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Aminoguanidine impedes human pancreatic tumor growth and metastasis development in nude mice

World Journal of Gastroenterology 2009年第9期15卷 1065-1071页

作者： Nora A Mohamad graciela p cricco Lorena A Sambuco Máximo Croci Vanina A Medina Alicia S Gutiérrez Rosa M Bergoc Elena S Rivera Gabriela A Martín Laboratory of Radioisotopes School of Pharmacy and BiochemistryUniversity of Buenos AiresJunín 954 (C1113AAB)Buenos AiresArgentina Institute of Immunooncology Dr. Ernesto Crescenti Av. Córdoba 3200 (C1187AAS)Buenos AiresArgentina National Research Council (CONICET) Av. Rivadavia 1917 (C1033AAJ)Buenos AiresArgentina

AIM:To study the action of aminoguanidine on pancreatic cancer xenografts in relation to cell proliferation,apoptosis,redox status and vascularization.METHODS:Xenografts of pANC-1 cells were developed in nude mice. The animals were separated into two groups:control and aminoguanidine treated. Tumor growth,survival and appearance of metastases were determined in vivo in both groups. Tumors were excised and ex vivo histochemical studies were performed. Cell growth was assessed by Ki-67 expression. Apoptosis was studied by intratumoral expression of B cell lymphoma-2 protein (Bcl-2) family proteins and Terminal deoxynucleotidyl transferase biotin-dUTp Nick End Labeling (Tunel). Redox status was evaluated by the expression of endothelial nitric oxide synthase (eNOS),catalase,copper-zinc superoxide dismutase (CuZnSOD),manganese superoxide dismutase (MnSOD) and glutathione peroxidase (Gpx). Finally,vascularization was determined by Massons trichromic staining,and by VEGF and CD34 expression.RESULTS:Tumor volumes after 32 d of treatment by aminoguanidine (AG) were significantly lower than in control mice (p p ppearance of both homolateral and contralateral palpable metastases was significantly delayed in AG group. Apoptotic cells,intratumoral vascularization (trichromic stain) and the expression of Ki-67,Bax,eNOS,CD34,VEGF,catalase,CuZnSOD and MnSOD were diminished in AG treated mice (p pression of Bcl-2 and Gpx did not change.CONCLUSION:The antitumoral action of aminoguanidine is associated with decreased cell proliferation,reduced angiogenesis,and reduced expression of antioxidant enzymes.

关键词：细胞生长氨基胍癌肿瘤胰腺癌内皮型一氧化氮合酶铜锌超氧化物歧化酶转移血管内皮生长因子

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Hepatocellular carcinoma in patients with metabolic dysfunctionassociated fatty liver disease: Can we stratify at-risk populations?

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World Journal of Hepatology 2022年第2期14卷 354-371页

作者： Eduardo Fassio Fernando J Barreyro M Soledad pérez Diana Dávila graciela Landeira Gisela Gualano Gabriela Ruffillo Hepatology Section Gastroenterology ServiceHospital Nacional Prof.Alejandro PosadasEl Palomar 1684Buenos AiresArgentina Biotechnology Institute of Misiones Faculty of Chemical and Natural SciencesNational University of MisionesPosadas N3300MisionesArgentina

Metabolic dysfunction-associated fatty liver disease(MAFLD)is a new nomenclature recently proposed by a panel of international experts so that the entity is defined based on positive criteria and linked to pathogenesis,replacing the traditional non-alcoholic fatty liver disease(NAFLD),a definition based on exclusion criteria.NAFLD/MAFLD is currently the most common form of chronic liver disease worldwide and is a growing risk factor for development of hepatocellular carcinoma(HCC).It is estimated than 25%of the global population have NAFLD and is projected to increase in the next years.Major Scientific Societies agree that surveillance for HCC should be indicated in patients with NAFLD/MAFLD and cirrhosis but differ in non-cirrhotic patients(including those with advanced fibrosis).Several studies have shown that the annual incidence rate of HCC in NAFLD-cirrhosis is greater than 1%,thus surveillance for HCC is costeffective.Risk factors that increase HCC incidence in these patients are male gender,older age,presence of diabetes and any degree of alcohol consumption.In non-cirrhotic patients,the incidence of HCC is much lower and variable,being a great challenge to stratify the risk of HCC in this group.Furthermore,large epidemiological studies based on the general population have shown that diabetes and obesity significantly increase risk of HCC.Some genetic variants may also play a role modifying the HCC occurrence among patients with NAFLD.The purpose of this review is to discuss the epidemiology,clinical and genetic risk factors that may influence the risk of HCC in NAFLD/MAFLD patients and propose screening strategy to translate into better patient care.

