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Gamma irradiation is a useful technology to change the physical and biological properties of natural molecules. In this study, we investigated whether gamma irradiation improve properties of chrysin as an anti-inflammatory candidates. Chrysin was converted into two compounds (CM1 and CM2) by gamma irradiation. We determined the therapeutic potential of these compounds in bone marrow-derived macrophages and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions in Balb/c mice. The structural changes to chrysin led to the reduction of cytotoxicity without loss of anti-inflammatory properties in BMDMs. Purified CM2 inhibited lipopolysaccharide (LPS)-induced overexpression of nitric oxide, tumor necrosis factor-α, interleukin (IL)-6, and surface molecules without cytotoxicity in BMDMs, while CM1 revealed strong cytotoxicity. Furthermore, treatment with CM2 significantly alleviated AD-like skin symptoms and clinical signs in DNCB-induced AD mice model. The suppression of AD mediated by CM2 treatment was accompanied by decrease inflammatory T cell cytokines (IFN-γ, IL-5, IL-4, and IL-17). The chemical structure of CM2 and structural transformation mechanism were determined by nuclear magnetic resonance and mass spectrometry. Our study findings provide evidence that CM2 produced by gamma irradiation of chrysin can be an attractive therapeutic agent for AD.

Objective The objective of this study was to evaluate the pharmacokinetics and bioequivalence of two formulations (the original capsule ("reference") and the new tablet ("test") formulations) of 135-mg choline fenofibrate under fed and fasted conditions. Materials and methods This was an open-label, randomized, single-dose, crossover bioequivalence study in healthy Korean males. A total of 40 individuals were separately enrolled in the high-fat fed and the fasting study, respectively, and were randomized in a 1:1 ratio into two sequences. Serial blood samples were collected over 72 hours after drug administration. Plasma concentrations of fenofibric acid were determined by a validated LC-MS/MS method. Pharmacokinetic (PK) parameters were estimated using noncompartmental methods. Results Overall, 37 and 35 individuals completed the fed and the fasting study, respectively, as planned. The estimated Cmax, AUC0-∞, and AUC0-last were comparable between the test and the reference formulations in both fed and fasting studies (p > 0.05). The 90% confidence intervals for the geometric mean ratios of Cmax, AUC0-∞, and AUC0-last were 0.92 - 1.06, 0.95 - 1.01, and 0.95 - 1.01 in the fed study; and 0.94 - 1.12, 0.94 - 1.00, and 0.94 - 1.00 in the fasting study, respectively. For both formulations, tmax was significantly prolonged under fed condition compared to fasting condition (p 0.05). Conclusion The reference and the test formulations of 135 mg choline fenofibrate show comparable pharmacokinetic profiles of fenofibric acid under both fed and fasted conditions and are considered bioequivalent. .

Background: Treating aged animals with plasma of an early developmental stage (e.g, umbilical cord plasma) showed an impressive potential to slow age-associated degradation of neuronal and cognitive functions. Translating such findings to clinical realities, however, requires effective ways for assessing treatment efficacy; ideal methods should be minimally invasive, amenable for serial assays, cost-effective, and quantitative. Methods: We developed a new biosensor approach to monitor anti-aging therapy. We advanced two key sensor components: i) a blood-borne metabolite was identified as a surrogate aging-marker; and ii) a compact and cost-effective assay system was developed for on-site applications. We treated aged mice either with human umbilical cord plasma or saline; unbiased metabolite profiling on mouse plasma revealed arachidonic acid (AA) as a potent indicator associated with anti-aging effect. We next implemented a competitive magneto-electrochemical sensor (cMES) optimized for AA detection directly from plasma. The developed platform could detect AA directly from small volumes of plasma (0.5 µL) within 1.5 hour. Results: cMES assays confirmed a strong correlation between AA levels and anti-aging effect: AA levels, while decreasing with aging, increased in the plasma-treated aged mice which also showed improved learning and memory performance. Conclusions: The cMES platform will empower both pre- and clinical anti-aging research by enabling minimally invasive, longitudinal treatment surveillance; these capacities will accelerate the development of anti-aging therapies, improving the quality of individual lives.

Pancreatic ductal adenocarcinoma (PDAC) is a common malignancy that shows high cancer-mortality and poor prognosis, in the absence of obvious symptoms and biomarkers for early diagnosis. Gemcitabine is a type of chemotherapy drug which commonly used to treat PDAC, however, the rapid acquisition of resistance to gemcitabine treatment has been observed in many of PDAC patients. The miRNA-producing enzymes Dicer is crucial for the maturation of miRNAs, and we found previously that ERK/Sp1 signaling transactivate both gene and protein expressions of Dicer, leading an acquisition of gemcitabine resistance in pancreatic cancer cells both in vitro and in vivo. In this study, we further identified that phosphomimetic S1016E of Dicer may regulate miRNAs maturation, resulting an imbalance of glutaminase (GLS) and glutamine synthetase (GS/GLUL). Metabolism analysis revealed that gemcitabine-resistant PANC-1 (PANC-1/GEM) cells have high glutamine dependence and GLS/GLUL ratio. Our study suggests that phosphomimetic Dicer S1016E plays a critical role in glutamine metabolism reprogramming and gemcitabine resistance of pancreatic cancer. Citation Format: Ching-Feng Chiu, Ji Min Park, Yu-Shiuan Shen, Chia-Ying Lin, Tung-Wei Hsu, Yen-Hao Su, Hsin-An Chen. Phosphomimetic Dicer rewires glutamine metabolism and gemcitabine resistance in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6386.

This study is designed to explore the effect of FTH1 on PDAC human pancreatic cancer cells, proline metabolism, and their crosstalk. Considering the high prevalence of pancreatic cancer with an absence of efficient therapy against PDAC, the present study may provide experimental evidence in support of the novel role of FTH1 in proline metabolism and suggest FTH1 as a potential target for PDAC patients. We further focus on the underlying molecular mechanism of how FTH1 cross-talks with PYCR1 and leads KRAS-mutated PDAC cell growth, investigating whether miRNAs regulation involves in FTH1 mediating PYCR1 expression. Taken together, our study provides a novel function of FTH1 and its cross-talk with PYCR1 may be a novel target for pancreatic cancer research and thus these findings will help us to find metabolite-based therapeutic strategies to improve KRAS-mutated PDAC. Citation Format: Ji Min Park, Ching-Feng Chiu. The cross-talk between FTH1 and PYCR1 drives pancreatic cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6378.

A Gram-stain-negative, aerobic, non-motile and ovoid or rod-shaped bacterial strain, designated BPTF-M20T, was isolated from tidal flat sediment in the Yellow Sea, Republic of Korea. Strain BPTF-M20T grew optimally at 30 °C, at pH 7.0–8.0 and in the presence of 2.0–3.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree of 16S rRNA gene sequences showed that strain BPTF-M20T fell within the clade comprising the type strains of Pseudoruegeria species. Strain BPTF-M20T exhibited 16S rRNA gene sequence similarity values of 97.4–98.3 % to the type strains of Pseudoruegeria haliotis , Pseudoruegeria lutimaris , ‘ Pseudoruegeria litorisediminis’ and Pseudoruegeria sabulilitoris and 96.4–96.9 % to the type strains of the other Pseudoruegeria species. Strain BPTF-M20T contained Q-10 as the predominant ubiquinone and C18 : 1 ω7c as the major fatty acid. The major polar lipids detected in strain BPTF-M20T were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminolipid and one unidentified glycolipid. The DNA G+C content of strain BPTF-M20T was 63.2 mol%. Mean DNA–DNA relatedness values of strain BPTF-M20T with the type strains of P. haliotis , P. lutimaris , P. sabulilitoris and ‘P. litorisediminis’ were 18–27 %. Differential phenotypic properties, together with the phylogenetic and genetic data, revealed that strain BPTF-M20T was separated from recognized Pseudoruegeria species. On the basis of the data presented here, strain BPTF-M20T is considered to represent a novel species of the genus Pseudoruegeria , for which the name Pseudoruegeria insulae sp. nov. is proposed. The type strain is BPTF-M20T (=KACC 19614T=KCTC 62422T=NBRC 113188T).

