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miR-99a-5p modulates doxorubicin resistance via the COX-2/ABCG2 axis in triple-negative breast cancer: from the discovery to in vivo studies

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Cancer Communications 2022年第12期42卷 1412-1416页

作者： Iris Garrido-Cano Anna Adam-Artigues Ana Lameirinhas juan F.Blandez Vicente Candela-Noguera Federico Rojo Sandra Zazo juan Madoz-Gúrpide Ana Lluch Begoña Bermejo Felix Sancenón juan miguel cejalvo Ramón Martínez-Mañez Pilar Eroles Biomedical Research Institute INCLIVA Valencia 46010Spain Bioengineering Biomaterials and Nanomedicine Networking Biomedical Research Centre(CIBER-BBN)Madrid 28029Spain Interuniversity Research Institute for Molecular Recognition and Technological Development(IDM) Polytechnic University of ValenciaUniversity of ValenciaValencia 46010Spain Joint Unit CIPF-UPV of Mechanisms of Diseases and Nanomedicine ValenciaPolytechnic University of ValenciaPrince Felipe Research CenterValencia 46012Spain Joint Research Unit in Nanomedicine and Sensors Polytechnic University of ValenciaMedical Research Institute Hospital La FeValencia 46026Spain Biomedical Research Networking Center in Oncology(CIBERONC) Madrid 28029Spain Department of Pathology Fundación Jiménez Díaz University Hospital Health Research InstituteMadrid 28040Spain Department of Clinical Oncology University Clinical Hospital of ValenciaValencia 46010Spain Department of Medicine University of ValenciaValencia 46010Spain Department of Physiology University of ValenciaValencia 46010Spain

Dear Editor,Breast cancer(BC)is the most commonly diagnosed cancer and the fifth cause of cancer-related death worldwide[1].Despite the advances in BC targeted therapies,cytotoxic chemotherapy is still widely used[2].However,around 20%-30%of BC patients develop metastasis after treatment as a consequence of drug resistance[3].In this context,microRNAs have emerged as potential therapeutic targets to overcome therapy resistance[4].Therefore,we aimed to elucidate the molecular mechanisms underlying resistance to doxorubicin,one of the most effective chemotherapeutic agents used in BC.Methods are detailed in Supplementary Materials.

关键词： doxorubicin ABCG2 chemotherapy

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Vertical Displacement Measurement in a Slow-Moving Sinkhole Using BOTDA

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Photonic Sensors 2024年第1期14卷 23-39页

作者： Pascual SEVILLANO Javier PRECIADO-GARBAYO Jorge SEVIL Francisco GUTIERREZ juan JMARTiNEZ Sonia MARTiN-LOPEZ miguel GONZALEZ-HERRAEZ Aragon Institute of Engineering Research(I3A) Universidad de ZaragozaZaragoza 50018Spain Electronic Enginering and Communicaton Dpartment EINAUniversidad de ZaragzaZaragza 50018Spain Aragon Photonics Labs. Zaragoza 50009Spain Department of Earth Sciences Universidad de ZaragozaZaragoza 50009Spain Department of Electronics Escuela Politecnica SuperiorUniversidad de AlcalaMadrid 28805Spain

The effectiveness of monitoring and early-warning systems for ground deformation phenomena,such as sinkholes,depends on their ability to accurately resolve the ongoing ground displacement and detect the subtle deformation preceding catastrophic failures.Sagging sinkholes with a slow subsidence rate and diffuse edges pose a significant challenge for subsidence monitoring due to the low deformation rates and limited lateral strain gradients.In this work,we satisfactorily illustrate the practicality of the Brillouin optical time domain analysis(BOTDA)to measure the spatial-temporal patterns of the vertical displacement in such challenging slow-moving sagging sinkholes.To assess the performance of the approach,we compare the strain recorded by the distributed optical fiber sensor with the vertical displacement measured by high-precision leveling.The results show a good spatial correlation with the ability to identify the maximum subsidence point.There is also a good temporal correlation with the detection of an acceleration phase in the subsidence associated with a flood event.

