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The subcellular localization of RNAs correlates with their function and how they are regulated. Most protein-coding mRNAs are exported into the cytoplasm for protein synthesis, while some mRNA species, long noncoding RNAs, and some regulatory element-associated unstable transcripts tend to be retained in the nucleus, where they function as a regulatory unit and/or are regulated by nuclear surveillance pathways. While the mechanisms regulating mRNA export and localization have been well summarized, the mechanisms governing nuclear retention of RNAs, especially of noncoding RNAs, are seldomly reviewed. In this review, we summarize recent advances in the mechanistic study of RNA nuclear retention, especially for noncoding RNAs, from the angle of cis-acting elements embedded in RNA transcripts and their interaction with trans-acting factors. We also try to illustrate the general principles of RNA nuclear retention and we discuss potential areas for future investigation.

// Xilan Yu 1, * , Wuxiang Mao 1, * , Yansheng Zhai 1 , Chong Tong 1 , Min Liu 1 , Lixin Ma 1 , Xiaolan Yu 1 , Shanshan Li 1 1 Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, College of Life Sciences, Hubei University, Wuhan, Hubei, China * These authors have equally contributed to this work Correspondence to: Xiaolan Yu, email: yxiaolan@163.com Shanshan Li, email: shl@hubu.edu.cn Keywords: metformin, therapeutic targets, metabolism, epigenetic modifications Received: September 22, 2016 Accepted: November 03, 2016 Published: November 26, 2016 ABSTRACT Metformin has been used to treat type 2 diabetes for over 50 years. Epidemiological, preclinical and clinical studies suggest that metformin treatment reduces cancer incidence in diabetes patients. Due to its potential as an anti-cancer agent and its low cost, metformin has gained intense research interest. Its traditional anti-cancer mechanisms involve both indirect and direct insulin-dependent pathways. Here, we discussed the anti-tumor mechanism of metformin from the aspects of cell metabolism and epigenetic modifications. The effects of metformin on anti-cancer immunity and apoptosis were also described. Understanding these mechanisms will shed lights on application of metformin in clinical trials and development of anti-cancer therapy.

We propose a theoretical design principle of polarization-insensitive metal–semiconductor–metal (MSM) structure for ultraviolet photodetectors based on one-dimensional nanogratings. Because the Fabry–Perot cavity modes supported by a 100-nm-thick ZnO layer with nanostructures for transverse electric and transverse magnetic polarized incidence overlap with each other, a polarization-insensitive absorption enhancement for the ZnO layer at UV wavelengths is achieved, which can be implemented as a nano-interdigitated electrode to address a long-existing limitation between the speed and the responsivity for conventional MSM photodetectors.

Stromal keratocyte apoptosis triggered by epithelial injury is one mechanism of corneal disorders. A model of epithelial injury by epithelial debridement is established, and keratocyte apoptosis is evidenced by DNA fragmentation and cellular morphological changes in the anterior stroma underlying the injured epithelium. Delivery of plasmid (pCMV-bcl-x(L)-eGFP) encoding an anti-apoptotic gene, the bcl-x(L) with a nano-carrier, polymeric micelles (PM) via eye drop to cornea after epithelial debridement, the mRNA level of bcl-x(L) was significantly increased (2.2-fold, P0.05) at 48 h and the eGFP mRNA was detected (4571.7 ± 1194.5 copies/μg total RNA). The bcl-x(L)-eGFP fusion protein was also detected in wounded cornea at 48 h after delivery, accompanying with decreased DNA fragmentation and lower caspase-3 activity (P0.05). In conclusion, eye drop of pCMV-bcl-x(L)-eGFP/PM reduced corneal apoptosis following epithelial debridement.

This study evaluates the eye drop delivery of genes with cornea-specific promoters, i.e., keratin 12 (K12) and keratocan (Kera3.2) promoters, by non-ionic poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) polymeric micelles (PM) to mouse and rabbit eyes, and investigates the underlying mechanisms.Three PM-formulated plasmids (pCMV-Lac Z, pK12-Lac Z and pKera3.2-Lac Z) containing the Lac Z gene for beta-galactosidase (beta-Gal) whose expression was driven by the promoter of either the cytomegalovirus early gene, the keratin 12 gene or the keratocan gene, were characterized by critical micelle concentration (CMC), dynamic light scattering (DLS), and atomic force microscopy (AFM). Transgene expression in ocular tissue after gene delivery was analyzed by 5-bromo-4-chloro-3-indolyl-beta-D-galactoside (X-Gal) color staining, 1,2-dioxetane beta-Gal enzymatic activity measurement, and real-time polymerase chain reaction (PCR) analysis. The delivery mechanisms of plasmid-PM on mouse and rabbit corneas were evaluated by EDTA and RGD (arginine-glycine-aspartic acid) peptide.The sizes of the three plasmid-PM complexes were around 150-200 nm with unimodal distribution. Enhanced stability was found for three plasmid-PM formulations after DNase I treatment. After six doses of eye drop delivery of pK12-Lac Z-PM three times a day, beta-Gal activity was significantly increased in both mouse and rabbit corneas. Stroma-specific Lac Z expression was only found in pKera3.2-Lac Z-PM-treated animals with pretreatment by 5 mM EDTA, an opener of junctions. Lac Z gene expression in both pK12-Lac Z-PM and pKera3.2-Lac Z-PM delivery groups was decreased by RGD peptide pretreatment.Cornea epithelium- and stroma-specific gene expression could be achieved using cornea-specific promoters of keratin 12 and keratocan genes, and the gene was delivered with PM formulation through non-invasive, eye drop in mice and rabbits. The transfection mechanism of plasmid-PM may involve endocytosis and particle size dependent paracellular transport.

For the purpose of improving reliability and robustness of a Smart Grid, a Dynamic Lightning Protection mode was developed. While the conventional mode focuses on the protection for each grid component individually, this dynamic mode focuses on protecting the whole electric grid in its entirety. Based on real time lightning detection, the dynamic protection system carries out flexible protection actions in advance. Furthermore, the mode results in minimizing the impacts of lightning-caused trips, disturbances and interruptions, which reduces the risk of a grid-scale blackout and facilitates the self-healing during the lightning storms. The dynamic protection mode, as discussed in the paper, provides more available applications of lightning detection and interactive Smart Grid lightning protection.

For the purpose of improving the stability and robustness of Smart Grid, a dynamic lightning protection mode which based on real time lightning detection was developed. While the conventional mode focuses on the protection for each individual grid element or component (transmission line, distribution line, transformer, substation, electronic equipment, etc) separately, the dynamic mode that named Active Lightning Protection (ALP) concentrates on protecting the whole electrical grid in its entirety. According the real time lightning detection information, the ALP mode carries out dynamic measures in advance, including adjusting the grid operation mode, optimizing the gird power flow distribution, controlling the generation units, switching the Microgrid. Furthermore, it leads the load to those parts of smart grid which are not threatened by lightning, so as to reduce the risk of grid-scale blackout. The dynamic protection mode, which discussed in the paper, provides more optional applications of lightning detection in the Smart Gird.