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Background In aged skin, reactive oxygen species (ROS) induces degradation of the extracellular matrix (ECM), leading to visible aging signs. Collagens in the ECM are cleaved by matrix metalloproteinases (MMPs). Syringaresinol (SYR), isolated from Panax ginseng berry, has various physiological activities, including anti-inflammatory action. However, the anti-aging effects of SYR via antioxidant and autophagy regulation have not been elucidated. Methods The preventive effect of SYR on skin aging was investigated in human HaCaT keratinocytes in the presence of H2O2, and the keratinocyte cells were treated with SYR (0–200 μg/mL). mRNA and protein levels of MMP-2 and -9 were determined by real-time PCR and Western blotting, respectively. Radical scavenging activity was researched by 2,2 diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. LC3B level was assessed by Western blotting and confocal microscopy. Results SYR significantly reduced gene expression and protein levels of MMP-9 and -2 in both H2O2-treated and untreated HaCaT cells. SYR did not show cytotoxicity to HaCaT cells. SYR exhibited DPPH and ABTS radical scavenging activities with an EC50 value of 10.77 and 10.35 μg/mL, respectively. SYR elevated total levels of endogenous and exogenous LC3B in H2O2-stimulated HaCaT cells. 3-Methyladenine (3-MA), an autophagy inhibitor, counteracted the inhibitory effect of SYR on MMP-2 expression. Conclusion SYR showed antioxidant activity and up-regulated autophagy activity in H2O2-stimulated HaCaT cells, lowering the expression of MMP-2 and MMP-9 associated with skin aging. Our results suggest that SYR has potential value as a cosmetic additive for prevention of skin aging.

BACKGROUND: The precise underlying mechanism of antioxidant effects of dexmedetomidine-induced neuroprotection against cerebral ischemia has not yet been fully elucidated. Activation of Nuclear factor erythroid 2-related factor (Nrf2) and Heme Oxygenase-1 (HO-1) represents a major antioxidant-defense mechanism. Therefore, we determined whether dexmedetomidine increases Nrf2/HO-1 expression after global transient cerebral ischemia and assessed the involvement of Protein Kinase C (PKC) in the dexmedetomidine-related antioxidant mechanism. METHODS: Thirty-eight rats were randomly assigned to five groups: sham (n...=...6), ischemic (n...=...8), chelerythrine (a PKC inhibitor; 5...mg.kg(-1) IV administered 30...min before cerebral ischemia) (n...=...8), dexmedetomidine (100.....g.kg(-1) IP administered 30...min before cerebral ischemia (n...=...8), and dexmedetomidine...+...chelerythrine (n...=...8). Global transient cerebral ischemia (10...min) was applied in all groups, except the sham group; histopathologic changes and levels of nuclear Nrf2 and cytoplasmic HO-1 were examined 24...hours after ischemia insult. RESULTS: We found fewer necrotic and apoptotic cells in the dexmedetomidine group relative to the ischemic group (p...

Charcot-Marie-Tooth disease (CMT) and related diseases are a genetically and clinically heterogeneous group of peripheral neuropathies. Particularly, mutations in several aminoacyl-tRNA synthetase (ARS) genes have been reported to cause axonal CMT (CMT2) or distal hereditary motor neuropathy (dHMN). However, the common pathogenesis among CMT subtypes by different ARS gene defects is not well understood. This study was performed to investigate ARS gene mutations in a CMT cohort of 710 Korean families. Whole-exome sequencing was applied to 710 CMT patients who were negative for PMP22 duplication. We identified 12 disease-causing variants (from 13 families) in GARS1, AARS1, HARS1, WARS1, and YARS1 genes. Seven variants were determined to be novel. The frequency of overall ARS gene mutations was 1.22% among all independent patients diagnosed with CMT and 1.83% in patients negative for PMP22 duplication. WARS1 mutations have been reported to cause dHMN; however, in our patients with WARS1 variants, CMT was associated with sensory involvement. We analyzed genotype-phenotype correlations and expanded the phenotypic spectrum of patients with CMT possessing ARS gene variants. We also characterized clinical phenotypes according to ARS genes. This study will be useful for performing exact molecular and clinical diagnoses and providing reference data for other population studies.

CLINICAL RELEVANCE Contact lens multipurpose solutions (MPSs) contain several components that have the potential to cause corneal epithelial cell toxicity. Evaluating the components and the toxic effect of MPS should be considered for effective eye care. BACKGROUND The cytotoxic and wound healing effects of five commercially available MPSs on human corneal epithelial cells (HCECs) are is investigated. METHODS The following commercially available MPSs were used: Queen's PLURISOL®, Frenz®, Boston SIMPLUS®, DL+PLUS EYE® (DL), and NEW YORK DEFINE® (NY). The proliferation of HCECs exposed to each MPS for 1, 6, and 24 h and the cytotoxicity of these solutions were analyzed using methyl thiazolyl tetrazolium-based colorimetric and lactate dehydrogenase leakage assays, respectively. The cellular morphology was evaluated by inverted phase-contrast and electron microscopy. A scratch-wound assay was performed to measure wound widths 24 h after confluent HCEC monolayers were scratch-wounded. RESULTS The tested MPS had a time-dependent inhibitory effect on HCEC proliferation and cytotoxicity, significantly at 24 h after exposure (p

Objective To analyze the relationship between body composition, metabolic parameters, and bone mineral density (BMD) according to sex and the degree of obesity in children and adolescents. Methods A total of 236 subjects with obesity, aged 10 to 15 years (36.9% girls), were enrolled. Obesity was classified into simple (SmOb) and extreme (ExOb) forms. The BMD of the total body, less head, was measured by dual energy x-ray absorptiometry, and the BMD z-score was used to evaluate the relationship of body composition with metabolic parameters. Results BMD z-scores were higher in subjects with ExOb than in those with SmOb. Lean mass index (LMI), body mass index z-score, and vitamin D intake showed positive relationships, whereas percentage of body fat and serum leptin level showed negative relationships with BMD z-scores in boys. In girls, LMI and body mass index z-score showed positive relationships with BMD z-scores. In multivariable linear regressions, serum leptin level showed negative relationships with BMD z-score, only in boys. In addition, positive relationships of LMI and negative relationships of percentage of body fat with BMD z-scores were observed in subjects with SmOb. However, positive relationships of LMI with BMD z-scores were attenuated in subjects with ExOb. Conclusion High BMD appears to be positively associated with lean mass in children and adolescents with obesity, which might be a natural protective mechanism to withstand the excess weight. However, excessive body fat appears to be negatively associated with BMD, which might attenuate the positive relationship between lean mass and BMD in subjects with ExOb.

Objectives To examine the risk of serious infections (SIs) among patients with rheumatoid arthritis (RA) treated with tocilizumab compared with tumor necrosis factor inhibitor (TNFi) in Korea. Methods We conducted a retrospective cohort study using the Korean National Health Insurance data. The study cohort included patients ≥18 years with RA who were initiated with tocilizumab or TNFi between January 2013 and June 2018. The primary outcome was a composite endpoint of SIs, defined as an infection resulting in intravenous antimicrobial therapy or hospitalization. Secondary outcomes were organ-specific SIs. To control for confounders, we used inverse probability of treatment weighting (IPTW) using propensity score. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a multivariable Cox regression model. Results A total of 8794 patients were identified: 1395 and 7399 patients initiated with tocilizumab and TNFi, respectively. The mean follow-up durations were 1.2 years for tocilizumab initiators and 1.0 year for TNFi initiators. After IPTW and adjustment, no increased risk of SIs was observed in tocilizumab versus TNFi (HR, 1.00; 95%CI, 0.90–1.11). In the secondary analysis, tocilizumab was associated with a higher risk of skin and subcutaneous tissue infections (HR, 1.26; 95%CI, 1.02–1.54) and a lower risk of urological and gynecological infections (HR, 0.65; 95%CI, 0.49–0.87) compared to TNFi. Conclusion In this population-based cohort of RA patients in Korea, tocilizumab was not associated with a higher risk of SI compared to TNFi. However, tocilizumab should be carefully used for patients at high risk for skin-related infections.

