worldwide,mainly due to human disturbances and loss of coastal wetlands.However,supratidal habitats as saltpans could play a role in buffering human impact.Saltpans have shown to be important as feeding or breeding sites of some shorebird species.A potential conservation strategy to increase shorebird populations in saltpans is to manipulate the cues that birds use to select optimal breeding habitat.Here it is hypothesized that shorebirds are attracted to bivalve shells due to the advantages they offer.Following this hypothesis,we supplemented a restored saltpan in 2019 and 2021 with bivalve shells,expecting an increase in the number of breeding birds’ nests.More than 75% of Kentish Plover(Charadrius alexandrinus) and Little Tern(Sternula albifrons) nests were found in patches with shells in both years.The best model for both species indicates that the presence of shells is the factor that most correlates with the location of nests.The probability of choosing one place over another to settle their nest increases in areas with an abundance of shells,double in the case of the Kentish Plover and triple in the case of the Little Tern.The result of this study may constitute a valuable tool for attracting birds to restored saltpans and could contribute to the success of expensive restoration projects where time is usually a constraint.

关键词： Habitat management Nest site selection Saltpan restoration Shell supplementation Shorebirds

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development of a Ready-to-Use PSMA-11 Kit Formulation and Biological Evaluation of Binding Affinity

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Advances in Molecular Imaging 2024年第2期13卷 7-22页

作者： Maria Renata Valente Brandão Freire Natália Marchesan Bexiga Marco Antonio Stephano João Ezequiel Oliveira Carlos Roberto Jorge Soares Ana Cláudia Camargo Miranda Anna Carolina de Alcântara Barbosa Marycel Figols de Barboza Laura Fernanda Garcia Luiz Felipe S. Teixeira Maria Helena Marumo Bellini Natanael Gomes da Silva Luiza Mascarenhas Balieiro Joel Mendes Elaine Bortoleti de Araújo Centro de Radiofarmcia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil departamento de Tecnologia Farmacutica Faculdade de Cincias Farmacuticas (USP) Cidade Universitria So Paulo Brasil Centro de biotecnologia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil departamento de Medicina Nuclear do Hospital Israelita Albert Einstein So Paulo/SP Brasil

Introduction: 68Ga-PSMA-11 is considered the gold standard in detection of micro and oligometastases in advanced prostate cancer, being used for therapeutic planning, as well as, potentially, for evaluating response to treatment. The development of ready-to-use lyophilized kit of PSMA-11 adds quality and safety to the routine use of this radiopharmaceutical and represents a pharmacotechnical challenge as it must preserve the integrity and specificity of the ligand. Methods: PSMA-11 kit formulation was proposed, considering radiolabeling parameters and the preservation of the peptide during the lyophilization process, using mannitol as an excipient. Critical temperature characterization studies were carried out using DSC equipment and the freeze-drying process was developed. The direct radiolabeling conditions were evaluated and standardized using 68Ge/68Ga generator eluate from two different manufacturers (ITG and Eckert & Ziegler). The radiochemical purity was evaluated by TLC and HPLC. Biological evaluation was carried out with lyophilized PSMA-11 to demonstrate the integrity of the peptide and preservation of biological activity after the lyophilization process. Results: Based on critical temperature characterization studies, the freeze-drying cycle was designed to reach a freezing temperature of around −40˚C and primary drying at 2˚C. Using 20 mg of mannitol, an intact and elegant lyophilized cake was obtained. PSMA-11 lyophilized kit was directly labeled with 68Ga eluate from 68Ge/68Ga GMP generators (ITG and Eckert & Ziegler) resulting in % RP > 95% at pH 4.0 to 4.5. The results obtained from in vitro and in vivo biological competition studies confirmed the preservation of PSMA-11 affinity for the receptor after lyophilization. Conclusion: A lyophilized formulation (Kit) of PSMA-11 was successfully obtained, which preserved the integrity and biological activity of the peptide and guaranteed radiolabeling efficiency.

