No abstract

Hepatocellular carcinoma (HCC) is an aggressive malignancy with increasing mortality in China. Angiogenesis is crucial for tumor formation, development and metastasis in HCC. Previous studies indicated that high expression levels of elongation factor 2 kinase (eEF2K), a protein kinase that negatively regulates the elongation stage of translation, were associated with poor prognosis of HCC. Here, we show that pharmacological inhibition or knockdown of eEF2K in highly metastatic liver cancer cells inhibits their colony forming and migratory capacities, as well as reducing their invasiveness. Importantly, knocking down eEF2K by lentiviral directed shRNA prevented tumor growth and angiogenesis of HCC in mice. Silencing of eEF2K in endothelial cells (HUVECs) led to a reduction in vascularization, evidenced by a decrease in capillary‐like structures in the matrigel. Notably, knocking down eEF2K reduced the expression of angiogenesis‐related growth factors in liver cancer cells and the expression of growth factor receptors on HUVECs, and thus restricted signaling crosstalk that promotes angiogenesis between HCC cells and endothelial cells. We also showed that silencing of eEF2K effectively reduced protein levels of SP1/KLF5 transcription factors and hence decreased the levels of bound SP1/KLF5 to the VEGF promoter, resulted in a decrease in VEGF mRNA expression. Knocking down eEF2K also led to a striking decrease in the phosphorylation of PI3K/Akt and STAT3, indicating inactivation of these tumorigenic pathways. Taken together, our data suggest that eEF2K contributes to angiogenesis and tumor progression in HCC via SP1/KLF5‐mediated VEGF expression, as well as the subsequent stimulation of PI3K/Akt and STAT3 signaling.

Interfacial energy storage contributes a new mechanism to the emergence of energy storage devices with not only a high-energy density of batteries but also a high-power density of capacitors. In this study, success was achieved in preparing a highly ordered two-dimensional (2D) carbon/TiO2 (C/TiO2) nanosheet composite using commercially available organic molecules with multifunctional groups and taking advantage of the wedge effects, oxidative polymerization, and carbonization. An experiment was conducted to validate the excellent performance of this 2D composite with respect to interfacial energy storage. The coin cell with 2D C/TiO2 nanosheet composite demonstrates a specific capacity of as high as 510 mAh g–1 and a high specific energy of 390.9 Wh kg–1 at a specific power of 75.9 W kg–1 with a current density of 0.1 A g–1, and it also remains 39.0 Wh kg–1 at a specific power of 8.2 kW kg–1 with a high current density of 12.8 A g–1. The excellent electrochemical performance can be attributed to the superior artificial interface capacitive Li+ storage capability, which would bridge the energy and power density gap between batteries and capacitors. Meanwhile, there are two varieties of carbon derivatives, 2D carbon nanosheet stacks and exfoliated carbon nanosheets, which can be obtained by wet-chemical etching and mechanical peeling. The experimental route is simple from commercially available raw materials, and it could be scalable at a low cost and large scale, which makes it suitable for application in various fields such as energy storage, nanocatalysis, sensors, and so on.

Intercalation of carbon nanosheets into two-dimensional (2D) inorganic materials could enhance their properties in terms of mechanics and electrochemistry, but sandwiching these two kinds of materials in an alternating sequence is a great challenge in synthesis. Herein, we report a novel strategy to construct TiO 2 nanosheets into 2D pillar-layer architectures by employing benzidine molecular assembly as pillars. Then, 2D carbon/TiO 2 nanosheet composite with a periodic interlayer distance of 1.1 nm was obtained following a polymerization and carbonization process. This method not only alleviates the strain arising from the torsion of binding during carbonization but also hinders the structural collapse of TiO 2 due to the intercalation of the carbon layer by rational control of annealing conditions. The composite material possesses a large carbon/TiO 2 interface, providing abundant active sites for ultrafast pseudocapacitive charge storage, thus displaying a superior high-rate performance with a specific capacity of 67.8 mAh g −1 at a current density of 12.8 A g −1 based on the total electrode and excellent cyclability with 87.4% capacity retention after 3000 cycles.

No abstract

Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract from Schisandra sphenanthera that is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ and the target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway.

We present the temporal evolution of magnetic field topology in the magnetotail with a southward IMF in order to identify the magnetic reconnection. The magnetic field topology is uniquely determined by the eigenvalues of the critical points, if they are not degenerated. This is because the critical points, their number, and the rules between them characterize the whole magnetic field pattern. At the critical points, the magnetics become zero. The magnetic vector field curves and surfaces are both integrated out along the principal directions of certain classes of critical points including the Earth's dipole magnetic field. The skeleton that includes the critical points, characteristic curves, and surfaces provides the three-dimensional topological structure of the reconnection. The change of the skeleton, i.e. the change of the topology, has revealed the occurrence of magnetic reconnection. Namely, threedimensional "X-points" or the more-than-two critical points that are saddle and connected each other are unstable and can move, vanish, and generated.

Abstract.A three-dimensional full electromagnetic particle-in-cell (PIC ) code, TRIS-TAN (Tridimensional Stanford) code, has been parallelized using High Performance Fortran (HPF) as a RPM (Real Parallel Machine). In the parallelized HPF code, the simulation domain is decomposed in one-dimension, and both the particle and field data located in each domain that we call the sub-domain are distributed on each processor. Both the particle and field data on a sub-domain are needed by the neighbor sub-domains and thus communications between the sub-domains are inevitable. Our simulation results using HPF exhibit the promising applicability of the HPF communications to a large scale scientific computing such as solar wind-magnetosphere interactions.