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From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

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Neural Regeneration Research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-pérez Gabriel Guízar-Sahagún Israel Grijalva-Otero Hospital Nacional de parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical Research Unit for Neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoratio

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

Impacts of pI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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Neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón pérez-Núñez María Fernanda González Ana María Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous *** injury and inflammation,astrocytes become reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** phosphoinositide 3-kinase(pI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the pI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/pI3K/AKT/connexin 43,and Notch/pI3K/AKT *** targeting the inactivation of the pI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the pI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

Astrocytes, reactive astrogliosis, and glial scar formation in traumatic brain injury

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Neural Regeneration Research 2025年第4期20卷 973-989页

作者： María Belén Cieri alberto Javier Ramos Laboratorio de Neuropatología Molecular IBCN UBA-CONICETFacultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

Traumatic brain injury is a global health crisis,causing significant death and disability *** that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this *** traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain *** astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are *** altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive *** addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional *** therapeutic strategies for traumatic brain injury are focused on preventing acute ***,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of *** this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRNAs or lncRNA,viral vectors,and repurposed drugs.

关键词： astrocyte glial scar innate immunity neuroinflammation stab injury Toll-like receptors

Does mesenchymal stem cell’s secretome affect spinal sensory circuits?Implication for pain therapies

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Neural Regeneration Research 2025年第1期20卷 181-183页

作者： Francesco Ferrini Esri H.Juárez Adalberto Merighi Department of Veterinary Sciences University of TurinGrugliascoTOItaly Department of psychiatry and Neuroscience UniversitéLavalQuébec CityQCCanada

Mesenchymal stem cells(MSCs)are multipotent adult stem cells of mesodermal origin that can be isolated from various tissues,including bone marrow,tooth pulp,adipose tissue,and umbilical *** have gained significant attention in regenerative medicine due to their ability to modulate the immune system and favor tissue *** enrich the medium in which they are cultivated with a broad range of bioactive molecules,including growth factors,cytokines,chemokines,enzymes,nucleic acids,and extracellular vesicles that collectively compose the MSC *** increasing number of pre-clinical studies suggest that delivering in vivo an MSC-conditioned medium(i.e.,the medium collected from MSC cultures after at least 3 days of exposure)exerts neuroprotective and anti-inflammatory effects in a variety of neurological conditions.

关键词： protective clinical collective

Liquid-liquid interfacial tension of equilibrated mixtures of ionic liquids and hydrocarbons

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Science China Chemistry 2012年第8期55卷 1519-1524页

作者： rodríguez Héctor ARCE alberto SOTO Ana Department of Chemical Engineering University of Santiago de Compostela E-15782 Santiago de Compostela Spain

Ionic liquids are possible alternative solvents for the separation of aromatic and aliphatic hydrocarbons by liquid-liquid extrac- tion. Interfacial tension is an important property to consider in the design of liquid-liquid extraction processes. In this work, the liquid-liquid interfacial tension and the mutual solubility at 25 ℃ have been measured for a series of biphasic, equilibrated mixtures of an ionic liquid and a hydrocarbon. In particular, the ionic liquids 1-alkyl-3-methylimidazolium bis（trifluorome- thanesulfonyl）imide （with the alkyl substituent being ethyl, hexyl or decyl）, 1-ethyl-3-methylimidazolium ethylsulfate, and 1-ethyl-3-methylimidazolium methanesulfonate have been selected, as well as the hydrocarbons benzene, hexane, ethylben- zene, and octane. The selected sets of ionic liquids and hydrocarbons allow the analysis of the influence of a series of effects on the interfacial tension. For example, the interfacial tension decreases with an increase in the length of the alkyl substituent chain of the cation or with an increase of the degree of charge delocalisation in the anion of the ionic liquid. Also, the interfa- cial tension with the aromatic hydrocarbons is markedly lower than that with the aliphatic hydrocarbons. A smaller effect is caused by variation of the size of the hydrocarbon. Some of the observed trends can be explained from the mutual solubility of the hydrocarbon and the ionic liquid.

关键词： ionic liquid aromatic hydrocarbon aliphatic hydrocarbon interfacial tension liquid-liquid equilibrium

Are assemblages of the fireworm Hermodice carunculata enhanced in sediments beneath offshore fish cages?

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Acta Oceanologica Sinica 2014年第4期33卷 108-111页

作者： rodrigo Riera Oscar pérez Myriam rodríguez Eva Ramos óscar Monterroso Centro de Investigaciones Medioambientales del Atlántico (CIMA SL) Department of Biodiversity Qatar Environment and Energy Research Institute (QEERI)

Abundances of the fireworm Hermodice carunculata were counted through a monitoring assessment study of fish cages in Barranco Hondo（NE Tenerife）. Seven campaigns were conducted from November 2007 to June 2010 and temporal variations were found, as well as differences among sampling stations. The polychaete H. carunculata obtained its highest abundance in sediments beneath fish cages throughout the study period. Thus, the assemblages of this omnivorous species were favoured by the presence of fish cages.