The internal electrical conductivity in plant stem (ECps) reflects its physiological activity including ion and water transport. Thus, monitoring the ECps can be used to predict physiological changes in plants due to environmental stresses that affect water and ion transport in them. The purpose of this study was to determine if ECps monitoring data could be used to indicate environmental stress induced by low temperature and salt by comparing ECps with chlorophyll and proline contents. Capsicum annuum was progressively exposed to day/night temperature of 21/16 °C and 14/9 °C as low-temperature stress. Salt stress was incrementally applied at 20 and 40 mmol/kg NaCl. The ECps of C. annuum was monitored over the experimental period. The ECps was lower under low-temperature stress, although visible changes were not observed. Both chlorophyll a and b contents were lower, and the proline content was higher in leaves under low-temperature stress compared to the control. The initial salt treatment increased the ECps and the subsequent salt treatment at 40 mmol/kg NaCl resulted in a sudden increase of the ECps. The decreased chlorophyll a and b, and the increased proline content of the leaves under salt stress were stress-induced responses. Sodium and chloride accumulation increased, and the potassium/sodium ratio decreased in salt-treated plants. The ECps reflected reduced ion and water transport under low-temperature stress and increased salt transport in stems under salt stress. Therefore, ECps monitoring can be used to diagnose physiological changes in plants caused by environmental stress conditions before symptoms appear.

BACKGROUND Minimal change disease (MCD) is one of the most common causes of nephrotic syndrome worldwide. Hyperuricemia increases the end-stage renal disease (ESRD) risk in glomerulonephritis. In this study, we aimed to determine the effect of high serum uric acid levels on the progression to ESRD in MCD. METHODS A total of 800 patients diagnosed with MCD by kidney biopsy were retrospectively analyzed. We determined the relationship of hyperuricemia with the progression to ESRD in MCD using the Cox proportional hazard model and Kaplan-Meier survival analysis. The primary outcome was defined as the initiation of dialysis or kidney transplantation. RESULTS A total of 42 patients (5.3%) progressed to ESRD during the follow-up period. In the restricted cubic spline curve, serum uric acid levels exhibited a positive correlation with ESRD progression in patients with MCD. In the fully adjusted model, the risk of MCD progression increased by 29% for every 1 mg/dL increase in the baseline serum uric acid level (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.09-1.54; p = 0.004). Falling into the high uric acid group (serum uric acid level > 7 mg/dL in men and > 6 mg/dL in women) was also a risk factor for progression of MCD to ESRD (HR, 3.40; 95% CI, 1.59-7.31; p < 0.001). CONCLUSION Our study shows that hyperuricemia is an independent risk factor for the progression to ESRD in patients with MCD.

Nitric oxide (NO) has the potential to modulate myofibroblast differentiation. In this study, we investigated the effect of exogenous NO on the myofibroblast differentiation of human keratocytes using sodium nitrite as a NO donor. Myofibroblasts were induced by exposing resting keratocytes to transforming growth factor (TGF)-β1. N-cadherin and α-smooth muscle actin (αSMA) were used as myofibroblast markers. Both resting keratocytes and -stimulated keratocytes were exposed to various concentrations of sodium nitrite (1 μM to 1000 mM) for 24 to 72 h. Exposure to sodium nitrite did not alter keratocytes’ viability up to a 10 mM concentration for 72 h. However, significant cytotoxicity was observed in higher concentrations of sodium nitrite (over 100 mM). The expression of αSMA and N-cadherin was significantly increased in keratocytes by TGF-β1 stimulation after 72 h incubation. The addition of sodium nitrite (1 mM) to TGF-β1-stimulated keratocytes significantly decreased αSMA and N cadherin expression. Smad3 phosphorylation decreased after sodium nitrite (1 mM) exposure in TGF-β1-stimulated keratocytes. The effect of NO was reversed when NO scavenger, 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) was added in the culture medium. Application of sodium nitrite resulted in significant decrease of corneal opacity when measured at 2 weeks after the chemical burn in the mouse. These results verified the potential therapeutic effect of NO to decrease myofibroblast differentiation of human keratocytes and corneal opacity after injury.

Background: The processes of destruction and crosslinking of macromolecules occur simultaneously under the influence of ultraviolet (UV) radiation in synthetic polymers, dry DNA and their concentrated solutions. Objective: The effect of UV radiation on calf thymus DNA in dilute solutions subjected to UV- irradiation was studied in this work. Methods: The calf thymus DNA was studied in dilute solutions using viscometry, absorption spectroscopy and electrophoresis. Results: It was shown that at a low concentration of DNA in the buffer solution ([DNA] = 85 μg / ml) under the influence of UV radiation, the processes of destruction of macromolecules and an increase in their flexibility predominate, which are accompanied by a gradual decrease in the viscosity of their solution. In addition, due to the low concentration of the solution, intramolecular crosslinking of macromolecules predominates, which also reduces their size and, consequently, the viscosity of the solution. Conclusion: It was concluded that in dilute DNA solutions, due to the predominance of the processes of intramolecular crosslinking of macromolecules over intermolecular, only constant processes of decreasing the sizes of DNA macromolecules occur. As a result, their solubility remains virtually unchanged during UV irradiation. The described explanations are also confirmed by the results of absorption spectroscopy and electrophoresis.

A Gram-positive, aerobic, rod-shaped, non-spore-forming bacterium, designated as BN140041T, was isolated from cave soil at Gubyeongsan Mountain, Boeun-gun, Chungbuk province in Republic of Korea. Phylogenetic analysis of the 16S rRNA gene sequence showed that the strain is closely related to Nocardioides silvaticus S-34 T, N. pelophilus THG-T63T, and N. immobilis FLL521T with 97.4%, 97.1%, and 96.8% similarity. The draft genome length was 4.27 Mb containing 424 contigs with a DNA G + C content of 70.5 mol%. The ANI value between strain BN140044T and its closely related species N. silvaticus S-34 T was 82.6%. The genome sequence of BN140041T displayed a key enzyme involved in the bioremediation of organic pollutants. The diagnostic diamino acid of peptidoglycan was LL-2,6-diaminopimelic acid. The major respiratory quinone was MK-8(H4), and the major fatty acids (> 5% of the total fatty acids) were iso-C16:0 (55.3%), C18:1ω9c (7.7%) and iso-C17:0 (5.7%). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, and phosphatidylinositol. The results of genotypical, physiological, and biochemical characterization allow the phenotypic differentiation of strain BN140041T from related the Nocardioides strains. Therefore, strain BN140041T represents a novel species of the genus Nocardioides, for which we propose the name Nocardioides antri sp. nov. The type strain is BN140041T (= KCTC 49080 T = CCTCC AB 2018226 T).

