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Engineering hyaluronic acid-based nanoassem.lies 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-est.vez 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 m.lecular 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,form.lation challenges *** challenges are the limited loading capacity(often insufficient to achieve clinical dosing),the com.lex form.lation methods,and the insufficient characterization of mAb-loaded ***,we present a new nanocarrier consisting of hyaluronic acid-based nanoassem.lies(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 sm.ll-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 assem.ling 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

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Differential Expression of Genes Related to Fruit Development and Capsaicinoids Synthesis in Habanero Pepper Plants Grown in Contrasting Soil Types

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Phyton-International Journal of Experimental Botany 2024年第2期93卷 151-183页

作者： Eduardo Burgos-Valencia Federico García-laynes Ileana Echevarría-machado Fatima medina-lara miriam monforte-González JoséNarváez-Zapata manuel martínez-est.vez Unidad de Bioquímica y Biología m.lecular de Plantas Centro de Investigación Científica de YucatánCalle 43#130Chuburnáde HidalgoMéridaYucatán97205México Instituto Politécnico Nacional-Centro de Biotecnología Genómica Blvd Del Maestro esq.Elias PiñaReynosaTamaulipas88710México

Habanero pepper(Capsicum chinense Jacq.)is a crop of economic relevance in the Peninsula of *** fruits have a high level of capsaicinoids compared to peppers grown in other regions of the world,which gives them industrial *** is an important factor that affects pepper development,nutritional quality,and capsaicinoid ***,the effect of soil type on fruit development and capsaicinoid metabolism has been little *** work aimed to compare the effect of soils with contrasting characteristics,black soil(BS)and red soil(RS),on the expression of genes related to the development of fruits,and capsaicinoid synthesis using a transcriptomic analysis of the habanero pepper *** growing in RS had bigger fruits and higher expression of genes related to floral development,fruit abscission,and softening which suggests that RS stim.lates fruit development from early stages until maturation *** from plants growing in BS had enrichment in metabolic pathways related to growth,sugars,and ***,these fruits had higher capsaicinoid accum.lation at 25 days post-anthesis,and higher expression of genes related to the branched-chain amino acids metabolism(ketol-acid reductisomerase KARI),pentose phosphate pathway and production of NADPH(glucose-6-phosphate-1-dehydrogenase G6PDH),and proteasome and vesicular traffic in cells(26S proteasome regulatory subunit T4 RPT4),which suggest that BS is better in the early stim.lation of pathways related to the nutritional quality and capsaicinoid metabolism in the fruits.

关键词： Capsicum chinense jacq soil types plant growth environmental conditions fruit quality capsaicinoid metabolism transcriptome

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Standardizing mI-TlIF, a Proposal for a Reproducible Technique

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Open Journal of modern Neurosurgery 2024年第2期14卷 91-103页

作者： Iván Ulises Sámano lópez Jesús Alberto Pérez Contreras Emmanuel Cantú Chávez Diana Chávez lizárraga ana Sofía Peña Blesa Thania Karina Gutiérrez Anchondo Á ngeles Pedregal Ciudad de México México

Background: minim.lly invasive transforaminal lumbar interbody fusion (mI TlIF) is a widely known and performed technique, however its versatility among different physicians continues to hinder its replication and results. Therefore, this study aimed to provide a step-by-step surgical guide to perform a safe mI-TlIF, based on the results obtained in patients operated on by a single surgeon over a period of 12 years. Patients and methods: A retrospective, single center, longitudinal, and observational cohort study was conducted with 931 patients who underwent mI TlIF by a single surgeon between 2010 and 2022 using the technique described on this paper, each with a minimum follow-up of 12 months. Criteria included Schizas classification, listhesis according to meyerding classification, number of levels treated, cage size, and com.lications (screw repositioning or cerebrospinal fluid leak). Patient clinical outcomes were assessed using the Oswestry Disability Index (ODI), Visual analog Scale (VAS) for pre- and postoperative radicular pain. Thin slice CT scans were used to assess the progression of the fusion using the Bridwell classification. In the statistical analysis, percentages, median, and interquartile range (IQR) were calculated. Results: Nine hundred and thirty one patients underwent mI TlIF using the technique described, eight hundred and eighty (94.5%) had a single level treated and fifty one (5.5%) had a 2 level procedure (982 levels), an 8mm cage was placed on five hundred and seventeenlevels (52.7%), six hundred and sixty three levels(67.6%) achieved grade I fusion, two hundred and sixty six levels (27.1%) achieved grade II fusion, 52 levels (5.3) achieved grade III fusion and one level (0.1) achieved a grade IV fusion or non-union. Revision surgery was performed on 3 patients (0.3%) for screw repositioning, cerebrospinal fluid leak was present on 2 patients during surgery and treated before closure. VAS scores and ODI were improved at 12 months postop (V

