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Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery-design,characterization,and biological insights

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Nano Research 2024年第10期17卷 9111-9125页

作者： Ana M.lópez-Estévez Y.Zhang maría Medel Iker Arriaga lucía sanjurjo Cristian Huck-Iriart Nicola G.A.Abrescia maría J.Vicent Defang Ouyang Dolores Torres maría José Alonso Center for Research in Molecular Medicine and Chronic Diseases(CiMUs) University of Santiago de CompostelaSantiago de Compostela 15782Spain Department of Pharmacology Pharmacy and Pharmaceutical TechnologySchool of PharmacyUniversity of Santiago de CompostelaSantiago de Compostela 15782Spain Health Research Institute of santiago de Compostela(IDIs) Santiago de Compostela 15782Spain state Key laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Polymer Therapeutics laboratory and CIBEROnc Prince Felipe Research Centre Valencia E-46012Spain structure and Cell Biology of Viruses lab CIC bioGUNEBasque Research and Technology Alliance(BRTA)Derio 48160Spain AlBA synchrotron light source Experiments DivisionCerdanyola del VallèsBarcelona 08290Spain IKERBAsQUE Basque Foundation for ScienceBilbao 48009Spain

The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies(mAbs).Despite their increasing potential,mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular *** offers promising solutions to overcome this limitation,however,formulation challenges *** challenges are the limited loading capacity(often insufficient to achieve clinical dosing),the complex formulation methods,and the insufficient characterization of mAb-loaded ***,we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies(HANAs)specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity(50%,w/w).HANAs composed by an mAb,modified HA and phosphatidylcholine(PC)resulted in sizes of~100 nm and neutral surface *** modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and *** composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy(cryo-TEM),asymmetrical flow field-flow fractionation(AF4),and small-angle X-ray scattering(sAXs).These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic *** vitro experiments in cancer cell lines and macrophages confirmed HANAs’low toxicity and ability to transport mAbs to the intracellular *** reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was *** conclusion,these results underscore the suitability of HANAs technology to load and deliver biologicals,which holds promise for future clinical translation.

关键词： monoclonal antibody nanoparticles hyaluronic acid characterization particle size computational modeling

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)oflower eyelid of each eye,and non-invasive 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 Plysis 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(Pllow-up from the first 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

Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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Neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón Pérez-Núñez maría Fernanda González Ana maría Avalos lisette leyton Cellular Communication laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDis) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous *** injury and inflammation,astrocytes become reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT *** targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

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 *** 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 *** this review,we briefly discuss the current knowledge regarding the role of autophagy and the primary cilium in *** 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

Twenty years of population dynamics in European beech-oak forest at their rear range margin anticipate changes in its structure and composition

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Forest Ecosystems 2024年第3期11卷 358-370页

作者： álvaro Rubio-Cuadrado Iciar Alberdi Isabel Canellas Fernando Montes Jesús Rodríguez-Calcerrada Rosana lópez Guillermo G.Gordaliza maría Valbuena-Carabana Nikos Nanos Ramón Perea luis Gil Departamento de dinamica y gestion forestal Instituto de Ciencias Forestales(ICIFOR-INIA)CSICCtra.La Coruna km 7.528040MadridSpain Departamento de sistemas y Recursos Naturales Escuela Tecnica Superior de Ingeniería de MontesForestal y del Medio NaturalUniversidad Politecnica de Madrid.Ciudad Universitaria s/n28040MadridSpain school of Forestry and Natural Environment Aristotle University of ThessalonikiUniversity Campus54124ThessalonikiGreece

There is an increasing interest in restoring degraded forests,which occupy half of the forest *** the forms of restoration,passive restoration,which involves the elimination of degrading factors and the free evolution of natural dynamics by applying minimal or no management,is gaining *** dynamics is difficult to predict due to the influence of multiple interacting factors such as climatic and edaphic conditions,composition and abundance of species,and the successional character of these ***,we study the natural dynamics of a mixed forest located in central spain,which maintained an open forest structure,due to intensive use,until grazing and cutting were banned in the *** most frequent woody species in this forest are Fagus sylvatica,Quercus petraea,Quercus pyrenaica,Ilex aquifolium,sorbus aucuparia,sorbus aria and Prunus avium,with contrasting shade and drought *** species are common in temperate European deciduous forest and are found here near their southern distribution limit,except for *** order to analyze forest dynamics and composition,three inventories were carried out in 1994,2005 and *** results show that,despite the Mediterranean influence,the natural dynamics of this forest has been mainly determined by different levels of shade *** the abandonment of grazing and cutting,*** expanded rapidly due to its lower shade tolerance,whereas after canopy closure and forest densification,shade-tolerant species gained ground,particularly ***,despite its lower drought and late-frost *** the current dynamics continue,*** will overtake the rest of the species,which will be relegated to sites with shallow soils and steep ***,all the multi-centennial beech trees,which are undergoing a rapid mortality and decline process,will disappear.

