Quercetin Induces Mitochondrial Apoptosis and Downregulates Ganglioside GD3 Expression in Melanoma Cells.

Malignant melanoma represents a form of skin cancer characterized by a bleak prognosis and heightened resistance to traditional therapies. Quercetin has demonstrated notable anti-carcinogenic, anti-inflammatory, anti-oxidant, and pharmacological effects across various cancer types. However, the intricate relationship between quercetin's anti-cancer properties and ganglioside expression in melanoma remains incompletely understood. In this study, quercetin manifests specific anti-proliferative, anti-migratory, and cell-cycle arrest effects, inducing mitochondrial dysfunction and apoptosis in two melanoma cancer cell lines. This positions quercetin as a promising candidate for treating malignant melanoma. Moreover, our investigation indicates that quercetin significantly reduces the expression levels of ganglioside GD3 and its synthetic enzyme. Notably, this reduction is achieved through the inhibition of the FAK/paxillin/Akt signaling pathway, which plays a crucial role in cancer development. Taken together, our findings suggest that quercetin may be a potent anti-cancer drug candidate for the treatment of malignant melanoma.

Population pharmacokinetic, pharmacodynamic and efficacy modeling of SB12 (proposed eculizumab biosimilar) and reference eculizumab.

PURPOSE: To describe, compare similarity of pharmacokinetic (PK), pharmacodynamic (PD) and efficacy of SB12 and reference eculizumab (ECU) and find clinically significant covariate relationships. METHODS: The PK, PD (terminal complement activity) and efficacy (LDH) data of SB12 and ECU were obtained from 289 subjects from phase I and phase III studies. One- and two-compartment PK models with first-order elimination were evaluated for SB12 and ECU. For PD and efficacy, both direct and indirect models were tested. The impact of covariates on PK, PD and efficacy parameters was assessed. Relationship between PK/PD and PD/efficacy was characterized. This modeling was performed using NONMEM version 7.4 (Icon Development Solutions, Ellicott City, MD, USA). RESULTS: The two-compartment model adequately described the PK of SB12 and ECU, and the subject's weight was chosen as a clinically significant covariate affecting drugs' clearance and central volume of distribution. Treatment group was not a significant covariate affecting clearance. The direct response model using inhibitory sigmoid Emax and sigmoid Emax relationship well described the PK/PD relationship and PD/efficacy relationship of SB12 and ECU, respectively. Through this modeling, the relationships between PK, PD and efficacy were characterized. There were no differences in PK, PD and efficacy parameters between SB12 and ECU in pooled populations of healthy subjects and paroxysmal nocturnal haemoglobinuria (PNH) patients. CONCLUSION: The population modeling showed PK, PD and efficacy similarities between SB12 and ECU in pooled population of healthy subjects and PNH patients, supporting the totality of evidence on biosimilarity for SB12.

The influence of age and orthodontic debonding on the prevalence and severity of enamel craze lines.

BACKGROUND: Craze lines may cause esthetic concerns, especially when noted on the incisors. Various light sources with additional recording apparatus have been proposed to visualize craze lines, but a standardized clinical protocol is yet to be determined. This study aimed to validate the application of near-infrared imaging (NIRI) from intraoral scans to evaluate craze lines and to determine the influence of age and orthodontic debonding on their prevalence and severity. METHODS: The NIRI of maxillary central incisors from a full-mouth intraoral scan and photographs from an orthodontic clinic (N = 284) were collected. The prevalence of craze lines and influence of age and orthodontic debonding history on severity were evaluated. RESULTS: Craze lines were detected reliably as white lines distinguishable from dark enamel using the NIRI from intraoral scans. The craze line prevalence was 50.7%, which was significantly higher in patients 20 years or older than in patients younger than 20 years (P < .001), with more frequent severe craze lines for those 40 years or older than in patients younger than 30 years (P < .05). Prevalence or severity was similar between patients with and without an orthodontic debonding history regardless of the type of appliance. CONCLUSION: The prevalence of craze lines in the maxillary central incisor was 50.7%, with a higher prevalence in adults than in adolescents. Orthodontic debonding did not affect the severity of craze lines. PRACTICAL IMPLICATIONS: Craze lines were reliably detected and documented by means of applying NIRI from intraoral scans. Intraoral scanning can provide new clinical information on enamel surface characteristics.