关键词： mITlIF lumbar Interbody Fusion Technique Pain Relief and Disability

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A Hybrid model Evaluation Based on PCA Regression Schemes Applied to Seasonal Precipitation Forecast

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Atmospheric and Climate Sciences 2024年第3期14卷 328-353页

作者： Pedro m. González-Jardines Aleida Rosquete-est.vez maibys Sierra-lorenzo Arnoldo Bezanilla-morlot Center for Atmospheric Physics Institute of Meteorology Havana Cuba

Possible changes in the structure and seasonal variability of the subtropical ridge may lead to changes in the rainfall’s variability modes over Caribbean region. This generates additional difficulties around water resource planning, therefore, obtaining seasonal prediction models that allow these variations to be characterized in detail, it’s a concern, specially for island states. This research proposes the construction of statistical-dynamic models based on PCA regression methods. It is used as predictand the monthly precipitation accum.lated, while the predictors (6) are extracted from the ECmWF-SEAS5 ensem.le mean forecasts with a lag of one month with respect to the target month. In the construction of the models, two sequential training schemes are evaluated, obtaining that only the shorter preserves the seasonal characteristics of the predictand. The evaluation metrics used, where cell-point and dichotomous methodologies are combined, suggest that the predictors related to sea surface temperatures do not adequately represent the seasonal variability of the predictand, however, others such as the temperature at 850 hPa and the Outgoing longwave Radiation are represented with a good approximation regardless of the model chosen. In this sense, the models built with the nearest neighbor methodology were the most efficient. Using the individual models with the best results, an ensem.le is built that allows improving the individual skill of the models selected as members by correcting the underestimation of precipitation in the dynamic model during the wet season, although problems of overestimation persist for thresholds lower than 50 mm.

关键词： Seasonal Forecast Principal Component Regression Statistical-Dynamic models

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Academic Stress Assessment Using Virtual Reality as an Educational Tool in Spine Surgery

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Open Journal of modern Neurosurgery 2024年第2期14卷 114-123页

作者： Diana Chávez lizárraga Jesús Alberto Pérez Contreras Fernando Alvarado Gómez Evelyn Quintero medina Emmanuel Cantú Chávez Iván Ulises Sámano lópez ana Sofía Peña Blesa Department of Neurosurgery ángeles Pedregal Ciudad de México México Department of Traumatology and Orthopedics Hospital Santa Fe Bogotá Colombia

Introduction: The evaluation of academic stress in medical students and residents is a topic of significant interest, given the considerable challenges they face during their learning process with traditional teaching methods. The use of technologies like virtual reality presents an opportunity to enhance their skills through sim.lations and training. The main objective of this study is to qualitatively assess the stress levels experienced by medical students and residents by integrating virtual reality into their current learning methods, aiming to improve their ability to manage stressors in their practice. material and methods: A questionnaire was conducted with 12 medical students and 12 Traumatology and orthopedics residents. The purpose of the questionnaire was to evaluate the levels of academic stress using the SISCO inventory. The stress levels were calculated by transforming average values into percentages, and the following criteria were assigned: 0 to 33% for m.ld Stress, 34 to 66% for moderate Stress, and 67 to 100% for Deep Stress. Then, a virtual reality class focused on spine surgery was provided. Both medical students and residents were trained using the Non Nocere SharpSurgeon software platform and Oculus Quest 2 virtual reality glasses. At the end of the session, a second questionnaire related to the practice with virtual reality was conducted with the same evaluation criteria and a comparative analysis was carried out. Results: 12 undergraduate students from Hospital Angeles mexico, CDmX and 12 traumatology and orthopedics residents at Hospital Santa Fe, Bogota were evaluated. The students in CDmX reported an average qualitative stress of 28.50% during habitual practices, which decreased to an average of 14.67% after virtual reality practice. Residents in Bogotá experienced an average qualitative stress of 30.50% with their current learning methods but this reduced to an average of 13.92% after using virtual reality. These findings indicate that t

关键词： Virtual Reality Academic Stress learning Strategies Spine Surgery Training

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Solid-liquid extraction for yttrium recovery using porous polymeric resin(XAD-7) functionalized with D_(2)EHPA

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Journal of Rare Earths 2024年第9期42卷 1764-1773,I0005页

作者： P.A.martínez-montoya R.G.Sanchez-Alvarado D.Y.medina-Velazquez m.l.Carrera-Jota P.Garnica-Chávez A.de J.morales-Ramirez Higher School of Chemical Engineering and Extractive Industries ESIQIEIPNDepartment of Metallurgical EngineeringUPALM S/NCol.LindavistaGustavo A.Madero Cd.de MéxicoC.P07738Mexico metropolitan Autonomous University Department of MaterialsBasic Sciences and EngineeringAv.San Pablo No.180Col.Reynosa TamaulipasCd.de MéxicoC.P02200Mexico Center for Research and Technological Innovation CIITECIPNCda.de CECATIs/nSanta CatarinaAzcapotzalcoC.P02250CDMXMexico

