Targeting phosphorylation circuits on CREB and CRTCs as the strategy to prevent acquired skin hyperpigmentation.

Background: The cAMP response element-binding protein (CREB) and CREB-regulated transcription coactivators (CRTCs) cooperate in the transcriptional activation of microphthalmia-associated transcription factor subtype M (MITF-M) that is a master regulator in the biogenesis, pigmentation and transfer of melanosomes at epidermal melanocytes. Here, we propose the targeting of phosphorylation circuits on CREB and CRTCs in the expression of MITF-M as the rationale to prevent skin hyperpigmentation by elucidating the inhibitory activity and mechanism of yakuchinone A (Yaku A) on facultative melanogenesis. Methods: We employed human epidermal melanocyte cell, mouse skin, and mouse melanoma cell, and applied Western blotting, reverse transcription-polymerase chain reaction, immunoprecipitation and confocal microscopy to conduct this study. Results: This study suggested that α-melanocyte stimulating hormone (α-MSH)-induced melanogenic programs could switch on the axis of protein kinase A-salt inducible kinases (PKA-SIKs) rather than that of PKA-AMP activated protein kinase (PKA-AMPK) during the dephosphorylation of CRTCs in the expression of MITF-M. SIK inhibitors rather than AMPK inhibitors stimulated melanin production in melanocyte cultures in the absence of extracellular melanogenic stimuli, wherein SIK inhibitors increased the dephosphorylation of CRTCs but bypassed the phosphorylation of CREB for the expression of MITF-M. Treatment with Yaku A prevented ultraviolet B (UV-B)-irradiated skin hyperpigmentation in mice and inhibited melanin production in α-MSH- or SIK inhibitor-activated melanocyte cultures. Mechanistically, Yaku A suppressed the expression of MITF-M via dually targeting the i) cAMP-dependent dissociation of PKA holoenzyme at the upstream from PKA-catalyzed phosphorylation of CREB coupled with PKA-SIKs axis-mediated dephosphorylation of CRTCs in α-MSH-induced melanogenic programs, and ii) nuclear import of CRTCs after SIK inhibitor-induced dephosphorylation of CRTCs. Conclusions: Taken together, the targeting phosphorylation circuits on CREB and CRTCs in the expression of MITF-M could be a suitable strategy to prevent pigmentary disorders in the skin.

Lanthanum Doping in Zinc Oxide for Highly Reliable Thin-Film Transistors on Flexible Substrates by Spray Pyrolysis.

Solution-processed metal-oxide thin-film transistors (TFTs) are considered as one of the most favorable devices for next-generation, large-area flexible electronics. In this paper, we demonstrate the excellent material properties of lanthanum-zinc oxide (LaZnO) thin films deposited by spray pyrolysis and their application to TFTs. The threshold voltage of the LaZnO TFTs shifts toward positive gate voltage, and the mobility decreases with increasing lanthanum ratio in ZnO from 0 to 20%. The purification of the LaZnO precursor (P-LaZnO) further improves the device performance. The P-LaZnO TFT exhibits a field-effect mobility of 22.43 cm2 V-1 s-1, zero hysteresis voltage, and negligible threshold voltage VTH shift under positive bias temperature stress. The enhancement in the electrical properties is due to a decrease in grain size, smooth surface roughness, and reduction in the trap density in the LaZnO film. X-ray photoelectron spectroscopy (XPS) results confirm the presence of La in the TFT channel and at/near the interface of the LaZnO and ZrOx gate insulator, leading to fewer interfacial traps. The flexible P-LaZnO TFT fabricated on the polyimide substrate exhibits a mobility of 17.64 cm2 V-1 s-1 and a negligible VTH shift under bias stress. Also, the inverter made of LZO TFTs is working well with a voltage gain of 17.74 (V/V) at 4 V. Therefore, the LaZnO TFT is a promising device for next-generation flexible displays.

Amorphous Tin Oxide Applied to Solution Processed Thin-Film Transistors.

The limited choice of materials for large area electronics limits the expansion of applications. Polycrystalline silicon (poly-Si) and indium gallium zinc oxide (IGZO) lead to thin-film transistors (TFTs) with high field-effect mobilities (>10 cm2/Vs) and high current ON/OFF ratios (IOn/IOff > ~107). But they both require vacuum processing that needs high investments and maintenance costs. Also, IGZO is prone to the scarcity and price of Ga and In. Other oxide semiconductors require the use of at least two cations (commonly chosen among Ga, Sn, Zn, and In) in order to obtain the amorphous phase. To solve these problems, we demonstrated an amorphous oxide material made using one earth-abundant metal: amorphous tin oxide (a-SnOx). Through XPS, AFM, optical analysis, and Hall effect, we determined that a-SnOx is a transparent n-type oxide semiconductor, where the SnO2 phase is predominant over the SnO phase. Used as the active material in TFTs having a bottom-gate, top-contact structure, a high field-effect mobility of ~100 cm2/Vs and an IOn/IOff ratio of ~108 were achieved. The stability under 1 h of negative positive gate bias stress revealed a Vth shift smaller than 1 V.