关键词： 68Ga-PSMA-11 Prostate-Specific Membrane Antigen (PSMA) Ready-to-Use Kit GMP-Grade Generators Metastatic Prostate Cancer PET Imaging

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Solar-assisted photocatalytic water splitting using defective UiO-66 solids from modulated synthesis

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Nano Research 2024年第5期17卷 4134-4150页

作者： Celia M.Rueda-Navarro María Cabrero-Antonino Paula Escamilla Valentín Díez-Cabanes Dong Fan Pedro Atienzar Belén Ferrer Ignacio Vayá Guillaume Maurin Herme G.Baldoví Sergio Navalón departamento de Química Universitat Politècnica de ValènciaCamino de Vera s/nValencia 46022Spain Instituto de Ciencia Molecular(ICMOL) Universitat de ValènciaPaterna 46980Spain ICGM Univ.MontpellierCNRSENSCMMontpellier34095France Instituto de Tecnología Química(UPV-CSIC) Universitat Politècnica de ValènciaAvenida de los Naranjos s/nValencia 46022Spain

Metal-organic frameworks(MOFs)are attracting increasing interests as photocatalysts for solar-driven hydrogen production from water.This paper reports on a comparative study of using either acetic acid(AA)or trifluoroacetic acid(TFA)as the representative UiO-66 organic modulators for synthesizing visible light responsive UiO-66(Zr)-X(X:NH_(2) or NO_(2))photocatalysts for water splitting.The results show that photocatalytic hydrogen generation from a water/methanol mixture can be improved by varying the nature and amount of the modulator employed to prepare the different UiO-66(Zr)-X(X:NH_(2) or NO_(2))solid derivatives.UiO-66(Zr)-NH_(2) was the most active photocatalyst,followed by UiO-66(Zr)-NO_(2),both prepared with 12 equivalents of AA with respect to the organic ligand.This UiO-66(Zr)-NH_(2) solid was more active than the parent MOF in photocatalytic overall water splitting(OWS)(H_(2) and O_(2) production of 450 and 160μmol·g^(-1),respectively,in 5 h;apparent quantum yield(AQY)at 400 nm of 0.06%)in the absence of methanol and compares favourably with analogous reports.Information on the photocatalytic activity of the most active solids of both series was obtained by means of a series of techniques,including ultraviolet-visible(UV-vis)diffuse reflectance,X-ray photoelectron spectroscopy(XPS),laser flash photolysis(LFP),electron spin resonance(ESR),photoluminescence and photoelectrochemical measurements together with density functional theory(DFT)calculations.The results showed that organic acid modulators can be used to enhance the photocatalytic activity of missing linker UiO-66 defective materials in solar-powered water splitting.

关键词： heterogeneous photocatalysis metal-organic frameworks(MOFs) UiO-66 materials carboxylic acid modulators water splitting solar light

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Exploring multifaceted factors in chronic kidney disease risk: A comprehensive analysis of biochemistry, lifestyle, and inflammation in elderly Chinese individuals

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World Journal of Clinical Cases 2024年第5期12卷 1033-1035页

作者： Fernando Cardona Unitat de Genètica Molecular Instituto de Biomedicina de Valencia–CSICValencia 46010Spain Centro de investigación Biomédica en Red Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud Carlos IIIMadrid 28029Spain departamento de Biotecnología Escuela Técnica Superior de Ingeniería Agronómica y del Medio Natural(ETSIAMN)Univeristat Politècnica de ValenciaValencia 46022Spain

This letter praises a recent article in the World Journal of Clinical Cases(Roles of biochemistry data,lifestyle,and inflammation in identifying abnormal renal function in old Chinese),examining factors affecting abnormal renal function in elderly Chinese using advanced machine learning.It highlights the importance of uric acid,age,hemoglobin,body mass index,sport hours,and systolic blood pressure.The study's holistic approach,integrating lifestyle and inflammation,offers a nuanced understanding of chronic kidney disease risk factors.The letter suggests exploring mechanistic pathways of hyperuricemia,the link between anemia and renal function,and the connection between body mass index and estimated glomerular filtration rate.It advocates investigating physical activity's impact on renal health and the independent effects of blood pressure.The study significantly contributes to chronic kidney disease understanding,proposing avenues for further exploration and interventions.Commendations are extended to the authors and the journal.

