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Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism:WLB-73502,an analgesic with improved efficacy and safety profile compared to strong opioids

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Acta Pharmaceutica Sinica B 2023年第1期13卷 82-99页

作者： Alba Vidal-Torres Begoña Fernández-Pastor mónica García Eva Ayet Anna Cabot Javier Burgueño Xavier monroy Bertrand Aubel Xavier Codony luz Romero Rosalía Pascual maria Teresa Serafini Gregorio Encina Carmen Almansa Daniel Zamanillo manuel merlos Josémiguel Vela WeLab Barcelona Parc Cientific de BarcelonaBarcelona 08028Spain

Opioids are the most effective painkillers,but their benefit-risk balance often hinder their therapeutic ***-73502 is a dual,bispecific compound that binds sigma-1(S1R)and mu-opioid(mOR)***-73502 is an antagonist at the *** behaved as a partial mOR agonist at the G-protein pathway and produced no/unsignificantβ-arrestin-2 recruitment,thus demonstrating low intrinsic efficacy on mOR at both signalling *** its partial mOR agonism,WLB-73502exerted full antinociceptive efficacy,with potency superior to morphine and similar to oxycodone against nociceptive,inflammatory and osteoarthritis pain,and superior to both morphine and oxycodone against neuropathic ***-73502 crosses the blood-brain barrier and binds brain S1R and mOR to an extent consistent with its antinociceptive *** to morphine and oxycodone,tolerance to its antinociceptive effect did not develop after repeated 4-week ***,contrary to opioid comparators,WLB-73502 did not inhibit gastrointestinal transit or respiratory function in rats at doses inducing full efficacy,and it was devoid of proemetic effect(retching and vomiting)in ferrets at potentially effective ***-73502 benefits from its bivalent S1R antagonist and partial mOR agonist nature to provide an improved antinociceptive and safety profile respect to strong opioid therapy.

关键词： WLB-73502 Sigma-1 receptor mu-opioid receptor Biased agonist Analgesic activity Chronic pain Neuropathic pain Safety

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myo-inositol reduces β-catenin activation in colitis

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World Journal of Gastroenterology 2017年第28期23卷 5115-5126页

作者： Emily m Bradford Corey A Thompson Tatiana Goretsky Guang-Yu Yang luz m Rodriguez Linheng Li Terrence A Barrett Division of Gastroenterology Department of Internal MedicineUniversity of Kentucky Department of Internal medicine Northwestern University Feinberg School of Medicine Division of Cancer Research National Cancer InstituteDCP/GOCRGBethesda Department of Surgery Walter Reed National Military Medical Center Department of Pathology and Laboratory medicine University of Kansas School of Medicine and Stowers Institute for Medical Research

AIm To assess dietary myo-inositol in reducing stem cell activation in colitis,and validate pβ-cateninS^(552) as a biomarker of recurrent *** We examined the effects of dietary myo-inositol treatment on inflammation,pβ-cateninS^(552) and p Akt levels by histology and western blot in IL-10-/-and dextran sodium sulfate-treated colitic mice. Additionally,we assessed nuclear pβ-cateninS^(552) in patients treated with myo-inositol in a clinical trial,and in patients with and without a history of colitis-induced *** In mice,pβ-cateninS^(552) staining faithfully reported the effects of myo-inositol in reducing inflammation and intestinal stem cell activation. In a pilot clinical trial of myo-inositol administration in patients with a history of low grade dysplasia(LGD),two patients had reduced numbers of intestinal stem cell activation compared to the placebo control patient. In humans,pβ-cateninS^(552) staining discriminated ulcerative colitis patients with a history of LGD from those with benign *** Enumerating crypts with increased numbers of pβ-cateninS^(552)-positive cells can be utilized as a biomarker in colitis-associated cancer chemoprevention trials.

关键词： Chemoprevention 发育异常 Biomarker 干细胞联系大肠炎的癌症

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Toxicity assessment of polyethylene microplastics in combination with a mix of emerging pollutants on Physalaemus cuvieri tadpoles

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Journal of Environmental Sciences 2023年第5期127卷 465-482页

