AGO-accessible anticancer siRNAs designed with synergistic miRNA-like activity.

Small interfering RNAs (siRNAs) therapeutically induce RNA interference (RNAi) of disease-causing genes, but they also silence hundreds of seed-matched off-targets as behaving similar to microRNAs (miRNAs). miRNAs control the pathophysiology of tumors, wherein their accessible binding sites can be sequenced by Argonaute crosslinking immunoprecipitation (AGO CLIP). Herein, based on AGO CLIP, we develop potent anticancer siRNAs utilizing miRNA-like activity (mi/siRNAs). The mi/siRNAs contain seed sequences (positions 2-7) of tumor-suppressive miRNAs while maintaining perfect sequence complementarity to the AGO-accessible tumor target sites. Initially, host miRNA interactions with human papillomavirus 18 (HPV18) were identified in cervical cancer by AGO CLIP, revealing tumor-suppressive activity of miR-1/206 and miR-218. Based on the AGO-miRNA binding sites, mi/siRNAs were designed to target E6 and E7 (E6/E7) transcript with seed sequences of miR-1/206 (206/E7) and miR-218 (218/E7). Synergistic anticancer activity of 206/E7 and 218/E7 was functionally validated and confirmed via RNA sequencing and in vivo xenograft models (206/E7). Other mi/siRNA sequences were additionally designed for cervical, ovarian, and breast cancer, and available as an online tool (http://ago.korea.ac.kr/misiRNA); some of the mi/siRNAs were validated for their augmented anticancer activity (206/EphA2 and 206/Her2). mi/siRNAs could coordinate miRNA-like activity with robust siRNA function, demonstrating the potential of AGO CLIP analysis for RNAi therapeutics.

A strain induced subwavelength-structure for a haze-free and highly transparent flexible plastic substrate.

This paper presents a method to produce subwavelength-scale (<250 nm) AgCl nanostructures on a flexible plastic film, which is indispensable for highly efficient flexible displays. Using Cl2 plasma treatment on an Ag-coated plastic film, AgCl nanostructures were produced through the reaction of Ag atoms with Cl radicals. During the reaction, the volume of AgCl expands, leading to drastically changed surface morphology from a two-dimensional (2D) flat Ag surface to a 3D subwavelength-scale AgCl nanostructure. The optical properties of AgCl on the plastic film were remarkably enhanced from 89.6% to 93.4% and the average transmittance ranged between 400 and 800 nm, while the average haze was retained below 0.3%. Consequently, OLEDs based on the subwavelength-scale AgCl nanostructure had an enhanced luminance efficiency (88.6 cd A-1 at 1000 cd m-2) of up to 10.7% without modifying the angular emission pattern, superior to that of the as-received PI film (efficiency of 80.0 cd A-1). The nanostructure enhances the transmission of electromagnetic (EM) waves as well as prohibits the scattering of EM waves, which was confirmed by finite-difference time-domain simulation and rigorous coupled wave analysis.

Extremely flat metal films implemented by surface roughness transfer for flexible electronics.

We present an innovative approach to fabricate an extremely flat (EF) metal film which was done by depositing metal on an extremely flat mother substrate, then detaching the metal from the substrate. The detached flexible metal films had a roughness that was within 2% of the roughness of the mother substrate, so EFs with R a < 1 nm could be fabricated using the surface roughness transfer method. With quantitative analysis using in situ synchrotron XPS, it was concluded that the chemical reaction of oxygen atoms with the metal film played a critical role in designing a peel-off system to get extremely flat metal films from the mother substrate. The OLED was successfully implemented on the metal film. The OLED's luminance could be increased from 15 142 to 17 100 cd m-2 at 25 mA m-2 by replacing the glass substrate with an EF copper (Cu) substrate, due to the enhanced heat dissipation during the operation. This novel method can be very useful for mass production of large scale, low-cost and high quality metal films using roll-to-roll process.

Simple and scalable growth of AgCl nanorods by plasma-assisted strain relaxation on flexible polymer substrates.

