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Synthesis, Electrochemistry and Antitumor Activity of 1’H, 3’H(Me)-spiro-[(aza)benzimidazoline-2’, 3-(1,2-diferrocenylcyclopropenes)], 2-(1,2-Diferrocenylvinyl)benz- and Azabenzimidazoles

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Open Journal of Synthesis Theory and Applications 2014年第4期3卷 44-56页

作者： Jessica J. Sánchez García Luis Ortiz-Frade elena martínez-klimova Juan C. García Ramos Marcos Flores-Alamo Teresa Ramírez Apan elena I. klimova Faculty of Chemistry University National Autonomous of México México City México Centre of Investigation and Development Technology in Electrochemistry S.C. Queretaro México Departament of Bioengineering South Kensington Imperial College London London UK Institute of Chemistry University National Autonomous of México México City México

A new method of synthesis of 2-(1,2-diferrocenylvinyl)benz- and azabenzimidazoles (3a-f), (4a-f) and 1’H,3’H(Me)-spiro-[(aza)benzimidazoline-2’,3-(1,2-diferrocenylcyclopropenes)] (5a-f) via reactions of diferrocenyl(methylsulfanyl)cyclopropenylium iodide (1) with aromatic o-diamines (2a-f) in the presence of Et3N (80°C - 82°C) is described. The structures of the resultant compounds are established using IR, 1H and 13C NMR spectroscopy, mass spectrometry and elemental analysis. The structure of one compound, cis-2-(1,2-diferrocenylvinyl)-1-methylbenzimidazole (3b), is confirmed by X-ray diffraction analysis. The electrochemical properties of compounds 3a, 3b, 3d and 5f are investigated using cyclic square wave voltammetry. Two electrochemical processes (I-II), attributed to oxidation of the ferrocene moieties, and the values of E0’(I), E0’(II), DE0’(II-I) and comporportionation constant Kcom are reported. The bioactivities of seven compounds 3a, 3c-f, 5d, 5f are evaluated. Compound 5f is the most active compound with a modest cytotoxic activity against six human cancer cell lines: U-251 (glioma), PC-3 (prostate cancer), K-562 (leukemia), HCT-15 (colon cancer), MCF-7 (breast cancer) and SKLU-1 (lung cancer).

关键词： Diferrocenyl(methylthio)cyclopropenylium 2-(1 2-Diferrocenylvinyl)(aza)benzimidazoles 1’H 3’H(Me)-spiro-[(aza)benzimidazoline-2’ 3-(1 2-diferrocenylcyclopropenes)] Electrochemistry Antitumor Activity

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Using lysosomal membrane stability of haemocytes in Ruditapes philippinarum as a biomarker of cellular stress to assess contamination by caffeine, ibuprofen, carbamazepine and novobiocin

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Journal of Environmental Sciences 2013年第7期25卷 1408-1418页

作者： Gabriela V. Aguirre-martínez Sara Buratti elena Fabbri Angel T. DelValls M. Laura martín-Díaz Unitwin/Unesco/WiCoP Physical Chemistry Department University of Cdiz Faculty of Marine and Environmental SciencesPolígono Río San Pedro s/n 11510 Puerto Real Cdiz Spain Andalusian Center for Marine Science and Technology (CACYTMAR) Campus Universitariode Puerto Real11510 Puerto Real Cdiz Spain University of Bologna Interdepartment Centre for Research in Environmental Sciences (CIRSA)via S. Alberto 16348123 Ravenna Italy

Although pharmaceuticals have beendetected in the environment only in the range from ng/L to μg/L, it has beendemonstrated that they can adversely affect the health status of aquatic organisms. Lysosomal membrane stability （LMS） has previously been applied as an indicator of cellularwell-being todetermine health status in bivalve mussels. The objective of this study is to evaluate LMS in Ruditapes philippinarum haemolymph using the neutral red retention assay （NRRA）. Clamswere exposed in laboratory conditions to caffeine （0.1, 5, 15, 50 μg/L）, ibuprofen （0.1, 5, 10, 50 μg/L）, carbamazepine and novobiocin （both at 0.1, 1, 10, 50 μg/L） for35days. Results show adose-dependent effect of the pharmaceuticals. The neutral red retention time measured at the end of the bioassaywas significantly reduced by 50% after exposure to environmental concentrations （p 〈 0.05）（caffeine = 15 μg/L; ibuprofen = 10 μg/L; carbamazepine = 1 μg/L and novobiocin = 1 μg/L）, compared to controls. Clams exposed to these pharmaceuticalswere considered to present adiminished health status （retention time 〈45 min）, significantlyworse than controls （96 min）（p 〈 0.05）. The predicted no environmental effect concentration （PNEC） results showed that these pharmaceuticals are very toxic at the environmental concentrations tested. Measurement of the alteration of LMS has been found to be a sensitive technique that enables evaluation of the health status of clams after exposure to pharmaceuticals under laboratory conditions, thus representing a robust Tier-1 screening biomarker.