Introduction Adding pertuzumab(P) on trastuzumab(H) with cytotoxic chemotherapy increased pathologic complete response (pCR) of early or locally advanced HER2 positive breast cancer (EBC) with neoadjuvant chemotherapy. Since 63.6% of pCR rate has been reported from TRYPHAENA trial, TCHP regimen has been used as a standard of neoadjuvant treatment regimen for patients with HER2 positive EBC. However, this regimen has profound toxicities in terms of myelosuppression, neurotoxicity, and etc. Furthermore we still need more information on clinical outcomes and toxicities with this regimen. Therefore, we report real world experience of EBC patients treated with neoadjuvant TCHP followed by curative surgery. Methods We retrospectively reviewed electronic medical record of EBC patients who received neoadjuvant TCHP. Information which we gathered included patients’ and tumor characteristics at the time of diagnosis, details of neoadjuvant chemotherapy, pathologic assessment of tumor response to neoadjuvant TCHP and recurrence free survival after curative surgery. pCR was defined as absence of residual invasive cancer on pathologic evaluation of the resected breast specimen and all sampled regional lymph nodes (ypT0/isN0). Results Between February 2016 and August 2019, 447 patients were treated with neoadjuvant TCHP followed by curative surgery. Median age at BC diagnosis was 56. In clinical stage, stage II was 54.6% and 45.4% of stage III and hormone receptor (HR) positive BC was 48.3%. Most commonly reported adverse event(AE) was mucositis (84%) followed by diarrhea (77%). In terms of Grade 3 AE, anorexia(6%), diarrhea(2%) were frequently observed and 9(2%) of febrile neutropenia occurred despite of prophylactic use of peg-filgrastim. Forty percent of patients experienced dose reduction due to AEs. Of 447 patients, 29% of patients underwent total mastectomy and 71% of breast conserving surgery. In terms of clinical outcome, pCR rate was 64%; 77% of HR negative BCs and 50% of HR positive BCs. Among baseline characteristics, high nuclear grade, high histologic grade, HR stats affected to pCR status (Ps Key words: neoadjuvant chemotherapy, HER2+ breast cancer, pertuzumab, pathologic complete response Citation Format: Ji-Yeon Kim, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Byung Joo Chae, Se Kyung Lee, Jai Min Ryu, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park. Real Would Evidence (RWE) of neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) in patients with HER2 positive early or locally advanced breast cancer treated Single institutional experience [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-38.

Background: Young-PEARL study showed median progression-free survival (PFS) of 20·1 months in the palbociclib plus endocrine therapy group versus 14·4 months in the capecitabine group (hazard ratio 0·659 [95% CI 0·437-0·994], log-rank p=0·0235). We conducted exploratory biomarker analysis to predict the efficacy of the trial. Methods: This was a phase II trial that randomized 184 patients with HR+ MBC in premenopausal women to palbociclib plus exemestane with GNRH agonist (Arm A, n=79) versus capecitabine (Arm B, n=62). We performed targeted sequencing (CancerSCANTM) containing 375 cancer-related genes (141 patients) and whole transcriptome sequencing (165 patients) using baseline tumor samples to examine genomic alteration in relation to drug response in terms of PFS. Result: By research-based PAM50 subtyping, 73% of patients classified as Luminal (Luminal A and Luminal B), and showed better prognosis in all patients and Arm A (p Conclusions: The alteration of a few genes including Rb1 loss may be associated with resistance of palbociclib in HR-positive premenopausal population with MBC. Luminal type showed better prognosis, and BRCA2 pathogenic mutation showed worse prognosis regardless luminal/non-luminal type. ESR1 mutation was found in low population frequency because all patients didn’t received AI therapy. Further exploration of molecular variables is warranted to determine and validate biomarkers of efficacy. Clinical trial information: NCT02592746. Citation Format: Kyunghee Park, Gun Min Kim, Kyung Hae Jung, Seok Yun Kang, In Hae Park, Jee Hyun Kim, Hee Kyung Ahn, Woong-Yang Park, Seock-Ah Im, Yeon Hee Park. Exploratory biomarker analysis of Young-PEARL [palbociclib plus exemestane with GnRH agonist versus capecitabine in premenopausal women with HR (hormone receptor)-positive, HER2-negative metastatic breast cancer (MBC)] study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-19.

Background: In the PAKT study, addition of the oral AKT inhibitor capivasertib to 1st-line paclitaxel therapy for metastatic TNBC resulted in significantly longer progression-free survival (PFS; primary endpoint; Schmid, J Clin Oncol 2020). The stratified PFS hazard ratio was 0.74 (95% CI, 0.50-1.08; one-sided P=0.06; predefined significance level of 0.10, one-sided; median PFS 5.9 vs 4.2 months with capivasertib vs placebo). Overall survival (OS) results were immature at the primary analysis with 53% of events but suggested long OS with capivasertib (HR, 0.61; 95% CI, 0.37-0.99; two-sided P=0.04). Here we report final results. Methods: This double-blind, placebo-controlled, randomised phase II trial, recruited women with untreated, metastatic TNBC. Total of 140 patients were randomly assigned (1:1) to paclitaxel 90mg/m2 (days 1, 8, 15) with either capivasertib (400mg twice daily) or placebo (days 2-5, 9-12, 16-19) every 28 days until disease progression or unacceptable toxicity. The primary endpoint was PFS. Secondary endpoints included OS in the ITT population and in patients with and without PIK3CA/AKT1/PTEN-alterations. Results: With a median F/U of 40.0 months, median OS was longer in the capivasertib arm (19.1 vs 13.5 months, stratified HR 0.70, 95% CI 0.47-1.05, p=0.085). In contrast to the earlier analysis, no meaningful differences were seen in terms of benefit with capivasertib between patients with or without alterations of PIK3CA/AKT1/PTEN. Median OS numerically favoured capivasertib vs placebo both in the PIK3CA/AKT1/PTEN-altered (stratified HR 0.58, 95% CI 0.21-1.58, p=0.290) and PIK3CA/AKT1/PTEN non-altered subgroup (stratified HR 0.74, 95% CI 0.47-1.18, p=0.207). The safety profile of capivasertib plus paclitaxel was unchanged. Conclusions: Final OS results show a numerical trend favouring capivasertib; effects were observed regardless of PIK3CA/AKT1/PTEN alterations. Consistent with the previously observed PFS benefit, these findings support further evaluation of first-line Capivasertib plus paclitaxel for metastatic TNBC in the ongoing Capitello290 randomised phase III trial in patients with and without PIK3CA/AKT1/PTEN alterations. Citation Format: Peter Schmid, Jacinta Abraham, Stephen Chan, Adrian Murray Brunt, Gia Nemsadze, Richard D Baird, Yeon Hee Park, Peter Hall, Timothy Perren, Robert C Stein, László Mangel, Jean-Marc Ferrero, Melissa Phillips, John Conibear, Javier Cortes, Andrew Foxley, Elza de Bruin, Robert McEwen, Myria Nikolaou, Daniel Stetson, Brian Dougherty, Aaron Prendergast, Max McLaughlin-Callan, Matthew Burgess, Cheryl Lawrence, Hayley Cartwright, Kelly Mousa, Nicholas Turner, Duncan Wheatley. Mature survival update of the double-blind placebo-controlled randomised phase II PAKT trial of first-line capivasertib plus paclitaxel for metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD1-11.