Implementing nanostructures on plastic film is indispensable for highly efficient flexible optoelectronic devices. However, due to the thermal and chemical fragility of plastic, nanostructuring approaches are limited to indirect transfer with low throughput. Here, we fabricate single-crystal AgCl nanorods by using a Cl2 plasma on Ag-coated polyimide. Cl radicals react with Ag to form AgCl nanorods. The AgCl is subjected to compressive strain at its interface with the Ag film because of the larger lattice constant of AgCl compared to Ag. To minimize strain energy, the AgCl nanorods grow in the [200] direction. The epitaxial relationship between AgCl (200) and Ag (111) induces a strain, which leads to a strain gradient at the periphery of AgCl nanorods. The gradient causes a strain-induced diffusion of Ag atoms to accelerate the nanorod growth. Nanorods grown for 45 s exhibit superior haze up to 100% and luminance of optical device increased by up to 33%.

MicroRNA Target Recognition: Insights from Transcriptome-Wide Non-Canonical Interactions.

MicroRNAs (miRNAs) are small non-coding RNAs (∼22 nucleotides) regulating gene expression at the post-transcriptional level. By directing the RNA-induced silencing complex (RISC) to bind specific target mRNAs, miRNA can repress target genes and affect various biological phenotypes. Functional miRNA target recognition is known to majorly attribute specificity to consecutive pairing with seed region (position 2-8) of miRNA. Recent advances in a transcriptome-wide method of mapping miRNA binding sites (Ago HITS-CLIP) elucidated that a large portion of miRNA-target interactions in vivo are mediated not only through the canonical "seed sites" but also via non-canonical sites (∼15-80%), setting the stage to expand and determine their properties. Here we focus on recent findings from transcriptome-wide non-canonical miRNA-target interactions, specifically regarding "nucleation bulges" and "seed-like motifs". We also discuss insights from Ago HITS-CLIP data alongside structural and biochemical studies, which highlight putative mechanisms of miRNA target recognition, and the biological significance of these non-canonical sites mediating marginal repression.

Wavelength-Scale Structures as Extremely High Haze Films for Efficient Polymer Solar Cells.

Wavelength-scale inverted pyramid structures with low reflectance and excellent haze have been designed for application to polymer solar cells (PSCs). The wavelength-scale structured haze films are fabricated on the back surface of glass without damages to organic active layer by using a soft lithographic technique with etched GaN molds. With a rigorous coupled-wave analysis of optical modeling, we find the shift of resonance peaks with the increase of pattern's diameter. Wavelength-scale structures could provide the number of resonances at the long wavelength spectrum (λ = 650-800 nm), yielding enhancement of power conversion efficiency (PCE) in the PSCs. Compared with a flat device (PCE = 7.12%, Jsc = 15.6 mA/cm(2)), improved PCE of 8.41% is achieved in a haze film, which is mainly due to the increased short circuit current density (Jsc) of 17.5 mA/cm(2). Hence, it opens up exciting opportunities for a variety of PSCs with wavelength-scale structures to further improve performance, simplify complicated process, and reduce costs.

Abasic pivot substitution harnesses target specificity of RNA interference.

Gene silencing via RNA interference inadvertently represses hundreds of off-target transcripts. Because small interfering RNAs (siRNAs) can function as microRNAs, avoiding miRNA-like off-target repression is a major challenge. Functional miRNA-target interactions are known to pre-require transitional nucleation, base pairs from position 2 to the pivot (position 6). Here, by substituting nucleotide in pivot with abasic spacers, which prevent base pairing and alleviate steric hindrance, we eliminate miRNA-like off-target repression while preserving on-target activity at ∼ 80-100%. Specifically, miR-124 containing dSpacer pivot substitution (6pi) loses seed-mediated transcriptome-wide target interactions, repression activity and biological function, whereas other conventional modifications are ineffective. Application of 6pi allows PCSK9 siRNA to efficiently lower plasma cholesterol concentration in vivo, and abolish potentially deleterious off-target phenotypes. The smallest spacer, C3, also shows the same improvement in target specificity. Abasic pivot substitution serves as a general means to harness the specificity of siRNA experiments and therapeutic applications.

Continuous 1D-Metallic Microfibers Web for Flexible Organic Solar Cells.