关键词： neutral red pharmaceuticals bioassay haemolymph bivalves health status Manila clam

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Characterization and QTL identification in eggplant introgression lines under two N fertilization levels

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Horticultural Plant Journal 2023年第5期9卷 971-985页

作者： elena Rosa-martínez Gloria Villanueva Ahmet Sahin Pietro Gramazio María Dolores García-martínez María Dolores Raig on Santiago Vilanova Jaime Prohens Mariola Plazas Instituto de Conservacion y Mejora de la Agrodiversidad Valenciana Universitat Politecnica de ValenciaCamino de Vera 1446022 ValenciaSpain Instituto de Biología Molecular y Celular de Plantas Consejo Superior de Investigaciones Científicas-Universitat Politecnica de ValenciaCamino de Vera 1446022 ValenciaSpain

Lowering nitrogen inputs is a major goal for sustainable *** the present study,a set of 10 Solanum melongena introgression lines(ILs)developed using Solanum incanum as the exotic donor parent were grown under two nitrogen fertilization doses supplied with the irrigation system:1)8.25 mmol·L-1NH4NO3,corresponding to the high nitrogen treatment(HN),and 2)no external nitrogen supply,corresponding to the low nitrogen treatment(LN).Twenty traits,including plant growth and yield parameters,fruit size and morphology,nitrogen and carbon content in leaf and fruit,and phenolics content in fruit,were *** aim was to select of potential materials for eggplant breeding under low N inputs,as well as to identify and locate putative QTLs associated with the traits *** significant differences were observed between the soil characteristics of the HN and LN treatments,except for nitrogen and iron content,which was slightly lower in the HN,probably as a consequence of higher nutrient removal from soil by plants in the latter *** of variance showed that lowering nitrogen inputs did not significantly affect the final yield,fruit morphology,size and phenolics *** agronomic traits were highly and positively correlated with each other under both treatments,as well as total phenolics with chlorogenic acid *** assessment of the differences between each IL and the recipient parent resulted in the identification of 36 QTLs associated with most of the traits—12 were specific to the HN,17 specific to the LN,and 7 were stable across *** introgressed fragment of *** generally had a negative effect on the trait,except for QTLs for fruit dry matter,for fruit length on chromosome 10 under the HN,and for fruit pedicel length on chromosome 9 under the *** increase over AN-S-26 of the allele of *** for the QTLs detected ranged between-73.98% and 26.03% in HN and-73.67%and 34.43% in *** findings provide useful tools fo

关键词： Solanum melongena Solanum incanum Wild relatives N fertilization Abiotic stress QTL

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Animal models used to study direct peripheral nerve repair: a systematic review

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Neural Regeneration Research 2020年第3期15卷 491-502页

作者： Francisco Javier Vela Guadalupe martínez-Chacón Alberto Ballestín JoséLuis Campos Francisco Miguel Sánchez-Margallo elena Abellán Department of Microsurgery Jesús Usón Minimally Invasive Surgery CentreCáceresSpain Scientific Director Jesús Usón Minimally Invasive Surgery CentreCáceresSpain