This study aimed to determine the association between consumption of ultra-processed foods and obesity among Korean adults. We used the data of 7364 participants (men 3219, women 4145) aged 19–64 years from the Korea National Health and Nutrition Examination Survey (KNHANES), 2016–2018. Food items were classified using the NOVA food classification system, depending on the extent and purpose of food processing: (1) unprocessed or minimally processed foods, (2) processed culinary ingredients, (3) processed foods, and (4) ultra-processed foods. Consumption of ultra-processed foods accounted for 26.8% of the total energy intake. After adjusting for potential confounders including sociodemographic and lifestyle characteristics, subjects with the highest consumption of ultra-processed foods (fourth quartile of % energy intake from ultra-processed foods) had 0.61 kg/m2 higher body mass index (BMI, 95% confidence interval [CI] 0.23–0.99, p-trend 0.0047), 1.34 cm higher waist circumference (WC, 95% CI 0.35–2.34, p-trend 0.0146), 51% higher odds of being obese (BMI &gt, 25 kg/m2, odds ratio [OR] 1.51, 95% CI 1.14–1.99, p-trend 0.0037), and 64% higher odds of abdominal obesity (men: WC ≥90 cm, women: WC ≥85 cm, OR 1.64, 95% CI 1.24–2.16, p-trend 0.0004) than those with the lowest consumption (first quartile) among women. However, no association was found in men. These findings provide evidence that high consumption of ultra-processed foods is positively associated with obesity in Korean women. Further studies with a large-scale cohort or intervention trial are needed to identify the mechanism of associations between consumption of ultra-processed foods and health-related outcomes including obesity in Korea.

Background: The oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation was reported to be the signature genetic event in most cases of pancreatic ductal adenocarcinoma (PDAC). Hepassocin (HPS/FGL1) is involved in regulating lipid metabolism and the progression of several cancer types; however, the underlying mechanism of HPS/FGL1 in the KRAS mutant PDAC cells undergoing eicosapentaenoic acid (EPA) treatment remains unclear. Methods: We measured HPS/FGL1 protein expressions in a human pancreatic ductal epithelial (HPNE) normal pancreas cell line, a KRAS-wild-type PDAC cell line (BxPC-3), and KRAS-mutant PDAC cell lines (PANC-1, MIA PaCa-2, and SUIT-2) by Western blot methods. HEK293T cells were transiently transfected with corresponding KRAS-expressing plasmids to examine the level of HPS expression with KRAS activation. We knocked-down HPS/FGL1 using lentiviral vectors in SUIT-2 cells and measured the cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenicity assays. Furthermore, a lipidomic analysis was performed to profile changes in lipid metabolism after HPS/FGL1 knockdown. Results: We found that the HPS/FGL1 level was significantly upregulated in KRAS-mutated PDAC cells and was involved in KRAS/phosphorylated (p)-signal transduction and activator of transcription 3 (STAT3) signaling, and the knockdown of HPS/FGL1 in SUIT-2 cells decreased cell proliferation through increasing G2/M cell cycle arrest and cyclin B1 expression. In addition, the knockdown of HPS/FGL1 in SUIT-2 cells significantly increased omega-3 polyunsaturated fatty acids (PUFAs) and EPA production but not docosahexaenoic acid (DHA). Moreover, EPA treatment in SUIT-2 cells reduced the expression of de novo lipogenic protein, acetyl coenzyme A carboxylase (ACC)-1, and decreased p-STAT3 and HPS/FGL1 expressions, resulting in the suppression of cell viability. Conclusions: Results of this study indicate that HPS is highly expressed by KRAS-mutated PDAC cells, and HPS/FGL1 plays a crucial role in altering lipid metabolism and increasing cell growth in pancreatic cancer. EPA supplements could potentially inhibit or reduce ACC-1-involved lipogenesis and HPS/FGL1-mediated cell survival in KRAS-mutated pancreatic cancer cells.

A self-organized n+/n homojunction is proposed to achieve ultrahigh performance of thin film transistors (TFTs) based on an amorphous (Zn,Ba)SnO3 (ZBTO) semiconductor with sufficiently limited scattering centers. A deposited Al layer can induce a highly O-deficient (n+) interface layer in the back channel of a-ZBTO without damaging the front channel layer via the formation of a metal-oxide interlayer between the metal and back channel. The n+ layer can significantly improve the field-effect mobility by providing a relatively high concentration of free electrons in the front n-channel ZBTO, where the scattering of carriers is already controlled. In comparison with a Ti layer, the Al metal layer is superior, as confirmed by first-principles density functional theory (DFT) calculations, due to the stronger metal-O bonds, which make it easier to form a metal oxide AlOx interlayer through the removal of oxygen from ZBTO. The field-effect mobility of a-ZBTO with an Al capping layer can reach 153.4 cm2/Vs, which is higher than that of the pristine device, i.e., 20.8 cm2/Vs. This result paves the way for the realization of a cost-effective method for implementing indium-free ZBTO devices in various applications, such as flat panel displays and large-area electronic circuits. A layer of aluminum improves the performance of electronic devices useful for high-resolution flat displays, according to researchers in South Korea. Thin-film transistors are ultrafast electrical switches comprising stacked layers of semiconductors, metals and oxide materials. Their tiny size and planar architecture make them useful for large-area electronics and displays. A key performance metric for these devices is mobility: a measure of how quickly a charged particle can move through the semiconductor. Ji-Min Park from Chungnam National University in Daejeon and colleagues have shown how adding a capping layer of a highly oxidizing metal such as aluminum can greatly enhance the mobility of zinc barium tin oxide thin-film transistors. This cost-effective and useful improvement was achieved without introducing significant defects into the semiconductor. The formation of the conductive region (n+ layer) in (Zn,Ba)SnO3 (ZBTO) semiconductor is proposed to achieve high performance of thin-film transistors (TFTs). The aluminum metal capping layer is adopted to enhance the field-effect mobility of ZBTO TFTs. The capped Al layer takes out oxygen in the back-channel region, where the AlOx interlayer is formed. As a result, the field-effect mobility of Al-capped ZBTO TFTs is remarkably increased from 20.8 to 153.4 cm2/Vs. Furthermore, the Al-capped ZBTO TFTs are stable even when exposed to air for 3 months.

An object's shape may be deformed by a combination of gravitational, hydrostatic, mechanical, and electromagnetic forces. Therefore, to predict the deformation, it is necessary to know each force's distribution inside the object. Various expressions and methods, such as the Lorentz, Kelvin, generalized, and Korteweg-Helmholtz forces, can be used to calculate the electromagnetic force on a dielectric or magnetic material. However, the distributions of the aforementioned forces inside materials may differ significantly. We adopt the concepts of infinitesimal particles and external electromagnetic fields to address this issue. Adopting these concepts enables the electromagnetic force densities inside dielectric or magnetic materials to be uniquely determined. We refer to this type of density as the locally defined electromagnetic force density (F LEM ). This study primarily focuses on the derivation of F (LEM )• Subsequently, the distribution of F LEM is then demonstrated using simple numerical models.

