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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 ***,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 *** researchers argue that these proteins are mere executors rather than primary causes of ***,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 ***,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

Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1166-1179页

作者： Sebastián díaz-López Jerónimo jiménez-Castro Carlos Enrique Robles-Barraza Carlos Ayala-de Miguel Manuel Chaves-Conde Medical Oncology department Hospital Universitario ValmeSeville 41014AndalucíaSpain

Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic *** are composed of a neuroendocrine(NE)and a non-NE compo-nent in at least 30%of each *** non-NE component can include different histological combinations of glandular,squamous,mucinous and sarcomatoid phenotypes,and one or both of the components can be low-or high grade *** changes in the nomenclature of these neoplasms might lead to great deal of confusion,and the lack of specific clinical trials is the main reason why their management is *** review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available *** would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that,due to their low incidence,will require long recruitment periods.

关键词： Mixed neuroendocrine non-neuroendocrine neoplasms Mixed adenoneuroendocrine carcinomas Mixed tumours Gastroenteropancreatic Treatment Etiology diagnosis

Integrative Analysis of Transcriptome and Phenolic Compounds Profile Provides Insights into the Quality of Soursop (Annona muricata L.) Fruit

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Phyton-International Journal of Experimental Botany 2024年第7期93卷 1717-1732页

作者： Yolotzin Apatzingán Palomino-Hermosillo Ángel Elpidio díaz-Jasso Rosendo Balois-Morales Verónica AlhelíOchoa-jiménez Pedro Ulises Bautista-Rosales Guillermo Berumen-Varela Unidad de Tecnología de Alimentos-Secretaría de Investigación y Posgrado Universidad Autónoma de Nayarit.Ciudad de la Cultura SNTepic63000NayaritMéxico Programa Académico de Biología Unidad Académica de AgriculturaUniversidad Autónoma de NayaritKm.9.Carretera Tepic-CompostelaXalisco63780NayaritMéxico Estancias Posdoctorales-Consejo Nacional de Humanidades Ciencias y TecnologíasCoordinación de Apoyos a Becarios e InvestigadoresDirección de PosgradoCiudad de México03940México

Soursop(Annona muricata L.)is a tropical fruit highly valued for its uniqueﬂavor,nutritional value,and health-promoting *** ripening process of soursop involves complex changes in gene expression and metabo-lite accumulation,which have been studied using various omics *** analysis has provided insights into the regulation of key genes involved in ripening,while metabolic compound analysis has revealed the presence of numerous bioactive compounds with potential health beneﬁ***,the integration of transcrip-tome and metabolite compound data has not been extensively explored in ***,in this paper,we present a comprehensive analysis of the transcriptome and phenolic compound proﬁles of soursop during *** integration analysis showed that the genes and phenolic compounds were mainly involved in the starch and sucrose metabolism pathways during soursop ***,the phenolic compounds Kaempferol 3-Q-galactoside,Procyanidin C1,Procyanidin trimmer C1,and m-Coumaric,as well as the genes Ubiquitin-like protein 5(UBL5_ARATH),ATP-dependent zinc metalloprotease FTSH8(FTSH8_ORYSJ),Zinc transporter 4(ZIP4_AR-ATH),Thioredoxin-like 3-1(TRL31_ORYSJ),Mitogen-activated protein kinase YOdA(YOdA_ARATH),R-man-delonitrile lyase-like(MGL_ARATH),26s protease regulatory subunit 6A homolog(PRS6_SOLLC),Cytochrome P45072A13(C7A13ARATH),Cytochrome P45084A1(C84A1_ARATH)and Homoserine O-trans-acetylase(MET2-ORYSJ)were correlated and differentially accumulated and expressed,*** study provides new insights into the molecular mechanisms underlying soursop ripening and may contribute to the development of strategies for improving the nutritional quality and shelf life of this important fruit.