Turn-On Fluorescent pH Probes for Monitoring Alkaline pHs Using Bis[2-(2'-hydroxyphenyl)benzazole] Derivatives.

For surveilling human health, industries, and the environment, pH monitoring is important. Numerous studies on fluorescent probes have been conducted to monitor various pH ranges. However, fluorescent probes that are capable of sensing alkaline regions are rare. In this study, we propose turn-on-type fluorescent probes for detecting alkaline pHs using bis[2-(2'-hydroxyphenyl)benzazole] (bis(HBX)) derivatives. These probes have high pKa values (from 9.7 to 10.8) and exhibit strong fluorescence intensity and color changes at alkaline pHs. Probes derived from bis(HBX) exhibit good photostability, reversibility, and anti-interference toward pH variations, which can be identified as a certain fluorescence change toward a basic pH. Therefore, compounds would be advantageous to use fluorescent probes for monitoring alkaline pH changes.

High-Performance Organic Source-Gated Transistors Enabled by the Indium-Tin Oxide-Diketopyrrolopyrrole Polymer Interface.

Source-gated transistors are a new driver of low-power high-gain thin-film electronics. However, source-gated transistors based on organic semiconductors are not widely investigated yet despite their potential for future display and sensor technologies. We report on the fabrication and modeling of high-performance organic source-gated transistors utilizing a critical junction formed between indium-tin oxide and diketopyrrolopyrrole polymer. This partially blocked hole-injection interface is shown to offer both a sufficient level of drain currents and a strong depletion effect necessary for source pinch-off. As a result, our transistors exhibit a set of outstanding metrics, including an intrinsic gain of 160 V/V, an output resistance of 4.6 GΩ, and a saturation coefficient of 0.2 at an operating voltage of 5 V. Drift-diffusion simulation is employed to reproduce and rationalize the experimental data. The modeling reveals that the effective contact length is significantly reduced in an interdigitated electrode geometry, eventually contributing to the realization of low-voltage saturation.

Efficient pure blue hyperfluorescence devices utilizing quadrupolar donor-acceptor-donor type of thermally activated delayed fluorescence sensitizers.

The hyperfluorescence (HF) system has drawn great attention in display technology. However, the energy loss mechanism by low reverse intersystem crossing rate (kRISC) and the Dexter energy transfer (DET) channel is still challenging. Here, we demonstrate that this can be mitigated by the quadrupolar donor-acceptor-donor (D-A-D) type of thermally activated delayed fluorescence (TADF) sensitizer materials, DBA-DmICz and DBA-DTMCz. Further, the HF device with DBA-DTMCz and ν-DABNA exhibited 43.9% of high maximum external quantum efficiency (EQEmax) with the Commission Internationale de l'Éclairage coordinates of (0.12, 0.16). The efficiency values recorded for the device are among the highest reported for HF devices. Such high efficiency is assisted by hindered DET process through i) high kRISC, and ii) shielded lowest unoccupied molecular orbital with the presence of two donors in D-A-D type of skeleton. Our current study provides an effective way of designing TADF sensitizer for future HF technology.

Exposure to Foreign Languages through Live Interaction Can Facilitate Children's Acceptance of Multiple Labeling Conventions across Languages.

The current research examined whether children's expectations about labeling conventions can be influenced by limited exposure to a foreign language. Three- to four-year-old Korean children were presented with two speakers who each assigned a novel label either in Korean or Spanish to a novel object. Children were asked whether both labels were acceptable for the object. Children who had more exposure to a foreign language through live social interaction, but not through media, were more likely to accept both Korean and Spanish labels. These findings indicate the influence of social interaction in foreign language exposure on children's understanding of different labeling conventions.

Manipulating Spectral Width and Emission Wavelength towards Highly Efficient Blue Asymmetric Carbazole Fused Multi-Resonance Emitters.

