A Foundational Study for NormalF8-Containing Mouse Models for the miRNA Regulation of Hemophilia A: Identification and Analysis of Mouse miRNAs that Downregulate the MurineF8Gene
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Authors: Jankowska, Katarzyna, I; Chattopadhyay, Maitreyi; Sauna, Zuben E.; Atreya, Chintamani D.
Hemophilia A (HA) is associated with defects in theF8gene, encoding coagulation factor VIII (FVIII). Our previous studies show that F8-targeting micro RNAs (miRNAs), a group of small RNAs involved in gene regulation, can downregulate F8 expression causing HA in individuals with normal F8-genotypes and increased HA severity in patients with mutations inF8. Understanding the mechanistic underpinnings of human genetic diseases caused or modulated by miRNAs require a small animal model, such as a mouse model. Here, we report a foundational study to develop such a model system. We identified the mouse 3 ' untranslated region (3 ' UTR) on murineF8-mRNA (muF8-mRNA) that can bind to murine miRNAs. We then selected three miRNAs for evaluation: miR-208a, miR-351 and miR-125a. We first demonstrate that these three miRNAs directly target the 3 ' UTR of muF8-mRNA and reduce the expression of a reporter gene (luciferase) mRNA fused to the muF8-3 ' UTR in mammalian cells. Furthermore, in mouse cells that endogenously express theF8gene and produce FVIII protein, the ectopic expression of these miRNAs downregulatedF8-mRNA and FVIII protein. These results provide proof-of-concept and reagents as a foundation for using a normalF8-containing mouse as a model for the miRNA regulation of normalF8in causing or aggravating the genetic disease HA.
Inorganic perovskite light emitting diodes with ZnO as the electron transport layer by direct atomic layer deposition
Authors: Li, Wei; Xu, Yun-Xiao; Wang, Dong; Chen, Fei; Chen, Zhi-Kuan
Inorganic n-type metal oxide materials, i.e., ZnO have been developed and employed as interface layers for energy level matching and electron transport in order to achieve high performance perovskites based optoelectronic devices. In this work, we successfully apply atomic layer deposition (ALD) technique to deposit ZnO directly on top of CsPbBr3 to serve as the electron transport layer. A regular perovskite light emitting diode (PeLED) in a configuration of glass/ITO/PEDOT: PSS/CsPbBr3/ZnO/Ag was fabricated. In the CsPbBr3 emitting layer, polyethyleneimine ethoxylated (PEIE) dissolved in an anti-solvent chlorobenzene (CB) was introduced to assist the nucleation and crystal growth of perovskite films, as well as providing surface reactive sites for ALD deposition of ZnO layer particularly. The ALD deposition temperature on the growth, crystallinity and morphology of ZnO and subsequent device performance was investigated. We obtained PeLEDs of the best performance with the best current and external quantum efficiency (EQE) of 0.49 cd/A and 0.14%, respectively, which is as 14 folds high as an inorganic CsPbBr3 device using F8 as the electron transport layer reported previously.