Search

Background Main bioactive constituents and pharmacological functions of ripened red ginseng berry (Panax ginseng Meyer) have been frequently reported. Yet, the research gap targeting the beneficial activities of transformed green ginseng berries has not reported elsewhere. Methods Ginsenosides of new green berry cultivar K-1 (GK-1) were identified by HPLC-QTOF/MS. Ginsenosides bioconversion in GK-1 by bgp1 enzyme was confirmed with HPLC and TLC. Then, mechanisms of GK-1 and β-glucosidase (bgp1) biotransformed GK-1 (BGK-1) were determined by Quantitative Reverse Transcription-Polymerase Chain Reaction and Western blot. Results GK-1 possesses highest ginsenosides especially ginsenoside-Re amongst seven ginseng cultivars including (Chunpoong, Huangsuk, Kumpoong, K-1, Honkaejong, Gopoong, and Yunpoong). Ginseng root’s biomass is not affected with the harvest of GK-1 at 3 weeks after flowering period. Then, Re is bio-converted into a promising pharmaceutical effect of Rg2 via bgp1. According to the results of cell assays, BGK-1 shows decrease of tyrosinase and melanin content in α-melanocyte-stimulating hormone challenged-murine melanoma B16 cells. BGK-1 which is comparatively more effective than GK-1 extract shows significant suppression of the nuclear factor (NF)-κB activation and inflammatory target genes, in LPS-stimulated RAW 264.7 cells. Conclusion These results reported effective whitening and anti-inflammatory of BGK-1 as compared to GK-1., Graphical abstract Image 1

Background: Conventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids.Methods: The LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing’s syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors.Results: The CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6β-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT.Conclusion: The combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.

To investigate the structure–function correlation analysed by full-field electroretinography (ffERG) and optical coherence tomography (OCT) in typical and pericentral subtypes of retinitis pigmentosa (RP). A retrospective, cross-sectional, observational study of right eyes was conducted. The primary analysis used ffERG data to compare the RP subtypes. The subgroup analysis was used to correlate the structure, analysed by OCT, and function, determined by ffERG. Linear regressions explored the relationship between best-corrected visual acuity (BCVA) and multiple parameters. A total of 188 eyes were included. Amplitudes of responses of rod, rod-cone, cone, and 30 Hz flicker of typical type were lower than those of pericentral and other types. In the subgroup analysis, 41 and 21 eyes of the typical and pericentral types were studied, respectively. The correlation between the estimated preserved photoreceptor area and all ffERG amplitude parameters were significant in the typical type, but not in pericentral type. Old age, decreased intact ellipsoid zone length, typical type, and thin central retinal thickness were negatively correlated with BCVA. Typical type RP developed more extensive degeneration and poorer BCVA compared to others. Strong structure–function correlation was found in typical type while not in pericentral type. OCT may be a useful tool for monitoring RP status in typical type, providing useful parameters for the prediction of BCVA.

Obesity is fast becoming a worldwide health concern and causes a chronic state of oxidative stress and low-grade inflammation, which could be major risk factors for a number of chronic diseases. We investigated the potential of the 61 probiotic candidates isolated from infant feces towards activity of lipid accumulation inhibition, and then we extended the study to evaluate their antidiabetic and antioxidant activity. Seven strains were finally selected based on their ability to inhibit lipid accumulation (>60%) and productivity yield (>1 × 1011 colony forming units [CFU]/g): Lactobacillus acidophilus MG4558; Lactobacillus paracasei MG4592; Lactobacillus plantarum MG4553 and MG4555; and Lactobacillus rhamnosus MG4502, MG4511, and MG4505. Selected strains showed high α-glucosidase-inhibiting activity (> 50%), except for MG4511 (19.8%), and similar antioxidant activities were reflected by the results of DPPH (21.6–27.5%) and ABTS (40.9–44.9%) assays. With respect to their functional properties as probiotics, most of the strains were resistant to simulated gastric (pH 3 and 4) and intestinal (pH 7 and 8) fluids, and possessed various probiotic-related factors, including autoaggregation ability, antibiotic susceptibility, enzyme production, and biochemical profiles, and were non-hemolytic. We conclude that our strains may be good probiotic candidates for functional food ingredients to prevent metabolic disorders such as obesity and diabetes.

Diabetes, a chronic metabolic disorder, is characterized by persistent hyperglycemia. This study aimed to evaluate the hypoglycemic and antioxidant activities of lactic acid bacteria strains isolated from humans and food products and investigate the probiotic properties of the selected four strains. The hypoglycemic activity of the isolated strains was examined by evaluating the α-glucosidase and α-amylase inhibitory activities. The antioxidant activity was measured using the DPPH, ABTS, and FRAP assays. Four strains (Lactiplantibacillus plantarum MG4229, MG4296, MG5025, and Lacticaseibacillus paracasei MG5012) exhibited potent α-glucosidase inhibitory (>75%) and α-amylase inhibitory (>85%) activities, which were comparable to those of acarbose (>50%; 1000 μg/mL). Similarly, the radical scavenging and antioxidant activities of the four strains were comparable to those of ascorbic acid (50 μg/mL). Additionally, the probiotic properties of the four selected strains were examined based on acid and bile salt tolerance, auto-aggregation ability, and antibiotic resistance. The four strains were resistant to pH 2 (>50% of survivability) and 0.5% bile salt (>80% of survivability). Therefore, we suggest that the selected strains with hypoglycemic, antioxidant, probiotic properties can potentially prevent diabetes. Supplementary Information The online version contains supplementary material available at 10.1007/s00284-021-02588-5.

Background Alcohol consumption is one of the modifiable risk factors for intracerebral hemorrhage, which accounts for approximately 10–20% of all strokes worldwide. We evaluated the association of stroke with genetic polymorphisms in the alcohol metabolizing genes, alcohol dehydrogenase 1B (ADH1B, rs1229984) and aldehyde dehydrogenase 2 (ALDH2, rs671) genes based on alcohol consumption. Methods Data were available for 19,500 Taiwan Biobank (TWB) participants. We used logistic regression models to test for associations between genetic variants and stroke. Overall, there were 890 individuals with ischemic stroke, 70 with hemorrhagic stroke, and 16,837 control individuals. Participants with ischemic but not hemorrhagic stroke were older than their control individuals (mean ± SE, 58.47 ± 8.17 vs. 48.33 ± 10.90 years, p Conclusions Our study suggests that the ADH1B rs1229984 TC + CC genotype and alcohol exposure of at least 150 ml/week may increase the risk of developing hemorrhagic stroke among Taiwanese adults.