The novel carbazole-based multiresonance types of thermally activated delayed fluorescence (MR-TADF) emitters of mICz-DABNA and BFCz-DABNA are reported, and their spectroscopic properties are investigated with the inductive effect on the central nitrogen atom for pure and deep blue emission. With the introduction of electron-donating/-withdrawing properties of substituents, emitters exhibited the bathochromic/hypsochromic shifted emission, respectively, compared to simple carbazole-based MR-TADF. Moreover, their spectral bandwidths became narrower. Theoretical calculation indicated that the meta-positioned bulky moiety restricts the molecular geometry discrepancy and reduces the Huang-Rhys factors. Particularly, the organic light-emitting diode (OLED) with 3% BFCz-DABNA exhibited the maximum external quantum efficiency of 28.0% with the Commission International de l'Éclairage (CIE) of (0.13, 0.09), which is the best record value among single-boron MR-TADF devices of CIE y < 0.10.

Color-Tunable All-Fluorescent White Organic Light-Emitting Diodes with a High External Quantum Efficiency Over 30% and Extended Device Lifetime.

White organic light-emitting diodes (WOLEDs) with high efficiencies and tunable colors attracts considerable interest from the industry and academia. Thermally activated delayed-fluorescence (TADF) emitters can revolutionize such WOLED devices; however, they still suffer from poor performances. In this study, an advanced double-emissive-layer device architecture capable of hole-trapping TADF-sensitized emissions is proposed to not only achieve a recombination zone shift for the tunable colors but also accelerate exciton emission dynamics for high efficiency and alleviated roll-off. The proof-of-concept WOLEDs exhibit significant shifts in their Commission Internationale de l'Eclairage (CIE) coordinates and correlated color temperatures from (0.40, 0.47) and 4088 K at 100 cd m-2 to (0.27, 0.33) and 9269 K at 5000 cd m-2 . Additionally, the maximum external quantum efficiency (EQE) reaches 30.7% and remains >25% over a wide luminance range of 500-5000 cd m-2 , along with an extended LT80 of over 20 000 h at an initial luminance of 100 cd m-2 . This is the first time that all-fluorescent WOLEDs have been used to realize an EQE exceeding 30%, thereby establishing a new benchmark in this field.

Evaluation of the Age- and Sex-Related Changes of the Osteogenic Differentiation Potentials of Healthy Bone Marrow-Derived Mesenchymal Stem Cells.

Background andObjectives: Human bone marrow-derived mesenchymal stem cells (BMSCs) are promising sources for cell-based regenerative therapy. The purpose of the present study was to elucidate the roles of age and sex on the cellular viability and osteogenic potential of BMSCs cultured in osteogenic media. Materials and Methods: Human BMSCs were isolated and expanded from 3 age groups-20s, 30s, and 50s-from both sexes. The total number of aspirates was ten, and each subgroup had five for 20s (two females and three males), three for 30s (one female and two male), and two for 50s (one female and one male). Analyses of the cell morphology, the cell viability, the expression of the stem cell marker SSEA-4, the secretion of human vascular endothelial growth factor (VEGF), the expression of Runx2 and collagen I, the metabolic activity, and the formation of mineralization nodules were performed. Results: No significant differences were found in the cell viability of human BMSCs cultured in osteogenic media among the different age groups. There were no significant differences in the expression of SSEA among the age groups or between males and females. There were no significant differences in the secretion of human VEGF between males and females. No significant differences in Runx2 or collagen I expression were noted by age or gender. Moreover, no significant differences were shown in osteogenesis by alizarin red staining. Conclusions: The human BMSCs showed no age-related decreases in cellular viability or osteogenic differentiation potential.

Acceptor-Donor-Acceptor-Type Orange-Red Thermally Activated Delayed Fluorescence Materials Realizing External Quantum Efficiency Over 30% with Low Efficiency Roll-Off.

Two new orange-red thermally activated delayed fluorescence (TADF) materials, PzTDBA and PzDBA, are reported. These materials are designed based on the acceptor-donor-acceptor (A-D-A) configuration, containing rigid boron acceptors and dihydrophenazine donor moieties. These materials exhibit a small ΔEST of 0.05-0.06 eV, photoluminescence quantum yield (PLQY) as high as near unity, and short delayed exciton lifetime (τd ) of less than 2.63 µs in 5 wt% doped film. Further, these materials show a high reverse intersystem crossing rate (krisc ) on the order of 106 s-1 . The TADF devices fabricated with 5 wt% PzTDBA and PzDBA as emitting dopants show maximum EQE of 30.3% and 21.8% with extremely low roll-off of 3.6% and 3.2% at 1000 cd m-2 and electroluminescence (EL) maxima at 576 nm and 595 nm, respectively. The low roll-off character of these materials is analyzed by using a roll-off model and the exciton annihilation quenching rates are found to be suppressed by the fast krisc and short delayed exciton lifetime. These devices show operating device lifetimes (LT50 ) of 159 and 193 h at 1000 cd m-2 for PzTDBA and PzDBA, respectively. The high efficiency and low roll-off of these materials are attributed to the good electronic properties originatng from the A-D-A molecular configuration.

