Tumor necrosis factor α (TNFα)‐ and interleukin 1β (IL‐1β)‐induced nuclear factor‐κB (NF‐κB) activation play key roles in inflammation, immunity, and cancer development. Here, we identified one of the deubiquitinating enzymes (DUBs), ubiquitin‐specific protease 15 (USP15), as a positive regulator in both TNFα‐ and IL‐1β‐induced NF‐κB activation. Overexpression of USP15 potentiated TNFα‐ or IL‐1β‐triggered NF‐κB activation and downstream gene transcription, whereas knockdown of USP15 had opposite effects. Mechanistically, upon TNFα stimulation, USP15 showed an enhanced interaction with transforming growth factor‐β activated kinase‐1 (TAK1)‐TAK1 binding protein (TAB) complex to inhibit the proteolysis of TAB2/3 by different pathways. Apart from deubiquitination dependently inducing cleavage of lysine 48‐linked TAB2 ubiquitination, USP15 also DUB independently inhibited lysosome‐associated TAB2 degradation, thus enhanced TAB2 stabilization. For TAB3, USP15 inhibited NBR1‐mediated selective autophagic TAB3 degradation independent of its deubiquitinating activity. Together, our results reveal a novel USP15‐mediated mechanism through which efficient NF‐κB activation is achieved by differentially maintaining the TAB2/3 stability.

No abstract

Acute liver injury is commonly caused by bacterial endotoxin/lipopolysaccharide (LPS), and by drug overdose such as acetaminophen (APAP). The exact role of epigenetic modification in acute liver injury remains elusive. Here, we investigated the role of histone methyltransferase G9a in LPS-or APAP overdose-induced acute liver injury. Under Dgalactosamine sensitization, liver-specific G9a-deficient mice (L-G9a −/−) exhibited 100% mortality after LPS injection, while the control and L-G9a +/− littermates showed very mild mortality. Moreover, abrogation of hepatic G9a or inhibiting the methyltransferase activity of G9a aggravated LPS-induced liver damage. Similarly, under sublethal APAP overdose, L-G9a −/− mice displayed more severe liver injury. Mechanistically, ablation of G9a inhibited H3K9me1 levels at the promoters of Gstp1/2, two liver detoxifying enzymes, and consequently suppressed their transcription. Notably, treating L-G9a −/− mice with recombinant mouse GSTP1 reversed the LPS-or APAP overdose-induced liver damage. Taken together, we identify a novel beneficial role of G9a-GSTP1 axis in protecting against acute liver injury.

Abnormalities of methyl-CpG binding protein 2 (Mecp2) cause neurological disorders with metabolic dysfunction; however, its role in adipose tissues remains unclear.Here, we report upregulated Mecp2 in white adipose tissues (WAT) of obese humans, as well as in obese mice and during in vitro adipogenesis. Normal chow-fed adipocyte-specific Mecp2 knockout mice (Mecp2 Adi KO mice) showed a lean phenotype, with downregulated lipogenic genes and upregulated thermogenic genes that were identified using RNA sequencing. Consistently, the deficiency of Mecp2 in adipocytes protected mice from high-fat diet (HFD)-induced obesity and inhibited in vitro adipogenesis. Furthermore, Mecp2 Adi KO mice showed increased browning under different stimuli, including cold treatment. Mechanistically, Mecp2 bound to the promoter of secretory leukocyte protease inhibitor (Slpi) and negatively regulated its expression. Knockdown of Slpi in inguinal WAT of Mecp2 Adi KO mice prevented cold-induced browning. Moreover, recombinant SLPI treatment reduced the HFD-induced obesity via enhancing browning. Together, our results suggest a novel non-central nervous system function of Mecp2 in obesity by suppressing browning, at least partially, through regulating adipokine Slpi.

Natural dyes are environmentally friendly and have become important alternatives to synthetic dyes in some dyeing products. Therefore, better extraction and dyeing techniques need to be developed for the dyeing process of natural dyes. In this work, cotton fabric was dyed using turmeric extraction solution under an ultralow liquor ratio (materials to liquor ratio of 1:5) and ultrasonic-assisted conditions. Dye extraction using different dispersants and pH values has been investigated and three-factor-three–level Box–Behnken design was employed to explore the dyeing conditions. It was found that sodium dodecyl sulfate systems and ultrasonic waves can effective improve the dyeing depth under neutral condition. The K/ S value can reach 2.53 with ultrasonic power of 200 W, dyeing time of 30 min and temperature of 40℃. Scanning electron microscope images showed that the application of ultrasound did not cause obvious fiber damage. The developed technique could be used in the textile industry to make dyeing cotton fibers with natural dyes more sustainable than it is at present.