SUMMARY Mitochondria play an integral role in cell death, autophagy, immunity, and inflammation. We previously showed that Nur77, an orphan nuclear receptor, induces apoptosis by targeting mitochondria. Here, we report that celastrol, a potent anti-inflammatory pentacyclic triterpene, binds Nur77 to inhibit inflammation and induce autophagy in a Nur77-dependent manner. Celastrol promotes Nur77 translocation from the nucleus to mitochondria, where it interacts with tumor necrosis factor receptor-associated factor 2 (TRAF2), a scaffold protein and E3 ubiquitin ligase important for inflammatory signaling. The interaction is mediated by an LxxLL motif in TRAF2 and results not only in the inhibition of TRAF2 ubiquitination but also in Lys63-linked Nur77 ubiquitination. Under inflammatory conditions, ubiquitinated Nur77 resides at mitochondria, rendering them sensitive to autophagy, an event involving Nur77 interaction with p62/SQSTM1. Together, our results identify Nur77 as a critical intracellular target for celastrol and unravel a mechanism of Nur77-dependent clearance of inflamed mitochondria to alleviate inflammation.

BackgroundGlycosyltransferases comprise a highly divergent and polyphyletic multigene family that is involved in widespread modification of plant secondary metabolites in a process called glycosylation. According to conserved domains identified in their amino acid sequences, these glycosyltransferases can be classified into a single UDP-glycosyltransferase (UGT) 1 superfamily.ResultsWe performed genome-wide comparative analysis of UGT genes to trace evolutionary history in algae, bryophytes, pteridophytes, and angiosperms; then, we further investigated the expansion mechanisms and function characterization of UGT gene families in Brassica rapa and Brassica oleracea. Using Hidden Markov Model search, we identified 3, 21, 140, 200, 115, 147, and 147 UGTs in Chlamydomonas reinhardtii, Physcomitrella patens, Selaginella moellendorffii, Oryza sativa, Arabidopsis thaliana, B. rapa, and B. oleracea, respectively. Phylogenetic analysis revealed that UGT80 gene family is an ancient gene family, which is shared by all plants and UGT74 gene family is shared by ferns and angiosperms, but the remaining UGT gene families were shared by angiosperms. In dicot lineage, UGTs among three species were classified into three subgroups containing 3, 6, and 12 UGT gene families. Analysis of chromosomal distribution indicates that 98.6 and 71.4% of UGTs were located on B. rapa and B. oleracea pseudo-molecules, respectively. Expansion mechanism analyses uncovered that whole genome duplication event exerted larger influence than tandem duplication on expansion of UGT gene families in B. rapa, and B. oleracea. Analysis of selection forces of UGT orthologous gene pairs in B. rapa, and B. oleracea compared to A. thaliana suggested that orthologous genes in B. rapa, and B. oleracea have undergone negative selection, but there were no significant differences between A. thaliana –B. rapa and A. thaliana –B. oleracea lineages. Our comparisons of expression profiling illustrated that UGTs in B. rapa performed more discrete expression patterns than these in B. oleracea indicating stronger function divergence. Combing with phylogeny and expression analysis, the UGTs in B. rapa and B. oleracea experienced parallel evolution after they diverged from a common ancestor.ConclusionWe first traced the evolutionary history of UGT gene families in plants and revealed its evolutionary and functional characterization of UGTs in B. rapa, and B. oleracea. This study provides novel insights into the evolutionary history and functional divergence of important traits or phenotype-related gene families in plants.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3844-x) contains supplementary material, which is available to authorized users.

