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Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease

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World Journal of Hepatology 2024年第5期16卷 832-842页

作者： Elisa carolina Lange Pabulo Henrique Rampelotto Larisse Longo Laura Bainy Rodrigues de Freitas carolina uribe-cruz Mario Reis Alvares-da-Silva Experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Brazil Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-007Brazil Bioinformatics and Biostatistics Core Facility Universidade Federal do Rio Grande do SulPorto Alegre 91501-970Brazil Graduate Program in Biological Sciences:Pharmacology and Therapeutics Universidade Federal do Rio Grande do SulPorto Alegre 90035-007Brazil Facultad de Ciencias de la Salud Universidad Católica de las MisionesPosadasMisiones 3300Argentina Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007RSBrazil Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)researcher Brasília 71605-001Brazil

BACKGROUND Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic *** suggest ornithine aspartate(LOLA)as drug *** To analyze the influence of LOLA intake on gut microbiota using a nutritional model of *** Adult male Sprague Dawley rats were randomized into three groups:Control(10 rats fed with a standard diet),MASLD(10 rats fed with a high-fat and choline-deficient diet),and LOLA(10 rats receiving 200 mg/kg/d LOLA,after the 16th week receiving high-fat and choline-deficient diet).After 28 wk of the experiment,animals were euthanized,and feces present in the intestine were *** fecal DNA extraction,the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™*** Alpha and beta diversity metrics were comparable between MASLD and LOLA.3 OTUs were differentially abundant between MASLD and LOLA,which belong to the species Helicobacter rodentium,Parabacteroides goldsteinii,and Parabacteroides *** functional prediction provided two different metabolic profiles between MASLD and *** 9 pathways differentially abundant in MASLD are related to a change in energy source,adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides *** 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate,including tricarboxylic acid cycle pathways,purine/guanosine nucleotides biosynthesis,pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA *** Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD,it was associated with changes in specific gut microbes and their related metabolic pathways.

关键词： Animal model Gut microbiota Metabolic-associated steatotic liver disease Metabolic prediction Ornithine aspartate

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Lipophagy and epigenetic alterations are related to metabolic dysfunction-associated steatotic liver disease progression in an experimental model

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World Journal of Hepatology 2024年第12期16卷 1468-1479页

作者： Felipe Schütz Larisse Longo Melina Belén Keingeski Eduardo Filippi-Chiela carolina uribe-cruz Mário ReisÁlvares-da-Silva Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-007Rio Grande do SulBrazil Experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Rio Grande do SulBrazil Center of Biotechnology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Department of Morphological Sciences Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Facultad de Ciencias de la Salud Universidad Católica de las MisionesPosadas 3300MisionesArgentina Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Rio Grande do SulBrazil Conselho Nacional de Desenvolvimento Científico e Tecnológico Brasilia 71.605-001Distrito FederalBrazil

BACKGROUND Genetic and epigenetic alterations are related to metabolic dysfunction-associated steatotic liver disease(MASLD)*** To evaluate micro(mi)RNAs and lipophagy markers in an experimental model of metabolic dysfunction-associated steatohepatitis(MASH).METHODS Adult male Sprague Dawley rats were randomized into two groups:Control group(n=10)fed a standard diet;and intervention group(n=10)fed a high-fat-choline-deficient diet for 16 *** evaluation of li-pophagy markers in liver tissue[sirtuin-1,p62/sequestosome-1,transcription factor-EB,perilipin-2(Plin2),Plin3,Plin5,lysosome-associated membrane proteins-2,rubicon,and Cd36],and serum miRNAs were *** Animals in the intervention group developed MASH and showed a significant decrease in sirtuin-1(P=0.020)and p62/sequestosome-1(P<0.001);the opposite was reported for transcription factor-EB(P=0.020),Plin2(P=0.003),Plin3(P=0.031),and Plin5(P=0.005)compared to the control *** was no significant difference between groups for lysosome-associated membrane proteins-2(P=0.715),rubicon(P=0.166),and Cd36(P=0.312).The intervention group showed a significant increase in miR-34a(P=0.005)and miR-21(P=0.043)compared to the *** was no significant difference between groups for miR-375(P=0.905),miR-26b(P=0.698),and miR-155(P=0.688).CONCLUSION Animals with MASH presented expression changes in markers related to lysosomal stress and autophagy as well as in miRNAs related to inflammation and fibrogenesis,processes that promote MASLD progression.