We synthesized [6,6,6]- and [6,6,7]-tricyclic compounds via intramolecular [4+2] cycloaddition by gold or copper catalysts. Substrates for cyclization were prepared by coupling reactions between eight types of diyne and four types of aromatic moieties. We have successfully synthesized eleven tricyclic compounds.

Heat-killed lactic acid bacteria perform immunomodulatory functions and are advantageous as probiotics, considering their long product shelf-life, easy storage, and convenient transportation. In this study, we aimed to develop appropriate heat treatments for industrial preparation of probiotics with antioxidant activity. Among 75 heat-killed strains, Lactococcus lactis MG5125 revealed the highest nitric oxide inhibition (86.2%), followed by Lactobacillus acidophilus MG4559 (86.0%), Lactobacillus plantarum MG5270 (85.7%), Lactobacillus fermentum MG4510 (85.3%), L. plantarum MG5239 (83.9%), L. plantarum MG5289 (83.2%), and L. plantarum MG5203 (81.8%). Moreover, the heat-killed selected strains markedly inhibited lipopolysaccharide-induced nitric oxide synthase and cyclooxygenase-2 expression. The use of heat-killed bacteria with intact bio-functionality can elongate the shelf-life and simplify the food processing steps of probiotic foods, given their high stability. The antioxidant and immune-modulatory activities of the heat-killed strains selected in this study indicate a strong potential for their utilization probiotic products manufacturing.

This study aimed to explore gene expression changes in the inferior colliculus (IC) after single-sided deafness (SSD). Forty 8-week-old female Sprague–Dawley rats were used. Twenty rats underwent right-side cochlear ablation, and IC tissues were harvested after 2 weeks (SSD 2-week group). Twenty rats underwent a sham operation and were sacrificed after 2 weeks (control group). Both sides of the IC were analyzed using a gene expression array. Pathway analyses were performed on genes that were differentially expressed compared with their levels in the control group. The expression levels of genes involved in the candidate pathways were confirmed using reverse transcription polymerase chain reaction (RT-PCR). Among the genes with ≥ 1.5-fold changes in expression levels and P

The Arabidopsis nucleoside diphosphate kinase 2 (AtNDPK2) gene is known to regulate the cellular redox state, and to enhance tolerance to multiple stressors in plants. In this study, we transferred AtNDPK2 under the stress-inducible promoter SWPA2 into Ardisia pusilla to enhance the plants’ ability to detoxify toluene gas. Thirty transgenic A. pusilla lines were confirmed by PCR analysis with AtNDPK2 and NPTII gene-specific primers. In addition, four transgenic A. pusilla lines were further confirmed by Southern blot analysis to verify the gene copy number. Three transgenic lines showed a single-copy transgene insertion, and one transgenic line had two transgene insertions. To test the gene expression of AtNDPK2 in the transgenic A. pusilla lines exposed to and not exposed to toluene treatment, qRT-PCR analysis was performed. The gene expression of AtNDPK2 in transgenic A. pusilla plants exposed to toluene treatment was significantly higher than that of transgenic plants not exposed to toluene treatment. Finally, we measured toluene removal efficiency of the transgenic and non-transgenic A. pusilla lines exposed to toluene-contaminated air. There was a statistically significant difference between the transgenic and non-transgenic A. pusilla lines at all time points (p

Importance The clinical implications of different morphologies of choroidal neovascularization (CNV), as evaluated by ocular coherence tomography angiography (OCTA) in neovascular age-related macular degeneration (nAMD), are lacking. Background To describe the morphology of CNV in nAMD using OCTA, and to compare the visual prognosis and other structural OCT biomarkers between different morphologic patterns. Design Retrospective cohort study. Participants One hundred and forty eyes with nAMD treated with anti-vascular endothelial growth factor (VEGF). Methods Patients were examined using OCTA prior to and at 3, 6 and 12 months after receiving anti-VEGF therapy. Main outcome measures Best-corrected visual acuity (BCVA) and morphologic retinal features. Results Organized CNV was identified in 110/140 eyes (78.6%) using OCTA. These CNV complexes could be divided into three OCTA patterns: the 'medusa' pattern (n = 41), characterized by branching vessels radiating in all directions; the 'seafan' pattern (n = 43), characterized by branching vessels radiating to one side of the lesion; and the 'tangled' pattern (n = 26), characterized by globular entwined vessels without a main trunk. At baseline, the eyes with the tangled pattern were from younger patients (P = .031) with better BCVA (P = .007). There were also fewer intraretinal cysts (P = .021), less fibrovascular pigment epithelial detachment (P = .009), and more pachychoroid (P = .007) in eyes with the tangled pattern on OCT. At 12 months post-treatment, patients with the tangled CNV pattern also showed greater visual improvement than patients with the other two patterns (P = .049). Conclusions and relevance Using OCTA, distinct morphologies of CNV in nAMD patients were identified. These different patterns might be useful predictors for the prognosis of nAMD patients after anti-VEGF therapy.

Oxidative stress can cause various diseases including inflammation, neurological disorders, cancer, diabetes, and cardiovascular diseases. Due to the current search for natural antioxidants, probiotics have received increasing scientific interest and are facing a growing industrial demand. Although various strains of lactobacilli and bifidobacteria are currently used in numerous health food supplements, their antioxidative activities have been relatively poorly identified. Therefore, in this work, we evaluated the in vitro effect of antioxidative activities (through assays of 2,2-diphenyl-l-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethylbenzothiazorine-6-sulfonate) (ABTS) radical scavenging) and probiotic functional properties (cell viability in a simulated gastrointestinal tract, enzyme production, carbohydrate availability, and safely assessments) of Lactobacillus spp. and Bifidobacterium spp. isolated from human origins. From the nitric oxide (NO) assay screening, four strains (Bifidobacterium animalis subsp. lactis MG741, B. breve MG729, L. reuteri MG505, and L. rhamnosus MG316) were selected based on the yield amount of ferment productivity (> × 1010 CFU/g) and showed high antioxidant activities ranging from 22.2% to 38.2% in DPPH free radical scavenging, and 50.0% to 93.6% in ABTS radical scavenging. Regarding their functional properties as probiotics, these four strains were resistant to simulated gastric (pH 3 and 4) and intestinal fluids (pH 7 and 8), and showed potential for the promotion of health based on hemolysis, auto-aggregation, antibiotic susceptibility, enzyme production, and biochemical profiles. Altogether, our results showed that the selected probiotic strains may be good candidates as food ingredients to mitigate oxidative stress-related symptoms.

