BACKGROUND Irritable bowel syndrome(IBS)is one of the most frequent and debilitating conditions leading to gastroenterological referrals.However,recommended treatments remain limited,yielding only limited therapeutic ...BACKGROUND Irritable bowel syndrome(IBS)is one of the most frequent and debilitating conditions leading to gastroenterological referrals.However,recommended treatments remain limited,yielding only limited therapeutic gains.Chitin-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 Authority.To 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 IBS.AIM To evaluate the roles of CG in visceral analgesia,intestinal inflammation,barrier function,and to develop computational molecular models.METHODS 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 rats.Intracolonic 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)groups.The 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 d.HT-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 method.Molecular modelling of CG,LPS,lipoteichoic acid(LTA),and phospholipomannan(PLM)was developed,and the ability of CG to chelate microbial pathogenic lipids was evaluated by docking and molecular dynamics simulations.Data were expressed as the mean±SEM.RESULTS Daily CG orally-administered to rats or mice was well tolerated without including diarrhea,visceral hypersensitivity,or inflammation,as evaluated at histological and molecular levels.In a model of CRD,CG at a dosage of 3 g/d HED significantly decreased visceral pain perception by 14%after 2 wk of administration(P<0.01)and reduced inflammation intensity by 50%,resulting in complete regeneration of the colonic mucosa in mice with DSS-induced colitis.To better reproduce the characteristics of visceral pain in patients with IBS,we then measured the therapeutic impact of CG in rats with TNBS-induced inflammation to long-lasting visceral hypersensitivity.CG at a dosage of 1.5 g/d HED decreased visceral pain perception by 20%five weeks after colitis induction(P<0.01).When the CG dosage was increased to 3.0 g/d HED,this analgesic effect surpassed that of the spasmolytic agent phloroglucinol,manifesting more rapidly within 3 wk and leading to a 50%inhibition of pain perception(P<0.0001).The underlying molecular mechanisms contributing to these analgesic and anti-inflammatory effects of CG involved,at least in part,a significant induction of MOR,CB2 receptor,and IL-10,as well as a significant decrease in pro-inflammatory cytokines IL-1b and IL-8.CG also significantly upregulated barrier-related genes including muc5AC,claudin-2,and ZO-2.Molecular modelling of CG revealed a new property of the molecule as a chelator of microbial pathogenic lipids,sequestering gram-negative LPS and gram-positive LTA bacterial toxins,as well as PLM in fungi at the lowesr energy conformations.CONCLUSION CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products,suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBSlike symptoms.展开更多
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 habits...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 habits.First-line recommended treatments are limited to combining drugs targeting predominant symptoms,particularly pain(antispasmodics),constipation(laxatives),and diarrhea(loperamide),yielding only a limited therapeutic gain.GASTRAP^(■)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 action.AIM To evaluate the efficacy,tolerability,and safety of 4-week GASTRAP^(■)DIRECT treatment in patients with IBS.METHODS 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 weeks.The primary endpoint was the responder rate,defined as the number of patients whose abdominal pain score decreased by≥30%from baseline to week(W)4.The analysis was performed using the per-protocol set.Cardinal symptoms,impact of global symptoms on daily life,change in stool consistency,and improvement in defecatory disorders were evaluated.RESULTS Overall,100 patients were evaluated.At W4,67%(95%CI:57-75)showed improvement in abdominal pain(score:5.8±2.4 vs 2.9±2.0,P<0.0001).Similar improvements were observed for bloating[8.0±1.7 vs 4.7±2.9,P<0.0001;60%(95%CI:50-70)responders],abdominal distension[7.2±2.1 vs 4.4±3.1,P<0.0001;53%(95%CI:43-63)responders],and impact of global symptoms on daily life[7.1±2.0 vs 4.6±2.9,P<0.0001;54%(95%CI:44-64)responders].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 W2.No severe adverse event occurred,and tolerability was rated“good”or“very good”by 93%of patients.CONCLUSION GASTRAP^(■)DIRECT is safe and well tolerated,alleviating IBS symptoms rapidly in 2 weeks.This open-label study suggests that the combination of chitin-glucan and simethicone could be beneficial in patients with IBS.展开更多
BACKGROUND Postoperative recurrence(POR)after ileocecal resection(ICR)affects most Crohn's disease patients within 3-5 years after surgery.Adherent-invasive Escherichia coli(AIEC)typified by the LF82 strain are pa...BACKGROUND Postoperative recurrence(POR)after ileocecal resection(ICR)affects most Crohn's disease patients within 3-5 years after surgery.Adherent-invasive Escherichia coli(AIEC)typified by the LF82 strain are pathobionts that are frequently detected in POR of Crohn's disease and have a potential role in the early stages of the disease pathogenesis.Saccharomyces cerevisiae CNCM I-3856 is a probiotic yeast reported to inhibit AIEC adhesion to intestinal epithelial cells and to favor their elimination from the gut.AIM To evaluate the efficacy of CNCM I-3856 in preventing POR induced by LF82 in an HLA-B27 transgenic(TgB27)rat model.METHODS Sixty-four rats[strain F344,38 TgB27,26 control non-Tg(nTg)]underwent an ICR at the 12th wk(W12)of life and were sacrificed at the 18th wk(W18)of life.TgB27 rats were challenged daily with oral administration of LF82(109 colony forming units(CFUs)/day(d),n=8),PBS(n=5),CNCM I-3856(109 CFUs/d,n=7)or a combination of LF82 and CNCM I-3856(n=18).nTg rats receiving LF82(n=5),PBS(n=5),CNCM I-3856(n=7)or CNCM I-3856 and LF82(n=9)under the same conditions were used as controls.POR was analyzed using macroscopic(from 0 to 4)and histologic(from 0 to 6)scores.Luminal LF82 quantifications were performed weekly for each animal.Adherent LF82 and inflammatory/regulatory cytokines were quantified in biopsies at W12 and W18.Data are expressed as the median with the interquartile range.RESULTS nTg animals did not develop POR.A total of 7/8(87%)of the TgB27 rats receiving LF82 alone had POR(macroscopic score≥2),which was significantly prevented by CNCM I-3856 administration[6/18(33%)TgB27 rats,P=0.01].Macroscopic lesions were located 2 cm above the anastomosis in the TgB27 rats receiving LF82 alone and consisted of ulcerations with a score of 3.5(2-4).Seven out of 18 TgB27 rats(39%)receiving CNCM I-3856 and LF82 had no macroscopic lesions.Compared to untreated TgB27 animals receiving LF82 alone,coadministration of CNCM I-3856 and LF82 significantly reduced the macroscopic[3.5(2-4)vs 1(0-3),P=0.002]and histological lesions by more than 50%[4.5(3.3-5.8)vs 2(1.3-3),P=0.003].The levels of adherent LF82 were correlated with anastomotic macroscopic scores in TgB27 rats(r=0.49,P=0.006),with a higher risk of POR in animals having high levels of luminal LF82(71.4%vs 25%,P=0.02).Administration of CNCM I-3856 significantly reduced the levels of luminal and adherent LF82,increased the production of interleukin(IL)-10 and decreased the production of IL-23 and IL-17 in TgB27 rats.CONCLUSION In a reliable model of POR induced by LF82 in TgB27 rats,CNCM I-3856 prevents macroscopic POR by decreasing LF82 infection and gut inflammation.展开更多
This paper introduced a novel microstructure-based constitutive model designed to comprehensively characterize the intricate mechanical behavior of anisotropic clay rocks under the influence of water saturation.The pr...This paper introduced a novel microstructure-based constitutive model designed to comprehensively characterize the intricate mechanical behavior of anisotropic clay rocks under the influence of water saturation.The proposed model encompasses elastoplastic deformation,time-dependent behavior,and induced damage.A two-step homogenization process incorporates mineral compositions and porosity to determine the macroscopic elastic tensor and plastic yield criterion.The model also considers interfacial debonding between the matrix and inclusions to capture rock damage.The application of the proposed model is demonstrated through an analysis of Callovo-Oxfordian clayey rocks,specifically in the context of radioactive waste disposal in France.Model parameters are determined,followed by numerical simulations of various laboratory tests including lateral decompression tests with constant mean stress,triaxial compression tests under different water saturation conditions,and creep tests.The numerical results are compared with corresponding experimental data to assess the efficacy of the proposed model.展开更多