关键词： Animal model Epigenetic Lipophagy MicroRNAs Metabolic dysfunction-associated steatotic liver disease Metabolic dysfunction-associated steatohepatitis

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Chronic exposure to ethanol causes steatosis and inflammation in zebrafish liver

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World Journal of Hepatology 2017年第8期9卷 418-426页

作者： Ana Claudia Reis Schneider Cleandra Gregório carolina uribe-cruz Ranieli Guizzo Tais Malysz Maria Cristina Faccioni-Heuser Larisse Longo Themis Reverbel da Silveira La-boratório Experimental de Hepatologia e Gastroenterologia Hospital de Clínicas de Porto Alegre Programa de Pós- Graduacao em Ciências Médicas Gastroenterologia e HepatologiaUniversidade Federal do Rio Grande do Sul Programa de Pós-Graduacao em Genética e Biologia Molecular(UFRGS) Instituto de Ciências Básicas da Saúde(UFRGS) Departamento de Ciências Morfológicas(UFRGS) Centro de Microscopia Eletronica(UFRGS)

AIM To evaluate the effects of chronic exposure to ethanol in the liver and the expression of inflammatory genesin *** Zebrafish(n = 104),wild type,adult,male and female,were divided into two groups:Control and ethanol(0.05 v/v).The ethanol was directly added into water;tanks water were changed every two days and the ethanol *** animals were fed twice a day with fish food until *** two and four weeks of trial,livers were dissected,histological analysis(hematoxilineosin and Oil Red staining) and gene expression assessment of adiponectin,adiponectin receptor 2(adipor2),sirtuin-1(sirt-1),tumor necrosis factor-alpha(tnf-a),interleukin-1b(il-1b) and interleukin-10(il-10) were *** evaluations were conducted at fourth *** Exposing zebrafish to 0.5% ethanol developed intense liver steatosis after four weeks,as demonstrated by oil red *** ethanol-treated animals,the main ultrastructural changes were related to cytoplasmic lipid particles and droplets,increased number of rough endoplasmic reticulum cisterns and glycogen *** two and four weeks,hepatic mR NA expression of il-1b,sirt-1 and adipor2 were upregulated,indicating that ethanol triggered signaling molecules which are key elements in both hepatic inflammatory and protective *** was not detected in the liver of animals exposed and not exposed to ethanol,and il-10 did not show significant *** Data suggest that inflammatory signaling and ultrastructural alterations play a significant role during hepatic steatosis in zebrafish chronically exposed to ethanol.

关键词： Ethanol Hepatic steatosis Inflammation Zebrafish Alcoholic fatty liver

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Gut dysbiosis and systemic inflammation promote cardiomyocyte abnormalities in an experimental model of steatohepatitis

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World Journal of Hepatology 2021年第12期13卷 2052-2070页

作者： Larisse Longo Pabulo Henrique Rampelotto Eduardo Filippi-Chiela Valessa Emanoele Gabriel de Souza Fernando Salvati Carlos Thadeu Cerski Themis Reverbel da Silveira Cláudia P Oliveira carolina uribe-cruz Mário ReisÁlvares-da-Silva Experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Graduate Program in Genetics and Molecular Biology Universidade Federal do Rio Grande do SulPorto Alegre 90035-903Rio Grande do SulBrazil Center of Biotechnology Universidade Federal do Rio Grande do SulPorto Alegre 91501-970Rio Grande do SulBrazil Department of Morphological Sciences Universidade Federal do Rio Grande do SulPorto Alegre 90050-170Rio Grande do SulBrazil Experimental Research Center Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil School of Medicine Instituto Meridional de Educação-IMEDPasso Fundo 99070-220Rio Grande do SulBrazil Unit of Surgical Pathology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Department of Gastroenterology(LIM07) Faculdade de Medicina da Universidade de São PauloSão Paulo 01246903Brazil Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil

BACKGROUND Cardiovascular disease is the main cause of death in metabolic-associated fatty liver disease,and gut microbiota dysbiosis is associated with both of *** To assess the relationship between gut dysbiosis and cardiovascular risk(CVR)in an experimental model of *** Adult male Sprague-Dawley rats were randomized to a control group(n=10)fed a standard diet and an intervention group(n=10)fed a high-fat choline-deficient diet for 16 ***,molecular,hepatic,and cardiac *** microbiota variables were *** The intervention group had a significantly higher atherogenic coefficient,Castelli’s risk index(CRI)-I and CRI-II,interleukin-1β,tissue inhibitor of metalloproteinase-1(all P<0.001),monocyte chemoattractant protein-1(P=0.005),and plasminogen activator inhibitor-1(P=0.037)than the control *** expression of miR-33a increased(P=0.001)and miR-126(P<0.001)decreased in the intervention *** with fibrosis was seen in the intervention group,and heart computerized histological imaging analysis showed a significant decrease in the percentage of cardiomyocytes with a normal morphometric appearance(P=0.007),reduction in the mean area of cardiomyocytes(P=0.037),and an increase of atrophic cardiomyocytes(P=0.007).There were significant correlations between the cardiomyocyte morphometry markers and those of progression and severity of liver disease and *** intervention group had a lower Shannon diversity index and fewer changes in the structural pattern of gut microbiota(both P<0.001)than *** microbial families that are involved in lipid metabolism were differentially abundant in intervention group and were significantly correlated with markers of liver injury and *** The study found a link between gut dysbiosis and significant cardiomyocyte abnormalities in animals with steatohepatitis.

关键词： Animal model Cardiovascular diseases Gut microbiota Metabolic-associated fatty liver disease Predicted lipid metabolism Risk cardiovascular Steatohepatitis

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Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease

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World Journal of Hepatology 2024年第1期16卷 75-90页

作者： Matheus Truccolo Michalczuk Larisse Longo Melina Belén Keingeski Bruno de Souza Basso Gabriel Tayguara Silveira Guerreiro Jessica T Ferrari JoséEduardo Vargas Cláudia P Oliveira carolina uribe-cruz Carlos Thadeu Schmidt Cerski Eduardo Filippi-Chiela Mário ReisÁlvares-da-Silva Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Laboratory of Inflammatory and Neoplastic Cells Universidade Federal do ParanáParaná81530900Brazil Department of Gastroenterology(LIM07) Faculdade de Medicina da Universidade de São PauloSão Paulo 01246903Brazil Facultad de Ciencias de la Salud Universidad Católica de las MisionesPosadasMisiones 3300Argentina Unit of Surgical Pathology Hospital de Clinicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Center of Biotechnology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Department of Morphological Sciences Universidade Federal do Rio Grande do SulPorto Alegre 90.050-170Rio Grande do SulBrazil Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)ResearcherBrasília 71.605-001Brazil

BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in *** Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(DEN)in drinking water and Veh gavage],and RIF[HFCD,DEN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were *** All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop *** animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(Mmp2),and metalloproteinases-9(Mmp9)were significantly higher in the *** opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(Map1 Lc3b),and p62/sequestosome-1(p62/SQSTM1)-*** with controls,Map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(P0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(P0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis throu

关键词： Animal model Autophagy Epigenetic Hepatocellular carcinoma Metabolic dysfunction-associated steatotic liver disease Rifaximin