To expect the positive physiological functions from probiotic consumption, the lactic acid bacteria should survive, partially, in the gastrointestinal (GI) tract. This study aimed to evaluate the viable stability of probiotic bacterial cells (Lactobacillus plantarum MG989, L. fermentum MG901, Streptococcus thermophilus MG5140, Lactococcus lactis MG5125, and Enterococcus faecium MG89-2) that were coated with sodium alginate and pumpkin powder (SP) by comparing their resistance in simulated intestinal fluid (with pancreatin) and simulated gastric fluid (with pepsin) in vitro with that of the non-coated free cells. The viable stability was determined by counting cells with colony forming unit (CFU) from agar plate culture of SP coated and non-coated free cells in simulated GI conditions. Survival rate enhanced up to 28.7% and 14.0% in the condition of simulated gastric fluid and simulated intestinal fluid, respectively. The results showed that the SP coated cells exhibited considerably greater resistance to the simulated gastric fluid than the activated cells (p < 0.001), showing that the SP coating may enhance the survival of probiotic bacteria after consumption during their transit through the GI tract after freeze-drying process.

An efficient protocol for multiple shoot induction and plant regeneration from axillary bud culture of Magnolia ‘Vulcan’ was developed in the present study. Primary shoots were obtained from axillary bud explants cultured on Murashige and Skoog (MS) medium containing 1.0 mg/L 6-benzylaminopurine (BA). To induce multiple shoots effectively, primary shoot tips were cultured on MS medium supplemented with different concentrations of BA and zeatin at 0, 0.2, 0.5, and 1.0 mg/L. Of these treatments, the MS medium with 0.5 mg/L BA resulted in the highest number of shoots per explant with an average value of 5.9, and it produced the greatest shoot height at 4.8 cm after 12 weeks of culturing. In the rooting of in vitro produced shoots, the greatest percentage of explants forming roots (91.3%), number of roots per explant (9.7), and root length (2.8 cm) were obtained in half-strength MS medium supplemented with 6.0 mg/L indole-3-butyric acid (IBA). Regenerated plantlets were successfully acclimatized and hardened off inside the culture room with 87.5% survival rate. Plants were transferred to a greenhouse with a 97.2% survival rate. The highly efficient shoot multiplication and plant regeneration system reported herein can be used for large-scale clonal propagation of valuable Magnolia species or cultivars.

Probiotic Gluconacetobacter strains are intestinal microbes with beneficial effects on human health. Recently, researchers have used these strains to biosynthesize metal and non-metal nanoparticles...

Background Glycemia is related to energy production during exercise. Coenzyme Q10 is an antioxidant that participates in adenosine triphosphate synthesis in mitochondria. The aim of this study was to investigate the level of coenzyme Q10, glucose parameters, and antioxidant capacity in athletes. Methods This study was designed as a cross-sectional study. Well-trained college athletes (n = 43) and age-gender matched healthy subjects (n = 25) were recruited from a college. The levels of glucose parameters, oxidative stress, antioxidant enzymes activity, Trolox equivalent antioxidant capacity (TAC), and coenzyme Q10 status were measured in the present study. Results The athletes had a significantly lower level of white blood cells (WBC) coenzyme Q10 than the healthy subjects (0.34 ± 0.24 vs. 0.65 ± 0.43 nmol/g, p

This study was to investigate the antioxidant and quality characteristics of madeleine prepared by various the amount of (0%, 3%, 5%, 7% and 10%) Citrus mandarin peel powder added. Moisture was higher in the supplemented groups added with Citrus peel powder than the control groups. The pH was significantly decreased with addition of the peel powder. The L value of the chromaticity decreased significantly as the powder addition increased, and the a and b values tended to increase. The hardness was significantly difference with the increase in the amount of Citrus mandarin peel powder added. In addition, the elasticity, cohesion, chewiness, and testability were significantly decreased with the increase in the amount of peel powder. DPPH radical scavenging activity and total flavonoid content, the addition of Citrus mandarin peel powder increased significantly. The addition of Citrus mandarin peel powder in madeleine had a lower increase in acid values for three weeks. In sensory evaluation, madeleine with the peel powder showed high aroma, texture, softness and taste and the 3% added group had the highest preference score in overall.

A practical and efficient approach for the total synthesis of arucadiol and 1-oxomiltirone is reported. The key step which involves an intramolecular [4+2] cycloaddition catalyzed by gold(III) bromide or copper(II) triflate leads to the formation of 6-6-6-fused aromatic abietane core.

Sleep fragmentation (SF) commonly occurs in several pathologic conditions and is especially associated with impairments of hippocampus-dependent neurocognitive functions. Although the effects of SF on hippocampus in terms of protein or gene levels were examined in several studies, the impact of SF at the metabolite level has not been investigated. Thus, in this study, the differentially expressed large-scale metabolite profiles of hippocampus in a rat model of SF were investigated using untargeted metabolomics approaches. Forty-eight rats were divided into the following 4 groups: 4-day SF group, 4-day exercise control (EC) group, 15-day SF group, and 15-day EC group (n = 12, each). SF was accomplished by forced exercise using a walking wheel system with 30-s on/90-s off cycles, and EC condition was set at 10-min on/30-min off. The metabolite profiles of rat hippocampi in the SF and EC groups were analyzed using liquid chromatography/mass spectrometry. Multivariate analysis revealed distinctive metabolic profiles and marker signals between the SF and corresponding EC groups. Metabolic changes were significant only in the 15-day SF group. In the 15-day SF group, L-tryptophan, myristoylcarnitine, and palmitoylcarnitine were significantly increased, while adenosine monophosphate, hypoxanthine, L-glutamate, L-aspartate, L-methionine, and glycerophosphocholine were decreased compared to the EC group. The alanine, aspartate, and glutamate metabolism pathway was observed as the common key pathway in the 15-day SF groups. The results from this untargeted metabolomics study provide a perspective on metabolic impact of SF on the hippocampus.