In this study, we developed a simple screening procedure for the determination of 18 anthelmintics (including benzimidazoles, macrocyclic lactones, salicylanilides, substituted phenols, tetrahydropyrimidines, and imidazothiazoles) in five animal-derived food matrices (chicken muscle, pork, beef, milk, and egg) using liquid chromatography-tandem mass spectrometry. Analytes were extracted using acetonitrile/1% acetic acid (milk and egg) and acetonitrile/1% acetic acid with 0.5 mL of distilled water (chicken muscle, pork, and beef), and purified using saturated n-hexane/acetonitrile. A reversed-phase analytical column and a mobile phase consisting of (A) 10 mM ammonium formate in distilled water and (B) methanol were used to achieve optimal chromatographic separation. Matrix-matched standard calibration curves (R2≥0.9752) were obtained for concentration equivalent to ×1/2, ×1, ×2, ×3, ×4, and ×5 fold the maximum residue limit (MRL) stipulated by the Korean Ministry of Food and Drug Safety. Recoveries of 61.2–118.4%, with relative standard deviations (RSDs) of ≤19.9% (intraday and interday), were obtained for each sample at three spiking concentrations (×1/2, ×1, and ×2 the MRL values). Limits of detection, limits of quantification, and matrix effects were 0.02–5.5 μg/kg, 0.06–10 μg/kg, and −98.8 to 13.9% (at 20 μg/kg), respectively. In five samples of each food matrix (chicken muscle, pork, beef, milk, and egg) purchased from large retailers in Seoul that were tested, none of the target analytes were detected. It has therefore been shown that this protocol is adaptable, accurate, and precise for the quantification of anthelmintic residues in foods of animal origin., Graphical abstract Image 1, Highlights • Multi-class determination of 18 anthelmintics in animal-derived food matrices were screened. • Samples were extracted using LLE and analyzed by LC-MS/MS. • The developed method provided satisfactory sensitivity and linearity. • None of the market samples was found to contain any measurable residues of the tested analytes. • The developed protocol is adaptable, accurate, and precise for quantification in foods of animal origin.

Purpose: This study reports the MTD, recommended phase 2 dose (RP2D), and preliminary efficacy of alpelisib or buparlisib used in combination with tamoxifen plus goserelin in premenopausal patients with hormone receptor–positive (HR+), HER2-negative (HER2−) advanced breast cancer (ABC). Patients and Methods: This study enrolled premenopausal women with HR+, HER2− ABC. Patients received tamoxifen (20 mg once daily) and goserelin acetate (3.6 mg every 28 days) with either alpelisib (350 mg once daily; n = 16) or buparlisib (100 mg once daily; n = 13) in 28-day cycles until MTD was observed. Results: The criteria for MTD were not met for both alpelisib and buparlisib. The RP2D of alpelisib and buparlisib in combination with tamoxifen and goserelin were 350 mg and 100 mg, respectively. Both combinations met protocol-specified criteria for tolerability. The most common grade 3/4 treatment-emergent adverse events (TEAE) were hypokalemia (12.5%), hyperglycemia (6.3%), and rash (6.3%) for alpelisib and alanine aminotransferase increase (30.8%), aspartate aminotransferase increase (23.1%), and anxiety (15.4%) for buparlisib. TEAEs led to treatment discontinuation in 18.8% and 53.8% of alpelisib- and buparlisib-treated patients, respectively. Progression-free survival was 25.2 months in the alpelisib group and 20.6 months in the buparlisib group. Conclusions: The RP2Ds of alpelisib and buparlisib were 350 mg and 100 mg, respectively. No unexpected safety findings were reported. Although an early-phase study, data suggest that alpelisib plus endocrine therapy may be a potentially efficacious treatment that warrants further evaluation for premenopausal patients with HR+, HER2− ABC. See related commentary by Clark et al., p. 371

Ocular surface diseases (OSD) can cause serious visual deterioration and discomfort. Commercial artificial tear solution containing hyaluronic acid (HA) show excellent biocompatibility and unique viscoelastic characteristics. Here, we developed a novel HA membrane (HAM) by chemical crosslinking using 1,4-butanediol diglycidyl ether for the effective treatment of OSDs. The main purpose of HAMs is to provide sustained release of HA to modulate the wound healing response in OSDs. The safety and efficacy of HAMs were investigated using primary cultured human corneal epithelial cells and various OSD rabbit models. In the dry state, the HAM is firm, transparent, and easy to manipulate. When hydrated, it swells rapidly with high water retention and over 90% transmission of visible light. Human corneal epithelial cells and rabbit eyes showed no toxic response to HAM. Addition of HAMs to the culture medium enhanced human corneal epithelial cell viability and expression of cell proliferation markers. Investigation of HAM wound healing efficacy using mechanical or chemical corneal trauma and conjunctival surgery in rabbits revealed that application of HAMs to the ocular surface enhanced healing of corneal epithelium and reduced corneal limbal vascularization, opacity and conjunctival fibrosis. The therapeutic potential of HAMs in various OSDs was successfully demonstrated.

Although considerable studies have focused on suppressing polysulfide shuttling in lithium–sulfur (Li–S) batteries by modifying separator surfaces, simultaneously achieving fast Li-ion transport and full active-material use remains a technological limitation. Herein, we present an effective method for anchoring zwitterionic sulfobetaine (SB) moieties on a separator surface that concurrently facilitates both selective Li-ion transport and polysulfide conversion. The platform that anchors the zwitterions was sequentially constructed by first introducing a polydopamine (PDA) coating to promote surface wettability and activity for further covalent SB binding using the aza-Michael addition reaction, which enabled the formation of a robust PDA/SB-coated separator. The zwitterion-functionalized separator exhibited a significant enhancement in ionic conductivity from 0.837 to 1.827 mS cm−1 and the Li-ion transference number from 0.186 to 0.511 due to the facile dissociation of lithium salts and selectively promoted the interactions between Li cations and the anionic sulfonate SB end groups. Along with the redox promoting effect, the polysulfide shuttling was further inhibited through strong dipole–dipole interactions. Furthermore, as Li2S precipitation was effectively mediated by the SB zwitterions and improved sulfur-conversion kinetics was achieved, outstanding Li–S battery performance with an initial discharge capacity of 1365.9 mA h g−1 was obtained, while delivering an ultra-low capacity decay rate of 0.034% during long-term cycling (up to 1200 cycles) at 3.0C, even at a high load. Therefore, we believe that the proposed study harnessing zwitterionic separator functionalization would enable the rational design of functional separators for the promoted kinetics and suppressed diffusion of unfavorable reaction intermediates for high performance batteries.

Structural parameters, such as metal-like semiconductor and electrochemical properties of functionalized polyaniline, hold great potential especially for the development of the cell–substrate interface due to its ion/electron transfer ability. We report the one-step synthesis of sulfonic acid-doped polyaniline nanobuds (s-PANINbs) with controlled shape/size under various oxidation potentials. The different oxidation states of s-PANINbs are used to investigate the cell-specific platform for the induction of neuronal networks in PC12 cells, including the growth, proliferation, and differentiation of cells. The unique structure of one-dimensional (1-D) s-PANINbs enhances its intrinsic conductive properties, and facilitates the dispersibility and electrochemical activity via covalent bonding with dopants. The protonated emeraldine salt nanobuds of s-PANINbs synthesized at 0.18 V anodic potential demonstrated low resistivity (∼81.18 mΩ) and charge transfer resistance (∼3253 Ω). The most biologically compatible protonated emeraldine salt was used in vitro to induce PC12 cells associated with neurite outgrowth, contributing to the electrophysiology of neuronal cells under an external electrical stimulation. The western blotting analysis and qRT-PCR results show that β-III Tubulin, synapsin I, and TREK-1 are highly expressed in PC12 cells, confirming their successful differentiation into neural-specific cells. Our approach demonstrates the promising role of the self-standing framework based on the s-PANINbs of the protonated emeraldine salt in peripheral nerve repair for the future in vivo cell-interface.