作者： Amanda Pereira da Costa Araújo Thiarlen marinho da luz mohamed Ahmed Ibrahim Ahmed mir mohammad Ali md.mostafizur Rahman Bojan Nataraj Daniela de melo e Silva DamiàBarceló Guilherme malafaia Post-Graduation Program in Environmental Sciences Federal University of GoiásGoianiaGO 74690-970Brazil Laboratory of Toxicology Applied to the Environment Goiano Federal InstituteUrutaíGO 75790-000Brazil Plant Protection Department Faculty of AgricultureAssiut UniversityAssiut 71526Egypt Department of Aquaculture Faculty of FisheriesAquaculture&Marine ScienceSher-e-Bangla Agricultural UniversityDhaka 1207Bangladesh Department of Environmental Sciences Jahangirnagar UniversitySavar 1342Bangladesh Unit of Toxicology Department of ZoologySchool of Life SciencesBharathiar UniversityCoimbatore 641046India Laboratory of Environmental mutagenesis Federal University of GoiásGoianiaGO 74690-970Brazil Catalan Institute for Water Research(ICRA-CERCA) H_(2)O BuildingScientific and Technological Park of the University of GironaEmili Grahit 101Girona 17003Spain Water and Soil Quality Research Group Department of Environmental ChemistryInstitute of Environmental Assessment and Water Research(IDAEA-CSIC)JordiGirona 1826Barcelona 08034Spain Post-Graduation Program in Conservation of Cerrado Natural Resources Goiano Federal InstituteUrutaíGO 75790-000Brazil Post-Graduation Program in Ecology Conservationand BiodiversityFederal University of UberlandiaUberlandiaMG 38400-902Brazil Post-Graduation Programa in Biotechnology and Biodiversity Federal University of GoiásGoianiaGO 74605-050Brazil

Studies in recent years have shown that aquatic pollution by microplastics(mPs)can be considered to pose additional stress to amphibian ***,our knowledge of how mPs affect amphibians is very rudimentary,and even more limited is our understanding of their effects in combination with other emerging ***,we aimed to evaluate the possible toxicity of polyethylene mPs(PE-mPs)(alone or in combination with a mix of pollutants)on the health of Physalaemus cuvieri *** 30 days of exposure,multiple biomarkers were measured,including morphological,biometric,and developmental indices,behavioral parameters,mutagenicity,cytotoxicity,antioxidant and cholinesterase responses,as well as the uptake and accumulation of PE-mPs in *** on the results,there was no significant change in any of the parameters measured in tadpoles exposed to treatments,but induced stress was observed in tadpoles exposed to PE-mPs combined with themixture of pollutants,reflecting significant changes in physiological and biochemical *** principal component analysis(PCA)and integrated biomarker response(IBR)assessment,effects induced by pollutants in each test group were distinguished,confirming that the exposure of *** tadpoles to the PE-mPs in combination with a mix of emerging pollutants induces an enhanced stress response,although the uptake and accumulation of PE-mPs in these animalswas ***,our study provides newinsight into the danger to amphibians of mPs coexisting with other pollutants in aquatic environments.

关键词： Amphibians Environmental toxicology micropollutants Emerging pollutants Aquatic pollution Biomarkers

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Photoluminescent Tb^(3+)-based metal-organic framework as a sensor for detection of methanol in ethanol fuel

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Journal of Rare Earths 2019年第3期37卷 225-231页

作者： Ramon R.F.Fonseca Rafael D.L.Gaspar Ivo m.Raimundo Jr. Priscilla P.luz Department of Chemistry Federal University of Espírito Santo Institute of Chemistry University of Campinas

The sensing capability of a Tb^(3+)-metal-organic framework, based on its photoluminescence, was used for detection of methanol in ethanol fuel. It was synthesized using terbium and trimesic acid as a metal ion center and ligand, respectively. Powder X-ray diffraction, infrared spectroscopy, thermogravimetric analysis and scanning electron microscopy were employed to characterize the synthesized mOF-76 structural features. According to the results, mOF-76 was successfully obtained with minor synthetic modification and its activated form(named TbTmA) was tested as a sensor for methanol. Tb^(3+) luminescence intensity increases as the methanol concentration in ethanol fuel also increases and the water content does not affect this response. Our findings indicate TbTmA as an appropriate sensor for evaluating ethanol fuel adulteration by methanol addition above the allowed limit.

关键词： Lanthanide metal-organic frameworks Luminescence Ethanol fuel Sensor Adulteration

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Acoustic contamination assessment during the transition between the COVID-19 restrictions and reactivation:A exploratory analysis in Guayaquil

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Geography and Sustainability 2023年第2期4卷 138-149页