关键词： Distributed fiber optic sensing(DFOS) vertical displacement measurement slow subsidence rate sinkhole hazard early-warning system

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Identification and functional characterization of fish IL‑17 receptors suggest important roles in the response to nodavirus infection

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Marine Life Science & Technology 2024年第2期6卷 252-265页

作者： Carmen González‑Fernández miguel A.García‑Álvarez Alberto Cuesta Department of Cell Biology and Histology Faculty of BiologyUniversity of Murcia30100 MurciaSpain Laboratoire d’écotoxicologie Centre de Lyon-VilleurbanneINRAEUR RiverLy69625 VilleurbanneFrance

Th17 is a lymphocyte T helper(Th)subpopulation relevant in the control and regulation of the immune response characterized by the production of interleukin(IL)-17.This crucial cytokine family acts through their binding to the IL-17 receptors(IL-17R),having up to six members.Although the biology of fish Th17 is well-recognized,the molecular and functional characterization of IL-17 and IL-17R has been limited.Thus,our aim was to identify and characterize the IL-17R repertory and regulation in the two main Mediterranean cultured fish species,the gilthead seabream(Sparus aurata)and the European sea bass(Dicentrarchus labrax).Our in silico results showed the clear identification of six members in each fish species,from IL-17RA to IL-17RE-like,with well-conserved gene structure and protein domains with their human orthologues.All of them showed wide and constitutive transcription in naïve tissues but with highest levels in mucosal tissues,namely skin,gill or intestine.In leucocytes,T mitogens showed the strongest up-regulation in most of the il17 receptors though il17ra resulted in inhibition by most stimulants.Interestingly,in vivo nodavirus infection resulted in alterations on the transcription of il17 receptors.While nodavirus infection led to some increments in the il17ra,il17rb,il17rc and il17rd transcripts in the susceptible European sea bass,many down-regulations were observed in the resistant gilthead seabream.Our data identify the presence and conservation of six coding IL-17R in gilthead seabream and European sea bass as well as their differential regulation in vitro and upon nodavirus infection.

关键词： Th17 cells IL-17 receptors Immunity Teleost fish Nodavirus(NNV) Aquaculture

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Debaryomyces hansenii supplementation in low fish meal diets promotes growth,modulates microbiota and enhances intestinal condition in juvenile marine fish

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Journal of Animal Science and Biotechnology 2024年第1期15卷 253-276页

作者： Ignasi Sanahuja Alberto Ruiz Joana P.Firmino Felipe E.Reyes-López juan B.Ortiz-Delgado Eva Vallejos-Vidal Lluis Tort Dariel Tovar-Ramírez Isabel M.Cerezo miguel A.Moriñigo Carmen Sarasquete Enric Gisbert Aquaculture Program Institute of Agrifood Research and Technology(IRTA)La Rapita 43540Spain Centro de Biotecnologia Acuicola Universidad de Santiago de ChileSantiagoChile Instituto de Ciencias Marinas de Andalucia(ICMAN-CSIC) Avda.Republica Saharaui no 2Campus Universitario Rio San PedroPuerto RealCadiz 11510Spain Nucleo de Investigaciones Aplicadas en Ciencias Veterinarias y Agronomicas Facultad de Medicina Veterinaria y AgronomiaUniversidad de Las AmericasSantiagoChile Department of Cell Biology Physiologyand ImmunologyUniversitat Autonoma de BarcelonaBarcelonaSpain Centro de Investigaciones Biologicas del Noroeste SC CIBNORLa PazMexico Department of Microbiology Instituto de Biotecnologia Y Desarrollo Azul(IBYDA)Faculty of SciencesUniversity of Malaga29010 MalagaSpain SCBI Bioinformatic UnitUniversity of Malaga29590 MalagaSpain