Perilla frutescens Extracts Enhance DNA Repair Response in UVB Damaged HaCaT Cells.

Physiological processes in skin are associated with exposure to UV light and are essential for skin maintenance and regeneration. Here, we investigated whether the leaf and callus extracts of Perilla frutescens (Perilla), a well-known Asian herb, affect DNA damage response and repair in skin and keratinocytes exposed to Untraviolet B (UVB) light. First, we examined the protective effects of Perilla leaf extracts in UVB damaged mouse skin in vivo. Second, we cultured calluses using plant tissue culture technology, from Perilla leaf explant and then examined the effects of the leaf and callus extracts of Perilla on UVB exposed keratinocytes. HaCaT cells treated with leaf and callus Perilla extracts exhibited antioxidant activities, smaller DNA fragment tails, and enhanced colony formation after UVB exposure. Interestingly, keratinocytes treated with the leaf and callus extracts of Perilla showed G1/S cell cycle arrest, reduced protein levels of cyclin D1, Cyclin Dependent Kinase 6 (CDK6), and γH2AX, and enhanced levels of phosphorylated checkpoint kinase 1 (pCHK1) following UVB exposure. These observations suggest that the leaf and callus extracts of Perilla are candidate nutraceuticals for the prevention of keratinocyte aging.

A New BODIPY Material for Pure Color and Long Lifetime Red Hyperfluorescence Organic Light-Emitting Diode.

A red fluorescent material, 1,3,7,9-tetrakis(4-(tert-butyl)phenyl)-5,5-difluoro-10-(2-methoxyphenyl)-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinine (4tBuMB), as an emitting dopant in a thermally activated delayed fluorescence (TADF) sensitized hyperfluorescence organic light-emitting diode (HFOLED) is reported. The 4tBuMB shows a high photoluminescence quantum yield (PLQY) of 99% with an emission maximum at 620 nm and a full width at half-maximum (fwhm) of 31 nm in solution. Further, it shows a deep lowest unoccupied molecular orbital (LUMO) of 3.83 eV. Thus, two TADF materials, 4CzIPN and 4CzTPN, as sensitizing hosts, are selected on the basis of a suitable LUMO level and spectrum overlap with 4tBuMB. The fabricated HFOLED device with 4CzTPN as a sensitizing host and 4tBuMB as an emitting dopant shows a maximum external quantum efficiency (EQE), an emission maximum, an fwhm, and CIE coordinates of 19.4%, 617 nm, 44 nm, and (0.64, 0.36), respectively. The electroluminance performances of the 4CzTPN sensitized device are higher than those of the 4CzIPN-based device, which is attributed to a higher Förster resonance energy transfer (FRET) rate and reduced intersystem crossing/reverse intersystem crossing (ISC/RISC) cycles of the former. Also, the 4CzTPN-based HF device shows a longer device lifetime (LT90) of 954 h than the 4CzIPN-baed device (LT90 of 57 h) at 3000 cd m-2. The higher device stability is due to the higher bond dissociation energies (BDEs) of 4CzTPN and 4tBuMB than that of 4CzIPN.

Morphological stability, cellular viability and stem cell marker expression of three-dimensional cultures of stem cells from bone marrow and periodontium.

