Radotinib Decreases Prion Propagation and Prolongs Survival Times in Models of Prion Disease.

The conversion of cellular prion protein (PrPC) into pathogenic prion isoforms (PrPSc) and the mutation of PRNP are definite causes of prion diseases. Unfortunately, without exception, prion diseases are untreatable and fatal neurodegenerative disorders; therefore, one area of research focuses on identifying medicines that can delay the progression of these diseases. According to the concept of drug repositioning, we investigated the efficacy of the c-Abl tyrosine kinase inhibitor radotinib, which is a drug that is approved for the treatment of chronic myeloid leukemia, in the treatment of disease progression in prion models, including prion-infected cell models, Tga20 and hamster cerebellar slice culture models, and 263K scrapie-infected hamster models. Radotinib inhibited PrPSc deposition in neuronal ZW13-2 cells that were infected with the 22L or 139A scrapie strains and in cerebellar slice cultures that were infected with the 22L or 263K scrapie strains. Interestingly, hamsters that were intraperitoneally injected with the 263K scrapie strain and intragastrically treated with radotinib (100 mg/kg) exhibited prolonged survival times (159 ± 28.6 days) compared to nontreated hamsters (135 ± 9.9 days) as well as reduced PrPSc deposition and ameliorated pathology. However, intraperitoneal injection of radotinib exerted a smaller effect on the survival rate of the hamsters. Additionally, we found that different concentrations of radotinib (60, 100, and 200 mg/kg) had similar effects on survival time, but this effect was not observed after treatment with a low dose (30 mg/kg) of radotinib. Interestingly, when radotinib was administered 4 or 8 weeks after prion inoculation, the treated hamsters survived longer than the vehicle-treated hamsters. Additionally, a pharmacokinetic assay revealed that radotinib effectively crossed the blood-brain barrier. Based on our findings, we suggest that radotinib is a new candidate anti-prion drug that could possibly be used to treat prion diseases and promote the remission of symptoms.

Combination treatment of peroxyacetic acid or lactic acid with UV-C to control Salmonella Enteritidis biofilms on food contact surface and chicken skin.

The risk of salmonellosis is expected to increase with the rise in the consumption of poultry meat. The aim of this study was to investigate the combination treatment of peroxyacetic acid (PAA) or lactic acid (LA) with UV-C against Salmonella Enteritidis biofilms formed on food contact surface (stainless steel [SS], silicone rubber [SR], and ultra-high molecular weight polyethylene [UHMWPE]) and chicken skin. The biofilm on food contact surface and chicken skin was significantly decreased (P < 0.05) by combination treatment of PAA or LA with UV-C. Combination treatment of PAA (50-500 µg/mL) with UV-C (5 and 10 min) reduced 3.10-6.41 log CFU/cm2 and LA (0.5-2.0%) with UV-C (5 and 10 min) reduced 3.35-6.41 log CFU/cm2 of S. Enteritidis biofilms on food contact surface. Salmonella Enteritidis biofilms on chicken skin was reduced around 2 log CFU/g with minor quality changes in color and texture by combination treatment of PAA (500 µg/mL) or LA (2.0%) with UV-C (10 min). Additional reduction occurred on SS and UHMWPE by PAA or LA with UV-C, while only LA with UV-C caused additional reduction on chicken skin. Also, it was visualized that the biofilm on food contact surface and chicken skin was removed through field emission scanning electron microscopy (FESEM) and death of cells constituting the biofilm was confirmed through confocal laser scanning microscopy (CLSM). These results indicating that the combination treatment of PAA or LA with UV-C could be used for S. Enteritidis biofilm control strategy in poultry industry.

Day-Ahead Hourly Solar Irradiance Forecasting Based on Multi-Attributed Spatio-Temporal Graph Convolutional Network.