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Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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Neural Regeneration Research 2025年第2期20卷 394-401页

作者： Josep Tomàs Víctor Cilleros-Mañé Laia Just-Borràs Marta Balanyà-Segura Aleksandra Polishchuk Laura Nadal Marta Tomàs carolina Silvera-Simón Manel M.Santafé Maria A.Lanuza Unitat d’Histologia i Neurobiologia(UHNeurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

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Scale dependency of Liolaemus lizards＇ home range in response to different environmental variables

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Current Zoology 2016年第6期62卷 521-530页

作者： Oscar Anibal STELLATELLI carolina BLOCK Debora Lina MORENO-AZOCAR Laura Estela VEGA Juan Pablo ISACCH Felix Benjamin cruz Laboratorio de Vertebrados Departamento de Biologia Instituto de Investigaciones Marinas y Costeras (IIMyC) CONICET-Facultad de Ciencias Exactas y Naturales Universidad Nacional de Mar del Plata. Defin Funes 3250 (B7602AYJ) Mar del Plata Buenos Aires Argentina Instituto de Investigaciones en Biodiversidad y Medioambiente (INIBIOMA) CONICET-Universidad Nacional del Comahue. Quintral 1250 (8400) San Carlos de Bariloche Rio Negro Argentina.

Animal habitat-use patterns cannot be isolated from scale issues. Consequently, multi-scale studies provide a complete characterization of ecological patterns that can further explain the observed variation. Liolaemus constitutes the world＇s second most speciose lizard genus. In this study, we assessed the relationships between home range size and environmental variables at 3 different spatial scales. The study at a local and regional scale was focused on the habitat specialist Liolaemus multimaculatus. The lizard＇s home range was calculated using the minimum convex polygon method in populations from grassland sites of the coastal sand dunes of the Argentinean Pampas under 2 different conditions, with or without forestations of Acacia Iongifolia. On the other hand, at a geographical scale we considered the evolutionary implications of 20 species of Liolaemus. Home range size, phylogeny, ecological, environmental, and climatic data were ob- tained from the literature and remote sensing. L. multimaculatus home range varied from 12.66 to 570.00 m. Regionally, this species had smaller home ranges in forested habitats （X： 94.02 m2） com- pared with the non-forested sites （X： 219.78m2）. Habitat structure, vegetation types, and food availability would explain the space use at finer scales. When the 20 species of Liolaernus were considered, high mean air temperature and broad thermal amplitudes showed an inverse relationship with home range size. Neither net primary productivity nor phylogeny was good predictors for home range variation at geographical scale. This study highlights the scale dependence of the explicative capability of a set of environmental and intrinsic variables on home range patterns.

关键词： environmental factors home range Liolaemus lizard scales

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Latitudinal pattern of the thermal sensitivity of running speed in the endemic lizard Liolaemus multimaculatus

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Integrative Zoology 2022年第4期17卷 619-637页

作者： Oscar Aníbal STELLATELLI Laura EVEGA carolina BLOCK Camila ROCCA Patricio BELLAGAMBA Juan Esteban DAJIL Félix Benjamín cruz Instituto de Investigaciones Marinas y Costeras(IIMyC) Universidad Nacional de Mar del Plata-CONICETFacultad de Ciencias Exactas y NaturalesMar del PlataArgentina Municipalidad de General Pueyrredón Mar del PlataArgentina Instituto de Investigaciones en Biodiversidad y Medioambiente(INIBIOMA) Universidad Nacional del Comahue-CONICETSan Carlos de BarilocheArgentina

