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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

Sex differences in Alzheimer's disease:an urgent research venue to follow

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Neural Regeneration Research 2024年第12期19卷 2569-2570页

作者： Raquel Jiménez-Herrera Ana Contreras juan D.Navarro-lópez lydia Jiménez-Díaz Neurophysiology&Behavior lab University of Castilla-La ManchaSchool of Medicine of Ciudad RealCiudad RealSpain

Due to increasing life expectancy,the amount of people with dementia worldwide is expected to experience a substantial rise,with estimates indicating a growth from 55 million in 2019 to a staggering 139 million by the year 2050.Among the various forms of dementia.Alzheimer's disease(AD)stands out as the predominant and most prevalent.

关键词： Alzheimer predominant estimates

Enhancement of the CO_(2)adsorption and hydrogenation to CH_(4)capacity of Ru–Na–Ca/γ–Al_(2)O_(3)dual function material by controlling the Ru calcination atmosphere

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Journal of Environmental Sciences 2024年第6期140卷 292-305页

作者： Alejandro Bermejo-lópez Beñat Pereda-Ayo Jon A.Onrubia-Calvo JoséA.González-Marcos juan R.González-Velasco Department of Chemical Engineering Faculty of Science and TechnologyUniversidad del País Vasco UPV/EHUBarrio Sarrienas/n48940 LeioaBizkaiaSpain

Integrated CO_(2)capture and utilization(ICCU)technology requires dual functional materials(DFMs)to carry out the process in a single reaction system.The influence of the calcination atmosphere on efficiency of 4%Ru-8%Na_(2)CO_(3)-8%CaO/γ-Al_(2)O_(3)DFM is studied.The adsorbent precursors are first co-impregnated onto alumina and calcined in air.Then,Ru precursor is impregnated and four aliquotes are subjected to different calcination protocols:static air in muffle or under different mixtures(10%H_(2)/N_(2),50%H_(2)/N_(2)and N_(2))streams.Samples are characterized by XRD,N_(2)adsorption-desorption,H_(2)chemisorption,TEM,XPS,H_(2)-TPD,H_(2)-TPR,CO_(2)-TPD and TPSR.The catalytic behavior is evaluated,in cycles of CO_(2)adsorption and hydrogenation to CH_(4),and temporal evolution of reactants and products concentrations is analyzed.The calcination atmosphere influences the physicochemical properties and,ultimately,activity of DFMs.Characterization data and catalytic performance discover the acccomodation of Ru nanoparticles disposition and basic sites is mostly influencing the catalytic activity.DFM calcined under N_(2)flow(RuNaCa-N_(2))shows the highest CH_(4)production(449μmol/g at 370℃),because a well-controlled decomposition of precursors which favors the better accomodation of adsorbent and Ru phases,maximizing the specific surface area,the Ru-basic sites interface and the participation of different basic sites in the CO_(2)methanation reaction.Thus,the calcination in a N_(2)flow is revealed as the optimal calcination protocol to achieve highly efficient DFM for integrated CO_(2)adsorption and hydrogenation applications.

关键词： CO_(2)methanation Integrated CO_(2)capture and utilization(ICCU) Dual functional material(DFM) Ru calcination atmosphere

Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer's disease rodents

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Neural Regeneration Research 2024年第8期19卷 1835-1841页

作者： Irene Navarro-lobato Mariam Masmudi-Martín Manuel F.lópez-Aranda juan F.lópez-Téllez Gloria Delgado Pablo Granados-Durán Celia Gaona-Romero Marta Carretero-Rey Sinforiano Posadas María E.Quiros-Ortega Zafar U.Khan laboratory of Neurobiology Centro de Investigaciones Médico Sanitarias(CIMES)University of MalagaMalagaSpain Department of Medicine Faculty of MedicineUniversity of MalagaMalagaSpain Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas(CIBERNED) Institute of Health Carlos IIIMadridSpain the Donders Institute for Brain Cognition and Behaviour Radboud UniversityNijmegenThe Netherlands the Brain Metastasis Group National Cancer Research Centre(CNIO)MadridSpain the Department of Neurobiology University of California-Los AngelesLos AngelesCAUSA

Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.

关键词： behavioral performance brain-derived neurotrophic factor cognitive dysfunction episodic memory memory circuit activation memory deficits memory enhancement object recognition memory prevention of memory loss regulator of G protein signaling

Brent vs.West Texas Intermediate in the US petro derivatives price formation

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Petroleum Science 2024年第1期21卷 729-739页

作者： Alejandro Almeida antonio A.Golpe juan Manuel Martín-Alvarez Jose Carlos Vides Universidad Internacional de la Rioja Department of Quantitative Methods for Economics and BusinessLa RiojaSpain University of Huelva Department of Economics and Centro de Estudios Avanzados en FisicaMatematicas y Computacion and ICEIHuelvaSpain Complutense University of Madrid Department of Applied and Structural Economics and History and ICEIMadridSpain

In this paper,we apply the spatial panel model to explore the relationship between the dynamic of two types of crude oil prices(WTI and Brent crude oil)and their refined products over time.Considering the turbulent months of 2011,when Cushing Oklahoma had reached capacity and the crude oil export ban removal in 2015 as breakpoints,we apply this method both in the full sample and the three resultant regimes.First,results suggest our results show that both WTI and Brent display very similar behaviour with the refined products.Second,when attending to each regime,results derived from the first and third regimes are quite similar to the full sample results.Therefore,during the second regime,Brent crude oil became the benchmark in the petrol market,and it influenced the distillate products.Furthermore,our model can let us determine the price-setters and price-followers in the price formation mechanism through refined products.These results possess important considerations to policymakers and the market participants and the price formation.