CO_(2)hydrogenation is an attractive way to store and utilize carbon dioxide generated by industrial processes,as well as to produce valuable chemicals from renewable and abundant resources.Iron catalysts are commonly...CO_(2)hydrogenation is an attractive way to store and utilize carbon dioxide generated by industrial processes,as well as to produce valuable chemicals from renewable and abundant resources.Iron catalysts are commonly used for the hydrogenation of carbon oxides to hydrocarbons.Iron-molybdenum catalysts have found numerous applications in catalysis,but have been never evaluated in the CO_(2)hydrogenation.In this work,the structural properties of iron-molybdenum catalysts without and with a promoting alkali metal(Li,Na,K,Rb,or Cs)were characterized using X-ray diffraction,hydrogen temperatureprogrammed reduction,CO_(2)temperature-programmed desorption,in-situ^(57)Fe Mossbauer spectroscopy and operando X-ray adsorption spectroscopy.Their catalytic performance was evaluated in the CO_(2)hydrogenation.During the reaction conditions,the catalysts undergo the formation of an iron(Ⅱ)molybdate structure,accompanied by a partial reduction of molybdenum and carbidization of iron.The rate of CO_(2)conversion and product selectivity strongly depend on the promoting alkali metals,and electronegativity was identified as an important factor affecting the catalytic performance.Higher CO_(2)conversion rates were observed with the promoters having higher electronegativity,while low electronegativity of alkali metals favors higher light olefin selectivity.展开更多
In this study, the hydromechanical behavior of a concrete fracture under coupled compressive and shear stresses was investigated. A special experimental device was designed to create a planar fracture in a cylindrical...In this study, the hydromechanical behavior of a concrete fracture under coupled compressive and shear stresses was investigated. A special experimental device was designed to create a planar fracture in a cylindrical sample and to carry out different kinds of hydromechanical tests on the fracture. Four series of laboratory tests were performed on an ordinary concrete sample. Hydrostatic compression tests were first conducted to characterize the normal compressibility of the fracture. In the second series, direct shear tests were conducted on the fracture under different normal stresses. The maximal shear stress of the fracture was determined as a function of the normal stress. In the third series, fluid flow tests were carried out in view of characterizing the overall hydraulic conductivity of the fracture as a function of its opening and closure. Shear tests with a constant fluid pressure were finally performed to investigate the influence of fluid pressure on the deformation behavior of concrete fractures. Based on the experimental investigation, an elastoplastic model is proposed. This model takes into account the nonlinear elastic behavior of a fracture under normal compression and the plastic deformation and failure due to shear stress. The model was coupled with the classical Darcy's law to describe the fluid flow along the fracture by considering the variation of permeability with fracture aperture. Numerical results agree with experimental data from various laboratory tests.展开更多
AIMTo confirm previous conclusions on Saccharomyces cerevisiae (S. cerevisiae) CNCM I-3856 for irritable bowel syndrome (IBS) management.METHODSAn individual patient data meta-analysis was performed on two randomized ...AIMTo confirm previous conclusions on Saccharomyces cerevisiae (S. cerevisiae) CNCM I-3856 for irritable bowel syndrome (IBS) management.METHODSAn individual patient data meta-analysis was performed on two randomized clinical trials studying the effect of S. cerevisiae CNCM I-3856 supplementation on gastrointestinal (GI) symptoms in IBS subjects. A total of 579 IBS subjects were included. Outcomes were the daily Likert scale scores of abdominal pain/discomfort and bloating [area under the curve (AUC) and weekly means], responder status, and bowel movements (stool frequency and consistency). Statistical analyses were conducted in Intent to Treat (ITT) population, IBS-C subjects and IBS-C subjects with an abdominal pain/discomfort score higher than or equal to 2 at baseline (“IBS-C ≥ 2 subpopulation”).RESULTSS. cerevisiae CNCM I-3856 significantly improved abdominal pain/discomfort and bloating during the second month of supplementation [AUC (W5-W8)] with improvement up to the minimal clinically relevant threshold of 10%: a 12.3% reduction of abdominal pain/discomfort in the ITT population compared to the Placebo group (P = 0.0134) has been observed. In the IBS-C ≥ 2 subpopulation, there were a 13.1% reduction of abdominal pain/discomfort and a 14.9% reduction of bloating compared to the Placebo group (P = 0.0194 and P = 0.0145, respectively). GI symptoms significantly decreased during supplementation but no statistical differences were reported between groups at the end of the supplementation period. Responder status was defined as a subject who experienced a decrease of 1 arbitrary unit (a.u.) or 50% of the abdominal discomfort score from baseline for at least 2 wk out of the last 4 wk of the study. A significant difference between groups was reported in the ITT population, when considering the first definition: subjects in the Active group had 1.510 higher odds to be a responder (reduction of 1 a.u. of abdominal pain/discomfort) compared with subjects in the Placebo group (P = 0.0240). At the end of supplementation period, stool consistency in the Active group of the ITT population was significantly improved and classified as “normal” compared to Placebo (respectively 3.13 ± 1.197 a.u. vs 2.58 ± 1.020 a.u., P = 0.0003). Similar results were seen in the IBS-C ≥ 2 subpopulation (Active group: 3.14 ± 1.219 a.u. vs Placebo group: 2.59 ± 1.017 a.u., P = 0.0009).CONCLUSIONThis meta-analysis supports previous data linking S. cerevisiae I-3856 and improvement of GI symptoms, in IBS overall population and in the IBS-C and IBS-C ≥ 2 subpopulations.展开更多
AIM:To investigate the association of 10 known common gene variants with susceptibility to type 2diabetes mellitus(T2D)among Omanis.METHODS:Using case-control design,a total of992 diabetic patients and 294 normoglycem...AIM:To investigate the association of 10 known common gene variants with susceptibility to type 2diabetes mellitus(T2D)among Omanis.METHODS:Using case-control design,a total of992 diabetic patients and 294 normoglycemic Omani Arabs were genotyped,by an allelic discrimination assay-by-design TaqMan method on fast real time polymerase chain reaction system,for the following gene variants:KCNJ11(rs5219),TCF7L2(rs7903146),CDKAL1(rs10946398),CDKN2A/B(rs10811661),FTO(rs9939609 and rs8050136),IGF2BP2(rs4402960),SLC30A8(rs13266634)CAPN10(rs3792267)and HHEX(rs1111875).T2D patients were recruited from the Diabetes Clinic(n=243)and inpatients(n=749)at Sultan Qaboos Univesity Hospital(SQUH),Muscat,Oman.Adult control participants(n=294)were volunteers from the community and from those visiting Family Medicine Clinic at SQU,for regular medical checkup.The difficulty in recruiting Omani participants with no family history of diabetes was the main reason behind the small number of control participants in this study.Almost all volunteers questioned had a relativewith diabetes mellitus.Inspite of the small number of normoglycemic controls in this study,this sample was sufficient for detection of genes and loci for common alleles influencing T2D with an odds ratio of≥1.3reaching at least 80%power.Data was collected from June 2010 to February 2012.RESULTS:Using binary logistic regression analysis,four gene variants showed significant association with T2D risk:KCNJ11(rs5219,P=5.8×10^(-6),OR=1.74),TCF7L2(rs7903146,P=0.001,OR=1.46),CDKAL1(rs10946398,P=0.002,OR=1.44)and CDKN2A/B(rs10811661,P=0.020,OR=1.40).The fixation index analysis of these four gene variants indicated significant genetic differentiation between diabetics and controls{[KCNJ11(rs5219),P<0.001],[TCF7L2(rs7903146),P<0.001],[CDKAL1(rs10946398),P<0.05],[CDKN2A/B(rs10811661),P<0.05]}.The highest genotype variation%between diabetics and controls was found at KCNJ11(2.07%)and TCF7L2(1.62%).This study was not able to detect an association of T2D risk with gene variants of IGF2BP2(rs4402960),SLC30A8(rs13266634),CAPN10(rs3792267)and HHEX(rs1111875).Moreover,no association was found between FTO gene variants(rs9939609 and rs8050136)and T2D risk.However,T2D risk was found to be significantly associated with obesity(P=0.002,OR=2.22);and with the Waist-to-Hip ratio(n=532,P=1.9×10^(-7),OR=2.4),[among males(n=234,P=1.2×10^(-4),OR=2.0)and females(n=298,P=0.001,OR=6.3)].CONCLUSION:Results confirmed the association of KCNJ11(rs5219),TCF7L2(rs7903146),CDKAL1(rs10946398)and CDKN2A/B(rs10811661)gene variants with susceptibility to T2D among Omani Arabs.展开更多
