Leisure sedentary behaviour increases the risk of venous thromboembolism: a Mendelian randomisation study.

BACKGROUND: Venous thromboembolism (VTE) is a substantial contributor to the global burden of disease. Observational studies have suggested that leisure sedentary behaviours (LSB) are related to the risk of VTE; however, the causal role of LSB in VTE remains unclear. METHODS: Using data obtained from genome-wide association studies in the UK Biobank (N = 422,218), we identified 84, 21, and 4 single nucleotide polymorphisms (SNPs) related to sedentary television (TV) watching, computer use, and driving, respectively. These SNPs were employed as instrumental variables. Summary statistics for SNP-VTE associations was obtained from the FinnGen study (5,403 cases and 130,235 controls). Two-sample Mendelian randomisation (MR) analyses were performed using inverse-variance weighted (IVW), MR-Egger,weighted median, and weighted mode approaches. Sensitivity analyses were conducted to ensure robustness of the results. RESULTS: The main IVW approach demonstrated a positive association between the genetically predicted sedentary TV watching and the risk of VTE [odds ratio (OR):1.35, 95% confidence interval (CI):1.02-1.80, P = 0.039]. However, no significant association was observed for genetically predicted sedentary computer use or driving and VTE risk. The results from our series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept test, and MR-Pleiotropy RESidual Sum and Outlier method, further supported these findings. CONCLUSION: This study provides evidence of an association between genetically predicted sedentary TV watching and the risk of VTE. Further studies are required to elucidate the underlying causal mechanisms.

YLL056C from Saccharomyces cerevisiae encodes a novel protein with aldehyde reductase activity.

The short-chain dehydrogenase/reductase (SDR) family, the largest family in dehydrogenase/reductase superfamily, is divided into "classical," "extended," "intermediate," "divergent," "complex," and "atypical" groups. Recently, several open reading frames (ORFs) were characterized as intermediate SDR aldehyde reductase genes in Saccharomyces cerevisiae. However, no functional protein in the atypical group has been characterized in S. cerevisiae till now. Herein, we report that an uncharacterized ORF YLL056C from S. cerevisiae was significantly upregulated under high furfural (2-furaldehyde) or 5-(hydroxymethyl)-2-furaldehyde concentrations, and transcription factors Yap1p, Hsf1p, Pdr1/3p, Yrr1p, and Stb5p likely controlled its upregulated transcription. This ORF indeed encoded a protein (Yll056cp), which was grouped into the atypical subgroup 7 in the SDR family and localized to the cytoplasm. Enzyme activity assays showed that Yll056cp is not a quinone or ketone reductase but an NADH-dependent aldehyde reductase, which can reduce at least seven aldehyde compounds. This enzyme showed the best Vmax, Kcat, and Kcat/Km to glycolaldehyde, but the highest affinity (Km) to formaldehyde. The optimum pH and temperature of this enzyme was pH 6.5 for reduction of glycolaldehyde, furfural, formaldehyde, butyraldehyde, and propylaldehyde, and 30 °C for reduction of formaldehyde or 35 °C for reduction of glycolaldehyde, furfural, butyraldehyde, and propylaldehyde. Temperature and pH affected stability of this enzyme and this influence varied with aldehyde substrate. Metal ions, salts, and chemical protective additives, especially at high concentrations, had different influence on enzyme activities for reduction of different aldehydes. This research provided guidelines for study of more uncharacterized atypical SDR enzymes from S. cerevisiae and other organisms.

Influence of reaction parameters on the fate of nitrogen during the supercritical water gasification of dewatered sewage sludge.

This study investigated the effects of different parameters on the fate of nitrogen (N) in products after supercritical water gasification (SCWG) of dewatered sewage sludge (DSS). N distribution and morphology were most affected by temperature, followed by reaction time and heating rate, while reaction pressure had little effect on them. In terms of specific performance, higher temperature, longer reaction time, and slower heating rate were beneficial to the increase of NH4+-N content in the liquid phase. Compared with raw sludge, after SCWG, the solid phase contained more inorganic-N and less protein-N, a certain proportion of quaternary-N and nitrile-N. The proportion of N-containing compounds in the biocrude phase was between 0.26%-20.34%, suggesting the importance of more research on N in the biocrude phase. The recovery rate of N in all samples was between 64.34%-93.82%. The major proportion of N (42.27%-60.91%) was transformed into the liquid phase, while the remaining entered the solid phase (10.54%-21.45%) and the biocrude phase (6.18%-15.78%). These findings are helpful to better understand the principle of N distribution in products of DSS after SCWG and provide some new ideas for reducing N-containing by-product formation in the future.