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Targeting epigenetic mechanisms in amyloid-β-mediated Alzheimer’s pathophysiology:unveiling therapeutic potential

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Neural regeneration research 2025年第1期20卷 54-66页

作者： Jennie z.li Nagendran ramalingam Shaomin li Ann romney Center for Neurologic Diseases Brigham and Women’s Hospital and Harvard Medical SchoolBostonMAUSA

Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to *** evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-βoligomers in the brain,influenced by complex genetic and environmental *** memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic *** life,environmental factors can lead to enduring changes in gene expression and the emergence of brain *** changes,known as epigenetic modifications,also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal *** this context,we highlight recent advances in understanding the roles played by key components of the epigenetic machinery,specifically DNA methylation,histone modification,and microrNAs,in the development of Alzheimer’s disease,synaptic function,and activity-dependent synaptic ***,we explore various strategies,including enriched environments,exposure to non-invasive brain stimulation,and the use of pharmacological agents,aimed at improving synaptic function and enhancing long-term potentiation,a process integral to epigenetic ***,we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s *** suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.

关键词： Alzheimer’s disease DNA methylation enriched environments histone modification microrNAs non-invasive brain stimulation synaptic plasticity

Polyethylene glycol fusion repair of severed rat sciatic nerves reestablishes axonal continuity and reorganizes sensory terminal fields in the spinal cord

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Neural regeneration research 2025年第7期20卷 2095-2107页

作者： Emily A.Hibbard liwen zhou Cathy z.Yang Karthik Venkudusamy Yessenia Montoya Alexa Olivarez George D.Bittner Dale r.Sengelaub Program in Neuroscience Indiana UniversityBloomingtonINUSA Department of Neuroscience University of Texas at AustinAustinTXUSA

Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically *** used a plasmalemmal fusogen,polyethylene glycol(PEG),to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic *** have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration,and PEG-fused animals exhibit rapid(within 2–6 weeks)and extensive locomotor ***,our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific,i.e.,spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target *** this study,we examined the consequences of PEG-fusion for sensory axons of the sciatic *** adult male and female rats(Sprague–Dawley)received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without(Negative Control)the application of *** action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury *** success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days *** 2–42 days postoperatively,we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish ***-fusion repair reestablished axonal *** to unoperated animals,labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn,as well as inappropriate mediolateral and rostrocaudal ***,despite having intact peripheral nerves,similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repa

关键词： axotomy dorsal horn peripheral nerve injury plasticity polyethylene glycol(PEG) sciatic nerve sensory terminals wheat germ agglutinin horseradish peroxidase

Preparation of neodymium-doped yttrium aluminum garnet powders and fibers

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Journal of rare Earths 2008年第5期26卷 670-673页

作者： r. lópez J. zárate E. A. Aguilar J. Muoz-Saldaa Instituto de Investigaciones Metalurgicas UMSNH Morelia Centro de Investigación y de Estudios Avanzados del IPN Unidad Queretaro

Using nitrate precursors, a novel spray-drying assisted citrate gel process for the preparation of neodymium-doped yttrium alumi- num garnet （YAG） phase was developed. Synthesis of single-phase polycrystalline YAG was achieved at temperatures as low as 800 ℃ using the spray-drying methodology whilst conventional approaches currently available require 1000 ℃. Initially, a solution was prepared by mixing aluminum and yttrium nitrates, citric acid, etilenglycol and neodymium oxide. This solution was dried by pulverization （spray dryer） to obtain aggregated precursor powders of the compound. These aggregates were calcined at 800, 850 and 900 ℃ to determine the phase evolution from amorphous to crystalline by X-ray diffraction （XrD）. The morphology of aggregates was characterized by scanning electron microscopy （SEM） and transmission electron microscopy （TEM）. Moreover, through XrD it was determined that the crystallization of YAG phase started at about 800 ℃ without any intermediate phases. The powders were composed of spherical aggregates with an average diameter of 1 um. From these powders, ceramic fibers with additions of 2at.% and 5at.% Nd, were extracted from the melt with diameters ranging from 30 um to 50 um.

关键词： spray-drying melt extraction fibers yttrium aluminum garnet rare earths

Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion

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Neural regeneration research 2025年第4期20卷 1192-1206页

作者： Tyler A.Smith liwen zhou Cameron l.Ghergherehchi Michelle Mikesh Cathy z.Yang Haley O.Tucker JuliAnne Allgood Jared S.Bushman George D.Bittner Department of Molecular Biosciences University of Texas at AustinAustinTXUSA Department of Neuroscience University of Texas at AustinAustinTXUSA Division of Pharmaceutical Sciences University of WyomingLaramieWYUSA

Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal ***,such peripheral nerve allografts undergo immunological rejection by the host immune *** contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian *** relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this *** hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral *** examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal ***-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host *** to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days *** morphological signs of rejection,such as col

