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SummaryBackground Current in vitro SPF screening method for plant oil body (oleosome)-based SPF products possesses significant inconsistency and low reliability in the SPF rating. Objectives The primary objective of this study was to evaluate the reliability and reproducibility of spectrophotometrically determined sun protection factor (SPF) from oleosome-based SPF products. The secondary objective was the data comparison of the spectrophotometric measurements against in vivo SPF testing to establish a reliable in vitro test method as a screening assay. Methods Octyl methoxycinnamate (UVB filter) and avobenzone (UVA filter) were loaded into safflower oil bodies and formulated into oil-in-water emulsion-based finished products. To evaluate the reliability between in vivo and spectrophotometric test methods, samples were dispatched to a clinical laboratory, and the reported SPF values were compared with spectrophotometric test results. Results The observed SPF from the in vivo and spectrophotometric test results demonstrated a high correlation for SPF 30 products. Proportional correlation between the two evaluation methods was observed for SPF 15 and 50 products with slightly lesser accuracy with a smaller number of population tested in the clinical studies. Conclusions A reliable spectrophotometric screening method for oil body-based SPF formulas has been developed using two broadly used organic UV sunscreen actives as a case study. The results demonstrated a high level of reproducibility and reliability compared to the US FDA-guided in vivo SPF testing method.

Mycobacterium tuberculosis is a causative agent leading to pleural effusion, characterized by the accumulation of fluid and immune cells in the pleural cavity. Although this phenomenon has been described before, detailed processes or mechanisms associated with the pleural effusion are still not well understood. Pleural mesothelial cells (PMCs) are specialized epithelial cells that cover the body wall and internal organs in pleural cavity playing a central role in pleural inflammation. Toll-like receptors are expressed in various cell types including mesothelial cells and initiate the recognition and defense against mycobacterial infection. In the present study, we investigated direct immune responses of PMCs against two mycobacterial strains, M. bovis vaccine strain Bacille Calmette-Guérin (BCG) and M. tuberculosis virulent strain H37Rv, and the role of TLR2 in such responses. Infection with BCG and H37Rv increased the production of IL-6, CXCL1, and CCL2 in WT PMCs, which was partially impaired in TLR2-deficient cells. In addition, the activation of NF-κB and MAPKs induced by BCG and H37Rv was suppressed in TLR2-deficient PMCs, as compared with the WT cells. TLR2 deficiency led to the decrease of nitric oxide (NO) production through the delayed gene expression of iNOS in PMCs. TLR2 was also shown to be essential for optimal expression of cellular adhesion molecules such as ICAM-1 and VCAM-1 in PMCs in response to BCG and H37Rv. These findings strongly suggest that TLR2 participates in mycobacteria-induced innate immune responses in PMCs and may play a role in pathogenesis of tuberculosis pleural effusion.

The aims of this research were to characterize magic realism by analyzing existing magical reality literature reviews and research and to identify material that may inspire ideas for stage and film costume design by analyzing and drawing design characteristics and magic realism of costumes from Director Tarsem Singh`s movie, `Mirror, Mirror`. For the methodology, characteristics of magic realism in literature and, movies were analyzed, with a theoretical consideration of these materials on magical realism. Data on costume design and magical realism characteristics for use in the analysis were collected from the main characters of `Mirror, Mirror` as well as from other characters. The result of this analysis was the emergence of five common characteristics of the magic realism Historicity, the most remarkable characteristic seen in Tarsem Singh films, was expressed through the symbolic meaning and decorative patterns shown by the traditional-style costumes, colors. Symbolization was expressed through the symbolic meaning, decorative elements, and traditional clothes, as shown by the colors and forms of the costumes. Fantasy was expressed through the colors, decorative elements, forms of traditional clothing, and forms with symbolic meaning. Reproducibility was expressed through the method of decorative element, symbolic meaning, traditional forms and de-structural clothes. Ambiguity, which can be associated with the combined characteristics of historicity and fantasy, was expressed in the clothes worn in the scenes that confounded time and space within the film.

