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Multitarget Thiol-Activated Tetrapyridyl Gold(Ⅲ)Complexes for Hypoxic Cancer Therapy

CCS Chemistry 2024年第3期6卷 783-797页

作者： Xue-Quan Zhou selda abyar Imma Carbo-Bague Lan Wang Sebastian Türck Maxime ASiegler Uttara Basu Ingo Ott Rongfang Liu Adriaan PIJzerman Sylvestre Bonnet Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate School(SIGS)Tsinghua UniversityShenzhen 518055 Leiden Institute of Chemistry Leiden University2333 CC Leiden Department of Chemistry Simon Fraser UniversityBurnabyBritish Columbia V5A 1S6 Institute of Medicinal and Pharmaceutical Chemistry Technische Universität Braunschweig38106 Braunschweig Department of Chemistry Johns Hopkins UniversityBaltimoreMaryland 21218 Division of Drug Discovery&Safety Leiden Academic Centre for Drug ResearchLeiden University2333 CC Leiden

Gold complexes have emerged as promising anticancer metallodrugs due to their efficient thioredoxin reductase(TrxR)inhibition,which disturbs the redox balance of cancer ***,in this model,the role of the ligand(s)coordinated to gold is often *** this work,we present a series of tetrapyridyl Au(Ⅲ)complexes that exhibit thiol-induced release of a Au(Ⅰ)ion and a tetrapyridyl *** formation of a free Au(Ⅰ)center is responsible for the expected TrxR ***,the released ligand,which was visible in cells due to its intense blue fluorescence,showed excellent binding properties to the hERG potassium ***,these ligands ended up in the lysosomes,resulting in significant lysosome ***,the Au(Ⅲ)complexes presented in this work showed broad-spectrum anticancer properties,both in hypoxic 2D monolayers and 3D tumor *** suggest that the interaction of the released Au(Ⅰ)center and the tetrapyridyl ligand with two different protein targets may combine into prodrugs that overcome hypoxia-induced drug deactivation.

关键词： anticancer Au(Ⅲ)complexes enzyme inhibtion potassium channel affinity lysosome damage cell imaging prodrug

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Experimental and Finite Element Analysis of Corroded High-Pressure Pipeline Repaired by Laminated Composite

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Computer Modeling in Engineering & Sciences 2024年第8期140卷 1783-1806页

作者： Seyed Mohammad Reza Abtahi Saeid Ansari Sadrabadi Gholam Hosein Rahimi Gaurav Singh Hamid abyar Daniele Amato Luigi Federico Faculty of Mechanical Engineering Tarbiat Modares UniversityTehran***Iran A.Leon Linton Department of Mechanical Robotics and Industrial EngineeringLawrence Technological UniversitySouthfieldMI48075USA Department of Mechanical Engineering Faculty of EngineeringMeybod UniversityYazd***Iran Department of Industrial Engineering University of SalernoVia Giovanni PaoloⅡFiscianoItaly Italian Aerospace Research Center(C.I.R.A.) Via MaioriseCapuaCE81043Italy

Repairs of corroded high-pressure pipelines are essential for fluids transportation under high *** of the methods used in their repairs is the use of layered *** composite used must have the necessary ***,the experiments and analytical solutions presented in this paper are performed according to the relevant standards and codes,including ASME PCC-2,ASME B31.8S,ASME B31.4,ISO 24817 and ASME *** addition,the experimental tests are replicated numerically using the finite element *** the strain gauges at different distances from the defect location,can reduce the nonlinear effects,deformation,and fluctuations due to the high *** direct relationship between the depth of an axial defect and the stress concentration is observed at the inner side edges of the *** reparation reduces the non-linearities related to the sharp variation of the geometry and a more reliable numerical simulation could be performed.

关键词： High-pressure pipeline composite repair ASME PCC-2 ISO 24817

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Different metabolic/obesity phenotypes are differentially associated with development of prediabetes in adults: Results from a 14-year cohort study

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World Journal of Diabetes 2019年第6期10卷 350-361页

作者： Fahimeh Haghighatdoost Masoud Amini Ashraf Aminorroaya Majid abyar Awat Feizi Food Security Research Center Isfahan University of Medical Sciences Isfahan 81746-73461 Iran Department of Community Nutrition School of Nutrition and Food Science Isfahan University of Medical Sciences Isfahan 81746-73461 Iran Isfahan Endocrine and Metabolism Research Center Isfahan University of Medical Sciences Isfahan 81746-73461 Iran Biostatistics and Epidemiology Department School of Health Isfahan University of Medical Sciences Isfahan 81746-73461 Iran