In the past decade, studies of non-coding RNAs increase. Non-coding RNAs are divided in two classes: small and long non-coding RNA. It was shown that long non-coding RNAs regulate expression of 70% of genes. Long non-...In the past decade, studies of non-coding RNAs increase. Non-coding RNAs are divided in two classes: small and long non-coding RNA. It was shown that long non-coding RNAs regulate expression of 70% of genes. Long non-coding RNAs are involved in several cellular processes like epigenetic regulation, dosage compensation, alternative splicing and stem cells maintenance for example. Misregulations of their expression induce diseases such as developmental syndrome or cancer. In this review, we describe some functions of long non-coding RNA in cells. Furthermore, we study the H19/IGF2 cluster: an imprinted genomic locus located on chromosome 11p15.5. Genomic imprinting allows gene expression from a single allele in a parent-origin-dependent manner. This cluster encode for the first long non-coding RNA identified: H19. In 1990, it was established that H19 functions as a riboregulator. Recently, it was shown that H19 is a precursor of microRNA (hsa-miR-675), and several news transcripts were identified at the H19/IGF2 locus. So, the complexity of this locus increasing, in this review, we summarize our current understanding about the H19/IGF2 cluster both in terms of transcription as well as in terms of functions in cells. We highlight the involvement of H19, its new antisense transcript 91H and its microRNA, in the regulation of IGF receptor function and in cell cycle progression.展开更多
Background Postprocedural aortic regurgitations following transcatheter aortic valve implantation （TAVI） procedures remain an is- sue. Benefit of oversizing strategies to prevent them isn＇t well established. We com...Background Postprocedural aortic regurgitations following transcatheter aortic valve implantation （TAVI） procedures remain an is- sue. Benefit of oversizing strategies to prevent them isn＇t well established. We compared different level of oversizing in our cohort of con- secutive patients to address if severe oversizing compared to normal sizing had an impact on post-procedural outcomes. Methods From January 2010 to August 2013, consecutive patients were referred for TAVI with preoperative Multislice-CT （MSCT） and the procedures were achieved using Edwards Sapien~ or Corevalve devices~. Retrospectively, according to pre-procedural MSCT and the valve size, pa- tients were classified into three groups： normal, moderate and severe oversizing; depending on the ratio between the prosthesis area and the annulus area indexed and measured on MSCT. Main endpoint was mid-term mortality and secondary endpoints were the Valve Academic Research Consortium （VARC-2） endpoints. Results Two hundred and sixty eight patients had a MSCT and underwent TAVI procedure, with mainly Corevalve~. While all-cause and cardiovascular mortality rates were similar in all groups, post-procedural new pacemaker （PM） implantation rate was significantly higher in the severe oversizing group （P = 0.03）, while we observed more in-hospital congestive heart-failure （P = 0.02） in the normal sizing group. There was a trend toward more moderate to severe aortic regurgitation （AR） in the normal sizing group （P = 0.07）. Conclusions Despite a higher rate of PM implantation, oversizing based on this ratio reduces aortic leak with lower rates of post-procedural complications and a similar mid-term survival.展开更多
The recent discovery of cancer cell plasticity,i.e.their ability to reprogram into cancer stem cells(CSCs)either naturally or under chemotherapy and/or radiotherapy,has changed,once again,the way we consider cancer tr...The recent discovery of cancer cell plasticity,i.e.their ability to reprogram into cancer stem cells(CSCs)either naturally or under chemotherapy and/or radiotherapy,has changed,once again,the way we consider cancer treatment.If cancer stemness is a reversible epigenetic state rather than a genetic identity,opportunities will arise for therapeutic strategies that remodel epigenetic landscapes of CSCs.However,the systematic use of DNA methyltransferase and histone deacetylase inhibitors,alone or in combination,in advanced solid tumors including colorectal cancers,regardless of their molecular subtypes,does not seem to be the best strategy.In this review,we first summarize the knowledge researchers have gathered on the epigenetic signatures of CSCs with the difficulty of isolating rare populations of cells.We raise questions about the relevant use of currently available epigenetic inhibitors(epidrugs)while the expression of numerous cancer stem cell markers are often repressed by epigenetic mechanisms.These markers include the three cluster of differentiation CD133,CD44 and CD166 that have been extensively used for the isolation of colon CSCs.and.Finally,we describe current treatment strategies using epidrugs,and we hypothesize that,using correlation tools comparing associations of relevant CSC markers with chromatin modifier expression,we could identify better candidates for epienzyme targeting.展开更多
The freshness and quality indices of whiting (Merlangius merlangus) influenced by a large number of chemical volatile compounds, are here analyzed in order to select the most relevant compounds as predictors for these...The freshness and quality indices of whiting (Merlangius merlangus) influenced by a large number of chemical volatile compounds, are here analyzed in order to select the most relevant compounds as predictors for these indices. The selection process was performed by means of recent statistical variable selection methods, namely robust model-free feature screening, based on quantile correlation and composite quantile correlation. On the one hand, compounds 2-Methyl-1-butanol, 3-Methyl-1-butanol, Ethanol, Trimethylamine, 3-Methyl butanal, 2-Methyl-1-propanol, Ethylacetate, 1-Butanol and 2,3-Butanedione were identified as major predictors for the freshness index and on the other hand, compounds 3-Methyl-1-butanol, 2-Methyl-1- butanol, Ethanol, 3-Methyl butanal, 3-Hydroxy-2-butanone, 1-Butanol, 2,3-Butane- dione, 3-Pentanol, 3-Pentanone and 2-Methyl-1-propanol were identified as major predictors for the quality index.展开更多
Some micromechanics-based constitutive models are presented in this study for porous geomaterials.These micro-macro mechanical models focus on the effect of porosity and the inclusions on the macroscopic elastoplastic...Some micromechanics-based constitutive models are presented in this study for porous geomaterials.These micro-macro mechanical models focus on the effect of porosity and the inclusions on the macroscopic elastoplastic behaviors of porous materials. In order to consider the effect of pores and the compressibility of the matrix, some macroscopic criteria are presented firstly for ductile porous medium having one population of pores with different types of matrix(von Mises, Green type, Misese Schleicher and Druckere Prager). Based on different homogenization techniques, these models are extended to the double porous materials with two populations of pores at different scales and a Druckere Prager solid phase at the microscale. Based on these macroscopic criteria, complete constitutive models are formulated and implemented to describe the overall responses of typical porous geomaterials(sandstone,porous chalk and argillite). Comparisons between the numerical predictions and experimental data with different confining pressures or different mineralogical composites show the capabilities of these micromechanics-based models, which take into account the effects of microstructure on the macroscopic behavior and significantly improve the phenomenological ones.展开更多
