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A tumor-associated heparan sulfate-related glycosaminoglycan promotes the generation of functional regulatory T cells

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Cellular & Molecular Immunology 2023年第12期20卷 1499-1512页

作者： Leticia Martín-Cruz Marcos Viñuela Ioanna Kalograiaki Alba Angelina Paola Oquist-Phillips Irene Real-Arévalo francisco javier Cañada JoséIgnacio Tudela Luis Moltó Jesús Moreno-Sierra JoséLuis Subiza Oscar Palomares Department of Biochemistry and Molecular Biology School of ChemistryComplutense University of MadridMadridSpain Inmunotek Alcaláde HenaresMadridSpain Fundación Investigación Hospital Clínico San Carlos Martin Lagos s/n28040MadridSpain Centro de Investigaciones Biológicas Margarita Salas CSICRamiro de Maetzu 928040MadridSpain CIBER de Enfermedades Respiratorias(CIBERES)Avda Monforte de Lemos3-528029MadridSpain Servicio de Urología Hospital Clínico San CarlosUniversidad Complutense de MadridMartín Lagos s/n28040MadridSpain

Functional Tregs play a key role in tumor development and progression,representing a major barrier to anticancer *** mechanisms by which Tregs are generated in cancer and the influence of the tumor microenvironment on these processes remain incompletely ***,by using NMR,chemoenzymatic structural assays and a plethora of in vitro and in vivo functional analyses,we demonstrate that the tumoral carbohydrate A10(Ca10),a cell-surface carbohydrate derived from Ehrlich’s tumor(ET)cells,is a heparan sulfate-related proteoglycan that enhances glycolysis and promotes the development of tolerogenic features in human ***10-stimulated human DCs generate highly suppressive Tregs by mechanisms partially dependent on metabolic reprogramming,PD-L1,IL-10,and ***10 also reprograms the differentiation of human monocytes into DCs with tolerogenic *** solid ET-bearing mice,we found positive correlations between Ca10 serum levels,tumor size and splenic Treg *** of isolated Ca10 also increases the proportion of splenic Tregs in tumor-free ***,we provide evidence supporting the presence of a circulating human Ca10 counterpart(Ca10H)and show,for the first time,that serum levels of Ca10H are increased in patients suffering from different cancer types compared to healthy *** note,these levels are higher in prostate cancer patients with bone metastases than in prostate cancer patients without ***,we reveal novel molecular mechanisms by which heparan sulfate-related structures associated with tumor cells promote the generation of functional Tregs in *** discovery of this novel structural-functional relationship may open new avenues of research with important clinical implications in cancer treatment.

关键词： Tumoral carbohydrate A10 Heparan sulfate-related proteoglycan Cancer immunology Dendritic cell Regulatory T cell

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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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Relationship between HSP90a, NPC2 and L-PGDS proteins to boar semen freezability

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Journal of Animal Science and Biotechnology 2017年第3期8卷 582-591页

作者： Julián Valencia Germán Gómez Walter López Henry Mesa francisco javier Henao Universidad de Caldas Faculty of Agricultural Sciences A.A. 275 Manizales Caldas Colombia

Background： The purpose of this study was to determine the association of three proteins involved in sperm function on the freezability of porcine semen： the heat shock protein 90 alpha（HSP90a）, the Niemann-Pick disease type C2 protein（NPC2）, and lipocalin-type prostaglandin D synthase（L-PGDS）.Six adult boars（each boar was ejaculated three times, 18 in total） were classified by freezability based on the percentage of functionally competent sperm. The male semen with highest freezability（MHF） and the male semen with lowest freezability（MLF） were centrifuged immediately after collection to separate seminal plasma and spermatozoa to make four possible combinations of these two components and to incubate them for 3 h,adjusting the temperature to 17 °C, to freeze them afterwards. The quantification of proteins was performed in two stages： at zero and at 3 h after incubation of the four ***： The spermatozoa × incubation time（IT） interaction only had effect（P 〈 0.01） on HSP90 a levels; this protein increased in seminal plasma, after 3 h of incubation, in larger quantity（P 〈 0.05） in combinations with MLF spermatozoa. In relation with the NPC2 protein, two isoforms of 16 and 19 kDa were identified. The 19 kDa isoform was affected（P 〈 0.01） only by the seminal plasma × IT interaction, with superior values（P 〈 0.01） both at zero and three hours of incubation, in the combinations with MHF seminal plasma; and 16 kDa isoform was affected（P 〈 0.01） only by the IT with reduction after 3 h of incubation. The levels of L-PGDS was affected（P 〈 0.01）only by the spermatozoa × IT interaction, which reduced（P 〈 0.01） in combinations with MLF spermatozoa after 3 h of ***： It is possible to consider that the three proteins evaluated were associated with freezability of boar semen due, especially, to the fact that mixtures with MLF spermatozoa showed greater increase levels of the HSP90 a protein and reduction of L-PGDS in plasma. In addition, the seminal