Solar irradiance forecasting is fundamental and essential for commercializing solar energy generation by overcoming output variability. Accurate forecasting depends on historical solar irradiance data, correlations between various meteorological variables (e.g., wind speed, humidity, and cloudiness), and influences between the weather contexts of spatially adjacent regions. However, existing studies have been limited to spatiotemporal analysis of a few variables, which have clear correlations with solar irradiance (e.g., sunshine duration), and do not attempt to establish atmospheric contextual information from a variety of meteorological variables. Therefore, this study proposes a novel solar irradiance forecasting model that represents atmospheric parameters observed from multiple stations as an attributed dynamic network and analyzes temporal changes in the network by extending existing spatio-temporal graph convolutional network (ST-GCN) models. By comparing the proposed model with existing models, we also investigated the contributions of (i) the spatial adjacency of the stations, (ii) temporal changes in the meteorological variables, and (iii) the variety of variables to the forecasting performance. We evaluated the performance of the proposed and existing models by predicting the hourly solar irradiance at observation stations in the Korean Peninsula. The experimental results showed that the three features are synergistic and have correlations that are difficult to establish using single-aspect analysis.

Evaluation of Dose-Dependent Obesity and Diabetes-Related Complications of Water Chestnut (Fruit of Trapa japonica) Extracts in Type II Obese Diabetic Mice Induced by 45% Kcal High-Fat Diet.

Background and Objectives: The currently used pharmacological agents for metabolic disorders such as type II diabetes have several limitations and adverse effects; thus, there is a need for alternative therapeutic drugs and health functional foods. Materials and Methods: This study investigated the pharmacological effects of water chestnut (fruit of Trapa japonica) extracts (WC: 50-200 mg/kg) for type II diabetes using a 45% Kcal high-fat diet (HFD)-fed type II obese diabetic mice model for a period of 84 days, and the effects were compared to those of metformin (250 mg/kg). Results: Increases in body weight, serum biochemical indices such as triglycerides, low-density lipoprotein, and blood urea nitrogen, increases in antioxidant defense system enzymes such as catalase, superoxide dismutase, and glutathione, and mRNA expressions (such as AMPKα1 and AMPKα2) in the liver tissue and mRNA expressions (such as AMPKα2 mRNA, leptin, and C/EBPα) in the adipose tissue were observed in the HFD control group. The WC (50 mg/kg)-administered group showed no significant improvements in diabetic complications. However, HFD-induced obesity and diabetes-related complications such as hyperlipidemia, diabetic nephropathy, nonalcoholic fatty liver disease (NAFLD), oxidative stress, activity of antioxidant defense systems, and gene expressions were significantly and dose-dependently inhibited and/or normalized by oral administration of WC (100 mg/kg and 200 mg/kg), particularly at a dose of 100 mg/kg. Conclusions: The results of this study suggest that WC at an appropriate dose could be used to develop an effective therapeutic drug or functional food for type II diabetes and various associated complications, including NAFLD.

First Observation of Ferroelectricity in ∼1 nm Ultrathin Semiconducting BaTiO3 Films.

The requirements of multifunctionality in thin-film systems have led to the discovery of unique physical properties and degrees of freedom, which exist only in film forms. With progress in growth techniques, one can decrease the film thickness to the scale of a few nanometers (∼nm), where its unique physical properties are still pronounced. Among advanced ultrathin film systems, ferroelectrics have generated tremendous interest. As a prototype ferroelectric, the electrical properties of BaTiO3 (BTO) films have been extensively studied, and it has been theoretically predicted that ferroelectricity sustains down to ∼nm thick films. However, efforts toward determining the minimum thickness for ferroelectric films have been hindered by practical issues surrounding large leakage currents. In this study, we used ∼nm thick BTO films, exhibiting semiconducting characteristics, grown on a LaAlO3/SrTiO3 (LAO/STO) heterostructure. In particular, we utilized two-dimensional electron gas at the LAO/STO heterointerface as the bottom electrode in these capacitor junctions. We demonstrate that the BTO film exhibits ferroelectricity at room temperature, even when it is only ∼2 unit-cells thick, and the total thickness of the capacitor junction can be reduced to less than ∼4 nm. Observation of ferroelectricity in ultrathin semiconducting films and the resulting shrunken capacitor thickness will expand the applicability of ferroelectrics in the next generation of functional devices.