Cancer cells can secrete exosomes under various stressful conditions, whose functions are involved in the delivery of various biologically active materials into host cells and/or modulation of host immune responses. Therefore, an improved understanding of the immunological interventions that stress-induced tumor exosomes have may provide novel therapeutic approaches and more effective vaccine designs. Here, we confirmed the phenotypical and functional alterations of dendritic cells (DCs), which act as a bridge between the innate and adaptive arms of immunity, following non-irradiated (N-exo) and gamma-irradiated melanoma cancer cell-derived exosome (G-exo) stimulation, and evaluated the N-exo- and G-exo-stimulated DCs as therapeutic cancer vaccine candidates. We demonstrated that G-exo-stimulated DCs result in DC maturation by the upregulation of surface molecule expression, pro-inflammatory cytokine release, and antigen-presenting ability, and the downregulation of endocytic capacity. In addition, these cells promoted T cell proliferation and the generation of T helper type 1 (Th1) and interferon (IFN)-&gamma, producing CD8+ T cells. However, N-exo-stimulated DCs induced semi-mature phenotypes and functions, eventually inhibiting T cell proliferation, decreasing IFN-&gamma, and increasing IL-10-producing CD4+ T cells. In addition, although N-exo and G-exo stimulations showed similar levels of antigen-specific IFN-&gamma, production, which served as tumor antigen sources in melanoma-specific T cells, G-exo-stimulated DC vaccination conferred a stronger tumor growth inhibition than N-exo-stimulated DC vaccination, further, this was accompanied by a high frequency of tumor-specific, multifunctional effector T cells. These results suggest that gamma irradiation could provide important clues for designing and developing effective exosome vaccines that can induce strong immunogenicity, especially tumor-specific multifunctional T cell responses.

Background Gender and fertility variation have an impact on mating dynamics in a population because they affect the gene exchange among parental members and the genetic composition of the resultant seed crops. Fertility is the proportional gametic contribution of parents to their progeny. An effective number of parents, derivative of effective population size, is the probability that two alleles randomly chosen from the gamete gene pool originated from the same parent. The effective number of parents is directly related to the fertility variation among parents, which should be monitored for manipulating gene diversity of seed crops. We formulated a fundamental equation of estimating the effective number of parents and applied it to a seed production population. Results Effective number of parents (Np) was derived from fertility variation (Ψ) considering covariance (correlation coefficient, r) between maternal and paternal fertility. The Ψ was calculated from the coefficient of variation in reproductive outputs and divided into female (ψf) and male (ψm) fertility variation in the population under study. The Np was estimated from the parental Ψ estimated by the fertility variation of maternal (ψf) and paternal (ψm) parents. The gene diversity of seed crops was monitored by Ψ and Np. in a 1.5 generation Pinus koraiensis seed orchard as a case of monoecious species. A large variation of female and male strobili production was observed among the studied 52 parents over four consecutive years, showing statistically significant differences across all studied years. Parental balance curve showed greater distortion in paternal than maternal parents. The Ψ ranged from 1.879 to 4.035 with greater ψm than ψf, and the Np varied from 14.8 to 36.8. When pooled, the relative effective number of parents was improved as 80.0% of the census number. Conclusions We recommend the use of fertility variation (i.e., CV, Ψ), Person’s product-moment correlation (r), and effective number of parents (Np) as tools for gauging gene diversity of seed crops in production populations. For increasing Np and gene diversity, additional management options such as mixing seed-lots, equal cone harvest and application of supplemental-mass-pollination are recommended.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus 2019 (COVID-19). No treatment is available. Micro-RNAs (miRNAs) in mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are potential novel therapeutic agents because of their ability to regulate gene expression by inhibiting mRNA. Thus, they may degrade the RNA genome of SARS-CoV-2. EVs can transfer miRNAs to recipient cells and regulate conditions within them. MSC-EVs harbor major therapeutic miRNAs that play important roles in the biological functions of virus-infected host cells. Here, we examined their potential impact on viral and immune responses. MSC-EVs contained 18 miRNAs predicted to interact directly with the 3’ UTR of SARS-CoV-2. These EVs suppressed SARS-CoV-2 replication in Vero E6 cells. In addition, five major miRNAs suppressed virus activity in a luciferase reporter assay by binding the 3’ UTR. MSC-EVs showed strong regenerative effects and potent anti-inflammatory activity which may prevent lethal cytokine storms. We confirmed that EVs regulated inflammatory responses by several cell types, including human brain cells that express the viral receptor ACE2, suggesting that the brain may be targeted by SARS-CoV-2. miRNAs in MSC-EVs have several advantages as therapeutic agents against SARS-CoV-2: 1) they bind specifically to the viral 3’ UTR, and are thus unlikely to have side effects; 2) because the 3’ UTR is highly conserved and rarely mutates, MSC-EV miRNAs could be used against novel variants arising during viral replication; and 3) unique cargoes carried by MSC-EVs can have diverse effects, such as regenerating damaged tissue and regulating immunity.

We utilize a novel identification strategy to analyze the impact of assets in place on firms' decisions for future projects. We exploit the context in the pharmaceutical industry, where the loss of market exclusivity for a branded drug can be used to separate the impact of cash flows generated by a firm's current assets in place from the characteristics of its future investment opportunities. We first show that around the exclusivity losses in our sample of large drugs, the affected firms' profitability drop significantly. The timing of this profitability decrease was predetermined many years ago, and therefore, arguably independent of current investment opportunities. Nevertheless, we find that R&D spending drops by approximately 25% over two years following the loss of exclusivity. We also find that stock repurchases and cash balances decline significantly. Our findings do not support the predictions of traditional capital budgeting, but are more consistent with the pecking order theory. These results further point to a lack of long-term lifecycle management that could mitigate the effect of predictable negative shocks to cash flows.

OBJECTIVES: This study aimed to investigate changes in serum antioxidant vitamin levels after consumption of balanced Korean diet (BKD), recommended American diet (RAD), and typical American diet (TAD) among Korean adults from a randomized controlled trial. METHODS: Among 54 adults aged 25–65 years with body mass index ≥23 kg/m(2) and blood LDL-cholesterol ≥120 mg/dL who finished a crossover feeding study conducted between 2015–2017, 16 subjects were selected for analyses of serum β-carotene, retinol, and α-tocopherol levels at baseline and after consumption of each diet for 4 weeks. Serum antioxidant vitamin levels were measured by high-performance liquid chromatography. RESULTS: Mean levels of serum β-carotene, retinol, and α-tocopherol at baseline were 0.37, 0.34, and 7.19 mg/L, respectively. After consumption of BKD, increase in serum β-carotene and retinol levels was observed compared to the baseline, whereas α-tocopherol level was decreased. After consumption of RAD, serum β-carotene, retinol, and α-tocopherol levels were increased. However, retinol level was reduced after consumption of TAD. CONCLUSIONS: This study may provide evidences about effects of diets on antioxidant vitamin levels in human body. FUNDING SOURCES: This work was carried out with the support of ‘Research Program for Agricultural Science and Technology Development’, National Institute of Agricultural Science, Rural Development Administration, Republic of Korea (Project No. PJ013475022018).

We utilize a novel identification strategy to analyze the impact of assets in place on firms' decisions for future projects. We exploit the context in the pharmaceutical industry, where the loss of market exclusivity for a branded drug can be used to separate the impact of cash flows generated by a firm's current assets in place from the characteristics of its future investment opportunities. We first show that around the exclusivity losses in our sample of large drugs, the affected firms' profitability drop significantly. The timing of this profitability decrease was predetermined many years ago, and therefore, arguably independent of current investment opportunities. Nevertheless, we find that R&D spending drops by approximately 25% over two years following the loss of exclusivity. We also find that stock repurchases and cash balances decline significantly. Our findings do not support the predictions of traditional capital budgeting, but are more consistent with the pecking order theory. These results further point to a lack of long-term lifecycle management that could mitigate the effect of predictable negative shocks to cash flows. Institutional subscribers to the NBER working paper series, and residents of developing countries may download this paper without additional charge at www.nber.org.

