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Exosomal glypican-1 is elevated in pancreatic cancer precursors and can signal genetic predisposition in the absence of endoscopic ultrasound abnormalities

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World Journal of Gastroenterology 2022年第31期28卷 4310-4327页

作者： Pedro Moutinho-Ribeiro Ines A Batista Sofia T Quintas Bárbara Adem Marco Silva Rui Morais Armando Peixoto Rosa Coelho Pedro Costa-Moreira Renato Medas Susana lopes Filipe Vilas-Boas Manuela Baptista Diogo Dias-Silva ana l esteves Filipa Martins Joanne lopes Helena Barroca Fátima Carneiro Guilherme Macedo Sonia A Melo Serviço de Gastrenterologia Centro Hospitalar Universitário de Sao JoaoPorto 4200Portugal Faculty of Medicine University of PortoPorto 4200Portugal Instituto de Investigacao e Inovacao em Saúde(i3S) Universidade do PortoPorto 4200Portugal IPATIMUP-Institute of Molecular Pathology and Immunology University of PortoPorto 4200Portugal Instituto de Ciencias Biomédicas Abel Salazar(ICBAS) University of PortoPorto 4050Portugal Servico de Cirurgia Geral Centro Hospitalar Universitário de Sao JoaoPorto 4200Portugal Unidade de Saúde Familiar Serpa Pinto ACeS Porto OcidentalPorto 4250Portugal Serviço de anatomia Patológica Centro Hospitalar Universitário de Sao JoaoPorto 4200Portugal

BACKGROUND Individuals within specific risk groups for pancreatic ductal adenocarcinoma(PDAC)[mucinous cystic lesions(MCls),hereditary risk(HR),and new-late onset diabetes mellitus(NlOD)]represent an opportunity for early cancer *** ultrasound(EUS)is a premium image modality for PDAC screening and precursor lesion *** no specific biomarker is currently clinically available for this purpose,glypican-1(GPC1)is overexpressed in the circulating exosomes(crExos)of patients with PDAC compared with healthy subjects or those harboring benign pancreatic *** To evaluate the capacity of GPC1+crExos to identify individuals at higher risk within these specific groups,all characterized by *** This cross-sectional study with a prospective unicentric cohort included 88 subjects:40 patients with MCl,20 individuals with HR,and 20 patients with NlOD.A control group(CG)was submitted to EUS for other reasons than pancreatic pathology,with normal pancreas and absence of hereditary risk factors(n=8).The inclusion period was between October 2016 and January 2019,and the study was approved by the Ethics Committee of Centro Hospitalar Universitário de São João,Porto,*** patients provided written informed *** and blood tests for quantification of GPC1+crExos by flow cytometry and carbohydrate antigen 19-9(CA 19-9)levels by ElISA were performed in all ***-guided tissue acquisition was done whenever *** statistical analysis,SPSS®27.0(IBM Corp.,Armonk,NY,United States)version was *** graphs were created using GraphPad Prism 7.00(GraphPad Software,San Diego,CA,United States).RESUlTS Half of MCls harbored worrisome features(WF)or high-risk stigmata(HRS).Pancreatic abnormalities were detected by EUS in 10.0%and 35.0%in HR and NlOD individuals,respectively,all considered non-malignant and“harmless.”Median levels of GPC1+crExos were statistically different:MCl[99.4%,interquartile range(IQR):94.9%-99.8%],HR(8

关键词： Glypican-1 Circulating exosomes Endoscopic ultrasound Pancreatic cancer risk groups Pancreatic cancer precursor lesions Genetic predisposition

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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... 详细信息

关键词： Alzheimer predominant estimates

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Knowledge Is Invented: Addressing Invention and the Art of Saying in the Psychoanalytic Field

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Philosophy Study 2024年第3期14卷 97-105页

作者： ana lúcia Mandelli de Marsillac Universidade Federal de Santa Catarina FlorianópolisBrasil

In the Freudian-lacanian field,there is an important distinction between knowledge and *** truth,of an unconscious nature,is something that inhabits us,directs us,but that escapes ***,in turn,is something to be invented,from the hole of the Real,the Unconscious truth,and the subjective *** relationships between playing,creating,and fantasizing;the dimension of the uncanny,fiction,and imagination in subjectivity;the invention of knowledge of oneself,derived from the pains and flavors of being who one is,are creative dimensions that inhabit the subject,permeate the analytical act,and transversalize *** the practice,we listen to and witness processes of analysis that awaken an invention/reinvention of oneself,in the process of remembering,repeating,and elaborating,but also in what the transference relationship *** of oneself,does not guarantee a life without mishaps,sadness,and illusions,but allows the invention and recognition of knowledge and a *** concept of Sinthome(2007),coined by Jacques lacan,comes in the wake of the processes of self-invention and is a knowing-doing with the symptom,with the paradoxes of joyful suffering,producing,as a result,an art of ***,in this communication,I will articulate elements of theory,practice,and psychoanalytic experience that allow us to expand knowledge of the themes of invention and imagination articulated with the concept of sinthome,their relationships with subjectivity,and the direction of psychoanalytic treatment.