Muscle atrophy, or loss of skeletal muscle, is caused by aging, malnutrition, immobility through injury, or diseases such as cancer. Chamomile (Matricaria chamomilla L.) contains various active components, including flavonoids, sesquiterpenes, polyacetylenes, and coumarins, and is used in various herbal medicines in the European Pharmacopoeia. In this study, we investigated the effects of ethanol extract of chamomile [Formula: see text](MC) on muscle wasting and its mechanism of action. Mice with dexamethasone (DEX)-induced muscle atrophy were orally administered MC (100, 200, and 300 mg/kg) for 4 weeks. Micro-computed tomography analysis showed that MC (200 and 300 mg/kg) significantly recovered DEX-induced loss of muscle volume, density, and weight and MC-treated DEX-induced mice also showed increased moving distance and grip strength. MC suppressed the mRNA level of muscle RING finger 1 (MuRF1) while increasing the expression of mitochondrial transcription factor A (TFAM), MyoD, and Myogenin-1. We found 25 peaks in MC samples through HPLC analysis and identified 6 peaks by comparison with a profile of standard compounds: chlorogenic acid (CGA), luteolin-7-O-glucoside (L7G), patulitrin, apigenin-7-O-glucoside (A7G), herniarin, and (E)-tonghaosu. Of these components, the gene expression of MyoD was significantly augmented by patulitrin, herniarin, CGA, and L7G in C2C12 cells, while Myogenin-1 gene expression was increased by A7G, patulitrin, herniarin, CGA, and L7G. Moreover, TFAM gene expression and phosphorylation of AKT were increased by all six ingredients. Based on our results, we suggest MC for use as a supplement or remedy for muscle wasting, including cachexia and sarcopenia.

Introduction Burn injuries are common afflictions; however, conservative wound care frequently leads to poor treatment compliance and physical disability in deep burn patients. Therefore, regenerative biologic materials, which are more effective for tissue repair, are required, particularly for deep second-degree burns. A novel spray formulation of basic fibroblast growth factors (bFGF) was produced by synthesizing fibroblast growth factor proteins. In this post-marketing surveillance (PMS) study, we assessed the safety and efficacy of bFGF and indirectly compared this formulation with cultured epidermal autografts (CEAs) for treating deep second-degree burns. Materials and methods A total of 3173 patients treated at 15 hospitals were used for PMS of bFGF in South Korea for six years. In total, 1635 patients with deep second–degree burns were selected for assessing adverse events (AEs) of bFGF treatments. Efficacy was evaluated according to time periods until re-epithelialization, and clinical usefulness of bFGF was indirectly compared with that of CEAs. Results AEs occurred in 37 patients (2.3%) and included application site pain (1.7%) and contact dermatitis (0.6%). All AEs were mild and were evaluated as probably unrelated with bFGF. The average time for re-epithelialization was 8 days; this time span was significantly longer after major burns (9.7 days) than after minor (7.8 days) or moderate burns (7.9 days). Most treated burn wounds (99.8%) were assessed as improved. The indirect comparison included 534 patients using the same inclusion criteria for CEA patients (n = 35). The bFGF treatment demonstrated superior efficacy compared to CEAs by significantly reducing the average post-burn day of application time (5.4 vs. 8.8 days) and re-epithelialization time (7.1 vs. 13.7 days). Conclusion Our study demonstrated that bFGF is a compelling regenerative therapy with competitive clinical efficacy and safety for deep second–degree burns and reduced treatment time, which is expected to reduce medical costs, particularly for deep second–degree burn patients.

Purpose YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC.Results In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.

In this work, bare Sn and carbon-coated Sn nanoparticles were prepared by a pulsed wire evaporation process. The effect of binder and pressing ratio on electrochemical properties of Sn/C composite electrodes was investigated to enhance the structural stability of Sn anode. The electrode containing the polyamide-imide (PAI) binder with high tensile strength (52 MPa) exhibited higher coulombic efficiency and better cycle performance compared to the electrode with the conventional polyvinylidene fluoride (PVdF) binder. The 5%-pressed Sn/C electrode with the proper porosity in the electrode demonstrated the best cycle performance corresponding to 45% of capacity retention ratio until 100 cycles.

Polyacrylonitrile (PAN)/Si composite fibers (electrodes) with flexibility were fabricated using an elec-trospinning method and then Si-embedded carbon (Si/C) fibers were prepared by carbonizing the composite fibers at 800, 900, and 1000°C. Si particles were distributed in the interior and exterior of entangled PAN fibers. After carbonization, the structure of electrodes was preserved but the diameter of fibers was decreased owing to the release of component elements constituting PAN such as nitrogen and oxygen. Crystalline Si particles existed in carbon fibers with both amorphous and crystalline phases. As carbonization temperature increased, the carbon content and the crys-tallinity of carbon increased. The electrode carbonized at 1000°C with the lowest charge transfer resistance exhibited the best electrochemical properties in terms of capacity, coulombic efficiency and cycle life.

In this study, the effects of the surface structure of electrospun polyvinylidene fluoride (PVDF) nanoweb on surface wettability were analyzed. The conditions of the surface structure representing the lotus and petal effects were derived, and the difference in the dynamic behavior of the water droplets on the surfaces was investigated. To this end, a PVDF nanoweb was fabricated by electrospinning various concentrations of PVDF solutions. The nanoscale roughness was adjusted by varying the CF4 plasma etching time. It was seen that when the concentration of the electrospun PVDF solution was 15 or 20 wt%, a hierarchical structure of microbeads and nanofibers was formed. In the 20 wt% nanoweb, droplets formed an apparent contact angle of 149.5 ± 2.2°, and the petal effect was observed in which the droplets were pinned on the surface and did not roll off even when the nanoweb was tilted by 180°. As a result of introducing fine nanostructures with CF4 plasma etching on the 20 wt% nanoweb, the apparent contact angle increased to 162.8–164.4°, and the shedding angle decreased to 5.3–8.1°, showing a wetting transition to the lotus effect, regardless of the plasma etching time. In addition, the lotus effect was observed when 15 wt% nanoweb was treated with CF4 plasma etching for more than 10 min. We confirmed that the lotus effect was exhibited when the three-phase contact line of the PVDF nanoweb/water/air was discontinuous, and the contact area between the surface and the water droplets was reduced with increased air pockets at this interface, which led to a decrease in the adhesive force and the impact of negative pressure.

