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To obtain superior surface-active properties while minimizing environmental risks, new fluorinated surfactants (F2HX-nEO) were designed to include a hybrid multi-chain with a short fluorocarbon (–CF2CF3) and nonionic ethylene oxide. They were simply synthesized by a straightforward reaction involving the addition of ethylene oxide to a hybrid fluorine alcohol, and their surface-active properties were optimized by controlling the hydrocarbon length and number of ethylene oxide units. Therefore, the desirable values of critical micelle concentration (0.3 mmol/L) and surface tension (24.3 mN/m) were obtained in spite of containing the short fluorocarbon chain. Particularly, F2HX–nEO showed excellent wetting properties on hydrophobic surfaces and very low toxicity level, which can be used in various fields as a promising alternative to long fluoroalkyl chain surfactants.

The interception of exotic ants and termites from stone and lumber imported into Korea is on the rise, including Solenopsis invicta. Currently, a relatively long exposure (24 h) of methyl bromide (MB) fumigation is the only practical disinfestation option for exotic ants and termites on imported stone and lumber. In this study, ethyl formate (EF) wase evaluated as a potential MB alternative to disinfest ants and termites in imported lumber, with a focus on S. invicta. As S. invicta is not established in Korea, we first determined whether Reticulitermes speratus, established in Korea, could be considered as an EF surrogate of S. invicta. From 1 h EF fumigation trials, workers of S. invicta were more sensitive to EF than those of R. speratus based on lethal concentration × time causing 99% mortality (LCt99%), supporting that R. speratus can be used as an EF surrogate of S. invicta. When R. speratus workers were further fumigated with EF for 4 h at four different temperatures, LCt99% values for R. speratus workers were 108.00, 63.31, 77.24, and 67.24 g h/m3 at 2, 5, 13, and 23 °C, respectively. From scale-up (0.65 m3) and commercial scale (76.4 m3) trials containing two infestation-prone lumber species, lauan (Shorea spp.) and acacia (Acacia spp.), 140 g/m3 EF at >5 °C for 4 h resulted in the complete control of R. speratus workers, suggesting that 140 g/m3 4 h-EF-fumigation may be applicable as a potential MB-alternative treatment for disinfestation of invasive S. invicta on imported lumber.

Purpose Translocator protein 18-kDa (TSPO) positron emission tomography (PET) is a valuable tool to detect neuroinflammed areas in a broad spectrum of neurodegenerative diseases. However, the clinical application of second-generation TSPO ligands as biomarkers is limited because of the presence of human rs6971 polymorphism that affects their binding. Here, we describe the ability of a new TSPO ligand, [18F]BS224, to identify abnormal TSPO expression in neuroinflammation independent of the rs6971 polymorphism. Methods An in vitro competitive inhibition assay of BS224 was conducted with [3H]PK 11195 using membrane proteins isolated from 293FT cells expressing TSPO-wild type (WT) or TSPO-mutant A147T (Mut), corresponding to a high-affinity binder (HAB) and low-affinity binder (LAB), respectively. Molecular docking was performed to investigate the interaction of BS224 with the binding sites of rat TSPO-WT and TSPO-Mut. We synthesized a new 18F-labeled imidazopyridine acetamide ([18F]BS224) using boronic acid pinacol ester 6 or iodotoluene tosylate precursor 7, respectively, via aromatic 18F-fluorination. Dynamic PET scanning was performed up to 90 min after the injection of [18F]BS224 to healthy mice, and PET imaging data were obtained to estimate its absorbed doses in organs. To evaluate in vivo TSPO-specific uptake of [18F]BS224, lipopolysaccharide (LPS)-induced inflammatory and ischemic stroke rat models were used. Results BS224 exhibited a high affinity (Ki = 0.51 nM) and selectivity for TSPO. The ratio of IC50 values of BS224 for LAB to that for HAB indicated that the TSPO binding affinity of BS224 has low binding sensitivity to the rs6971 polymorphism and it was comparable to that of PK 11195, which is not sensitive to the polymorphism. Docking simulations showed that the binding mode of BS224 is not affected by the A147T mutation and consequently supported the observed in vitro selectivity of [18F]BS224 regardless of polymorphisms. With optimal radiochemical yield (39 ± 6.8%, decay-corrected) and purity (> 99%), [18F]BS224 provided a clear visible image of the inflammatory lesion with a high signal-to-background ratio in both animal models (BPND = 1.43 ± 0.17 and 1.57 ± 0.37 in the LPS-induced inflammatory and ischemic stroke rat models, respectively) without skull uptake. Conclusion Our results suggest that [18F]BS224 may be a promising TSPO ligand to gauge neuroinflammatory disease-related areas in a broad range of patients irrespective of the common rs6971 polymorphism.

Drought stress is one of the major constraints for soybean growth and productivity worldwide. The study was aimed to investigate drought-induced physiological and proteomic changes in soybeans, as well as drought relief using exogenous hydrogen peroxide (H2O2). In drought-stressed plants, H2O2 spray on the leaf surface improved relative water content (RWC), net photosynthetic rate (Pn), and stomatal conductance (Gs). Furthermore, exogenous H2O2 reduced drought stress-induced endogenous MDA and H2O2 levels, as well as increased the key antioxidant enzymes (SOD,CAT, APX and POD) activity and proline content in H2O2-treated soybean plants. These findings showed that H2O2 treatment significantly reduced drought stress by increasing the antioxidative defense system and osmotic adjustment. Furthermore, using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, a total of 27 differently expressed proteins was identified, wherein 23 were up-regulated and 4 were down-regulated under drought condition. These proteins were found to be involved in photosynthesis, energy and metabolism, plant defense and antioxidant, signaling and transport, and transcription regulation in response to H2O2 treatment in soybean under drought stress, according to in silico interactome analysis. These findings add to our understanding of H2O2-mediated drought stress alleviation, as well as the physiological and molecular responses of soybean to drought stress.

Developmentally regulated GTP-binding protein 2 (DRG2) participates in the regulation of proliferation and differentiation of multiple cells. However, whether DRG2 regulates adipocyte differentiation and related metabolic control remains elusive. This study revealed increases in body weight and adiposity in DRG2 transgenic (Tg) mice overexpressing DRG2. Consistent with these results, DRG2 Tg mice showed increased expression of genes involved in adipogenesis and lipid metabolism in the white adipose tissue. DRG2 was also identified to control adipogenesis by cooperating with peroxisome proliferator activated receptor-γ (PPAR-γ) in cultured adipocytes. Overall, the findings of the current study suggest that DRG2 plays an active role in regulating adipocyte differentiation, and thus participates in the development of obesity during exposure to a fat-rich diet.