关键词： Biochemistry data Lifestyle Machine learning Renal function

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Novel insights into D-Pinitol based therapies:a link between tau hyperphosphorylation and insulin resistance

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Neural Regeneration Research 2024年第2期19卷 289-295页

作者： Dina Medina-Vera Antonio Jesús López-Gambero Juan Antonio Navarro Carlos Sanjuan Elena Baixeras Juan decara Fernando Rodríguez de Fonseca Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND UGC Salud MentalMálagaSpain Facultad de Ciencias Universidad de MálagaMálagaSpain CIBER Enfermedades Cardiovasculares(CIBERCV) Hospital Universitario Virgen de la VictoriaUGC del CorazónMálagaSpain University of Bordeaux INSERMNeurocentre MagendieBordeauxFrance Euronutra S.L.Calle Johannes Kepler MálagaSpain departamento de Bioquímica y Biología Molecular Facultad de MedicinaUniversidad de MálagaMálagaSpain

Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.

关键词： Alzheimer’s disease cyclin-dependent kinase 5 diabetes D-Pinitol inositols insulin resistance kinases phosphorylation PI3K/Akt tau

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Tribologically induced nanostructural evolution of carbon materials: A new perspective

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Friction 2024年第1期12卷 144-163页

作者： Guilherme Oliveira NEVES Nicolás ARAYA Diego Berti SALVARO Thiago de Souza LAMIM Renan Oss GIACOMELLI Cristiano BINdeR Aloisio Nelmo KLEIN JoséDaniel Biasoli de MELLO Laboratório de Materiais Universidade Federal de Santa CatarinaSanta Catarina 88040-900Brazil departamento de Ingeniería Mecánica Facultad de IngenieríaUniversidad del Bío-BíoConcepcion 4070-386Chile Universidad de Concepción Concepcion 4070-386Chile SENAI Innovation Institute for Laser Processing Santa Catarina 89218-153Brazil Universidade Federal de Uberlândia Minas Gerais 38408-100Brazil

Carbon-based solid lubricants are excellent options to reduce friction and wear,especially with the carbon capability to adopt different allotropes forms.On the macroscale,these materials are sheared on the contact along with debris and contaminants to form tribolayers that govern the tribosystem performance.Using a recently developed advanced Raman analysis on the tribolayers,it was possible to quantify the contactinduced defects in the crystalline structure of a wide range of allotropes of carbon-based solid lubricants,from graphite and carbide-derived carbon particles to multi-layer graphene and carbon nanotubes.In addition,these materials were tested under various dry sliding conditions,with different geometries,topographies,and solid-lubricant application strategies.Regardless of the initial tribosystem conditions and allotrope level of atomic ordering,there is a remarkable trend of increasing the point and line defects density until a specific saturation limit in the same order of magnitude for all the materials tested.

关键词： carbon nanostructures tribology Raman spectroscopy defects quantification tribolayer solid lubrication

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Oligodendroctyes:the forgotten players of diabetes pathophysiology

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Neural Regeneration Research 2024年第11期19卷 2349-2350页

作者： Juan Antonio López-Villodres Beatriz García-Díaz departamento Fisiología Humana Histología HumanaAnatomía Patológica y Educación Física y DeportivaFacultad de MedicinaUniversidad de MálagaMálagaSpain UGC Neurociencia.Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina(IBIMA Plataforma Bionand) MálagaSpain

Oligodendrocytes(OLs),glial cells that provide myelin sheaths to axons in the central nervous system(CNS),have a dual role.First,this myelin fatty cover around the axons protects the nerves and is crucial for the saltatory propagation of action potentials.Second and not less important,OLs provide trophic support to neurons and axons.Thus,OL metabolism is important for OL well-being and the proper accomplishment of their functions,and OL metabolism energetics directly affect the energy metabolism of neighboring neurons.

关键词： metabolism nerves myelin

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