Search

Melanosomes are specialized membrane-bound organelles where melanin is synthesized and stored. The levels of melanin can be effectively reduced by inhibiting melanin synthesis or promoting melanosome degradation via autophagy. Ceramide, a key component in the metabolism of sphingolipids, is crucial for preserving the skin barrier, keeping it hydrated, and warding off the signs of aging. Our preliminary study indicated that a long-chain C22-ceramide compound (Ehux-C22) isolated from the marine microalga Emiliania huxleyi, reduced melanin levels via melanosomal autophagy in B16 cells. Recently, microRNAs (miRNAs) were shown to act as melanogenesis-regulating molecules in melanocytes. However, whether the ceramide Ehux-C22 can induce melanosome autophagy at the post-transcriptional level, and which potential autophagy-dependent mechanisms are involved, remains unknown. Here, miR-199a-3p was screened and identified as a novel upregulated miRNA in Ehux-C22-treated B16 cells. An in vitro high melanin expression model in cultured mouse melanoma cells (B16 cells) was established by using 0.2 μM alpha-melanocyte-stimulating hormone(α-MSH) and used for subsequent analyses. miR-199a-3p overexpression significantly enhanced melanin degradation, as indicated by a reduction in the melanin level and an increase in melanosome autophagy. Further investigation demonstrated that in B16 cells, Ehux-C22 activated miR-199a-3p and inhibited mammalian target of rapamycin(mTOR) level, thus activating the mTOR-ULK1 signaling pathway by promoting the expression of unc-51-like autophagy activating kinase 1 (ULK1), B-cell lymphoma-2 (Bcl-2), Beclin-1, autophagy-related gene 5 (ATG5), and microtubule-associated protein light chain 3 (LC3-II) and degrading p62. Therefore, the roles of Ehux-C22-regulated miR-199a-3p and the mTOR pathway in melanosomal autophagy were elucidated. This research may provide novel perspectives on the post-translational regulation of melanin metabolism, which involves the coordinated control of melanosomes. [ABSTRACT FROM AUTHOR]

Diamond Schottky barrier diodes (SBDs) could theoretically operate at high voltage, high temperature, and high frequency and be potentially used in power electronics. However, the device breaks down prematurely and cannot operate stably at high voltages due to the edge electric field crowding. In this work, a vertical diamond SBD with a curved field plate (CFP) was prepared using a chemical reflow method, inductively coupled plasma etching, and electron-beam evaporation. This structure alleviates the electric field crowding at the edge of the Schottky electrode and results in a breakdown voltage and current density of 380 V and over 3000 A/cm2, respectively. After repetitive measurements, we found that the device can repeatedly breakdown at around 380 V. These results indicate that CFP structure diamond SBDs have great application in high-voltage and high-power electronic devices. [ABSTRACT FROM AUTHOR]

Normally Off diamond field-effect transistor (FET) is demanded for energy saving and safety for practical application. Metal/diamond Schottky junction serving as the gate is a simple and effective approach to deplete holes under the gate, whereas low Schottky barrier height (SBH) is undesirable. In this work, a dual-barrier Schottky gate hydrogen,oxygen-terminated diamond (H,O-diamond) FET (DBG-FET) with Al gate was realized. Normally Off DBG-FET with enhanced SBH and reduced leakage was achieved. H,O-diamond, which was defined by x-ray photoelectron spectroscopy (XPS) technique, was realized by ultraviolet ozone (UV/O3) treatment with nanoparticle-Al mask. The enlarged SBH of 0.94 eV owing to the C–O bond minimized the diode reverse current and nicely shut down the DBG-FET at zero gate bias. Moreover, the forward current of diode can be well-reduced by hundred times ascribed to oxidized Al nanoparticles during the UV/O3 process. Based on this diode gate structure, the maximum drain current density, transconductance, on/off ratio, and subthreshold swing of the normally off DBG-FET are 21.8 mA/mm, 9.1 mS/mm, 109, and 96 mV/dec, respectively. The DBG-FET is expected to promote the development of normally off diamond FETs. [ABSTRACT FROM AUTHOR]

The development of novel drug candidates for treating microbial infections and cancer turns into a challenging task. The biopolymer-based nanomaterials have gained popularity for their effective roles in the pharmaceutical sector. The present investigation aims to valorize crab shell wastes to extract chitosan. The obtained (chitosan) biomass was utilized to synthesize chitosan-zinc oxide nanoparticles (Ch-ZnO-NPs). The nanomaterial characterization was achieved by a variety of physicochemical techniques including UV, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), elemental analysis, and High-resolution transmission electron microscopic (HR-TEM) examination. The synthesized nanomaterials have a particle size range of 35-80 nm and are more stable with a zeta potential value of (-40.78) mv. Additionally, the designed nanomaterials were utilized to evaluate the biological efficiency. The minimal inhibitory concentration value of Ch-ZnO-NPs was observed as 10 &#181g/mL. The designed nanomaterials significantly reduced the growth of Vibrio alginolyticus and Bacillus cereus and inhibited biofilm formation. The synthesized Ch-ZnO-NPs unveiled cytotoxic effects on A549 cells with an IC50 (half-maximal inhibitory concentration) of 20 µg/mL. Furthermore, substantial increase in cell death was noticed in A549 cells treated with Ch-ZnO-NPs. Consequently, this investigation concludes that Ch-ZnO-NPs may act as a biomedicine. [ABSTRACT FROM AUTHOR]

Introduction: There is a high morbidity and mortality rate in mechanical trauma (MT)-induced hepatic injury. Currently, the molecular mechanisms underlying liver MT are largely unclear. Exploring the underlying mechanisms and developing safe and effective medicines to alleviate MT-induced hepatic injury is an urgent requirement. The aim of this study was to reveal the role of mitochondria-associated ER membranes (MAMs) in post-traumatic liver injury, and ascertain whether melatonin protects against MT-induced hepatic injury by regulating MAMs. Methods: Hepatic mechanical injury was established in Sprague–Dawley rats and primary hepatocytes. A variety of experimental methods were employed to assess the effects of melatonin on hepatic injury, apoptosis, MAMs formation, mitochondrial function and signaling pathways. Results: Significant increase of IP3R1 expression and MAMs formation were observed in MT-induced hepatic injury. Melatonin treatment at the dose of 30 mg/kg inhibited IP3R1-mediated MAMs and attenuated MT-induced liver injury in vivo. In vitro, primary hepatocytes cultured in 20% trauma serum (TS) for 12 h showed upregulated IP3R1 expression, increased MAMs formation and cell injury, which were suppressed by melatonin (100 μmol/L) treatment. Consequently, melatonin suppressed mitochondrial calcium overload, increased mitochondrial membrane potential and improved mitochondrial function under traumatic condition. Melatonin's inhibitory effects on MAMs formation and mitochondrial calcium overload were blunted when IP3R1 was overexpressed. Mechanistically, melatonin bound to its receptor (MR) and increased the expression of phosphorylated ERK1/2, which interacted with FoxO1 and inhibited the activation of FoxO1 that bound to the IP3R1 promoter to inhibit MAMs formation. Conclusion: Melatonin prevents the formation of MAMs via the MR-ERK1/2-FoxO1-IP3R1 pathway, thereby alleviating the development of MT-induced liver injury. Melatonin-modulated MAMs may be a promising therapeutic therapy for traumatic hepatic injury. [ABSTRACT FROM AUTHOR]