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that exhibit multiple extraglycemic effects. However, there are conflicting results regarding the effects of SGLT2 inhibition on energy expenditure and thermogenesis. Therefore, we investigated the effect of ipragliflozin (a selective SGLT2 inhibitor) on energy metabolism.Methods: Six-week-old male 129S6/Sv mice with a high propensity for adipose tissue browning were randomly assigned to three groups: normal chow control, 60% high-fat diet (HFD)-fed control, and 60% HFD-fed ipragliflozin-treated groups. The administration of diet and medication was continued for 16 weeks.Results: The HFD-fed mice became obese and developed hepatic steatosis and adipose tissue hypertrophy, but their random glucose levels were within the normal ranges; these features are similar to the metabolic features of a prediabetic condition. Ipragliflozin treatment markedly attenuated HFD-induced hepatic steatosis and reduced the size of hypertrophied adipocytes to that of smaller adipocytes. In the ipragliflozin treatment group, uncoupling protein 1 (Ucp1) and other thermogenesis-related genes were significantly upregulated in the visceral and subcutaneous adipose tissue, and fatty acid oxidation was increased in the brown adipose tissue. These effects were associated with a significant reduction in the insulin-to-glucagon ratio and the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver and adipose tissue.Conclusion: SGLT2 inhibition by ipragliflozin showed beneficial metabolic effects in 129S6/Sv mice with HFD-induced obesity that mimics prediabetic conditions. Our data suggest that SGLT2 inhibitors, through their upregulation of energy expenditure, may have therapeutic potential in prediabetic obesity.

Purpose: To evaluate the associations of fluorescein angiographic findings with recurrence of human leukocyte antigen (HLA)-B27-associated anterior uveitis.Methods: Medical records of 56 eyes of 56 patients with first-onset, treatment-naive HLA-B27-associated anterior uveitis who performed fluorescein angiography was analyzed. We recorded the fluorescein angiographic findings of optic disc and peripheral vascular leakage and anterior chamber inflammation at the first visit. The 1-year recurrences and times to the first recurrences and the associations between them were investigated.Results: Fluorescein angiography revealed optic disc leakage in 23 patients (41.1%) and peripheral vascular leakage in 36 (64.3%). We found no significant association between the anterior chamber inflammation grade and either optic disc (p = 0.841) or peripheral vascular (p = 0.775) leakage. The 1-year recurrence rate in the optic disc leakage-positive group was significantly higher than in the leakage-negative group (14 patients, 60.9% vs. 11 patients, 33.3%) (p = 0.041), but peripheral vascular leakage status did not significantly affect the recurrence rate (19 leakage-positive patients, 52.8% vs. 8 leakage-negative patients, 40.0%) (p = 0.602). The time to first recurrence was not significantly associated with age (p = 0.772), anterior chamber inflammation (p = 0.841), optic disc leakage (p = 0.108), or systemic corticosteroid use (p = 0.321).Conclusions: We sought correlations between angiographic leakage in patients with HLA-B27-associated anterior uveitis, and the 1-year recurrence rate and the time to first recurrence. Careful follow-up for at least 1 year after initial diagnosis is essential to monitor possible recurrence in patients with optic disc leakage.

Ethyl formate (EF) was evaluated as a potential alternative to methyl bromide (MB) for phytosanitary treatment of imported citrus fruit in the Republic of Korea. Planococcus citri (Risso) (Hemiptera: Pseudococcidae), a mealybug with known tolerance against EF and MB, was used as a representative pest to test efficacy of the two fumigants against eggs. In nine commercial-scale refrigerated container (67.5 m3) trials using imported orange, lemon and grapefruit, EF applied at the currently approved dose for citrus (70 g·m-3 at 5°C for 4 h, developed for Aspidiotus excisus Green (Hemiptera: Diaspididae), a species less EF tolerant than P. citri) resulted in 76.9–98.3% mortality of P. citri eggs. The EF treatment did not affect the sugar content or the color of peel and pulp of the treated fruit. When oranges were treated according to the current MB (64 g·m-3 at >5°C for 2 h) or EF treatment guidelines, the concentration of fumigant around the fruit fluctuated between 9.4 and 185.1 ppm for EF and 9.5–203.0 ppm for MB during the 72-h post-fumigation processes (venting [0–2 h], transportation to storage [2–24 h], and storage periods [24–72 h]) with both EF and MB maintained between 10 and 100 ppm during the storage period. Considering the efficacy of EF, its apparent lack of phytotoxicity, and its more manageable threshold limit value for humans (100 ppm EF compared to 1 ppm MB for an 8-h time weighted average exposure), our results suggest that EF may be a promising alternative to MB for the phytosanitary treatment of imported citrus in Korea.

Fumigation of fruits and vegetables during quarantine and pre-shipment (QPS) treatment should be effective with a shorter fumigation time to minimize phytotoxicity. In this research study, a shorter fumigation time, 2 hours exposure which is shorter than that of the current commercial fumigation procedures using a lower dose of ethyl formate (EF) mixed with phosphine (PH3) on strawberry was investigated. The reciprocal effect between EF and PH3 against nymphs and adult Myzus persicae (Sulzer) and Tetranychus urticae (Koch) was evaluated. In addition, L(Ct)50 and L(Ct)99 of EF only and EF mixed with PH3 were analyzed at 5°C and 20°C. The synergistic ratio (SR) of L(Ct)50 and L(Ct)99 for the nymph and adult stages of M. persicae were >1.0, which indicated a synergistic effect between EF and PH3. However, the SR values of L(Ct)50 and L(Ct)99 of the nymph and adult stages of T. urticae were ≤1.0 indicating that there was no synergistic effect between the two fumigants against T. urticae. Our results showed that the reciprocal effect between EF and PH3 has different effects on M. persicae and T. urticae. This could be attributed to the biological and physical differences between the class Arachnida and Insecta. The synergistic effect between EF and PH3 against M. persicae within a shorter exposure period and without phytotoxicity on fruits and vegetables will significantly benefit the horticultural industry.

Background Gintonin, isolated from ginseng, acts as a ginseng-derived lysophosphatidic acid (LPA) receptor ligand and elicits the [Ca2+]i transient through six LPA receptor subtypes (LPARSs). However, the long-term effects of gintonin-enriched fraction (GEF) on the gene expression of six LPARSs remain unknown. We examined changes in the gene expression of six LPA receptors in the mouse whole brain, heart, lungs, liver, kidneys, spleen, small intestine, colon, and testis after long-term oral GEF administration. Methods C57BL/6 mice were divided into two groups: control vehicle and GEF (100 mg/kg, p.o.). After 21-day saline or GEF treatment, total RNA was extracted from nine mouse organs. Quantitative-real-time PCR (qRT-PCR) and western blot were performed to quantify changes in the gene and protein expression of the six LPARSs, respectively. Results qRT-PCR analysis before GEF treatment revealed that the LPA6 RS was predominant in all organs except the small intestine. The LPA2 RS was most abundant in the small intestine. Long-term GEF administration differentially regulated the six LPARSs. Upon GEF treatment, the LPA6 RS significantly increased in the liver, small intestine, colon, and testis but decreased in the whole brain, heart, lungs, and kidneys. Western blot analysis of the LPA6 RS confirmed the differential effects of GEF on LPA6 receptor protein levels in the whole brain, liver, small intestine, and testis. Conclusion The LPA6 receptor was predominantly expressed in all nine organs examined; long-term oral GEF administration differentially regulated LPA3, LPA4, and LPA6 receptors in the whole brain, heart, lungs, liver, kidneys, small intestine, and testis., Graphical abstract Image 1

Bifidobacterium bifidum BGN4 has been shown to improve the immune system by regulating interleukin (IL)-6 in RAW 264.7 macrophage cells. In this study, the dead cells of B. bifidum BGN4 were produced by enzymatic and physical processing to enhance the inhibition properties of pro-inflammatory cytokines using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Notably, the secretion levels of cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α were decreased by the cell-wall disrupted extracts compared to heat-killed cells. The result suggests that the exposed interior-surface of B. bifidum BGN4 has a potential ability to regulate the immune-responses in the gastrointestinal tract due to major substances in inside-cell wall such as peptidoglycan and teichoic acids. In conclusion, the lysed and disrupted cells from the inside out of B. bifidum BGN4 have anti-inflammatory properties as paraprobiotic agents to control chronic inflammatory related-diseases.