关键词： allograft rejection axotomy macrophage myelin nerve repair polyethylene glycol(PEG) sciatic nerve T cell transplantation Wallerian degeneration

rare earth element geochemistry of Post-to Neo-archean shales from Singhbhum mobile belt, Eastern India: implications for tectonic setting and paleo-oxidation conditions

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Chinese Journal Of Geochemistry 2015年第3期34卷 401-409页

作者： Akhtar r.mir Department of Earth Sciences University of Kashmir

In the present study, trace element(including rare earth element) chemical data has been interpreted with the aim to decipher the tectonic setting and paleo-redox conditions of the Post- to Neo-archean shales from the Singhbhum Mobile Belt, eastern India. The data show moderate enrichment of compatible elements [such as Cu(avg. 59.28 ppm), Ni(avg. 59.49 ppm), V(avg.234.24 ppm) and Cr(avg. 181.23 ppm)] relative to the Post-Archean Australian Shale. Their chondrite normalized light rare earth elements are moderately fractionated [(la/Sm)Nranges from 2.21 to 5.78], whereas heavy rare earth elements show a nearly flat pattern [(Gd/lu)Nranges from0.74 to 1.68]; this indicates that the rare earth element(rEE) concentrations, rather than being severely affected by the diagenesis and weathering processes, decreased gradually from Gd to lu. The Post-Archean Australian Shale normalized multi-element diagram shows the slight enrichment of Cr, V, zr, Y, U and Sc, whereas Sr, Pb, Hf and Th are depleted. The notable negative anomaly of Sr indicates the least accumulation of plagioclase, which is also supported by the negative Eu-anomaly in these *** la–Th–Sc and Th–zr–Sc tectonic setting diagrams indicate their continental arc setting. The geochemical parameters, such as U/Th, V/Cr, Ni/Co, and Cu/zn, indicate that these shales were deposited under oxic to anoxic environmental conditions.

关键词：稀土元素地球化学特征新太古代页岩印度构造意义氧化条件移动氧化还原条件

Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains

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Neural regeneration research 2025年第9期20卷 2667-2681页

作者： liwen zhou Karthik Venkudusamy Emily A.Hibbard Yessenia Montoya Alexa Olivarez Cathy z.Yang Adelaide leung Varun Gokhale Guhan Periyasamy zeal Pathak Dale r.Sengelaub George D.Bittner Department of Neuroscience University of TexasAustinTXUSA Program in Neuroscience Indiana UniversityBloomingtonINUSA Department of Molecular Biosciences University of TexasAustinTXUSA

Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary *** preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion *** the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred lewis *** nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the *** von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve *** withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not *** thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated *** sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the ***,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative

关键词： autophagia axotomy collateral sprouting neuropathic pain peripheral nerve repair polyethylene glycol fusion(PEG-fusion) saphenous nerve sensory neurons sex and strain Wallerian degeneration

Transport mechanism in chemically reactive hybrid nanofluid flow containing gyrotactic micro-organisms over a curved oscillatory surface

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 177-192页

作者： M.NAVEED M.IMrAN T.ASGHAr z.ABBAS Department of Mathematics Division of Science and TechnologyUniversity of Education Department of Mathematics The Islamia University of Bahawalpur

This paper examines the transport analysis, including both heat transfer and mass transfer, in hybrid nanofluid flow containing gyrotactic microorganisms towards a curved oscillatory surface. The influence of magnetic fields is also inspected in terms of their physical characteristics. To depict the phenomena of transport, modified versions of both Fick's and Fourier's laws are used. Additionally, the characteristics of both heterogeneous and homogeneous chemical reactions are also incorporated. Utilizing a curvilinear coordinate system, the flow problem is formulated as partial differential equations(PDEs)for momentum, concentration, microorganism field, and energy. An analytical solution to the obtained flow equations is achieved utilizing the homotopy analysis method(HAM).The effects of significant flow parameters on the pressure and microorganism fields, velocity, oscillation velocity, concentration, and temperature distributions are shown via graphs. Furthermore, the variations in skin friction, mass transfer rate, heat transfer rate, and local motile number due to different involved parameters are presented in tables and are analyzed in detail. Graphical results indicate that the curves of velocity and temperature fields are enhanced as the values of the solid volume fraction variables *** is also verified that the concentration rate field decreases as the values of the homogeneous reaction strength parameter and the radius of curvature parameter increase, and it increases with the Schmidt number and the heterogeneous reaction strength *** outcomes show a favorable response of the motile number to advanced values of the Peclet number, the Schmidt number, the microorganism difference parameter, and the bio-convective lewis number.