Background The development of a sustainable business model with social acceptance,makes necessary to develop new strategies to guarantee the growth,health,and well-being of farmed animals.Debaryomyces hansenii is a yeast species that can be used as a probiotic in aquaculture due to its capacity to i)promote cell proliferation and differen-tiation,ii)have immunostimulatory effects,iii)modulate gut microbiota,and/or iv)enhance the digestive function.To provide inside into the effects of D.hansenii on juveniles of gilthead seabream(Sparus aurata)condition,we inte-grated the evaluation of the main key performance indicators coupled with the integrative analysis of the intestine condition,through histological and microbiota state,and its transcriptomic profiling.Results After 70 days of a nutritional trial in which a diet with low levels of fishmeal(7%)was supplemented with 1.1%of D.hansenii(17.2×10^(5) CFU),an increase of ca.12%in somatic growth was observed together with an improve-ment in feed conversion in fish fed a yeast-supplemented diet.In terms of intestinal condition,this probiotic modu-lated gut microbiota without affecting the intestine cell organization,whereas an increase in the staining intensity of mucins rich in carboxylated and weakly sulphated glycoconjugates coupled with changes in the affinity for certain lectins were noted in goblet cells.Changes in microbiota were characterized by the reduction in abundance of several groups of Proteobacteria,especially those characterized as opportunistic groups.The microarrays-based transcrip-tomic analysis found 232 differential expressed genes in the anterior-mid intestine of S.aurata,that were mostly related to metabolic,antioxidant,immune,and symbiotic processes.Conclusions Dietary administration of D.hansenii enhanced somatic growth and improved feed efficiency param-eters,results that were coupled to an improvement of intestinal condition as histochemical and transcriptomic tools indicated.This probiotic yeast stimulated host-microbiota interactions with

关键词： Debaryomyces hansenii Intestine condition Low fish meal diet Microbiota Transcriptomics Yeast probiotic

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Long-term effects of gestational diabetes mellitus on the pancreas of female mouse offspring

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World Journal of Diabetes 2024年第4期15卷 758-768页

作者： Enriqueta Muñoz-Islas Edgar David Santiago-SanMartin Eduardo Mendoza-Sánchez Héctor Fabián Torres-Rodríguez Laura Yanneth Ramírez-Quintanilla Christopher Michael Peters juan miguel Jiménez-Andrade Unidad Académica Multidisciplinaria Reynosa-Aztlán Universidad Autónoma de TamaulipasReynosa 88740TamaulipasMexico Department of Anesthesiology Wake Forest University School of MedicineWinston SalemNC 27101United States

BACKGROUND Prolonged fetal exposure to hyperglycemia may increase the risk of developing abnormal glucose metabolism and type-2 diabetes during childhood,adolescence,and adulthood;however,the mechanisms by which gestational diabetes mellitus(GDM)predisposes offspring to metabolic disorders remain unknown.AIM To quantify the nerve axons,macrophages,and vasculature in the pancreas from adult offspring born from mouse dams with GDM.METHODS GDM was induced by i.***.administration of streptozotocin(STZ)in ICR mouse dams.At 12 wk old,fasting blood glucose levels were determined in offspring.At 15 wk old,female offspring born from dams with and without GDM were sacrificed and pancreata were processed for immunohistochemistry.We quantified the density of sensory[calcitonin gene-related peptide(CGRP)]and tyrosine hydroxylase(TH)axons,blood vessels(endomucin),and macro-phages(CD68)in the splenic pancreas using confocal microscopy.RESULTS Offspring mice born from STZ-treated dams had similar body weight and blood glucose values compared to offspring born from vehicle-treated dams.However,the density of CGRP+and TH+axons,endomucin+blood vessels,and CD68+macrophages in the exocrine pancreas was significantly greater in offspring from mothers with GDM vs control offspring.Likewise,the microvasculature in the islets was significantly greater,but not the number of macrophages within the islets of offspring born from dams with GDM compared to control mice.CONCLUSION GDM induces neuronal,vascular,and inflammatory changes in the pancreas of adult progeny,which may partially explain the higher propensity for offspring of mothers with GDM to develop metabolic diseases.