The trade-off between performance and stability in amorphous oxide semiconductor-based thin-film transistors (TFTs) has been a critical challenge, meaning that it is difficult to simultaneously achieve high mobility and stability under bias and light stresses. Here, an amorphous mixture of two indium-free BaSnO

Small-sized non-antibody scaffolds have attracted considerable interest as alternatives to immunoglobulin antibodies. However, their short half-life is considered a drawback in the development of therapeutic agents. Here we demonstrate that a homo-dimeric form of a repebody enhances the anti-tumor activity than a monomeric form through prolonged blood circulation. Spytag and spycatcher were genetically fused to the C-terminus of a respective human IL-6-specific repebody, and the resulting two repebody constructs were mixed at an equimolar ratio to produce a homo-dimeric form through interaction between spytag and spycatcher. The homo-dimeric repebody was detected as a single band in the SDS-PAGE analysis with an expected molecular size (78 kDa), showing high stability and homogeneity. The dimeric repebody was shown to simultaneously accommodate two hIL-6 molecules, and its binding affinity for hIL-6 was estimated to be comparable to a monomeric repebody. The serum concentration of the dimeric repebody was observed to be about 5.5 times higher than a monomeric repebody, consequently leading to considerably higher tumor suppression effect in human tumor xenograft mice. The present approach can be effectively used for prolonging the blood half-life of small-sized protein binders, resulting in enhanced therapeutic efficacy.

A Gram-stain-negative, non-motile, aerobic and rod-shaped or ovoid bacterial strain, designated MYP2-2T, was isolated from the intestinal tract of a squid (Todarodes pacificus) collected from the East Sea, South Korea, and subjected to a polyphasic taxonomic study. Strain MYP2-2T grew optimally at 30–35 °C and in the presence of 2.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences revealed that strain MYP2-2T belonged to the genus Vitellibacter . Strain MYP2-2T exhibited 16S rRNA gene sequence similarities of 95.4–96.6 % to the type strains of Vitellibacter species and of less than 94.5 % to the type strains of other recognized species examined. Strain MYP2-2T contained menaquinone MK-6 as the predominant respiratory quinone and iso-C15 : 0 and iso-C17 : 0 3-OH as the major fatty acids. The major polar lipids detected in strain MYP2-2T were phosphatidylethanolamine and one unidentified lipid. The DNA G+C content of strain MYP2-2T was 41.6 mol%. Differential phenotypic properties, together with its phylogenetic distinctiveness, revealed that strain MYP2-2T is separated from recognized species of the genus Vitellibacter . On the basis of the data presented, strain MYP2-2T is considered to represent a novel species of the genus Vitellibacter , for which the name Vitellibacter todarodis sp. nov. is proposed. The type strain is MYP2-2T (=KCTC 62141T=NBRC 113025T).

A Gram-stain-negative, non-motile and ovoid or rod-shaped bacterial strain, DBTF-13T, which was isolated from a tidal flat sediment of the Yellow Sea in South Korea, was characterized taxonomically. Strain DBTF-13T grew optimally at 25–30 °C and pH 7.0–8.0, and in the presence of 2.0 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences revealed that strain DBTF-13T formed an evolutionary lineage independent of other genera, including the genera Pseudooctadecabacter and Octadecabacter . Strain DBTF-13T exhibited 16S rRNA gene sequence similarity values of 96.9 % to the type strain of Pseudooctadecabacter jejudonensis , and of 95.8–96.5 % to the type strains of Octadecabacter species. Strain DBTF-13T contained Q-10 as the predominant ubiquinone and C18 : 1 ω7c and C16 : 0 as the major fatty acids. The major polar lipids of strain DBTF-13T were phosphatidylcholine, phosphatidylglycerol, one unidentified aminolipid and one unidentified lipid. The DNA G+C content of strain DBTF-13T was 61.6 mol%. The chemotaxonomic data and other differential phenotypic properties made it reasonable to differentiate strain DBTF-13T from the genera Pseudooctadecabacter and Octadecabacter . On the basis of the data presented, strain DBTF-13T constitutes a new genus and species within the class Alphaproteobacteria , for which the name Aestuariibius insulae gen. nov., sp. nov. is proposed. The type strain is DBTF-13T (=KACC 19432T=NBRC 113038T).

A Gram-stain-negative, non-motile and ovoid or rod-shaped bacterial strain, DBTF-15T, was isolated from a tidal flat sediment on the Yellow Sea in South Korea. Strain DBTF-15T grew optimally at 25–30 °C, at pH 7.0–8.0 and in the presence of 2.0 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences revealed that strain DBTF-15T joined the cluster comprising the type strains of species of the genus Palleronia . Strain DBTF-15T exhibited higher 16S rRNA gene sequence similarity values to the type strains (96.5–96.7 %) of Maribius pelagius and Maribius salinus than to those (94.6–96.1 %) of the three species of the genus Palleronia . It exhibited 16S rRNA gene sequence similarity values of less than 93.9 % to the type strains of the other recognized species. Strain DBTF-15T contained Q-10 as the predominant ubiquinone and C18 : 1 ω7c as the major fatty acid. The major polar lipids of strain DBTF-15T were phosphatidylcholine, phosphatidylglycerol and one unidentified aminolipid. The DNA G+C content of strain DBTF-15T was 68.7 mol%. The chemotaxonomic data and other differential phenotypic properties made it possible to distinguish strain DBTF-15T from the genera Maribius and Palleronia . On the basis of the data presented, strain DBTF-15T constitutes a novel genus and species within the class Alphaproteobacteria , for which the name Pseudomaribius aestuariivivens gen. nov., sp. nov. is proposed. The type strain is DBTF-15T (=KACC 19431T=NBRC 113039T).

A Gram-stain-negative, non-motile, aerobic, ovoid or rod-shaped bacterium, designated AH-MY3T, was isolated from a tidal flat on Aphae island of the south-western sea, South Korea, and subjected to a polyphasic taxonomic study. Strain AH-MY3T grew optimally at 35 °C, at pH 7.0–8.0 and in the presence of 2.0–3.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that strain AH-MY3T joined the cluster comprising the type strains of Yeosuana aromativorans, Snuella lapsa and Meridianimaribacter flavus, showing sequence similarities of 93.9, 93.7 and 92.6 %, respectively. Strain AH-MY3T exhibited 16S rRNA gene sequence similarity values of 94.0–94.7 % to the type strains of ‘Aestuariibaculum scopimerae’, Winogradskyella aquimaris, Winogradskyella poriferorum and Gaetbulibacter aestuarii. Strain AH-MY3T contained MK-6 as the predominant menaquinone. The fatty acid and polar lipid profiles of strain AH-MY3T could be distinguished from those of the type strains of phylogenetically related taxa. The DNA G+C content of strain AH-MY3T was 37 mol%. The phylogenetic data and differential chemotaxonomic and other phenotypic properties revealed that strain AH-MY3T represents a novel genus and species within the family Flavobacteriaceae, for which the name Aestuariivivens insulae gen. nov., sp. nov. is proposed. The type strain of Aestuariivivens insulae is AH-MY3T ( = KCTC 42350T = NBRC 110723T).

Phosphatidylinositol (PI) 4-kinase (PI4K) has emerged as a potential target for anti-cancer treatment. We recently reported that simeprevir, an anti-hepatitis C viral (HCV) agent, radiosensitized diverse human cancer cells by inhibiting PI4K IIIα in vitro. In this study, we investigated the radiosensitizing effect of simeprevir in an in vivo tumor xenograft model and the mechanism of its interaction. The immune modulatory effect of PI4K IIIα was evaluated in an immune-competent syngeneic murine tumor model. In in vivo xenograft models using BT474 breast cancer and U251 brain tumor cells, inhibition of PI4K IIIα induced by simeprevir combined with radiation significantly delayed tumor growth compared to either treatment alone. PI4K IIIα inhibition led to eversion of the epithelial-mesenchymal transition as suggested by decreased invasion/migration and vascular tube formation. Simeprevir down-regulated PI3Kδ expression and PI3Kδ inhibition using RNA interference radiosensitized breast cancer cells. PI4K IIIα inhibition enhanced the radiosensitizing effect of anti-programmed death-ligand 1 (PD-L1) and decreased the expression of PI3Kδ, phosphorylated-Akt, and PD-L1 in breast cancer cells co-cultured with human T-lymphocytes. The immune modulatory effect in vivo was evaluated in immune-competent syngeneic 4T1 murine tumor models. Simeprevir showed significant radiosensitizing effect and immune modulatory function by affecting the CD4(+)/CD8(+) ratio of tumor infiltrating lymphocytes. These findings suggest that targeting PI4K IIIα with an anti-HCV agent is a viable drug repositioning approach for enhancing the therapeutic efficacy of radiation therapy. The immune regulatory function of PI4K IIIα via modulation of PI3Kδ suggests a strategy for enhancing the radiosensitizing effect of immune checkpoint blockades.