Objectives To investigate the genetic characteristics associated with eradication failure of Staphylococcus aureus in infants below 90 days old. Methods S. aureus isolated from clinical specimen cultures (blood, surgical tissue, or drainage, pus, etc.) and routine screening cultures in the neonatal intensive care unit (nasal and axillary skin swab) from patients below 90 days old were collected prospectively for 1 year, from August 2017 to July 2018. The isolates underwent typing and screening for genes associated with chlorhexidine (qacA/B), quaternary ammonium (smr), and mupirocin resistance (iles mutation, mupA, mupB), as well as Panton-Valentine leukocidin (PVL) toxin. Results During the study period, 40 nonduplicate isolates were included for analyses, of which 70.0% were methicillin-resistant S. aureus (MRSA). Mupirocin resistance was found in 25% of the total isolates; 17.4% of the colonizers; and 35.3% of the pathogens (P = 0.196). Chlorhexidine resistance gene was found in 3 MRSA isolates colonized in the nares of preterm infants. All isolates harbored the disinfectant quaternary ammonium compound (QAC) resistance gene. PVL toxin gene was found in 57.5%, and the presence of PVL gene among colonizers and pathogens was similar (69.6% vs. 41.2%, P = 0.072). Conclusions Mupirocin, chlorhexidine, and QAC-resistant MRSAs harboring the PVL toxin gene were found in the nasal carriages of preterm infants. In this highly vulnerable patient population, one-fourth of the isolates harbored mupirocin-resistant genes, and all were resistant to QAC disinfectants. These strains are associated with persistence in both carriage and environmental reservoirs within the hospitals.

Polyurethane (PU) nanofibers containing three different essential oils (teatree, cinnamon bark, clove) were produced by electrospinning method. Morphology of the electrospun nanofibrous was studied using Field Emission Scanning Electron Microscope (FE-SEM). We were studying to reveal that different concentration of essential oil display different mechanical properties for the nanofibrous mat. The antibacterial properties of the nanofibrous loaded with the essential oil were studied quantitatively and qualitatively using three strains (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa). The antibacterial evaluation showed higher antibacterial activity for nanofibrous loaded with essential oil compares to control sample. In vitro cell culture were proceed to confirm biocompatibility of the nanofibrous contained essential oils. In this study, we present a comparison of the samples for each of the experiment based on the derived test items and test methods. The results of this study demonstrate that the proposed nanofibrous mat loaded with essential oil will be a promising future material for different biomedical applications.

BACKGROUND: Poly (ADP-ribose) polymerase inhibitors combined with immunotherapy have shown antitumour activity in preclinical studies. We aimed to assess the safety and activity of olaparib in combination with the PD-L1-inhibitor, durvalumab, in patients with germline BRCA1-mutated or BRCA2-mutated metastatic breast cancer.METHODS: The MEDIOLA trial is a multicentre, open-label, phase 1/2, basket trial of durvalumab and olaparib in solid tumours. Patients were enrolled into four initial cohorts: germline BRCA-mutated, metastatic breast cancer; germline BRCA-mutated, metastatic ovarian cancer; metastatic gastric cancer; and relapsed small-cell lung cancer. Here, we report on the cohort of patients with breast cancer. Patients who were aged 18 years or older (or aged 19 years or older in South Korea) with germline BRCA1-mutated or BRCA2-mutated or both and histologically confirmed, progressive, HER2-negative, metastatic breast cancer were enrolled from 14 health centres in the UK, the USA, Israel, France, Switzerland, and South Korea. Patients should not have received more than two previous lines of chemotherapy for metastatic breast cancer. Patients received 300 mg olaparib in tablet form orally twice daily for 4 weeks and thereafter a combination of olaparib 300 mg twice daily and durvalumab 1·5 g via intravenous infusion every 4 weeks until disease progression. Primary endpoints were safety and tolerability, and 12-week disease control rate. Safety was analysed in patients who received at least one dose of study treatment, and activity analyses were done in the full-analysis set (patients who received at least one dose of study treatment and were not excluded from the study). Recruitment has completed and the study is ongoing. This trial is registered with ClinicalTrials.gov, NCT02734004.FINDINGS: Between June 14, 2016, and May 2, 2017, 34 patients were enrolled and received both study drugs and were included in the safety analysis. 11 (32%) patients experienced grade 3 or worse adverse events, of which the most common were anaemia (four [12%]), neutropenia (three [9%]), and pancreatitis (two [6%]). Three (9%) patients discontinued due to adverse events and four (12%) patients experienced a total of six serious adverse events. There were no treatment-related deaths. 24 (80%; 90% CI 64·3-90·9) of 30 patients eligible for activity analysis had disease control at 12 weeks.INTERPRETATION: Combination of olaparib and durvalumab showed promising antitumour activity and safety similar to that previously observed in olaparib and durvalumab monotherapy studies. Further research in a randomised setting is needed to determine predictors of therapeutic benefit and whether addition of durvalumab improves long-term clinical outcomes compared with olaparib monotherapy.FUNDING: AstraZeneca.

Stent-mediated therapy is minimally invasive and fairly effective for the specific tissue and organs with tubal structures such as the esophagus, intestine, and blood vessels. Cerebral arteries are one of the most critical tubal structures to maintain the physiological function and the life of the human. Since the retrieval of the implanted vascular stent is difficult and risky, the one-step stent therapy is imperative. However, the placement of a current pipe-typed stent can also limit the nutritional supply to the vascular wall. Also, the non-degradable polymeric layer is possibly sensitized to the recipient as a foreign body after prolonged period after implantation. Herein, we developed PLGA/PCL nanofiber-coated stent for blocking the flow towards the aneurysm cavity as well as allowing nutritional support to the vessel with the biodegradability. The PLGA/PCL nanofiber-coated stent (NCS) was fabricated via electrospinning composite nanofibers onto a self-expandable mater metal stent. The as-fabricated NCS was physicochemically characterized using FT-IR, FE-SEM, and UTM, and experimented in vivo as implanted in porcine models and radiologically and histologically analyzed. The NCS demonstrated improved physicochemical properties for intracranial aneurysmal treatment including enhanced mechanical properties. The bioabsorbability of NCS was confirmed in the animal model.

Here, we report the synthesis of three-dimensional (3D) polycaprolactone (PCL) nanofiber incorporated with core-satellite platinum nanoparticles (PtNPs, 2–3 nm) coated gold nanospheres (AuNPs, 30 nm) via the simple lactic acid assisted self-assembly electrospinning technique. The Pt-AuNPs nanoparticle in core-satellite form has been prepared by following solution based methods and characterized with TEM, HR-TEM, UV-Visible, and XRD spectroscopic techniques. The surface morphology and structural analysis of 3D nanofiber scaffolds have been performed with FTIR, TGA, FESEM, and HR-TEM analysis techniques and shown the successful preparation of 3D electrospun fibrous structure composed of Pt-AuNPs loaded PCL (PCL@Pt-AuNPs) as a potential biomaterial for bone tissue engineering applications.

In the thriving field of nano-materials science, the nanofibrous structure with immobilizednanoparticles (NPs) inside or outside of the fibers currently received great interest for their potential synergic effects. In the cooperative combining strategy, electrospun nanofibers in a tailored manner are promising materials as a platform to mutually gain both advantages of the interconnected fibrous structure and unique properties of NPs. Herein, we presented the one-step fabrication method for in-situ synthesis of novel uprightly stood extra-long hierarchical multi-metallic (Fe/Cu/S) nano-needles (NNs) on polyurethane (PU) electrospun nanofibers (PU@FeCuS). The multi-metallic nanostructures (FeCuSNNs) were in-situ synthesized by simply immersing PU nanofiber into the supersaturated FeSO4/CuSO4 solution. The results of SEM, FE-SEM, EDX mapping and 3D rendering model simulation with CAE software revealed the morphology, the composition of FeCuSNNs, and the significantly increased surface area. The possible crystallization mechanism of the formation of NNs was discussed.