The return to old building methods by mixing crop by-products with mineral binders is arousing great interest in Europe since about 25 years.The use of these bio-aggregates based materials for the design of building e...The return to old building methods by mixing crop by-products with mineral binders is arousing great interest in Europe since about 25 years.The use of these bio-aggregates based materials for the design of building envelopes is a valuable opportunity to deal with increasingly demanding thermal regulations.In addition,the regulatory framework is moving towards reducing the overall car-bon footprint of new buildings.Some traditional and historic buildings are based on timber framing with earth-straw as infill material for instance.Hemp concrete is a bio-based material that can be manually tamped in timber stud walls or more recently in the form of precast blocks.Owing to their low compressive strength,bio-based concretes using a large volume fraction of plant-derived aggregates are only considered as thermal and sound insulation materials.The structural design practice of wood frame walls does not assume any mechanical contribution of hemp concrete whereas it may contribute to the racking strength of the structure.In this context,more research is needed regarding the shear behavior of crop by-products and bio-based concretes.In this case,the objective of the study was to perform direct shear tests under three levels of normal pressure on hemp shiv and rice husk as unbound crop by-products.The results showed that the friction angle of the granular skeleton based on rice husk for a given relative displacement was significantly lower than that measured on hemp shiv.This is in accordance with what had been observed on bio-based concretes cast by mixing aggregates with lime and shear strength parameters measured by means of triaxial compression.展开更多
Recently,Artificial Neural Networks(ANNs)have been used for various scientific and engineering applications essentially because they allow the modeling of a process,which starts from the database containing the variab...Recently,Artificial Neural Networks(ANNs)have been used for various scientific and engineering applications essentially because they allow the modeling of a process,which starts from the database containing the variables that describe that particular process.They have already been applied to the study of landslides in particular,with reference to the indirect determination of the triggering展开更多
The first International Symposium on Advances in Pharmaceutical Analysis (APA 2017) was started and held successfully in Wuhan University, China from November 17 to 19, 2017. The organization of the 2nd International ...The first International Symposium on Advances in Pharmaceutical Analysis (APA 2017) was started and held successfully in Wuhan University, China from November 17 to 19, 2017. The organization of the 2nd International Symposium on Advances in Pharmaceutical Analysis in the capital city of Flanders, Lille, was both an exciting and challenging project because the idea of an annual meeting between our two long cooperating Schools of Pharmaceutical Sciences of Wuhan and Lille, stood to reason.展开更多
Liver X receptors(LXRs)are members of the nuclear receptor superfamily,which have been implicated in lipid ho-meostasis and more recently in glucose metabolism.Here,we show that glucose does not change LXRα protein l...Liver X receptors(LXRs)are members of the nuclear receptor superfamily,which have been implicated in lipid ho-meostasis and more recently in glucose metabolism.Here,we show that glucose does not change LXRα protein level,but affects its localization in pancreatic β-cells.LXRα is found in the nucleus at 8 mM glucose and in the cytoplasm at4.2 mM.Addition of glucose translocates LXRα from the cytoplasm into the nucleus.Moreover,after the activation ofLXR by its synthetic non-steroidal agonist(T0901317),insulin secretion and glucose uptake are increased at 8 mM anddecreased at 4.2 mM glucose in a dose-dependent manner.Furthermore,at low glucose condition,okadaic acid reversedLXRα effect on insulin secretion,suggesting the involvement of glucose signaling through a phosphorylation-dependentmechanism.展开更多
BACKGROUND The antidepressant escitalopram is widely prescribed for the treatment of depression.It is generally well-tolerated,and cholestasis is not mentioned in its summary of product characteristics(Sm PC).We prese...BACKGROUND The antidepressant escitalopram is widely prescribed for the treatment of depression.It is generally well-tolerated,and cholestasis is not mentioned in its summary of product characteristics(Sm PC).We present a case of cholestatic and cytolysis liver injury due to escitalopram and a Vigi Base?study.CASE SUMMARY A 68-year-old man was admitted to our emergency unit due to clinical jaundice associated with hepatitis,pruritus and dark urine.We tested the patient for the most common etiologies of jaundice,including hemolysis,viral hepatitis,cirrhosis,carcinoma,cholangitis,cholelithiasis and intrahepatic or extrahepatic obstruction.The etiological study was negative,and an adverse drug reaction was the sole possible explanation.The patient was receiving treatment with escitalopram.Two days after its withdrawal,pruritus was resolved.Ten days after withdrawal,clinical jaundice disappeared.It took a month and three weeks after withdrawal for the patient to have normalized liver function tests.To our knowledge,this is the first reported case of cholestasis where treatment with escitalopram was the only possible cause,with a highly probable causality.In addition,we determined whether escitalopram is associated with hepatotoxicity and cholestasis by performing a disproportionality analysis.All cases of hepatobiliary disorders induced by escitalopram and reported in the World Health Organization pharmacovigilance database(Vigi Base?)were analyzed to characterize this toxicity.We found that patients treated with escitalopram had an increased risk of hepatitis[odds ratio(OR)=1.938(1.186-3.166)]and cholestasis[OR=1.866(1.279-2.724)][OR(95%confidence interval)].The median duration between the introduction of escitalopram and the occurrence of acute hepatitis and/or cholestasis was ten days+/-seven days.CONCLUSION Although extremely rare,this case report,the review of the literature and the pharmacovigilance update confirm that escitalopram can cause drug-induced hepatotoxicity and cholestasis,generally within a week after initiation.Thus,escitalopram should be withdrawn immediately if an iatrogenic cause cannot be excluded.If its responsibility is ascertained,escitalopram should be consequently contraindicated.In addition,serotoninergic antidepressants in patients with nonsevere depression are ineffective and harmful.Finally,the Sm PC of escitalopram should be updated to alert for this risk and give clear clinical guidelines.展开更多
In this paper,the thermo-hydro-mechanical(THM)response of claystone is studied via a series of parametric studies,considering the evolution of mechanical properties and deformation behavior of corroded steel.The numer...In this paper,the thermo-hydro-mechanical(THM)response of claystone is studied via a series of parametric studies,considering the evolution of mechanical properties and deformation behavior of corroded steel.The numerical simulations are performed by using a coupled THM finite element code and two different constitutive models:a visco-elastoplastic model for geological formation and a von Mises type model for steel liner.The mechanical properties and deformation behavior of corroded steel are described in a conceptual model.Finally,a disposal tunnel supported by a steel liner is studied and a series of parametric studies is defined to demonstrate the corrosion effects of steel liner on the THM response of the claystone.The comparison of different numerical calculations exhibits that the volumetric expansion related to corrosion products has an important impact on the stress and displacement fields in the claystone surrounding the disposal tunnel.However,the evolutions of temperature and liquid pressure in the claystone are essentially controlled by its THM properties and independent of the steel corrosion.展开更多
基金Supported by the Service Public de Wallonie(SPW-EER,convention 8588,Belgium).