作者： Andrés Velastegui-montoya Geancarlo Guerrero-cabrera Sandra Gonzalez-Camba Yadira Jaramillo-Lindao Ricardo murillo-Portillo J.Hidalgo-Crespo Luis Encalada-Abarca Centro de Investigación y Proyectos Aplicados a las Ciencias de la Tierra(CIPAT) ESPOL Polytechnic UniversityP.O.Box 09-01-5863GuayaquilEcuador Facultad de Ingeniería en Ciencias de la Tierra(FICT) ESPOL Polytechnic UniversityP.O.Box 09-01-5863GuayaquilEcuador Geoscience Institute Federal University of Pará66075-110BelémBrazil Facultad de Ciencias Naturales y matemáticas(FCNm) ESPOL Polytechnic UniversityP.O.Box 09-01-5863GuayaquilEcuador Sciences pour la Conception l’Optimisation et la Production(G-SCOP)Centre National de la Recherche Scientifique(CNRS)UniversitéGrenoble Alpes38000GrenobleFrance Facultad de Ingeniería Industrial Universidad de Guayaquil090150GuayaquilEcuador Centre of Geographical Studies Institute of Geography and Spatial PlanningUniversity of Lisbon1600-276LisbonPortugal Universidad Espíritu Santo SamborondónEcuador

Noise pollution is becoming a critical health risk for city *** 2020,the COVID-19 pandemic forced many cities to implement several mobility *** restrictions changed human activity patterns and decreased the noise levels and noise pollution that often affect urban *** the number of infections decreased,so did the outdoor activities,influencing the population’s perception of *** paper aims to evaluate the changes in noise levels associated with mobility restrictions between 2020 and 2021 in Guayaquil,*** study used crowdsourcing with the help of smartphones and mobile applications to collect geo-referenced environmental noise *** data was used to generate noise maps in different time ***,noise level maps were created using GIS-based tools to identify the urban areas that experienced the highest noise level variation during the study *** results show that the most significant noise increase occurred at ***,when analyzing noise level changes in different urban areas,the western area of Guayaquil was the one that experienced the most significant noise level *** inform the perception of noise pollution and could potentially serve as a reference for decision-makers during the proposal of public policies that ensure a better quality of life for its citizens.

关键词： Acoustic contamination Crowdsourcing Data scrubbing Kriging Noise map

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DBD-Corona Discharge for Degradation of Toxic Gases

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Plasma Science and Technology 2007年第6期9卷 682-685页

作者： m.PACHECO-PACHECO J.PACHECO-SOTELO H.mORENO-SAAVEDRA J.A.DIAZ-GOmEZ A.mERCADO-cabrera m.YOUSFI National Institute of Nuclear Research OcoyoacacMexico Toluca Institute of Technology TolucaMexico Center of Plasma Physics and their Applications of Toulouse France

The non-thermal plasma technology is a promising technique to treat SO2 and NOx. Chemical radicals produced with this technology can remove several pollutants at atmospheric pressure in a very short period of time simultaneously. Both theoretical and experimental study on SO2 and NOx removal, by a dielectric barrier discharge （DBD） with corona effect, is presented.

关键词： DBD-corona de-NOx process de-SO2 process

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Application of two forms of silicon and their impact on the postharvest and the content of bioactive compounds in cucumber(Cucumis sativus L.)fruits

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BIOCELL 2022年第11期46卷 2497-2506页

作者： YOLANDA GONZÁLEZ-GARCÍA VALERIA FLORES-ROBLES GREGORIO CADENAS-PLIEGO ADALBERTO BENAVIDES-mENDOZA mARCELINO cabrera DE LA FUENTE ALBERTO SANDOVAL-RANGEL ANTONIO JUÁREZ-mALDONADO Departamento de Botánica Universidad Autónoma Agraria Antonio NarroSaltillo25315México maestría en Ciencias en Horticultura Universidad Autónoma Agraria Antonio NarroSaltillo25315México Centro de Investigación en Química Aplicada Saltillo25294México Departamento de Horticultura Universidad Autónoma Agraria Antonio NarroSaltillo25315México

The metabolic activity of the fruits continues even after harvest,which results in the loss of bioactive compounds,a decrease in the quality of the fruits,softening and browning,among other negative *** use of certain elements such as silicon can improve postharvest quality,since it is involved in the metabolic,physiological and structural activity of plants,moreover can increase the quality of the *** addition,nanotechnology has had a positive impact on crop yield,nutritional value,fruit quality and can improve antioxidant *** these reasons,the use of beneficial elements such as silicon in the form of nanoparticles can be a viable option to improve the characteristics of the *** the present study was evaluated the application of potassium silicate(125,250 and 500 mg L^(−1))and SiO_(2) nanoparticles(125,250 and 500 mg L^(−1))during the development of the *** results showed that the application of silicon(potassium silicate and silicon nanoparticles)increased the content of total soluble solids(up to 15.6%higher than control),titratable acidity(up to 38.8%higher than control),vitamin C(up to 78.2%higher than control),phenols(up to 22%higher than control),flavonoids(up to 64.6%higher than control),and antioxidant activity in lipophilic compounds(up to 56.2%higher than control).This study suggests that the use of silicon can be a good option to increase the content of bioactive compounds in cucumber fruits when they are applied during the development of the crop.