Sodium-tungsten-manganese supported on silica (Na-W-Mn/SiO2) and hydroxyapatite (HAp) are representative catalysts for oxidative coupling of methane (OCM). In this work, the effect of the HAp doping in a Na-W-Mn/SiO2 catalysts on the OCM performance was studied. To enhance the ethylene selectivity of the Na-W-Mn/SiO2 catalyst, silica supports were coated with HAp containing hydroxyl and phosphate groups as oxygen species. A series of Na-W-Mn/xHAp_SiO2 (x=1, 3, 5 and 7) catalysts with the different HAp coating cycles were prepared through the alternative soaking method, and X-ray diffraction (XRD) and scanning electron microscopy (SEM) showed that the amount of HAp doping was dependent on the HAp coating cycles. In addition, the change of oxygen species upon HAp doping was examined with X-ray photoelectron spectroscopy (XPS) and oxygen temperature-programmed desorption (O2-TPD) techniques. With HAp doping, the increase of oxygen species assigned to metal oxide responsible for selective oxidation of methane to ethylene was observed in O 1s XPS spectra. In addition, weakly bound oxygen species were observed with the introduction of HAp doping in O2-TPD profiles of prepared catalysts. The influence of these oxygen species on OCM catalytic performance was evaluated at an operating temperature of 775 °C and gas hourly space velocity of 18,000 ml/gcat·h. The amount of HAp doping provided reactive oxygen species for oxidative dehydrogenation of ethane, which resulted in as much as 120% increase in C2H4/C2H6 ratio over the Na-W-Mn/3HAp_SiO2 catalyst compared to the Na-W-Mn/SiO2 catalyst.

Background This case report presents a case of Vulvar Crohn’s disease (VCD) in an adolescent, that is an uncommon manifestation of Crohn’s disease (CD) without gastrointestinal symptoms. Before treating CD itself with proper medication, vulvar abscess continued to recur without improvement. Case presentation We report the case of an 18-year-old woman with VCD. After treatment with azathioprine 50 mg daily and mesalazine 1 g three times daily, vulvar lesions resolved after 6 weeks. We collected electronic medical data on patient characteristics, and evaluated findings of physical examinations, pelvic MRI, and biopsy specimen obtained from gastroduodenoscopy/colonoscopy. Conclusions VCD is a rare manifestation of CD that may be misdiagnosed in the absence of gastrointestinal symptoms leading to delayed treatment. If a patient has an unexplained vulvar inflammatory lesion and with repeated failed surgical treatment, gynecologists should consider the possibility of a VCD.

Enhancing therapeutic efficacy of drugs from reactive oxygen species (ROS) and glutathione (GSH)-responsive matrix and minimizing toxic effects on normal cells remains a challenge in programmable anticancer drug delivery. Herein, ROS- and GSH-responsive paclitaxel (PTX)-loaded polymer dot (PD) with mitochondria-targeting capability was designed by constructing diselenide linkage and triphenylphosphonium (TPP) for tunable PTX release and fluorescence for cancer theranostics. PD-TPP nanocarrier could improve the PTX stability after loading (PD-TPP(PTX)), and the cleavage of diselenide bond in the presence of H2O2 and GSH triggered the controllable PTX release, providing higher fluorescence intensity. As the levels of H2O2 and GSH are higher in cancer cells compared to normal cells, PTX was selectively released from PD-TPP in cancer cells, reducing cell viability (∼25%) and causing enhanced apoptosis of cancer cells compared to normal cells. The PD-TPP(PTX) selectivity was also reflected by distinct fluorescence intensity in HeLa and PC-3 cells (cancer) compared to CHO-K1 cells (normal). Furthermore, conjugated TPP promoted the PD-TPP(PTX) accumulation in mitochondria due to specific targeting of TPP towards mitochondria, allowing PTX release in mitochondria of cancer cells. Hence, this approach could be a potential strategy to enhance therapeutic efficacy of cancer drugs and minimize the side effects on normal cells.

PURPOSE: Patients with triple negative breast cancer (TNBC) who do not achieve pathological complete response (pCR) following neoadjuvant chemotherapy have a high risk of recurrence and death. Molecular characterization may identify patients unlikely to achieve pCR. This neoadjuvant trial was conducted to determine the pCR rate with docetaxel and carboplatin, and to identify molecular alterations and/or immune gene signatures predicting pCR. EXPERIMENTAL DESIGN: Patients with clinical stages II/III TNBC received 6 cycles of docetaxel and carboplatin. The primary objective was to determine if neoadjuvant docetaxel and carboplatin would increase the pCR rate in TNBC compared to historical expectations. We performed whole exome sequencing (WES) and immune profiling on pre-treatment tumor samples to identify alterations that may predict pCR. Thirteen matching on-treatment samples were also analyzed to assess changes in molecular profiles. RESULTS: Fifty-eight of 127 (45.7%) patients achieved pCR. There was a non-significant trend towards higher mutation burden for patients with residual cancer burden (RCB) 0/I versus RCB II/III (median 80, versus 68 variants, p 0.88). TP53 was the most frequently mutated gene, observed in 85.7% of tumors. EGFR, RB1, RAD51AP2, SDK2, L1CAM, KPRP, PCDHA1, CACNA1S, CFAP58, COL22A1, and COL4A5 mutations were observed almost exclusively in pre-treatment samples from patients who achieved pCR. Seven mutations in PCDHA1 were observed in pre-treatment samples from patients who did not achieve pCR. Several immune gene signatures including IDO1, PD-L1, interferon gamma signaling, CTLA4, cytotoxicity, tumor inflammation signature, inflammatory chemokines, cytotoxic cells, lymphoid, PD-L2, exhausted CD8, Tregs, and immunoproteosome were upregulated in pre-treatment samples from patients who achieved pCR. CONCLUSIONS: Neoadjuvant docetaxel and carboplatin resulted in a pCR of 45.7%. WES and immune profiling differentiated patients with and without pCR. TRIAL REGISTRATION: Clinical trial information: NCT02124902, Registered 24 April 2014, & NCT02547987, Registered 10 September 2015.

