PPA1 promotes adipogenesis by regulating the stability of C/EBPs.

Adipogenesis significantly contributes to healthy adipose tissue expansion in obesity. Increasing adipocyte number or function to alleviate adipose tissue overload could serve as a therapeutic strategy for both lipodystrophy and obesity-related metabolic syndrome. Inorganic pyrophosphatase (PPA1) is an enzyme that catalyzes the hydrolysis of pyrophosphate (PPi) and is involved in many biochemical reactions, but its function in adipose tissue has not been studied previously. In this study, we demonstrated that adipose-specific PPA1 knockout (PPA1AKO) mice showed lipodystrophy and spontaneously developed hepatic steatosis and severe insulin resistance under normal chow diet feeding. PPA1 deficiency suppressed the differentiation of primary adipocyte precursors and 3T3-L1 cells. Notably, PPA1 overexpression can restore inhibited adipogenesis in preadipocytes isolated from db/db mice and type 2 diabetes patients. Mechanistic studies have revealed that PPA1 acts as a positive regulator of early adipocyte differentiation by promoting CCAAT/enhancer-binding proteinß and δ (C/EBPß and δ) protein stability. Moreover, the function of PPA1 in adipogenesis is independent of its PPi catalytic activity. Collectively, our in vivo and in vitro findings demonstrated that PPA1 is a novel critical upstream regulator of adipogenesis, controlling adipose tissue development and whole-body metabolic homeostasis.

Tf2O-Mediated Direct Synthesis of 4-Sulfenylated Oxazoles from ß-Keto Sulfoxides and Nitriles.

A general and efficient method for the synthesis of 4-sulfenylated oxazoles is described. Trisubstituted oxazoles are obtained in good to excellent yields from ß-keto sulfoxides and nitriles. The mechanistic study suggests that the reaction proceeds via the nucleophilic addition of nitriles to the in situ formed α-carbonyl cation followed by intramolecular cyclization.

Copper-catalyzed direct sulfenoamination of saturated ketones via in situ formed enaminones.

A sequential and efficient protocol for the synthesis of α-thiolated enaminones has been developed using copper-TEMPO systems. This reaction features a broad substrate scope to afford the desired product in good to excellent yields with high stereoselectivity. A preliminary mechanistic study suggests that the in situ formed enaminone acts as the key intermediate.

Switchable Synthesis of Sulfoxides and α-Alkoxy-ß-ketothioethers Regulated by Temperature in a Selectfluor-Methanol System.

A switchable and benign protocol for chemoselective synthesis of sulfoxides and α-alkoxy-ß-ketothioethers has been developed. It was determined that various thiophenols and alkenes/alkynes are compatible to realize the target compounds from a medium to a high yield by regulating the reaction temperature. In particular, methanol not only served as a solvent but also participated in the reaction process as a hydrogen donor. In this study, Selectfluor has been proved to be an efficient multifunctional reagent in the reaction system.

Metabolomics study of fibroblasts damaged by UVB and BaP.

We have recently shown that both UVB and BaP can induce the production of ROS, apoptosis and even cancer. However, the differences in the metabolic profiles of skin damaged by UVB, BaP or UVB combined with BaP have not been studied. Therefore, we examined the metabolic changes in the human foreskin fibroblast injured by UVB or BaP or the combination of the two, using ultra performance liquid chromatography (UPLC) coupled with quadrupole time-of-flight mass spectrometry (qTOF-MS). 24 metabolites were altered in the UVB damage group, 25 in the BaP damage group, and 33 in the UVB combined with BaP group. These alterations indicated that the metabolic mechanisms of HFF-1 cells treated with UVB or BaP are related to multiple main metabolites including glycerophosphocholine (PC), lactosylceramide (LacCer), guanidinosuccinic acid (GSA), glutathione(GSH), and lysophosphatidylcholine (LysoPC) and the main mechanisms involved glycerophospholipid and glutathione metabolism. Thus, our report provided useful insight into the underlying mechanisms of UVB and BaP damage to skin cells.

Exploration of potential lipid biomarkers for premature canities by UPLC-QTOF-MS analyses of hair follicle roots.

BACKGROUND: The rate of premature greying, referred to as canities, varies among populations, and effective treatments are lacking. However, few studies at the molecular level have been reported. OBJECTIVES: Comparing lipid profiles of individuals with premature canities and healthy volunteers to explore the mechanism of premature canities. METHODS: Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to detect lipids in the hair follicle root. Multivariate data analysis was used to show lipid changes in follicle roots. RESULTS: We identified lipids in the hair follicle root that differ between black and white hair and analysed key lipids contributing to white hair development. We divided the samples into three groups: PC-WH (Premature canities-White hair), PC-PH (Premature canities-Pigmented hair), Control-PH (Pigmented hair). Phosphatidylethanolamine (PE), phosphatidylcholine (PC), vitamin D3 (VD3) and cholesterol in Control-PH were higher than those in PC-WH. Sphingomyelin (SP), phosphatidic acid (PA), VD3 and diglyceride (DG) were lower in PC-WH than in PC-PH. Levels of VD3 were highest in Control-PH, gradually decreased as the severity of PC-PH increased and were lowest in PC-WH. CONCLUSION: There are 7 main class candidate compounds involved in the generation of white hair. VD3 showed a substantial decrease in white hair and was a potential target for further studies of premature canities.

Prediction of neonatal acne based on maternal lipidomic profiling.

BACKGROUND: Neonatal acne occurs in the first few weeks after birth. Some lesions are more serious and leave scars. Maternal surface skin lipids (SSL) have a strong correlation with SSL of infants. The establishment of prediction rank model based on maternal SSL is essential to the prevention and treatment of neonatal acne. METHOD: Surface skin lipids samples were collected from the mothers (M) of 56 neonatal acne patients and the mothers (HM) of 19 healthy infants. Surface skin lipids from the right forehead were collected using a noninvasive method. UPLC-QTOF-MS was applied to detect SSL. Partial least squares discriminant analysis and receiver operating characteristic (ROC) analysis were performed to screen and validate potential lipids. Random forest (RF) and ROC analysis were used to establish a prediction model and evaluate its accuracy. RESULTS: Sixteen altered potential lipids belonging to fatty acids, sphingomyelins, and glycerides were associated with M. M had less lipids than HM. Spearman's correlation of 16 lipids revealed 9 with high correlation. They were chosen as characteristic values of the RF prediction model. And the model showed an average accuracy of 98% in the validation set. CONCLUSION: We have established an RF model for predicting neonatal acne and have shown that high skin barrier-related lipids were markers for predicting neonatal acne.