关键词： psychoanalysis invention imagination knowledge sinthome

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Spatial analysis of Dengue through the reproduction numbers relating to socioeconomic features:Case studies on two Brazilian urban centers

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Infectious Disease Modelling 2024年第1期9卷 142-157页

作者： ana T.C.Silva Rejane C.Dorn lívia R.Tomás leonardo B.l.Santos lacita M.Skalinski Suani T.R.Pinho Departamento de Física Universidade Estadual de Feira de SantanaAv.Transnordestinas/n.Novo HorizonteFeira de Santana44036-900BABrazil Instituto de Física Universidade Federal da BahiaRua Barão de Jeremoabo s/nCampus Universitário de OndinaSalvador40170-115BABrazil Centro Nacional de Monitoramento e Alertas de Desastres Naturais(CEMADEN) Estrada Dr.Altino Bondensan500São Josédos Campos12247-016SPBrazil Universidade Estadual de Santa Cruz Campus Soane Nazaréde AndradeRodovia Jorge AmadoKm 16SalobrinhoIlhéus45662-900BABrazil Instituto de Saúde Coletiva Universidade Federal da BahiaR.Basílio da Gamas/n-CanelaSalvador40110-140BABrazil Instituto Nacional de Ciência e Tecnologia-Sistemas Complexos Virtual InstitutionBrazil

The study of the propagation of infectious diseases in urban centers finds a close connection with their population's social characteristics and *** work performs a spatial analysis of dengue cases in urban centers based on the basic reproduction numbers,R0,and incidence by planning areas(PAs),as well as their correlations with the Human Development Index(HDI)and the number of *** analyzed dengue epidemics in 2002 at two Brazilian urban centers,Belo Horizonte(BH)and Rio de Janeiro(RJ),using PAs as spatial *** results reveal heterogeneous spatial scenarios for both cities,with very weak correlations between R0 and both the number of trips and the HDI;in BH,the values of R0 show a less spatial heterogeneous pattern than in *** BH,there are moderate correlations between incidence and both the number of trips and the HDI;meanwhile,they weakly correlate for ***,the absence of strong correlations between the considered measures indicates that the transmission process should be treated considering the city as a whole.

关键词： Dengue Mathematical mode lBasic reproduction number Urban mobility Urban indices

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Functional mechanism study of the allelochemical myrigalone A identifies a group of ultrapotent inhibitors of ethylene biosynthesis in plants

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Plant Communications 2024年第6期5卷 246-262页

作者： George Heslop-Harrison Kazumi Nakabayashi ana Espinosa-Ruiz Francesca Robertson Robert Baines Christopher R.l.Thompson Katrin Hermann David Alabadí Gerhard leubner-Metzger Robin S.B.Williams Centre for Biomedical Sciences Department of Biological SciencesRoyal Holloway University of LondonEgham TW200EXUK Centre for Plant Molecular Sciences Department of Biological SciencesRoyal Holloway University of LondonEgham TW200EXUK Instituto de Biología Molecular y Celular de Plantas(CSIC-UPV) 46022 ValenciaSpain Centre for life’s Origins and Evolution Department of GeneticsEvolution and EnvironmentUniversity College LondonLondonUK Syngenta Crop Protection AGSteinSwitzerland

Allelochemicals represent a class of natural products released by plants as root,leaf,and fruit exudates that interfere with the growth and survival of neighboring *** how allelochemicals function to regulate plant responses may provide valuable new approaches to better control plant *** such allelochemical,Myrigalone A(MyA)produced by Myrica gale,inhibits seed germination and seedling growth through an unknown ***,we investigate MyA using the tractable modelDictyostelium discoideum and reveal that its activity depends on the conserved homolog of the plant ethylenesynthesis protein 1-aminocyclopropane-1-carboxylic acid oxidase(ACO).Furthermore,in silico modeling predicts the direct binding of MyA to ACO within the catalytic *** ***,ablation of ACO mimics the MyA-dependent developmental delay,which is partially restored by exogenous ethylene,and MyA reduces ethylene *** Arabidopsis thaliana,MyA treatment delays seed germination,and this effect is rescued by exogenous *** also mimics the effect of established ACO inhibitors on root and hypocotyl extension,blocks ethylenedependent root hair production,and reduces ethylene ***,in silico binding analyses identify a rangeof highlypotentethylene inhibitorsthatblock ethylene-dependent responseand reduce ethyleneproduction in ***,we demonstrate a molecular mechanism by which the allelochemical MyA reduces ethylene biosynthesis and identify a range of ultrapotent inhibitors of ethylene-regulated responses.