Sickness symptoms exerted via inflammatory responses occur in several infectious and chronic diseases. A growing body of evidence suggests that altered nutrient availability and metabolism are tightly coupled to inflammatory processes. However, the relationship between metabolic shifts and the development of the sickness response has not been explored fully. Therefore, we aimed to evaluate metabolic phenotypes with a mouse model showing sickness symptoms via systemic administration of lipopolysaccharide (LPS) in the present study. LPS injection elevated the lipid utilization and circulating levels of fatty acids. It also increased the levels of β-hydroxybutyric acid, a ketone body produced from fatty acids. We confirmed the functional connectivity between nutrient utilization and inflammatory responses and demonstrated enhanced lipid utilization in the hypothalamus providing insights into hypothalamic control of sickness responses. Collectively, these findings could help develop new therapeutic strategies to treat patients with severe sickness symptoms associated with infectious and chronic human diseases.

Purpose To investigate the long-term progression of pericentral hydroxychloroquine retinopathy. Design Multicenter, retrospective cohort study. Participants Eighty eyes (60 with pericentral pattern) of 41 Korean patients with hydroxychloroquine retinopathy followed up for 2 years or more after drug cessation. Methods Patients were screened for hydroxychloroquine retinopathy using spectral-domain or swept-source OCT, fundus autofluorescence (FAF), and Humphrey visual field (VF) tests. Follow-up was divided into short-term (≤2 years) and subsequent periods, and progression was evaluated in each period and severity group. Retinopathy progression on OCT was defined as increased length of the ellipsoid zone defect, decreased distance from the fovea to the photoreceptor defects, or newly developed or enlarged retinal pigment epithelium defects. On FAF, progression was defined as an increase in the area of hyperautofluorescence or hypoautofluorescence. Functional progression was defined as a regression coefficient of less than 0 dB/year for mean deviation and more than 0 dB/year for pattern standard deviation, based on linear regression analysis of 3 or more VF tests. Structural and functional progression rates were calculated using the slopes of retinal thicknesses on the Early Treatment Diabetic Retinopathy Study grid and perimetric parameters over time, respectively. Main Outcome Measures Structural and functional progression of retinopathy. Results Approximately one third of eyes with early pericentral retinopathy showed limited progression during the short-term period after drug cessation, but they subsequently showed stable or improved photoreceptors. Most eyes with moderate pericentral retinopathy showed continuous progression, particularly when converted to the severe stage. Severe eyes showed progressive damage throughout the follow-up period. In all severity groups, the rates of retinal thinning decreased over time. In eyes with pericentral retinopathy showing progression, circumferential enlargement of retinal damage was prominent in earlier stages, whereas centripetal enlargement of the ring-shaped lesion was noted in advanced stages. Functional progression, noted in 58.7% of the pericentral eyes, corresponded with structural progression. Conclusions Pericentral hydroxychloroquine retinopathy showed severity-dependent progression. Moderate pericentral retinopathy usually progressed, but centripetal progression threatening the fovea was remarkable mostly in severe retinopathy. Our results suggest that early detection of retinopathy may minimize the risk of progression to foveal involvement in pericentral retinopathy.

Background Glycemic variability is associated with the development of diabetic complications and hypoglycemia. However, the effect of sodium-glucose transporter 2 (SGLT2) inhibitors on glycemic variability is controversial. We aimed to examine the effect of dapagliflozin as an add-on therapy to insulin on the glycemic variability assessed using continuous glucose monitoring (CGM) in subjects with type 2 diabetes mellitus. Methods In this multicenter, placebo-controlled, double-blind, randomized study, 84 subjects received 10 mg of dapagliflozin (n=41) or the placebo (n=43) for 12 weeks. CGM was performed before and after treatment to compare the changes in glycemic variability measures (standard deviation [SD], mean amplitude of glycemic excursions [MAGEs]). Results At week 12, significant reductions in glycosylated hemoglobin (−0.74%±0.66% vs. 0.01%±0.65%, P

Background Direct oral anticoagulants (DOACs) have replaced vitamin K antagonists as the standard of care for stroke prevention in patients with atrial fibrillation (AF). However, DOAC prescriptions at dosages that do not adhere to labeling are common in daily practice. This analysis from the observational Global Edoxaban Treatment in routiNe clinical prActice (ETNA)-AF program focuses on edoxaban-treated patients from South Korea and Taiwan to identify patient baseline characteristics that may be associated with non-recommended dosing. Methods We report baseline data from ETNA-AF, including patient demographics, clinical characteristics, and bleeding/stroke history of patients receiving recommended or non-recommended edoxaban dosing. Results A total of 2677 patients were enrolled. Among 1543 patients who did not meet dose-reduction criteria, 1033 (66.9%) were prescribed the recommended 60-mg dose, and 510 (33.1%) were prescribed the non-recommended 30-mg dose. Among 1134 patients meeting ≥1 of the dose-reduction criteria, 863 (76.1%) were prescribed the recommended 30-mg dose; 271 (23.9%) were prescribed the nonrecommended 60-mg dose. Compared with the recommended 60-mg group, the nonrecommended 30-mg group had a higher proportion of patients aged ≥75 years, higher stroke and bleeding risks, and a history of major bleeding. The non-recommended 60-mg group had a lower proportion of patients aged ≥75 years, a higher history of stroke, and lower history of bleeding compared with the recommended 30-mg group. Conclusion The baseline data from ETNA-AF indicate that physicians take patient clinical characteristics (e.g., bleeding risks) into consideration when deviating from the dosing recommendation per label.

When thickness-dependent carrier mobility is coupled with Thomas-Fermi screening and interlayer resistance effects in two-dimensional (2D) multilayer materials, a conducting channel migrates from the bottom surface to the top surface under electrostatic bias conditions. However, various factors including (i) insufficient carrier density, (ii) atomically thin material thickness, and (iii) numerous oxide traps/defects considerably limit our deep understanding of the carrier transport mechanism in 2D multilayer materials. Herein, we report the restricted conducting channel migration in 2D multilayer ReS2 after a constant voltage stress of gate dielectrics is applied. At a given gate bias condition, a gradual increase in the drain bias enables a sensitive change in the interlayer resistance of ReS2, leading to a modification of the shape of the transconductance curves, and consequently, demonstrates the conducting channel migration along the thickness of ReS2 before the stress. Meanwhile, this distinct conduction feature disappears after stress, indicating the formation of additional oxide trap sites inside the gate dielectrics that degrade the carrier mobility and eventually restrict the channel migration. Our theoretical and experimental study based on the resistor network model and Thomas-Fermi charge screening theory provides further insights into the origins of channel migration and restriction in 2D multilayer devices.

