Nobiletin attenuates neurotoxic mitochondrial calcium overload through K+ influx and ΔΨm across mitochondrial inner membrane.

Mitochondrial calcium overload is a crucial event in determining the fate of neuronal cell survival and death, implicated in pathogenesis of neurodegenerative diseases. One of the driving forces of calcium influx into mitochondria is mitochondria membrane potential (ΔΨm). Therefore, pharmacological manipulation of ΔΨm can be a promising strategy to prevent neuronal cell death against brain insults. Based on these issues, we investigated here whether nobiletin, a Citrus polymethoxylated flavone, prevents neurotoxic neuronal calcium overload and cell death via regulating basal ΔΨm against neuronal insult in primary cortical neurons and pure brain mitochondria isolated from rat cortices. Results demonstrated that nobiletin treatment significantly increased cell viability against glutamate toxicity (100 µM, 20 min) in primary cortical neurons. Real-time imaging-based fluorometry data reveal that nobiletin evokes partial mitochondrial depolarization in these neurons. Nobiletin markedly attenuated mitochondrial calcium overload and reactive oxygen species (ROS) generation in glutamate (100 µM)-stimulated cortical neurons and isolated pure mitochondria exposed to high concentration of Ca2+ (5 µM). Nobiletin-induced partial mitochondrial depolarization in intact neurons was confirmed in isolated brain mitochondria using a fluorescence microplate reader. Nobiletin effects on basal ΔΨm were completely abolished in K+-free medium on pure isolated mitochondria. Taken together, results demonstrate that K+ influx into mitochondria is critically involved in partial mitochondrial depolarization-related neuroprotective effect of nobiletin. Nobiletin-induced mitochondrial K+ influx is probably mediated, at least in part, by activation of mitochondrial K+ channels. However, further detailed studies should be conducted to determine exact molecular targets of nobiletin in mitochondria.

Deep Learning Model for Cosmetic Gel Classification Based on a Short-Time Fourier Transform and Spectrogram.

Cosmetics and topical medications, such as gels, foams, creams, and lotions, are viscoelastic substances that are applied to the skin or mucous membranes. The human perception of these materials is complex and involves multiple sensory modalities. Traditional panel-based sensory evaluations have limitations due to individual differences in sensory receptors and factors such as age, race, and gender. Therefore, this study proposes a deep-learning-based method for systematically analyzing and effectively identifying the physical properties of cosmetic gels. Time-series friction signals generated by rubbing the gels were measured. These signals were preprocessed through short-time Fourier transform (STFT) and continuous wavelet transform (CWT), respectively, and the frequency factors that change over time were distinguished and analyzed. The deep learning model employed a ResNet-based convolution neural network (CNN) structure with optimization achieved through a learning rate scheduler. The optimized STFT-based 2D CNN model outperforms the CWT-based 2D and 1D CNN models. The optimized STFT-based 2D CNN model also demonstrated robustness and reliability through k-fold cross-validation. This study suggests the potential for an innovative approach to replace traditional expert panel evaluations and objectively assess the user experience of cosmetics.

Development of Pelubiprofen Tromethamine with Improved Gastrointestinal Safety and Absorption.

Pelubiprofen (PEL), which is a commercialized non-steroidal anti-inflammatory drug (NSAID), is associated with the risk of gastrointestinal (GI) adverse events following long-term exposure and has poor water-soluble properties. Here, a new pelubiprofen tromethamine (PEL-T) with improved solubility, permeability, GI safety, and absorption, compared to PEL, has been developed. The nuclear magnetic resonance spectroscopy (NMR), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR) results confirmed that the PEL-T was well formed. The powder of PEL-T showed the presence of additional 6H protons at δ 3.66-3.61 in the 1H NMR spectrum, and shifted the sharp endothermic peaks at 129 °C in DSC, and the spectrum of distinct absorption peaks in FT-IR. In addition, compared with PEL, PEL-T showed a significantly improved solubility in various media and an increased permeability coefficient (Kp) in Caco-2 cells. Furthermore, compared to PEL oral administration, PEL-T was found to significantly reduce the damaged area in an acute gastric damage rat model. The pharmacokinetic study of the PEL-T powder showed higher maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from 0 h to the last time point (AUCt) than those of the PEL powder. Taken together, our data suggest that PEL-T is a recommendable candidate with enhanced gastrointestinal safety and better absorption compared with commercial PEL.

Improvement of light output power of InGaN/GaN light-emitting diode by lateral epitaxial overgrowth using pyramidal-shaped SiO(2).

We report on the improvement of light output power of InGaN/GaN blue light-emitting diodes (LEDs) by lateral epitaxial overgrowth (LEO) of GaN using a pyramidal-shaped SiO(2) mask. The light output power was increased by 80% at 20 mA of injection current compared with that of conventional LEDs without LEO structures. This improvement is attributed to an increased internal quantum efficiency by a significant reduction in threading dislocation and by an enhancement of light extraction efficiency by pyramidal-shaped SiO(2) LEO mask.

Surface plasmon-enhanced light-emitting diodes using silver nanoparticles embedded in p-GaN.

We demonstrate the surface plasmon-enhanced blue light-emitting diodes (LEDs) using Ag nanoparticles embedded in p-GaN. A large increase in optical output power of 38% is achieved at an injection current of 20 mA due to an improved internal quantum efficiency of the LEDs. The enhancement of optical output power is dependent on the density of the Ag nanoparticles. This improvement can be attributed to an increase in the spontaneous emission rate through resonance coupling between the excitons in multiple quantum wells and localized surface plasmons in Ag nanoparticles embedded in p-GaN.