关键词： Hepatocellular carcinoma Metabolic dysfunction-associated fatty liver disease Nonalcoholic fatty liver disease Surveillance for hepatocellular carcinoma Incidence of hepatocellular carcinoma Nonalcoholic steatohepatitis

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Involvement of Met receptor pathway in aggressive behavior of colorectal cancer cells induced by parathyroid hormone-related peptide

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World Journal of Gastroenterology 2022年第26期28卷 3177-3200页

作者： María Belén Novoa Díaz pedro Carriere graciela Gigola Ariel Osvaldo Zwenger Natalia Calvo Claudia Gentili Departamento de Biología Bioquímica y FarmaciaUniversidad Nacional del Sur(UNS)-INBIOSUR(CONICET-UNS)Bahía Blanca 8000Buenos AiresArgentina Centro de Estudios Clínicos SAGA CEC SAGASantiago de Chile 8320000Chile

BACKGROUND parathyroid hormone-related peptide(pTHrp)plays a key role in the development and progression of many tumors.We found that in colorectal cancer(CRC)HCT116 cells,the binding of pTHrp to its receptor pTHR type 1(pTHR1)activates events associated with an aggressive phenotype.In HCT116 cell xenografts,pTHrp modulates the expression of molecular markers linked to tumor progression.Empirical evidence suggests that the Met receptor is involved in the development and evolution of CRC.Based on these data,we hypothesized that the signaling pathway trigged by pTHrp could be involved in the transactivation of Met and consequently in the aggressive behavior of CRC cells.AIM To elucidate the relationship among pTHR1,pTHrp,and Met in CRC models.METHODS For in vitro assays,HCT116 and Caco-2 cells derived from human CRC were incubated in the absence or presence of pTHrp(1-34)(10-8 M).Where indicated,cells were pre-incubated with specific kinase inhibitors or dimethylsulfoxide,the vehicle of the inhibitors.The protein levels were evaluated by Western blot technique.Real-time polymerase chain reaction(RT-qpCR)was carried out to determine the changes in gene expression.Wound healing assay and morpho logical monitoring were performed to evaluate cell migration and changes related to the epithelialmesenchymal transition(EMT),respectively.The number of viable HCT116 cells was counted by trypan blue dye exclusion test to evaluate the effects of irinotecan(CpT-11),oxaliplatin(OXA),or doxorubicin(DOXO)with or without pTHrp.For in vivo tests,HCT116 cell xenografts on 6-wk-old male N:NIH(S)_nu mice received daily intratumoral injections of pTHrp(40μg/kg)in 100μL phosphate-buffered saline(pBS)or the vehicle(pBS)as a control during 20 d.Humanitarian slaughter was carried out and the tumors were removed,weighed,and fixed in a 4%formaldehyde solution for subsequent treatment by immunoassays.To evaluate the expression of molecular markers in human tumor samples,we studied 23 specimens obtained from CRC patients which were treated at t

关键词： pTHrp MET receptor tyrosine kinase parathyroid hormone receptor type 1 Colorectal cancer Drug resistance

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In Vitro-propagation of Agave tequilana Weber cv.azul in a Temporary Immersion System

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phyton-International Journal of Experimental Botany 2022年第1期91卷 83-96页

作者： Otilio Vázquez-Martínez Héctor Gordon Núñez-palenius Eugenio M.pérez-Molphe Balch Mauricio Valencia-posadas Luis pérez-Moreno graciela M.L.Ruiz-Aguilar M.Gómez-Lim División de Ciencias de la Vida Universidad de GuanajuatoIrapuato36500México Departamento de Química Centro de Ciencias BásicasUniversidad Autónoma de AguascalientesAguascalientes20131México Departamento de Ingeniería Genética CINVESTAV Unidad IrapuatoIrapuato36500México