Parabens are widely used preservatives in cosmetics and pharmaceutical products and are approved as food additives. These chemicals have been considered safe for many years. However, the literature classifies parabens as endocrine-disrupting chemicals, and an assessment of their influence on the endocrine system and systemic toxicity is important. This study explored long-term systemic toxicity, effects on the endocrine system, and toxicokinetic behavior after repeated subcutaneous administration of butylparaben to Sprague-Dawley rats. Rats were treated with vehicle (4% Tween 80) or butylparaben at dose levels of 2, 10, and 50 mg/kg/day for 13 weeks. Assessment of systemic toxicity and endocrine-disrupting effects was based on mortality; clinical signs; body weight; food and water consumption; ophthalmological findings; urinalysis; hematology and clinical biochemistry; organ weights; necropsy and histopathological findings; regularity and length of the estrous cycle; semen quality; and toxicokinetic behavior. Female uterine weight and estrous cycle, and male semen quality indicated no estrogenic effects. Butylparaben induced local irritation at the injection site in both sexes at a dose of 50 mg/kg/day, but systemic toxicity was not observed. Therefore, the no-observed-adverse-effect level of butylparaben is set at 50 mg/kg/day in rats of both sexes. Butylparaben was without endocrine system effects at this dose. Butylparaben displays dose-dependent systemic exposure up to the maximum dose of 50 mg/kg/day and repeated administration of butylparaben for 13 weeks shows no bioaccumulation.

Spotted wing drosophila, Drosophila suzukii (Diptera: Drosophilidae), is a serious invasive pest of berries and cherries in the U.S. and Europe and has become a major phytosanitary trade barrier. In this pilot study, we explored the potential of using stand-alone ethyl formate (EF) treatment and a combinatory treatment of EF and cold temperature as postharvest control options for D. suzukii in imported blueberries. Stand-alone EF fumigations were effective against D. suzukii with LCt99% of 207.7 and 168.5 g·h·m−3 for eggs, the most tolerant life stage, at 5 and 21 °C, respectively. In a scale-up (10 m3) trial conducted at 5 °C, complete control of D. suzukii eggs placed inside and outside of blueberry boxes was achieved using 70 g·m−3 EF for 4 h with 5% blueberry loading ratio without deleterious impact on blueberry appearance such as soft spot or berry shrivel. In small scale pilot studies, 9-d stand-alone cold treatment at 5 °C was sufficient for complete control of D. suzukii eggs and larvae tested, but not pupae. The efficacy of this cold treatment appeared to be improved when D. suzukii eggs were first treated with low-dose EF (LCt50% level) prior to the cold treatment. The combination treatment resulted in complete mortality of D. suzukii eggs, larvae, and pupae tested after 7, 5, and 9 d of cold treatment, respectively. Together, these results suggest that stand-alone EF treatment, or the combination treatment of low-dose EF and cold as a systems approach may have a potential as postharvest treatments for D. suzukii in blueberries.

Physical homogenization was applied to the production of a starch-lipid complex formed through a hydrophobic interaction between amylose and fatty acid molecules. In addition, vegetable oils as a source of fatty acids and wheat starch as a source of amylose molecules were used to produce the starch-lipid complex. The complex index was significantly (p

Among the structural isomers of sucrose, turanose has been considered as one of good candidates as novel sweetener due to its mild taste, low calorie, and anti-cariogenicity. Here, various physicochemical properties of turanose, such as solubility, temperature and pH stabilities, viscosity, non-enzymatic browning reaction, and dynamic vapor sorption, were investigated by comparing them to those of other commercial sugars. Turanose did not significantly hydrolyze through the simulated digestion tract overall but in the artificial small intestinal environment specifically, turanose degraded by only 18% when sucrose was hydrolyzed by 36% after 4 h. In addition, physicochemical properties of turanose confirmed that it had a potential to replace sucrose due to similar or better product qualities as a food ingredient than other types of sugars with similar chemical structure. Thus, our study suggests that turanose can be applied as a functional sweetener or bulking agent in food processing.

Retinal implants electrically stimulate surviving retinal neurons to restore vision in people blinded by outer retinal degeneration. Although the healthy retina is known to transmit a vast amount of visual information to the brain, it has not been studied whether prosthetic vision contains a similar amount of information. Here, we assessed the neural information transmitted by population responses arising in brisk transient (BT) and brisk sustained (BS) subtypes of ON and OFF retinal ganglion cells (RGCs) in the rabbit retina. To correlate the response heterogeneity and the information transmission, we first quantified the cell-to-cell heterogeneity by calculating the spike time tiling coefficient (STTC) across spiking patterns of RGCs in each type. Then, we computed the neural information encoded by the RGC population in a given type. In responses to light stimulation, spiking activities were more heterogeneous in OFF than ON RGCs (STTCAVG = 0.36, 0.45, 0.77 and 0.55 for OFF BT, OFF BS, ON BT, and ON BS, respectively). Interestingly, however, in responses to electric stimulation, both BT and BS subtypes of OFF RGCs showed remarkably homogeneous spiking patterns across cells (STTCAVG = 0.93 and 0.82 for BT and BS, respectively), whereas the two subtypes of ON RGCs showed slightly increased populational heterogeneity compared to light-evoked responses (STTCAVG = 0.71 and 0.63 for BT and BS, respectively). Consequently, the neural information encoded by the electrically-evoked responses of a population of 15 RGCs was substantially lower in the OFF than the ON pathway: OFF BT and BS cells transmit only ~23% and ~53% of the neural information transmitted by their ON counterparts. Together with previously-reported natural spiking activities in ON RGCs, the higher neural information may make ON responses more recognizable, eliciting the biased percepts of bright phosphenes.

Purpose To investigate the use of a retinal thickness deviation map generated from swept-source (SS) OCT images for hydroxychloroquine retinopathy screening. Design Retrospective cohort study. Participants This study included 1192 Korean patients with a history of hydroxychloroquine treatment: 881 patients (1723 eyes) in the discovery set and 311 patients (591 eyes) in the validation set. Patients were screened for retinal toxicity using SS OCT, fundus autofluorescence, and standard automated perimetry. Methods According to the 2016 American Academy of Ophthalmology guidelines, hydroxychloroquine retinopathy was diagnosed by the presence of abnormalities on ≥1 objective structural tests alongside corresponding visual field defects. The 12 × 9-mm2 macular volume SS OCT scan was performed, and the retinal thickness deviation map was generated automatically using the built-in software. On this map, yellow (retinal thickness, Main Outcome Measures The rate and patterns of abnormalities on the retinal thickness deviation map and sensitivity and specificity of the diagnostic criteria. Results The retinal thickness deviation map showed the following abnormal patterns in eyes with hydroxychloroquine retinopathy: pericentral (36.0%) or parafoveal (6.1%) ring, mixed-ring (34.2%), central island (13.2%), and whole macular thinning (10.5%). The criterion of ≥5 contiguous red pixels showing 1 of the 5 characteristic patterns in both eyes yielded the greatest diagnostic performance (sensitivity and specificity of 98.2% and 89.1% and of 100% and 87.5% in the discovery and validation set data, respectively). Moreover, the area of abnormal pixels on the map was correlated significantly with the mean deviation (P Conclusions The retinal thickness deviation map may facilitate the objective evaluation of hydroxychloroquine retinopathy because it does not require subjective, morphologic evaluation of the outer retinal layers. The map has the potential to enhance hydroxychloroquine retinopathy screening when used in conjunction with conventional screening methods.