关键词： 1-aminocyclopropane-1-carboxylic acid ACC ACC oxidase ACO allelochemicals ethylene synthesis inhibitors structure-activity relationship

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Characterizing occurrence of emerging organic contaminants in Dinaric karst catchment of Jadro andZrnovnica springs,Croatia

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Emerging Contaminants 2024年第3期10卷 158-169页

作者： ana Selak Jasmina lukac Reberski Ivana Boljat Josip Terzic HGI-CGS-Croatian Geological Survey Department of Hydrogeology and Engineering GeologySachsova 210000ZagrebCroatia

The occurrence of emerging organic contaminants(EOCs)was investigated in vulnerable Dinaric karst catchment of Jadro andZrnovnica springs in Croatia,under varying flow conditions and across three different water resource types(groundwater,springs,and surface water).The maximal EOCs concentration in both springs were observed following autumn recharge events,while during peak discharge no detection above the limits of detection(lOD)was recorded due to dilution *** to springs,groundwater from deep borehole exhibited highest total EOCs concentration under low flow conditions,underscoring the considerable karst aquifer vulnerability and its oligotrophic *** peak EOCs concentration in karstic Cetina River coincided with the river's lowest *** highest mass flux of 1013 g/day was determined for very mobile pharmaceutical metformin detected in *** presence of potentially persistent to very persistent compounds,like DEET and 1H-benzotriazole,which exhibited highest detection frequencies across all sampling sites,was observed in association with varying hydrological *** regarding the occurrence of identified EOCs include surface contamination infiltrating directly through ponors and highly karstified areas,potential persistence in the epikarst and aquifer matrix,and site-specific contamination sources for compounds such as 1H-benzotriazole,gabapentin,and ketoprofen found in *** evaluate the risk of inadvertent human exposure to EOCs across various age groups,we utilized measured spring concentrations and calculated drinking water equivalent levels(DWEl),which ranged from 1.4 mg/l for cotinine to 503 mg/l for sucralose,both detected in Jadro *** EOCs concentrations in ng/l are unlikely to pose a significant risk to healthy population,long-term exposure to EOCs mixture remains *** scarcity of research on EOCs in karst environments on both global and national levels,our study enhances comp

关键词： Karst groundwater Emerging organic contaminants Pharmaceuticals Human exposure DEET 1H-benzotriazole

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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 *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** 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 *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** 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 *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** 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 ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,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 ***,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 *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

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

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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

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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 Molecular 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 multifactorial 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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Towards efficient strain engineering of 2D materials:A four-points bending approach for compressive strain

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Nano Research 2024年第6期17卷 5317-5325页

作者： Hao li Félix Carrascoso ana Borrás Gloria P.Moreno Francisco J.Aparicio Ángel Barranco Andrés Castellanos Gómez Campus de Cantoblanco Instituto de Ciencia de Materiales de MadridC.Sor Juana Inés de la Cruz328049 MadridSpain Nanotechnology on Surfaces and Plasma lab Instituto de Ciencia de Materiales de Sevilla(CSIC-Universidad de Sevilla).C/Americo Vespucio 49E-41092 SevilleSpain Departamento de Física Aplicada I Escuela Politécnica SuperiorUniversidad de Sevillac/Virgen deÁfrica 7E-41011 SevilleSpain

Strain engineering,as a powerful strategy to tune the optical and electrical properties of two-dimensional(2D)materials by deforming their crystal lattice,has attracted significant interest in recent years.2D materials can sustain ultra-high strains,even up to 10%,due to the lack of dangling bonds on their surface,making them ideal brittle *** remarkable mechanical resilience,together with a strong strain-tunable band structure,endows 2D materials with a broad optical and electrical response upon ***,strain engineering based on 2D materials is restricted by their nanoscale and strain quantification *** this study,we have modified a homebuilt three-points bending apparatus to transform it into a four-points bending apparatus that allows for the application of both compressive and tensile strains on 2D *** approach allows for the efficient and reproducible construction of a strain system and minimizes the buckling effect caused by the van der Waals interaction by adamantane encapsulation *** results demonstrate the feasibility of introducing compressive strain on 2D materials and the potential for tuning their optical and physical properties through this approach.

关键词： uniaxial compressive strain polymer encapsulation differential reflectance spectroscopy exciton tunability

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