Compatibility between host cells and heterologous pathways is a challenge for constructing organisms with high productivity or gain of function. Designer yeast cells incorporating the Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) system provide a platform for generating genotype diversity. Here we construct a genetic AND gate to enable precise control of the SCRaMbLE method to generate synthetic haploid and diploid yeast with desired phenotypes. The yield of carotenoids is increased to 1.5-fold by SCRaMbLEing haploid strains and we determine that the deletion of YEL013W is responsible for the increase. Based on the SCRaMbLEing in diploid strains, we develop a strategy called Multiplex SCRaMbLE Iterative Cycling (MuSIC) to increase the production of carotenoids up to 38.8-fold through 5 iterative cycles of SCRaMbLE. This strategy is potentially a powerful tool for increasing the production of bio-based chemicals and for mining deep knowledge.

AimIL-1β was considered as an important inflammatory cytokine in diabetic cardiovascular complications. DCM is one of the major manifestations of diabetic cardiovascular complications whose specific mechanisms are still unclear. In this study, we investigated the role of IL-1β in myocytes apoptosis in DCM.MethodsIn the in vitro study, high- glucose medium and/or IL-1β were used to incubate the isolated primary myocytes. siRNA was used to knockdown the irak2 gene expression. Apoptosis was evaluated by Hoechst and TUNEL staining. In the in vivo study, DCM in rats was induced by STZ injection and confirmed by cardiac hemodynamic determinations. The IL-1 receptor antagonist, IL-1Ra was also used to treat DCM rats. Myocardial apoptosis was assessed by TUNEL assay. In both in vitro and in vivo studies, expression levels of GRP-78, IRAK-2 and CHOP were analyzed by Western Blotting. ELISA was employed to exam the IL-1β content in serum and cell supernatants.ResultsMyocytes were not identified as the source of IL-1β secretion under high- glucose incubation. High glucose incubation and/or IL-1β incubation elevated ER- stress mediated myocytes apoptosis which was attenuated by irak2 silencing. Dramatically increased circulating and myocardial IL-1β levels were found in DCM rats which stimulated activation of ER stress and lead to elevated myocytes apoptosis. The administration of IL-1Ra, however, attenuated IRAK2/CHOP induced apoptosis without affecting fasting blood glucose concentration.ConclusionsElevated circulating IL-1β contributed to promote ER stress- induced myocytes apoptosis by affecting IRAK-2/CHOP pathway in DCM.

ObjectiveThe current overweight and central adiposity guidelines based on Western populations were not consistent with many studied based on the Asian populations. Uighur people live in Xinjiang Uighur Autonomous Region which is located in the center of Asia. Their overweight and central cutoffs were largely unknown. We aimed to identify cutoffs for body mass index (BMI; in kg/m2) and waist circumference (WC; in cm) for categorization of overweight and central adiposity among Uighur adults in Xinjiang.Methods4767 Uighur participants were selected from the Cardiovascular Risk Survey (CRS) which was carried out from October 2007 to March 2010. The age of the participants were from 35 to 101 years old with the mean age of 50.09 years. Anthropometric data, blood pressure, serum concentration of serum total cholesterol, triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL) and fasting glucose were documented. The prevalence, sensitivity, specificity and distance on the receiver operating characteristic (ROC) curve of each BMI and waist circumference values were calculated.ResultsThe prevalence of hypertension, hypercholesterolemia and hypertriglyceridemia were higher with higher BMI for both men and women. The prevalence of hypertension and hypercholesterolemia were higher with higher waist circumference for both men and women. In women, the prevalence of hypertriglyceridemia was noticed to increase as the waist circumference increased. The shortest distance in the receiver operating characteristic curves for hypertension, dyslipidemia, diabetes, or ≥ 2 of these risk factors suggested a BMI cutoff of 26 and a waist circumference cutoff of 90 cm for both men and women.ConclusionsHigher cutoffs for BMI and waist circumference are needed in the identification of Uighur patients at high risk of cardiovascular disease.

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Lactobacillus plantarum MA2 was isolated from traditional Chinese Tibetan kefir grains. Its antioxidant properties had been demonstrated in vitro and in vivo previously. In the present study, the probiotic characteristics of this strain were further evaluated by investigating its acid and bile salt tolerances, cell surface hydrophobicity, and autoaggregation, respectively. In addition, the cellular antioxidant activity (CAA) assay was applied to test the antioxidant capacity of the isolate in different growth phases. Same method was also used to evaluate the antioxidant capacity of its fermentation supernatant, cell-free extract, and intact cell quantitatively. The results of probiotic characteristic tests showed that MA2 could survive at pH 2.5 and 0.3% bile salt. Meanwhile, the measurements of cell surface hydrophobicity and autoaggregation were 45.29 ± 2.15 and 6.30 ± 0.34%, respectively. The results of cellular antioxidant activity tests indicated that MA2 had high antioxidant potential. The CAA value of logarithmic phase cell-free extract of MA2 (39,450.00 ± 424.05 μmol quercetin equivalents/100 g sample) was significantly higher than that in stationary phase cell-free extract (3395.98 ± 126.06 μmol quercetin equivalents/100 g sample) and that of fermentation supernatant in logarithmic phase (2174.41 ± 224.47 μmol quercetin equivalents/100 g sample) (p < 0.05). The CAA method was successively applied to evaluate the antioxidant capacity of MA2 in this study, which suggests that it could be used as a useful method for lactic acid bacteria antioxidant potential evaluation.