To understand the role of small heat shock protein (sHSPs) in rice plant response to various stresses such as the heat and oxidative stresses, a cDNA encoding a 24.1 kDa mitochondrial small HSP (Oshsp24.1) was isolated from rice by rapid amplification of cDNA ends (RACE) PCR. The deduced amino acid sequence shows very high similarity with other plant small HSPs. DNA gel blot analysis suggests that the rice genome contains more than one copy of Oshsp24.1. High level of expression of Oshsp24.1 transcript was observed in rice seedlings in response to heat, methyl viologen, hydrogen peroxide, ozone, salt and heavy metal stresses. Recombinant OsHSP24.1 protein was produced in E. coli cells for biochemical assay. The protein formed oligomeric complex when incubated with Sulfo-EGS (ethylene glycol bis (succinimidyl succinate)). Our results shows that Oshsp24.1 has an important role in abiotic stress response and have potential for developing stress-tolerant plants.

Methylated bis-triethylene glycolic crown-5-calix[4]arene (M-BTC5A) as a phase-transfer catalyst showed the best performance among other analogues and even conventional Kryptofix 222 in the nucleophilic aromatic 18F-fluorination of diaryliodonium tosylate precursors owing to (i) the efficient release of reactive "naked" [18F]fluoride, (ii) the high stabilization of the precursor in the reaction, and, presumably, (iii) the ease of access between the precursor and the K18F/M-BTC5A complex facilitated by π-π interactions. [18F]Flumazenil was produced in high radiochemical yield using M-BTC5A.

In this letter, a new silicon-controlled rectifier (SCR) structure fabricated using 4H-SiC materials has been proposed and investigated. The proposed structure alleviates the strong-snapback phenomenon that occurs in the 4H-SiC SCR and demonstrates low trigger voltage and high holding voltage characteristics. The proposed device exhibits improved snapback characteristics with very high holding voltage against electrostatic discharge surges owing to the structural features and application of segment topology. It also has excellent on-resistance and improved thermal reliability owing to the physical characteristics of 4H-SiC. Traditional SCR and low-voltage trigger SCR (LVTSCR) are fabricated with 4H-SiC under the same conditions and their electrical characteristics are comparatively analyzed with those of the proposed SCR. This study also evaluates the electrical characteristics at high temperatures (300–500 K) to verify the high- temperature reliability of the proposed structure.

Introduction Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely prescribed for type 2 diabetes (T2D) and their glycemic control effects are well studied. However, information regarding the effects of switching DPP-4 inhibitors is limited, especially in older patients. Research Design and Methods We investigated whether switching from linagliptin to teneligliptin decreases blood glucose in older (≥65 years) T2D patients. In total, 164 patients with T2D who switched from linagliptin to teneligliptin for >12 weeks were included and the primary outcome was glycemic changes. Results Switching from linagliptin to teneligliptin ameliorated fasting blood glucose (148.1 ± 47.1 to 139.6 ± 43.4 mg/dL), glycated hemoglobin (HbA1c; 7.9 ± 1.3 to 7.5 ± 1.2%), and postprandial blood glucose (224.8 ± 77.4 to 205.8 ± 70.8 mg/dL) levels (all P 8.0%) and chronic kidney disease (estimated glomerular filtration rate

Calculations of chemical equilibrium for multicomponent aqueous systems of the HyBRID dissolution of magnetite were performed by using the HSC Chemistry. They were done by using a Pitzer-based aqueous solution model with the recipe of raw materials in experiments conducted at KAERI. The change in the amounts of species and ions and the pH values of the solution at equilibrium was observed as functions of temperature and raw amount of CuSO4. Precipitation of Cu2O occurred at a large amount of CuSO4 added to the solution, while no precipitation of Cu(OH)2 was found at any amounts of CuSO4. The E-pH diagrams for Cu were constructed at various Cu concentrations to provide the effect of the Cu concentration on the pH values at boundaries where the coexistence of Cu+ ion and Cu2O solid occurred. To prevent Cu+ ions from being precipitated to Cu2O, the raw amount of CuSO4 should be adjusted so that the pH value of the solution from the equilibrium calculation is less than that from the E-pH diagram. We provided guidelines for the raw amount of CuSO4 and the pH value of the solution, which prevent the formation of Cu2O precipitates in the HyBRID dissolution experiments for magnetite.

Condensin is a Structural Maintenance of Chromosomes (SMC) complex needed for the compaction of DNA into chromatids during mitosis. Lengthwise DNA compaction by condensin is facilitated by ATPase-driven loop extrusion, a process that is believed to be the fundamental activity of most, if not all SMC complexes. In order to obtain molecular insights, we obtained cryo-EM structures of yeast condensin in the presence of a slowly-hydrolysable ATP analogue and linear, as well as circular DNAs. The DNAs were shown to be “clamped” between the engaged heterodimeric SMC ATPase heads and the Ycs4 subunit, in a manner similar to previously reported DNA-bound SMC complex structures. Ycgl, the other non-SMC subunit was only flexibly bound to the complex, while also binding DNA tightly, and often remaining at a distance from the head module. In the clamped state, the DNA is encircled, or topologically entrapped, by the kleisin Brnl and the two engaged head domains of Smc2 and Smc4, and this tripartite ring is closed at all interfaces, including at the neck of Smc2. We show that the neck gate opens upon head engagement in the absence of DNA, but it remains shut when DNA is present. Our work demonstrates that condensin and other SMC complexes go through similar conformations of the head modules during their ATPase cycle. In contrast, the behaviour of the Ycgl subunit in the condensin complex might indicate differences in the implementation of the extrusion reactions and our findings will constrain further mechanistic models of loop extrusion by SMC complexes.SIGNIFICANCE STATEMENTDNA needs to be compacted dramatically to fit into nuclei and during cell division, when dense chromatids are formed for their mechanical segregation, a process that depends on the protein complex condensin. It forms and enlarges loops in DNA through loop extrusion. Our work resolves the atomic structure of a DNA-bound state of condensin in which ATP has not been hydrolysed. The DNA is clamped within a compartment that has been reported previously in other SMC complexes, including Rad50, cohesin and MukBEF. With the caveat of important differences that we also uncovered, it means that all SMC complexes cycle through at least some similar states and undergo similar conformational changes in their head modules, while hydrolysing ATP and translocating DNA.

High-pressure (HP) deuterium (D2) annealing was applied to a gate-all-around (GAA) MOSFET to improve device reliability and memory performance. The structure had gate dielectrics of oxide–nitride–oxide (ONO), which completely straddled vertically stacked multiple silicon nanowires (Si-NWs) with n+ poly-Si gates. The HP D2 annealing was effective for the vertically stacked GAA MOSFET as it was for a conventional planar MOSFET. In addition, the resistance of the n+ poly-Si gate was also reduced after the HP D2 annealing. This is attributed to the passivation of defects among adjacent poly-Si grains by the HP D2. The reduced gate resistance ( ${R}_{G}$ ) is advantageous for decreasing RC delay. Direct characterizations of dc ${I}$ – ${V}$ and analyses of ac low-frequency noise (LFN) supported the abovementioned behaviors.