文摘BACKGROUND Irritable bowel syndrome(IBS)is one of the most frequent and debilitating conditions leading to gastroenterological referrals.However,recommended treatments remain limited,yielding only limited therapeutic gains.Chitin-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 Authority.To 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 IBS.AIM To evaluate the roles of CG in visceral analgesia,intestinal inflammation,barrier function,and to develop computational molecular models.METHODS 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 rats.Intracolonic 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)groups.The 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 d.HT-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 method.Molecular modelling of CG,LPS,lipoteichoic acid(LTA),and phospholipomannan(PLM)was developed,and the ability of CG to chelate microbial pathogenic lipids was evaluated by docking and molecular dynamics simulations.Data were expressed as the mean±SEM.RESULTS Daily CG orally-administered to rats or mice was well tolerated without including diarrhea,visceral hypersensitivity,or inflammation,as evaluated at histological and molecular levels.In a model of CRD,CG at a dosage of 3 g/d HED significantly decreased visceral pain perception by 14%after 2 wk of administration(P<0.01)and reduced inflammation intensity by 50%,resulting in complete regeneration of the colonic mucosa in mice with DSS-induced colitis.To better reproduce the characteristics of visceral pain in patients with IBS,we then measured the therapeutic impact of CG in rats with TNBS-induced inflammation to long-lasting visceral hypersensitivity.CG at a dosage of 1.5 g/d HED decreased visceral pain perception by 20%five weeks after colitis induction(P<0.01).When the CG dosage was increased to 3.0 g/d HED,this analgesic effect surpassed that of the spasmolytic agent phloroglucinol,manifesting more rapidly within 3 wk and leading to a 50%inhibition of pain perception(P<0.0001).The underlying molecular mechanisms contributing to these analgesic and anti-inflammatory effects of CG involved,at least in part,a significant induction of MOR,CB2 receptor,and IL-10,as well as a significant decrease in pro-inflammatory cytokines IL-1b and IL-8.CG also significantly upregulated barrier-related genes including muc5AC,claudin-2,and ZO-2.Molecular modelling of CG revealed a new property of the molecule as a chelator of microbial pathogenic lipids,sequestering gram-negative LPS and gram-positive LTA bacterial toxins,as well as PLM in fungi at the lowesr energy conformations.CONCLUSION CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products,suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBSlike symptoms.
文摘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 habits.First-line recommended treatments are limited to combining drugs targeting predominant symptoms,particularly pain(antispasmodics),constipation(laxatives),and diarrhea(loperamide),yielding only a limited therapeutic gain.GASTRAP^(■)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 action.AIM To evaluate the efficacy,tolerability,and safety of 4-week GASTRAP^(■)DIRECT treatment in patients with IBS.METHODS 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 weeks.The primary endpoint was the responder rate,defined as the number of patients whose abdominal pain score decreased by≥30%from baseline to week(W)4.The analysis was performed using the per-protocol set.Cardinal symptoms,impact of global symptoms on daily life,change in stool consistency,and improvement in defecatory disorders were evaluated.RESULTS Overall,100 patients were evaluated.At W4,67%(95%CI:57-75)showed improvement in abdominal pain(score:5.8±2.4 vs 2.9±2.0,P<0.0001).Similar improvements were observed for bloating[8.0±1.7 vs 4.7±2.9,P<0.0001;60%(95%CI:50-70)responders],abdominal distension[7.2±2.1 vs 4.4±3.1,P<0.0001;53%(95%CI:43-63)responders],and impact of global symptoms on daily life[7.1±2.0 vs 4.6±2.9,P<0.0001;54%(95%CI:44-64)responders].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 W2.No severe adverse event occurred,and tolerability was rated“good”or“very good”by 93%of patients.CONCLUSION GASTRAP^(■)DIRECT is safe and well tolerated,alleviating IBS symptoms rapidly in 2 weeks.This open-label study suggests that the combination of chitin-glucan and simethicone could be beneficial in patients with IBS.
基金the Foundation DigestScience for its help in the breeding of the HLA-B27 transgenic animals and Lesaffre Company for the provision of S.cerevisiae CNCM I-3856.
文摘BACKGROUND Postoperative recurrence(POR)after ileocecal resection(ICR)affects most Crohn's disease patients within 3-5 years after surgery.Adherent-invasive Escherichia coli(AIEC)typified by the LF82 strain are pathobionts that are frequently detected in POR of Crohn's disease and have a potential role in the early stages of the disease pathogenesis.Saccharomyces cerevisiae CNCM I-3856 is a probiotic yeast reported to inhibit AIEC adhesion to intestinal epithelial cells and to favor their elimination from the gut.AIM To evaluate the efficacy of CNCM I-3856 in preventing POR induced by LF82 in an HLA-B27 transgenic(TgB27)rat model.METHODS Sixty-four rats[strain F344,38 TgB27,26 control non-Tg(nTg)]underwent an ICR at the 12th wk(W12)of life and were sacrificed at the 18th wk(W18)of life.TgB27 rats were challenged daily with oral administration of LF82(109 colony forming units(CFUs)/day(d),n=8),PBS(n=5),CNCM I-3856(109 CFUs/d,n=7)or a combination of LF82 and CNCM I-3856(n=18).nTg rats receiving LF82(n=5),PBS(n=5),CNCM I-3856(n=7)or CNCM I-3856 and LF82(n=9)under the same conditions were used as controls.POR was analyzed using macroscopic(from 0 to 4)and histologic(from 0 to 6)scores.Luminal LF82 quantifications were performed weekly for each animal.Adherent LF82 and inflammatory/regulatory cytokines were quantified in biopsies at W12 and W18.Data are expressed as the median with the interquartile range.RESULTS nTg animals did not develop POR.A total of 7/8(87%)of the TgB27 rats receiving LF82 alone had POR(macroscopic score≥2),which was significantly prevented by CNCM I-3856 administration[6/18(33%)TgB27 rats,P=0.01].Macroscopic lesions were located 2 cm above the anastomosis in the TgB27 rats receiving LF82 alone and consisted of ulcerations with a score of 3.5(2-4).Seven out of 18 TgB27 rats(39%)receiving CNCM I-3856 and LF82 had no macroscopic lesions.Compared to untreated TgB27 animals receiving LF82 alone,coadministration of CNCM I-3856 and LF82 significantly reduced the macroscopic[3.5(2-4)vs 1(0-3),P=0.002]and histological lesions by more than 50%[4.5(3.3-5.8)vs 2(1.3-3),P=0.003].The levels of adherent LF82 were correlated with anastomotic macroscopic scores in TgB27 rats(r=0.49,P=0.006),with a higher risk of POR in animals having high levels of luminal LF82(71.4%vs 25%,P=0.02).Administration of CNCM I-3856 significantly reduced the levels of luminal and adherent LF82,increased the production of interleukin(IL)-10 and decreased the production of IL-23 and IL-17 in TgB27 rats.CONCLUSION In a reliable model of POR induced by LF82 in TgB27 rats,CNCM I-3856 prevents macroscopic POR by decreasing LF82 infection and gut inflammation.