关键词： aquaculture organic enrichment environmental impact polychaeta Hermodice carunculata Tenerife Canary Islands Atlantic Ocean

Weak Continuity of Riemann Integrable Functions in Lebesgue-Bochner Spaces

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Acta Mathematica Sinica,English Series 2010年第2期26卷 241-248页

作者： J.M.CALABUIG J.rodríguez E.A.SNCHEZ-prez Instituto Universitario de Matemlica pura y Aplicada Universidad Politcnica de Valencia

In general, Banach space-valued Riemann integrable functions defined on [0, 1] （equipped with the Lebesgue measure） need not be weakly continuous almost everywhere. A Banach space is said to have the weak Lebesgue property if every Riemann integrable function taking values in it is weakly continuous almost everywhere. In this paper we discuss this property for the Banach space LX^1 of all Bochner integrable functions from [0, 1] to the Banach space X. We show that LX^1 has the weak Lebesgue property whenever X has the Radon-Nikodym property and X＊ is separable. This generalizes the result by Chonghu Wang and Kang Wan [Rocky Mountain J. Math., 31（2）, 697-703 （2001）] that L^1[0, 1] has the weak Lebesgue property.

关键词： Riemann integral Bochner integral Lebesgue-Bochner space weak Lebesgue property

META-R:A software to analyze data from multi-environment plant breeding trials

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The Crop Journal 2020年第5期8卷 745-756页

作者： Gregorio Alvarado Francisco M.rodríguez Angela pacheco Juan Burgueño JoséCrossa Mateo Vargas paulino pérez-rodríguez Marco A.Lopez-Cruz Biometrics and Statistics Unit International Maize and Wheat Improvement Center(CIMMYT)MexicoDF 6-64106600Mexico Centro de Investigación en Matemáticas(CIMAT)A.C. Jalisco S/NCol.ValencianaGuanajuatoGto 40236023Mexico Universidad Autónoma Chapingo Carretera Federal México-Texcoco km 38.5TexcocoMéxico 6356230Mexico Colegio de postgraduados Carretera México-Texcoco Km.36.5MontecilloTexcoco 6356231Mexico Department of plant Soil and Microbial SciencesMichigan State University1066 Bogue StEast LansingMI 48824USA

META-R(multi-environment trial analysis in R)is a suite of R scripts linked by a graphical user interface(GUI)designed in Java *** objective of META-R is to accurately analyze multi-environment plant breeding trials(METs)by fitting mixed and fixed linear models from experimental designs such as the randomized complete block design(RCBD)and the alpha-lattice/lattice ***-R simultaneously estimates the best linear and unbiased estimators(BLUEs)and the best linear and unbiased predictors(BLUps).Additionally,it computes the variance-covariance parameters,as well as some statistical and genetic parameters such as the least significant difference(LSD)at 5%significance,the coefficient of variation in percentage(CV),the genetic variance,and the broad-sense *** parameters are very important in the selection of top performing genotypes in plant ***-R also computes the phenotypic and genetic correlations among environments and between traits,as well as their statistical *** genetic correlations between environments or traits can be visualized in a biplot graph or a tree diagram(dendrogram).Genetic correlations are very important for identifying environments with similar behavior or making indirect selection and identifying the most highly associated ***-R performs multi-environment analyses by using the residual maximum likelihood(REML)method;these analyses can be done by environment,across environments by grouping factors(stress conditions,nitrogen content,etc.)and across environments;the analyses across environments can be done with a pre-defined degree of heritability.

关键词： environments breeding variance

Removal of carbofuran is not affected by co-application of chlorpyrifos in a coconut fiber/compost based biomixture after aging or pre-exposure

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Journal of Environmental Sciences 2016年第8期28卷 182-189页

作者： Juan Salvador Chin-pampillo mario Masís-Mora Karla Ruiz-Hidalgo Elizabeth Carazo-Rojas Carlos E.rodríguez-rodríguez Research Center of Environmental Contamination (CICA) University of Costa Rica

Biomixtures constitute the biologically active part of biopurification systems（BpS）, which are used to treat pesticide-containing wastewater. The aim of this work was to determine whether co-application of chlorpyrifos（CLp） affects the removal of carbofuran（CFN）（both insecticide/nematicides） in a coconut fiber–compost–soil biomixture（FCS biomixture）, after aging or previous exposure to CFN. Removal of CFN and two of its transformation products（3-hydroxycarbofuran and 3-ketocarbofuran） was enhanced in pre-exposed biomixtures in comparison to aged biomixtures. The co-application of CLp did not affect CFN removal, which suggests that CLp does not inhibit microbial populations in charge of CFN *** to the removal behavior, mineralization of radiolabeled14C-pesticides showed higher mineralization rates of CFN in aged biomixtures（with respect to freshly prepared or pre-exposed biomixtures）. In the case of CLp, mineralization was favored in freshly prepared biomixtures, which could be ascribed to high sorption during aging and microbial inhibition by CFN in pre-exposure. Regardless of removal and mineralization results, toxicological assays revealed a steep decrease in the acute toxicity of the matrix on the microcrustacean Daphnia magna（over 97%） after 8 days of treatment of individual pesticides or the mixture CFN/*** suggest that FCS biomixtures are suitable to be used in BpS for the treatment of wastewater in fields where both pesticides are employed.

关键词： Biomixture pesticide Mineralization Toxicity Biopurification system