关键词： Fruit quality Nanotechnology Silicon nanoparticles Potassium silicate Antioxidant compounds Antioxidant capacity

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Agro-Industrial Waste as a Source of Raw material:Eggshell and Ash of Agave salmiana Useful for the Synthesis of Hydroxyapatite

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Journal of Renewable materials 2022年第12期10卷 3559-3572页

作者： Nora Elizondo-Villarreal luz HVerástegui-Dominguez Jose JQuijano-Briones Francisco JVázquez-Rodríguez Eden Rodríguez-Castellanos Enrique López-Cuellar Ernesto Torres-Lopez Victor mCastaño-meneses Universidad Autónoma de Nuevo León Facultad de Ciencias Fisico MatemáticasCiudad UniversitariaSan Nicolás de los GarzaNuevo LeónMéxico Universidad Autónoma de Nuevo León Facultad de ArquitecturaCiudad UniversiariaSan Nicolás de los GarzaNuevo LeónMéxico Universidad Autónoma de Nuevo León Facultad de Ingeniería Mecainicay EléctricaCiudad UniversitariaSan Nicolás de los GarzaNuevo LeónMéxico Centro de Física Aplicada y Tecnología Avanzada Universidad Nacional Autonoma de MéxicoQuerétaroMéxico

Agave salmiana ash and poultry eggshell powder as CaO sources were used for obtaining nanostructured hydro-xyapatite(HAP).The synthesis was carried out by the Green Chemistry Hydrothermal Biosynthesis at 180℃ with a pH of 5,by reacting CaO from Agave Salmiana ash and Eggshell powder,with dibasic caldium phosphate(CaH-PO_(4)+2H_(2)O)in an aqueous solution,with Aloe barbadensis *** product was characterized by X-ray dif-fraction,Fourier transform infrared spectroscopy(FT-IR),Scanning Electron microscopy(SEm),and Transmission Electron microscopy(TEm).The size and shape of the hydroxyapatite particles changed dramati-cally in the presence of Aloe *** crystals of Hydroxyapatite were observed when Eggshell powder and Agave salmiana ash were used as raw materials in the presence of the Aloe barbadensis *** with shapes of ribbons and plates from 1 micrometers to 8 micrometers were observed when using the eggshell powder in the presence of Aloe bar badensis and,in the case of Agave salmiana ash in the presence of Aloe bar-badensis,crystals with shapes of quadra ngular prisms and hexagonal(polyhedra)with sizes from 2 micrometers to 20 micrometers were *** was therefore successfully biosynthesized by a green and sus-tainable method that reduces the environmental impact.

关键词： Hydroxyapatite raw materials Agave salmiana eggshell Aloe barbadensis surfactant

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Performance and calibration of quark/gluon-jet taggers using 140 fb^(-1) of pp collisions at √s=13 TeV with the ATLAS detector

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Chinese Physics C 2024年第2期48卷 1-25页