Aloe is widely used as a cosmetic and medicinal plant. Numerous studies have reported that aloe gel extract has antioxidant, anticancer, antidiabetic, immunity, and skin antiaging properties. However, few studies have investigated the properties of fermentation products of aloe processing byproducts. Aloe stalks and leaves remain as byproducts after the aloe beverage manufacturing process. This study evaluated whether fermentation products of blender and press extracts of aloe processing byproducts (BF and PF, respectively) that remain after beverage manufacturing were useful as functional biomaterial by investigating their effects on adipocyte differentiation, hyaluronic acid (HA) production, tyrosinase activity, and antioxidant activity. Co-fermentation of G. xylinus and S. cerevisiae was conducted for fermentation of aloe processing byproducts. The BF and PF products did not induce observable cytotoxicity effects. However, BF and PF products did inhibit a 3T3-L1 adipocyte differentiation compared with control, with the BF product displaying greater inhibition of 3T3-L1 adipocyte differentiation than the PF product. HA production increased in HaCaT cell cultures as the concentration of the MF product increased, as compared with the untreated control. The levels of tyrosinase inhibition, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, and superoxide dismutase (SOD)-like activity also depended on the MF product concentration. This study indicates that the fermented products of aloe processing byproducts have biological potential for applications in the manufacturing of cosmetics, pharmaceuticals, and beverages. These laboratory bench results provide the foundation for future studies of scaling and practical applications at the industrial level.

There is a lack of studies regarding the long-term outcomes of Asian adults with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. We hypothesized that adults with CAH are at higher metabolic risk than their age-, and sex-matched controls. We further investigated the long-term health outcome-related factors in adults with CAH. We compared metabolic risk between adults with CAH (71 men, 93 women) and age-, and sex-matched controls (190 men, 261 women) from the Korean National Health and Nutrition Examination Survey data. The presence of obesity, testicular adrenal rest tumors (TARTs), and menstrual irregularity was assessed. Hormone status and treatment regimens were compared according to the presence of adverse outcomes. The median age was 27.0 y and 28.0 y for men and women, respectively. Adults with CAH had a higher waist circumference (88.0 vs. 82.3 cm in men, and 83.5 vs. 72.3 cm in women), and blood pressure (125.0 vs. 113.0 mmHg in men, and 120.0 vs. 104.0 mmHg in women) than age- and sex-matched controls (PPP

Electroretinography (ERG) is an important and well-established examination for retinal and visual pathway diseases. This study reviewed the medical records of patients who received full-field ERG (ffERG) at a single medical center between 2012 and 2019, which was an 8-year experience in the clinical contribution of ERG. Based on the indication for scheduling ffERG and the final diagnosis, patients could be classified into six groups: ‘retinal dystrophies’, ‘other retinal or macular diseases’, ‘optic neuropathies’, ‘visual complaints’, ‘systemic diseases’, and ‘others’. A total of 1921 full-field electroretinograms (ffERGs) (1655 patients) were included. The average number of ffERGs performed per year was 262 and the number of annual ffERGs was constant. The ‘retinal dystrophies’ group accounted for 36.5% of the studied population, followed by the ‘other retinal or macular diseases’ group (20.2%). The most common systemic disease was central nervous system disease. The rates of abnormal ffERGs in the ‘systemic diseases’, ‘optic neuropathies’, and ‘visual complaints’ groups were 27.3%, 22.6%, and 10.1%, respectively (p &lt, 0.001). Higher rates were found in patients &lt, 20 years old in the ‘systemic diseases’ and ‘optic neuropathies’ groups, epilepsy and optic nerve atrophy were the most common diagnoses, respectively. In brief, by quantifying the functional response in the retina, ffERG is indispensable for diagnosis and prognosis in ophthalmologic and multidisciplinary practice.

Fipronil is a broad-spectrum insecticide widely used in agriculture and residential areas; its indiscriminate use leads to environmental pollution and poses health hazards. Early detection of fipronil is critical to prevent the deleterious effects. However, current insecticide analysis methods such as HPLC, LC/MS, and GC/MS are incompetent; they are costly, immobile, time-consuming, laborious, and need skilled technicians. Hence, a sensitive, specific, and cheap biosensor are essential to containing the contamination. Here, we designed two novel biosensors—the first design relied on fluorescent labeling/quenching, while the second sensor focused on label-free detection using Thioflavin T displacement. Altogether, we identified four candidate aptamers, predicted secondary structures, and performed 3D molecular modeling to predict the binding pocket of fipronil in FiPA6B aptamer. Furthermore, the aptameric sensors showed high sensitivity to fipronil of sub-ppb level LOD, attributed to stringent experimental design. The biosensors displayed high specificity against other phenylpyrazole insecticides and demonstrated robust sensitivity for fipronil in real samples like cabbage and cucumber. Notably, to the best of our knowledge, this is the first demonstration of noncanonical G4-quadruplex-like aptamer binding to fipronil, verified using CD spectroscopy. Such aptasensors possess considerable potential for real-time measurements of hazardous insecticides as point-of-care technology.

Fenitrothion is an insecticide belonging to the organophosphate family of pesticides that is widely used around the world in agriculture and living environments. Today, it is one of the most hazardous chemicals that causes severe environmental pollution. However, detection of fenitrothion residues in the environment is considered a significant challenge due to the small molecule nature of the insecticide and lack of molecular recognition elements that can detect it with high specificity. We performed in vitro selection experiments using the SELEX process to isolate the DNA aptamers that can bind to fenitrothion. We found that newly discovered DNA aptamers have a strong ability to distinguish fenitrothion from other organophosphate insecticides (non-specific targets). Furthermore, we identified a fenitrothion-specific aptamer, FenA2, that can interact with Thioflavin T (ThT) to produce a label-free detection mode with a Kd of 33.57 nM (9.30 ppb) and LOD of 14 nM (3.88 ppb). Additionally, the FenA2 aptamer exhibited very low cross-reactivity with non-specific targets. This is the first report showing an aptamer sensor with a G4-quadruplex-like structure to detect fenitrothion. Moreover, these aptamers have the potential to be further developed into analytical tools for real-time detection of fenitrothion from a wide range of samples.

Oxidative stress is a phenomenon caused by an imbalance between the production of reactive oxygen species and antioxidant defenses. It plays an important role in numerous disease states, including chronic kidney disease, neurological disorders, cardiovascular diseases, diabetes, and cancer. Lactic acid bacteria (LAB) are known to have prominent antioxidant properties. Therefore, this study aimed to measure the antioxidant activity and anti-inflammatory potential of LAB isolated from animals for the efficient use of probiotics with host specificity. Antioxidant activity measurements of sixteen strains revealed that ABTS radical scavenging activities ranged from 26.3 to 57.4%, and DPPH free radical scavenging activities ranged from 4.7 to 13.5%. Based on the antioxidant activity assessment, five strains (Enterococcus faecium MG9003(YH9003), Enterococcus faecium MG9007(YH9007), Lactobacillus reuteri MG9012(YH9012), Lactobacillus fermentum MG9014(YH9014), and Pediococcus pentosaceus MG9015(YH9015)) were selected with the consideration of fermentation productivity (>1 × 109 CFU/g). The selected strains exhibited nitric oxide inhibition and inhibited inducible nitric oxide synthase and cyclooxygenase expression. Furthermore, probiotic properties, including intestinal adhesion and stability, were identified. Our results show that the selected animal-derived strains can be effective probiotic candidates for potential effects on animal hosts.