文摘This paper introduced a novel microstructure-based constitutive model designed to comprehensively characterize the intricate mechanical behavior of anisotropic clay rocks under the influence of water saturation.The proposed model encompasses elastoplastic deformation,time-dependent behavior,and induced damage.A two-step homogenization process incorporates mineral compositions and porosity to determine the macroscopic elastic tensor and plastic yield criterion.The model also considers interfacial debonding between the matrix and inclusions to capture rock damage.The application of the proposed model is demonstrated through an analysis of Callovo-Oxfordian clayey rocks,specifically in the context of radioactive waste disposal in France.Model parameters are determined,followed by numerical simulations of various laboratory tests including lateral decompression tests with constant mean stress,triaxial compression tests under different water saturation conditions,and creep tests.The numerical results are compared with corresponding experimental data to assess the efficacy of the proposed model.
基金financial support from European Union(Interreg FWVL V project PSYCHE)from the French National Research Agency(Multiprobe project,ANR-20-CE42-0007)。
文摘CO_(2)hydrogenation is an attractive way to store and utilize carbon dioxide generated by industrial processes,as well as to produce valuable chemicals from renewable and abundant resources.Iron catalysts are commonly used for the hydrogenation of carbon oxides to hydrocarbons.Iron-molybdenum catalysts have found numerous applications in catalysis,but have been never evaluated in the CO_(2)hydrogenation.In this work,the structural properties of iron-molybdenum catalysts without and with a promoting alkali metal(Li,Na,K,Rb,or Cs)were characterized using X-ray diffraction,hydrogen temperatureprogrammed reduction,CO_(2)temperature-programmed desorption,in-situ^(57)Fe Mossbauer spectroscopy and operando X-ray adsorption spectroscopy.Their catalytic performance was evaluated in the CO_(2)hydrogenation.During the reaction conditions,the catalysts undergo the formation of an iron(Ⅱ)molybdate structure,accompanied by a partial reduction of molybdenum and carbidization of iron.The rate of CO_(2)conversion and product selectivity strongly depend on the promoting alkali metals,and electronegativity was identified as an important factor affecting the catalytic performance.Higher CO_(2)conversion rates were observed with the promoters having higher electronegativity,while low electronegativity of alkali metals favors higher light olefin selectivity.
基金supported by the National Key Basic Research Program of China(Grant No.2006CB400502)the French National Agency for Radioactive Waste Management(Grant No.51992)the European Commission through the Collaborative Project Cebama(Grant No.662147)
文摘In this study, the hydromechanical behavior of a concrete fracture under coupled compressive and shear stresses was investigated. A special experimental device was designed to create a planar fracture in a cylindrical sample and to carry out different kinds of hydromechanical tests on the fracture. Four series of laboratory tests were performed on an ordinary concrete sample. Hydrostatic compression tests were first conducted to characterize the normal compressibility of the fracture. In the second series, direct shear tests were conducted on the fracture under different normal stresses. The maximal shear stress of the fracture was determined as a function of the normal stress. In the third series, fluid flow tests were carried out in view of characterizing the overall hydraulic conductivity of the fracture as a function of its opening and closure. Shear tests with a constant fluid pressure were finally performed to investigate the influence of fluid pressure on the deformation behavior of concrete fractures. Based on the experimental investigation, an elastoplastic model is proposed. This model takes into account the nonlinear elastic behavior of a fracture under normal compression and the plastic deformation and failure due to shear stress. The model was coupled with the classical Darcy's law to describe the fluid flow along the fracture by considering the variation of permeability with fracture aperture. Numerical results agree with experimental data from various laboratory tests.
文摘AIMTo confirm previous conclusions on Saccharomyces cerevisiae (S. cerevisiae) CNCM I-3856 for irritable bowel syndrome (IBS) management.METHODSAn individual patient data meta-analysis was performed on two randomized clinical trials studying the effect of S. cerevisiae CNCM I-3856 supplementation on gastrointestinal (GI) symptoms in IBS subjects. A total of 579 IBS subjects were included. Outcomes were the daily Likert scale scores of abdominal pain/discomfort and bloating [area under the curve (AUC) and weekly means], responder status, and bowel movements (stool frequency and consistency). Statistical analyses were conducted in Intent to Treat (ITT) population, IBS-C subjects and IBS-C subjects with an abdominal pain/discomfort score higher than or equal to 2 at baseline (“IBS-C ≥ 2 subpopulation”).RESULTSS. cerevisiae CNCM I-3856 significantly improved abdominal pain/discomfort and bloating during the second month of supplementation [AUC (W5-W8)] with improvement up to the minimal clinically relevant threshold of 10%: a 12.3% reduction of abdominal pain/discomfort in the ITT population compared to the Placebo group (P = 0.0134) has been observed. In the IBS-C ≥ 2 subpopulation, there were a 13.1% reduction of abdominal pain/discomfort and a 14.9% reduction of bloating compared to the Placebo group (P = 0.0194 and P = 0.0145, respectively). GI symptoms significantly decreased during supplementation but no statistical differences were reported between groups at the end of the supplementation period. Responder status was defined as a subject who experienced a decrease of 1 arbitrary unit (a.u.) or 50% of the abdominal discomfort score from baseline for at least 2 wk out of the last 4 wk of the study. A significant difference between groups was reported in the ITT population, when considering the first definition: subjects in the Active group had 1.510 higher odds to be a responder (reduction of 1 a.u. of abdominal pain/discomfort) compared with subjects in the Placebo group (P = 0.0240). At the end of supplementation period, stool consistency in the Active group of the ITT population was significantly improved and classified as “normal” compared to Placebo (respectively 3.13 ± 1.197 a.u. vs 2.58 ± 1.020 a.u., P = 0.0003). Similar results were seen in the IBS-C ≥ 2 subpopulation (Active group: 3.14 ± 1.219 a.u. vs Placebo group: 2.59 ± 1.017 a.u., P = 0.0009).CONCLUSIONThis meta-analysis supports previous data linking S. cerevisiae I-3856 and improvement of GI symptoms, in IBS overall population and in the IBS-C and IBS-C ≥ 2 subpopulations.
