Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes

DNA methylation variations are prevalent in human obesity but evidence of a causative role in disease pathogenesis is limited. Here, we combine epigenome-wide association and integrative genomics to investigate the impact of adipocyte DNA methylation variations in human obesity. We discover extensive DNA methylation changes that are robustly associated with obesity (N = 190 samples, 691 loci in subcutaneous and 173 loci in visceral adipocytes, P 500 target genes, and identify putative methylation-transcription factor interactions. Through Mendelian Randomisation, we infer causal effects of methylation on obesity and obesity-induced metabolic disturbances at 59 independent loci. Targeted methylation sequencing, CRISPR-activation and gene silencing in adipocytes, further identifies regional methylation variations, underlying regulatory elements and novel cellular metabolic effects. Our results indicate DNA methylation is an important determinant of human obesity and its metabolic complications, and reveal mechanisms through which altered methylation may impact adipocyte functions

Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes

DNA methylation variations are prevalent in human obesity but evidence of a causative role in disease pathogenesis is limited. Here, we combine epigenome-wide association and integrative genomics to investigate the impact of adipocyte DNA methylation variations in human obesity. We discover extensive DNA methylation changes that are robustly associated with obesity (N = 190 samples, 691 loci in subcutaneous and 173 loci in visceral adipocytes, P 500 target genes, and identify putative methylation-transcription factor interactions. Through Mendelian Randomisation, we infer causal effects of methylation on obesity and obesity-induced metabolic disturbances at 59 independent loci. Targeted methylation sequencing, CRISPR-activation and gene silencing in adipocytes, further identifies regional methylation variations, underlying regulatory elements and novel cellular metabolic effects. Our results indicate DNA methylation is an important determinant of human obesity and its metabolic complications, and reveal mechanisms through which altered methylation may impact adipocyte functions

Impacts of lubricating oil and its formulations on diesel engine particle characteristics

© 2020 Lubricating oil-related engine emission reduction is now a key path to further control the engine-out emission level and to meet the restrict regulations, especially in the manner of particulate number emission. This work experimentally studied the contribution of lubricating oil and its key constituents to the particle emission via monitoring the combustion process and analyzing the particle physic-chemical characteristics. Two sets of experiments were conducted to understand how the lubricating oil alters the regular combustion cycles and to study the effects of oil sulfur and metallic-ash constituents on the particle chemical characteristics, respectively. Details of the surface oxygenated functional groups and carbon chemical state on the particle surface were analyzed by XPS, while the FTIR was employed to characterize the possible functional groups in the bulk particle samples and the bonding patterns of the sulfur element. The effects on the particle morphology and elemental compositions were analyzed by SEM-EDS. Results show that the lubricating oil could shorten the ignition-delay phase combustion effectively, for instance, by 20% when 1wt% oil is burned along with diesel. Furthermore, more oxygenated surface functional groups and relatively more sp3 hybridization carbon shows up in the oil-derived particles. The sulfur element in the oil increases the oxygenated functional groups and lowers the aliphatic C[sbnd]H group by forming –SH radical. On the contrary, the metallic-ash fraction reduces the amount of oxygenated functional groups because the inorganic sulfates/phosphates occupy some oxygen atoms during the combustion reaction. Both the sulfur and ash tend to generate more un-substituted and meta-disubstituted benzene instead of the mono-disubstituted benzene structure, which is popular in diesel fuel-related particles mainly. Last but not the least, the sulfur and ash content significantly increase the concentration of the sulfates and phosphates of Iron, Calcium, and Zinc in the particles

A photonanozyme with light-empowered specific peroxidase-mimicking activity

Although nanozymes have been widely developed, directly utilizing light to drive catalytic reactions like natural photoenzymes still remains challenging. Here, we propose that photonanozymes (PNZs), as a novel kind of nanozyme, exclusively possess enzyme-mimicking activity under illumination. Only in the presence of visible light, the as-synthesized TiO2 proposed in this contribution shows excellent specificity of peroxidase-like without any oxidase- or catalase-like activity. The driving force of the light-empowered peroxidase-like photonanozymatic activity is explicated in terms of the photogenerated hot charge carriers in TiO2 PNZs and the accompanied reactive oxygen species. The co-substrates for photonanozymatic reaction over TiO2 PNZs facilitate the formation of the precarious and reactive peroxo-oxygen bridge between TiO2 and H2O2, enabling the catalytic specificity. With the TiO2 PNZ-based biosensing platform for visual glucose detection exemplifying the concept of the application of PNZs, this work may evoke more inspirations to explore strategies for enlarging the scope of photoenzyme mimics