关键词： Gestational diabetes mellitus Immunohistochemistry Confocal microscopy Pancreas Offspring

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VisuaLizations As Intermediate Representations (VLAIR): An approach for applying deep learning-based computer vision to non-image-based data

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Visual Informatics 2022年第3期6卷 35-50页

作者： Ai Jiang miguel A.Nacenta juan Ye School of Computer Science University of St AndrewsUK University of Victoria Canada

Deep learning algorithms increasingly support automated systems in areas such as human activity recognition and purchase recommendation.We identify a current trend in which data is transformed first into abstract visualizations and then processed by a computer vision deep learning pipeline.We call this VisuaLization As Intermediate Representation(VLAIR)and believe that it can be instrumental to support accurate recognition in a number of fields while also enhancing humans’ability to interpret deep learning models for debugging purposes or for personal use.In this paper we describe the potential advantages of this approach and explore various visualization mappings and deep learning architectures.We evaluate several VLAIR alternatives for a specific problem(human activity recognition in an apartment)and show that VLAIR attains classification accuracy above classical machine learning algorithms and several other non-image-based deep learning algorithms with several data representations.

关键词： Information visualization Convolutional neural networks Human activity recognition Smart homes Data representation Intermediate representations Interpretability Machine learning Deep learning

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Dietary(poly)phenol intake is associated with cardiometabolic health parameters in adolescents

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Food Science and Human Wellness 2024年

作者： Emily P.Laveriano-Santos Sara Castro-Barquero Camila Arancibia-Riveros Ana María Ruiz-León Rosa Casas Ramón Estruch Patricia Bodega Mercedes de miguel Amaya de Cos-Gandoy Jesús Martínez-Gómez Gloria Santos-Beneit juan M.Fernández-Alvira Rodrigo Fernández-Jiménez Rosa M.Lamuela-Raventós Anna Tresserra-Rimbau The Zena and Michael A.Wiener Cardiovascular Institute Icahn School of Medicine at Mount Sinai Department de Nutrició Ciències de l'Alimentació I Gastronomia XIA Facultat de Farmàcia i Ciències de l'alimentació Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB) Universitat de Barcelona Department of Internal Medicine Hospital Clínic Institutd'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) University of Barcelona Consorcio CIBER M.P.Fisiopatología de la Obesidad y Nutrición (CIBERObn) Instituto de Salud Carlos III (ISCIII) Mediterranean Diet Foundation 5. Foundation for Science Health and Education (SHE) 6. Centro Nacional de Investigaciones Cardiovasculares (CNIC) CIBER de Enfermedades Cardiovasculares (CIBERCV) 9. Hospital Universitario Clínico San Carlos

Background: The protective role of (poly)phenols against metabolic disorders has been extensively studied in adults but not in adolescents.Objective: To assess associations of dietary (poly)phenols and their subclasses with cardiometabolic health parameters in adolescents. Methods: A cross-sectional study was conducted in 944 individuals aged 11 to 14 years enrolled in the SI! Program for Secondary Schools trial (NCT03504059). (Poly)phenol intake was assessed using semi-quantitative food frequency questionnaires and the Phenol-Explorer database. The measured cardiometabolic parameters were waist circumference (WC) age-sex z-score， blood pressure (BP) age-sex z-score， blood glucose (BG)， triglycerides (TG)， and high-density lipoprotein cholesterol (HDL-c). Multilevel mixed-effect linear regression models were applied to examine the association between (poly)phenol quintiles and cardiometabolic health parameters.Results: Compared to the lowest quintile， adolescents in the highest quintile of total (poly)phenol intake had lower WC z-scores (β=-0.09， 95%CI=-0.09;-0.08， P-for trend=0.002)， mean arterial pressure z-scores (β =-0.11， 95%CI=-0.12;-0.09， P-for trend=0.206)， and HDL-c (β=-1.52， 95%CI=-2.90;-0.14， P-for trend=0.108)， after multivariable adjustment. The WC z-scores (β=-0.11， 95%CI=-0.19;-0.03， P-for trend=0.013) and HDL-c (β=-2.16， 95%CI=-3.78;-0.53， P-for trend=0.046) were lower in the highest quintile of flavonoid intake compared to the lowest quintile. The highest quintile of phenolic acid intake was associated with a lower WC z-score (β=-0.14， 95%CI=-0.26;-0.02， P-for trend=0.011) and TG levels (β=-8.83， 95%CI=-12.37;-5.30， P-for trend <0.001)， and the highest quintile of stilbene intake with lower BG (β=-1.83， 95%CI= -3.103;-0.64， P-for trend <0.001) and TG (β=-3.22， 95%CI= -4.95;-1.49， P-for trend=0.034)， and with higher HDL-c (β=2.328， 95%CI= 1.40;3.17， P-for trend=0.466) compared to the lowest quintile. Conclusion: A higher intake of (poly)phenols， especially flavonoids， phenolic acids， and stilbenes

