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Thiopurine-methyltransferase variants in inflammatory bowel disease:Prevalence and toxicity in brazilian patients

World Journal of Gastroenterology 2014年第12期20卷 3327-3334页

作者： ana Teresa P Carvalho barbara C Esberard Renata S b Fróes Davy C M Rapozo ana b grinman Tatiana A Simo Juliana C V C Santos Antonio José V Carneiro Luis Felipe Ribeiro-Pinto Heitor S P de Souza Disciplina de Gastroenterologia e Endoscopia Digestiva Universidade do Estado do Rio de Janeiro Programa de Carcinogênese Molecular Instituto Nacional de Cancer Laboratório de Toxicologia e biologia Molecular Universidade do Estado do Rio de Janeiro Servi?o de Gastroenterologia Departamento de Clínica MédicaUniversidade Federal do Rio de Janeiro

AIM:To analyze the prevalence of thiopurine-methyltransferase(TPMT)genotypes and their associationwith drug toxicity in inflammatory bowel disease(IbD)patients from southeastern brazil.METHODS:A total of 219 consecutive patients with IbD,of which 146 had Crohn’s disease and 73 had ulcerative colitis,regularly seen at the outpatient unit of the Division of Gastroenterology at the University Hospital Pedro Ernesto of the State University of Rio de Janeiro,a tertiary referral center,were enrolled in this study from February 2009 to January 2011.We analyzed the presence of major TPMT genetic variants(TPMT*2,*3A,*3C)in IbD patients by means of a specific allele and RFLP-PCR.Genomic DNA was isolated from peripheral blood leukocytes by proteinase-K/Sodium Dodecyl Sulfate digestion and phenol-chloroform extraction.TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes were detected by real-time polymerase chain reaction followed by direct sequencing with specific primers.Clinical data were systematically recorded,and correlated with the genotype results.RESULTS:The distribution of the selected TPMT gene polymorphism TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes was 3.6%,5.4%,and 7.7%of the patients,respectively.Among the side effects recorded from patients taking azathioprine,14 patients presented with pancreatitis and/or an elevation of pancreatic enzymes,while 6 patients had liver toxicity,and 2 patients exhibited myelosuppression/neutropenia.TPMT polymorphisms were detected in 37/219 patients(8 heterozygous for*2,11 heterozygous for*3A,and 18 heterozygous for*3C).No homozygotic polymorphisms were found.Despite the prevalence of the TPMT*3C genotype,no differences among the genotype frequencies were significant.Although no association was detected regarding myelotoxicity or hepatotoxicity,a trend towards the elevation of pancreatic enzymes was observed for TPMT*2 and TPMT*3C genotypes.CONCLUSION:The prevalence of TPMT genotypes was high among brazilian patients.Variants genes*2and*3C may be ass

关键词： Inflammatory bowel disease Thiopurinemethyl-transf

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Protein glycation:a wolf in sweet sheep’s clothing behind neurodegeneration

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Neural Regeneration Research 2024年第5期19卷 975-976页

作者： ana b.Uceda Francisco Leal-Pérez Miquel Adrover Institut Universitari d’Investigacióen Ciències de la Salut(IUNICS) Institut d’InvestigacióSanitària Illes balears(IdISba) Departament de Química Universitat de les Illes BalearsCtraPalma de MallorcaSpain

At the beginning of the 16th century,Paracelsus coined the maxim:“the dose makes the poison”.This principle can be applied to all living organisms,including organs and cells.The brain and its glial and neuronal cells are no exception.Even small compounds that are essential for the life of brain cells can become truly toxic when overdosed.

关键词： organs sheep sweet

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Design multifunctional Mg–Zr coatings regulating Mg alloy bioabsorption

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Journal of Magnesium and Alloys 2024年第4期12卷 1461-1478页

作者： Zohra benzarti Sandesh Itani JoséDavid Castro Sandra Carvalho ana Sofia Ramos University of Coimbra CEMMPREARISEDepartment of Mechanical EngineeringRua Luís Reis Santos3030-788CoimbraPortugal Laboratory of Multifunctional Materials and Applications(LaMMA) Department of PhysicsFaculty of Sciences of SfaxUniversity of SfaxSoukra Road km 3.5B.P.1171Sfax3000Tunisia

