Never in Mitosis (NIMA) Related Kinase 2 (NEK2) plays a key role in regulating mitotic processes, including centrosome duplication and separation, microtubule stabilization, kinetochore attachment and spindle assembly checkpoint. NEK2 is aberrantly overexpressed in a wide variety of human cancers and has been implicated in various aspects of malignant transformation, including tumorigenesis, drug resistance and tumor progression. The close relationship between NEK2 and cancer has made it an attractive target for anticancer therapeutic development; however, the mechanisms of how NEK2 coordinates altered signaling to malignant transformation remains unclear. In this paper, we discuss the functional roles of NEK2 in cancer development; highlight some of the significant NEK2 signaling in cancer, and summarize recent advances in the development of NEK2 inhibitors.

No abstract

The high cost and over-potential loss of the cathode are primary bottlenecks of the microbial electrolysis cell (MEC) technology for efficient H 2 production from renewable biomass. In this study, novel NiFe layered double hydroxide (NiFe LDH) electrocatalyst was directly grown on nickel foam for H 2 evolution from actual brewery wastewater and its fermentation effluent. The new cathode demonstrated comparable high H 2 rate (2.01-2.12 m 3-H 2 /m 3 /d) with benchmark Pt catalyst but showed higher H 2 recovery (76-80% vs. 55-66%), which is twice as much as the rate obtained from popular stainless steel mesh and bare nickel foam cathodes. More interestingly, different from the Pt-coated cathode, the NiFe LDH/Ni foam cathode demonstrated very stable and even increased performance overtime when operated in real wastewater. The one-step in situ growth of catalyst on nickel substrate eliminates polymer binders and current collector, which greatly simplifies the manufacture process and reduces costs in large scale systems.

Among various advanced oxidation processes, coupled photocatalysis and heterogeneous Fenton-like catalysis (known as photo-Fenton-like catalysis) to generate highly reactive species for environmental remediation has attracted wide interests. As an emerging metal-free photocatalyst, graphitic carbon nitride (g-C 3 N 4 , CN) has been recently recognized as a promising candidate to catalyze robustly heterogeneous photo-Fenton-like reactions for wastewater remediation. This review summarizes recent progress in fabricating various types of CN-based catalysts for the photo-Fenton-like reaction process. Innovative engineering strategies on the CN matrix are outlined, ranging from morphology control, defect engineering, nonmetal atom doping, organic molecule doping to modification by metal-containing species. The photo-Fenton-like catalytic activities of CN loaded with auxiliary sub-nanoscale (e.g., quantum dots, organometallic molecules, metal cations, and single atom metals) and nanoscale metal-based materials are critically evaluated. Hybridization of CN with bandgap-matching semiconductors for the construction of type-II and Z-scheme heterojunctions are also examined. The critical factors (e.g., morphology, dimensionality, light absorption, charge excitation/migration, catalytic sites, H 2 O 2 generation and activation) that determine the performance of CN-based photocatalysts in Fenton-like catalysis are systematically discussed. After examining the structure-activity relationship, research perspectives are proposed for further development of CN-based photocatalysts toward more efficient photo-Fenton-like reactions and their application in practical water treatment.

Dasatinib (BMS-354825) is a FDA-approved multitargeted kinase inhibitor of BCR/ABL and Src kinases. It is now used in the treatment of chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapies, including imatinib. Here we report a novel effect of dasatinib on inducing the differentiation of acute myeloid leukemia (AML) cells through MEK/ERK-dependent activation of signal transducer and activator of transcription 1 (STAT1). We found that dasatinib could induce the differentiation of AML cells as demonstrated by the expression of differentiation marker CD11b, G0/G1 phase arrest and decreased ratio of nucleus to cytoplasm. Of note, dasatinib induced robust phosphorylation of STAT1 both at Tyr701 and Ser727 as well as the redistribution of STAT1 from the cytoplasm to the nucleus, thus leading to the transcription of STAT1-targeted genes. Knocking down STAT1 expression by shRNA significantly attenuated dasatinib-induced differentiation, indicating an important role of STAT1 in myeloid maturation. We further found that dasatinib-induced activation of STAT1 was regulated by the MEK/ERK kinases. The phosporylation of MEK and ERK occurred rapidly upon dasatinib treatment and increased progressively as differentiation was induced. MEK inhibitors PD98059 and U0216 not only inhibited the phosphorylation of STAT1, but also abrogated dasatinib-induced myeloid differentiation, suggesting that MEK/ERK dependent phosphorylation of STAT1 might be indispensable for the differentiating effect of dasatinib in AML cells. Taken together, our study suggests that STAT1 is an important mediator in dasatinib-induced differentiation of AML cells, whose activation requires the activation of MEK/ERK cascades.