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Topical ocular administration of DPP-Ⅳ inhibitors:a new approach for treating diabetes-induced retinal neurodegeneration

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Neural Regeneration Research 2024年第4期19卷 713-714页

作者： Rafael Simó Cristina hernández Diabetes and Metabolism Research Unit Vall d’Hebron Research Institute(VHIR) Department of Medicine Autonomous University of Barcelona Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas(CIBERDEM) Instituto de Salud CarlosⅢ(ICSⅢ)

Retinal neurodegeneration plays a significant role in the pathogenesis of diabetic retinopathy(DR),the leading cause of preventable blindness.In fact,the American Diabetes Association has defined DR as a highly specific neurovascular complication(Solomon et al.,2017).Therefore,it is no longer acceptable to consider DR as merely a microvascular complication.In this regard,the term diabetic retinal disease(DRD)has been proposed as a broader term comprising microangiopathy and neurodegeneration.However,there are currently no treatments available that directly target the neurodegenerative changes of DR.This paper will give new insights into the translational research in this field with particular emphasis on glucagon-like peptide 1/dipeptidyl peptidase IV(GLP-1/DPP-IV)inhibitors.

关键词： neurodegeneration ocular insight

AN OPTIMAL CONTROL PROBLEM FOR A LOTKA-VOLTERRA COMPETITION MODEL WITH CHEMO-REPULSION

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Acta Mathematica Scientia 2024年第2期44卷 721-751页

作者： Diana I.hernÁndez Diego A.RUEDA-GOMEZ Élder J.VILLAMIZAR-ROA Universidad Industrial de Santander Escuela de MatemáticasA.A.678BucaramangaColombia

In this paper we study a bilinear optimal control problem for a diffusive Lotka-Volterra competition model with chemo-repulsion in a bounded domain of ℝ^(ℕ),N=2,3.This model describes the competition of two species in which one of them avoid encounters with rivals through a chemo-repulsion mechanism.We prove the existence and uniqueness of weak-strong solutions,and then we analyze the existence of a global optimal solution for a related bilinear optimal control problem,where the control is acting on the chemical signal.Posteriorly,we derive first-order optimality conditions for local optimal solutions using the Lagrange multipliers theory.Finally,we propose a discrete approximation scheme of the optimality system based on the gradient method,which is validated with some computational experiments.

关键词： Lotka-Volterra chemo-repulsion optimal control optimality conditions

Deep optics preconditioner for modulation-free pyramid wavefront sensing

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Photonics Research 2024年第2期12卷 301-312页

作者： FELIPE GUZMÁN JORGE TAPIA CAMILO WEINBERGER NICOLÁS hernÁndez JORGE BACCA BENOIT NEICHEL ESTEBAN VERA School of Electrical Engineering Pontificia Universidad Católica de Valparaı´soValparaı´soChile Department of Systems Engineering Universidad Industrial de SantanderBucaramangaColombia Laboratoire d’Astrophysique de Marseille MarseilleFrance

The pyramid wavefront sensor(PWFS)can provide the sensitivity needed for demanding adaptive optics applications,such as imaging exoplanets using the future extremely large telescopes of over 30 m of diameter(D).However,its exquisite sensitivity has a limited linear range of operation,or dynamic range,although it can be extended through the use of beam modulation—despite sacrificing sensitivity and requiring additional optical hardware.Inspired by artificial intelligence techniques,this work proposes to train an optical layer—comprising a passive diffractive element placed at a conjugated Fourier plane of the pyramid prism—to boost the linear response of the pyramid sensor without the need for cumbersome modulation.We develop an end-2-end simulation to train the diffractive element,which acts as an optical preconditioner to the traditional least-square modal phase estimation process.Simulation results with a large range of turbulence conditions show a noticeable improvement in the aberration estimation performance equivalent to over 3λ∕D of modulation when using the optically preconditioned deep PWFS(DPWFS).Experimental results validate the advantages of using the designed optical layer,where the DPWFS can pair the performance of a traditional PWFS with 2λ∕D of modulation.Designing and adding an optical preconditioner to the PWFS is just the tip of the iceberg,since the proposed deep optics methodology can be used for the design of a completely new generation of wavefront sensors that can better fit the demands of sophisticated adaptive optics applications such as ground-to-space and underwater optical communications and imaging through scattering media.

