EZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is a highly conserved histone methyltransferase that methylates lysine 27 of histone 3. Overexpression of EZH2 has been found in a wide range of cancers, including those of the prostate and breast. In this review, we address the current understanding of the oncogenic role of EZH2, including its PRC2-dependent transcriptional repression and PRC2-independent gene activation. We also discuss the connections between EZH2 and other silencing enzymes, such as DNA methyltransferase and histone deacetylase. We comprehensively address the architecture of the PRC2 complex and the crucial roles of each subunit. Finally, we summarize new progress in developing EZH2 inhibitors, which could be a new epigenetic therapy for cancers.

We report here that des-methyl, des-amino pateamine A (DMDA-PatA), a structurally simplified analogue of the marine natural product pateamine A, has potent antiproliferative activity against a wide variety of human cancer cell lines while showing relatively low cytotoxicity against nonproliferating, quiescent human fibroblasts. DMDAPatA retains almost full in vitro potency in P-glycoprotein-overexpressing MES-SA/Dx5-Rx1 human uterine sarcoma cells that are significantly resistant to paclitaxel, suggesting that DMDA-PatA is not a substrate for P-glycoprotein-mediated drug efflux. Treatment of proliferating cells with DMDA-PatA leads to rapid shutdown of DNA synthesis in the S phase of the cell cycle. Cell-free studies show that DMDA-PatA directly inhibits DNA polymerases α and γ in vitro albeit at concentrations considerably higher than those that inhibit cell proliferation. DMDA-PatA shows potent anticancer activity in several human cancer xenograft models in nude mice, including significant regressions observed in the LOX and MDA-MB-435 melanoma models. DMDA-PatA thus represents a promising natural product-based anticancer agent that warrants further investigation.

The future of energy supply depends on innovative breakthroughs in the development of highly efficient, sustainable and low-cost systems for renewable energy conversion and storage. Water splitting is a promising and appealing solution. In this work, we report Co(OH)2 on the carbon nanotube/polyimide film (PI/CNT-Co(OH)2) as an efficient electrocatalyst for the oxygen evolution reaction (OER). The PI/CNT film allows intimate growth of Co(OH)2 nanosheets on its surface. The nanosheet structure of Co(OH)2 and the underlying PI/CNT film facilitate the good OER performance of the PI/CNT-Co(OH)2 film. Co(OH)2 nanosheets on the PI/CNT film afford an earlier onset of oxygen evolution, a low overpotential of 317 mV and a small Tafel slope of 49 mV per decade in alkaline media. This work applies the PI/CNT film in water splitting to enhance the OER electrocatalytic activity of Co(OH)2, which opens up a promising avenue for the exploration of highly active electrocatalysts that can replace noble-metal based catalysts for the OER.

Promising catalytic activity of MoSe2 in the hydrogen evolution reaction (HER) is synthesized on a new reduced graphene oxide/polyimide (rGO/PI) substrate by a simple electrochemical method. The MoSe2 nanoparticles have excellent photo‐responsive properties; the potential difference could reach 0.45 V with the photo‐responsive time just 0.6 s. Furthermore, MoSe2 thin film exhibits superior catalytic activity in the hydrogen evolution reaction (HER). It has a greater cathode current at more positive potential compared to other MoSe2 and MoS2, and the efficiency of H2 evolution is strongly influenced by illumination; this suggests that MoSe2 composite film has good photoelectrocatalysis properties for hydrogen evolution. Besides, both dark and illumination MoSe2 films exhibit extremely high stability in acidic solution as the HER catalytic activity shows no degradation after 100 cycles for two hours. All results indicate that MoSe2–rGO/PI composite film has potential to be a better catalyst for HER.

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wileyonlinelibrary.comAs a typical transition-metal dichalcogenide, MoS 2 is a promising electrocatalyst for HER. Both computational and experimental results have confi rmed that the HER activity of MoS 2 stemmed from the sulfur edges, whereas the basal planes were catalytically inert. [ 16,17 ] As a result, nanosized MoS 2 should be more active for HER electrocatalysis than the relatively inert bulk forms due to the presence of more exposed sulfur edges. Besides, the electrical conductivity of catalysts is crucial to the catalytic activity because a high conductivity can ensure a fast electron transfer during a catalytic process. [ 18,19 ] It is well-known that MoS 2 exhibits poor intrinsic conductivity originated from its large bandgap, [ 20 ] which signifi cantly limits the overall HER rate. The past years have witnessed expanding endeavors in improving the conductivity of MoS 2 -based electrocatalysts. Carbon materials have been widely used to improve the catalytic activity of MoS 2 , relying on their unique physicochemical properties. Dai and coworkers synthesized MoS 2 /RGO composite and achieved high HER catalytic activity at a low overpotential. [ 21 ] Chorkendorff and co-workers reported a highly active and stable carbon fi bre/ MoS x composite for electrochemical hydrogen evolution. [ 22 ] Cheng and co-workers synthesized CoS 2 /RGO-CNT composites for high effi cient HER electrocatalysts. [ 23 ] Such fi ndings suggest the signifi cance of carbon materials in HER electrocatalysis. MoS 2 /carbon composites have been successfully applied for the electrocatalytic HER, where carbon materials play the role of hosting MoS 2 as well as enhancing the conductivity of the composites.Although the HER properties of MoS 2 /carbon composites have been investigated, the electrocatalytic activity of MoS 2 supported on carbon materials in the form of a conducting polymer fi lm has not been studied. In this work, we synthesized MoS 2 on the reduced graphene oxide-modifi ed carbon nanotube/ polyimide (PI/CNT-RGO) fi lm by an electrochemical method. CNT can greatly improve the mechanical and electrical properties of CNT/polymer composites, leading to the good conductivity and mechanical properties of PI/CNT fi lm. [ 24,25 ] PI/CNT fi lm can be used over a wide temperature range of −200 to 300 °C and in the condition of strong acid or alkaline. We prepared PI/CNT fi lm and modifi ed the fi lm with RGO which further improved the conductivity of PI/CNT fi lm and affected the morphology of

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Apratoxin A is a natural product with potent antiproliferative activity against many human cancer cell lines. However, we and other investigators observed that it has a narrow therapeutic window in vivo. Previous mechanistic studies have suggested its involvement in the secretory pathway as well as the process of chaperone-mediated autophagy. Still the link between the biologic activities of apratoxin A and its in vivo toxicity has remained largely unknown. A better understanding of this relationship is critically important for any further development of apratoxin A as an anticancer drug. Here, we describe a detailed pathologic analysis that revealed a specific pancreas-targeting activity of apratoxin A, such that severe pancreatic atrophy was observed in apratoxin A-treated animals. Follow-up tissue distribution studies further uncovered a unique drug distribution profile for apratoxin A, showing high drug exposure in pancreas and salivary gland. It has been shown previously that apratoxin A inhibits the protein secretory pathway by preventing cotranslational translocation. However, the molecule targeted by apratoxin A in this pathway has not been well defined. By using a 3 H-labeled apratoxin A probe and specific Sec 61a/b antibodies, we identified that the Sec 61 complex is the molecular target of apratoxin A. We conclude that apratoxin A in vivo toxicity is likely caused by pancreas atrophy due to high apratoxin A exposure.