Recently, air quality is seriously worsening because of micro dust. As a result, respiratory and heart disease patients are also increasing every year. Therefore, the development of a highly efficient air filter media is required. In this study, we developed an antibacterial air filter media with activated carbon (AC) and cinnamon essential oil (CO). 12 wt.% polyurethane (PU) solution mixed with CO and AC was electrospun to prepare the AC+CO+PU nanofiber mat. We studied various characteristics of the AC+CO+PU nanofibrous mat. The surface morphology of mats in different concentration ratios was observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). We confirmed the antimicrobial activity of the nanofibrous mat using zone of inhibition test with Staphylococcus aureus and Escherichia coli. Air filter test was carried out to observe air filtration efficiency and pressure drop. This data was used to calculate the quality factor of the fabricated nanofiber air filter media. The fabricated antimicrobial nanofiber air filter media can be applied to various fields such as personal masks, air purification devices and bio applications.

Enzymatic hydrolysis is a common finishing method for cellulosic materials, to improve fabric softness, appearance, and surface properties. However, its potential to trigger superhydrophobicity has not been studied in depth. In this study, a superhydrophobic cellulose fabric was fabricated in two steps. Micro-/nano-hierarchical roughness on the fabric surface was achieved by cellulase from Aspergillus niger, through enzymatic hydrolysis. Subsequently, hydrophobization was carried out by a dip coating method, using polydimethylsiloxane (PDMS). Enzyme concentration and treatment temperature were varied to find the values that provided the greatest superhydrophobicity. As enzyme concentration and temperature increased, the nano-scale roughness increased, along with weight reduction. The degree of crystallinity and reduction in tensile strength were also increased with weight loss via enzyme hydrolysis. As air pockets were formed by micro-/nano-structures on the fiber surface, the water contact angle increased and the shedding angle tended to decrease. The sample treated with 5 g/l enzyme at 60 ℃ for 60 min and coated with PDMS 1 wt.% coating solution had the greatest superhydrophobicity, with a water contact angle of 162° and a shedding angle of 7.0°. The weight loss and reduction in tensile strength of the developed superhydrophobic fabrics were 2.9% and 39.0%, respectively. This approach reduces the necessity for an additional process to introduce nano-scale roughness, and it has the potential to produce superhydrophobic cellulosic biomass for outdoor clothing.

In this study, lactic acid bacteria strains (LABs) were isolated from Korean traditional fermented food and examined as potential probiotics using in vitro methods. Ten LAB strains survived in de Man, Rogosa and Sharpe broth adjusted to pH 2.5 were tested for resistance to acidic conditions and bile, antimicrobial activity, and α-glucosidase inhibitory activity. Among them, strain MBEL1397 showed antimicrobial activity against Bacillus cereus and exhibited survival rates of over 97% in acidic and bile conditions. The α-glucosidase inhibitory activity was 3.91 ± 0.25%, corresponding to approximately 2.3 times higher than that of acarbose. MBEL1397 was susceptible to ampicillin, erythromycin, and penicillin G and identified as Lactobacillus sakei. It was deposited to Korean Collection for Type Culture (KCTC) as KCTC14037BP. In conclusion, these results demonstrate that L. sakei MBEL1397 might be prominent probiotics with potential hypoglycemic effects.

Sphingosine kinase1 (SphK1) is an acetyl-CoA dependent acetyltransferase which acts on cyclooxygenase2 (COX2) in neurons in a model of Alzheimer’s disease (AD). However, the mechanism underlying this activity was unexplored. Here we show that N-acetyl sphingosine (N-AS) is first generated by acetyl-CoA and sphingosine through SphK1. N-AS then acetylates serine 565 (S565) of COX2, and the N-AS-acetylated COX2 induces the production of specialized pro-resolving mediators (SPMs). In a mouse model of AD, microglia show a reduction in N-AS generation, leading to decreased acetyl-S565 COX2 and SPM production. Treatment with N-AS increases acetylated COX2 and N-AS-triggered SPMs in microglia of AD mice, leading to resolution of neuroinflammation, an increase in microglial phagocytosis, and improved memory. Taken together, these results identify a role of N-AS in the dysfunction of microglia in AD., Neuronal sphingosine kinase 1 (SphK1) acetylates COX2 which is needed for microglial phagocytosis activity, and release of pro-resolving mediators (SPMs) from neurons. Here the authors examine how SphK1-mediates COX2 acetylation, and how this leads to increased secretion of SPMs from neurons in the context of Alzheimer’s disease models.

The OlympiAD Phase III study (NCT02000622) established the clinical benefits of olaparib tablet monotherapy (300 mg twice daily) over chemotherapy treatment of physician’s choice (TPC) in patients with a germline BRCA1/2 mutation (gBRCAm) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who had received ≤2 chemotherapy lines in the metastatic setting. Here, we report pre-specified analyses of data from Asian (China, Japan, Korea and Taiwan) patients in the study. All patients were randomized 2:1 to olaparib tablets (300 mg twice daily) or single-agent chemotherapy TPC (21-day cycles of either capecitabine, eribulin or vinorelbine). The primary endpoint was progression-free survival assessed by blinded independent central review. The prevalence of gBRCAm in the OlympiAD Asian subgroup screened for study recruitment was 13.5%. Patient demographics and disease characteristics of the Asian subgroup (87/302 patients) were generally well balanced between treatment arms. Asian patients in the olaparib arm achieved longer median progression-free survival, assessed by blinded independent central review, versus the chemotherapy TPC arm (5.7 vs 4.2 months; HR = 0.53 [95% CI: 0.29–0.97]), which was consistent with findings in the global OlympiAD study population. Findings on secondary efficacy and safety/tolerability outcome measures in Asian patients were also similar to those observed in the global OlympiAD study population. The OlympiAD study was not powered to detect race-related differences between treatment groups; however, the consistency of our findings with the global OlympiAD study population suggests that previously reported findings are generalizable to Asian patients.

Background BMS-470539, a recently introduced selective agonist of the melanocortin 1 receptor, is known to have anti-inflammatory properties. In this study, we investigated the effects of BMS-470539 on lipopolysaccharide (LPS)-induced inflammatory responses and delayed apoptosis with its signaling pathways in human neutrophils. Methods Isolated human neutrophils were incubated with various concentrations of BMS-470539 (1, 10, and 100 µM) in the presence or absence of LPS (100 ng/ml), and the expression of pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β, were assessed. The effects of BMS-470539 on the expression of mitogen-activated protein kinases (MAPKs), such as p38, extracellular-signal-regulated kinase 1/2, and c-Jun N-terminal kinase, and the expression of nuclear factor kappa B (NF-κB) in LPS-stimulated human neutrophils, were evaluated by enzyme-linked immunosorbent assay. Neutrophil apoptosis was also measured by fluorescence-activated cell sorting (annexin V/propidium iodide) in LPS-stimulated neutrophils under treatment with BMS-470539. Results BMS-470539 attenuated LPS-induced expression of pro-inflammatory cytokines, and phosphorylation of MAPKs and NF-κB. LPS stimulation reduced neutrophil apoptosis compared to the controls; however, BMS-470539 significantly inhibited the reduction of neutrophil apoptosis. Conclusions BMS-470539 can suppress the inflammatory responses of LPS-stimulated neutrophils by inhibition of MAPK pathways or NF-κB pathway, and it can also inhibit LPS-delayed neutrophil apoptosis.