The goal of this study was to develop a starter strain of Limosilactobacillus fermentum which is beneficial for human health and suitable for rice fermentation. To achieve the goal, the characteristics of 25 strains of L. fermentum were compared in terms of health promoting potentials and rice fermenting abilities. L. fermentum MG7011 was selected as a superior strain to meet the required properties. First, as probiotic traits, the strain had tolerance to gastrointestinal conditions and ability to adhere to Caco-2 and HT-29 cells. The strain showed the antioxidative activity, anti-inflammatory activity, and a protective effect on the epithelial barrier. Next, as starter traits for rice fermentation, MG7011 exhibited proper fermentation profiles in rice solution, such as fast growth rate, pH and metabolite changes, amylase and phytase activities, and optimal viscosity changes for beverage. In conclusion, L. fermentum MG7011 has excellent probiotic activities and proper starter traits in rice, thereby it can be used as a suitable probiotic starter for rice fermentation.

Air pollution-related particulate matter (PM) exposure reportedly enhances allergic airway inflammation. Some studies have shown an association between PM exposure and a risk for allergic rhinitis (AR). However, the effect of PM for AR is not fully understood. An AR mouse model was developed by intranasal administration of 100 μg/mouse PM with a less than or equal to 2.5 μm in aerodynamic diameter (PM2.5) solution, and then by intraperitoneal injection of ovalbumin (OVA) with alum and intranasal challenging with 10 mg/mL OVA. The effects of PM2.5 on oxidative stress and inflammatory response via the Nrf2/NF-κB signaling pathway in mice with or without AR indicating by histological, serum, and protein analyses were examined. PM2.5 administration enhanced allergic inflammatory cell expression in the nasal mucosa through increasing the expression of inflammatory cytokine and reducing the release of Treg cytokine in OVA-induced AR mice, although PM2.5 exposure itself induced neither allergic responses nor damage to nasal and lung tissues. Notably, repeated OVA-immunization markedly impaired the nasal mucosa in the septum region. Moreover, AR with PM2.5 exposure reinforced this impairment in OVA-induced AR mice. Long-term PM2.5 exposure strengthened allergic reactions by inducing the oxidative through malondialdehyde production. The present study also provided evidence, for the first time, that activity of the Nrf2 signaling pathway is inhibited in PM2.5 exposed AR mice. Furthermore, PM2.5 exposure increased the histopathological changes of nasal and lung tissues and related the inflammatory cytokine, and clearly enhanced PM2.5 phagocytosis by alveolar macrophages via activating the NF-κB signaling pathway. These obtained results suggest that AR patients may experience exacerbation of allergic responses in areas with prolonged PM2.5 exposure.

The purpose of this study was to evaluate the capacity of Lactiplantibacillus plantarum MG4296 (MG4296) and Lacticaseibacillus paracasei MG5012 (MG5012) on insulin resistance (IR) and diabetes-related metabolic changes in palmitic acid (PA)-induced HepG2 cells and high-fat diet-induced mice. In vitro, cell-free extracts of MG4296 and MG5012 alleviated IR by increasing glucose uptake and glycogen content in PA-induced insulin-resistant HepG2 cells. In vivo, MG4296 and MG5012 supplementation markedly decreased body weight and glucose tolerance. Administration of both strains also improved serum glucose, glycated hemoglobin, insulin, triglyceride, LDL/HDL ratio, and homeostatic model assessment of IR (HOMA-IR). Histopathological analysis of liver tissue demonstrated a significant reduction in lipid accumulation and glycogen content. Moreover, MG4296 and MG5012 treatment enhanced phosphoinositide-3 kinase (PI3K)/protein kinase B (Akt) expression in the liver. Overall, MG4296 and MG5012 could prevent HFD-induced glucose tolerance and hyperglycemia by improving IR. Therefore, L. plantarum MG4296 and L. paracasei MG5012 could be useful as new probiotics candidates to improve T2DM.

Megalin has been proposed as an endocytic receptor for aminoglycosides as well as estrogen and androgen. We aimed to investigate the otoprotective effects of antiandrogens (flutamide, FM) on kanamycin (KM)-induced hearing loss in rats. Rats were divided into four groups. The KM group was administered KM (20 mg/kg/day) for 5 days, while the FM group received FM (15 mg/kg/day) for 10 days. In the KM + FM group, KM and FM (15 mg/kg/day) were simultaneously injected for 5 days and then FM was injected for 5 days. Auditory brainstem responses were measured. Western blotting and/or quantitative reverse transcriptase-polymerase chain reaction were performed for megalin, cytochrome P450 1A1 (Cyp1a1), Cyp1b1, metallothionein 1A (MT1A), MT2A, tumor necrosis factor (TNF)-α, caspase 3, and cleaved caspase 3. The FM + KM group showed attenuated auditory thresholds when compared with the KM group at 4, 8, 16, and 32 kHz (all p &lt, 0.05). The KM + FM group showed lower megalin and Cyp1b1 levels than the KM group (all p &lt, 0.05). The KM + FM group revealed lower MT1A, TNFα, and caspase 3 protein levels, compared with those in the KM group (all p &lt, 0.05). Androgen receptor inhibition protects against cochlear injuries in KM-induced hearing loss rats by attenuating megalin expression, revealing anti-inflammatory and anti-apoptotic effects.

Dart1-24, one of the 37 autonomous DNA transposon Dart1s, was heritably activated by the demethylation of the 5' region following 5-azaC treatment of rice seeds. Transposons are controlled by epigenetic regulations. To obtain newly activated autonomous elements of Dart1, a DNA transposon, in rice, seeds of a stable pale yellow leaf (pyl-stb) mutant caused by the insertion of nDart1-0, a nonautonomous element in OsClpP5, were treated with 5-azaC, a demethylating agent. In the 5-azaC-treated M1 plants, 60-70% of the plants displayed variegated pale yellow leaf (pyl-v) phenotype, depending on the concentration of 5-azaC used, suggesting that inactivated Dart1 might become highly activated by 5-azaC treatment and nDart1-0 was excised from OsClpP5 by the activated Dart1s. Although the M2 plants derived from most of these pyl-v plants showed stable pyl phenotypes, some variegated M1 plants generated pyl-v M2 progeny. These results indicated that most M1 pyl-v phenotypes at M1 were not heritable. Dart1-24, 1-27 and 1-28 were expressed in the M2 pyl-v plants, and mapping analysis confirmed that Dart1-24 was newly activated. Further, the transgenerational activation of Dart1-24 was demonstrated to be caused by the demethylation of nucleotides in its 5' region.