Objective:Peripheral nerve repair is required after traumatic *** common condition represents a major public health problem *** after nerve repair depends on several factors,including the severity of the injury,the nerve involved,and the surgeon’s technical *** the precise microsurgical repair of nerve lesions,adequate functional recovery is not always achieved and,therefore,the regeneration process and surgical techniques are still being ***-clinical animal models are essential for this research and,for this reason,the focus of the present systematic review(according to the PRISMA statement)was to analyze the different animal models used in pre-clinical peripheral nerve repair *** sources:Original articles,published in English from 2000 to 2018,were collected using the Web of Science,Scopus,and PubMed *** selection:Only preclinical trials on direct nerve repair were included in this *** articles were evaluated by the first two authors,in accordance with predefined data *** measures:The primary outcomes included functional motor abilities,daily activity and regeneration *** outcomes included coaptation technique and animal ***:This review yielded 267 articles,of which,after completion of the screening,49 studies were *** were 1425 animals in those 49 studies,being rats,mice,guinea pigs,rabbits,cats and dogs the different pre-clinical *** nerves used were classified into three groups:head and neck(11),forelimb(8)and hindlimb(30).The techniques used to perform the coaptation were:microsuture(46),glue(12),laser(8)and mechanical(2).The follow-up examinations were histology(43),electrophysiological analysis(24)and behavioral observation(22).Conclusion:The most widely used animal model in the study of peripheral nerve repair is the *** animal models are also used but the cost-benefit of the rat model provides several strengths over the ***

关键词： nerve microsurgery peripheral nerve regeneration repair reconstruction direct nerve repair animal model coaptation PRISMA systematic review

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“Anti-Michael” and Michael Additions in the Reactions of 2-Arylmethyliden-1,3-Indandiones with 2-Aminothiophenol

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International Journal of Organic Chemistry 2017年第1期7卷 57-81页

作者： Jessica J. Sá nchez Garcí a Alberto D. Herná ndez-Suzan elena martí nez-klimova Marcos Flores-Alamo Teresa Ramí rez Apan elena I. klimova Departamento de Quí mica Orgá nica Universidad Nacional Aut&oacute noma de Mé xico Facultad de Qu&iacute mica Cd. Universitaria Ciudad de M&eacute xico M&eacute xico Instituto de Quí mica Universidad Nacional Aut&oacute noma de Mé xico Facultad de Qu&iacute mica Cd. Universitaria Ciudad de M&eacute xico M&eacute xico

A novel 2-indano[2,3b]-2-ferrocenyl- and 2-indano[2,3b]-2-(p-methoxy-phenyl)[1,5]benzo-2,5-dihydrothiazepine 5a,b (addition Michael/cyclization) (~30.32%), indano[2,3b]-2-ferrocenyl- and 2-(p-methoxyphenyl)[1,4] benzothiazine 4a,b (addition “anti-Michael”/cyclization) (~45.43%), respectively, were obtained by the condensation of 2-ferrocenyl-and 2-(p-methoxy-phenyl)methyliden-1,3-indandiones 1a,b with o-aminothiophenol 2 in the presence of AcOH and HCl. A new “anti-Michael” addition reaction of 1,4-bis-heteronucleophile 2 into 2-arylmethyliden-1,3-indandiones was reported. As a result of this reaction the product 1a,b was obtained. The structures of the resultant compounds were elucidated by IR, 1H and 13C NMR spectroscopy, mass spectrometry, elemental and X-ray diffraction analysis. The in vitro antitumor activity of the obtained products was researched using the following human cancer cell lines: glioblastoma (CNS U-251), prostatic adenocarcinoma (PC-3), chronic myelogenous leukemia (K562), colorectal adenocarcinoma (HCT-15), mammary adenocarcinoma (MCF-7), and small cell lung cancer (SKLU) and the sulforhodamine B (SRB) method. Among these new compounds some thiazine and thiazepine derivatives showed compelling in vitro antitumor effects on cell lines K-562, HCT-15, SKLU-1 and MCF-7.

关键词： Ferrocene Addition “Anti-Michael” Reaction Cyclization 1 5-Thiazepines 4-Thiazines Antitumor Cell Lines

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Left Nostril Agenesis in a Fetus with VACTERL Association: A Case Report

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Open Journal of Obstetrics and Gynecology 2023年第4期13卷 693-698页

作者： martha martínez-Gómez elena Satorres-Pérez Alicia martínez-Varea Department of Obstetrics and Gynaecology La Fe University and Polytechnic Hospital Valencia Spain

VACTERL association represents a rare condition with a broad spectrum of coexisting congenital abnormalities. Although a multifactorial origin has been described, the etiology is still unclear. Prenatal diagnosis can be challenging, as specific characteristics may be difficult to be determined before birth. This case report describes the finding of multiple congenital abnormalities in a male fetus at 30 weeks of gestation. The most notable findings were the presence of duodenal stenosis, esophageal atresia with distal tracheoesophageal fistula (type 3), interatrial septal communication foramen ovale, and left nostril and choana agenesis. After birth and making a broad differential diagnosis, all these characteristics oriented the diagnosis towards the VACTERL association. To the best of our knowledge, no cases of VACTERL association and unilateral nostril and choana agenesis have been previously described.

