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Genetic and epigenetic targets of natural dietary compounds as anti-Alzheimer's agents

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Neural Regeneration Research 2024年第4期19卷 846-854页

作者： Willian Orlando Castillo-Ordoñez Nohelia Cajas-salazar Mayra Alejandra Velasco-Reyes Facultad de Ciencias Naturales-Exactas y de la Educación Departamento de Biología.Universidad del Cauca Departamento de Estudios Psicológicos Universidad Icesi

Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older *** factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to *** pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental *** are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onsets)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PsEN1 and PsEN2)genes in an autosomaldominantly fashion with closely 100%*** contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its ***,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic ***,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in *** recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s *** epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective *** we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.

关键词： Alzheimer’s disease epigenetics genes methylation natural products

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 ***-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon *** 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 *** 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 *** results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of *** 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 *** contrast,the same dose showed toxic effects on the regeneration of myelinated ***,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 ***,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 *** findings open the possibility of therapeutic pharmacological intervention targeting Rho A/R

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

Photosynthetic Gas Exchange and Nitrogen Assimilation in Green Bean Plants supplied with Two sources of silicon

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Phyton-International Journal of Experimental Botany 2024年第5期93卷 963-980页

作者： Julio C.Anchondo-Páez Esteban sánchez Carlos A.Ramírez-Estrada Alondra salcido-Martínez Erick H.Ochoa-Chaparro Department of Plant Physiology Centro de Investigación en Alimentación y DesarrolloCiudad Delicias33089México

Beans contain a wide range of vitamins,proteins,calcium,and zinc which make them an important food source for many *** meet the demand for bean production worldwide,large amounts of fertilizers and pesticides are ***,the cost of production and environmental impact *** produce food sustainably,the use of beneficial nutrients such as silicon as a biostimulant has been ***,information about the effect of different sources of silicon on the metabolism of bean plants is *** plants *** were grown in pots for 60 days and the effect of foliar application of silicon nanoparticles and the silicon-based biostimulant Codasilat 4 concentrations(0,1,2,and 4 mM)on total biomass,yield,photosynthetic pigment concentration,photosynthetic activity,stomatal conductance,transpiration rate,chlorophyll fluorescence,and nitrogen assimilation were *** results obtained showed that the supply of silicon at a dose of 1 mM functioned as a biostimulant,favoring gas exchange and nitrogen assimilation within the plant,which stimulated growth and *** results of this research work allowed a better comprehension of the effects of silicon application through silicon nanoparticles and the biostimulant Codasilon the physiology of green bean plants.

关键词： Nanoparticles silicon Phaseolus vulgaris L.

Interindividual Age-Independent Differences in Human CX43 Impact Ventricular Arrhythmic Risk

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Research 2024年第3期6卷 417-432页

作者： Laura García-Mendívil María Pérez-Zabalza Antoni Oliver-Gelabert JoséMaría Vallejo-Gil Javier Fañanás-Mastral Manuel Vázquez-sancho Javier AndréBellido-Morales Alexánder sebastián Vaca-Núñez Carlos Ballester-Cuenca Emiliano Diez Laura Ordovás Esther Pueyo Biomedical signal Interpretation and Computational simulation group(BsICos) Aragón Institute of Engineering ResearchUniversity of ZaragozaZaragoza 50018Spain BsICos Instituto de Investigación Sanitaria Aragón(IISA)Zaragoza 50018Spain Centro Universitario de la Defensa(CUD) Zaragoza 50090Spain. Department of Cardiovascular surgery University Hospital Miguel ServetZaragoza 50009Spain. Institute of Experimental Medicine and Biology of Cuyo(IMBECU) CONICETMendoza 5500Argentina. Fundación Agencia Aragonesa para la Investigación y el Desarrollo(ARAID) Zaragoza 50018Spain. Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine(CIBER-BBN)Zaragoza 50018Spain.