BACKGROUND The risk of developing prediabetes based on the metabolic/obesity phenotypes has been poorly investigated. AIM To examine the association of baseline metabolic/obesity phenotypes and their changes over time with the risk of prediabetes development. METHODS In a population-based cohort study, 1741 adults (aged > 19 years) with normal blood glucose were followed for 14 years. Anthropometric and biochemical measures were evaluated regularly during the follow-up period. According to body mass index and metabolic health status, participants were categorized into four groups: Metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW) and metabolically unhealthy obese (MUO). Multivariable Cox regression analysis was used to measure the risk of prediabetes according to the baseline metabolic/obesity phenotype and their changes during the follow-up. RESULTS In the whole population with a mean (95CCI for mean) follow up duration of 12.7 years (12.6-12.9), all three MUNW, MHO, MUO groups were at higher risk for developing prediabetes compared to the MHNW group (P = 0.022). The MUNW group had the highest risk for developing prediabetes (hazard ratio (HR): 3.84, 95%CI: 1.20, 12.27). In stratified analysis by sex, no significant association was found in men, while women in the MUNW group were at the greatest risk for prediabetes (HR: 6.74, 95%CI: 1.53, 29.66). Transforming from each phenotype to MHNW or MHO was not related to the risk of prediabetes development, whereas transforming from each phenotype to MUO was associated with an increased risk of prediabetes (HR > 1;P < 0.05). CONCLUSION Our findings indicate that MHO is not a high risk, unless it transforms into MUO over time. However, people in the MUNW group have the greatest risk for developing prediabetes, and therefore, they should be screened and treated.

关键词： Prediabetes Obesity Metabolic status Cohort study

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Severity of the metabolic syndrome as a predictor of prediabetes and type 2 diabetes in first degree relatives of type 2 diabetic patients:A 15-year prospective cohort study

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World Journal of Diabetes 2020年第5期11卷 202-212页

作者： Rokhsareh Meamar Masoud Amini Ashraf Aminorroaya Maryam Nasri Majid abyar Awat Feizi Isfahan Endocrine and Metabolism Research Center Isfahan Clinical Toxicology Research CenterIsfahan University of Medical SciencesIsfahan 81746-73461Iran Isfahan Endocrine and Metabolism Research Center Isfahan University of Medical SciencesIsfahan 81746-73461Iran Grovemead Health Center London NW4-3EBUnited Kingdom Department of Biostatistics and Epidemiology School of HealthIsfahan University of Medical SciencesIsfahan 81746-73461Iran

BACKGROUND Type 2 diabetes mellitus(T2DM)has high morbidity and mortality worldwide,therefore there is of paramount importance to identify the risk factors in the populations at risk early in the course of illness.A strong correlation between severity of metabolic syndrome(MetS)and HbA1c,fasting insulin and insulin resistance has been ***,the MetS severity score(or MestS Zscore)can potentially be used to predict the risk of T2DM progression over *** To evaluate the association the of MestS Z-score in first degree relatives(FDRs)of T2DM with the risk of prediabetes and type 2 diabetes in *** A prospective open cohort study was conducted between *** baseline,the sample comprised of 1766 FDRs of patients with T2DM who had a normal glucose tolerance *** risk(RR)and 95%confidence interval were calculated based on logistic *** receiver-operator characteristic analysis and area under the curve based on MetS Z-score were used to evaluate the risk of prediabetes and diabetes among the FDR *** Baseline MetS Z-scores were associated with the its latest values(P<0.0001).Compared with individuals who were T2DM free at the end of follow up,those who developed T2DM had higher MetS Z-score at baseline(P<0.001).In multivariable logistic regression analyses for every unit elevation in MetS Z-score at the baseline,the RR for developing future T2DM and prediabetes was(RR=1.94,RR=3.84),(RR=1.5,RR=2.17)in total population and female group,respectively(P<0.05).The associations remained significant after adjusting the potential confounding variables.A cut off value of 0.97 and 0.94 was defined in the receiver-operator characteristic curve based on the MetS Z-score for differentiating female patients with diabetes and prediabetes from the normal population,*** The MetS Z-score was associated with an increased risk of future *** interventions at earlier stages for preventing and att

关键词： Insulin resistance Metabolic syndrome Risk Type 2 diabetes mellitus Prediabetes First degree relative

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