关键词： Crude oil prices Spatial panel model Refined products Price formation

Anti-amyloid antibodies in Alzheimer’s disease: what did clinical trials teach us?

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Neural Regeneration Research 2025年第4期20卷 1092-1093页

作者： Danko Jeremic lydia Jiménez-Díaz juan D.Navarro-lópez NeuroPhysiology&Behavior lab University of Castilla-La ManchaBiomedical Research Center(CRIB)School of Medicine of Ciudad RealCiudad RealSpain

Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the pathology.However,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one another.Some researchers argue that these proteins are mere executors rather than primary causes of pathology.Therefore,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early AD.Moreover,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).

关键词： amyloid Alzheimer additive

Metastatic pancreatic and lung cancer patient in complete remission following immunotherapy: A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2233-2240页

作者： Joaquina Martínez-Galán Cristina Jiménez-luna Isabel Rodriguez Elisabeth Maza Carlos García-Collado antonio Rodríguez-Fernández Javier luis lópez-Hidalgo Octavio Caba Department of Medical Oncology Virgen de las Nieves University HospitalGranada 18014Spain Instituto de Investigación Biosanitaria Ibs.GranadaGranada 18012Spain Institute of Biopathology and Regenerative Medicine(IBIMER) University of GranadaGranada 18016Spain Pharmacogenetics Unit Virgen de las Nieves University HospitalGranada 18014Spain Department of Medicina Nuclear Virgen de las Nieves University HospitalGranada 18014Spain Department of Anatomía Patológica Virgen de las Nieves University HospitalGranada 18014Spain

BACKGROUND Metastatic pancreatic ductal adenocarcinoma(PDAC)is a lethal malignancy with dispiriting survival data.Immunotherapy is a promising approach to many cancer types,but achieves poor outcomes in advanced PDAC due to its immunosuppressive tumor microenvironment.We describe a case of metastatic PDAC effectively treated with pembrolizumab.CASE SUMMARY We report the case of a 67-year-old woman with unresectable locally advanced PDAC,treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus capecitabine.At nine months,pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary,confirmed by left lung biopsy.Systemic immunotherapy was then initiated with pembrolizumab,an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor types.The patient showed a complete metabolic response that was maintained throughout the treatment.The patient continues to be disease-free at 5.6 years since the start of immunotherapy.CONClUSION These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic PDAC.To our knowledge,this is the first reported case of a patient with metastatic PDAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative surgery.Further studies are required to determine biomarkers that identify PDAC patients most likely to benefit from this immunotherapy.

关键词： Pancreatic ductal adenocarcinoma lung cancer Immunotherapy Pembrolizumab Programmed cell death protein-1 Case report

Prevalence and ecological factors affecting the distribution of plant-parasitic nematodes in Prunus groves in Spain

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Journal of Integrative Agriculture 2024年第2期23卷 566-589页

作者： Ilenia Clavero-Camacho antonio Archidona-Yuste Carolina Cantalapiedra-Navarrete Pablo Castillo juan Emilio Palomares-Rius Institute for Sustainable Agriculture(IAS) Spanish National Research Council(CSIC)Córdoba 14004Spain Andalusian Institute of Agricultural and Fisheries Research and Training(IFAPA) Centro Alameda del ObispoCórdoba 14004Spain

A wide survey was conducted to study plant-parasitic nematodes(PPNs)associated with Prunus groves in Spain.This research aimed to determine the prevalence and distribution of PPNs in Prunus groves,as well as the influence of explanatory variables describing soil,climate and agricultural management in structuring the variation of PPNs community composition.A total of 218 sampling sites were surveyed and 84 PPN species belonging to 32 genera were identified based of an integrative taxonomic approach.PPN species considered as potential limiting factors in Prunus production,such as Meloidogyne arenaria,M.incognita,M.javanica,Pratylenchus penetrans and P.vulnus,were identified in this survey.Seven soil physico-chemical(C,Mg,N,Na,OM,P,pH and clay,loamy sand and sandy loam texture classes),four climate(Bio04,Bio05,Bio13 and Bio14)and four agricultural management variables(grove-use history less than 10 years,irrigation,apricot seedling rootstock,and Montclar rootstock)were identified as the most influential variables driving spatial patterns of PPNs communities.In particular,younger plantations showed higher values for species richness and diversity indices than groves cultivated for more than 20 years with Prunus spp.Our study increases the knowledge of the distribution and prevalence of PPNs associated with Prunus rhizosphere,as well as on the influence of explanatory variables driving the spatial structure PPNs communities,which has important implications for the successful design of sustainable management strategies in the future in this agricultural system.

关键词： nematodes Meloidogyne Pratylenchus Paratylenchus rootstock distribution soil grove-use almond peach

Cosmological Model in Four Time and Four Space Dimensions

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Journal of Applied Mathematics and Physics 2024年第3期12卷 829-840页

作者： juan antonio Nieto Facultad de Ciencias Físico-Matemáticas de la Universidad Autónoma de Sinaloa Culiacán Sinaloa México

We develop a cosmological model in a physical background scenario of four time and four space dimensions ((4+4)-dimensions or (4+4)-universe). We show that in this framework the (1+3)-universe is deeply connected with the (3+1)-universe. We argue that this means that in the (4+4)-universe there exists a duality relation between the (1+3)-universe and the (3+1)-universe.

关键词： Cosmological Model (4+4)-Dimensions Duality Symmetry