Magnesium(Mg)alloys are widely used for temporary bone implants due to their favorable biodegradability,cytocompatibility,hemocompatibility,and close mechanical properties to bone.However,rapid degradation and inadequate strength limit their applicability.To overcome this,the direct current magnetron sputtering technique is employed for surface coating in Mg-based alloys using various zirconium(Zr)content.This approach presents a promising strategy for simultaneously improving corrosion resistance,maintaining biocompatibility,and enhancing strength without compromising osseointegration.by leveraging Mg’s inherent biodegradability,it has the potential to minimize the need for secondary surgeries,thereby reducing costs and resources.This paper is a systematic study aimed at understanding the corrosion mechanisms of Mg–Zr coatings,denoted Mg-xZr(x=0–5 at.%).Zr-doped coatings exhibited columnar growth leading to denser and refined structures with increasing Zr content.XRD analysis confirmed the presence of the Mg(00.2)basal plane,shifting towards higher angles(1.15°)with 5 at.%Zr doping due to lattice parameter changes(i.e.,decrease and increase of“c”and“a”lattice parameters,respectively).Mg–Zr coatings exhibited“liquidphilic”behavior,while Young’s modulus retained a steady value around 80 GPa across all samples.However,the hardness has significantly improved across all samples’coating,reaching the highest value of(2.2±0.3)GPa for 5 at.%Zr.Electrochemical testing in simulated body fluid(SbF)at 37℃ revealed a significant enhancement in corrosion resistance for Mg–Zr coatings containing 1.0–3.4 at.%Zr.Compared with the 5 at.%Zr coating which exhibited a corrosion rate of 32 mm/year,these coatings displayed lower corrosion rates,ranging from 1 to 12 mm/year.This synergistic enhancement in mechanical properties and corrosion resistance,achieved with 2.0–3.4 at.%Zr,suggests potential ability for reducing stress shielding and controlled degradation performance,and consequently,promising functional biodegradable materials f

关键词： Mg-Zr coatings Magnetron sputtering Nanoindentation Corrosion resistance bone implants

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Combining thermal scanning probe lithography and dry etching for grayscale nanopattern amplification

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Microsystems & Nanoengineering 2024年第1期10卷 335-344页

作者： berke Erbas ana Conde-Rubio Xia Liu Joffrey Pernollet Zhenyu Wang Arnaud bertsch Marcos Penedo Georg Fantner Mitali banerjee Andras Kis Giovanni boero Juergen brugger Microsystems Laboratory École Polytechnique Fédérale de Lausanne(EPFL)Lausanne 1015Switzerland Center of MicroNanoTechnology(CMi) EPFLLausanne 1015Switzerland Laboratory of Nanoscale Electronics and Structures École Polytechnique Fédérale de Lausanne(EPFL)Lausanne 1015Switzerland Laboratory for bio-and Nano-Instrumentation École Polytechnique Fédérale de Lausanne(EPFL)Lausanne 1015Switzerland Laboratory of Quantum Physics Topology and CorrelationsÉcole Polytechnique Fédérale de Lausanne(EPFL)Lausanne 1015Switzerland Present address:Institute of Materials Science of barcelona ICMAb-CSIC Campus UABBellaterra 08193Spain Present address:School of Integrated Circuits and Electronics MIIT Key Laboratory for Low-Dimensional Quantum Structure and DevicesBeijing Institute of TechnologyBeijing 100081China

Grayscale structured surfaces with nanometer-scale features are used in a growing number of applications in optics and fluidics.Thermal scanning probe lithography achieves a lateral resolution below 10 nm and a vertical resolution below 1 nm,but its maximum depth in polymers is limited.Here,we present an innovative combination of nanowriting in thermal resist and plasma dry etching with substrate cooling,which achieves up to 10-fold amplification of polymer nanopatterns into SiO_(2) without proportionally increasing surface roughness.Sinusoidal nanopatterns in SiO_(2) with 400 nm pitch and 150 nm depth are fabricated free of shape distortion after dry etching.To exemplify the possible applications of the proposed method,grayscale dielectric nanostructures are used for scalable manufacturing through nanoimprint lithography and for strain nanoengineering of 2D materials.Such a method for aspect ratio amplification and smooth grayscale nanopatterning has the potential to find application in the fabrication of photonic and nanoelectronic devices.

关键词： lithography thermal pattern

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Sol-gel derived b_(2)O_(3)-CaO borate bioactive glasses with hemostatic,antibacterial and pro-angiogenic activities

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Regenerative biomaterials 2024年第1期3卷 108-118页

作者： Kai Zheng Faina bider Mahshid Monavari Zhiyan Xu Christina Janko Christoph Alexiou ana M.beltran Aldo R.boccaccini Jiangsu Province Engineering Research Center of Stomatological Translational Medicine College of StomatologyNanjing Medical UniversityNanjing 210029China Jiangsu Key Laboratory of Oral Diseases Nanjing Medical UniversityNanjing 210029China Institute of biomaterials University of Erlangen-Nuremberg91058 ErlangenGermany Department of Oto-Rhino-Laryngology Head and Neck SurgerySection of Experimental Oncology and Nanomedicine(SEON)Else Kroener-Fresenius-Stiftung ProfessorshipUniversitaetsklinikum Erlangen91058 ErlangenGermany Departamento de Ingenier�ıa y Ciencia de los Materiales y del Transporte Escuela Politecnica