关键词： Bioinformatics data integration genes metabolites postharvest storage ripening

Soluble ST2:A new and promising activity marker in ulcerative colitis

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World Journal of Gastroenterology 2011年第17期17卷 2181-2190页

作者： david díaz-jiménez Lucía E Núez Caroll J Beltrán Enzo Candia Cristóbal Suazo Manuel varez-Lobos María-Julieta González Marcela A Hermoso Rodrigo Quera disciplinary Program of Immunology Institute of Biomedical SciencesFaculty of MedicineUniversidad de ChileSantiagoCL 8380453Chile department of Clinical Investigation Hospital Clínico de la Universidad de ChileSantiagoCL 8380456Chile Laboratory of Oncology and Molecular Genetics Colorectal Surgery UnitClínica Las CondesLo Fontecilla 441SantiagoCL 7591046Chile department of Gastroenterology Pontificia Universidad Católica de ChileSantiagoCL 8380074Chile Cell and Molecular Biology Program Biomedical Sciences InstituteFaculty of MedicineUniversidad de ChileSantiagoCL 8380453Chile Gastroenterology Unit Department of Internal MedicineHospital Clínico de la Universidad de ChileSantiagoCL 8380456Chile Gastroenterology Unit Clínica Las CondesLo Fontecilla 441SantiagoCL 7591046Chile

AIM:To correlate circulating soluble ST2(sST2) levels with the severity of ulcerative colitis(UC) and serum levels of pro-inflammatory cytokines,and to demonstrate the predictive power of sST2 levels for differentiation between active and inactive ***:We recruited 153 patients:82 with UC,26 with Crohn's disease(Cd) and 43 disease controls [non-inflammatory bowel disease(IBd)].Subjects were excluded if they had diagnosis of asthma,autoimmune diseases or *** serum levels of sST2 and pro-inflammatory cytokines [pg/mL;median(25th-75th)] as well as clinical features,endoscopic and histological features,were subjected to *** sST2 performance for discrimination between active and inactive UC,non-IBd and healthy controls(HC) was determined with regard to sensitivity and specificity,and Spearman's rank correlation coefficient(r).To validate the method,the area under the curve(AUC) of receiver-operator characteristic(ROC) was determined(AUC,95% CI) and the total ST2 content of the colonic mucosa in UC patients was correlated with circulating levels of ***:The serum sST2 value was significantly higher in patients with active [235.80(90.65-367.90) pg/mL] rather than inactive UC [33.19(20.04-65.32) pg/mL],based on clinical,endoscopic and histopathological characteristics,as well as compared with non-IBd and HC(P dian level of sST2 in Cd patients was 54.17(35.02-122.0) pg/mL,significantly higher than that of the HC group only(P d ability to correctly classify UC,according to activity,were 83.33%,83.33% and 83.33%,*** AUC of the ROC curve to assess the ability of this molecule to discriminate between active vs inactive UC was 0.92(0.86-0.97,P d with endoscopic and histo-pathological scores(r =

关键词：煽动性的肠疾病 Ulcerative 大肠炎可溶的 ST2 Biomarkers

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

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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 *** reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in *** 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 ***,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 ***,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 *** 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

Predicting grain size-dependent superplastic properties in friction stir processed ZK30 magnesium alloy with machine learning methods

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Journal of Magnesium and Alloys 2024年第5期12卷 1931-1943页

作者： Farid Bahari-Sambran Fernando Carreno C.M.Cepeda-jiménez Alberto Orozco-Caballero Physical Metallurgy department CENIM-CSICAv.Gregorio del Amo 828040 MadridSpain department of Mechanical Engineering Chemistry and Industrial DesignPolytechnic University of MadridRonda de Valencia 328012MadridSpain