关键词： process optics pyramid

Influence of biomass burning on ozone levels in the Megalopolis of Central Mexico during the COVID-19 lockdown

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Journal of Environmental Sciences 2024年第9期143卷 99-115页

作者： Victor Almanza Luis Gerardo Ruiz-Suárez Ricardo Torres-Jardón Agustín García-Reynoso Iván Y.hernández-Paniagua Institute for Atmospheric Sciences and Climate Change National Autonomous University of MexicoCoyoacan 04510Mexico CityMexico

The massive reductions in anthropogenic emissions resulting from the COVID-19 lockdown provided a unique opportunity to evaluate the effect of mitigation measures aiming to abate air pollution.In Mexico,the total lockdown period took place during the dry-hot season when biomass burning activity is enhanced.Here,we investigate the role of biomass burning emissions on regional ozone levels in the Megalopolis of Central Mexico.The studied period covers the lockdown phases 2 and 3,and the first month of the New Normal.We applied a factor separation technique and process analysis to estimate the pure and synergistic contributions of emission reductions under lockdown and that from biomass burning to daily ozone maximum concentrations in 7 metropolitan areas of different states in the Megalopolis.The results revealed that biomass burning plumes likely masked the effect of massive reductions from mobile emissions,impacted the PBL development during phase 3 and favored transition and mixed NO_(x)-limited and VOC-limited regional regimes.This contributed to increased ozone production in the middle to lower PBL by changing the regional background levels which potentially could bias high ozone production efficiency estimations.Given the Megalopolis contribution to economic and societal development at national scale,our study suggests that ozone mitigation measures during the dry-hot season targeting mainly mobile emissions will likely be offset by biomass burning plumes.A regional and synergic policy aiming to control biomass burning would help to reduce the occurrence of high ozone levels in Central Mexico with the co-benefit of tackling short-lived climate pollutants.

关键词： COVID-19 Mexico Megalopolis Ozone Factor Separation Process Analysis

Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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Neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso JoséMartínez-hernández Alejandro Martín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández Ana Esther Moreno-Martínez Mar Cuadrado-Tejedor Ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for Neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain Neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resil

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

Quality-adjusted life years and surgical waiting list:Systematic review of the literature

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1155-1164页

作者： Roberto de la Plaza Llamas Lorena Ortega Azor Marina hernández Yuste Ludovica Gorini Raquel Aránzazu Latorre-Fragua Daniel Alejandro Díaz Candelas Farah Al Shwely Abduljabar Ignacio antonio Gemio del Rey Department of General and Digestive Surgery Hospital Universitario de GuadalajaraGuadalajara 19002Spain Department of Surgery Medical and Social SciencesFaculty of Medicine and Health SciencesUniversity of AlcaláAlcaláde Henares 28871MadridSpain

BACKGROUND The quality-adjusted life year(QALY)is a metric that is increasingly used today in the field of health economics to evaluate the value of different medical treatments and procedures.Surgical waiting lists(SWLs)represent a pressing problem in public healthcare.The QALY measure has rarely been used in the context of surgery.It would be interesting to know how many QALYs are lost by patients on SWLs.AIM To investigate the relationship between QALYs and SWLs in a systematic review of the scientific literature.METHODS The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement.An unlimited search was carried out in PubMed,updated on January 19,2024.Data on the following variables were investigated and analyzed:Specialty,country of study,procedure under study,scale used to measure QALYs,the use of a theoretical or real-life model,objectives of the study and items measured,the economic value assigned to the QALY in the country in question,and the results and conclusions published.RESULTS Forty-eight articles were selected for the study.No data were found regarding QALYs lost on SWLs.The specialties in which QALYs were studied the most in relation to the waiting list were urology and general surgery,with 15 articles each.The country in which the most studies of QALYs were carried out was the United States(n=21),followed by the United Kingdom(n=9)and Canada(n=7).The most studied procedure was organ transplantation(n=39),including 15 kidney,14 liver,5 heart,4 lung,and 1 intestinal.Arthroplasty(n=4),cataract surgery(n=2),bariatric surgery(n=1),mosaicplasty(n=1),and septoplasty(n=1)completed the surgical interventions included.Thirty-nine of the models used were theoretical(the most frequently applied being the Markov model,n=34),and nine were real-life.The survey used to measure quality of life in 11 articles was the European Quality of Life-5 dimensions,but in 32 articles the survey was not specified.The willingness-to-pay per QALY gained ranged fro

关键词： Quality-adjusted life year Waitlist Quality of life Surgery Systematic review

Metal-modulated epitaxy of Mg-doped Al_(0.80)In_(0.20)N-based layer for application as the electron blocking layer in deep ultraviolet light-emitting diodes

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Journal of Semiconductors 2024年第5期45卷 80-89页