Sol-gel borate bioactive glasses(bGs)are promising ion-releasing biomaterials for wound healing applications.Here,we report the synthesis of a series of binary b_(2)O_(3)-CaO borate bGs(CaO ranging from 50 to 90mol%)using a sol-gel-based method.The influence of CaO content in b_(2)O_(3)-CaO borate bG on morphology,structure and ion release behavior was investigated in detail.Reduced dissolution(ion release)and crystallization could be observed in borate bGs when CaO content increased,while the morphology was not significantly altered by increasing CaO content.Our results evidenced that the ion release behavior of borate bGs could be tailored by tuning the b_(2)O_(3)/CaO molar ratio.We also evaluated the in vitro cytotoxicity,hemostatic,antibacterial and angiogenic activities of borate bGs.Cytocompatibility was validated for all borate bGs.However,borate bGs exhibited composition-dependent hemostatic,antibacterial and angiogenic activities.Generally,higher contents of Ca in borate bGs facilitated hemostatic activity,while higher contents of b_(2)O_(3) were beneficial for pro-angiogenic activity.The synthesized sol-gel-derived borate bGs are promising materials for developing advanced wound healing dressings,given their fast ion release behavior and favorable hemostatic,antibacterial and angiogenic activities.

关键词： borate glasses sol-gel processing glass composition wound healing

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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 system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The 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 results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κb serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We 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 pathways.While 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 outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models

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

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Synthesis and applications of lanthanoid complexes of pentadentate and hexadentate N_(5) and N_(6) macrocycles:A review

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Journal of Rare Earths 2024年第1期42卷 1-15,I0001页

作者： Julio Corredoira-Vázquez Cristina González-barreira Paula Oreiro-Martínez ana M.García-Deibe Jesús Sanmartín-Matalobos Matilde Fondo Departamento de Química Inorganica Facultade de QuímicaUniversidade de Santiago de CompostelaCampus Vida15782Santiago de CompostelaSpain Phantom-g CICECO-Aveiro Institute of MaterialsDepartment of PhysicsUniversity of Aveiro3810-193AveiroPortugal Institute of Materials(iMATUS) Universidade de Santiago de Compostela15782Santiago de CompostelaSpain

In this paper,the lanthanoid complexes of N_(5) and N_(6) macrocycle ligands,without pendant arms or additional heteroatoms,are surveyed.This review covers the period from 2015 to the current date,since in 2014 Schiff base macrocyclic ligands incorporating the pyridine moiety,and their complexes,were revised,and in 2015 the chemistry of pentaaza macrocycle ligands with rare earth metals was also summarized.Porphyrin and phthalocyanine ligands are not included in this review,which primarily focuses on complexes with Schiff bases and amines without pendant arms or any additional donor other than nitrogen.The synthetic methods,structural characterization,based on single X-ray crystal data,and properties of the lanthanoid complexes,with special attention to magneto-structural correlations,are presented herein.

关键词： Lanthanoid N_(5),N_(6)macrocycle Coordination chemistry Chirality biological activity Molecule magnet

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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 solids.This remarkable mechanical resilience,together with a strong strain-tunable band structure,endows 2D materials with a broad optical and electrical response upon strain.However,strain engineering based on 2D materials is restricted by their nanoscale and strain quantification troubles.In 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 materials.This 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 strategy.Our 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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Vanadium mineralization at Los Chihuidos sediment-hosted Cu-V deposit,Neuquén basin,Argentina:An approach to vanadium ore forming processes

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Geoscience Frontiers 2024年第1期15卷 225-246页

作者： ana L.Rainoldi Daniel beaufort Marta b.Franchini Adolfo Giusiano Sabine Petit Patricia Patrier M.Josefina Pons Dpto.de Geología Universidad Nacional del Sur(UNS)8000 Bahía BlancaArgentina Consejo Nacional de Investigaciones Científicas y Técnicas Centro Patagónico de Estudios MetalogenéticosArgentina Universitéde Poitiers IC2MPCNRS-UMR 7285HydrasaF-86022 Poitiers CedexFrance Universidad Nacional del Comahue Facultad de IngenieríaDepartamento de Geología y Petróleo8300 NeuquénArgentina Consultant Geologist 8300 NeuquénArgentina Universidad Nacional de Río Negro Instituto de Investigación en Paleobiología y GeologíaRío NegroArgentina