In Mexico,there is a need to produce large quantities of plantlets for the establishment and replanting of blue(cv.azul)agave production areas.Most of these plots are within the origin denomination area(DOT,Spanish acronym)of the distilled product of this plant,known as tequila.The objective of this study was to develop an in vitropropagation protocol for Agave tequilana Weber cv.azul using segmented stems in both:solid and liquid media.A disinfection and in vitro technique were developed to obtain shoots,through plantlets collected in commercial plots,which attained 100%surface-disinfection and budding rate.At the multiplication stage,the effects of 6-Benzylaminopurine(BA)(0.0,4.4 and 13.2μM)and kinetin(0.0,9.4,18.8 and 37.6μM)were evaluated on lateralshoot production of segmented sagittal stems.These were cultivated on Murashige&Skoog(MS)medium,with the addition of 3.0%sucrose and 8 g L−1 agar.It was observed that BA and kinetin increased the number of shoots per explant,obtaining up to 18 and 26,respectively.Furthermore,it was found that just the sagittal segmentation of explants increased axillary budding.On the other hand,segmented-stem bases were grown in MS liquid medium with 3.0%sucrose,inside a RITAsystem,programmed by a 5 min immersion step with a frequency of every 4 h.The effect of Indole−3-Acetic acid(IAA)(0.57,2.9,5.7μM)was evaluated,while maintaining a concentration of BA(13.2μM).It was observed that the greatest concentration of IAA led to the formation of more than 20 buds per explant.These results offer a new methodology to increase the efficiency of A.tequilana Weber cv.azul-in vitro multiplication by sagittal segmentation of stems and the addition of BA and/or IAA.

关键词： plant tissue culture stem-disk culture tequila in vitro culture

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Therapeutic effect of Streptococcus thermophilus CRL 1190-fermented milk on chronic gastritis

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World Journal of Gastroenterology 2010年第13期16卷 1622-1630页

作者： Cecilia Rodríguez Marta Medici Fernanda Mozzi graciela Font de Valdez Centro de Referencia para Lactobacilos (CERELA)-CONICET Cátedra Microbiología Superior Facultad de Bioquímica Química y Farmacia Universidad Nacional de Tucumán

AIM: To investigate the potential therapeutic effect of exopolysaccharide (EpS)-producing Streptococcus thermophilus (S. thermophilus) CRL 1190 fermented milk on chronic gastritis in Balb/c mice. METHODS: Balb/c mice were fed with the fermented milk for 7 d after inducing gastritis with acetyl-salicylic acid (ASA, 400 mg/kg body weight per day for 10 d). Omeprazole was included in this study as a positive therapeutic control. The gastric in? ammatory activity was evaluated from gastric histology and in? ammation score, number of interleukin-10 (IL-10), interferon-γ (INFγ) and tumor necrosis factor-α (TNF-α) cytokine-producing cells in the gastric mucosa, and thickness of the mucus layer. RESULTS: Animals receiving treatment with the EpS-producing S. thermophilus CRL 1190 fermented milk showed a conserved gastric mucosa structure similar to that of healthy animals. In? ammation scores of the fermented milk-treated mice were lower than those of mice in the gastritis group (0.2 ± 0.03 vs 2.0 ± 0.6, p p p p pared to the gastritis group, was observed. Also, an increase in the thickness of the mucus gel layer (2.2 ± 0.6 vs 1.0 ± 0.3; 5.1 ± 0.8 vs 1.5 ± 0.4 in the corpus and antrum mucosa, respectively, p pared with the gastritis group was noted. A milk suspension of the purif ied EpS from S. thermophilus CRL1190 was also effective as therapy for gastritis.