The aim of the present study was to evaluate the morphology, cellular viability and stem cell marker expression of three-dimensional cultures of bone marrow and gingiva-derived stem cells in different ratios. Stem cell spheroids were made with bone marrow and gingiva-derived stem cells using ratios of 6:0 (Group 1), 4:2 (Group 2), 3:3 (Group 3), 2:4 (Group 4) and 0:6 (Group 5), respectively. The viability of cell spheroids was analyzed using a Live/Dead kit assay and a Cell Counting Kit-8 assay. Total RNA extraction and reverse transcription-quantitative PCR were performed to detect the mRNA expression levels of Nanog and ß-actin in each group. Stem cell spheroids were well formed in silicone elastomer-based concave microwells with different ratios of bone marrow and gingiva-derived stem cells. The shape of the spheroids and their viability were maintained throughout the entirety of the experimental procedure. Statistically significant increases in spheroid diameters were noted in Groups 4 and 5 on day 1 when compared with Group 1 on day 1. There was a significant increase in the cell viability values seen in Group 3 on day 1 when compared with Group 1 on day 1. Highest levels of Nanog expression was seen in Group 3 on day 10, but the increase was not significant when compared with Group 1 on day 1. Co-culturing with higher ratios of gingiva-derived stem cells produced stem cell spheroids with larger diameters and increased cellular viability. This co-culture technique may be used in stem cell therapy with allogenic stem cell transplantation.

Anti-Helicobacter pylori activity of acomplex mixture of Lactobacillus paracasei HP7 including the extract of Perilla frutescens var. acuta and Glycyrrhiza glabra.

The effect of standard therapeutic strategies on Helicobacter pylori infection is diminished over time owing to the emergence of drug resistant strains. In this study, we would like to confirm the enhanced effect of L. paracasei HP7, which has been reported to exert antibacterial and gastric mucosal protective effects, in combination with Perilla frutescens var. acuta (P. frutescens)and Glycyrrhiza glabra (G. glabra) extracts. P. frutescens extract and G. glabra extract were found to inhibit the growth of H. pylori in a concentration-dependent manner, and the combination of L. paracasei HP7 and P. frutescens extract and G. glabra extract effectively inhibited H. pylori from attaching to AGS a gastric epithelial cells. Moreover, L. paracasei HP7 complex mixture containing P. frutescens and G. glabra extracts has been shown to inhibit H. pylori virulence genes such as AlpA, CagA, FlaA and UreA. When H. pylori-infected mice were administered a complex mixture of L. paracasei HP7 containing P. frutescens and G. glabra extract, the infection rate of H. pylori was significantly reduced. In addition, the L. paracasei HP7 complex mixture significantly reduced serum IL-8 levels and stomach inflammation in H. pylori infected mice. These results suggest that a complex mixture of L. paracasei HP7 containing P. frutescens and G. glabra extracts may be an alternative to treating diseases caused by H. pylori infection.

Asymmetric Host Molecule Bearing Pyridine Core for Highly Efficient Blue Thermally Activated Delayed Fluorescence OLEDs.

In this study, two host materials, pCzBzbCz and pCzPybCz, are synthesized to achieve a high efficiency and long lifetime of blue thermally activated delayed fluorescence organic light-emitting diodes (TADF-OLEDs). The molecular design strategy involves the introduction of a pyridine group into the core structure of pCzPybCz as an electron-withdrawing unit, and an electron-donating phenyl group into the structure of pCzBzbCz. These host materials demonstrate good thermal stability and high triplet energy (T1 =3.07 eV for pCzBzbCz and 3.06 eV for pCzPybCz) for the fabrication of blue TADF-OLEDs. In particular, pCzPybCz-based OLED devices demonstrate an external quantum efficiency (EQE) of 22.7 % and an operational lifetime of 24 h (LT90 , time to attain 90 % of initial luminance) at an initial luminance of 1000 cd m-2 . This superior lifetime could be explained by the C-N bond dissociation energy (BDE) in the host molecular structure. Furthermore, a mixed-host system using the electron-deficient 2,4-bis(dibenzo[b,d]furan-2-yl)-6-phenyl-1,3,5-triazine (DDBFT) is proposed to inhibit the formation of the anion state of our host materials. In short, the device operational lifetime is further improved by applying DDBFT. The carbazole-based asymmetric host molecule containing a pyridine core realizes a high-efficiency blue TADF-OLED showing a positive effect on the operating lifetime, and can provide useful strategies for designing new host materials.

Cell cycle profile data on splenocytes of high fat diet induced obese mice treated with ferulic acid.

