Expression of cytochrome P450s (P450s) is regulated by epigenetic factors, such as DNA methylation, histone modifications, and noncoding RNAs through different mechanisms. Among these factors, long noncoding RNAs (lncRNAs) have been shown to play important roles in the regulation of gene expression; however, little is known about the effects of lncRNAs on the regulation of P450 expression. The aim of this study was to explore the role of lncRNAs in the regulation of P450 expression by using human liver tissues and hepatoma Huh7 cells. Through lncRNA microarray analysis and quantitative polymerase chain reaction in human liver tissues, we found that the lncRNA hepatocyte nuclear factor 1 alpha antisense 1 (HNF1a-AS1), an antisense RNA of HNF1a, is positively correlated with the mRNA expression of CYP2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 as well as pregnane X receptor (PXR) and constitutive androstane receptor (CAR). Gain-and loss-of-function studies in Huh7 cells transfected with small interfering RNAs or overexpression plasmids showed that HNF1a not only regulated the expression of HNF1a-AS1 and P450s, but also regulated the expression of CAR, PXR, and aryl hydrocarbon receptor (AhR). In turn, HNF1a-AS1 regulated the expression of PXR and most P450s without affecting the expression of HNF1a, AhR, and CAR. Moreover, the rifampicin-induced expression of P450s was also affected by HNF1a and HNF1a-AS1. In summary, the results of this study suggested that HNF1a-AS1 is involved in the HNF1a-mediated regulation of P450s in the liver at both basal and drug-induced levels.
Dielectric elastomer actuators (DEAs) are able to undergo large deformation in response to external electric stimuli and have been widely used to drive soft robotic systems, due to their advantageous attributes comparable to biological muscles. However, due to their isotropic material properties, it has been challenging to generate programmable actuation, e.g., along a predefined direction. In this paper, we provide an innovative solution to this problem by harnessing honeycomb metastructures to program the mechanical behavior of dielectric elastomers. The honeycomb metastructures not only provide mechanical prestretches for DEAs but, more importantly, transfer the areal expansion of DEAs into directional deformation, by virtue of the inherent anisotropy. To achieve uniaxial actuation and maximize its magnitude, we develop a finite element analysis model and study how the prestretch ratios and the honeycomb structuring tailor the voltage-induced deformation. We also provide an easy-to-implement and scalable fabrication solution by directly printing honeycomb lattices made of thermoplastic polyurethane on dielectric membranes with natural bonding. The preliminary experiments demonstrate that our designed DEA is able to undergo unidirectional motion, with the nominal strain reaching up to 15.8%. Our work represents an initial step to program deformation of DEAs with metastructures.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.