Connexin 43 (CX43) is one of the major components of gap junctions, the structures responsible for the intercellular communication and transmission of the electrical impulse in the left ventricle. There is limited information on the histological changes of CX43 with age and their effect on electrophysiology, especially in humans. Here, we analyzed left ventricular biopsies from living donors starting at midlife to characterize age-related CX43 remodeling. We assessed its quantity, degree of lateralization, and spatial heterogeneity together with fibrotic deposition. We observed no significant age-related remodeling of CX43. Only spatial heterogeneity increased slightly with age, and this increase was better explained by biological age than by chronological age. Importantly, we found that CX43 features varied considerably among individuals in our population with no relevant relationship to age or fibrosis content, in contrast to animal species. We used our experimental results to feed computational models of human ventricular electrophysiology and to assess the effects of interindividual differences in specific features of CX43 and fibrosis on conduction velocity, action potential duration, and arrhythmogenicity. We found that larger amounts of fibrosis were associated with the highest arrhythmic risk, with this risk being increased when fibrosis deposition was combined with a reduction in CX43 amount and/or with an increase in CX43 spatial heterogeneity. These mechanisms underlying high arrhythmic risk in some individuals were not associated with age in our study population. In conclusion, our data rule out CX43 remodeling as an age-related arrhythmic substrate in the population beyond midlife, but highlight its potential as a proarrhythmic factor at the individual level, especially when combined with increased fibrosis.

关键词： CX43 rhythm Independent

The ILux^(®) compared to the mechanical meibomian gland expression for the treatment of moderate and severe meibomian gland dysfunction

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1042-1048页

作者： María Ximena Núñez Andrea Acosta-Ortega Guillermo Raul Vera-Duarte Catalina Gómez-Duarte Unit of Cornea Cataract and Refractive SurgeryVision Sana Research GroupClínica de Oftalmología de CaliFaculty of Medicine Pontificia Universidad Javeriana CaliCali 760031Colombia Department of Ophthalmology Faculty of Medicine Pontificia Universidad Javeriana CaliCali 760031Colombia Department of Ophthalmology Hospital de ClínicasNational University of AsunciónAsunción 111421Paraguay

AIM:To compare the safety and effectiveness of eyelid treatment with the ILux®-MGD Treatment system in one session versus five sessions of mechanical meibomian gland expression(MMGE)in patients with moderate to severe meibomian gland dysfunction(MGD).METHODs:A prospective,randomized,open-label,and controlled clinical trial that compared one session of the ILux®MGD Treatment system versus five sessions of MMGE in both eyes of 130 patients aged≥18y with Ocular surface Disease Index(OsDI)scores≥13,total meibomian gland scores(MGs)ofsive tear break-up time(NI-TBUT)s,who were randomized 1:1 to ILux®or ***:The mean age was 58±*** total MGs scores in both treatment groups were *** follow-up,there were significant differences in total MGs and per sector with Psis was performed using generalized estimating equations corresponding to the generalized linear model for repeated means to determine the treatment relationship with total MGs,NIBUT,and *** was a significant difference between ILux®and MMGE(Pst to the twelfth month in MGs,NI-BUT,and OsDI *** adverse events were ***:ILux®treatment compared to MMGE significantly improves symptoms and signs in patients with moderate to severe MGD for one year without adverse events.

关键词： meibomian gland dysfunction ILux® ocular surface dry eye

Differential Expression of Genes Related to Fruit Development and Capsaicinoids synthesis in Habanero Pepper Plants Grown in Contrasting soil Types

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Phyton-International Journal of Experimental Botany 2024年第2期93卷 151-183页

作者： Eduardo Burgos-Valencia Federico García-Laynes Ileana Echevarría-Machado Fatima Medina-Lara Miriam Monforte-González JoséNarváez-Zapata Manuel Martínez-Estévez Unidad de Bioquímica y Biología Molecular de Plantas Centro de Investigación Científica de YucatánCalle 43#130Chuburnáde HidalgoMéridaYucatán97205México Instituto Politécnico Nacional-Centro de Biotecnología Genómica Blvd Del Maestro esq.Elias PiñaReynosaTamaulipas88710México