We report the use of a continuous 1D-metallic microfibers web (MFW) as transparent electrode for organic solar cells (OSCs). The MFW electrode can be produced with a process that involves simple electrospinning and wet etching of metal thin film. Au MFW exhibits a maximum optical transmittance of 90.8% (at 15 Ω/sq of the sheet resistance) and excellent mechanical flexibility. The MFW structure has an average width in the range from 4 to 6 µm and a junction-free structure, resulting in very smooth surface roughness. The OSCs with Au MFW electrode exhibited a higher power conversion efficiency (PCE) of 3.50% than the device with an indium tin oxide electrode (PCE = 3.20%). The optical modeling calculation showed that the Au MFW electrode induced light scattering and improved the light absorption in the active layer, resulting in an improved PCE in the OSCs.

A Challenge Beyond Bottom Cells: Top-Illuminated Flexible Organic Solar Cells with Nanostructured Dielectric/Metal/Polymer (DMP) Films.

Top-illuminated flexible organic solar cells with a high power conversion efficiency (≈6.75%) are fabricated using a dielectric/metal/polymer (DMP) electrode. Employing a polymer layer (n = 1.49) makes it possible to show the high transmittance, which is insensitive to film thickness, and the excellent haze induced by well-ordered nanopatterns on the DMP electrode, leading to a 28% of enhancement in efficiency compared to bottom cells.

Eco-friendly graphene synthesis on Cu foil electroplated by reusing Cu etchants.

Graphene film grown by chemical vapor deposition using Cu substrate is promising for industrial applications. After etching the Cu substrate, which is essential step in graphene transfer process, the etchant solution must be chemically treated to prevent water pollution. Here we investigated that a method of reusing Cu etchant used to synthesize graphene, the synthesis of graphene on the resulting reused Cu films (R-G), and the application of R-G to organic light-emitting diodes (OLEDs) and organic photovoltaic cells (OPVs). The turn-on voltage of OLEDs based on the R-G electrode was 4.2 V, and the efficiencies of OPVs based on the R-G electrode were 5.9-5.95%, that are similar to or better than those of the indium-tin-oxide-based devices. These results suggest that the reusing of Cu foil by the electroplating method could reduce the cost of graphene synthesis, thus opening a wide range of applications in graphene electronics.

miRTCat: a comprehensive map of human and mouse microRNA target sites including non-canonical nucleation bulges.

SUMMARY: MicroRNAs (miRNAs) regulate various biological functions by binding hundreds of transcripts to impart post-transcriptional repression. Recently, by applying a transcriptome-wide experimental method for identifying miRNA target sites (Ago HITS-CLIP), a novel non-canonical target site, named 'nucleation bulge', was discovered as widespread, functional and evolutionally conserved. Although such non-canonical nucleation bulges have been proven to be predictive by using 'pivot pairing rule' and sequence conservation, this approach has not been applied yet. To facilitate the functional studies of non-canonical miRNA targets, we implement miRTCat: a comprehensive searchable map of miRNA target sites, including non-canonical nucleation bulges, not only mapped in experimentally verified miRNA-bound regions but also predicted in all 3'-untranslated regions (3'-UTRs) derived from human and mouse (∼15.6% as expected false-positive results). AVAILABILITY: http://ion.skku.edu/mirtcat. CONTACT: swchi@skku.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Nano-branched transparent conducting oxides: beyond the brittleness limit for flexible electrode applications.

Although the performance of transparent conducting oxides based on bixbyite In(2)O(3) (Sn doped In(2)O(3): ITO) and wurtzite ZnO (Al, In, and Ga doped ZnO) is sufficient in conventional optoelectronic devices, their flexibility remains insufficient for demands in mobile and foldable electronics generation. A lot of alternative materials such as metallic nanowires and carbon based nano-structures have been tried for transparent flexible electrodes, but poor thermal stability of metal nanowires and limits in conductivity of carbon based nano-structures are still waiting for permanent solutions. Here, we show that the cross-linked ITO nano-branches have superior mechanical flexibility compared to ITO bulk film without any cracks even with a bending radius of 0.1 cm. Moreover, for equivalent sheet resistivity, the ITO nano-branches exhibit optical transmittance comparable to that of commercial metallic nanowires (such as Ag and Cu in the visible spectrum) but show far superior thermal stability in conductivity without any degradation even at a temperature of 200 °C and a humidity of 90%.