The recovery of yttrium is proposed by applying a solid-liquid extraction process using di-2-ethyl hexylphosphoric acid(D2EHPA) as extracting *** extracting agents were supported on a macro porous polymeric resin XAD-7(solid phase).Yttrium ions extraction and discharge tests were performed,firstly from a synthetic aqueous solution of 100 mg/l Y(liquid phase) at 25℃ with *** effects of pH of aqueous solutions bearing yttrium,volume fraction of extracting agents and the solid/liquid(S/l)ratio on the yttrium recovery were *** most favorable conditions for yttrium ions extraction are;20 vol% D_(2)EHPA functionalized resin,pH=1.5 and an S/l ratio of 10 mg/ml The discharge of yttrium ions was done under the same conditions of extraction stage,using a 2 m.l/l [H_(2)SO_(4)] as stripping *** to 80% yttrium is extracted,while 75% yttrium is recovered in the striping *** all experiments,the reaction equilibrium is reached after 20 min,and the kinetics for the extraction stage was determined as a second-order ***,experiments were carried out to discharge the yttriumloaded resins,and it has been determined that the best pH value to strip the Y ions is *** tests of extraction and discharge for yttrium ions show that the functionalized resin can work at least five cycles without decreasing its ***,the proposed process was tested in a real solution with Y ions fro m a waste fluorescent la mp powder leached in H_(2)SO_(4),demonstrating the ability to effectively recover yttrium,separating it from various metals from the studied residue.

关键词： Yttrium recovery Rare earth solid-liquid extraction XAD-7 resin Fluorescent lamps recycling Solid-liquid kinetics extraction

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Hydroxytyrosol and Parkinson's disease:protective actions against alpha-synuclein toxicity

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Neural Regeneration Research 2024年第7期19卷 1427-1428页

作者： Ruth Hornedo-Ortega ana m.Espinosa-Oliva Departamento de Nutrición y Bromatología Toxicología y Medicina LegalFacultad de FarmaciaUniversidad de SevillaSevilleSpain Instituto de Biomedicina de Sevilla IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaSpain Departamento de Bioquímica y Biología m.lecular Facultad de FarmaciaUniversidad de SevillaSevillaSpain

Parkinson’s disease:Parkinson’s disease(PD) is the second most prevalent neurodegenerative disease,after Alzheimer’s disease,affecting 1%of the general population over the age of *** to data from the World Health Organization(WHO),its prevalence has doubled in the past 25 *** 2019,global estimates indicated over 8.5 m.llion individuals with PD and it is suggested that PD caused 329000 deaths,an increase of over 100% since 2000(WHO,2022).

关键词： protective Alzheimer prevalence

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Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

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Neural Regeneration Research 2024年第11期19卷 2532-2542页

作者： Aina Bellver-Sanchis Pedro AAvila-lópez Iva Tic David Valle-García marta Ribalta-Vilella luis labrador Deb Ranjan Banerjee ana Guerrero Gemma Casadesus Coralie Poulard mercè Pallàs Christian Grinán-Ferré Department of Pharmacology and Therapeutic Chemistry Institut de Neurociències-Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and m.lecular Genetics Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Institute of Biotechnology National Autonomous University of MexicoCuernavacaMexico Department of Pharmacology and Therapeutics Health Science Center-University of FloridaGainesvilleFLUSA Department of Chemistry National Institute of Technology DurgapurM G AvenueDurgapurWest BengalIndia Cancer Research Cancer lyon Universitéde LyonLyonFrance Inserm U1052 Centre de Recherche en Cancérologie de LyonLyonFrance CNRS UmR5286 Centre de Recherche en Cancérlogie de LyonLyonFrance Centro de Investigación en Red Enfermedades Neurodegenerativas(CIBERNED)Instituto de Salud Carlos IIIMadridSpain Neuroimmunology Department National Institute of Neurology and Neurosurgery“Manuel Velasco Suárez”Mexico CityMexico

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative ***,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in m.ltifactorial diseases such as Alzheimer’s ***,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and *** better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAmP8)control mice and SAmP8 treated with G9a inhibitor *** found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)***,Pparg gene expression levels were higher in the SAmP8 group treated with G9a inhibitor than in the SAmP8 control *** also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a *** confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative *** this setting,treatment with G9a inhibitor increases both cell survival and antioxidant ***,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and *** addition,we also described that the PPARγ/AmPK axis partially explains the regulation of autophagy markers ***,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a ***,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

