ABSTRACT
Two-dimensional (2D) boron-doped graphene (B-G) exhibits remarkable properties for advanced applications in electronics, sensing and catalysis. However, the synthesis of large-area uniformly ordered 2D B-G remains a grand challenge due to the low doping level and uncontrolled distribution of dopants or even the phase separation from the competitive growth of boron polymorphs and graphene. Here, we theoretically explored the mechanism of the epitaxial growth of 2D uniformly ordered B-G on a metal substrate via ab initio calculations. We show that, by establishing the substrate-mediated thermodynamic phase diagrams, the controllable growth of 2D ordered B-G with different B/C stoichiometry can be achieved on appropriate substrates within distinct chemical potential windows of the feedstock by beating the competitive growth of graphene and other impurity phases. It is suggested that a suitable substrate for the controllable epitaxial growth of 2D ordered B-G can be efficiently screened based on the symmetry match and interaction between 2D B-G and the surfaces. Importantly, by carefully considering the chemical potential of boron/carbon as a function of temperature and partial pressure of the feedstock with the aid of the standard thermochemical tables, the optimal experimental parameters for the controllable growth of 2D ordered B-G are also suggested accordingly. This work provides a comprehensive and insightful understanding of the mechanism of controllable growth of 2D B-G, which will guide future experimental design.
ABSTRACT
Diabetes mellitus is characterized by pancreatic ß cell dysfunction. Previous studies have indicated that epidermal growth factor (EGF) and microRNA-124a (miR-124a) play opposite roles in insulin biosynthesis and secretion by beta cells. However, the underlying mechanisms remain poorly understood. In the present study, we demonstrated that EGF could inhibit miR-124a expression in beta cell lines through downstream signaling pathways, including mitogen-activated protein kinase kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) cascades. Further, the transcription factor ETS2, a member of the ETS (E26 transformation-specific) family, was identified to be responsible for the EGF-mediated suppression of miR-124a expression, which was dependent on ETS2 phosphorylation at threonine 72. Activation of ETS2 decreased miR-124a promoter transcriptional activity through the putative conserved binding sites AGGAANA/TN in three miR-124a promoters located in different chromosomes. Of note, ETS2 played a positive role in regulating beta cell function-related genes, including miR-124a targets, Forkhead box a2 (FOXA2) and Neurogenic differentiation 1 (NEUROD1), which may have partly been through the inhibition of miR-124 expression. Knockdown and overexpression of ETS2 led to the prevention and promotion of insulin biosynthesis respectively, while barely affecting the secretion ability. These results suggest that EGF may induce the activation of ETS2 to inhibit miR-124a expression to maintain proper beta cell functions and that ETS2, as a novel regulator of insulin production, is a potential therapeutic target for diabetes mellitus treatment.