IMPORTANCE Micro-RNAs (miRNAs) have been studied as new biomarkers or mediators in various diseases, but the value of aqueous humour (AH) miRNAs in diabetic macular oedema (DMO) is still not known. BACKGROUND To compare AH miRNAs and related cytokine expression in DMO patients and healthy controls. DESIGN Prospective cross-sectional study. PARTICIPANTS Twenty naive DMO patients and 13 control subjects, who were scheduled for intravitreal injection and cataract surgery, respectively. METHODS AH samples were collected at the beginning of each procedure and analysed using a miRNA polymerase chain reaction (PCR) array composed of 84 miRNAs, reverse transcripase-quantitative PCR (qPCR) for verifying selected differentially expressed miRNAs, and a cytokine assay, the results of which were compared with bioinformatics conducted to find out genes associated with DMO-related miRNAs. MAIN OUTCOMES MEASURES AH expression of miRNAs and cytokines and the bioinformatics results. RESULTS Five miRNAs (hsa-miR-185-5p, hsa-miR-17-5p, hsa-miR-20a-5p, hsa-miR-15b-5p and hsa-miR-15a-5p) showing a fold change greater than -50 in log2 values in the miRNA PCR array were selected, all significantly down-regulated in the DMO group compared to the control group (P

Measuring the translational diffusion of proteins under physiological conditions can be very informative, especially when multiple diffusing species can be distinguished. Diffusion NMR or diffusion-ordered spectroscopy (DOSY) is widely used to study molecular diffusion, where protons are used as probes, which can be further edited by the proton-attached heteronuclei to provide additional resolution. For example, the combination of the backbone amide protons ((1)H(N)) to measure diffusion with the well-resolved (1)H/(15)N correlations has afforded high-resolution DOSY experiments. However, significant amide-water proton exchange at physiological temperature and pH can affect the accuracy of diffusion data or cause complete loss of DOSY signals. Although aliphatic protons do not exchange with water protons and thus are potential probes to measure diffusion rates, (1)H/(13)C correlations are often in spectral overlap or masked by the water signal, which hampers the use of these correlations. In this report, a method was developed that separates the nuclei used for diffusion (alpha protons, (1)H(α)) and those used for detection ((1)H/(15)N and (13)C’/(15)N correlations). This approach enabled high-resolution diffusion measurements of polypeptides in a mixture of biomolecules, thereby providing a powerful tool to investigate coexisting species under physiological conditions.

A bioinspired three-dimensional (3D) fibrous structure possesses biomimicry, valuable functionality, and performance to scaffolding in tissue engineering. In particular, an electrospun fibrous mesh has been studied as a scaffold material in various tissue regeneration applications. We produced a low-density 3D polycaprolactone/lactic acid (LA) fibrous mesh (3D-PCLS) via the novel lactic-assisted 3D electrospinning technique exploiting the catalytic properties of LA as we reported previously. In the study, we demonstrated a strategy of recycling the LA component to synthesize the osteoinductive biomolecules in situ, calcium lactate (CaL), thereby forming a 3D bioactive PCL/CaL fibrous scaffold (3D-SCaL) for bone tissue engineering. The fiber morphology of 3D-PCLS and its packing degree could have been tailored by modifying the spinning solution and the collector design. 3D-SCaL demonstrated successful conversion of CaL from LA and exhibited the significantly enhanced biomineralization capacity, cell infiltration and proliferation rate, and osteoblastic differentiation in vitro with two different cell lines, MC3T3-e1 and bone marrow stem cells. In conclusion, 3D-SCaL proves to be a highly practical and accessible strategy using a variety of polymers to produce 3D fibers as a potential candidate for future regenerative medicine and tissue engineering applications.

In this study, the antioxidant effects of seven types of commercial Chunjang from China (C1∼3) and Korea (K1∼4) were compared for their ability to protect against H2O2-induced DNA damage. Outputs included total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH RSA), oxygen radical absorbance capacity (ORAC), total radical trapping antioxidant potential (TRAP), and comet assays. TPC was the highest in C3 (1,250.8 mg gallic acid equivalent/100 g). C1 exhibited a significantly higher DPPH RSA IC50 (7.5 mg/mL) and ORAC concentration (8.22 μM Trolox equivalent) compared with all other samples, and C1 and K1 exhibited the highest TRAPs. H2O2-induced DNA damage was effectively protected by Chunjang, with a higher observed in C2, C3, and K1 (24.2∼25.3 μg/mL) compared with the other samples (28.3∼30.0 μg/mL). Our results showed that commercial Chunjang contains polyphenol and antioxidant activities. The differences between the samples might be attributed to different origins, materials, and processing methods.

A renewable cellulose-based dual network ionogel electrolyte is synthesized by phosphorylating and dissolving a microcrystalline cellulose network in a tailor-made 1,3-dimethylimidazolium methyl phosphite [DMIM][MeO(H)PO3] ionic liquid mixture, with subsequent polymerization of the 2-hydroxyethyl methacrylate monomer in the presence of a cellulose network. The as-synthesized ionogel electrolytes exhibit high ionic conductivity (2.6–22.4 mS cm−1) over a wide temperature range (30–120 °C), with a maximum toughness of 1.46 MJ m−3 at 30 °C. A renewable flexible supercapacitor is fabricated by sandwiching the cellulose-based ionogel electrolyte between two activated carbon electrodes, delivering high specific capacitance and rate capability of 174 F g−1 and 88% at 120 °C at a cell voltage of 2.5 V. These remarkable capacitive features at elevated temperature are associated with fast dynamics, facilitated by thermally activated ion transport, as demonstrated by the Vogel-Tammann-Fulcher and Nyquist plots.

Background: Although the consumption of vitamin beverages has increased because of the recent interest in health and beauty, guidelines addressing appropriate consumption habits are lacking. Thus, the aim of this study was to investigate the erosive potential of several vitamin beverages and to propose guidelines for the appropriate intake of these drinks.Methods: Five vitamin beverages were selected after a pre-investigation of the current beverage market. Coca-Cola and mineral water were selected as the control beverages. The pH of the beverages was measured with a calibrated pH meter, and the titratable acidity (TA) was determined by using 1 M sodium hydroxide to reach pH 5.5 (TA5.5) and 7.0 (TA7.0). The screening method suggested by the International Organization for Standardization was used to measure pH variation (𝚫pH) by using an under-saturated hydroxyapatite solution to determine the difference between the initial and final pH of the screening solution. All measurements were performed in triplicate.Results: All vitamin beverages tested in this study exhibited a low pH (2.53∼2.99), similar to Coca-Cola, which is known to be a highly acidic beverage. The highest TA5.5 and TA7.0 values of the vitamin beverages were 7.03 ml and 8.81 ml, respectively. The largest change in pH determined by using the screening solution was found in Bacchus D (𝚫pH 1.44±0.05). The mean 𝚫pH of the vitamin beverages was 1.12±0.29, which was higher than that of Coca-Cola (positive control, 𝚫pH 0.58±0.05).Conclusion: Vitamin beverages exhibited an erosive potential capable of damaging enamel surfaces. Therefore, the frequency of vitamin beverage intake should be limited, and individuals consuming these drinks should try to restore normal oral pH as quickly as possible.