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Chitin-glucan improves important pathophysiological features of irritable bowel syndrome

World Journal of Gastroenterology 2024年第16期30卷 2258-2271页

作者： Caroline Valibouze Caroline Dubuquoy Philippe Chavatte Michaël Genin Veronique Maquet Salvatore Modica Pierre desreumaux Christel Rousseaux department of Digestive Surgery and Transplantation Lille UniversityLille 59037France Intestinal Biotech development Facultéde MédicineLille 59045France U1286-INFINITE-Institute for Translational Research in Inflammation Universitéde LilleLille 59000France ULR 2694-METRICS Évaluation des Technologies de santéet des Pratiques MédicalesUniversity of LilleLille 59000France KitoZyme SA Institution SociétéAnonymeZone 2Parc des Hauts SartsRue de MilmortHerstal 4040Belgium Hepato-Gastroenterology department Lille University HospitalLille 59037France

BACKGROUND Irritable bowel syndrome(IBS)is one of the most frequent and debilitating conditions leading to gastroenterological ***,recommended treatments remain limited,yielding only limited therapeutic ***-glucan(CG)is a novel dietary prebiotic classically used in humans at a dosage of 1.5-3.0 g/d and is considered a safe food ingredient by the European Food Safety *** provide an alternative approach to managing patients with IBS,we performed preclinical molecular,cellular,and animal studies to evaluate the role of chitin-glucan in the main pathophysiological mechanisms involved in *** To evaluate the roles of CG in visceral analgesia,intestinal inflammation,barrier function,and to develop computational molecular *** Visceral pain was recorded through colorectal distension(CRD)in a model of long-lasting colon hypersensitivity induced by an intra-rectal administration of TNBS[15 milligrams(mg)/kilogram(kg)]in 33 Sprague-Dawley *** pressure was regularly assessed during the 9 wk-experiment(weeks 0,3,5,and 7)in animals receiving CG(n=14)at a human equivalent dose(HED)of 1.5 g/d or 3.0 g/d and compared to negative control(tap water,n=11)and positive control(phloroglucinol at 1.5 g/d HED,n=8)*** anti-inflammatory effect of CG was evaluated using clinical and histological scores in 30 C57bl6 male mice with colitis induced by dextran sodium sulfate(DSS)administered in their drinking water during 14 ***-29 cells under basal conditions and after stimulation with lipopolysaccharide(LPS)were treated with CG to evaluate changes in pathways related to analgesia μ-opioid receptor(MOR),cannabinoid receptor 2(CB2),peroxisome proliferator-activated receptor alpha,inflammation[interleukin(IL)-10,IL-1b,and IL-8]and barrier function[mucin 2-5AC,claudin-2,zonula occludens(ZO)-1,ZO-2]using the real-time PCR *** modelling of CG,LPS,lipoteichoic acid(LTA),and phospholipomannan(PLM)was developed,and the abili

关键词： Chitin-glucan Irritable bowel syndrome Abdominal pain Inflammation Intestinal barrier Molecular modelling Microbial cell walls chelation

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Late-onset Very long-chain acyl-CoA dehydrogenase deficiency diagnosis complicated by fulminant myocarditis in adult patient

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Journal of Intensive Medicine 2024年第3期4卷 400-402页

作者： Martin Gérard Clair Douillard Julien Poissy Mehdi Marzouk Christophe Vinsonneau Intensive Care Unit Centre Hospitalier de Bethune-BeuvryBethuneFrance Endocrinology diabetologymetabolism departmentLille reference centre of inborn errors of metabolismLille University HospitalLilleFrance Inserm U1285 CHU LillePôle de réanimationCNRSUMR 8576-UGSF-Unitéde Glycobiologie Structurale et FonctionnelleUniv.LilleLilleFrance

Introduction A 21-year-old woman presented to the emergency department with fatigue,abdominal pain and *** physical activity in school was strictly *** had no family medical history and no personal history but reported frequent episodes of nausea and vomiting lasting 2 to 7 days during the past two years,as well as a weight loss of 9 kg due to reactive anorexia(Body Mass Index 17.5),without triggering factors or *** gastrointestinal symptoms led to the detection of isolated elevated transaminases(aspartate aminotransferase[AST]190 U/L and alanine aminotransferase[ALT]170 U/L);however,the patient did not pursue the proposed etiological *** has been using cannabis once a day for several years,with an increase in consumption over the past year,but no *** reported no other recent change in her habits.