Physiological performance in lizards may be affected by climate across latitudinal or altitudinal *** the coastal dune barriers in central-eastern Argentina,the annual maximum environmental temperature decreases up to 2℃ from low to high latitudes,while the mean relative humidity of the air decreases from 50%to 25%.Liolaemus multimaculatus,a lizard in the family Liolaemidae,is restricted to these coastal *** investigated the locomotor performance of the species at 6 different sites distributed throughout its range in these dune *** inquired whether locomotor performance metrics were sensitive to the thermal regime attributable to *** thermal performance breadth increased from 7%to 82%with latitude,due to a decrease in its critical thermal minimum of up to 5℃ at higher *** from high latitude sites showed a thermal optimum,that is,the body temperature at which maximum speed is achieved,up to 4℃lower than that of lizards from the low *** relatively low temperatures,the maximum running speed of high-latitude individuals was faster than that of low-latitude *** parameters of locomotor performance were labile,decreasing as a function of *** results show populations of *** adjust thermal physiology to cope with local climatic *** suggests that thermal sensitivity responds to the magnitude of latitudinal fluctuations in environmental temperature.

关键词： latitude Liolaemus reptile running speed temperature thermal sensitivity

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Coupling of bioelectrochemical toluene oxidation and trichloroethene reductive dechlorination for single-stage treatment of groundwater containing multiple contaminants

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Environmental Science and Ecotechnology 2022年第3期11卷 32-39页

作者： carolina cruz Viggi Matteo Tucci Marco Resitano Simona Crognale Maria Letizia Di Franca Simona Rossetti Federico Aulenta Water Research Institute(IRSA) National Research Council(CNR)Via Salaria Km 2930000015MonterotondoRMItaly

Bioremediation of groundwater contaminated by a mixture of aromatic hydrocarbons and chlorinated solvents is typically challenged because these contaminants are degraded via distinctive oxidative and reductive pathways,thus requiring different amendments and redox ***,we provided the proof-of-concept of a single-stage treatment of synthetic groundwater containing toluene and trichloroethene(TCE)in a tubular bioelectrochemical reactor,known as a“bioelectric well”.Toluene was degraded by a microbial bioanode(up to 150 mmol L^(-1) d^(-1))with a polarized graphite anode(t0.2 V ***)serving as the terminal electron *** electric current deriving from microbially-driven toluene oxidation resulted in(abiotic)hydrogen production(at a stainless-steel cathode),which sustained the reductive dechlorination of TCE to less-chlorinated intermediates(i.e.,cis-DCE,VC,and ETH),at a maximum rate of 500 meq L^(-1) d^(-1),in the bulk of the reactor.A phylogenetic and functional genebased analysis of the“bioelectric well”confirmed the establishment of a microbiome harboring the metabolic potential for anaerobic toluene oxidation and TCE reductive ***,Toluene degradation and current generation were found to be rate-limited by external mass transport phenomena,thus indicating the existing potential for further process optimization.

关键词： Bioelectric well Dehalococcoides mccartyi Electrobioremediation Groundwater remediation Toluene Trichloroethene

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Radiomics in pancreatic cancer for oncologist:Present and future

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Hepatobiliary & Pancreatic Diseases International 2022年第4期21卷 356-361页

作者： carolina de la Pinta Radiation Oncology Department Ramón y Cajal University HospitalIRYCISAlcaláUniversity28034 MadridSpain

Radiomics is changing the world of medicine and more specifically the world of *** diagnosis and treatment improve the prognosis of patients with *** treatment,the evaluation of the response will determine future *** oncology,every change in treatment means a loss of therapeutic options and this is key in pancreatic *** has been developed in oncology in the early diagnosis and differential diagnosis of benign and malignant lesions,in the evaluation of response,in the prediction of possible side effects,marking the risk of recurrence,survival and prognosis of the *** studies have validated its use to differentiate normal tissues from tumor tissues with high sensitivity and specificity,and to differentiate cystic lesions and pancreatic neuroendocrine tumor grades with texture *** addition,these parameters have been related to survival in patients with pancreatic cancer and to response to radiotherapy and *** review aimed to establish the current status of the use of radiomics in pancreatic cancer and future perspectives.

关键词： Pancreatic cancer Radiomics Radiogenomics

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