关键词： VACTERL Association Nostril Agenesis Fetal Ultrasound Fetal MRI

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Hepatotoxicity induced by acute and chronic paracetamol overdose in children: Where do we stand?

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World Journal of Pediatrics 2017年第1期13卷 76-83页

作者： Hoi Yan Tong Nicolás Medrano Alberto Manuel Borobia JoséAntonio Ruiz Ana María martínez Julia martín Manuel Quintana Santos Garcfa Antonio Jos6 Carcas elena Ramirez Department of Clinical Pharmacology Hospital Universitario La PazIdiPAZSchool of MedicineUniversidad Autónoma de MadridMadridSpain Pediatric Emergency Department Hospital Universitario La PazIdiPAZMadridSpain General Emergency Department Hospital Universitario La PazIdiPAZMadridSpain

Background:There are few data Oll hepatotoxicity induced by acute or chronic paracetamol poisoning in the pediatric *** poisoning data can reveal the weakn嗍ofparacetamol poisoning management ***:We retrospectively studied the patients of less than 18 years old with measurable paracetamol levels,who were brought to the emergency department(ED)of La Paz University Hospital,Madrid,Spain,for suspected paracetamol overdoses between 2005 and 2010.

关键词： acute liver failure hepatotoxicity paracetamol poisoning

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Healthy diet,depression and quality of life:A narrative review of biological mechanisms and primary prevention opportunities

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World Journal of Psychiatry 2021年第11期11卷 997-1016页

作者： Octavio Pano elena H martínez-Lapiscina Carmen Sayón-Orea Miguel Angel martinez-Gonzalez Jose Alfredo martinez Almudena Sanchez-Villegas Preventive Medicine and Public Health University of NavarrePamplona 31008Spain Department of Neurology Center of Neuroimmunology Hospital Clinic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi SunyerBarcelona 08036Spain Department of Preventive Medicine and Public Health University of NavarraPamplona 31008Spain IdiSNA Navarra Institute for Health ResearchPamplona 31008Spain Department of Public Health Navarra Institute of Public Health and EpidemiologyPamplona 31003Spain CIBER Pathophysiology of Obesity and Nutrition Institute of Health Carlos IIIMadrid 28049Spain Department of Nutrition Harvard T.H.Chan School of Public HealthBostonMA 02115United States Department of Food Sciences and Physiology University of NavarrePamplona 31008Spain Precision Nutrition and Cardiometabolic Health Program IMDEA Food InstituteMadrid 28049Spain Department of Clinical Sciences University of Las Palmas Gran CanariaLas Palmas Gran Canaria 35080Spain

Unipolar depressive disorder(UDD)affects more than 264 million people worldwide and was projected well before the severe acute respiratory syndrome coronavirus 2 pandemic to be the leading cause of disability-adjusted life years lost in *** is imperative for leading economies to implement preventive strategies targeted towards UDD,given consistent policies are currently *** established similarities between the aetiological hypotheses of depression and cardiometabolic diseases are shifting paradigms within this *** is believed that dietary practices could potentially reduce the incidence of depression;similar to their effects on ***,the aim of this review was to compile current evidence on healthy dietary patterns as suitable contributors towards primary prevention strategies against *** of the well-known biological mechanisms behind depression have been positively associated with healthful diets and dietary patterns to varying ***,a common factor of UDD is the production and overall effects of inflammatory cytokines,such as interleukin-6,tumor necrosis factor-α,and Creactive *** compounds have been associated with depressive symptoms,disturbances in neuroendocrine function,leaky gut,monoamine activity and brain function,while also being key factors in the development of cardiometabolic *** Mediterranean diet(MD)in particular,is well supported by first-level evidence regarding its preventive qualities against metabolic and cardiovascular diseases and thus considered a model for healthy eating by various *** one of the few clinical trials investigating these associations,the PREDIMED trial,individuals with diabetes assigned to a MD supplemented with mixed tree nuts experienced a 41%relative risk reduction for developing ***,there is a need to include health related quality of life as an indicator of physical and mental well-being,considering its putative associations