关键词： aging cognitive decline epigenetics G9a inhibition microRNAs miR-128 peroxisome-proliferator activator receptorγ(PPARγ) PPARG SAmP8

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The Iberian Roma Population Variant Server(IRPVS)

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Journal of Genetics and Genomics 2024年第7期51卷 769-773页

作者： Fabiola mavillard Javier Perez-Florido Francisco m.Ortuño Amador Valladares miren l.Álvarez-Villegas Gema Roldán Rosario Carmona manuel Soriano Santiago Susarte Pilar Fuentes Daniel lópez-lópez ana maría Nuñez-Negrillo Alejandra Carvajal Yolanda morgado Daniel Arteaga Rosa Ufano Pablo mir Juan F.Gam.lla Joaquín Dopazo Carmen Paradas macarena Cabrera-Serrano Instituto de Biomedicina de Sevilla(IBiS) Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaSpain Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud CarlosⅢSevillaSpain Plataforma Andaluza de medicina Computacional Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevillaSpain Grupo de medicina computacional de sistemas Instituto de Biomedicina de Sevilla(IBiS)Hospital Virgen del RocíoSevillaSpain Nodo de Genómica Funcional (INB-ELIXIR-es)Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevilla 41013Spain Bioinformática en Enfermedades raras(BiER) Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER)Instituto de salud CarlosⅢSevillaSpain Departamento de Ingeniería de Computadores Automática y RobóticaUniversidad de GranadaGranadaSpain Servicio de Urgencias de Atención Primaria Distrito SevillaSevillaSpain Centro de Servicios Sociales Negociado de Servicios EspecializadosAyuntamiento de SevillaSevillaSpain Departamento de Enfermería Facultad de Ciencias de la SaludUniversidad de GranadaGranadaSpain Departamento de Neurología Hospital Virgen de las NievesGranadaSpain Departamento de Neurología Hospital Virgen de ValmeSevillaSpain Centro de Salud Utrera Sur SevillaSpain Centro de Salud Polígono Sur SevillaSpain Unidad de Trastornos del movimiento Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain Departamento de medicina Facultad de MedicinaUniversidad de SevillaSevilleSpain Departamento de Antropología Social Universidad de GranadaSpain Unidad Enfermedades Neuromusculares Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain

In recent years,the number of known disease genes has exponentially grown due to the widespread adoption of cost-effective massive parallel *** identify new disease variants,especially in monogenic disorders,a frequen... 详细信息

关键词： Server filtering massive

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Therm.l properties and high-temperature ablation of high-entropy (Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2) coating on graphite substrate

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Journal of Advanced Ceramics 2024年第8期13卷 1268-1281页

作者： ana C.Feltrin Daniel Hedman Farid Akhtar Division of materials Science Lulea University of TechnologyLulea 97187Sweden Center for m.ltidimensional Carbon materials(CmCm) Institute for Basic Science(IBS)Ulsan 44919Republic of Korea

An entropy-stabilized m.lticomponent ultrahigh-temperature ceramic(UHTC)coating,(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2),on a graphite substrate was in-situ sintered by spark plasma sintering(SPs)from constituent transition metal diboride ***(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2) coating had a hardness of 31.2±2.1 GPa and resisted 36.9 GPa of stress before delamination,as observed at the *** temperature-dependent therm.l properties of the m.lticomponent diboride(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2) were obtained by m.lecular dynamics(mD)sim.lations driven by a machine learning force field(mlFF)trained on density functional theory(DFT)*** therm.l conductivity,density,heat capacity,and coefficient of therm.l expansion obtained by the mD sim.lations were used in time-dependent therm.l stress finite element model(FEm)*** low therm.l conductivity(m^(-1)·K^(-1))of the m.lticomponent diboride coupled with its sim.lar coefficient of therm.l expansion to that of graphite indicated that stresses of less than 10 GPa were generated at the interface at high temperatures,and therefore,the coating was mechanically resistant to the therm.l stress induced during *** experiments at 220℃ showed that the m.lticomponent diboride coating was resistant to therm.l stresses with no visible cracking or *** ablation mechanisms were mechanical denudation and evaporation of B_(2)O_(5) and light V-Ti oxides,which caused a decrease in the mass and thickness of the coating and resulted in mass and linear ablation rates of-0.51 mg·s^(-1) and -1.38μm·s^(-1),respectively,after 60 *** findings demonstrated the therm.l and mechanical stability of m.lticomponent entropy-stabilized diborides as coatings for carbon materials in engineering components under extreme environments.

关键词： entropy-stabilized diborides ultrahigh temperature ceramics m.lecular dynamics(mD)sim.lations density functional theory(DFT) ablation properties

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