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Effectiveness of statins vs.exercise on reducing postprandial hypertriglyceridemia in dyslipidemic population:A systematic review and network meta-analysis

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Journal of Sport and Health Science 2022年第5期11卷 567-577页

作者： Laura Alvarez-Jimenez Alfonso Moreno-Cabanas miguel Ramirez-Jimenez Felix Morales-Palomo juan FOrtega Ricardo Mora-Rodriguez Exercise Physiology Lab at Toledo Sports Science DepartmentUniversity of Castilla-La ManchaToledo 45004Spain

Background:Individuals at risk of suffering cardiovascular disease(CVD) present with larger increases in blood trigyceride(TG) concentration after a high-fat meal than do healthy individuals.These postprandial hypertriglyceride levels are an independent risk factor for CVD.Prescription of statins and a bout of prolonged exercise are both effective in lowering postprandial hypertriglyceride levels.We aimed to evaluate the comparative effectiveness of statins vs.a bout of aerobic exercise in reducing fasting and postprandial TG(PPTG) concentrations in indiv、duals at high nsk of developing CVD.Methods:Thirty-seven sltudies from a systematic literature search of the PubMed,EMBASE,and Cochrane databases were included in this review.The selected studies conducted trials involving statin therapy(n=20) or a bout of aerobic exercise(n=19) and measured their impact on PPTG levels as the outcome.Two studies analyzed both treatments and were included in duplicate.The meta-analysis was constructed using a random-effects model to calculate the mean difference(MD).The Student t test was used to compare the data sets for statins vs.exercise.Results:Overall,statin and exercise interventions showed similar reductions in PPTG levels,with an MD of-0.65 mmol/L for statins(95% confidence interval(95%CI):-0.54 to-0.77;p <0.001) and-0.46 mmol/L for exercise(95%CI:-0.21 to-0.71;p <0.01).However,statins lowered fasting TG levels more than exercise(MD=-1.54 mmol/L,95%CI:-2.25 to-0.83;p=0.009).Conclusion:Although aerobic exercise is effective in lowering blood TG levels,statins seem to be more efficient,especially in the fasted state.A combination of exercise and statins might reveal a valuable approach to the treatment and prevention of CVD.More studies are required to determine the underlying mechanisms and the possible additive effects of these interventions.

关键词： Aerobic exercise Cardiovascular disease Hydroxymethylglutaryl-CoA reductase inhibitor Meta-analysis Metabolic syndrome

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A novel Ga(Ⅲ)coordination complex as an efficient sensitizer for enhancing photocatalytic activity of TiO_(2)/rGO nanocomposite

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Journal of Rare Earths 2023年第7期41卷 1004-1013,I0002页

作者： Amir Hossein Cheshme Khavar Neda Khedri Rubén Rizo juan miguel Feliu Martínez Ali Reza Mahjoub Masoumeh Doolabi Ehsan Aghayani Department of Chemistry Farhangian UniversityTehranIran Department of Chemistry Faculty of Basic SciencesTarbiat Modares UniversityTehranIran Instituto de Electroquímica y Departamento de Química Física Universidad de Alicante03080AlicanteSpain Research Center for Environmental Contaminants Abadan University of Medical SciencesAbadanIran Department of Environmental Health Engineering Abadan University of Medical SciencesAbadanIran