关键词： Lactic acid bacteria probiotics Gastritis Streptococcus thermophilus Exopolysaccharides

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prostate cancer upgrading or downgrading of biopsy Gleason scores at radical prostatectomy:prediction of"regression to the mean"using routine clinical features with correlating biochemical relapse rates

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Asian Journal of Andrology 2019年第6期21卷 598-604页

作者： Muammer Altok patricia Troncoso Mary F Achim Surena F Matin graciela N Gonzalez John W Davis Department of Urology University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Department of pathology University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Department of Biostatistics University of Texas MD Anderson Cancer CenterHoustonTX 77030USA.

Recommendations for managing clinically localized prostate cancer are structured around clinical risk criteria,with prostate biopsy(pB)Gleason score(GS)being the most important factor.Biopsy to radical prostatectomy(Rp)specimen upgrading/downgrading is welldescribed,and is often the ratio nale for costly imaging or genomic studies.We prese nt simple,no-cost an a lyses of clinical parametersto predict which GS 6 and GS 8 patients will change to GS 7 at prostatectomy.From May 2006 to December 2012,1590 patientsunderwent robot-assisted radical prostatectomy(RARp).After exclusions,we identified a GS 6 cohort of 374 patients and a GS 8cohort of 91 patients.During this era,>1000 additional patients were enrolled in an active surveillanee(AS)program.For GS 6,265(70.9%)of 374 patients were upgraded,and the cohort included 183(48.9%)patients eligible for AS by the prostate Cancer ResearchInternational Active Surveillance Study(pRIAS)standards,of which 57.9%were upgraded.pB features that predicted a>90%chanceof upgrading included≥7 cores positive,maximum foci length≥8 mm in any core,and total tumor involvement≥30%.For GS 8,downgrading occurred in 46(50.5%),which was significantly higher for single core versus multiple cores(80.4%vs 19.6%,p=0.011).Biochemical recurre nee(BCR)occurred in 3.4%of GS 6 upgraded versus 0%non upgraded,and in GS 8,19.6%downgraded versus42.2%nondown graded.In coun seling men with clin ically localized prostate can cer,the odds of GS cha nge should be presented,andcertain men with high-volume GS 6 or low-volume GS 8 can be counseled with GS 7-based recommendations.

关键词： biopsy down grade Gleas on score prostate cancer upgrade

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Chemical and spectroscopic characterization of humic substances from sediment and riparian soil of a highly polluted urban river(Suquía River,Córdoba,Argentina)

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International Journal of Sediment Research 2020年第3期35卷 287-294页

作者： Carolina Merlo Carolina Vázquez Ana graciela Iriarte Carlos Matías Romero Instituto Multidisciplinario de Biologia Vegetal (CONICET) Facultad de Ciencias Agropecuarias Universidad Nacional de Cordoba INFIQC Departament of FisicoquimicaFacultad de Ciencias QuimicasUniversidad Nacional de Cordoba Agriculture and Agri-Food Canada Lethbridge Research and Development Centre Department of Biological Sciences University of Lethbridge

The Suquia River,the largest urban river in Cordoba(Argentina),has been severely polluted for decades.Actions must be taken to restore its environmental quality by managing riparian zones for increased water-self purification.The current study aimed to characterize organic matter(OM) dynamics and humic substances(HS) spectrochemical properties along the lower-middle basin of the Suquia River.Riparian soil(0-20 cm) and sediment(0-10 cm) samples were collected from a reference location(S1)and four polluted sites(S2-S5) during a low-flow period.The contents of soil and sedimentary OM and HS fractions were analyzed by wet oxidation,as well as HS Fourier transform infrared(FT-IR) and ultraviolet-visible(UV-Vis) spectrochemical properties.The OM and HS fractions from riparian soil were high upstream of Cordoba City(S1 and S2,50.2-50.4 g/kg OM) and within a 50 km downstream location(S5,30.9 g/kg OM) owing to a surplus of fresh plant biomass-carbon(C) inputs.Highly heterogeneous sediment samples did not show any significant differences among sites(p> 0.05).The lowest values of the ratio of absorbances at 465 and 665 nm(E4/E6)(1.78) and the Δ log K(0.15) coefficient(a measure of HS maturity degree) were obtained downstream of Cordoba City,for both riparian soil and sediment,indicating that HS were enriched by more condensed aromatic structures within highly degraded portions of the river.All samples exhibited similar IR spectra,implying overlapping recalcitrant-C structures at the functional group level,but with different absorbance intensity.Data from the current study constitute a baseline for understanding the chemical nature of HS from sediment and riparian soil along the Suquia River and can be used as a reference for future studies tracking OM compositional changes over time.