关键词： Forest succession secondary forest Woodland Mixed forest Competition Recruitment

Habitat and food preferences of European rabbits in core and edge populations along the invasion front PatagoniaMonte,Argentina

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Current Zoology 2024年第3期70卷 310-319页

作者： sabrina Yasmin Bobadilla maría A.Dacar Fabián M.Jaksic Ricardo A.Ojeda maría Fernanda Cuevas Ecología de Mamíferos de Tierras secas IADIZACCT-Mendoza CONICETAv.Ruiz Leal s/nParque General San MartínMendoza 5500MendozaArgentina laboratorio de Filogeografía Taxonomía Integrativa y Ecología(LFTIE)IADIZACCT-Mendoza CONICETAv.Ruiz Leal s/nParque General San MartínMendoza 5500MendozaArgentina Center of Applied Ecology and sustainability(CAPEs) Pontifcia Universidad Católica de ChileAv.Libertador Bernardo O'Higgins 340Santiago 8320000Región MetropolitanaChile

The European rabbit Oryctolagus cuniculus is an exotic herbivorous mammal undergoing an active phase of geographical expansion in the arid ecosystems of *** Adaptive Flexibility Hypothesis states that populations at the range edge(new populations)will exhibit greater fexibility in the use of resources compared with populations located in the range core(older populations).The objective of this work was to compare the rabbit’s use of spatial and trophic resources in relation to the establishment time of their *** sampling was carried out for 2 years(2017 and 2018)in sites with different establishment times for rabbit *** sampling stratifed by type of habitat was applied using 115 fxed strip transects of 1,000 m^(2) laid out across the study *** rabbit signs were recorded in each transect,and environmental and anthropic variables were *** results show that the individuals from the range edge are more selective in the use of habitat than those from the range *** the microhabitat level,we observed a pattern in the particular components of habitat use by rabbits mainly linked to food availability and proximity to *** a trophic perspective,rabbits could show fexible adjustment to novel conditions and environments in the range *** variability in resource use by the European rabbit confrms its ecological fexibility,pivotal for their advance toward new environments in Argentina.

关键词： Arid ecosystems invasive species novel environments range invasion spatial use trophic use

A texture-modified dessert with high nutritional value designed for people with dysphagia:effect of refrigeration and frozen storage

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Food science and Human Wellness 2024年第1期13卷 462-471页

作者： maría Cartagena larisa Giura Diana Ansorena Iciar Astiasaran Department of Nutrition Food Science and PhysiologyFaculty of Pharmacy and NutritionUniversidad de NavarraC/Irunlarrea s/nPamplona 31008Spain Center for Nutrition Research University of Navarrac/Irunlarrea 1Pamplona 31008Spain Instituto de Investigación sanitaria de Navarra IDISNAPamplona 31008Spain National Centre for Food Technology and safety(CNTA)—Technology and Knowledge for Food sector Competitiveness NavarreCrta-Na 134-km 53San Adrian 31570Spain

Dysphagia is commonly associated with malnutrition and an increased choking *** overcome these complications,food designed for people with dysphagia should have an appropriate texture and a high nutritional *** this study,six formulations of a strawberry dessert enriched in protein(calcium caseinate)and fiber(wheat dextrin or inulin)were developed using different hydrocolloids(xanthan gum,carboxymethyl cellulose or modified starch)to provide desirable texture and *** value was calculated and total phenolic content and antioxidant activity of the samples were ***-extrusion test,rheological measurements and sensory analysis were performed in refrigerated and frozen samples to characterize their textural and viscoelastic *** high content in protein(14.7 g/100 g)and fiber(7.9-8.7 g/100 g)made possible to use the claims“high protein”and“high fiber”.Phytochemicals supplied by strawberries contributed to the antioxidant properties of the *** tangent ranged 0.28-0.35 for all the formulations,indicating a weak gel behavior,which could be considered safe to *** formulations with dextrin in combination with carboxymethyl cellulose or xanthan gum seemed to be less susceptible to structural changes during frozen *** work provides insights for the development of a nutrient-dense dessert that meets the requirements of people with dysphagia.

关键词： Malnutrition Texture-modified-food Hydrocolloids Viscoelastic properties Food texture

Tracking the change in spanish greenhouse gas emissions through an lMDI decomposition model:A global and sectoral approach

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Journal of Environmental sciences 2024年第5期139卷 114-122页

作者： Paula Fernández González maría José Presno Manuel landajo Department of Applied Economics University of OviedoAuda del Cristos/n 33011 OviedoSpain

The reduction of GHG emissions to reverse the greenhouse effect is one of the main challenges in this *** this paper we pursue two ***,we analyze the evolution of GHG emissions in spain in 2008–2018,at both the global and sectoral levels,with the variation in emissions decomposed into a set of determining ***,we propose several actions specifically oriented to more tightly controlling the level of *** results showed a remarkable reduction(18.44%)in GHG emissions,mainly due to the intensity effect,but also to the production-per-capita *** detected somewhat different patterns among the various sectors *** the intensity effect was the most influential one in the agricultural,transport,and others sectors,the production-per-capita effect was predominant in the case of *** carbonization effect was revealed as crucial in the commerce *** above findings highlight the importance of the energy efficiency measures taken in recent years in the spanish economy,also pointing to the need to deepen those strategies and to propose new measures that entail greater efficiency in *** efforts in areas like innovation,R&D,diffusion of more eco-friendly technologies,and a greater use of greener energies all prove to be essential reduction actions to fight the greenhouse effect.

关键词： lMDI Decomposition spain GHG emissions