关键词： diagnosis patient elevated

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Systematic review of risk factors,prognosis,and management of colorectal signet-ring cell carcinoma

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2141-2158页

作者： Frederiek Nuytens Vincent Drubay Clarisse Eveno Florence Renaud Guillaume Piessen department of Digestive and Oncological Surgery University LilleClaude Huriez University HospitalLille 59000France department of Digestive and Hepatobiliary/Pancreatic Surgery AZ GroeningeKortrijk 8500Belgium Cambrai Hospital Center and Sainte Marie Group of Hospitals of The Catholic Institute of LilleCambrai 59400France CNRS InsermUMR9020-U1277-CANTHER-CancerUniversity LilleCHU LilleLille 59000France

BACKGROUND Colorectal signet-ring cell carcinoma(CSRCC)is a rare clinical entity which accounts for approximately 1%of all colorectal *** multiple studies concerning this specific topic have been published in the past decades,the pathogenesis,associated risk factors,and potential implications on treatment are still poorly *** the low incidence,historically confusing histological criteria have resulted in confusing ***,the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis,highlight the actual interest to synthesize the known literature regarding *** To provide an updated overview of risk factors,prognosis,and management of *** A literature search in the MEDLINE/PubMed database was conducted with the following search terms used:‘Signet ring cell carcinoma’and‘colorectal’.Studies in English language,published after January 1980,were *** included in the qualitative synthesis were evaluated for content concerning epidemiology,risk factors,and clinical,diagnostic,histological,and molecular features,as well as metastatic pattern and therapeutic *** possible,presented data was extracted in order to present a more detailed overview of the *** In total,67 articles were included for qualitative analysis,of which 54 were eligible for detailed data *** has a reported incidence between 0.1%-2.4%and frequently presents with advanced disease stage at the time of *** is associated with an impaired overall survival(5-year OS:0%-46%)and a worse stagecorrected outcome compared to mucinous and not otherwise specified *** systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been *** is the mainstay of treatment,although the rates of curative resection in CSRCC(21%-82%)are lower compared to those in other histological *** case of peritoneal

关键词： Colorectal cancer Signet-ring cell histology Poorly cohesive cells Systematic review Risk factors Prognosis Therapeutic management

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Severe acute respiratory syndrome coronavirus-2-related and imputable deaths in children:results from the French pediatric national registry

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World Journal of Pediatrics 2024年第6期20卷 611-620页

作者： Marguerite Lockhart-Bouron Noemie Vanel Michael Levy Anais R.Briant Etienne Javouhey Sophie Breinig Julia Dina Marion Caseris Francois Angoulvant Stephane Leteurtre Morgan Recher David W.Brossier Univ.lille CHU LilleULR 2694-METRICS:Evaluation Des Technologies de Sante Et Des Pratiques Medicales59000LilleFrance Pediatric Intensive Care Unit CHU de MarseilleMarseilleFrance Pediatric Intensive Care Unit CHU Robert-DebreAssistance Publique Hopitaux de ParisParisFrance universitéParis-Cite ParisFrance Biostatistics and Clinical Research Unit CHU de Caen Normandie14000CaenFrance Pediatric Intensive Care Hospices Civils de LyonLyonFrance Neonatal andPediatric IntensiveCare Unit Children's HospitalToulouseFrance Virology department INSERM U1311 DynamicureUniv CAEN NormandieCHU de Caen14000 CaenFrance Medical School Universite Caen Normandie14000 CaenFrance department of Pediatrics CHU Robert-DebréAssistance Publique Hopitaux de ParisParisFrance department Women-Mother-Child Service of PediatricsLausanne University Hospital(CHUV)LausanneSwitzerland Pediatric Intensive Care Unit Réanimation Et Soins Intensifs PéediatriquesCHU de CAENAvenue de La Cote de Nacre14000 CaenFrance CHU Sainte Justine Research Center MontréalCanada

