Hot Deformation Behavior and Microstructure Evolution of a Graphene/Copper Composite.

Graphene/copper composites are promising in electronic and energy fields due to their superior conductivity, but microstructure control during thermal mechanical processing (TMP) remains a crucial issue for the manufacturing of high-performance graphene/copper composites. In this study, the hot deformation behavior of graphene/copper composites was investigated by isothermal compression tests at deformation temperatures of 700~850 °C and strain rates of 0.01~10 s-1, and a constitutive equation based on the Arrhenius model and hot processing map was established. Results demonstrate that the deformation mechanism of the graphene/copper composites mainly involves dynamic recrystallization (DRX), and such DRX-mediated deformation behavior can be accurately described by the established Arrhenius model. In addition, it was found that the strain rate has a stronger impact on the DRX grain size than the deformation temperature. The optimum deformation temperature and strain rate were determined to be 800 °C and 1 s-1, respectively, with which a uniform microstructure with fine grains can be obtained.

PTC124 Rescues Nonsense Mutation of Two Tumor Suppressor Genes NOTCH1 and FAT1 to Repress HNSCC Cell Proliferation.

(1) Background: PTC124 (Ataluren) is an investigational drug for the treatment of nonsense mutation-mediated genetic diseases. With the exception of the TP53 tumor suppressor gene, there has been little research on cancers with nonsense mutation. By conducting a database search, we found that another two tumor suppressor genes, NOTCH1 and FAT1, have a high nonsense mutation rate in head and neck squamous cell carcinoma (HNSCC). PTC124 may re-express the functional NOTCH1 or FAT1 in nonsense mutation NOTCH1 or FAT1 in HSNCC (2) Methods: DOK (with NOTCH1 Y550X) or HO-1-u-1 (with FAT1 E378X) HNSCC cells were treated with PTC124, and the NOTCH1 or FAT1 expression, cell viability, and NOTCH1- or FAT1-related downstream gene profiles were assayed. (3) Results: PTC124 was able to induce NOTCH1 or FAT1 expression in DOK and HO-1-u-1 cells. PTC124 was able to upregulate NOTCH downstream genes HES5, AJUBA, and ADAM10 in DOK cells. PTC124 enhanced DDIT4, which is under the control of the FAT1-YAP1 pathway, in HO-1-u-1 cells. FLI-06 (a NOTCH signaling inhibitor) reversed PTC124-mediated cell growth inhibition in DOK cells. PTC124 could reverse TT-10 (a YAP signaling activator)-mediated HO-1-u-1 cell proliferation. (4) Conclusions: PTC124 can rescue nonsense mutation of NOTCH1 and FAT1 to repress HNSCC cell proliferation.

Microstructure and Properties of a Graphene Reinforced Cu-Cr-Mg Composite.

To improve the graphene/copper interfacial bonding and the strength of the copper matrix, Cu-Cr-Mg alloy powder and graphene nanosheets (GNPs) have been used as raw materials in the preparation of a layered graphene/Cu-Cr-Mg composite through high-energy ball-milling and fast hot-pressing sintering. The microstructure of the composite after sintering, as well as the effect of graphene on the mechanical properties and conductivity of the composite, are also studied. The results show that the tensile strength of the composite material reached a value of 349 MPa, which is 46% higher than that of the copper matrix, and the reinforcement efficiency of graphene is as large as 136. Furthermore, the electrical conductivity of the composite material was 81.6% IACS, which is only 0.90% IACS lower than that of the copper matrix. The Cr and Mg elements are found to diffuse to the interface of the graphene/copper composite during sintering, and finely dispersed chromium carbide particles are found to significantly improve the interfacial bonding strength of the composite. Thus, graphene could effectively improve the mechanical properties of the composite while maintaining a high electrical conductivity.

P63 and P73 Activation in Cancers with p53 Mutation.

The members of the p53 family comprise p53, p63, and p73, and full-length isoforms of the p53 family have a tumor suppressor function. However, p53, but not p63 or p73, has a high mutation rate in cancers causing it to lose its tumor suppressor function. The top and second-most prevalent p53 mutations are missense and nonsense mutations, respectively. In this review, we discuss possible drug therapies for nonsense mutation and a missense mutation in p53. p63 and p73 activators may be able to replace mutant p53 and act as anti-cancer drugs. Herein, these p63 and p73 activators are summarized and how to improve these activator responses, particularly focusing on p53 gain-of-function mutants, is discussed.

NAMPT Inhibitor and P73 Activator Represses P53 R175H Mutated HNSCC Cell Proliferation in a Synergistic Manner.

The p53 family has the following three members: p53, p63 and p73. p53 is a tumor suppressor gene that frequently exhibits mutation in head and neck cancer. Most p53 mutants are loss-of-function (LoF) mutants, but some acquire some oncogenic function, such as gain of function (GoF). It is known that the aggregation of mutant p53 can induce p53 GoF. The p73 activators RETRA and NSC59984 have an anti-cancer effect in p53 mutation cells, but we found that p73 activators were not effective in all head and neck squamous cell carcinoma (HNSCC) cell lines, with different p53 mutants. A comparison of the gene expression profiles of several regulator(s) in mutant HNSCC cells with or without aggregation of p53 revealed that nicotinamide phosphoribosyltransferase (NAMPT) is a key regulator of mutant p53 aggregation. An NAMPT inhibitor, to reduce abnormal aggregation of mutant p53, used in combination with a p73 activator, was able to effectively repress growth in HNSCC cells with p53 GoF mutants. This study, therefore, suggests a potential combination therapy approach for HNSCC with a p53 GoF mutation.