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Metabolomic fingerprinting of pig seminal plasma identifies in vivo fertility biomarkers

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Journal of Animal Science and Biotechnology 2022年第2期13卷 473-487页

作者： Yentel Mateo-Otero Pol Fernández-lópez Ariadna Delgado-Bermúdez Pau Nolis Jordi roca Jordi miró Isabel Barranco Marc Yeste Biotechnology of Animal and Human reproduction(TechnoSperm) Institute of Food and Agricultural TechnologyUniversity of GironaES-17003 GironaSpain Department of Biology Unit of Cell BiologyFaculty of SciencesUniversity of GironaES-17003 GironaSpain Centre d’Estudis Avançats de Blanes(CEAB) Spanish Research Council(CSIC)ES-17300 GironaSpain Magnetic Nuclear resonance Facility Autonomous University of BarcelonaBellaterraES-08193 Cerdanyola del VallèsSpain Department of Animal Medicine and Surgery Faculty of Veterinary MedicineUniversity of MurciaES-30100 MurciaSpain Equine reproduction Service Department of Animal Medicine and SurgeryFaculty of Veterinary MedicineAutonomous University of BarcelonaBellaterraES-08193 Cerdanyola del VallèsSpain Department of Veterinary Medical Sciences University of BolognaIT-40064 Ozzano dell’EmiliaBolognaItaly

Background:Metabolomic approaches,which include the study of low molecular weight molecules,are an emerging-omics technology useful for identification of *** this field,nuclear magnetic resonance(NMr)spectroscopy has already been used to uncover(in)fertility biomarkers in the seminal plasma(SP)of several mammalian ***,NMr studies profiling the porcine SP metabolome to uncover in vivo fertility biomarkers are yet to be carried ***,this study aimed to evaluate the putative relationship between SPmetabolites and in vivo fertility *** this end,24 entire ejaculates(three ejaculates per boar)were collected from artificial insemination(AI)-boars throughout a year(one ejaculate every 4 months).Immediately after collection,ejaculates were centrifuged to obtain SP-samples,which were stored for subsequent metabolomic analysis by NMr *** outcomes from 1525 inseminations were recorded over a year,including farrowing rate,litter size,stillbirths per litter and the duration of ***:A total of 24 metabolites were identified and quantified in all *** operating characteristic(rOC)curve analysis showed that lactate levels in SP had discriminative capacity for farrowing rate(area under the curve[AUC]=0.764)while carnitine(AUC=0.847),hypotaurine(AUC=0.819),sn-glycero-3-phosphocholine(AUC=0.833),glutamate(AUC=0.799)and glucose(AUC=0.750)showed it for litter ***,citrate(AUC=0.743),creatine(AUC=0.812),phenylalanine(AUC=0.750),tyrosine(AUC=0.753)and malonate(AUC=0.868)levels had discriminative capacity for stillbirths per litter;and malonate(AUC=0.767)and fumarate(AUC=0.868)levels for gestation ***:The assessment of selected SP-metabolites in ejaculates through NMr spectroscopy could be considered as a promising non-invasive tool to predict in vivo fertility outcomes in ***,supplementing AI-doses with specific metabolites should also be envisaged as a way to improve their f

关键词： Artificial insemination in vivo fertility Metabolomics NMr Pregnancy outcomes Seminal plasma

Patterns of trends in niveograph characteristics across the western United States from snow telemetry data

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Frontiers of Earth Science 2020年第2期14卷 315-325页

作者： S.r.FASSNACHT J.I.lÓpez-MOrENO ESS-Watershed Science Colorado State UniversityFort CollinsCO 80523-1472USA Cooperative Institute for research in the Atmosphere Colorado State UniversityFort CollinsCO 80523-1375USA Natural resources Ecology laboratory Colorado State UniversityFort CollinsCO 80523-1499USA Instituto Pirenaico de Ecología CSICCampus de Aula Dei 50080Spain

The snowpack is changing across the globe,as the climate warms and *** used daily snow water equivalent(SWE)niveograph(time series of SWE)data from 458 snow telemetry(SNOTEl)stations for the period 1982 through *** indices based on amount,timing,time length,and rates were used to describe the annual temporal evolution in SWE accumulation and *** trends in these annual indices were computed over the time period for each station using the Theil-Sen *** trends were then clustered into four groups to determine the spatial pattern of SWE *** and precipitation data were extracted from the PrISM data set,due to the shorter time period of temperature measurement at the SNOTEl *** show that SNOTEl stations can be clustered in four clusters according to the observed trends in snow *** 1 stations are mostly located in the Eastern-and South-eastern most parts of the study area and they exhibit a generalized decrease in the indices related with peak SWE and snow *** stations recorded a negative trend in precipitation and an increase in *** 4 that is mostly restricted to the North and North-west of the study area shows an almost opposite pattern to cluster 1,due to months with positive trends and a more moderate increase of *** grouped in clusters 2 and 3 appear mixed with clusters 1 and 4,in general they show very little trends in the snow indices.

关键词： snow water equivalent cluster analysis SNOTEl