There are reports that pregnant women infected with SARS-CoV-2 not only have increased morbidity but also increased complications and evidence of maternal and fetal vascular malperfusion on placental pathology. This was a retrospective study of pregnant women diagnosed with SARS-CoV-2 infection after March 2020. The results of reverse transcription polymerase chain reaction testing and IgM and IgG antibody testing of the amniotic fluid, cord blood, placenta, and maternal blood were confirmed at delivery. Placentas were evaluated histopathologically. The study included seven pregnant women diagnosed with SARS-CoV-2 infection during pregnancy at a mean gestational age of 14.5 weeks. Out of the seven women, five were infected during the first trimester. The mean gestational age at delivery was 38.4 weeks. The reverse transcription polymerase chain reaction results for maternal plasma, cord blood, placenta, and amniotic fluid were negative and IgG antibodies were detected in maternal plasma and cord blood. On placental pathology, maternal vascular malperfusion was found in only one case, fetal vascular malperfusion in four cases, and inflammatory changes were found in two cases. Pregnancy outcomes for women diagnosed with SARS-CoV-2 infection during early pregnancy are positive and it is likely that maternal antibodies are passed to the fetus, which results in a period of immunity.

A Gram-stain-negative, aerobic, non-motile and ovoid or rod-shaped bacterial strain, designated OITF-22T, was isolated from a tidal flat of Oido, an island of South Korea, and subjected to a polyphasic taxonomic study. Strain OITF-22T grew optimally at 25 °C, at pH 7.0–8.0 and in the presence of 2.0–3.0 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences showed that strain OITF-22T fell within the clade comprising the type strains of Polaribacter species. Strain OITF-22T exhibited 16S rRNA gene sequence similarity values of 97.2–99.4 % to the type strains of Polaribacter vadi , P. haliotis , P. atrinae , P. dokdonensis , P. litorisediminis, P. reichenbachii , P. irgensii and P. marinaquae , and of 93.0–96.9 % to the type strains of the other Polaribacter species. Strain OITF-22T contained MK-6 as the predominant menaquinone and iso-C15 : 0 and iso-C15 : 0 3-OH as the major fatty acids. The major polar lipids detected in strain OITF-22T were phosphatidylethanolamine and one unidentified lipid. The DNA G+C content of strain OITF-22T was 32.3 mol% and its DNA–DNA relatedness values with the type strains of the eight phylogenetically most closely related Polaribacter species were 9–32 %. Differential phenotypic properties, together with phylogenetic and genetic distinctiveness, revealed that strain OITF-22T is separated from recognized species of the genus Polaribacter . On the basis of the data presented, strain OITF-22T is considered to represent a novel species of the genus Polaribacter , for which the name Polaribacter insulae sp. nov. is proposed. The type strain is OITF-22T (=KCTC 52658T=NBRC 112706T).

A Gram-stain-negative, non-motile, aerobic and rod-shaped or ovoid bacterial strain, designated KEM-106T, was isolated from water of an estuary environment on the Yellow Sea, South Korea, and subjected to a polyphasic taxonomic study. Strain KEM-106T grew optimally at 30 °C and pH 7.0–8.0 and in the presence of 1.0–2.0 % (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences revealed that strain KEM-106T belonged to the genus Algoriphagus , clustering with the type strains of Algoriphagus litorisediminis and Algoriphagus aquaemixtae. Strain KEM-106T exhibited 16S rRNA gene sequence similarities of 96.5, 96.2 and 96.0 % to the type strains of Algoriphagus boritolerans , A. litorisediminis and A. aquaemixtae, respectively, and of 92.5–95.8 % to the type strains of the other Algoriphagus species. Strain KEM-106T contained MK-7 as the predominant menaquinone and iso-C15 : 0 and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) as the major fatty acids. The major polar lipids were phosphatidylethanolamine and phosphatidylcholine. The DNA G+C content of strain KEM-106T was 42.7 mol%. Differential phenotypic properties, together with its phylogenetic distinctiveness, revealed that strain KEM-106T is separated from recognized species of the genus Algoriphagus . On the basis of the data presented, strain KEM-106T is considered to represent a novel species of the genus Algoriphagus , for which the name Algoriphagus marisflavi sp. nov. is proposed. The type strain is KEM-106T (=KCTC 52979T=NBRC 112904T).

Objective To investigate the anti-inflammatory effects of decursin and decursinol angelate-rich Angelica gigas Nakai (AGNE) on dextran sulfate sodium (DSS)-induced murine ulcerative colitis (UC). Methods The therapeutic effect of an AGNE was analyzed in a mouse model of UC induced by DSS. Disease activity index values were measured by clinical signs such as a weight loss, stool consistency, rectal bleeding and colon length. A histological analysis was performed using hematoxylin and eosin staining. Key inflammatory cytokines and mediators including IL-6, TNF-α, PGE2, COX-2 and HIF-1α were assayed by enzyme-linked immunosorbent assay or western blotting. Results Treatment with the AGNE at 10, 20, and 40 mg/kg alleviated weight loss, decreased disease activity index scores, and reduced colon shortening in mice with DSS-induced UC. AGNE inhibited the production of IL-6 and TNF-α in serum and colon tissue. Moreover, AGNE suppressed the increased expression of COX-2 and HIF-1α and the increased production of PGE2 in colon tissue were observed in mice with DSS-induced UC. Additionally, histological damage was also alleviated by AGNE treatment. Conclusions The findings of this study verified that AGNE significantly improves clinical symptoms and reduces the activity of various inflammatory mediators. These results indicate the AGNE has the therapeutic potential in mice with DSS-induced UC.

A Gram-stain-negative, aerobic, non-spore-forming, motile and ovoid or rod-shaped bacterial strain, JDTF-113T, was isolated from a tidal flat in Jindo, an island of South Korea. Strain JDTF-113T grew optimally at 30 °C, at pH 7.0–8.0 and in the presence of 2.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree, based on 16S rRNA gene sequences, revealed that strain JDTF-113T fell within the clade enclosing the type strains of species of the genus Alteromonas . Strain JDTF-113T exhibited 16S rRNA gene sequence similarity values of 97.1–98.1 % to the type strains of Alteromonas lipolytica , Alteromonas litorea , Alteromonas mediterranea , Alteromonas confluentis , Alteromonas hispanica , Alteromonas genovensis and Alteromonas marina , and of 94.8–96.9 % to those of the other species of the genus Alteromonas . Strain JDTF-113T contained Q-8 as the predominant ubiquinone and C16 : 0, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C18 : 1ω7c as the major fatty acids. The major polar lipids of strain JDTF-113T were phosphatidylethanolamine, phosphatidylglycerol and one unidentified glycolipid. The DNA G+C content of strain JDTF-113T was 51.1 mol% and its mean DNA–DNA relatedness values with the type strains of seven closely phylogenetically related species of the genus Alteromonas were was 10–23 %. The differential phenotypic properties and phylogenetic and genetic distinctiveness support strain JDTF-113T being separated from species of the genus Alteromonas with validly published names . On the basis of the data presented, strain JDTF-113T is considered to represent a novel species of the genus Alteromonas , for which the name Alteromonas aestuariivivens sp. nov. is proposed. The type strain is JDTF-113T (=KCTC 52655T=NBRC 112708T).