In Artemisia annua plants, glandular trichomes (GTs) are responsible for the biosynthesis and secretion of sesquiterpene lactones including artemisinin/arteannuin B. Nonspecific lipid transfer proteins (LTPs) in plants bind and carry lipid molecules across the cell membrane and are also known as secretary proteins. Interestingly, the transcripts of LTP genes are exceptionally abundant in the GTs of A. annua. In the present study, we isolated two trichome-specific LTP genes (AaLTP3 and AaLTP4) from a Korean ecotype of A. annua. AaLTP3 was expressed abundantly in shoots, whereas AaLTP4 was expressed in flowers. The GUS signal driven by the AaLTP3 or AaLTP4 promoter in transgenic A. annua plants revealed that the AaLTP3 promoter was active on hair-like non-GTs and that the AaLTP4 promoter was active on GTs. Analysis of enhanced cyan fluorescent protein (ECFP) fluorescence fused with the AaLTP3 or AaLTP4 protein in transgenic tobacco revealed that ECFP florescence was very bright on secreted lipids of long GTs. Moreover, the florescence was also bright on the head cells of short trichomes and their secreted granules. Immunoblotting analysis of GT exudates in petioles of A. annua revealed a strong positive signal against the AaLTP4 antibody. Overexpression of AaLTP3 or AaLTP4 in transgenic A. annua plants resulted in enhanced production of sesquiterpene lactones (arteannuin B, artemisinin, dihydroartemisinic acid and artemisinic acid) compared with those of wild type. The present study shows that LTP genes (AaLTP3 or AaLTP4) play important roles in the sequestration and secretion of lipids in GTs of A. annua, which is useful for the enhanced production of sesquiterpene lactones by genetic engineering.

To explore the impact of macular ischaemia on vision in diabetic macular oedema (DMO) by analysing the correlations between visual acuity and macular microvascular parameters using optical coherence tomography angiography (OCTA). OCTA was performed in 81 eyes of 48 patients with DMO, and 3 × 3-mm2 en face OCTA images of the superficial capillary plexus and deep capillary plexus in the central macula were retrospectively collected. Microvascular parameters including the number of microaneurysms, area of foveal avascular zone (FAZ), acircularity index of FAZ, vessel density, skeleton density, vessel density index and fractal dimension were measured. Central retinal thickness (CRT) and the presence of ellipsoid zone disruption at the fovea were also recorded. Linear mixed models were used to evaluate the correlations between best-corrected visual acuity (BCVA) and the microvascular parameters. After adjustment for CRT and ellipsoid zone disruption at the fovea, lower skeleton density and lower fractal dimension in the deep capillary plexus were correlated with poorer BCVA (P = 0.030 and 0.024, respectively). None of the microvascular parameters of the superficial capillary plexus were correlated with BCVA after adjustment for CRT and ellipsoid zone disruption (all, P > 0.05). For eyes with DMO, low skeleton density and low branching complexity in the deep capillary plexus of central macula were correlated with poor vision. OCTA could offer quantified parameters of macular microvasculature to measure the impact of macular ischaemia on visual acuity in DMO.

Rates of microbial drug resistance are increasing worldwide; therefore, antimicrobial peptides (AMPs) are considered promising alternative therapeutic agents to antibiotics. AMPs are essential components of the innate immune system and exhibit broad-spectrum antimicrobial activity. P5 is a Cecropin A-Magainin 2 hybrid analog peptide with antimicrobial activity against Gram-negative and Gram-positive bacteria. In the present study, truncated peptides were designed to reduction length, retainment their antimicrobial activity and low toxicity at high concentrations compared with that of the parent peptide P5. The truncated peptides P5-CT1 and P5-NT1 exhibited antibacterial activities against both Gram-negative and Gram-positive bacteria. In contrast, P5-CT2, P5-CT3, P5-NT2, and P5-NT3 showed higher antibacterial activities against gram-positive bacteria compared to Gram-negative bacteria at low concentration of peptides. The truncated peptides showed lower hemolytic activity and toxic effects against mammalian cells compared with those of the parent peptide P5. The levels of several truncated peptides were maintained in the presence of physiological concentrations of salts, indicating their high stability. The results of flow cytometry, propidium iodide uptake, n-phenyl-1-naphthylamine uptake, and 3,3′-dipropylthiadicarbocyanine iodide assays showed that these truncated peptides killed microbial cells by increasing membrane permeability, thereby causing membrane damage. The results suggested that truncated peptides of P5 have good potential for use as novel antimicrobial agents.

Background: Clinical assessments of peripheral artery disease (PAD) severity are insensitive to pathophysiological changes in muscle tissue oxygenation and energy metabolism distal to the affected artery. Purpose: To quantify the blood oxygenation level-dependent (BOLD) response and phosphocreatine (PCr) recovery kinetics on a clinical MR system during a single exercise-recovery session in PAD patients. Study Type: Case–control study. Subjects: Fifteen Fontaine stage II patients, and 18 healthy control subjects. Field Strength/Sequence: Interleaved dynamic multiecho gradient-echo 1H T 2* mapping and adiabatic pulse-acquire 31P-MR spectroscopy at 3T. Assessment: Blood pressure in the arms and ankles were measured to determine the ankle-brachial index (ABI). Subjects performed a plantar flexion exercise-recovery protocol. The gastrocnemius and soleus muscle BOLD responses were characterized using the T 2* maps. High-energy phosphate metabolite concentrations were quantified by fitting the series of 31P-MR spectra. The PCr recovery time constant (τ PCr) was derived as a measure of in vivo mitochondrial oxidative capacity. Statistical Tests: Comparisons between groups were performed using two-sided Mann–Whitney U-tests. Relations between variables were assessed by Pearson's r correlation coefficients. Results: The amplitude of the functional hyperemic BOLD response in the gastrocnemius muscle was higher in PAD patients compared with healthy subjects (–3.8 ± 1.4% vs. –1.4 ± 0.3%; P < 0.001), and correlated with the ABI (r = 0.79; P < 0.001). PCr recovery was slower in PAD patients (τ PCr = 52.0 ± 13.5 vs. 30.3 ± 9.7 sec; P < 0.0001), and correlated with the ABI (r = –0.64; P < 0.001). Moreover, τ PCr correlated with the hyperemic BOLD response in the gastrocnemius muscle (r = –0.66; P < 0.01). Data Conclusion: MR readouts of calf muscle tissue oxygenation and high-energy phosphate metabolism were acquired essentially simultaneously during a single exercise-recovery session. A pronounced hypoxia-triggered vasodilation in PAD is associated with a reduced mitochondrial oxidative capacity. Level of Evidence: 2. Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:98–107.