Vanadium mineralization at Los Chihuidos deposit of the Neuquén basin is linked to the development of a redox front system related to the inflow of hydrocarbons into the red sandstone of the Huincul Formation.Interaction of hydrocarbons with oxidized red beds and connate water generated redox reactions where hematite was dissolved due to iron reduction resulting in the discoloration of the red strata.At the contact between oxidized red sandstone and reduced white sandstone,precipitation of specific mineral phases resulted in the V ore with minor amounts of Cu.With the implementation of the redox interface,abundant V-montmorillonite and V-hematite precipitated at the more oxidizing conditions and Cu-V-corrensite-type at the more reducing conditions of the redox front.As the redox front advanced with fluids constantly migrating into the reservoir,more reducing conditions were stablished,promoting chloritization and minor illitization with V-Cu incorporation and continuous upgrading of the ore.Main ore mineralogy consists of clay minerals including V-bearing montmorillonite,Cu-V-corrensite-type,V-di-trioctahedral chlorite and Cu-tri-trioctahedral chlorite with minor V-illite-smectite mixed-layer minerals and associated secondary V-hematite.Chloritization over illitization was favored due to high amounts of Fe and Mg in detrital clasts and in connate fluids and by low K availability related to low amounts of detrital K-feldspar.The spatial transition of V and/or Cu bearing clay minerals observed through the mineralized redox front at Los Chihuidos deposit(kaolinite→smectite→illite/smectite→corrensite-type→di-trioctahedral-chlorite→tri-trioctahedral-chlorite)and the related variation of V-Cu concentrations in bulk rock are indicative of increasing pH and decreasing Eh of resident solutions from red to white sandstones during the hypogene mineralization process.Late influx of Cu-rich oxidized basinal brines precipitated main copper ore with Cu-sulfides in the white sandstone up to the contact with the redox front in co

关键词： Clay minerals V-chlorite Redox front bleaching Hydrocarbons

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Digestive and breast cancer patients managed during the first wave of COVID-19 pandemic:Short and middle term outcomes

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World Journal of Methodology 2024年第2期14卷 107-126页

作者： Jacobo Trébol ana Carabias-Orgaz María Carmen Esteban-Velasco Asunción García-Plaza Juan Ignacio González-Munoz ana belén Sánchez-Casado Felipe Carlos Parreno-Manchado Marta Eguía-Larrea José Antonio Alcázar-Montero Cirugía General y del Aparato Digestivo Complejo Asistencial Universitario de SalamancaSalamanca 37007SalamancaSpain Cirugía Universidad de SalamancaSalamanca 37007SalamancaSpain Oftalmología Complejo Asistencial Universitario de SalamancaSalamanca 37007SalamancaSpain

bACKGROUND The first wave of coronavirus disease 2019(COVID-19)pandemic in Spain lasted from middle March to the end of June 2020.Spanish population was subjected to lockdown periods and scheduled surgeries were discontinued or reduced during variable periods.In our centre,we managed patients previously and newly diagnosed with cancer.We established a strategy based on limiting perioperative social contacts,preoperative screening(symptoms and reverse transcriptionpolymerase chain reaction)and creating separated in-hospital COVID-19-free pathways for non-infected patients.We also adopted some practice modifications(surgery in different facilities,changes in staff and guidelines,using continuously changing personal protective equipment…),that supposed new inconveniences.AIM To analyse cancer patients with a decision for surgery managed during the first wave,focalizing on outcomes and pandemic-related modifications.METHODS We prospectively included adults with a confirmed diagnosis of colorectal,oesophago-gastric,liver-pancreatic or breast cancer with a decision for surgery,regardless of whether they ultimately underwent surgery.We analysed short-term outcomes[30-d postoperative morbimortality and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection]and outcomes after 3 years(adjuvant therapies,oncological events,death,SARS-CoV-2 infection and vaccination).We also investigated modifications to usual practice.RESULTS From 96 included patients,seven didn’t receive treatment that period and four never(3 due to COVID-19).Operated patients:28 colon and 21 rectal cancers;laparoscopy 53.6%/90.0%,mortality 3.57%/0%,major complications 7.04%/25.00%,anastomotic leaks 0%/5.00%,3-years disease-free survival(DFS)82.14%/52.4%and overall survival(OS)78.57%/76.2%.Six liver metastases and six pancreatic cancers:no mortality,one major complication,three grade A/b liver failures,one bile leak;3-year DFS 0%/33.3%and OS 50.0%/33.3%(liver metastases/pancreatic carcinoma).5 gastric and 2 oesophageal tumours:mortality 0%/50

关键词： COVID-19 SARS-CoV-2 Colon cancer Rectal cancer breast cancer Liver cancer Pancreatic cancer Gastric cancer Oesophageal cancer Surgery

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