Growing evidence indicates that tumor suppressor gene TP-53 and non-coding RNA miR-34b/c independently and/or jointly play crucial roles in carcinogenesis. We hypothesized that the polymorphisms of rs4938723 in the promoter region of pri-miR-34b/c and TP-53 Arg72-Pro may be related to the risk of nasopharyngeal carcinoma (NPC). We performed a case-control study between 217 patients with NPC and 360 healthy controls in a Chinese population using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. A significantly increased risk of NPC was observed in the miR-34b/c rs4938723 CT/CC genotypes compared with the TT genotype (adjusted OR=1.44, 95 % CI 1.02-2.03, p=0.04), and also the C allele (adjusted OR=1.33, 95 % CI 1.04-1.70, p=0.03). The gene-gene interaction of miR-34b/c rs4938723 and TP-53 Arg72-Pro showed that the combined genotypes of rs4938723CT/CC and TP-53CG/CC increased the risk of NPC (rs4938723CT/CC + TP-53CG/CC vs. rs4938723 TT+TP-53 CG/CC: OR=1.58, 95 % CI 1.04-2.42, p=0.03). These findings suggest that miR-34b/c rs4938723 and TP-53 Arg72Pro polymorphisms may singly or collaboratively contribute to the risk of NPC.

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Recent biocatalysis studies have shown that many enzymes exhibit catalytic activity and enhanced thermal stability in essentially anhydrous nonpolar solvents. At present we do not understand the important role that water plays in protein structure stabilization and in enzyme mechanisms in nonaqueous environments. In this study, the NH-exchange rates of oxidized horse cytochrome c suspended in tetrahydrofuran (THF) containing 1% D20 (vol/vol) at 37 °C, pH 8.9, have been determined indirectly by 2D NH-exchange NMR spectroscopy. In such a solvent system, we have allowed j ust enough water molecules to form approximately a monolayer surrounding the protein. A hydrophobic tripeptide N-acetyl-(Ala)3-OCH3 was used to calculate the intrinsic amide-exchange rate directly for a random-coil peptide in THF/1% D20. The relative solvent protection factors for amide exchange of cytochrome c in THF/1% D20 have been determined for 35 amide protons and compared with the results obtained at the same pH in aqueous solution. Almost all of these protected protons are located in the three major a-helical regions or involved in crystallographically defined intramolecular hydrogen bonding. In both aqueous solution and THF/1% D20 at pH 8.9, the NH-exchange profile for cytochrome c is similar to that in the native state (pD 7.0: Jeng, et al., Biochemistry 1990,29,10433-10437).The protection factors against exchange were greatest for the NH protons of PhelO and those in the central part of the C-terminal helix, Ile95, Tyr97, and Leu98. The protection factors from the majority of observable NH protons for cytochrome c in purely aqueous solution, pH 8.9, vary between 104 and 10*. These are about <50-fold smaller than those in the native state at pD 7.0 but are 103-104 larger than those in the molten globule state. The protection factors in THF/1% D20 at pH 8.9 vary between 101 2 345678and 10s, which are in turn 102-103-fold smaller than those observed at pH 8.9 in purely aqueous solution. These results suggest that while cytochrome c remains folded and compact at pH 8.9 in both purely aqueous solution and THF/1% D20, the flexibility of the protein is clearly enhanced, especially in the organic medium. However, some differences were also observed between the two solvent systems. Most noticeably part of the C-terminal helix (Leu94, Ala96, and Lys99) has the lowest NH-exchange rates in D20, whereas in THF/1% D20 these exchange rates increased dramatically. This may reflect differences in tertiary interactions in the two solvents. The N-terminal and C-terminal helices fold over each other in the native structure. The decrease in protection factor for those residues of the C-terminal helix facing the N-terminal helix suggests that this helix interaction is destabilized in the hydrated organic solvent, exposing to the surface residues Leu94, Ala96, and Lys99. These hydrogenexchange results on cytochrome c suggest that water serves to "lubricate" the local dynamics of the protein in THF/1% D20 and that the slightly hydrated organic solvent enhances ...

Exploring multi-functional properties in a single material is the focus for future material design and applications. In this work, we investigated the multiferroic property of Cu doped ZnO films using a combination of X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray absorption spectroscopy (XAS), classical magnetometry and electric measurements. The results show that the texture of Cu doped ZnO films is deteriorated with an increase in Cu contents, whereas the dielectric property is improved due to the introduction of Cu ions. The XAS result reveals that the Cu atoms occupy the substitutional Zn sites in the ZnO host, and thus induce local electric dipoles owing to the displacement of the Cu-O bond. The presence of oxygen vacancies together with Cu ions facilitates the movement of the ferroelectric domain boundary, and contributes to the ferromagnetism due to the indirect exchange between Cu atoms and large-sized vacancy orbitals. The Cu doped ZnO film is a feasible promising candidate for applications in multiferroic devices.

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