The aim of this work is to predict,for the first time,the high temperature flow stress dependency with the grain size and the underlaid deformation mechanism using two machine learning models,random forest(RF)and artificial neural network(ANN).With that purpose,a ZK30 magnesium alloy was friction stir processed(FSP)using three different severe conditions to obtain fine grain microstructures(with average grain sizes between 2 and 3μm)prone to extensive superplastic *** three friction stir processed samples clearly deformed by grain boundary sliding(GBS)deformation mechanism at high *** maximum elongations to failure,well over 400% at high strain rate of 10^(-2)s^(-1),were reached at 400℃ in the material with coarsest grain size of 2.8μm,and at 300℃ for the finest grain size of 2μ***,the superplastic response decreased at 350℃ and 400℃ due to thermal instabilities and grain coarsening,which makes it difficult to assess the operative deformation mechanism at such *** work highlights that the machine learning models considered,especially the ANN model with higher accuracy in predicting flow stress values,allow determining adequately the superplastic creep behavior including other possible grain size scenarios.

关键词： Machine learning Artificial intelligence Magnesium alloys Superplasticity Friction stir processing Grain coarsening

Rumen microbial degradation of bromoform from red seaweed(Asparagopsis taxiformis)and the impact on rumen fermentation and methanogenic archaea

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Journal of Animal Science and Biotechnology 2024年第1期15卷 412-426页

作者： Pedro Romero Alejandro Belanche Elisabeth jiménez Rafael Hueso Eva Ramos-Morales Joan King Salwen Ermias Kebreab david R.Yáñez-Ruiz Estacion Experimental del Zaidin Consejo Superior de Investigaciones Cientificas(CSIC)Profesor Albareda 1Granada 18008Spain department of Animal Production and Food Sciences University of ZaragozaMiguel Servet 177Saragossa 50013Spain Blue Ocean Barns Inc. Redwood CityCAUSA department of Animal Science University of CaliforniaDavisCA 95618USA

Background The red macroalgae Asparagopsis is an effective methanogenesis inhibitor due to the presence of halogenated methane(CH_(4))analogues,primarily bromoform(CHBr_(3)).This study aimed to investigate the degradation process of CHBr3 from A taxiformis in the rumen and whether this process is *** in vitro batch culture system was used according to a 2×2 factorial design,assessing two A taxiformis inclusion rates[0(CTL)and 2%dM diet(AT)]and two diets[high-concentrate(HC)and high-forage diet(HF)].Incubations lasted for 72 h and samples of headspace and fermentation liquid were taken at 0,0.5,1,3,6,8,12,16,24,48 and 72 h to assess the pattern of degradation of CHBr_(3) into dibromomethane(CH_(2)Br_(2))and fermentation ***,an in vitro experiment with pure cultures of seven methanogens strains(Methanobrevibacter smithii,Methanobrevibacter ruminantium,Methanosphaera stadtmanae,Methanosarcina barkeri,Methanobrevibacter millerae,Methanorhermobacter wolfei and Methanobacterium mobile)was conducted to test the effects of increasing concentrations of CHBr3(0.4,2,10and 50μmol/L).Results The addition of AT significantly decreased CH_(4) production(P=0.002)and the acetate:propionate ratio(P=0.003)during a 72-h *** concentrations of CHBr_(3) showed a rapid decrease with nearly 90%degraded within the first 3 h of *** the contrary,CH_(2)Br_(2) concentration quickly increased during the first 6 h and then gradually decreased towards the end of the *** CHBr_(3) degradation nor CH_(2)Br_(2) synthesis were affected by the type of diet used as substrate,suggesting that the fermentation rate is not a driving factor involved in CHBr_(3)*** in vitro culture of methanogens showed a dose-response effect of CHBr3 by inhibiting the growth of ***,***,***,***,***,***,and *** The present work demonstrated that CHBr_(3) from *** is quickly degrad

关键词： Bromoform metabolism dibromomethane metabolism Methane mitigation Methanogens Rumen microbiota Seaweed

Glucocorticosteroid therapy in inflammatory bowel diseases: From clinical practice to molecular biology