关键词： Boar freezability HSP90a L-PGDS NPC2 Semen preservation Seminal plasma

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The ρ-variation of the Hermitian Riesz Transform

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Acta Mathematica Sinica,English Series 2010年第10期26卷 1827-1838页

作者： Raquel CRESCIMBENI francisco javier MARTíN-REYES Alberto DE LA TORRE José L.TORREA Departamento de Matemática Universidad Nacional del Comahue Facultad de Economía y Administración Departamento de Análisis Matemático Facultad de Ciencias Universidad de Málaga Facultad de Ciencias Universidad Autónoma de Madrid ICMAT-CSIC-UAM-UCM-UC3M

In this paper we prove the behaviour in weighted Lp spaces of the oscillation and variation of the Hilbert transform and the Riesz transform associated with the Hermite operator of dimension 1. We prove that this operator maps LP（R, w（x）dx） into itself when w is a weight in the Ap class for 1 〈 p 〈 ∞. For p = 1 we get weak type for the A1 class. Weighted estimated are also obtained in the extreme case p = ∞.

关键词： Oscillation-p-variation-singular integral-Hermite operator

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ON CONSERVATIVE APPROXIMATION BY LINEAR POLYNOMIAL OPERATORS AN EXTENSION OF THE BERNSTEIN'S OPERATOR

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Analysis in Theory and Applications 1995年第1期11卷 62-71页

作者： francisco-javier Munoz-Delgado Victoriano Ramirez-Gonzalez Paul Sablonniere Universidad de Jaen SpainUniversidad de Granada SpainInstitut National des Sciences Appliquees France

In this work we slwly linear polynomial operators preserving some consecutive i-convexities and leaving in-verant the polynomtals up to a certain degree. First we study the existence of an incompatibility between the conservation of cenain i-cotivexities and the invariance of a space of polynomials. Interpolation properties are obtained and a theorem by Berens and DcVore about the Bernstein's operator ts extended. Finally, from these results a genera'ized Bernstein's operator is obtained.

关键词： LPO ON CONSERVATIVE APPROXIMATION BY LINEAR POLYNOMIAL OPERATORS AN EXTENSION OF THE BERNSTEIN’S OPERATOR

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Discovery of gargantulides B and C,new 52-membered macrolactones from Amycolatopsis *** absolute stereochemistry of the gargantulide family

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Organic Chemistry Frontiers 2022年第2期9卷 462-470页

作者： Daniel Carretero-Molina francisco javier Ortiz-López Tetiana Gren Daniel Oves-Costales Jesús Martín Fernando Román-Hurtado Tue Sparholt Jorgensen Mercedes de la Cruz Caridad Díaz Francisca Vicente Kai Blin Fernando Reyes Tilmann Weber Olga Genilloud Fundación MEDINA Centro de Excelencia en Investigación de Medicamentos Innovadores en AndalucíaAvda.del Conocimiento 3418016 ArmillaGranadaSpain The Novo Nordisk Foundation Center for Biosustainability Technical University of DenmarkKemitorvetbuilding 2202800 Kgs.LyngbyDenmark

Gargantulides B and C,two new and highly complex 52-membered glycosylated macrolactones,were isolated from Amycolatopsis *** CA-230715 during an antibacterial screening *** structures of these giant macrolides were elucidated by 2D NMR spectroscopy and shown to be related to gargantulide A,although containing additional β-glucopyranose and/orα-arabinofuranose monosaccharides separately attached to their *** sequencing allowed the identification of a strikingly large 216 kbp biosynthetic gene cluster,among the largest type Ⅰ PKS clusters described so far,and the proposal of a previously unreported biosynthetic pathway for gargantulides *** absolute configurations of gargantulides B and C were assigned based on a combination of NMR and bioinformatics analysis of ketoreductase and enoylreductase domains within the multimodular type Ⅰ *** addition,the absolute stereochemistry of gargantulide A has now been revised and *** B and C display potent antibacterial activity against a set of drug-resistant Gram-positive bacteria and moderate activity against the clinically relevant Gram-negative pathogen Acinetobacter baumannii.

