Cdc48/p97, a ubiquitin-selective chaperone, orchestrates the function of E3 ligases and deubiquitylases (DUBs). Here, we identify a new function of Cdc48 in ubiquitin-dependent regulation of mitochondrial dynamics. The DUBs Ubp12 and Ubp2 exert opposing effects on mitochondrial fusion and cleave different ubiquitin chains on the mitofusin Fzo1. We demonstrate that Cdc48 integrates the activities of these two DUBs, which are themselves ubiquitylated. First, Cdc48 promotes proteolysis of Ubp12, stabilizing profusion ubiquitylation on Fzo1. Second, loss of Ubp12 stabilizes Ubp2 and thereby facilitates removal of ubiquitin chains on Fzo1 inhibiting fusion. Thus, Cdc48 synergistically regulates the ubiquitylation status of Fzo1, allowing to control the balance between activation or repression of mitochondrial fusion. In conclusion, we unravel a new cascade of ubiquitylation events, comprising Cdc48 and two DUBs, fine-tuning the fusogenic activity of Fzo1.

Coordinated translation initiation is coupled with cell cycle progression and cell growth, whereas excessive ribosome biogenesis and translation initiation often lead to tumor transformation and survival. Hepatocellular carcinoma (HCC) is among the most common and aggressive cancers worldwide and generally displays inherently high resistance to chemotherapeutic drugs. We found that RACK1, the receptor for activated C-kinase 1, was highly expressed in normal liver and frequently upregulated in HCC. Aberrant expression of RACK1 contributed to in vitro chemoresistance as well as in vivo tumor growth of HCC. These effects depended on ribosome localization of RACK1. Ribosomal RACK1 coupled with PKCβII to promote the phosphorylation of eukaryotic initiation factor 4E (eIF4E), which led to preferential translation of the potent factors involved in growth and survival. Inhibition of PKCβII or depletion of eIF4E abolished RACK1-mediated chemotherapy resistance of HCC in vitro. Our results imply that RACK1 may function as an internal factor involved in the growth and survival of HCC and suggest that targeting RACK1 may be an efficacious strategy for HCC treatment.

Silk fibroin is a useful protein polymer for biomaterials and tissue engineering. In this work, porogen leached scaffolds prepared from aqueous and HFIP silk solutions were reinforced through the addition of silk particles. This led to about 40 times increase in the specific compressive modulus and the yield strength of HFIP-based scaffolds. This increase in mechanical properties resulted from the high interfacial cohesion between the silk matrix and the reinforcing silk particles, due to partial solubility of the silk particles in HFIP. The porosity of scaffolds was reduced from ≈90% (control) to ≈75% for the HFIP systems containing 200% particle reinforcement, while maintaining pore interconnectivity. The presence of the particles slowed the enzymatic degradation of silk scaffolds.

Anatase TiO2 modified FeS nanowires assembled by numerous nanosheets were synthesized by using a typical hydrothermal method. The carbon-free nanocoated composite electrodes exhibit improved reversible capacity of 510 mAh g−1 after 100 discharge/charge cycles at 200 mA g−1, much higher than that of the pristine FeS nanostructures, and long-term cycling stability with little performance degradation even after 500 discharge/charge cycles at current density of 400 mA g−1. Full batteries fabricated using the FeS@TiO2 nanostructures anode and the LiMn2O4 nanowires cathode with excellent stability, and good rate capacities could also be achieved. The enhanced electrochemical performance of the composite electrodes can be attributed to the improved conductively of the integrated electrodes and the enhanced kinetics of lithium insertion/extraction at the electrode/electrolyte interface because of the incorporation of anatase TiO2 phase.

Ordered WO 3 nanowire arrays on carbon cloth (WNCC) conductive substrates are successfully prepared by a facile hydrothermal method. The as-prepared samples were characterized by XRD, SEM and TEM and directly functionalized as supercapacitor (SC) and lithium-ion battery (LIB) electrodes without using any ancillary materials such as carbon black or binder. The unique structural features endow them with excellent electrochemical performance. The SCs demonstrate high specific capacitance of 521 F g À1 at 1 A g À1 and 5.21 F cm À2 at 10 A cm À2 and excellent cyclic performance with nearly 100% capacity retention after 2000 cycles at a current density of 3 A g À1 . All-solid-state SCs based on the integrated electrodes are also presented, exhibiting high flexibility without obvious performance declination at different bending states. A high capacity of 662 mA h g À1 after 140 cycles at a 0.28 C rate and excellent rate capabilities are also obtained for LIBs due to the unique structures of the integrated electrodes.

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Tumor-associated macrophages (TAMs) are major components of the tumor microenvironment. Although a role for TAMs in promoting tumor progression has been revealed, the differentiation mechanisms and intrinsic signals of TAMs regulated by the tumor microenvironment remain unclear. Here we constructed an in vitro TAMs cell model, TES-TAMs, which is from tumor-extract-stimulated bone-marrow-derived macrophages. We performed a comparative proteomics analysis of bone-marrow-derived macrophages and TES-TAMs, which indicated that TES-TAMs possessed characteristic molecular expression of TAMs. Intriguingly, the signal pathways enriched in up-regulated differentially expressed proteins of TAMs demonstrated that glycolysis metabolism reprogramming may play an important role in TAM differentiation. We found that hexokinase-2, a key mediator of aerobic glycolysis, and the downstream proteins PFKL and ENO1 were remarkably increased in both TES-TAMs and primary TAMs from our MMTV-PyMT mice model. This phenomenon was then verified in human THP-1 cell lines stimulated by tumor extract solution from breast cancer patient. Taken together, our study provides insight into the induction of TAM differentiation by the tumor microenvironment through metabolic reprogramming.

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