关键词： Depression Nutrition Mediterranean Quality of life Primary prevention Epidemiology

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Chronic pain, posttraumatic stress disorder, and opioid intake: A systematic review

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World Journal of Clinical Cases 2019年第24期7卷 4254-4269页

作者： Alicia E López-martínez ángela Reyes-Pérez elena Rocío Serrano-Ibá?ez Rosa Esteve Carmen Ramírez-Maestre Facultad de Psicología Instituto de Investigaciones Biomédicas (IBIMA)Universidad de Málaga

BACKGROUND The literature suggests that there is a high degree of co-occurrence between chronic pain and posttraumatic stress disorder(PTSD). An association has been found between PTSD and substance abuse. PTSD is a severe disorder that should be taken into account when opioids are prescribed. It has been found that the prevalence of opioid use disorder(OUD) in chronic pain patients is higher among those with PTSD than those without this *** To perform a systematic review on the association between PTSD, chronic noncancer pain(CNCP), and opioid intake(i.e., prescription, misuse, and abuse).METHODS We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Patient, Intervention,Comparator, and Outcomes(PICOS) criteria were formulated a priori in the protocol of the systematic review. A search was conducted of the PROSPERO database. In March 2019, searches were also conducted of 5 other databases:Pub Med, MEDLINE, Psyc INFO, Web of Science, and PILOTS. The Scottish Intercollegiate Guidelines Network checklist for cohort studies was used to assess the selected studies for their methodological quality and risk of bias. Each study was evaluated according to its internal validity, participant sampling,confounding variables, and the statistical *** A total of 151 potentially eligible studies were identified of which 17 were retained for analysis. Only 10 met the selection criteria. All the studies were published between 2008 and 2018 and were conducted in the United States. The eligible studies included a total of 1622785 unique participants. Of these, 196516 had comorbid CNCP and PTSD and were consuming opiates. The participants had a cross-study mean age of 35.2 years. The majority of participants were men(81.6%). The most common chronic pain condition was musculoskeletal pain:back pain(47.14% across studies;range: 16%-60.6%), arthritis and joint pain(31.1%;range: 18%-67.5%), and

关键词： Posttraumatic stress disorder Chronic pain Opioid prescription Opioid misuse Opioid abuse

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Tax avoidance and earnings management:a neural network approach for the largest European economies

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Financial Innovation 2023年第1期9卷 558-582页

作者： Francisco J.Delgado elena Fernández‑Rodríguez Roberto García‑Fernández Manuel Landajo Antonio martínez‑Arias Department of Economics Faculty of Economics and BusinessUniversity of OviedoAvda.del CristoS/N33071 OviedoSpain Department of Accounting Faculty of Economics and BusinessUniversity of OviedoAvda.del CristoS/N33071 OviedoSpain Department of Applied Economics Faculty of Economics and BusinessUniversity of OviedoAvda.del CristoS/N33071 OviedoSpain

In this study,we investigate the relationship between tax avoidance and earnings management in the largest five European Union economies by using artificial neural network *** methodology allows us to deal with nonlinearities detected in the data,which is the principal contribution to the previous *** ana-lyzed Compustat data for Germany,the United Kingdom,France,Italy,and Spain for the 2006–2015 period,focusing on discretionary *** considered three tax avoidance measures,two based on the effective tax rate(ETR)and one on book-tax differences(BTD).Our results indicate the presence of nonlinear patterns and a posi-tive,statistically significant relationship between discretionary accruals and both ETR indicators implying that when companies resort to earnings management,a larger tax-able income—and thus higher ETR and lesser tax avoidance–would ***,as also highlighted by the fact that discretionary accruals do not appear to affect BTD,our evidence does not suggest that companies are exploiting tax manipulation to reduce their tax payments;thus,the gap between accounting and taxation seems largely unaf-fected by earnings management.

关键词： Tax avoidance Earnings management Artificial neural networks European Union

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