Serum metabolomics profiles in response to n-3 fatty acids in Chinese patients with type 2 diabetes: a double-blind randomised controlled trial.

We aimed to investigate the change of serum metabolomics in response to n-3 fatty acid supplements in Chinese patients with type 2 diabetes (T2D). In a double-blind parallel randomised controlled trial, 59 Chinese T2D patients were randomised to receive either fish oil (FO), flaxseed oil (FSO) or corn oil capsules (CO, served as a control group) and followed up for 180 days. An additional 17 healthy non-T2D participants were recruited at baseline for cross-sectional comparison between cases and non-cases. A total of 296 serum metabolites were measured among healthy controls and T2D patients before and after the intervention. Serum 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) (P-interaction = 1.8 × 10(-7)) was the most significant metabolite identified by repeated-measures ANOVA, followed by eicosapentaenoate (P-interaction = 4.6 × 10(-6)), 1-eicosapentaenoylglycerophosphocholine (P-interaction = 3.4 × 10(-4)), docosahexaenoate (P-interaction = 0.001), linolenate (n-3 or n-6, P-interaction = 0.005) and docosapentaenoate (n-3, P-interaction = 0.021). CMPF level was lower in T2D patients than in the healthy controls (P = 0.014) and it was significantly increased in the FO compared with CO group (P = 1.17 × 10(-7)). Furthermore, change of CMPF during the intervention was negatively correlated with change of serum triglycerides (P = 0.016). In conclusion, furan fatty acid metabolite CMPF was the strongest biomarker of fish oil intake. The association of CMPF with metabolic markers warrants further investigation.This study was funded by the National Basic Research Program of China (973 Program: 2015CB553604); by National Natural Science Foundation of China (NSFC: 81273054); and by the Ph.D. Programs Foundation of Ministry of Education of China (20120101110107). J.-S.Z. acknowledges support from MRC Epidemiology Unit (MC_UU_12015/5) and the Cambridge Initiative – Nutrition (RG71466, SJAH/004). F.I. acknowledges support from the MRC Epidemiology Unit (MC_UU_12015/5).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep2952

Numerical Study on Combustion and Atomization Characteristics of Coaxial Injectors for LOX/Methane Engine

The LOX/methane engine has an admirable performance under a supercritical state. However, the properties of methane change drastically with varying injection temperature. Because the injector can greatly affect the atomization and combustion, this study performed a three-dimensional numerical simulation of atomization, combustion, and heat transfer in a subscale LOX/methane engine to evaluate the effect of the main fluid parameters with different methane injection temperatures and different injectors on atomization performance and combustion performance. The results show that the larger propellant momentum ratio and Weber number can improve the heat flux and combustion stability in shear coaxial injector, while the influence in swirl coaxial injector is relatively small. Moreover, in shear coaxial injector and in swirl coaxial injector, the larger propellant momentum ratio and Weber number can reduce the droplet size, enhance atomization performance, and improve the combustion efficiency. The numerical model provides an economical method to evaluate the main fluid parameters and proposes new design principles of injectors in LOX/methane engine

Monitoring Inbreeding of WHBE Rabbits Using Microsatellites

Microsatellite polymorphisms were analyzed in F5, F6 and F7 WHBE rabbits ( Oryctolagus cuniculus ) to monitor inbreeding. Out of 21 microsatellite loci, 11 were successfully amplified and showed polymorphic. For the F5 WHBE rabbits, the number of alleles per locus (Na) ranged from 3 to 9 and the mean effective number of alleles (Ne) was 1.81. The mean value of observed heterozygosity (Ho) and polymorphism information content (PIC) of the 11 polymorphic loci were 0.381 and 0.524, respectively. The power of cumulative discrimination (CDP) was 1.0. The value of cumulative exclusion probability of the 11 polymorphic loci in the absence (CPE-1) or in the presence of genetic information on the first parent (CPE-2) was 0.926 and 0.993, respectively. For the F6 WHBE rabbits, Na per locus ranged from 3 to 8 and the mean value of Ne was 1.68. The mean value of Ho, PIC, CDP, CPE-1, CPE-2 of the 11 polymorphic loci were 0.356, 0.548, 1.0, 0.931, 0.994 respectively. For the F7 WHBE rabbits, Na per locus ranged from 2 to 6 and the mean value of Ne was 1.51. The mean value of Ho, PIC, CDP, CPE-1, CPE-2 of the 11 polymorphic loci were 0.287, 0.498, 1.0, 0.891, 0.986 respectively. The average number of effective alleles and the average observed heterozygosity were decreasing continuously in F 5, F6 and F7, suggesting that the purity of WHBE rabbits was increasing continuously

Patient-specific iPSC-derived cardiomyocytes reveal aberrant activation of Wnt/β-catenin signaling in SCN5A-related Brugada syndrome

Abstract Background Mutations in the cardiac sodium channel gene SCN5A cause Brugada syndrome (BrS), an arrhythmic disorder that is a leading cause of sudden death and lacks effective treatment. An association between SCN5A and Wnt/β-catenin signaling has been recently established. However, the role of Wnt/β-catenin signaling in BrS and underlying mechanisms remains unknown. Methods Three healthy control subjects and one BrS patient carrying a novel frameshift mutation (T1788fs) in the SCN5A gene were recruited in this study. Control and BrS patient-specific induced pluripotent stem cells (iPSCs) were generated from skin fibroblasts using nonintegrated Sendai virus. All iPSCs were differentiated into cardiomyocytes using monolayer-based differentiation protocol. Action potentials and sodium currents were recorded from control and BrS iPSC-derived cardiomyocytes (iPSC-CMs) by single-cell patch clamp. Results BrS iPSC-CMs exhibited increased burden of arrhythmias and abnormal action potential profile featured by slower depolarization, decreased action potential amplitude, and increased beating interval variation. Moreover, BrS iPSC-CMs showed cardiac sodium channel (Nav1.5) loss-of-function as compared to control iPSC-CMs. Interestingly, the electrophysiological abnormalities and Nav1.5 loss-of-function observed in BrS iPSC-CMs were accompanied by aberrant activation of Wnt/β-catenin signaling. Notably, inhibition of Wnt/β-catenin significantly rescued Nav1.5 defects and arrhythmic phenotype in BrS iPSC-CMs. Mechanistically, SCN5A-encoded Nav1.5 interacts with β-catenin, and reduced expression of Nav1.5 leads to re-localization of β-catenin in BrS iPSC-CMs, which aberrantly activates Wnt/β-catenin signaling to suppress SCN5A transcription. Conclusions Our findings suggest that aberrant activation of Wnt/β-catenin signaling contributes to the pathogenesis of SCN5A-related BrS and point to Wnt/β-catenin as a potential therapeutic target