关键词： Lotic ecosystems Organic matter Humic acids FT-IR spectroscopy UV-Vis spectroscopy

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Cigarette smoking, dietary habits and genetic polymorphisms in GSTT1, GSTM1 and CYp1A1 metabolic genes: A case-control study in oncohematological diseases

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世界临床肿瘤学杂志：英文版 2016年第5期7卷 395-405页

作者： María Belén Cerliani Walter pavicic Juan Antonio Gili graciela Klein Silvia Saba Silvina Richard Instituto Multidisciplinario de Biología Celular (CIC UNLP CONICET) Laboratorio de Epidemiología Genética (ECLAMC CEMIC CONICET CABA) Unidad de Diagnóstico Tratamiento y Sostén de Enfermedades Hematológicas Hospital Interzonal General de Agudos Prof. Dr. Rodolfo Rossi

AIM To analyze the association between oncohematological diseases and GSTT1 /GSTM1 /CYp1A1 polymorphisms, dietary habits and smoking, in an argentine hospitalbased case-control study.METHODS This hospital-based case-control study involved 125 patients with oncohematological diseases and 310 control subjects. A questionnaire was used to obtain sociodemographic data and information about habits. Blood samples were collected, and DNA was extracted using salting out methods. Deletions in GSTT1 and GSTM1 (null genotypes) were addressed by pCR. CYp1A1 MspI polymorphism was detected by pCR-RFLp. Odds ratio(OR) and 95%CI were calculated to estimate the association between each variable studied and oncohematological disease.RESULTS Women showed lower risk of disease compared to men(OR 0.52, 95%CI: 0.34-0.82, p = 0.003). Higher levels of education(> 12 years) were significantly associated with an increased risk, compared to complete primary school or less(OR 3.68, 95%CI: 1.82-7.40, p pect to tobacco, none of the smoking categories showed association with oncohematological diseases. Regarding dietary habits, consumption of grilled/barbecued meat 3 or more times per month showed significant association with an increased risk of disease(OR 1.72, 95%CI: 1.08-2.75, p = 0.02). Daily consumption of coffee also was associated with an increased risk(OR 1.77, 95%CI: 1.03-3.03, p = 0.03). Results for GSTT1, GSTM1 and CYp1A1 polymorphisms showed no significant association with oncohematological diseases. When analyzing the interaction between polymorphisms and tobacco smoking or dietary habits, no statistically significant associations that modify disease risk were found. CONCLUSION We reported an increased risk of oncohematological diseases associated with meat and coffee intake. We did not find significant associations between genetic polymorphisms and blood cancer.

关键词： Cancer Oncohematological disease Casecontrol study Lifestyle Diet Tobacco Xenobiotic metabolizing genes GSTT1 GSTM1 CYp1A1

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Survival effect of probiotics in a rat model of colorectal cancer treated with capecitabine

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World Journal of Gastrointestinal Oncology 2021年第10期13卷 1518-1531页

作者： graciela Gigola pedro Carriere María Belén Novoa Díaz Gabriela perdigon Ariel Osvaldo Zwenger Claudia Gentili Biología Bioquímica y FarmaciaUniversidad Nacional del Sur(UNS)-INBIOSUR(CONICET-UNS)Bahía Blanca 8000Buenos Aires ProvinciaArgentina San Miguel de Tucumán 4000Argentina Centro de Estudios Clínicos SAGA CEC SAGASantiago de Chile 8320000Chile