Background Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)is responsible for an important mortality rate *** aimed to evaluate the actual imputability of SARS-CoV-2 on the mortality rate associated with SARS-CoV-2-related illnesses in the pediatric intensive care unit(PICU).Secondary objectives were to identify risk factors for *** This national multicenter comparative study comprised all patients under 18 years old with positive SARS-CoV-2 polymerase chain reactions(PCRs)[acute corona virus disease 2019(COVID-19)or incidental SARS-CoV-2 infection]and/or pediatric inflammatory multisystem syndrome(PIMS)recorded in the French PICU registry(PICURe)between September 1,2021,and August 31,*** patients were classified and compared according to their living status at the end of their PICU *** patients were evaluated by four experts in the field of pediatric infectiology and/or pediatric intensive *** imputability of SARS-CoV-2 as the cause of death was classified into four categories:certain,very probable,possible,or unlikely,and was defined by any of the first three *** There were 948 patients included of which 43 died(4.5%).From this,26 deaths(67%)could be attributed to SARS-CoV-2 infection,with an overall mortality rate of 2.8%.The imputability of death to SARS-CoV-2 was considered certain in only one case(O.1%).deceased patients suffered more often from comorbidities,especially heart disease,neurological disorders,hematological disease,cancer,and *** of the deceased patients were admitted for pediatric inflam-matory multisystem syndrome(PIMS).Mortality risk factors were male gender,cardiac comorbidities,cancer,and acute respiratorydistress *** SARS-CoV-2 mortality in the French pediatric population was *** though the imputability of SARS-Cov-2 on mortality was considered in almost two-thirds of cases,this imputability was considered certain in only one case.

关键词： death Pediatric intensive care unit SARS-CoV-2

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Efficacy and tolerability of chitin-glucan combined with simethicone(GASTRAP^(■)DIRECT)in irritable bowel syndrome:A prospective,open-label,multicenter study

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2024年第3期15卷 10-22页

作者： Nathalie Talbodec Pauline Le Roy Peggy Fournier Benoit Lesage Elodie Lepoutre François Castex Jean Michel Godchaux Lionel Vandeville Benjamin Bismuth Xavier Lesage Pauline Bayart Michael Genin Christel Rousseaux Veronique Maquet Salvatore Modica Pierre desreumaux Caroline Valibouze department of Gastroenterology Hôpital privéLe BoisLille 59000France department of Gastroenterology Hôpital privéde Villeneuve d’AscqVilleneuve d’Ascq 59650France Univ.lille CHU LilleULR 2694–METRICSÉvaluation des Technologies de Santéet des Pratiques MédicalesLille 59000France development of Intestinal Biotech 1 Avenue Oscar LambretLille 59045France KitoZyme SA Parc Industriel des hauts Sarts Zone 2Rue de MilmortHerstal 4040Belgium BiOkuris A Parc Industriel des hauts Sarts Zone 2Rue de MilmortHerstal 4040Belgium department of Hepato-Gastroenterology Lille University HospitalLille 59000France U1286-INFINITE Institute for Translational Research in InflammationUniv.LilleInsermCHU LilleLille 59000France department of Digestive Surgery and Transplantation Lille University HospitalLille 59037France