A continuous stirred tank reactor (CSTR) was operated for more than 120 days with fixed hydraulic retention time of 6 h at mesophilic temperature along with a periodic recovery phase towards hydrogen production and stimulated by the existence of 5-hydroxy methyl furfural concentration (5-HMF). Interestingly, CSTR mixed with a small amount of 5-HMF, range of 0.3–0.6 g/L showed at least 50% higher hydrogen production rate than control without 5-HMF. However, when 5-HMF concentration was higher than 0.6 g/L, the performance was significantly inhibited. The bacterial community shifted by 5-HMF from Clostridium-dominated to Lactobacillus-dominated population. Regardless of the remain 5-HMF concentration in CSTR, the microbial community and hydrogen producing performance were restored by stop mixing the 5-HMF from the feedstock. The high-rate hydrogen production of 20.0 ± 1.8 L H2/L/d was achieved in the presence of 5-HMF using the threshold information and recovery strategy.

Purpose: In this study, we aim to study the functionality of multiple effects of peptide collagen and naturally derived compounds through in vitro experiments and human application tests. Method: Cytotoxicity of inner beauty film (IBF), pro-collagen generation ability, elastase and collagenase inhibition, DPPH radical scavenging and tyrosinase inhibition ability were measured, and skin improvement, through in vitro and human application test. Results: Cytotoxicity was not confirmed up to 1000 μg/mL. Elastase inhibition was 7.2% at a concentration of 125 μg/mL, and collagenase showed an inhibition rate of 16.3% at 31.3 μg/mL. The pro-collagen synthesis showed expression of 34%, compared with the negative control when the concentration was 62.5 μg/mL. The antioxidant activity of 250 μg/mL and whitening effect of 62.5 μg/mL are showed in the Results section, and there was no observed deformation or color change even after confirming the stability for 6 months. Even in the human clinical study, the wrinkle improvement before and after using the IBF was 32.2% at maximum, skin melanin and brown spot improvement was 32.5%, pore improvement was 31.5%, and skin density improvement was 12.8%, as shown in the Results section. Conclusion: Therefore, the IBF containing the complex of peptide collagen and naturally derived compounds has a positive effect on wrinkle improvement, skin melanin and brown spot improvement, skin pore improvement, and skin density improvement, as well as exhibiting antioxidant and whitening effects. As a result, IBF can be developed as a key material for cosmetics and foods.

Ethyl formate (EF) is becoming an insecticide of choice for protecting stored commodities. Along with EF, methyl salicylate (MS) is also naturally occurring, and both are generally regarded as safe fumigants for their higher threshold limit values (TLV) and residual status below minimum residue limit (MRL). Sub-lethal doses of EF and MS were evaluated to determine if there was a synergistic effect on fumigation against life stages of the adzuki bean beetle, Callosobruchus chinensis (L.) infesting adzuki bean grains. Based on lethal dose (LD) values, the C. chinensis eggs and adults were equally susceptible to EF followed by larvae and pupae. Adults were the most MS-sensitive followed by eggs and larvae, and pupae were the most tolerant stage. The mortalities of all the life stages of C. chinensis by combined fumigation with sub-lethal EF and MS doses were significantly higher compared to the sum of their separate fumigations revealing a notable synergistic effect. Moreover, the maximum doses of EF and MS tested for synergistic fumigation test did not hamper the germination potential of adzuki been seeds. The synergistic effect between EF and MS can significantly reduce the dose rate of flammable EF against C. chinensis thereby offering a good prospect for EF + MS formulation as an alternative to safeguard stored adzuki bean.

Enzymatic hydrolysis and self-assembly are considered promising methods for preparation of starch nanoparticles (SNPs) because they are environmentally friendly, and time- and cost-effective. These methods are based on the self-assembly of short-chain glucans released from the α-1,6 bonds in amylopectin. Since their discovery, many studies have described the structural and physicochemical properties of self-assembled SNPs. Self-assembled SNPs can be prepared by two methods: using only the soluble portion containing the short-chain glucans, or using the whole hydrolyzate including both insoluble and soluble fractions. Although the structural and physical properties of self-assembled SNPs can be attributed to the composition of the hydrolyzates that participate in self-assembly, this aspect has not yet been discussed. This review focuses on SNPs self-assembled with only soluble short-chain glucans and addresses their characteristics, including formation mechanisms as well as structural and physicochemical properties, compared with SNPs prepared with total hydrolyzates.

Background/Aims: The diagnosis of immune thrombocytopenia (ITP) is based on clinical manifestations and there is no gold standard. Thus, even hematologic malignancy is sometimes misdiagnosed as ITP and adequate treatment is de layed. Therefore, novel diagnostic parameters are needed to distinguish ITP from other causes of thrombocytopenia. Immature platelet fraction (IPF) has been pro posed as one of new parameters. In this study, we assessed the usefulness of IPF and developed a diagnostic predictive scoring model for ITP. Methods: We retrospectively studied 568 patients with thrombocytopenia. Blood samples were collected and IPF quantified using a fully-automated hematology analyzer. We also estimated other variables that could affect thrombocytopenia by logistic regression analysis. Results: The median IPF was significantly higher in the ITP group than in the non-ITP group (8.7% vs. 5.1%). The optimal cut-off value of IPF for differentiating ITP was 7.0%. We evaluated other laboratory variables via logistic regression anal ysis. IPF, hemoglobin, lactate dehydrogenase (LDH), and ferritin were statistically significant and comprised a diagnostic predictive scoring model. Our model gave points to each of variables: 1 to high hemoglobin (> 12 g/dL), low ferritin (≤ 177 ng/ mL), normal LDH (≤ upper limit of normal) and IPF ≥ 7 and < 10, 2 to IPF ≥ 10. The final score was obtained by summing the points. We defined that ITP could be predicted in patients with more than 3 points. Conclusions: IPF could be a useful parameter to distinguish ITP from other caus es of thrombocytopenia. We developed the predictive scoring model. This model could predict ITP with high probability.

Amylosucrase (AS) catalyzes the transfer of a glucosyl unit from sucrose onto α-1,4-linked glucan polymers in starch. In this study, AS from Deinococcus geothermalis (DgAS) was applied to produce modified rice starches with slowly digestible properties. DgAS-treated waxy and normal rice starches showed significantly (p

Presence of formaldehyde as a preservative in commonly available fishes (Labeo rohita, Catla catla, Anabas testudineus and Clarias gariepinus) has become a serious health concern in the public health of eastern region of India. Formaldehyde content was determined using high-performance liquid chromatography (HPLC). Results showed high formaldehyde content in frozen carp (19.66 and 23.3 mg/kg in Labeo rohita and Catla catla, respectively); however, the amount of formaldehyde was significantly reduced in boiled and fried fish (80 °C and 100 °C for 5 min) in mustard, coconut, and sesame oils. However, formaldehyde contents in non-carp fishes (Anabas testudineus and Clarias gariepinus) were almost negligible, compared to those in L. rohita and C. catla. In vivo toxicity studies showed a time-dependent increase in blood formaldehyde levels in rats after they were fed formaldehyde-contaminated fish (23.3 mg/kg) for 7 days. Histopathological analysis of the stomach of rats fed contaminated fish showed destruction and granulation of the protective mucus layer and detachment from the secretory layer. Taken together, our results indicated that continuous consumption of formaldehyde-contaminated carps commonly available in the eastern region of India may be associated with adverse health effects.