BACKGROUND probiotics are used to manage a number of gastrointestinal disorders due to their beneficial properties.Clinical reports showed that probiotics also improve the life quality of patients with colorectal cancer(CRC)subjected to oncologic treatment.In a CRC animal model,probiotics supplementation has the potential to decrease the formation of aberrant crypts and ameliorate tumor malignancy,enhancing the antitumor effect of 5-fluorouracil(5-FU)chemotherapy.Based on these data,we hypothesize that the administration of probiotics impact positively in the overall survival and life quality of rats with CRC under the treatment of capecitabine,which is the pro drug of 5-FU.AIM To evaluate the probiotics effects in a rat CRC model treated with capecitabine and followed until the end of life.METHODS 1,2-Dimethylhidrazine dihydrochloride(1,2-DMH)was employed as carcinogen inductor of CRC.Fifty male Wistar-Lewis rats were randomly assigned to one of five following groups:Control(n=5),Control+probiotics(Control-p group,n=5),1,2-DMH alone(DMH group,n=10),1,2-DMH+capecitabine(DMH-C group,n=10),1,2-DMH+probiotics(DMH-p group,n=10)and 1,2-DMH+capecitabine+probiotics(DMH-C-p group,n=10).All parametric data were expressed as the mean±SD.The statistical significance of differences was analyzed using one-way ANOVA.Data were analyzed with InfoStat software.The results were considered statistically significant at pplan-Meier estimator with the log-rank test.RESULTS The data of mean overall survival for DMH,DMH-p,DMH-C,DMH-C-p,Control and Control-p groups were 250 d[95%confidence interval(CI):242.5-253.1],268 d(95%CI:246.3-271.4),380 d(95%CI:337.8-421.9),480 d(95%CI:436.9-530.7),588 d(95%CI:565.8-609.3)and 590 d(95%CI:564.3-612.9),respectively,with a significant difference between DMH-C and DMH-C-p groups(p=0.001).Comparing all groups by Kaplan-Meier estimator,we found a significantly different in the overall survival of DMH and DMH-p groups respect to DMH-C(p=0.001)and DMH-C-p(p=

关键词： Colorectal cancer Capecitabine probiotics Survival Life quality Animal experimentation

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Kinetics and thermodynamic studies of Methyl Orange removal by polyvinylidene fluoride-pEDOT mats

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Journal of Environmental Sciences 2021年第2期33卷 62-73页

作者： Romario J.da Silva Lizeth Carolina Mojica-Sanchez Filipe D.S.Gorza graciela C.pedro Bruna G.Maciel Gabriela p.Ratkovski Herica D.daRocha Kamila T.O.do Nascimento Juan CMedina-Llamas Alicia E.Chavez-Guajardo Jose J.Alcaraz-Espinoza Celso p.de Melo program a de pos-Graduagao em Ciencia de Materials U niversidade Federal de Pernambuco50670-901 RecifePEBrazil Departamento de Ffsica Uniuersidade Federal de Pemambiico50670-901 Reci/ePEBrazil Centro de Estudios Cientificosy Tecnologicos No.18 Instituto Politecnico Nacional98160 ZacatecasZacMexico Unidad Academica de Ciencias de la Tierra Uniuersidad Aut6noma de Zacatecas98058 ZacatecasZacMexico Departamento de Quimica Universidad Autonoma Metropolitana09340Ciudad de MexicoMexico

We report the preparation of poly(3,4-ethylene dioxythiophene)(pEDOT)-modified polyvinylidene fluoride electrospun fibers and their use as a novel adsorbent material for the removal of the anionic dye Methyl Orange(MO)from aqueous media.This novel adsorbent material can be used to selectively remove MO on a wide p H range(3.0-10.0),with a maximum capacity of 143.8 mg/g at p H 3.0.When used in a recirculating filtration system,the maximum absorption capacity was reached in a shorter time(20 min)than that observed for batch mode experiments(360 min).Based on the analyses of the kinetics and adsorption isotherm data,one can conclude that the predominant mechanism of interaction between the membrane and the dissolved dye molecules is electrostatic.Besides,considering the estimated values for the Gibbs energy,and entropy and enthalpy changes,it was established that the adsorption process is spontaneous and occurs in an endothermic manner.The good mechanical and environmental stability of these membranes allowed their use in at least 20 consecutive adsorption/desorption cycles,without significant loss of their characteristics.We suggest that the physical-chemical characteristics of pEDOT make these hybrid mats a promising adsorbent material for use in water remediation protocols and effluent treatment systems.

关键词： Electrospinning Composite mats pedot pvdf mats Dye removal Water remediation

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