BACKGROUND Irritable bowel syndrome(IBS),defined according to the Rome IV diagnostic criteria,is a chronic functional gastrointestinal disorder characterized by recurrent abdominal pain related to altered bowel ***-line recommended treatments are limited to combining drugs targeting predominant symptoms,particularly pain(antispasmodics),constipation(laxatives),and diarrhea(loperamide),yielding only a limited therapeutic ***^(■)DIRECT is a class IIa medical formulation composed of a combination of chitin-glucan and simethicone indicated for the symptomatic treatment of gas-related gastrointestinal disorders by combining different mechanisms of *** To evaluate the efficacy,tolerability,and safety of 4-week GASTRAP^(■)DIRECT treatment in patients with *** In this prospective,multicenter,open-label trial,120 patients with IBS received three sticks of GASTRAP^(■)DIRECT(1.5 g/d of chitin-glucan and 0.75 mg/d of simethicone)per day for 4 *** primary endpoint was the responder rate,defined as the number of patients whose abdominal pain score decreased by≥30%from baseline to week(W)*** analysis was performed using the per-protocol *** symptoms,impact of global symptoms on daily life,change in stool consistency,and improvement in defecatory disorders were *** Overall,100 patients were *** W4,67%(95%CI:57-75)showed improvement in abdominal pain(score:5.8±2.4 vs 2.9±2.0,Pders],abdominal distension[7.2±2.1 vs 4.4±3.1,Pders],and impact of global symptoms on daily life[7.1±2.0 vs 4.6±2.9,Pders].Stool consistency improved in most patients(90%and 57%for patients with liquid and hard stools,respectively).Overall,42%of patients with defecatory disorders reported very much/considerable improvements by *** severe adverse event occurred,and tolerabil

关键词： Chitin-glucan Irritable bowel syndrome Abdominal pain Flatulence defecatory disorders Stool consistency Natural non-pharmacological treatment

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Targeted therapy for capillary-venous malformations

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3024-3039页

作者： Lola Zerbib Sophia Ladraa Antoine Fraissenon Charles Bayard Marina Firpion Quitterie Venot Sanela Protic Clément Hoguin Amandine Thomas Sylvie Fraitag Jean-Paul Duong Sophie Kaltenbach Estelle Balducci Coline Lefevre Patrick Villarese Vahid Asnafi Christine Broissand Nicolas Goudin Ivan Nemazanyy Gwennhael Autret Bertrand Tavitian Christophe Legendre Nadia Arzouk Veronique Minard-Colin Caroline Chopinet Michael Dussiot denise MAdams Tristan Mirault Laurent Guibaud Paul Isenring Guillaume Canaud universitéParis Cité ParisFrance INSERM U1151 Institut Necker-Enfants MaladesParisFrance Service d’Imagerie Pédiatrique Hôpital Femme-Mère-EnfantHCLBronFrance CREATIS UMR 5220 Villeurbanne 69100France Service de Radiologie Mère-Enfant Hôpital NordSaint EtienneFrance Service d’Anatomie pathologique Hôpital Necker-Enfants MaladesAP-HPParisFrance Laboratoire d’Oncohématologie Hôpital Necker-Enfants MaladesAP-HPParisFrance Pharmacie Hôpital Necker-Enfants MaladesAP-HPParisFrance Necker Bio-Image Analysis INSERM US24/CNRS UMS 3633ParisFrance Platform for Metabolic Analyses Structure Fédérative de Recherche NeckerINSERM US24/CNRS UMS 3633ParisFrance Plateforme Imageries du Vivant Universitéde ParisPARCCINSERMParisFrance Service de Néphrologie Transplantation AdultesHôpital Necker-Enfants MaladesAP-HPParisFrance Service de Transplantation Hôpital La PitiéSalpétrièreAP-HPParisFrance department of Pediatric and Adolescent Oncology INSERM 1015Gustave RoussyUniversitéParis-SaclayVillejuifFrance Service de Physiologie&Explorations Fonctionnelles Cardiovasculaires CHU de LilleLille 59000France INSERM U1163 Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic ImplicationsLaboratoire d’Excellence GR-ExParisFrance Division of Oncology Comprehensive Vascular Anomalies ProgramChildren’s Hospital of PhiladelphiaPhiladelphiaPAUSA Service de Médecine Vasculaire hôpital Européen Georges-PompidouParisFrance Nephrology Research Group L’Hôtel-Dieu de Québec Research CenterDepartment of MedicineFaculty of MedicineLaval UniversityQuebecQC G1R2J6Canada Unitéde médecine translationnelle et thérapies ciblées Hôpital Necker-Enfants MaladesAP-HPParisFrance CNRS UMR8253 Institut Necker-Enfants MaladesParisFrance

Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through *** malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening *** authorized medical treatment exists for patients with venous ***,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient *** showed that these malformations only partially signal through AKT *** compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse *** demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging *** these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous *** assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each *** demonstrated improvement in all 25 *** malformations previously considered intractable were reduced and clinical symptoms were *** showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and TEK malformations respectively,over 6 months on *** conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.

关键词： PIK3CA malformations venous

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Wafer-level vapor cells filled with laser-actuated hermetic seals for integrated atomic devices

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Microsystems & Nanoengineering 2022年第6期8卷 225-235页

作者： Vincent Maurice Clément Carlé Shervin Keshavarzi Ravinder Chutani Samuel Queste Ludovic Gauthier-Manuel Jean-Marc Cote Rémy Vicarini Moustafa Abdel Hafiz Rodolphe Boudot Nicolas Passilly IEMN-Institut d’Electronique de Microélectronique et de Nanotechnologie UMR8520 CNRSUniversitéLilleCentrale LilleF-59000 LilleFrance FEMTO-ST Institute UMR6174 CNRSUniversitéBourgogne Franche-ComtéF-25030 BesançonFrance

Atomic devices such as atomic clocks and optically-pumped magnetometers rely on the interrogation of atoms contained in a cell whose inner content has to meet high standards of purity and ***-blowing techniques and craftsmanship have evolved over many decades to achieve such standards in macroscopic vapor *** the emergence of chip-scale atomic devices,the need for miniaturization and mass fabrication has led to the adoption of microfabrication techniques to make millimeter-scale vapor ***,many shortcomings remain and no process has been able to match the quality and versatility of glass-blown ***,we introduce a novel approach to structure,fill and seal microfabricated vapor cells inspired from the century-old approach of glass-blowing,through opening and closing single-use zero-leak microfabricated *** valves are actuated exclusively by laser,and operate in the same way as the“make-seals”and“break-seals”found in the filling apparatus of traditional *** structures are employed to fill cesium vapor cells at the *** make-seal structure consists of a glass membrane that can be locally heated and deflected to seal a *** break-seal is obtained by breaching a silicon wall between *** new approach allows adapting processes previously restricted to glass-blown *** can also be extended to vacuum microelectronics and vacuum-packaging of micro-electro-mechanical systems(MEMS)devices.

关键词： filled vacuum heated

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Moisture-Induced Non-Equilibrium Phase Segregation in Triple Cation Mixed Halide Perovskite Monitored by In Situ Characterization Techniques and Solid-State NMR

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Energy & Environmental Materials 2023年第2期6卷 185-194页

作者： Mohammad Ali Akhavan Kazemi Nicolas Folastre Parth Raval Michel Sliwa Jean Marie Vianney Nsanzimana Sema Golonu Arnaud demortiere Jean Rousset Olivier Lafon Laurent delevoye G.N.Manjunatha Reddy Frédéric Sauvage Laboratoire de Réactivité et Chimie des Solides(LRCS) UMR CNRS 7314-Institut de Chimie de Picardie FR 3085Université de Picardie Jules Verne33 rue Saint LeuAmiens Cedex FR-80039France CNRS Centrale LilleUMR 8181UCCSUnitéde Catalyse et Chimie du SolideUniversité de LilleUniversitéd’ArtoisLille F-59000France UMR 8516-LASIRE-Laboratoire de Spectroscopie pour les Interactions la Réactivité et l’EnvironnementCNRSUniversitéde LilleLille F-59000France EDF R&D EDF LabBoulevard Gaspard MongePalaiseau 91120France