基金Supported by The Research Council(TRC),Muscat,Oman,No.RC/MED/BIOC/10/01
文摘AIM:To investigate the association of 10 known common gene variants with susceptibility to type 2diabetes mellitus(T2D)among Omanis.METHODS:Using case-control design,a total of992 diabetic patients and 294 normoglycemic Omani Arabs were genotyped,by an allelic discrimination assay-by-design TaqMan method on fast real time polymerase chain reaction system,for the following gene variants:KCNJ11(rs5219),TCF7L2(rs7903146),CDKAL1(rs10946398),CDKN2A/B(rs10811661),FTO(rs9939609 and rs8050136),IGF2BP2(rs4402960),SLC30A8(rs13266634)CAPN10(rs3792267)and HHEX(rs1111875).T2D patients were recruited from the Diabetes Clinic(n=243)and inpatients(n=749)at Sultan Qaboos Univesity Hospital(SQUH),Muscat,Oman.Adult control participants(n=294)were volunteers from the community and from those visiting Family Medicine Clinic at SQU,for regular medical checkup.The difficulty in recruiting Omani participants with no family history of diabetes was the main reason behind the small number of control participants in this study.Almost all volunteers questioned had a relativewith diabetes mellitus.Inspite of the small number of normoglycemic controls in this study,this sample was sufficient for detection of genes and loci for common alleles influencing T2D with an odds ratio of≥1.3reaching at least 80%power.Data was collected from June 2010 to February 2012.RESULTS:Using binary logistic regression analysis,four gene variants showed significant association with T2D risk:KCNJ11(rs5219,P=5.8×10^(-6),OR=1.74),TCF7L2(rs7903146,P=0.001,OR=1.46),CDKAL1(rs10946398,P=0.002,OR=1.44)and CDKN2A/B(rs10811661,P=0.020,OR=1.40).The fixation index analysis of these four gene variants indicated significant genetic differentiation between diabetics and controls{[KCNJ11(rs5219),P<0.001],[TCF7L2(rs7903146),P<0.001],[CDKAL1(rs10946398),P<0.05],[CDKN2A/B(rs10811661),P<0.05]}.The highest genotype variation%between diabetics and controls was found at KCNJ11(2.07%)and TCF7L2(1.62%).This study was not able to detect an association of T2D risk with gene variants of IGF2BP2(rs4402960),SLC30A8(rs13266634),CAPN10(rs3792267)and HHEX(rs1111875).Moreover,no association was found between FTO gene variants(rs9939609 and rs8050136)and T2D risk.However,T2D risk was found to be significantly associated with obesity(P=0.002,OR=2.22);and with the Waist-to-Hip ratio(n=532,P=1.9×10^(-7),OR=2.4),[among males(n=234,P=1.2×10^(-4),OR=2.0)and females(n=298,P=0.001,OR=6.3)].CONCLUSION:Results confirmed the association of KCNJ11(rs5219),TCF7L2(rs7903146),CDKAL1(rs10946398)and CDKN2A/B(rs10811661)gene variants with susceptibility to T2D among Omani Arabs.
文摘In the past decade, studies of non-coding RNAs increase. Non-coding RNAs are divided in two classes: small and long non-coding RNA. It was shown that long non-coding RNAs regulate expression of 70% of genes. Long non-coding RNAs are involved in several cellular processes like epigenetic regulation, dosage compensation, alternative splicing and stem cells maintenance for example. Misregulations of their expression induce diseases such as developmental syndrome or cancer. In this review, we describe some functions of long non-coding RNA in cells. Furthermore, we study the H19/IGF2 cluster: an imprinted genomic locus located on chromosome 11p15.5. Genomic imprinting allows gene expression from a single allele in a parent-origin-dependent manner. This cluster encode for the first long non-coding RNA identified: H19. In 1990, it was established that H19 functions as a riboregulator. Recently, it was shown that H19 is a precursor of microRNA (hsa-miR-675), and several news transcripts were identified at the H19/IGF2 locus. So, the complexity of this locus increasing, in this review, we summarize our current understanding about the H19/IGF2 cluster both in terms of transcription as well as in terms of functions in cells. We highlight the involvement of H19, its new antisense transcript 91H and its microRNA, in the regulation of IGF receptor function and in cell cycle progression.
文摘Background Postprocedural aortic regurgitations following transcatheter aortic valve implantation （TAVI） procedures remain an is- sue. Benefit of oversizing strategies to prevent them isn＇t well established. We compared different level of oversizing in our cohort of con- secutive patients to address if severe oversizing compared to normal sizing had an impact on post-procedural outcomes. Methods From January 2010 to August 2013, consecutive patients were referred for TAVI with preoperative Multislice-CT （MSCT） and the procedures were achieved using Edwards Sapien~ or Corevalve devices~. Retrospectively, according to pre-procedural MSCT and the valve size, pa- tients were classified into three groups： normal, moderate and severe oversizing; depending on the ratio between the prosthesis area and the annulus area indexed and measured on MSCT. Main endpoint was mid-term mortality and secondary endpoints were the Valve Academic Research Consortium （VARC-2） endpoints. Results Two hundred and sixty eight patients had a MSCT and underwent TAVI procedure, with mainly Corevalve~. While all-cause and cardiovascular mortality rates were similar in all groups, post-procedural new pacemaker （PM） implantation rate was significantly higher in the severe oversizing group （P = 0.03）, while we observed more in-hospital congestive heart-failure （P = 0.02） in the normal sizing group. There was a trend toward more moderate to severe aortic regurgitation （AR） in the normal sizing group （P = 0.07）. Conclusions Despite a higher rate of PM implantation, oversizing based on this ratio reduces aortic leak with lower rates of post-procedural complications and a similar mid-term survival.
基金Supported by"Institut National de la Sante et de la Recherche Médicale"(Inserm)"Centre National de la Recherche Scientifique"(CNRS)"la Ligue Nationale contre le Cancer"(Committees 59,60 and 62)
文摘The recent discovery of cancer cell plasticity,i.e.their ability to reprogram into cancer stem cells(CSCs)either naturally or under chemotherapy and/or radiotherapy,has changed,once again,the way we consider cancer treatment.If cancer stemness is a reversible epigenetic state rather than a genetic identity,opportunities will arise for therapeutic strategies that remodel epigenetic landscapes of CSCs.However,the systematic use of DNA methyltransferase and histone deacetylase inhibitors,alone or in combination,in advanced solid tumors including colorectal cancers,regardless of their molecular subtypes,does not seem to be the best strategy.In this review,we first summarize the knowledge researchers have gathered on the epigenetic signatures of CSCs with the difficulty of isolating rare populations of cells.We raise questions about the relevant use of currently available epigenetic inhibitors(epidrugs)while the expression of numerous cancer stem cell markers are often repressed by epigenetic mechanisms.These markers include the three cluster of differentiation CD133,CD44 and CD166 that have been extensively used for the isolation of colon CSCs.and.Finally,we describe current treatment strategies using epidrugs,and we hypothesize that,using correlation tools comparing associations of relevant CSC markers with chromatin modifier expression,we could identify better candidates for epienzyme targeting.