Schizochytrium was a known docosahexaenoic acid producing marine microalgae. In this study, we have developed a novel transformation approach of Schizochytrium using the Agrobacterium tumefaciens (A. tumefaciens) binary vector system. After co-cultivation of Schizochytrium protoplasts with A. tumefaciens harboring pCAMBIA2301 containing the neomycin phosphotransferase II (NPT II) gene as the selectable marker which confers resistance to G418, the Schizochytrium transformants were successfully obtained on the G418-containing plates. The integration and expression of the transgenes were confirmed by PCR analysis and GUS activity assay. To further validate the transformation system, pCAMBIA2301-EGFP containing the egfp gene was introduced into Schizochytrium. The following results demonstrated that the exogenous egfp gene has been successfully incorporated into the genome of Schizochytrium. In addition, the introduced egfp gene expressed efficiently according to the Western blot and fluorescence assay results. More importantly, the majority of the transformants displayed similar biomass and fatty acid production comparing with the wild type strain. Our results demonstrated that exogenous genes could be expressed efficiently in transgenic Schizochytrium, suggesting that genetically engineered Schizochytrium could be explored by this system.

Polycystic ovary syndrome (PCOS) is a major health problem in reproductive-aged women worldwide, but the precise pathogenesis of PCOS remains unclear. Our previous study revealed that hypoxia-inducible factor (HIF)-1a mediated endothelin (ET)-2 signaling plays an important role in ovulation in rats. Therefore, the present study used a PCOS rat model to test the hypotheses that HIF-1a signaling is expressed and inhibited in ovaries during PCOS formation and that the HIF-1a/ET-2 signaling pathway is a target of dimethyldiguanide (DMBG) in the clinical treatment of PCOS. First, the development of a PCOS model and the effect of DMBG treatment were examined through ovarian histology and serum hormone levels, which were consistent with previous reports. Second, HIF-1a and ET-2 expression were detected by immunohistochemistry and western blot. The results showed decreased HIF-1a/ET-2 expression in the ovaries of PCOS rats, whereas DMBG treatment reversed the protein decreases and improved the PCOS symptoms. Third, to understand the molecular mechanism, HIF-1a/ET-2 mRNA expression was also examined. Interestingly, HIF-1a mRNA increased in the ovaries of PCOS rats, while ET-2 mRNA decreased, indicating that HIF-1a protein degradation may be involved in POCS development and treatment. Finally, HIF prolyl hydroxylase (PHD) activity was examined to further clarify the contribution of HIF-1a signaling to the development and treatment of PCOS. The results suggested that the inhibition of HIF-1a/ET-2 signaling may be caused by increased PHD activity in PCOS. DMBG-treated PCOS may further activate HIF-1a signaling at least partly through inhibiting PHD activity. Taken together, these results indicate that HIF-1a signaling is inhibited in a PCOS rat model through increasing PHD activity. DMBG treatment improved PCOS by rescuing this pathway, suggesting that HIF-1a signaling plays an important role in the development and treatment of PCOS. This HIF-1a-mediated ET-2 signaling pathway may be an important mechanism regulating PCOS formation and treatment in mammalian ovaries in vivo and should be a new clinical target for PCOS prevention and treatment in the future.

Shape-programmable hydrogel-based soft actuators that can adaptively respond to external stimuli are of paramount significance for the development of bioinspired aquatic smart soft robots. Herein, we report the design and synthesis of near-infrared (NIR) light-driven hydrogel actuators through in situ photopolymerization of poly(N-isopropylacrylamide) (PNIPAM) hydrogels loaded with metal−organic frameworks (MOFs) onto the surface of the poly(dimethylsiloxane) (PDMS) thin film. The MOFs can not only function as an excellent photothermal nanotransducer but also accelerate the adsorption/desorption of water due to their porous nanostructure, which speeds up the response rate of the actuators. Shape-programmable hydrogel actuators are fabricated by tailoring the patterning of PDMS thin film, and thus different shape-morphing modes such as directional bending and chiral twisting are observed under the NIR light irradiations. As the proof-of-concept demonstrations, an artificial hand, biomimetic mimosa, and flower are conceptualized with light-driven MOF-containing hydrogel actuators. Interestingly, we are able to achieve an octopus-inspired light-driven soft swimmer upon cyclic NIR illumination due to the fast photoresponsiveness of as-prepared hydrogel actuators. This work can offer insights for fabricating programmable and reconfigurable smart aquatic soft actuators, thus shining a light into their potential applications in emerging fields including soft robots, biomedical devices, and beyond.