Habanero pepper(Capsicum chinense Jacq.)is a crop of economic relevance in the Peninsula of *** fruits have a high level of capsaicinoids compared to peppers grown in other regions of the world,which gives them industrial *** is an important factor that affects pepper development,nutritional quality,and capsaicinoid ***,the effect of soil type on fruit development and capsaicinoid metabolism has been little *** work aimed to compare the effect of soils with contrasting characteristics,black soil(Bs)and red soil(Rs),on the expression of genes related to the development of fruits,and capsaicinoid synthesis using a transcriptomic analysis of the habanero pepper *** growing in Rs had bigger fruits and higher expression of genes related to floral development,fruit abscission,and softening which suggests that Rs stimulates fruit development from early stages until maturation *** from plants growing in Bs had enrichment in metabolic pathways related to growth,sugars,and ***,these fruits had higher capsaicinoid accumulation at 25 days post-anthesis,and higher expression of genes related to the branched-chain amino acids metabolism(ketol-acid reductisomerase KARI),pentose phosphate pathway and production of NADPH(glucose-6-phosphate-1-dehydrogenase G6PDH),and proteasome and vesicular traffic in cells(26s proteasome regulatory subunit T4 RPT4),which suggest that Bs is better in the early stimulation of pathways related to the nutritional quality and capsaicinoid metabolism in the fruits.

关键词： Capsicum chinense jacq soil types plant growth environmental conditions fruit quality capsaicinoid metabolism transcriptome

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 *** 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 *** 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 ***-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 *** 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 *** 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)*** 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

Numerical modeling of cracking pattern's influence on the dynamic response of thickened tailings disposals: a periodic approach

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Earthquake Engineering and Engineering Vibration 2018年第1期17卷 179-190页

作者： Gabriel Ferrer Esteban sáez Christian Ledezma school of Engineering Pontificia Universidad Católica de Chile National Research Center for Integrated Natural Disaster Management

Copper production is an essential component of the Chilean economy. During the extraction process of copper, large quantities of waste materials（tailings） are produced, which are typically stored in large tailing ponds. Thickened Tailings Disposal（TTD） is an alternative to conventional tailings ponds. In TTD, a considerable amount of water is extracted from the tailings before their deposition. Once a thickened tailings layer is deposited, it loses water and it shrinks, forming a relatively regular structure of tailings blocks with vertical cracks in between, which are then filled up with ＂fresh＂ tailings once the new upper layer is deposited. The dynamic response of a representative column of this complex structure made out of tailings blocks with softer material in between was analyzed using a periodic half-space finite element model. The tailings＇ behavior was modeled using an elasto-plastic multi-yielding constitutive model, and Chilean earthquake records were used for the seismic analyses. special attention was given to the liquefaction potential evaluation of TTD.

关键词： Thickened tailings Liquefaction Periodic modeling

synthesis and characterization of bulk composite Fe-si-B alloys with small concentration of Nb and Mo

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Acta Metallurgica sinica(English Letters) 2010年第6期23卷 401-408页

作者： s.Bez I.Betancourt I.A.Figueroa Institute for Materials Research National Autonomous University of Mexico (UNAM)

The preparation and some mechanical, thermal and magnetic properties of the as cast bulk composite ***4 （M=Nb, Mo） alloys obtained by suction casting are presented and discussed. The microstructrural results showed the existence of a crystalline a-Fe（si） phase embedded in a glassy matrix. The values of microhardness （/Iv） and yield strength （ay） for the Nb-containing alloy are exceptionally high, i.e. （12.65~0.3） GPa and （4.22~0.10） GPa, respectively. The saturation polarization values are found to be as high as 1.24 T for both composite ~11oys. It is thought that the interplay between the secondary crystalline phases and amorphous matrix could be responsible for the mechanical and magnetic behaviour of these alloys.

关键词： Bulk composite alloys Magnetic properties Mechanical proper- ties Thermal stability and suction casting