文摘The freshness and quality indices of whiting (Merlangius merlangus) influenced by a large number of chemical volatile compounds, are here analyzed in order to select the most relevant compounds as predictors for these indices. The selection process was performed by means of recent statistical variable selection methods, namely robust model-free feature screening, based on quantile correlation and composite quantile correlation. On the one hand, compounds 2-Methyl-1-butanol, 3-Methyl-1-butanol, Ethanol, Trimethylamine, 3-Methyl butanal, 2-Methyl-1-propanol, Ethylacetate, 1-Butanol and 2,3-Butanedione were identified as major predictors for the freshness index and on the other hand, compounds 3-Methyl-1-butanol, 2-Methyl-1- butanol, Ethanol, 3-Methyl butanal, 3-Hydroxy-2-butanone, 1-Butanol, 2,3-Butane- dione, 3-Pentanol, 3-Pentanone and 2-Methyl-1-propanol were identified as major predictors for the quality index.
文摘Some micromechanics-based constitutive models are presented in this study for porous geomaterials.These micro-macro mechanical models focus on the effect of porosity and the inclusions on the macroscopic elastoplastic behaviors of porous materials. In order to consider the effect of pores and the compressibility of the matrix, some macroscopic criteria are presented firstly for ductile porous medium having one population of pores with different types of matrix(von Mises, Green type, Misese Schleicher and Druckere Prager). Based on different homogenization techniques, these models are extended to the double porous materials with two populations of pores at different scales and a Druckere Prager solid phase at the microscale. Based on these macroscopic criteria, complete constitutive models are formulated and implemented to describe the overall responses of typical porous geomaterials(sandstone,porous chalk and argillite). Comparisons between the numerical predictions and experimental data with different confining pressures or different mineralogical composites show the capabilities of these micromechanics-based models, which take into account the effects of microstructure on the macroscopic behavior and significantly improve the phenomenological ones.
文摘The return to old building methods by mixing crop by-products with mineral binders is arousing great interest in Europe since about 25 years.The use of these bio-aggregates based materials for the design of building envelopes is a valuable opportunity to deal with increasingly demanding thermal regulations.In addition,the regulatory framework is moving towards reducing the overall car-bon footprint of new buildings.Some traditional and historic buildings are based on timber framing with earth-straw as infill material for instance.Hemp concrete is a bio-based material that can be manually tamped in timber stud walls or more recently in the form of precast blocks.Owing to their low compressive strength,bio-based concretes using a large volume fraction of plant-derived aggregates are only considered as thermal and sound insulation materials.The structural design practice of wood frame walls does not assume any mechanical contribution of hemp concrete whereas it may contribute to the racking strength of the structure.In this context,more research is needed regarding the shear behavior of crop by-products and bio-based concretes.In this case,the objective of the study was to perform direct shear tests under three levels of normal pressure on hemp shiv and rice husk as unbound crop by-products.The results showed that the friction angle of the granular skeleton based on rice husk for a given relative displacement was significantly lower than that measured on hemp shiv.This is in accordance with what had been observed on bio-based concretes cast by mixing aggregates with lime and shear strength parameters measured by means of triaxial compression.
文摘Recently,Artificial Neural Networks(ANNs)have been used for various scientific and engineering applications essentially because they allow the modeling of a process,which starts from the database containing the variables that describe that particular process.They have already been applied to the study of landslides in particular,with reference to the indirect determination of the triggering
文摘The first International Symposium on Advances in Pharmaceutical Analysis (APA 2017) was started and held successfully in Wuhan University, China from November 17 to 19, 2017. The organization of the 2nd International Symposium on Advances in Pharmaceutical Analysis in the capital city of Flanders, Lille, was both an exciting and challenging project because the idea of an annual meeting between our two long cooperating Schools of Pharmaceutical Sciences of Wuhan and Lille, stood to reason.
文摘Liver X receptors(LXRs)are members of the nuclear receptor superfamily,which have been implicated in lipid ho-meostasis and more recently in glucose metabolism.Here,we show that glucose does not change LXRα protein level,but affects its localization in pancreatic β-cells.LXRα is found in the nucleus at 8 mM glucose and in the cytoplasm at4.2 mM.Addition of glucose translocates LXRα from the cytoplasm into the nucleus.Moreover,after the activation ofLXR by its synthetic non-steroidal agonist(T0901317),insulin secretion and glucose uptake are increased at 8 mM anddecreased at 4.2 mM glucose in a dose-dependent manner.Furthermore,at low glucose condition,okadaic acid reversedLXRα effect on insulin secretion,suggesting the involvement of glucose signaling through a phosphorylation-dependentmechanism.
文摘BACKGROUND The antidepressant escitalopram is widely prescribed for the treatment of depression.It is generally well-tolerated,and cholestasis is not mentioned in its summary of product characteristics(Sm PC).We present a case of cholestatic and cytolysis liver injury due to escitalopram and a Vigi Base?study.CASE SUMMARY A 68-year-old man was admitted to our emergency unit due to clinical jaundice associated with hepatitis,pruritus and dark urine.We tested the patient for the most common etiologies of jaundice,including hemolysis,viral hepatitis,cirrhosis,carcinoma,cholangitis,cholelithiasis and intrahepatic or extrahepatic obstruction.The etiological study was negative,and an adverse drug reaction was the sole possible explanation.The patient was receiving treatment with escitalopram.Two days after its withdrawal,pruritus was resolved.Ten days after withdrawal,clinical jaundice disappeared.It took a month and three weeks after withdrawal for the patient to have normalized liver function tests.To our knowledge,this is the first reported case of cholestasis where treatment with escitalopram was the only possible cause,with a highly probable causality.In addition,we determined whether escitalopram is associated with hepatotoxicity and cholestasis by performing a disproportionality analysis.All cases of hepatobiliary disorders induced by escitalopram and reported in the World Health Organization pharmacovigilance database(Vigi Base?)were analyzed to characterize this toxicity.We found that patients treated with escitalopram had an increased risk of hepatitis[odds ratio(OR)=1.938(1.186-3.166)]and cholestasis[OR=1.866(1.279-2.724)][OR(95%confidence interval)].The median duration between the introduction of escitalopram and the occurrence of acute hepatitis and/or cholestasis was ten days+/-seven days.CONCLUSION Although extremely rare,this case report,the review of the literature and the pharmacovigilance update confirm that escitalopram can cause drug-induced hepatotoxicity and cholestasis,generally within a week after initiation.Thus,escitalopram should be withdrawn immediately if an iatrogenic cause cannot be excluded.If its responsibility is ascertained,escitalopram should be consequently contraindicated.In addition,serotoninergic antidepressants in patients with nonsevere depression are ineffective and harmful.Finally,the Sm PC of escitalopram should be updated to alert for this risk and give clear clinical guidelines.
基金supported by the National Natural Science Foundation of China (NSFC) (Grant No. 51609081)
文摘In this paper,the thermo-hydro-mechanical(THM)response of claystone is studied via a series of parametric studies,considering the evolution of mechanical properties and deformation behavior of corroded steel.The numerical simulations are performed by using a coupled THM finite element code and two different constitutive models:a visco-elastoplastic model for geological formation and a von Mises type model for steel liner.The mechanical properties and deformation behavior of corroded steel are described in a conceptual model.Finally,a disposal tunnel supported by a steel liner is studied and a series of parametric studies is defined to demonstrate the corrosion effects of steel liner on the THM response of the claystone.The comparison of different numerical calculations exhibits that the volumetric expansion related to corrosion products has an important impact on the stress and displacement fields in the claystone surrounding the disposal tunnel.However,the evolutions of temperature and liquid pressure in the claystone are essentially controlled by its THM properties and independent of the steel corrosion.
