Insight into the mechanism of DNA methylation and miRNA-mRNA regulatory network in ischemic stroke.

BACKGROUND: Epigenetic changes, such as DNA methylation and miRNA-target gene mechanisms, have recently emerged as key provokers in Ischemic stroke (IS) onset. However, cellular and molecular events harboring these epigenetic alterations are poorly understood. Therefore, the present study aimed to explore the potential biomarkers and therapeutic targets for IS. METHODS: miRNAs, mRNAs and DNA methylation datasets of IS were derived from the GEO database and normalized by PCA sample analysis. Differentially expressed genes (DEGs) were identified, and GO and KEGG enrichment analyses were performed. The overlapped genes were utilized to construct a protein-protein interaction network (PPI). Meanwhile, differentially expressed mRNAs and miRNAs interaction pairs were obtained from the miRDB, TargetScan, miRanda, miRMap and miTarBase databases. We constructed differential miRNA-target gene regulatory networks based on mRNA-miRNA interactions. RESULTS: A total of 27 up-regulated and 15 down-regulated differential miRNAs were identified. Dataset analysis identified 1053 and 132 up-regulated and 1294 and 9068 down-regulated differentially expressed genes in the GSE16561 and GSE140275 datasets, respectively. Moreover, 9301 hypermethylated and 3356 hypomethylated differentially methylated sites were also identified. Moreover, DEGs were enriched in terms related to translation, peptide biosynthesis, gene expression, autophagy, Th1 and Th2 cell differentiation, primary immunodeficiency, oxidative phosphorylation and T cell receptor signaling pathway. MRPS9, MRPL22, MRPL32 and RPS15 were identified as hub genes. Finally, a differential miRNA-target gene regulatory network was constructed. CONCLUSIONS: RPS15, along with hsa-miR-363-3p and hsa-miR-320e have been identified in the differential DNA methylation protein interaction network and miRNA-target gene regulatory network, respectively. These findings strongly posit the differentially expressed miRNAs as potential biomarkers to improve ischemic stroke diagnosis and prognosis.

Carrier Transport Regulation of Pixel Graphene Transparent Electrodes for Active-Matrix Organic Light-Emitting Diode Display.

Integrating a graphene transparent electrode (TE) matrix with driving circuits is essential for the practical use of graphene in optoelectronics such as active-matrix organic light-emitting diode (OLED) display, however it is disabled by the transport of carriers between graphene pixels after deposition of a semiconductor functional layer caused by the atomic thickness of graphene. Here, the carrier transport regulation of a graphene TE matrix by using an insulating polyethyleneimine (PEIE) layer is reported. The PEIE forms an ultrathin uniform film (≤10 nm) to fill the gap of the graphene matrix, blocking horizontal electron transport between graphene pixels. Meanwhile, it can reduce the work function of graphene, improving the vertical electron injection through electron tunneling. This enables the fabrication of inverted OLED pixels with record high current and power efficiencies of 90.7 cd A-1 and 89.1 lm W-1 , respectively. By integrating these inverted OLED pixels with a carbon nanotube-based thin-film transistor (CNT-TFT)-driven circuit, an inch-size flexible active-matrix OLED display is demonstrated, in which all OLED pixels are independently controlled by CNT-TFTs. This research paves a way for the application of graphene-like atomically thin TE pixels in flexible optoelectronics such as displays, smart wearables, and free-form surface lighting.

A Flexible Carbon Nanotube Sen-Memory Device.

In a modern electronics system, charge-coupled devices and data storage devices are the two most indispensable components. Although there has been rapid and independent progress in their development during the last three decades, a cofunctionality of both sensing and memory at single-unit level is yet premature for flexible electronics. For wearable electronics that work in ultralow power conditions and involve strains, conventional sensing-and-memory systems suffer from low sensitivity and are not able to directly transform sensed information into sufficient memory. Here, a new transformative device is demonstrated, which is called "sen-memory", that exhibits the dual functionality of sensing and memory in a monolithic integrated circuit. The active channel of the device is formed by a carbon nanotube thin film and the floating gate is formed by a controllably oxidized aluminum nanoparticle array for electrical- and optical-programming. The device exhibits a high on-off current ratio of ≈106 , a long-term retention of ≈108 s, and durable flexibility at a bending strain of 0.4%. It is shown that the device senses a photogenerated pattern in seconds at zero bias and memorizes an image for a couple of years.