关键词： absolute membered backbone

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Amyotrophic lateral sclerosis: a complex syndrome that needs an integrated research approach

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Neural Regeneration Research 2019年第2期14卷 193-196页

作者： javier Riancho francisco J.Gil-Bea Ana Santurtun Adolfo López de Munaín Service of Neurology Hospital Sierrallana-Idival CIBERNED (Center for Networked Biomedical Research on Neurodegenerative Diseases Ministry of Economy and Competitiveness Institute Carlos Ⅲ) Neurosciences Area Institute Biodonostia Department of Physiology and Pharmacology University of Cantabria-Idival Department of Neurology University Hospital Donostia Department of Neurosciences University of the Basque Country Universidad País Vasco-Euskal Herria Unibertsitatea

Amyotrophic lateral sclerosis, the most common neurodegenerative disease affecting motor neurons, lacks an effective treatment. A small fraction of amyotrophic lateral sclerosis cases have a familial origin, related to mutations in causative genes, while the vast majority of amyotrophic lateral sclerosis cases are considered to be sporadic, resulting from the interaction between genes and environmental factors in predisposed individuals. During the past few years, dozens of drugs have been postulated as promising strategies for the disease after showing some beneficial effects in preclinical cellular and murine models. However, the translation into clinical practice has been largely unsuccessful and the compounds failed when were tested in clinical trials. This might be explained, at least partially, by the enormous complexity of the disease both from clinico-epidemiological and a pathogenic points of view. In this review, we will briefly comment on the complexity of the disease focusing on some recent findings, and we will suggest how amyotrophic lateral sclerosis research might be reoriented to foster the advance in the diagnostic and therapeutic questions.

关键词： amyotrophic lateral sclerosis ALS environment epidemiology genes phenotype therapy

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Preoperative calculation of angles of vision and working area in laparoscopic surgery to treat a giant hiatal hernia

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World Journal of Gastrointestinal Surgery 2021年第12期13卷 1638-1650页

作者： francisco javier Perez Lara Rogelio Zubizarreta Jimenez francisco javier Moya Donoso Jose Manuel Hernández Gonzalez Tatiana Prieto-Puga Arjona Arturo del Rey Moreno Maria Pitarch Martinez Surgery Service Antequera HospitalRincón de la Victoria 29730MálagaSpain DOXA Microfluidics Rincon de la Victoria 29738MálagaSpain

BACKGROUND Giant hiatal hernias still pose a major challenge to digestive surgeons,and their repair is sometimes a highly complex *** is usually performed by laparoscopy,while the role of the thoracoscopic approach has yet to be clearly *** To preoperatively detect patients with a giant hiatal hernia in whom it would not be safe to perform laparoscopic surgery and who,therefore,would be candidates for a thoracoscopic *** In the present study,using imaging test we preoperatively simulate the field of vision of the camera and the working area(instrumental access)that can be obtained in each patient when the laparoscopic approach is *** From data obtained,we can calculate the access angles that will be obtained in a preoperative computerised axial tomography coronal section,according to the location of the *** also provide the formula for performing the angle calculations If the trocars are placed in loss common situations,thus enabling us to determine the visibility and manoeuvrability for any position of the *** The working area determines the cases in which we can operate safely and those in which certain areas of the hernia cannot be accessed,which is when the thoracoscopic approach would be safer.

关键词： Hiatal hernia Angles Approach Laparoscopy Thoracoscopy

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Microbial Degradation of Organophosphate Pesticides： A Review

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Pedosphere 2018年第2期28卷 190-208页

作者： Shardendu KUMAR Garima KAUSHIK Mohd Ashraf DAR Surendra NIMESH Ulrico javier LOPEZ-CHUKEN Juan francisco VILLARREAL-CHIU Department of Environmental Science School of Earth Sciences Central University of Rajasthan Ajmer 305817 (India) Department of Biotechnology School of Life Sciences Central University of Rajasthan Ajmer 305817 (India) Laboratorio de InvestigaciSn en Ciencias Ambientales Facultad de Cieneias Quimicas Universidad AutSnoma de Nuevo León Nuevo LeSn 66455 (Mexico) Laboratorio de Biotecnologla Facultad de Ciencias Qulmicas Universidad AutSnoma de Nuevo LeSn Nuevo Ledn 66455 (Mexico)