Allergic rhinitis (AR) is an allergic nasal disease characterized by nasal obstruction, rhinorrhea, sneezing, and itching. Type 1 helper T cells (Th1)/type 2 helper T cells (Th2) imbalance has been identified as an important immunological mechanism of AR. In addition, up-regulation of type 17 helper T cells (Th17) also increase the risk of developing AR. Gallic acid (3, 4, 5-trihydroxybenzoic acid, GA), a polyphenol natural product, is obtained from various herbs, red wine, and green tea. It is known to have diverse biological effects such as anti-oxidation, anti-inflammation, anti-microbial and anti-cancer. In the present study, the effect of GA on airway inflammation and expression of Th1, Th2 and Th17 cytokines in an ovalbumin (OVA)-induced AR mouse model were investigated. GA alleviated the nasal allergic symptoms, reduced the thickness of nasal mucosa, attenuated goblet cell hyperplasia and eosinophil cell infiltration in the nasal mucosa, decreased the levels of interleukin (IL)-4, IL-5, IL-13 and IL-17 in nasal lavage fluid (NALF), and diminished the levels of OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a in serum. However, GA increased the expression of interferon-gamma and IL-12 in NALF. Taken together, it suggests that GA may be used as a therapeutic agent for AR.

Background/objectives Myopic traction maculopathy of the retinoschisis type is a unique entity that has been frequently overlooked in refraction correction in daily practice in myopic eyes. The objective of this study was to describe the imaging characteristics of myopic traction maculopathy (MTM) seen on optical coherence tomography angiography (OCTA) and to detect biomarkers of the associated functional changes. Subjects/methods We performed OCTA on eyes with MTM and retinoschisis (RS group; n = 27) and highly myopic eyes without MTM (control group; n = 27). The RS group was further divided into a dome-shaped macula (DSM) group and a non-DSM group. The groups were compared for morphologic and perfusion characteristics. Results The RS and control groups had comparable spherical equivalence (p = 0.65), but the RS group had worse best-corrected visual acuity (p

Objectives Clinical manifestations of lipoid pneumonia (LP) vary depending on the causative agents or underlying causes. The aim of the present study was to investigate the clinical and radiological features of LP, classified according to etiologic agents. Methods The clinico-radiological characteristics of LP patients were retrospectively compared among groups: exogenous versus idiopathic and squalene versus omega-3-acid ethyl esters (O-3-AEE) versus idiopathic. Idiopathic group was defined as LP with no proven or reported etiological evidence. Results Twenty-two patients met the diagnostic criteria for LP: squalene (9 [41%]), O-3-AEE (6 [27%]), olive oil (1 [5%]), and idiopathic (7 [32%]). Compared with the exogenous group, the idiopathic group showed a higher recurrence rate; higher frequencies of bronchial anthracofibrosis (BAF) and bronchoalveolar lavage (BAL) lymphocytosis; and a higher rate of crazy-paving pattern and lower rate of consolidation on computed tomography scan. In three-group tests, compared with the O-3-AEE group, the squalene group exhibited a significantly higher percentage of neutrophils and a higher rate of right middle lobe (RML) involvement. Conclusions In comparison with the exogenous group, the idiopathic group demonstrated BAL lymphocytosis, higher rates of recurrence and BAF, and a higher rate of crazy-paving pattern. Compared with the O-3-AEE group, the squlaene group showed a higher percentage of BAL neutrophils and predominant RML involvement.

Ethnopharmacological relevance Dryopteris crassirhizoma (DC) is used as a traditional herbal remedy to treat various diseases, the tapeworm infection, common cold, and cancer in Korea, Japan, and China. DC also has the antioxidant anti-inflammatory and antibacterial activities. However, the anti-allergic inflammatory effect of DC and some of its mechanisms in allergic rhinitis model are unknown well. Aim of this study The purpose of this study is to investigate the anti-allergic inflammatory effect of DC on the allergic rhinitis model, mast cell activation and histamine release. Materials and methods Allergic rhinitis was induced in BALB/c mice by sensitization and challenge with ovalbumin (OVA). Different concentration of DC and dexamethasone was administrated by oral gavage on 1 h before the OVA challenge. Mice of the control group were treated with saline only. Then mice were evaluated for the presence of nasal mucosa inflammation, the production of allergen-specific cytokine response and the histology of nasal mucosa. Results DC significantly ameliorated the nasal symptoms and the inflammation of nasal mucosa. DC also reduced the infiltration of eosinophils and mast cells in these tissues and the release of histamine in blood. Meanwhile, DC evidently inhibited the overproduction of Th2 cytokines and increased the Th1 and Treg cytokines in nasal lavage fluid by OVA. DC also reduced the levels of OVA-specific IgE, IgG1 and IgG2a in blood. Conclusions This study suggests that DC has a significant anti-allergic inflammatory effect in the nasal cavity. DC may have the therapeutic effect of allergic rhinitis.

The widespread presence of organic pollutants in water resources poses potentially grave health and environment problems. Oxidation processes, which involve in situ generation of reactive oxidant species, are widely employed to treat and remove the pollutants. The conventional advanced oxidation processes (AOPs) typically utilize energy sources and/or additives including catalysts, but the treatment time is still too long. Here, we devise a novel fluidic sonolysis system with a superhydrophobic Si nanowire structured channel, providing an air-water interfacial cavitation for efficient generation of OH· that is promoted by the structure itself without any additional energy inputs or additives. The system removes various organic pollutants including 4-chlorophenol, bisphenol A, carbamazepine and propranolol completely within 12 min, as opposed to hours needed by other AOPs. These results substantiate the promise of the air-water interfacial fluidic sonolysis system for fast and continuous-flow water treatment.

