The development of hepatocellular carcinomas (HCC) depends on their local microenvironment and the induction of neovascularization is a decisive step in tumor progression, since the growth of solid tumors is limited by nutrient and oxygen supply. Hypoxia is the critical factor that induces transcription of the hypoxia inducible factor-1α (HIF-1α) encoding gene HIF1A and HIF-1α protein accumulation to promote angiogenesis. However, the basis for the transcriptional regulation of HIF1A expression in HCC is still unclear. Here, we show that Bclaf1 levels are highly correlated with HIF-1α levels in HCC tissues, and that knockdown of Bclaf1 in HCC cell lines significantly reduces hypoxia-induced HIF1A expression. Furthermore, we found that Bclaf1 promotes HIF1A transcription via its bZIP domain, leading subsequently to increased transcription of the HIF-1α downstream targets VEGFA, TGFB, and EPO that in turn promote HCC-associated angiogenesis and thus survival and thriving of HCC cells. Moreover, we demonstrate that HIF-1α levels and microvessel density decrease after the shRNA-mediated Bclaf1 knockdown in xenograft tumors. Finally, we found that Bclaf1 levels increase in hypoxia in a HIF-1α dependent manner. Therefore, our study identifies Bclaf1 as a novel positive regulator of HIF-1α in the hypoxic microenvironment, providing new incentives for promoting Bcalf1 as a potential therapeutic target for an anti-HCC strategy.

Thaumatin-like protein (TLP) is present as a large family in plants, and individual members play different roles in various responses to biotic and abiotic stresses. Here we studied the role of 33 putative grape (Vitis vinifera L.) TLP genes (VvTLP) in grape disease resistance. Heat maps analysis compared the expression profiles of 33 genes in disease resistant and susceptible grape species infected with anthracnose (Elsinoe ampelina), powdery mildew (Erysiphe necator) or Botrytis cinerea. Among these 33 genes, the expression level of TLP29 increased following the three pathogens inoculations, and its homolog from the disease resistant Chinese wild grape V. quinquangularis cv. ‘Shang-24’, was focused for functional studies. Over-expression of TLP29 from grape ‘Shang-24’ (VqTLP29) in Arabidopsis thaliana enhanced its resistance to powdery mildew and the bacterium Pseudomonas syringae pv. tomato DC3000, but decreased resistance to B. cinerea. Moreover, the stomatal closure immunity response to pathogen associated molecular patterns was strengthened in the transgenic lines. A comparison of the expression profiles of various resistance-related genes after infection with different pathogens indicated that VqTLP29 may be involved in the salicylic acid and jasmonic acid/ethylene signaling pathways.

Transition metal nitrides have applications in a range of technological elds. Recent experiments have shown that new nitrogen-bearing compounds can be accessed through a combination of high temperatures and pressures, revealing a richer chemistry than was previously assumed. Here, we show that at pressures above 50 GPa and temperatures greater than 1500 K the elemental copper reacts with nitrogen forming copper diazenide (CuN 2 ). Through a combination of synchrotron X-ray diraction and rst-principles calculations we have explored the stability and electronic structure of CuN 2 . We nd that the novel compound remains stable down to 25 GPa before decomposing to its constituent elements. Electronic structure calculations show that CuN 2 is metallic and exhibits partially lled N 2 antibonding orbitals, leading to an ambiguous electronic structure between Cu + /Cu 2+ . This leads to weak Cu-N bonds and the lowest bulk modulus observed for any transition metal nitride. Graphical TOC Entry

Uniform Eu 3+ doped CdWO 4 nanorods were prepared via a simple hydrothermal method and characterized by X-ray diffraction, transmission electron microscopy, photoluminescence (PL) spectroscopy and PL lifetime measurement. The results indicate that the obtained Eu 3+ doped CdWO 4 nanorods have monoclinic phase structure, and the phase structure can be retained at Eu 3+ doping concentrations of 0.4%~4.0%. The diameter of nanorods decreases from 27 to 15 nm with an increase in the doping concentrations, and the morphology becomes irregular at the Eu 3+ doping concentration of 6.5%. Under the excitation of ultraviolet light, the relative intensities of blue-green emission ascribed to WO 4 2and red emission from Eu 3+ can be tuned through doping Eu 3+ ions into the CdWO 4 nanorods and thus altering the energy transfer between WO 4 2and Eu 3+ . Hence, the multi-color luminescence in a same host under single excited wavelength can be realized simply by altering the doping concentration of Eu 3+ . These luminescent nanomaterials may have potential applications in displays, light sources, bioimaging and so on.

Through a series of Raman spectroscopy studies, we investigate the behaviour of hydrogen-helium and hydrogen-nitrogen mixtures at high pressure across wide ranging concentrations. We find that there is no evidence of chemical association, miscibility, nor any demixing of hydrogen and helium in the solid state up to pressures of 250 GPa at 300 K. In contrast, we observe the formation of concentration-dependent N 2 -H 2 van der Waals solids, which react to form N-H bonded compounds above 50 GPa. Through this combined study, we can demonstrate that the recently claimed chemical association of H 2 -He can be attributed to significant N 2 contamination and subsequent formation of N 2 -H 2 compounds.Understanding the behaviour of molecular mixtures under pressure is of a great importance to many scientific fields varying from chemistry to the studies of internal structures of astronomical bodies [1, 3]. A wide range of phenomena have been observed in high-pressure molecular-mixtures such as phase separation, co-crystallisation, host-guest structures and chemical reaction [4][5][6][7]. Since the discovery of solid van der Waals compounds in the highpressure helium-nitrogen system [8], binary mixtures of elemental gasses have attracted much attention. Subsequently, each binary mixture of the four lightest elemental gasses: H 2 , He, N 2 and O 2 have been studied at high pressure [9][10][11][12][13][14][15]. Recently, there has been renewed interest in studies of both the hydrogen-helium and hydrogen-nitrogen systems at high pressure investigating the synthesis of compounds through the reaction of the constituent molecules [1-3, 18, 19].H 2 and helium are predicted to be chemically inert with one another, across a wide P-T and concentration regime [21][22][23][24][25][26]. Theoretical simulations motivated by potential miscibility within the Jovian planets, find evidence that even at these extreme conditions, hydrogen and helium are still phase separated. Due to the theoretical predictions of no chemical reactivity between hydrogen and helium, there have been few experimental studies on mixtures. Early studies exploring the eutectic phase diagram of hydrogen-helium mixtures found that in the two-fluid state the hydrogen intramolecular vibrational mode is markedly redshifted in Herich concentrations, and was explained semiquantitatively by a helium compressional effect.[10] However in the solid state, the two species were shown to be completely immiscible up to 15 GPa. This observation of immiscibility was utilized to grow single crystals of H 2 , and measure the equation of state up to 100 GPa without an observable reaction between the two. [13] A recent high pressure study exploring H 2 -He interactions as a function of mixture concentration, claimed the unprecedented appearance of hydrogen-helium solids at pressures below 75 GPa [1]. Through the appearance of a vibrational Raman band at an approximate frequency to that calculated for the H-He stretch in a linear H-He-F molecule, the authors claim the formation of H-He b...