Network and Pathway-Based Integrated Analysis Identified a Novel "rs28457673-miR-15/16/195/424/497 Family-IGF1R-MAPK Signaling Pathway" Axis Associated With Post-stroke Depression.

Single-nucleotide polymorphisms (SNPs) of microRNA (miRNA) (miRSNP) are SNPs located on miRNA genes or miRNA target sites, which have been supposed to be involved in the development of central nervous system diseases by interfering with miRNA-mediated regulatory functions. However, the association of miRSNP with post-stroke depression (PSD) has not been well-investigated. In this study, we collected 54 PSD risk genes via manual literature-mining and integrated PSD-related risk pathways based on multiple public databases. Furthermore, we systematically screened candidate functional miRSNPs for PSD and integrated a miRSNP-based PSD-associated pathway network, which included 99 miRNAs that target 12 PSD risk pathways. We also reviewed the association between three risk pathways and PSD pathogenetic mechanism thoroughly. Combining literature mining and network analysis, our results proposed an underlying mechanism of "miRSNP → miRNA → risk gene → pathway" axis effects on PSD pathogenesis, especially for rs28457673 (miR-15/16/195/424/497 family) → IGF1R → hsa04010 (MAPK signaling pathway). Our studies revealed a functional role in genetic modifier at the system level in the pathogenesis of PSD, which might provide further information for the miRSNP studies in PSD.

Di (2-ethylhexyl) phthalate Disorders Lipid Metabolism via TYK2/STAT1 and Autophagy in Rats.

OBJECTIVE: Previous studies have indicated that the plasticizer di (2-ethylhexyl) phthalate (DEHP) affects lipid accumulation; however, its underlying mechanism remains unclear. We aim to clarify the effect of DEHP on lipid metabolism and the role of TYK2/STAT1 and autophagy. METHODS: In total, 160 Wistar rats were exposed to DEHP [0, 5, 50, 500 mg/(kg•d)] for 8 weeks. Lipid levels, as well as mRNA and protein levels of TYK2, STAT1, PPARγ, AOX, FAS, LPL, and LC3 were detected. RESULTS: The results indicate that DEHP exposure may lead to increased weight gain and altered serum lipids. We observed that DEHP exposure affected liver parenchyma and increased the volume or number of fat cells. In adipose tissue, decreased TYK2 and STAT1 promoted the expression of PPARγ and FAS. The mRNA and protein expression of LC3 in 50 and 500 mg/(kg•d) groups was increased significantly. In the liver, TYK2 and STAT1 increased compensatorily; however, the expression of FAS and AOX increased, while LPL expression decreased. Joint exposure to both a high-fat diet and DEHP led to complete disorder of lipid metabolism. CONCLUSION: It is suggested that DEHP induces lipid metabolism disorder by regulating TYK2/STAT1. Autophagy may play a potential role in this process as well. High-fat diet, in combination with DEHP exposure, may jointly have an effect on lipid metabolism disorder.

Flexible 64 × 64 Pixel AMOLED Displays Driven by Uniform Carbon Nanotube Thin-Film Transistors.

Carbon nanotube (CNT) thin-film transistors are expected to be promising for use in flexible electronics including flexible and transparent integrated circuits and in wearable chemical and physical sensors and for driving the circuits of flexible display panels. However, current devices based on CNT channels suffer from poor performance uniformity and low manufacturing yield; therefore, they are still far from being practical. This is usually caused by nonuniform deposition of the semiconducting CNTs and the rough surface of flexible substrates. Here, we report CNT thin-film transistors (TFTs) driving a flexible 64 × 64 pixel active matrix light-emitting diode display (AMOLED) by improving the formation of uniform CNT films and developing a new pretreatment technique for flexible substrates. The achieved AMOLED has uniform brightness and a high yield of 99.93% in its 4096 pixels. More than 8000 TFTs with high-purity semiconducting CNTs as the channel material show an average on-off current ratio of ∼107 and a carrier mobility of 16 cm2 V-1 s-1. The standard deviations of the on-state current and the carrier mobility are 4.1 and 6.5%, respectively. Our result shows that the panel driven by high-purity semiconducting CNTs is a promising strategy for the development of next-generation flexible, large-area displays.