Environmental stability is a major bottleneck of perovskite solar *** a handful of studies are investigating the effect of moisture on the structural degradation of the *** mostly rely on ex situ experiments and on completely degraded samples,which restrict the assessment on initial and final *** combining in situ X-ray diffraction under controlled 85%relative humidity,and live observations of the water-induced degradation using liquid-cell transmission electron microscopy,we reveal two competitive degradation paths leading on one hand to the decomposition of state-of-theart mixed cation/anion(Cs_(0.05)(MA_(0.17)FA_(0.83))_(0.95)Pb(Br_(0.17)I_(0.83))_(3)(CsMAFA)into PbI_(2) through a dissolution/recrystallization mechanism and,on the other hand,to a non-equilibrium phase segregation leading to CsPb_(2)Br_(5) and a Cesium-poor/iodide-rich Cs_(0.05)-x(MA_(0.17)FA_(0.83))_(0.95)Pb(Br_(0.17-2y)I_(0.83)+2y)_(3) *** degradation mechanism is corroborated at atomic-scale resolution through solid-state ^(1)H and ^(133)Cs NMR *** to moisture leads to a film containing important heterogeneities in terms of morphology,photoluminescence intensities,and *** results provide new insights and consensus that complex perovskite compositions,though very performant as champion devices,are comparatively metastable,a trait that limits the chances to achieve long-term stability.

关键词： liquid-cell transmission electron microscopy moisture degradation perovskite stability phase segregation solid-state NMR

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Transaction fees optimization in the Ethereum blockchain

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Blockchain(Research and Applications) 2022年第3期3卷 12-22页

作者： Arnaud Laurent Luce Brotcorne Bernard Fortz INRIA lille Nord-Europe 40 Avenue HalleyLille59000France universitélibre de Bruxelles Bruxelles1050Belgium

In blockchains,transaction fees are fixed by the *** probability for a transaction to be processed quickly increases with the fee *** this paper,we study the transaction fee optimization problem in the Ethereum *** problem consists of determining the minimum price a user should pay so that its transaction is processed with a given probability in a given amount of *** reach this goal,we define a new solution method based on a Monte Carlo approach to predict the probability that a transaction will be mined within a given time *** results on real data highlight the quality of the results.

关键词： Pricing Blockchain Ethereum Optimization Gasprice Ether Monte-Carlo

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The Effect of Different Freeze-Thaw Cycles on Mortar Gas Permeability and Pore Structure

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Fluid Dynamics & Materials Processing 2023年第6期19卷 1623-1636页

作者： Wei Chen Ao Xu Hejun Zhang Mingquan Sheng Yue Liang Frederic Skoczylas School of Civil Engineering Architecture and EnvironmentHubei University of TechnologyWuhanChina CNRS Centrale LilleUMR9013-LaMcube-Laboratoire de Mécanique Multiphysique et MultiéchelleUniversitéde LilleLilleFrance

Two different freeze-thaw cycles(FTC)are considered in this study to assess the related impact on gas permeability and micro-pore structure of a *** are the water-freezing/water-thawing(WF-WT)and the air-freezing/air-thawing(AF-AT)*** problem is addressed experimentally through an advanced nuclear magnetic resonance(NMR)technique able to provide meaningful information on the relationships among gas permeability,pore structure,mechanical properties,and the number of *** is shown that the mortar gas permeability increases with the number of FTCs,the increase factor being 20 and 12.83 after 40 cycles for the WF-WT and AF-AT,*** results also confirm that gas permeability hysteresis phenomena occur during the confining pressure loading and unloading process.

关键词： Mortar freeze-thaw cycles gas permeability pore structure NMR mechanical properties

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