// Taeryool Koo 1, * , Bong Jun Cho 2, * , Dan Hyo Kim 2 , Ji Min Park 1, 2 , Eun Jung Choi 2 , Hans H. Kim 2 , David J Lee 2 and In Ah Kim 1, 2, 3, 4 1 Department of Radiation Oncology, Graduate School of Medicine, Seoul National University, Seoul, Republic of Korea 2 Medical Science Research Institute, Seoul National University Bundang Hospital, Seongnam, Republic of Korea 3 Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea 4 Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea * These authors contributed equally to this work Correspondence to: In Ah Kim, email: inah228@snu.ac.kr Keywords: microRNA-200c, EGFR-associated signaling network, radiosensitization, human cancer cells Received: February 13, 2016 Accepted: February 06, 2017 Published: July 03, 2017 ABSTRACT MicroRNA-200c (miR-200c) recently was found to have tumor-suppressive properties by inhibiting the epithelial-mesenchymal transition (EMT) in several cancers. miR-200c also interacts with various cellular signaling molecules and regulates many important signaling pathways. In this study, we investigated the radiosensitizing effect of miR-200c and its mechanism in a panel of human cancer cell lines. Malignant glioma (U251, T98G), breast cancer (MDA-MB-468), and lung carcinoma (A549) cells were transfected with control pre-microRNA, pre-miR-200c, or anti-miR-200c. Then, RT-PCR, clonogenic assays, immunoblotting, and immunocytochemisty were performed. To predict the potential targets of miR-200c, microRNA databases were used for bioinformatics analysis. Ectopic overexpression of miR-200c downregulated p-EGFR and p-AKT and increased the radiosensitivity of U251, T98G, A549, and MDA-MB-468 cells. In contrast, miR-200c inhibition upregulated p-EGFR and p-AKT, and decreased radiation-induced cell killing. miR-200c led to persistent γH2AX focus formation and downregulated pDNA-PKc expression. Autophagy and apoptosis were major modes of cell death. Bioinformatics analysis predicted that miR-200c may be associated with EGFR, AKT2, MAPK1, VEGFA, and HIF1AN . We also confirmed that miR-200c downregulated the expression of VEGF, HIF-1α, and MMP2 in U251 and A549 cells. In these cells, overexpressing miR-200c inhibited invasion, migration, and vascular tube formation. These phenotypic changes were associated with E-cadherin and EphA2 downregulation and N-cadherin upregulation. miR-200c showed no observable cytotoxic effect on normal human fibroblasts and astrocytes. Taken together, our data suggest that miR-200c is an attractive target for improving the efficacy of radiotherapy via a unique modulation of the complex regulatory network controlling cancer pro-survival signaling and EMT.

Small molecules that target the adrenergic family of G protein–coupled receptors (GPCRs) show promising therapeutic efficacy for the treatment of various cancers. In this study, we report that human colon cancer cell line SW480 expresses low-density functional α1B-adrenergic receptors (ARs) as revealed by label-free dynamic mass redistribution (DMR) signaling technology and confirmed by quantitative reverse-transcriptase polymerase chain reaction analysis. Remarkably, although endogenous α1B-ARs are not detectable via either [3H]-prazosin–binding analysis or phosphoinositol hydrolysis assays, their activation leads to robust DMR and enhanced cell viability. We provide pharmacological evidence that stimulation of α1B-ARs enhances SW480 cell viability without affecting proliferation, whereas stimulating β-ARs diminishes both viability and proliferation of SW480 cells. Our study illustrates the power of label-free DMR technology for identifying and characterizing low-density GPCRs in cells and suggests that drugs targeting both α1B- and β-ARs may represent valuable small-molecule therapeutics for the treatment of colon cancer.

To explore optic disc and peripapillary retinal nerve fiber layer (RNFL) features associated with glaucomatous optic disc (GOD) in young myopia. Presence of GOD, optic disc tilt, and disc torsion were determined using fundus photographs. If the measured disc tilt ratio was >1.3, the optic disc was classified as tilted. Optic disc torsion was defined as a >15° deviation in the long axis of the optic disc from the vertical meridian. The average and four quadrants RNFL thicknesses were assessed using spectral domain optical coherence tomography (SD-OCT). Logistic regression analyses were performed to identify factors associated with the presence of GOD. Nine hundred and sixty myopic subjects were recruited from four refractive surgery clinic databases. The mean age was 26.6 ± 5.7 years and spherical equivalent (SE) was −5.5 ± 2.5 diopters. Among 960 eyes, 26 (2.7%) received GOD group classification. Among 934 normal eyes, 290 (31.0%) had titled optic discs. Eighteen eyes (69.2%) in the GOD group had tilted optic discs. When compared to normal eyes, the GOD group had significantly higher tilt ratios (1.4 ± 0.2 vs. 1.2 ± 0.1, p

Background Pancreatic polypeptide (PP) hormone is a 36-amino-acid peptide released from the pancreas, the serum levels of which have been shown to rise upon food intake. The underlying mechanism for metabolic surgery in the treatment of patients with type 2 diabetes mellitus (T2DM) remains intriguing. We compared post-oral glucose challenge PP levels between patients undergoing laparoscopic gastric bypass (GB) and sleeve gastrectomy (SG) at 1 year after surgery. Methods This hospital-based, prospective study followed up a total of 12 laparoscopic GB and 12 laparoscopic SG patients and evaluated their glucose homeostasis. One year after metabolic surgery, 75-g oral glucose tolerance tests (OGTTs) were performed in the patients in the GB and SG groups and the blood levels of PP were evaluated. Results The laparoscopic GB group had stable serum PP levels within 120 min after OGTT; however, the levels were significantly higher in the laparoscopic SG group at 30 min after OGTT. The patients with complete T2DM remission did not exhibit significantly different PP levels at fasting and post-OGTT than those in patients without remission after GB. Similarly, after SG, patients with T2DM remission did not show significantly different PP levels at fasting and post-OGTT than those in patients without T2DM remission. Conclusions No significant difference was found in plasma PP levels after OGTT in T2DM patients that received either GB or SG, or in T2DM remitters or non-remitters 1 year after metabolic surgery.

A bacterial strain, DBTF-3T, was isolated from a tidal flat of Republic of Korea. Phylogenetic trees of 16S rRNA gene sequences showed that strain DBTF-3T belonged to the genus Polaribacter. Strain DBTF-3T exhibited 16S rRNA gene sequence similarities of 97.1–98.1% to type strains of P. dokdonensis, P. haliotis, P. marinaquae, P. insulae, P. vadi, P. glomeratus, P. irgensii and P. reichenbachii, and 94.0–96.9% to those of the other Polaribacter species. DNA–DNA relatedness values of strain DBTF-3T with type strains of P. marinaquae and P. insulae were 14–19%. Average nucleotide identity and digital DNA–DNA hybridization values between strain DBTF-3T and type strains of six other Polaribacter species were 76.5–83.5% and 20.9–27.1%, respectively. Strain DBTF-3T contained MK-6 as the predominant menaquinone, and iso-C15:0, summed feature 3, iso-C15:1 G and iso-C15:0 3-OH as the major fatty acids. The major polar lipids were phosphatidylethanolamine and one unidentified lipid. Differential phenotypic properties, together with its phylogenetic and genetic distinctiveness, revealed that strain DBTF-3T is separated from Polaribacter species. On the basis of the data presented, strain DBTF-3T (= KACC 19612T = NBRC 113191T) represents a novel species of the genus Polaribacter, for which the name Polaribacter aestuariivivens sp. nov. is proposed.

