Conversion of FeCo from soft to hard magnetic material by lattice engineering and nanopatterning

The development of magnetic materials with large uniaxial magnetic anisotropy (K-u) and high saturation magnetization has attracted much attention in various areas such as high-density magnetic storage, spintronic devices, and permanent magnets. Although FeCo alloys with the body-centred cubic structure exhibit the highest M-s among all transition metal alloys, their low K-u and coercivity (H-c) make them unsuitable for these applications. However, recent first-principles calculations have predicted large K-u for the FeCo films with the body-centred tetragonal structure. In this work, we experimentally investigated the hard magnetic properties and magnetic domain structures of nanopatterned FeCo alloy thin films. As a result, a relatively large value of the perpendicular uniaxial magnetic anisotropy K-u = 2.1 x 10(6) J.m(-3) was obtained, while the H-c of the nanopatterned FeCo layers increased with decreasing dot pattern size. The maximum H-c measured in this study was 4.8 x 10(5) A.m(-1), and the corresponding value of mu H-0(c) was 0.60 T, where mu(0) represented the vacuum permeability

Jun Activation Domain-binding Protein 1 (JAB1) Is Required for the Optimal Response to Interferons

Degradation of IFN receptor (IFNR) protein is one of the mechanisms to limit the extent of cellular responses to interferons. Tyrosine kinase 2 (TYK2), a JAK family kinase, has been reported to bind to and stabilize IFNR, indicating that TYK2 is a fundamental component of IFNR complex. Herein, we identified Jun activation domain-binding protein 1 (JAB1) as a new TYK2 binding partner and investigated its role in the regulation of IFN responses. siRNA knockdown of JAB1 resulted in suppression of IFN-induced phosphorylation of STAT proteins and their transcriptional activation. Importantly, JAB1 knockdown induced the activation of SCF ubiquitin ligase complex containing Cullin 1 (CUL1), as judged by the enhancement of covalent modification of CUL1 with the ubiquitin-like protein NEDD8, and markedly reduced the basal protein level of IFNR. In contrast, NEDD8 knockdown or inhibition of NEDD8 modification by NEDD8-activating enzyme inhibitor resulted in increased IFNR protein concomitantly with a reduction of NEDD8-modified CUL1. Furthermore, NEDD8-activating enzyme inhibitor treatment enhanced the susceptibility to IFN-alpha in HeLa cells. These data suggest that the NEDD8 modification pathway is involved in the proteolysis of IFNR and that JAB1 acts as a positive regulator of IFN responses by stabilizing IFNR through antagonizing the NEDD8 pathway

GTN057, a komaroviquinone derivative, induced myeloma cells' death in vivo and inhibited c‐MET tyrosine kinase

Abstract Objective Despite the development of newly developed drugs, most multiple myeloma (MM) patients with high‐risk cytogenetic abnormalities such as t(4;14) or del17p relapse at anin early stage of their clinical course. We previously reported that a natural product,komaroviquinone (KQN), isolated from the perennial semi‐shrub Dracocephalum komarovi, i.e., komaroviquinone (KQN) and its derivative GTN024 induced the apoptosis of MM cells by producing reactive oxygen species (ROS), but both exhibited significant hematological toxicity. Aim of this study is to clarify anti‐tumor activity, safety and pharmacokinetics of GTN057, an optimization compound of KQN in vivo. Methods ICR/SCID xenograft model of KMS11, a t(4;14) translocation‐positive MM cell line, was used for in vivo study. Mice pharmacokinetics of GTN057 and the degradation products were analyzed by LC‐MS/MS. Results Herein, our in vitro experiments revealed that GTN057 is much less toxic to normal hematopoietic cells, induced the apoptosis of both MM cell lines andpatient samples, including those with high‐risk cytogenetic changes. A xenograft model of a high‐risk MM cell line demonstrated that GTN057 significantly delayed the tumor growth with no apparent hematological or systemic toxicities in vivo. The pathological examination of GTN057‐treated tumors in vivoshowed revealed apoptosis of MM cells and anti‐angiogenesis. In addition to the production of ROS, GTN057 inhibited the downstream signaling of c‐MET, a receptor tyrosine kinase a receptor forand hepatocyte growth factor (HGF) receptor. Thus, GTN057 is less toxic and is able tomay be a candidate drug for treating MM patients, via multifunctional mechanisms. We have also extensively studied the pharmacologyical analysis of GTN057. The metabolites of GTN057, (e.g.,such as GTN054), may also have anti‐tumorantitumor activity. Conclusion Natural products or and their derivatives can could be good sources of antineoplastic drugs even for high‐risk cancer