Efficacy of disinfectant and bacteriophage mixture against planktonic and biofilm state of Listeria monocytogenes to control in the food industry.

Fresh produce and animal-based products contaminated with Listeria monocytogenes have been the main cause of listeriosis outbreaks for many years. The present investigation explored the potential of combination treatment of disinfectants with a bacteriophage cocktail to control L. monocytogenes contamination in the food industry. A mixture of 1 minimal inhibitory concentration (MIC) of disinfectants (sodium hypochlorite [NaOCl], hydrogen peroxide [H2O2], and lactic acid [LA]) and multiplicity of infection (MOI) 100 of phage cocktail was applied to both planktonic cells in vitro and already-formed biofilm cells on food contact materials (FCMs; polyethylene, polypropylene, and stainless steel) and foods (celery and chicken meat). All the combinations significantly lowered the population, biofilm-forming ability, and the expression of flaA, motB, hlyA, prfA, actA, and sigB genes of L. monocytogenes. Additionally, in the antibiofilm test, approximately 4 log CFU/cm2 was eradicated by 6 h treatment on FCMs, and 3 log CFU/g was eradicated within 3 days on celery. However, <2 log CFU/g was eradicated in chicken meat, and regrowth of L. monocytogenes was observed on foods after 5 days. The biofilm eradication efficacy of the combination treatment was proven through visualization using scanning electron microscopy (SEM) and confocal microscopy. In the SEM images, the unusual behavior of L. monocytogenes invading from the surface to the inside was observed after treating celery with NaOCl+P or H2O2 + P. These results suggested that combination of disinfectants (NaOCl, H2O2, and LA) with Listeria-specific phage cocktail can be employed in the food industry as a novel antimicrobial and antibiofilm approach, and further research of L. monocytogenes behavior after disinfection is needed.

Biofilm eradication ability of phage cocktail against Listeria monocytogenes biofilms formed on food contact materials and effect on virulence-related genes and biofilm structure.

Listeria monocytogenes is a foodborne pathogen that can form biofilms in food processing facilities even under unfavorable growth environment. This study aimed to evaluate the biofilm eradication ability of Listeria-specific bacteriophage (phage) cocktail (LMPC01+02+03) against L. monocytogenes young (1 day) and mature (3 days) biofilms formed on food contact materials (FCMs: polyethylene, polypropylene, and stainless steel) at 4, 15, and 30 °C. In addition, virulence-related genes and biofilm structure parameters of the phage-treated biofilms were investigated. The biofilm eradication ability of the phage cocktail was evaluated on 96 well and MBEC plate, and the results revealed that a multiplicity-of-infection (MOI) 100 of the phage cocktail exhibited the ability of eradicate biofilms. Using MOI 100, the phage cocktail treatment on the biofilms formed on FCMs for 8 h reduced over 2 log CFU/cm2 of the young biofilms, and approximately 1 log CFU/cm2 of the mature biofilms. In addition, the phage treatment against the biofilms resulted in a significant up-regulation of two genes (flaA and motB), and up/down-regulation or no changes in three genes (hlyA, prfA, and actA). Confocal and scanning electron microscopy images revealed the loss of the biofilm matrix after the phage treatment, and quantitative analysis revealed a reduction in the structural parameters of the biofilm, except the microcolonies at the substratum level, which increased. These results suggested that MOI 100 of the phage cocktail (LMPC01+02+03) was an effective tool for eradicating L. monocytogenes biofilms formed on FCMs, and it is essential to develop a countermeasure to eradicate the biofilm remaining after phage treatment.

Designing Nonfullerene Acceptors with Oligo(Ethylene Glycol) Side Chains: Unraveling the Origin of Increased Open-Circuit Voltage and Balanced Charge Carrier Mobilities.