A Gram-stain-negative, aerobic, non-motile and coccoid-, ovoid- or rod-shaped bacterial strain, designated SSKS-13T, was isolated from sediment sampled at the junction between the ocean and a freshwater spring at Jeju island, Republic of Korea. Strain SSKS-13T grew optimally at 37 °C and in the presence of 2.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree of 16S rRNA gene sequences showed that strain SSKS-13T fell within the clade comprising the type strains of Altererythrobacter species, clustering with the type strains of Altererythrobacter lauratis , Altererythrobacter palmitatis and Altererythrobacter buctensis having 16S rRNA gene sequence similarities of 97.2–97.6 %. Strain SSKS-13T exhibited 16S rRNA gene sequence similarities of less than 97.0 % to the type strains of the other recognized species. Strain SSKS-13T contained Q-10 as the predominant ubiquinone and C18 : 1 ω7c as the major fatty acid. The major polar lipids detected in strain SSKS-13T were phosphatidylethanolamine, phosphatidylglycerol and sphingoglycolipid. The DNA G+C content of strain SSKS-13T was 64.6 mol%. The mean DNA–DNA relatedness values of strain SSKS-13T with the type strains of A. lauratis , A. palmitatis and A. buctensis were 11.7–25.3 %. Differential phenotypic properties, together with the phylogenetic and genetic data, proved that strain SSKS-13T is distinct from recognized Altererythrobacter species. On the basis of the data presented here, strain SSKS-13T is considered to represent a novel species of the genus Altererythrobacter , for which the name Altererythrobacter aquimixticola sp. nov. is proposed. The type strain is SSKS-13T (=KACC 19863T=KCTC 62900T=NBRC 113545T).

A lipolytic, Gram-stain-negative, aerobic, non-motile and coccoid, ovoid or rod-shaped bacterial strain, designated BPTF-M16T, was isolated from tidal flat sediment on the Yellow Sea in the Republic of Korea. Strain BPTF-M16T grew optimally at 30 °C and in the presence of 2.0–3.0 % (w/v) NaCl. A phylogenetic tree of 16S rRNA gene sequences showed that strain BPTF-M16T fell within the clade comprising the type strains of Altererythrobacter species. Strain BPTF-M16T exhibited 16S rRNA gene sequence similarity values of 98.0 and 97.1 % to the type strains of Altererythrobacter ishigakiensis and A ltererythrobacter marinus , respectively, and of less than 97.0 % to the type strains of the other recognized species. Strain BPTF-M16T contained Q-10 as the predominant ubiquinone and C18 : 1 ω7c as the major fatty acid. The major polar lipids detected in strain BPTF-M16T were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, sphingoglycolipid and one unidentified glycolipid. Mean DNA–DNA relatedness values of strain BPTF-M16T with the type strains of A. ishigakiensis and A. marinus were 22 and 13 %, respectively. The average nucleotide identity value between strain BPTF-M16T and the type strain of A. ishigakiensis was 76.80 %. Differential phenotypic properties, together with the phylogenetic and genetic data, revealed that strain BPTF-M16T is separated from recognized Altererythrobacter species. On the basis of the data presented here, strain BPTF-M16T is considered to represent a novel species of the genus Altererythrobacter , for which the name Altererythrobacter insulae sp. nov. is proposed. The type strain is BPTF-M16T (=KCTC 62421T=KACC 19609T=NBRC 113190T).

Background: The oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation was reported to be the signature genetic event in most cases of pancreatic ductal adenocarcinoma (PDAC). Hepassocin (HPS/FGL1) is involved in regulating lipid metabolism and the progression of several cancer types, however, the underlying mechanism of HPS/FGL1 in the KRAS mutant PDAC cells undergoing eicosapentaenoic acid (EPA) treatment remains unclear. Methods: We measured HPS/FGL1 protein expressions in a human pancreatic ductal epithelial (HPNE) normal pancreas cell line, a KRAS-wild-type PDAC cell line (BxPC-3), and KRAS-mutant PDAC cell lines (PANC-1, MIA PaCa-2, and SUIT-2) by Western blot methods. HEK293T cells were transiently transfected with corresponding KRAS-expressing plasmids to examine the level of HPS expression with KRAS activation. We knocked-down HPS/FGL1 using lentiviral vectors in SUIT-2 cells and measured the cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenicity assays. Furthermore, a lipidomic analysis was performed to profile changes in lipid metabolism after HPS/FGL1 knockdown. Results: We found that the HPS/FGL1 level was significantly upregulated in KRAS-mutated PDAC cells and was involved in KRAS/phosphorylated (p)-signal transduction and activator of transcription 3 (STAT3) signaling, and the knockdown of HPS/FGL1 in SUIT-2 cells decreased cell proliferation through increasing G2/M cell cycle arrest and cyclin B1 expression. In addition, the knockdown of HPS/FGL1 in SUIT-2 cells significantly increased omega-3 polyunsaturated fatty acids (PUFAs) and EPA production but not docosahexaenoic acid (DHA). Moreover, EPA treatment in SUIT-2 cells reduced the expression of de novo lipogenic protein, acetyl coenzyme A carboxylase (ACC)-1, and decreased p-STAT3 and HPS/FGL1 expressions, resulting in the suppression of cell viability. Conclusions: Results of this study indicate that HPS is highly expressed by KRAS-mutated PDAC cells, and HPS/FGL1 plays a crucial role in altering lipid metabolism and increasing cell growth in pancreatic cancer. EPA supplements could potentially inhibit or reduce ACC-1-involved lipogenesis and HPS/FGL1-mediated cell survival in KRAS-mutated pancreatic cancer cells.

The amorphous oxide semiconductors (AOSs) such as In-Ga-Zn-O (IGZO) and Zn-Sn-O (ZTO) have been extensively studied as the active layers for thin film transistors (TFTs) in display backplanes due to its high mobility (>10cm2/Vs), transparency, low process temperature and large area uniformity. However, many studies on AOSs have reported that there is trade-off relationship between electrical performance and device stability. Generally, the mobility increases with increasing indium or tin content, while the stability is degraded simultaneously. Furthermore, because the indium is a rare metal and expensive, incorporating indium in active materials is one of the critical reasons for increasing overall process costs. For this reason, the development of an indium-free oxide semiconductor materials with high mobility and stability is continuously required. Recently, (Zn1-xBax)SnO3 (ZBTO) has been reported to be a very stable oxide semiconductor with high electron mobility results from its small effective mass and less defective structure. Based on these desirable material properties, it has been adopted as an active material for cost-effective and high-performance TFTs. Also, in order to improve electrical performance dramatically, an additional metal layers are introduced. The metal capping layers have been reported to improve the performance of TFTs by various mechanisms, including the elimination of the scattering/trapping centers, low-temperature crystallization, and electron injection. However, although many research have been performed to demonstrate the origin of the mobility enhancement by the metal capping layer, the exact mechanism has not been confirmed. Also, former reports of this method showed several drawback such as the induced crystallization and need for stabilization time, which may limit its application on large-area displays. To investigate the effect of metal capping layer, the device was fabricated using In-free active material. The ZBTO active layer were deposited via RF magnetron sputtering on the p++ Si/SiOx substrate. All sample was annealed at 350℃ for 1 hour in air ambient, and patterned using shadow masks. The channel width (W) and length (L) were 800 and 200 μm, respectively. In case of metal capped device, 20 nm-thick Al or Ti metal layer was sputtered selectively between the source/drain electrodes with dimensions W/L = 1300/100 μm. In this work, the formation of conductive region in active layer induced by metal capping layer was suggested as new mechanism of the mobility improvement. Due to the strong oxidation power of Al metal, oxygen deficiency is easily induced in active layer near the interface between Al and ZBTO during Al oxidation. This conductive region in active layer generates free electrons, which can be transported without serious scattering owing to the low defect density of ZBTO. These phenomena were confirmed by TEM and XPS results. As a result, the ZBTO TFTs with an Al metal layer exhibited significantly improved field-effect mobility from 20.8 cm2/Vs to 153.4 cm2/Vs without degradation of other transfer parameters. Furthermore, the ZBTO TFTs showed far superior mobility improvement compared to other conventional oxide TFTs. The carrier transport mechanisms was investigated by 1/f noise measurements, which indicated that carrier transport of ZBTO TFTs with the Al capping layer is enhanced by the reduced bulk trap sites. Moreover, reliability tests including NBS, PBS indicated that the front channel of ZBTO active layer was relatively less affected. Our results indicate that adopt of stable active material with small defect density, in this case ZBTO, is a key factor in the fabrication of metal-assisted TFTs capable of ultra-high performance.