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World Journal of Gastroenterology 2017年第36期23卷 6628-6638页

作者： Karen dubois-Camacho Payton A Ottum daniel Franco-Munoz Marjorie de la Fuente Alejandro Torres-Riquelme david díaz-jiménez Mauricio Olivares-Morales Gonzalo Astudillo Rodrigo Quera Marcela A Hermoso Innate Immunity Laboratory Immunology ProgramInstitute of Biomedical SciencesFaculty of MedicineUniversidad de Chile Neuroimmunology Laboratory Immunology ProgramInstitute of Biomedical SciencesFaculty of MedicineUniversidad de Chile division of Research Clínica Las Condes Gastroenterology department Inflammatory Bowel Disease ProgramClínica Las Condes

Inflammatory bowel diseases(IBds),such as ulcerative colitis and Crohn's disease,are chronic pathologies associated with a deregulated immune response in the intestinal mucosa,and they are triggered by environmental factors in genetically susceptible *** glucocorticoids(GCs)are widely used as anti-inflammatory therapy in *** the past,patients with moderate or severe states of inflammation received GCs as a first line therapy with an important effectiveness in terms of reduction of the disease activity and the induction of ***,this treatment often results in detrimental side *** downside drove the development of second generation GCs and more precise(non-systemic)drugdelivery *** clinical trials show that most of these new treatments have similar effectiveness to first generation GCs with fewer adverse *** remaining challenge in successful treatment of IBds concerns the refractoriness and dependency that some patients encounter during GCs treatment.A deeper understanding of the molecular mechanisms underlying GC response is key to personalizing drug choice for IBds patients to optimize their response to *** this review,we examine the clinical characteristics of treatment with GCs,followed by an in depth analysis of the proposed molecular mechanisms involved in its resistance and dependence associated with *** thorough analysis of current clinical and biomedical literature may help guide physicians in determining a course of treatment for IBds patients and identifies important areas needing further study.

关键词： Inflammatory bowel diseases Ulcerative colitis Crohn's disease Glucocorticoid dependence Glucocorticoid resistance

Reuse of port industrial heritage in tourist cities:Shipyards as case studies

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Frontiers of Architectural Research 2024年第1期13卷 164-183页

作者： María J.Andrade Eduardo jiménez-Morales Rachel Rodríguez-Ramos Pablo Martínez-Ramírez department of Art and Architecture School of ArchitectureMalaga UniversityMalaga 29013Spain

The progressive deindustrialisation of many western cities since the 1980s has led to many industrial zones linked to port activities being abandoned or falling into *** such as Barcelona,Naples,Lisbon,Amsterdam,and Hamburg have port industrial complexes of high tangible and intangible heritage value that could totally or partially disappear,resulting in an irreparable loss of their scientific,architectural,social,technological,and historical *** that in mind,Adaptive Reuse(AR)of the built heritage allows the industrial memory of the ports to be preserved by turning them into new functional centres within the existing urban *** occurs in the context of the contemporary challenges of those cities,such as touristification,the circular economy and climate change,while guaranteeing the life cycle of those *** article analyses two case studies—the Nederlandsche Scheepsbouw Maatschappij(NdSM)and the Rotterdamsche droogdok Maatschappij(RdM)shipyards,both in the Netherlands—in order to contribute to the knowledge of AR of Port Industrial *** are two examples of good practices in port industrial heritage interventions,where the factors behind their acclaim can be easily highlighted.A multi-scale methodology is therefore used and tailored to the case of port industrial heritage,based on analysing previous studies of the heritage in different spheres and on different scales.A relationship matrix tool is thus *** enables a comparative study to be conducted,using key variables and indicators,and considering qualitative and quantitative *** provides extensive output information for each case study,which is summarised in the most favourable factors for the success of the AR of this port industrial heritage.

关键词： Industrial heritage Port-city Adaptive reuse Best practices Circular economy HUL Touristification