作者： Horacio Irán Solís-Cisneros Carlos Alberto hernández-Gutiérrez Enrique Campos-González Máximo López-López Optomechatronics Group Tecnológico Nacional de México Campus Tuxtla Gutiérrezcarretera Panamericana 1080C.P.29050Tuxtla GutiérrezChiapasMéxico Departamento de Física Instituto Nacional de Investigaciones NuclearesCarretera México-Toluca s/nC.P.52750La Marquesa OcoyoacacMéxico Departamento de Física Centro de Investigación y estudios Avanzados del Instituto Politécnico NacionalAv.Instituto Politécnico Nacional 2508San Pedro ZacatencoGustavo A.Madero07360 Ciudad de MéxicoCDMXMéxico

This work reports the growth and characterization of p-AlInN layers doped with Mg by plasma-assisted molecular beam epitaxy(PAMBE).AlInN was grown with an Al molar fraction of 0.80 by metal-modulated epitaxy(MME)with a thickness of 180 nm on Si(111)substrates using AlN as buffer layers.Low substrate temperatures were used to enhance the incorporation of indium atoms into the alloy without clustering,as confirmed by X-ray diffraction(XRD).Cathodoluminescence measurements revealed ultraviolet(UV)range emissions.Meanwhile,Hall effect measurements indicated a maximum hole mobility of 146 cm^(2)/(V∙s),corresponding to a free hole concentration of 1.23×10^(19)cm^(−3).The samples were analyzed by X-ray photoelectron spectroscopy(XPS)estimating the alloy composition and extracting the Fermi level by valence band analysis.Mg-doped AlInN layers were studied for use as the electron-blocking layer(EBL)in LED structures.We varied the Al composition in the EBL from 0.84 to 0.96 molar fraction to assess its theoretical effects on electroluminescence,carrier concentration,and electric field,using SILVACO Atlas.The results from this study highlight the importance and capability of producing high-quality Mg-doped p-AlInN layers through PAMBE.Our simulations suggest that an Al content of 0.86 is optimal for achieving desired outcomes in electroluminescence,carrier concentration,and electric field.

关键词： metal-modulated epitaxy AlInN DUV-LED EBL simulation

Role of lipids in the control of autophagy and primary cilium signaling in neurons

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Neural Regeneration Research 2024年第2期19卷 264-271页

作者： María Paz hernández-Cáceres Daniela Pinto-Nuñez Patricia Rivera Paulina Burgos Francisco Díaz-Castro Alfredo Criollo Maria Jose Yañez Eugenia Morselli Instituto de Investigación en Ciencias Odontológicas(ICOD) Facultad de OdontologíaUniversidad de ChileSantiagoChile Department of Basic Sciences Faculty of Medicine and ScienceUniversidad San SebastiánSantiagoChile Physiology Department Faculty of Biological SciencesPontificia Universidad Católica de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Facultad de Ciencias Químicas y Farmacéuticas&Facultad de MedicinaUniversidad de ChileSantiagoChile Autophagy Research Center SantiagoChile

The brain is,after the adipose tissue,the organ with the greatest amount of lipids and diversity in their composition in the human body.In neurons,lipids are involved in signaling pathways controlling autophagy,a lysosome-dependent catabolic process essential for the maintenance of neuronal homeostasis and the function of the primary cilium,a cellular antenna that acts as a communication hub that transfers extracellular signals into intracellular responses required for neurogenesis and brain development.A crosstalk between primary cilia and autophagy has been established;however,its role in the control of neuronal activity and homeostasis is barely known.In this review,we briefly discuss the current knowledge regarding the role of autophagy and the primary cilium in neurons.Then we review the recent literature about specific lipid subclasses in the regulation of autophagy,in the control of primary cilium structure and its dependent cellular signaling in physiological and pathological conditions,specifically focusing on neurons,an area of research that could have major implications in neurodevelopment,energy homeostasis,and neurodegeneration.

关键词： autophagic flux cholesterol fatty acids GPCR lysosomal storage diseases neurons NPC1 phosphoinositides primary cilium

Dendritic spine degeneration:a primary mechanism in the aging process

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Neural Regeneration Research 2025年第6期 1696-1698页

作者： Gonzalo Flores Leonardo Aguilar-hernández Fernado García-Dolores Humberto Nicolini Andrea Judith Vázquez-hernández Hiram Tendilla-Beltrán Instituto de Fisiología Benemérita Universidad Autónoma de Puebla (BUAP) Instituto de Ciencias Forenses (INCIFO) Tribunal Superior de Justicia de la Ciudad de México (TSJCDMX) Instituto Nacional de Medicina Genómica (INMEGEN)

Recent reports suggest that aging is not solely a physiological process in living beings; instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome(GM)(Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism(Mayer et al., 2022; Aguilarhernández et al., 2023).

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