A Gram-stain-negative, aerobic, non-flagellated, motile by gliding and ovoid or rod-shaped bacterial strain, designated YKTF-7T, was isolated from a tidal flat sediment on the Yellow Sea, South Korea. Strain YKTF-7T grew optimally at pH 7.0-8.0, at 30-37 °C and in the presence of 0.5-2.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that strain YKTF-7T fell within the clade comprising the type strains of species of the genus Pontibacter, clustering with the type strains of Pontibacterodishensis and Pontibacterkorlensis with which it exhibited 98.0-98.7 % sequence similarity. Strain YKTF-7T exhibited 16S rRNA gene sequence similarities of 94.7-96.8 % to the type strains of the other species of the genus Pontibacter and of less than 91.7 % to those of other recognized species. Strain YKTF-7T contained MK-7 as the predominant menaquinone and summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B) and iso-C15 : 0 as the major fatty acids. The major polar lipids were phosphatidylethanolamine and two unidentified lipids. The DNA G+C content of strain YKTF-7T was 54.0 mol%, and its mean DNA-DNA relatedness values with the type strains of P. odishensis and P. korlensis were 25 and 14 %, respectively. Differential phenotypic properties, together with the phylogenetic and genetic distinctiveness, revealed that strain YKTF-7T is separated from recognized species of the genus Pontibacter. On the basis of the data presented, strain YKTF-7T is considered to represent a novel species of the genus Pontibacter, for which the name Pontibacterlitorisediminis sp. nov. is proposed. The type strain is YKTF-7T(=KCTC 52252T=NBRC 112298T).

High Ni content layered oxide materials for the positive electrode in lithium-ion batteries have high specific capacity. However, their poor electrochemical and thermal stability at elevated temperature restrict the practical use. A small amount of was added to the mixture of transition metal hydroxide and lithium hydroxide. The was simultaneously doped and coated with during heat-treatment. Electrochemical characteristics of modified were evaluated by the galvanostatic cycling and the LSTA(linear sweep thermmametry) at the constant voltage conditions. The nano-sized added materials show better cycle performance at elevated temperature than that of micro-sized . As the added amount of nano- increased, the thermal stability of electrode also enhanced, but the use of 2.5 mol% Al showed the best high temperature performance.

The α1D-adrenergic receptor (ADRA1D) is a key regulator of cardiovascular, prostate, and central nervous system functions. This clinically relevant G protein-coupled receptor has proven difficult to study, as it must form an obligate modular homodimer containing the PDZ proteins scribble and syntrophin or become retained in the endoplasmic reticulum as non-functional protein. We previously determined that targeted removal of the N-terminal (NT) 79 amino acids facilitates ADRA1D plasma membrane expression and agonist-stimulated functional responses. However, whether such an event occurs in physiological contexts was unknown. Herein, we report the ADRA1D is subjected to innate NT processing in cultured human cells. SNAP near-infrared imaging and tandem-affinity purification revealed the ADRA1D is expressed as both full-length and NT truncated forms in multiple human cell lines. Serial truncation mapping identified the cleavage site as Leu(90)/Val(91) in the 95-amino acid ADRA1D NT domain, suggesting human cells express a Δ1-91 ADRA1D species. Tandem-affinity purification MS/MS and co-immunoprecipitation analysis indicate NT processing of ADRA1D is not required to form scribble-syntrophin macromolecular complexes. Yet, label-free dynamic mass redistribution signaling assays demonstrate that Δ1-91 ADRA1D agonist responses were greater than WT ADRA1D. Mutagenesis of the cleavage site nullified the processing event, resulting in ADRA1D agonist responses less than the WT receptor. Thus, we propose that processing of the ADRA1D NT domain is a physiological mechanism employed by cells to generate a functional ADRA1D isoform with optimal pharmacodynamic properties.

To compare progression of primary open angle glaucoma (POAG) in asymmetrically myopic eyes within the same subject and evaluate whether the degree of myopia is related to glaucoma progression. POAG patients with asymmetric myopia (axial length [AXL] ≥24 mm in both eyes, and the AXL difference between the right and left eyes to be ≥0.5 mm) were included. Glaucoma progression was determined either by optic disc/retinal nerve fiber layer (RNFL) photographs or by serial visual field (VF) data. The progression rates of VF mean deviation (dB/year) and spectral domain optical coherence tomography measured RNFL thickness (μm/year) were compared between the more myopic eye (MME) and the less myopic eye (LME) within the same subject. A total of 55 patients (mean follow up period; 4.5 ± 1.0 years) were included. The mean AXL demonstrated a significant difference between MME and LME (26.3 ± 1.7 vs. 25.6 ± 1.7 mm; p = 0.036). The mean baseline VF MD (−3.8 ± 5.4 vs. −2.6 ± 4.7 dB; p = 0.21) and average RNFL thickness (77.5 ± 10.6 vs. 79.9 ± 12.3 μm; p = 0.36) did not differ between the MME and LME. Among the 55 patients, optic disc/RNFL photographic progression was noted in the MME in 15 patients, in the LME in 19 patients, and in both eyes in seven patients. VF progression was noted in the MME in seven patients, in the LME in seven patients, and in both eyes in four patients. The VF MD progression rates were −0.25 ± 0.34 dB/year in MME and −0.26 ± 0.34 dB/year in LME cases (p = 0.91). The mean progression rate of the average RNFL thickness also did not differ between the MME and LME (−0.59 ± 0.67 vs. -0.66 ± 0.72 μm/year, p = 0.68). The degree of myopia was not associated with glaucoma progression when assessing the same patient using either the VF or optic disc/RNFL criteria in asymmetrically myopic patients.

A Gram-stain-negative, non-flagellated, non-spore-forming bacterial strain motile by gliding, designated RSS1-6T, was isolated from a golden sea squirt Halocynthia aurantium and its taxonomic position was investigated by using a polyphasic approach. Strain RSS1-6T grew optimally at 30-37 °C and in the presence of 1.0-4.0 % (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences showed that strain RSS1-6T fell within the clade comprising species of the genus Tenacibaculum, clustering with the type strains of Tenacibaculum discolor, Tenacibaculum litoreum and Tenacibaculum gallaicum with which it exhibited 16S rRNA gene sequence similarity values of 98.5-99.5 %. Strain RSS1-6T contained MK-6 as the predominant menaquinone and iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) as the major fatty acids. The major polar lipids of strain RSS1-6T were phosphatidylethanolamine, two unidentified lipids, one unidentified aminophospholipid and one unidentified glycolipid. The DNA G+C content was 32.5 mol% and the mean DNA-DNA relatedness values with the type strains of T. discolor, T. litoreum and T. gallaicum were 17.3-25.2 %. The differential phenotypic properties, together with the phylogenetic and genetic distinctiveness, revealed that strain RSS1-6T is separated from other recognized species of the genus Tenacibaculum. On the basis of the data presented, strain RSS1-6T is considered to represent a novel species of the genus Tenacibaculum, for which the name Tenacibaculum ascidiaceicola sp. nov. is proposed. The type strain is RSS1-6T ( = KCTC 42702T = NBRC 111225T).