The reported data are related to the article entitled "Ferulic acid maintains the self-renewal capacity of embryo stem cells and adipose-derived mesenchymal stem cells in high fat diet-induced obese mice" [1]. Ferulic acid is a natural bioactive compound and demonstrated potential to serve as a self-renewing biomarker in an alkaline phosphate assay and caused increased Nanog mRNA levels in embryonic stem cells. In these data, we examined another functional aspect of ferulic acid, namely the effect of ferulic acid on the cell cycle of splenocytes. These data were collected from the splenocytes of C57BL/6 J male mice that were fed either a high fat diet (HFD) alone or an HFD diet supplemented with ferulic acid (5 g/kg diet) for 8 weeks. As expected, the HFD resulted in a significant increase in mouse body weight, liver weight, and epididymal fat tissue weight compared to the control diet (Cho and Park, 2020). The cell cycle profile of mouse splenocytes in HFD-induced obese mice was evaluated by FACS. Since the G1 checkpoint is the point at which cells enter the cell cycle, an internal or external stimulation can cause the cell to delay passing G1 and instead enter a quiescent state known as G0 without proceeding past the restriction checkpoint. DNA damage is the main trigger that can cause a cell to "restrict" itself and not enter the cell cycle [2]. These results show that ferulic acid helps attenuate G1/S arrest in splenocytes in HFD-induced obese mice.

Recent Advancement in Boron-Based Efficient and Pure Blue Thermally Activated Delayed Fluorescence Materials for Organic Light-Emitting Diodes.

In the last few years, electron-deficient materials have been actively researched for application in organic light-emitting diode (OLED) as dopant and electron-transporting materials. The boron-containing materials are interesting as they give good emissive properties in solid state with an electron-accepting character. Recently, many boron-containing materials are used as emissive materials for thermally activated delayed fluorescence (TADF) OLED applications. In this review, boron acceptor-based push-pull small molecules used for application in blue TADF OLEDs are reviewed, covering their different types of acceptor, molecular design, structure-property relation, material properties, and device properties. Also, the importance of boron acceptors to address the key issue of blue TADF OLEDs is discussed.

External Quantum Efficiency Exceeding 24% with CIEy Value of 0.08 using a Novel Carbene-Based Iridium Complex in Deep-Blue Phosphorescent Organic Light-Emitting Diodes.

Deep-blue triplet emitters remain far inferior to standard red and green triplet emitters in terms of exhibiting high-color-purity Commission International de l'Éclairage (CIE) y values of ≤0.1, external quantum efficiencies (EQEs), and high electroluminescent brightnesses in phosphorescent organic light-emitting diodes. In fact, no deep-blue triplet emitter with color purity and high device performance has previously been reported. In this study, a deep-blue triplet emitter, mer-tris(N-phenyl, N-benzyl-pyridoimidazol-2-yl)iridium(III) (mer-Ir1) is developed, which meets the requirements of the National Television System Committee (NTSC) CIE(x, y) coordinates of (0.149, 0.085) with an extremely high EQE of 24.8% and maximum brightness (Lmax ) of 6453 cd m-2 , by a device with a 40 vol% doping ratio. Moreover, another device demonstrates an EQEmax of 21.3%, an Lmax of 5247 cd m-2 , and CIE(x, y) coordinates of (0.151, 0.086) at a 30 vol% doping ratio. This is the first report of a high-performance, deep-blue phosphor, carbene-based Ir(III) complex device with outstanding CIE(x, y) color coordinates and a high EQE. The results of this study indicate that the novel dopant mer-Ir1 is a promising candidate for reducing power consumption in display applications.

Fourteen- to Eighteen-Month-Old Infants Use Explicit Linguistic Information to Update an Agent's False Belief.

The current research examined how infants exploit linguistic information to update an agent's false belief about an object's location. Fourteen- to eighteen-month-old infants first watched a series of events involving two agents, a ball, and two containers (a box and a cup). Agent1 repeatedly acted on the ball and then put it in the box in the presence of agent2. Then agent1 disappeared from the scene and agent2 switched the ball's location from the box to the cup. Upon agent1's return, agent2 told her, "The ball is in the cup!" Agent1 then reached for either the cup (cup event) or the box (box event). The infants looked reliably longer if shown the box event as opposed to the cup event. However, when agent2 simply said, "The ball and the cup!" - which does not explicitly mention the ball's new location - infants looked significantly longer if shown the cup event as opposed the box event. These findings thus provide new evidence for false-belief understanding in infancy and suggest that infants expect an agent's false belief to be updated only by explicit verbal information.