Despite the recent rapid development of organic solar cells (OSCs), the low dielectric constant (ϵr =3-4) of organic semiconducting materials limits their performance lower than inorganic and perovskite solar cells. In this work, we introduce oligo(ethylene glycol) (OEG) side chains into the dicyanodistyrylbenzene-based non-fullerene acceptors (NIDCS) to increase its ϵr up to 5.4. In particular, a NIDCS acceptor bearing two triethylene glycol chains (NIDCS-EO3) shows VOC as high as 1.12 V in an OSC device with a polymer donor PTB7, which is attributed to reduced exciton binding energy of the blend film. Also, the larger size grain formation with well-ordered stacking structure of the NIDCS-EO3 blend film leads to the increased charge mobility and thus to the improved charge mobility balance, resulting in higher JSC , FF, and PCE in the OSC device compared to those of a device using the hexyl chain-based NIDCS acceptor (NIDCS-HO). Finally, we fabricate NIDCS-EO3 devices with various commercial donors including P3HT, DTS-F, and PCE11 to show higher photovoltaic performance than the NIDCS-HO devices, suggesting versatility of NIDCS-EO3.

Structural and Electronic Origin of Bis-Lactam-Based High-Performance Organic Thin-Film Transistors.

We describe herein the comprehensive theoretical and experimental studies on the transistor mobility of organic semiconductors by correlating a two-dimensional (2D) intermolecular interaction with thin-film morphology and the electronic coupling structure. We developed a novel bis-lactam-based small molecule, 1,5-dioctyl-3,7-di(thiophen-2-yl)-1,5-naphthyridine-2,6-dione (C8-NTDT), with a 2D-type C-H···O═C intermolecular interaction along the in-plane directions of the crystal packing structure, which is characteristically different from the one-dimensional-type intermolecular interaction shown in the typical bis-lactam molecule of 2,5-dioctyl-3,6-di(thiophen-2-yl)pyrrolo[3,4- c]pyrrole-1,4-dione (C8-DPPT). Experimentally and theoretically, C8-NTDT exhibited more favorable thin-film morphology and an electronic coupling structure for charge transport because of its unique 2D intermolecular interactions compared with C8-DPPT. In fact, C8-NTDT exhibited a hole mobility of up to 1.29 cm2 V-1 s-1 and an on/off ratio of 107 in a vacuum-processed device. Moreover, the high solubility with the 2D electronic coupling structure of C8-NTDT enables versatile solution processing for device fabrication without performance degradation compared to the vacuum-processed device. As an example, we could demonstrate a hole mobility of up to 1.10 cm2 V-1 s-1 for the spin-coated devices, which is one of the best performances among the solution-processed organic field-effect transistors based on bis-lactam-containing small molecules.

Sargaquinoic Acid Inhibits TNF-α-Induced NF-κB Signaling, Thereby Contributing to Decreased Monocyte Adhesion to Human Umbilical Vein Endothelial Cells (HUVECs).

Sargaquinoic acid (SQA) has been known for its antioxidant and anti-inflammatory properties. This study investigated the effects of SQA isolated from Sargassum serratifolium on the inhibition of tumor necrosis factor (TNF)-α-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). SQA decreased the expression of cell adhesion molecules such as intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 as well as chemotactic cytokines such as interleukin-8 and monocyte chemoattractant protein-1 in TNF-α-treated HUVECs. As a result, SQA prevented monocyte adhesion to TNF-α-induced adhesion. SQA also inhibited TNF-α-induced nuclear factor kappa B (NF-κB) translocation into the nucleus by preventing proteolytic degradation of inhibitor κB-α. Overall, SQA protects against TNF-α-induced vascular inflammation through inhibition of the NF-κB pathway in HUVECs. These data suggest that SQA may be used as a therapeutic agent for vascular inflammatory diseases such as atherosclerosis.