Although major adverse effects associated with nonsteroidal anti-inflammatory drugs (NSAIDs) are gastric injury, assessment of NSAIDs-induced gastrointestinal adverse effects is mostly dependent on endoscopy due to the lack of plasma biomarkers. Several amino acids associated with collagenase activity and gastric mucosal mass have been suggested as plasma biomarker candidates for gastric injury. Therefore, this study aimed to develop a liquid chromatography-tandem mass spectrometry (LC–MS/MS) method for the plasma biomarker candidates, i.e., acetylcarnitine, proline, hydroxyproline, citrulline, and arginine and evaluate their potential as a biomarker for NSAIDs-induced gastric injury. The method utilized simple protein precipitation with methanol and D4-citrulline as an internal standard (IS). The assay resulted in the lower limit of quantification (LLOQ) of 0.1 μg/mL for acetylcarnitine and 1 μg/mL for proline, hydroxyproline, citrulline, and arginine in the surrogate blank plasma. The intra- and inter-day accuracy ranged 82.5–111.2% for acetylcarnitine, 95.4–103.3% for proline, 98.9–106.4% for hydroxyproline, 99.5–103.5% for citrulline, and 87.4–105.3% for arginine. The precision was within 6.17%, 3.63%, 6.20%, 6.31%, and 6.17% for acetylcarnitine, proline, hydroxyproline, citrulline, and arginine, respectively. The developed assay was successfully applied to monitor the changes of the plasma levels of the five amino acids in rats and Beagle dogs following repeated oral administrations of aceclofenac. In rats, plasma concentrations of proline, hydroxyproline, and citrulline were significantly reduced after 4 days of aceclofenac administration compared to the control group. In dogs, plasma concentrations of proline and citrulline were significantly decreased after 7 days of aceclofenac administration compared to those obtained after the first aceclofenac administration. These data indicate that plasma levels of proline, hydroxyproline, and citrulline may be used as quantitative biomarkers of NSAIDs-induced gastric damage. The present assay could also be utilized to monitor the changes of these amino acids as potential indicators for various physiological and pathophysiological conditions.

Though p-xylene derived from naphtha reformate is in high demand as a raw material in the production of polyesters and polyethylene terephthalates, its separation from the FCC reformate is not easy due to close boiling points among the components in the reformate. When a proper solvent for the p-xylene separation is available, an extractive distillation can be applied in the separation. Currently the separation utilizes an adsorption process requiring a large amount of costly adsorbent and a desorption process followed by distillation. In the proposed extractive distillation here, p-dinitrobenzene has been utilized to improve the separation of p-xylene from its ethylbenzene mixture. The VLE data of the ternary mixture estimated with the UNIFAC were compared to those computed from molecular simulation to show their reliability. An extractive distillation and solvent recovery were applied to obtain 99.6% purity p-xylene with 99.1% recovery. The economics of the proposed process demonstrates its comparability to the existing Parex process.

The occurrence of dental caries is mainly associated with oral pathogens, especially cariogenic Streptococcus mutans and Porphyromonas gingivalis. The objective of this study was to investigate antimicrobial activity against cariogenic associated pathogens, acid tolerance, bile salt tolerance, and autoaggregation of 12 presumptive Lactobacillus spp. isolated from human and fermented foods. Five strains were selected after qualitatively identifying high levels of antimicrobial activity against bacteria including S. mutans. Results show that selected strains survivability was tested in bile salt and acidic conditions to show their potential use as probiotics in the gastrointestinal tract. Indirect adhesion activity of selected strains measured by autoaggregation assay showed more than 60% autoaggregation after 5 h standing. Further studies are underway to demonstrate that the selected strains can be applied as potential probiotics for recovering oral ecosystem.

We previously developed a novel series of vinyl sulfones as nuclear factor erythroid 2-related factor 2 (Nrf2) activators with therapeutic potential for Parkinson’s disease (PD). However, the previously developed lead compound (1) exhibited undesirable druglike properties. Here, we optimized vinyl sulfones by introducing nitrogen heterocycles to improve druglike properties. Among the synthesized compounds, 17e was the most promising drug candidate with good druglike properties. Compound 17e showed superior effects on Nrf2 activation in cell-based assays compared to compound 1 (17e: half-maximal effective concentration (EC50) = 346 nM; 1: EC50 = 530 nM). Compound 17e was further confirmed to induce expression of Nrf2-dependent antioxidant enzymes at both mRNA and protein levels. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD, 17e significantly attenuated loss of tyrosine hydroxylase-immunopositive dopaminergic neurons, suppressed microglial activation, and alleviated PD-associa...

The R&D on SiC/SiC composites under the broader approach (BA) activities between Japan and the EU for fusion DEMO developed a fundamental database of mechanical (Task-1) and physical/chemical (Task-2) properties, with a primary target of the application of SiC/SiC composites as functional structure to be used in the dual coolant breeding blanket concept. This paper aims to summarize previous 10-years activities of the R&D of Japan and to provide the key deliverables toward the DEMO design. In Task-1, good creep and fatigue durability were first demonstrated. Besides, in-plane and inter-laminar strength anisotropy maps at elevated temperatures were comprehensively identified. In parallel, the irradiation effects of SiC materials were specifically determined as input parameters of the analytical model to provide for the irradiation-induced residual stresses. In Task-2, the apparent dose-dependence of the radiation-induced electrical conductivity and the indicative radiation-induced electrical degradation was identified by various irradiation sources. In addition, good gas confinement was identified. Furthermore, no accelerated corrosion for duration of 3000 h at below 1173 K was first demonstrated. With these achievements, it is suggested that the in-vessel component technology, e.g., material corrosion database development, activated corrosion product evaluation code development, compact module tests for validation of the key functions of the components, technology integration assessment for fusion nuclear tests, etc., should be further developed toward DEMO in near-term.

The lead-lithium (Pb-Li) alloy is considered as a coolant and a tritium breeder for fusion reactor blanket systems. One of the critical requirements in realization of the systems is the compatibility of silicon carbide (SiC) and its composites, as structural and/or functional materials of the blanket, with liquid Pb-Li flow at high temperatures. This study aims to clarify the corrosion process of high-purity SiC materials under flow condition of liquid Pb-Li for 3000 h at 700 and 900 °C, respectively, by using the rotating disc corrosion equipment. Furthermore, the effect of wall flow velocity on the compatibility was specifically evaluated. For that purpose the decrease rate (about 32–37%) of the wall flow velocity on disc type’s sample by the dragging effect by fluidic viscosity was first calculated by numerical analysis of the rotating flow condition. The wall flow velocity dependence on the reaction layer’s thickness was then evaluated for both high purity SiC and SiC/SiC composites. The test results show that the formation process of the surface reaction layer mainly depends on both the time required for the chemical reaction and the wall flow velocity in the initial stage but the reaction layer thickness tended to approach to the constant regardless of the wall flow velocity with increasing exposed time. In short, no accelerated corrosion was found for about 3000 h. It was also found that there was no significant difference of the temperatures between 700 and 900 °C. Finally the key corrosion mechanism, i.e., the reaction of oxide impurities, e.g., Li2O, in liquid Pb-Li with the Si-oxide layer over SiC, was identified.