Modification of chestnut starch with amylosucrase from Deinococcus geothermalis (DGAS) increases the proportion of resistant starch. DGAS-modified chestnut starch (DMCS) attenuates obesity in diet-induced obese mice via a receptor of short chain fatty acids (SCFAs), G-protein-coupled receptor 43. SCFAs are gut microbial metabolites produced by fermenting resistant starch and have key roles in the obesity-ameliorating effects of DMCS. Here, we evaluated the mechanical links among DMCS-induced changes in the gut microbiota, consequent production of microbial metabolites, and host genetic responses. Supplementation with DMCS altered the proportions of cecal microbiota, such as Ruminococcaceae and Bacteroides; microbial metabolites, such as acetic acid; and some carbohydrate metabolites. DMCS also induced changes in the expression of some genes in cecal epithelial cells, including genes involved in energy production, the cell cycle, and cellular junctions. Changes in the gut microbiota, microbial metabolites, and host gene expression were found to be significantly correlated. Our findings demonstrated the integrated and incorporated association among the gut microbiota, their beneficial metabolites, and the host transcriptome, which contributed to clarifying the anti-obesity effects of DMCS as a prebiotic. Therefore, fortifying resistant starch by modification of chestnut starch using DGAS may be a good strategy in the functional food industry.

Background and objectivesFTY720 ((2-amino-2-)2-[4-octylphenyl]ethyl)-1,3-propanediol) is an Food and Drug Administration (FDA)-approved immunomodulatory drug for treating multiple sclerosis. It inhibits lymphocyte egression from lymphoid tissues by downregulating sphingosine-1 phosphate receptor (S1PR). To date, there has been no study on the effects of FTY720 on the chronic stage of the complex regional pain syndrome (CRPS) rodent model, despite its antiallodynic effect in previous studies. Thus, the aim of this study is to investigate the effect of FTY720 in a chronic stage of the CRPS mouse model.MethodThe authors used a mouse model of CRPS, involving tibia fracture/cast immobilization, to test the efficacy of intrathecal FTY720 (2.5 or 25 ng daily; 6 days) or vehicle during the chronic (7 weeks after fracture) stage of CRPS.ResultsIntrathecal recombinant FTY720 administration was antiallodynic in the chronic stage of the CRPS mouse model, and such an effect of FTY720 developed by modulating astrocyte activation in the spinal cord. Additionally, according to the in vitro data, the FTY720 treatment inhibited S1P-induced increase in the nitric oxide production and suppression of the NF-κB pathway, by inhibiting the phosphorylation of NF-κB/p65 in astrocytes without toxic effect on astrocytes.ConclusionCollectively, these results demonstrate that intrathecally administered FTY720 attenuates mechanical allodynia in the chronic stage of the CRPS mouse model.

Detoxifying effects of hyperoxia, which is widely used in clinical practice, were investigated using HaCat cells (human keratinocytes) treated with benzo[a]pyrene (B[a]P) as a model agent to induce adverse effects in the skin. It is well-established that B[a]P may produce toxicities including cancer, endocrine disruption, and phototoxicity involving DNA damage, free radical generation, and down regulation of nuclear factor erythroid 2-related factor 2 (Nrf2). It is well-known that Nrf2 is associated increase of antioxidant enzyme catalase (CAT) or detoxification enzyme glutathione S-transferase (GST) in HaCat cells treated with B[a]P under optimal condition of hyperoxia (40% oxygenation) conditions. To further examine the underlying basis of this phenomenon, factors affecting the expression of Nrf2 were determined. Nrf2 was upregulated accompanied by a rise in p38 MAPK, sequestosome-1 (also known as p62) and NF-κB. In contrast, Nrf2 was downregulated associated with an elevation in glycogen synthase kinase 3 beta (GSK-3β) and peroxisome proliferator-activated receptor alpha (PPARα). Hyperoxia was also found to diminish DNA damage and generation of free radicals initiated in B[a]P-treated cells which was attributed to an significant rise of Nrf2, leading to elevated antioxidant activities or detoxification proteins including heme oxygenase 1 (HO-1), superoxide dismutase (SOD), glutathione peroxidase-1/2 (GPX-1/2), CAT, GST and glutathione (GSH). In addition, factors related to skin aging were also altered by hyperoxia. Data suggest that optimal hyperoxia exposure of 40% oxygenation may reduce cellular toxicity induced by B[a]P in HaCat cells as evidenced by inhibition of DNA damage, free radical generation, and down-regulation of Nrf2.

Objective: This study investigated whether serum bilirubin levels can predict the progression of carotid atherosclerosis in individuals with type 2 diabetes mellitus (T2DM). Methods: This observational study included 1,381 subjects with T2DM in whom serial measurements of carotid intima-media thickness (CIMT) were made at 1- to 2-year intervals for 6–8 years. The progression of carotid atherosclerosis was defined as newly detected plaque lesions on repeat ultrasonography. After dividing total serum bilirubin levels into tertiles, the association between total serum bilirubin at baseline and plaque progression status was analyzed. Results: Among 1,381 T2DM patients, 599 (43.4%) were categorized as having plaque progression in their carotid arteries. Those with plaque progression were significantly older; showed a higher prevalence of hypertension, abdominal obesity, and chronic kidney disease; and had a longer duration of T2DM, higher levels of total cholesterol (TC), triglycerides, and insulin resistance, and lower total bilirubin concentrations than those with no plaque progression. When total serum bilirubin levels were divided into tertiles, the highest tertile group was younger than the lowest tertile group, with higher levels of TC and high-density lipoprotein cholesterol. Multiple logistic regression analysis demonstrated that higher serum bilirubin levels were associated with a significantly lower risk of CIMT progression (odds ratio, 0.584; 95% confidence interval, 0.392–0.870; p=0.008). Age (p

The effect of thiourea on the nano-mechanical and chemical properties of Ni-P foil was studied to develop a high performance Ni-P deposit for automobile and machinery parts. The Ni-P deposit was prepared by electroforming in a modified sulphate bath with different amounts of thiourea. Chemical analysis of the electrodeposited Ni-P foils by energy dispersive spectroscopy showed that phosphorous in the foil was reduced with thiourea. Structural analysis by X-ray diffractometry revealed that the (111) plane of the Ni-P deposits grew preferentially with increasing crystallinity. Surface analysis by atomic force microscopy and fieldemission scanning electron microscopy showed that the surfaces of the Ni-P electrodeposited with 0 and 0.01 g/L thiourea were relatively smooth and clean showing no nodules, whereas, the cauliflower-like nodules were observed on the surfaces of the deposits prepared with 0.03, 0.05, 0.07 and 0.1 g/L thiourea. The surface roughness (RRMS) of the deposits increased by addition of 0.1 ppm of thiourea from 6 to 54 nm. Nanomechanical properties of the Ni-P foil such as elastic modulus, hardness and stiffness determined by tribonano- indenter were tended to increase by addition of 0.1 ppm of thiourea from 77 to 156 GPa, 6.6 to 8.9 GPa and 109.6 to 186.6 μN/nm, respectively. (Received September 16, 2019; Accepted November 30, 2019)