作者： G. Aad B. Abbott K. Abeling N.J. Abicht S.H. Abidi A. Aboulhorma H. Abramowicz H. Abreu Y. Abulaiti B.S. Acharya C. Adam Bourdarios L. Adamczyk S.V. Addepalli m.J. Addison J. Adelman A. Adiguzel T. Adye A.A. Affolder Y. Afik m.N. Agaras J. Agarwala A. Aggarwal C. Agheorghiesei A. Ahmad F. Ahmadov W.S. Ahmed S. Ahuja X. Ai G. Aielli A. Aikot m. Ait Tamlihat B. Aitbenchikh I. Aizenberg m. Akbiyik T.P.A. Åkesson A.V. Akimov D. Akiyama N.N. Akolkar K. Al Khoury G.L. Alberghi J. Albert P. Albicocco G.L. Albouy S. Alderweireldt m. Aleksa I.N. Aleksandrov C. Alexa T. Alexopoulos F. Alfonsi m. Algren m. Alhroob B. Ali H.m.J. Ali S. Ali S.W. Alibocus m. Aliev G. Alimonti W. Alkakhi C. Allaire B.m.m. Allbrooke J.F. Allen C.A. Allendes Flores P.P. Allport A. Aloisio F. Alonso C. Alpigiani m. Alvarez Estevez A. Alvarez fernandez m. Alves Cardoso m.G. Alviggi m. Aly Y. Amaral Coutinho A. Ambler C. Amelung m. Amerl C.G. Ames D. Amidei S.P. Amor Dos Santos K.R. Amos V. Ananiev C. Anastopoulos T. Andeen J.K. Anders S.Y. Andrean A. Andreazza S. Angelidakis A. Angerami A.V. Anisenkov A. Annovi C. Antel m.T. Anthony E. Antipov m. Antonelli F. Anulli m. Aoki T. Aoki J.A. Aparisi Pozo m.A. Aparo L. Aperio Bella C. Appelt A. Apyan N. Aranzabal S.J. Arbiol Val C. Arcangeletti A.T.H. Arce E. Arena J-F. Arguin S. Argyropoulos J.-H. Arling O. Arnaez H. Arnold G. Artoni H. Asada K. Asai S. Asai N.A. Asbah J. Assahsah K. Assamagan R. Astalos S. Atashi R.J. Atkin m. Atkinson H. Atmani P.A. Atmasiddha K. Augsten S. Auricchio A.D. Auriol V.A. Austrup G. Avolio K. Axiotis G. Azuelos D. Babal H. Bachacou K. Bachas A. Bachiu F. Backman A. Badea P. Bagnaia m. Bahmani A.J. Bailey V.R. Bailey J.T. Baines L. Baines O.K. Baker E. Bakos D. Bakshi Gupta V. Balakrishnan R. Balasubramanian E.m. Baldin P. Balek E. Ballabene F. Balli L.m. Baltes W.K. Balunas J. Balz E. Banas m. Bandieramonte A. Bandyopadhyay S. Bansal L. Barak m. Barakat E.L. Barberio D. Barberis m. Barbero m.Z. Barel K.N. Barends T. Barillari m-S. Barisits T. Barklow P. Baron D.A. Baron mo The ATLAS Collaboration

The identification of jets originating from quarks and gluons,often referred to as quark/gluon tagging,plays an important role in various analyses performed at the Large Hadron Collider,as Standard model measurements and searches for new particles decaying to quarks often rely on suppressing a large gluon-induced *** paper describes the measurement of the efficiencies of quark/gluon taggers developed within the ATLAS Collaboration,using √s=13 TeV proton–proton collision data with an integrated luminosity of 140 fb^(-1) collected by the ATLAS *** taggers with high performances in rejecting jets from gluon over jets from quarks are studied:one tagger is based on requirements on the number of inner-detector tracks associated with the jet,and the other combines several jet substructure observables using a boosted decision tree.A method is established to determine the quark/gluon fraction in data,by using quark/gluon-enriched subsamples defined by the jet *** in tagging efficiency between data and simulation are provided for jets with transverse momentum between 500 GeV and 2 TeV and for multiple tagger working points.

关键词： ATLAS JET QUARK GLUON TAGGING

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A decrease of docosahexaenoic acid in testes of mice fed a high-fat diet is associated with impaired sperm acrosome reaction and fertility

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Asian Journal of Andrology 2021年第3期23卷 306-313页

作者： Julio Bunay luz-maria Gallardo Jorge Luis Torres-Fuentes m Veronica Aguirre-Arias Renan Orellana Nestor Sepulveda Ricardo D moreno Physiology Department Faculty of Biological SciencesPontificia Universidad Cat6lica de Chile(PUC)Santiago 8331150Chile Department of Chemistry and Biological Sciences Health Sciences FacultyUniversidad Bernardo 0 HigginsSantiago 8370854Chile Center of Excellence in Biotechnology of Reproduction Universidad de la FronteraTemuco 4780000Chile.

Obesity is a major worldwide health problem that is related to most chronic diseases,including male *** to its wide impact on health,mechanisms underlying obesity-related infertility remain *** this study,we report that mice fed a high-fat diet(HFD)for over 2 months showed reduced fertility rates and increased germ cell apoptosis,seminiferous tubule degeneration,and decreased intratesticular estradiol(E2)and E2-to-testosterone ***,we also detected a decrease in testicular fatty acid levels,behenic acid(C22:0),and docosahexaenoic acid(DHA,22:6n-3),which may be related to the production of dysfunctional ***,we did not detect any changes in the frequency of seminiferous tubule stages,sperm count,or rate of in vitro ***,there was an increase in spontaneous and progesterone-induced acrosomal exocytosis(acrosome reaction)in spermatozoa from HFD-fed *** data suggest that a decrease in E2 and fatty acid levels influences spermatogenesis and some steps of acrosome biogenesis that will have consequences for ***,our results add new evidence about the adverse effect of obesity in male reproduction and suggest that the acrosomal reaction can also be affected under this condition.

关键词： cholesterol estradiol fat acid testis testosterone

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