Pesticides have become an inevitable part of the modern environment as they are widely used in agriculture,household,and public health sectors and,hence,are extensively distributed throughout most ***,organophosphate pesticides are the most commercially favored group of pesticides,with large application areas all over the *** on their fate,these organophosphorus compounds may become bioavailable for microbial *** microbes,such as Aspergillus,Pseudomonas,Chlorella,and Arthrobacter,are capable of coupling a variety of physical and biochemical mechanisms for the degradation of organophosphate pesticides,including adsorption,hydrolysis of P–O alkyl and aryl bonds,photodegradation,and enzymatic ***,such as esterase,diisopropyl fluorophosphatase,phosphotriesterase,somanase,parathion hydrolase,and paraoxonase,have been isolated from microbes to study and understand the catabolic pathways involved in the biotransformation of these xenobiotic *** review highlights various aspects of biodegradation of organophosphate pesticides along with biological and molecular characterization of some organophosphate pesticide-degrading bacteria.

关键词： biodegradation enzymes insecticide metabolic pathways pesticide-degrading bacteria organophosphorus compound xenobiotics

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Characteristics and in-hospital mortality of elderly patients with heart failure in Spanish hospitals

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Journal of Geriatric Cardiology 2023年第4期20卷 247-255页

作者： Alberto Esteban-Fernández Manuel Anguita-Sánchez Juan Luis Bonilla-Palomas María Anguita-Gámez María García JoséLuis Bernal Náyade Del Prado Cristina Fernández-Pérez Julián Pérez-Villacastin Juan JoséGómez-Doblas francisco javier Elola Cardiology Department Hospital Universitario Severo OchoaMadridSpain Cardiology Department Hospital Universitario Reina SofíaCórdobaSpain Cardiology Department Hospital San Juan de la CruzÚbedaSpain Cardiology Department Hospital Clínico San CarlosMadridSpain Fundación Instituto para la Mejora de la Asistencia Sanitaria MadridSpain Management Control Department Hospital Universitario 12 de OctubreMadridSpain Department of Preventive Medicine Área Sanitaria de Santiago de Compostela y BarbanzaInstituto de Investigación de SantiagoSantiago de CompostelaSpain Cardiology Department Hospital Universitario Virgen de la VictoriaMálagaSpain

BACKGROUND The prevalence of heart failure(HF)increases with age,and it is one of the leading causes of hospitalization and death in older ***,there are little data on in-hospital mortality in patients with HF≥75 years in *** A retrospective analysis of the Spanish Minimum Basic Data Set was performed,including all HF episodes discharged from public hospitals in Spain between 2016 and *** was performed using the International Classification of Diseases,10th ***≥75 years with HF as the principal diagnosis were *** calculated:(1)the crude in-hospital mortality rate and its distribution according to age and sex;(2)the risk-standardized in-hospital mortality ratio;and(3)the association between in-hospital mortality and the availability of an intensive cardiac care unit(ICCU)in the *** We included 354,792 HF episodes of patients over 75 *** mean age was 85.2±5.5 years,and 59.2%of patients were *** most frequent comorbidities were renal failure(46.1%),diabetes mellitus(35.5%),valvular disease(33.9%),cardiorespiratory failure(29.8%),and hypertension(26.9%).In-hospital mortality was 12.7%,and increased with age[odds ratio(OR)=1.07,95%CI:1.07–1.07,P<0.001]and was lower in women(OR=0.96,95%CI:0.92–0.97,P<0.001).The main predictors of mortality were the presence of cardiogenic shock(OR=19.5,95%CI:16.8–22.7,P<0.001),stroke(OR=3.5,95%CI:3.0–4.0,P<0.001)and advanced cancer(OR=2.6,95%CI:2.5–2.8,P<0.001).In hospitals with ICCU,the in-hospital risk-adjusted mortality tended to be lower(OR=0.85,95%CI:0.72–1.00,P=0.053).CONCLUSIONS In-hospital mortality in patients with HF≥75 years between 2016 and 2019 was 12.7%,higher in males and elderly *** main predictors of mortality were cardiogenic shock,stroke,and advanced *** was a trend toward lower mortality in centers with an ICCU.

关键词： patients mortality diagnosis

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