Narrow solar-light response range and rapid charges recombination are the main technical barriers in TiO_(2) photocatalysis technology.To overcome these restrictions,in this work we synthesized a novel binuclear gadolinium(Ⅲ) coordination complex,[Gd_(2)(DPDB)_6(DMF)_6(H_(2)O_()2)](DPDB=[(4-dimethylamino)phenyldiazenyl] benzenesulfonate),which was used as an inorganic sensitizer for boosting the visible light-harvesting and quantum efficiency of TiO_(2) supported-reduced graphene oxide(rGO) nanocomposite.Crystal structure of [Gd_(2)(DPDB)_6(DMF)_6(H_(2)O)_(2)](Gd-CMP) was determined from single-crystal X-ray diffraction data,which indicates three-dimensional(3D) supramolecular architecture through hydrogen bonding and CH…π_(ph) interactions.The prepared nanohybrid(Gd-CMP/TG) reveals significantly enhanced visible-light-induced photocatalytic activity for degradation of acetaminophen(ACT).The complete removal of 10 mg/L ACT is achieved over Gd-CMP/TG,and the corresponding rate constant of ACT degradation of nanohybrid is 40-fold higher than that of bare TiO_(2).In prepared ternary nanohybrid,metal-coordination sensitizer(Gd-CMP) acts as an electron donor,and at the same time,rGO serves as an electron acceptor,and the synergistic effect between them efficiently enhances charges separation and inhibits e/h pair recombination in the hybridized species.The radical scavenger tests indicate that the photo-induced O_(2)^(-·) radicals dominate ACT degradation.On the basis of the experimental results and calculated energy of electronic levels,a possible mechanism for the improved photocatalytic activity is discussed.

关键词： Gadolinium Coordination complex Sensitizer Photocatalytic Light-harvesting Rare earths

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Origin and Evolution of Ultramafic Rocks along the Sagaing Fault, Myanmar

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Journal of Earth Science 2023年第1期34卷 122-132页

作者： Tomoaki Morishita Hnin Min Soe Hla Htay Than Htut Lwin juan miguel Guotana Akihiro Tamura Tomoyuki Mizukami Khin Zaw 无 Faculty of Geosciences and Civil Engineering Kanazawa UniversityKanazawa920-1192Japan Lamont-Doherty Earth Observatory Columbia UniversityPalisadesNY10964USA Volcanoes and Earth’s Interior Research Center Japan Agency for Marine-Earth Science and Technology2-15 NatsushimaKanagawa237-0061Japan Geology Department University of MandalayMandalay05092Myanmar Geology Department Dagon UniversityNorth Dagon11422Myanmar Taunggoke Degree College TaunggokeTaunggoke Township07161Myanmar Graduate School of Natural Science and Technology Kanazawa UniversityKanazawaIshikawa920-1192Japan CODES ARC Centre of Excellence in Ore Deposits University of TasmaniaTasmania7001Australia

The active Sagaing fault in Myanmar defines the boundary between the Indian Plate and the Eurasian Plate and causes seismic damage in the major cities of Myanmar. Small bodies of serpentinite occur along the fault. We for the first time investigated the highly sheared serpentinite bodies in the Sheinmagar area and Yega Inn area along the Sagaing fault. Extensively sheared/brecciated serpentinites and related rocks, such as talc and/or chlorite-bearing rocks contains small rock fragments of serpentinites. Serpentine texture and mineral chemistry indicate that the protolith of these serpentinites were mainly harzburgite with minor amounts of dunite, some of which are cut by gabbroic veins. No shape-preferred orientation of the antigorite is present, indicating that the serpentinization was occurred under relatively static conditions. Protolith and serpentine minerals are similar to those of the jadeitite-bearing serpentinites in the north of the Sagaing fault(the Jade Mine belt). Chemical variations of spinels in the studied area are within the compositional range of forearc peridotites and those in the mantle section of nearby ophiolites. After the formation of antigorite serpentinite under static conditions, these serpentinites were subsequently, but locally deformed, probably due to the activity of the Sagaing fault, resulting in the formation of serpentinite schist/brecciated rock. The presence of the less-deformed antigorite serpentinite in the sheared/brecciated zone indicates the strain localization mainly along the surrounding serpentine-talc(±chlorite) schistose rocks, which is probably formed by the reaction between serpentinite and country rocks. Further studies are needed to better understand whether the distribution of serpentinized peridotites cause variations in the activity of the Sagaing fault.

关键词： Sagaing fault serpentinite deformation ophiolite

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