Objectives Few long-term studies have been conducted on the serotype and antibiotic resistance patterns of Salmonella speices (spp.) The aim of this study was to determine the serotypes and antibiotic resistance patterns of Salmonella spp. isolated at Jeollanam-do in Korea from 2004 to 2014. Methods A total of 276 Salmonella samples were evaluated. Serotyping was carried out according to the Kauffmann–White scheme. Antibiotic susceptibility was determined using the Vitek II system with an AST-N169 card. Results A total of 22 different serotypes were identified, and the major serotypes were Salmonella Enteritidis (116 strains, 42.0%) and Salmonella Typhimurium (60 strains, 21.7%). The highest resistance was observed in response to nalidixic acid (43.4%), followed by ampicillin (40.5%) and tetracycline (31.6%). Resistance to nalidixic acid was detected in 81.0% of S. Enteritidis. Multidrug resistance was detected in 43.3% of Salmonella spp. S. Enteritidis and S. Typhimurium presented the highest resistance (98.3%) and multidrug resistance rate (73.3%), respectively. The most highly observed antibiotic resistance pattern among Salmonella spp. in this study was ampicillin-chloramphenicol (14 strains, 5.7%), Conclusion Overall, S. Enteritidis and S. Typhimurium showed higher antibiotic resistance than the other Salmonella serotypes tested in this study. Our study will provide useful information for investigating the sources of Salmonella infections, as well as selecting effective antibiotics for treatment.

Additional file 1. Additional tables and figures.

Additional file 1. Online supplementary material.

High glucose condition impairs neuronal integrity and function by regulating amyloidogenesis and neuroinflammation. Here, we pursue to investigate whether high glucose condition leads impairments in neuronal integrity/function by inducing amyloidogenesis and neuroinflammation, and whether piceatannol (PIC) restores high glucose condition-induced deteriorations in neuronal cells. High glucose condition was induced by maintaining SH-SY5Y neuroblastoma cells in 25 mM glucose. In addition, amyloid-beta was applied to make the cells having amyloidogenesis-mediated deleterious alterations. Cells were maintained in low glucose (2.5 mM glucose) or high glucose (25 mM glucose) condition. And, two doses (10 and 20 μM) of PIC and/or 10 μM of amyloid-beta were treated in a subset of cells for 24 h. There were no significant differences in cell morphology and cell viability among groups. PIC treatment did not show cell toxicity based on cell viability assessed by PrestoBlue assay. High concentration of glucose and amyloid-beta treatments increased amyloid-beta concentrations in cell lysates and conditioned media, which were reduced by PIC. 10 μM PIC treatment for 24 h decreased amyloid precursor protein (APP), beta-site amyloid precursor protein cleaving enzyme-1, presenilin (PS) 1 and tau. Among analyzed inflammatory markers, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were reduced in conditioned media by 10 μM PIC administration for 24 h. These data indicate that high glucose condition may result in excessive levels of amyloidogenesis and neuroinflammation as well as subsequent changes in neuronal integrity/function, and that PIC treatment may ameliorate the deleterious consequences from high glucose and amyloid-beta treatments.

The increase in canine skin and soft tissue infections, such as pyoderma and otitis, caused by Staphylococcus schleiferi strains, is of significant zoonotic concern. In this study, we report the first complete genome sequence for a methicillin-resistant clinical isolate of S. schleiferi (MRSS) designated as SS4, obtained from a dog with otitis externa, in Korea. The genome of SS4 strain was of 2,539,409 bp and presented high G+C content ratio (35.90%) with no plasmid. Comparative analysis of SS4 genome revealed that it is closely related to 2142-05 and 5909-02 strains isolated from the canine skin infections in the USA.

In this study, a heterogeneous catalyst prepared by pyrolysis of waste cork (Quercus suber) was used for the transesterification of waste cooking oil (WCO). Physicochemical properties of the synthesized biochar catalyst were studied using BET, SEM, FTIR, and XRD. The experiment results demonstrate that heterogeneous catalyst synthesized at 600 °C showed maximum fatty acids methyl esters (FAMEs) conversion (98%) at alcohol:oil (25:1), catalyst loading (1.5% w/v) and temperature 65 °C. Biodiesel produced from WCO (Canola oil) mainly composed of FAMEs in following order C18:1 > C18:2 > C16:0 > C18:0 > C20:0. Properties of produced biodiesel were analysed as cetane number (CN) 50.56, higher heating value (HHV) 39.5, kinematic viscosity (ʋ) 3.9, and density (ρ) 0.87.

This paper presents a metaheuristic-based temperature controller for an exothermic batch process. Developing a suitable temperature controller for an exothermic process is a challenging task because large amount of heat is released rapidly during the process. The exothermic behavior will further increase the reaction rate and cause more heat to be liberated. As the result, the improper temperature control might cause the reaction becomes unstable and consequently poses safety concern to the plant personnel and equipment. The conventional non-metaheuristic-based controller, such as fuzzy logic requires empirical data or knowledge about the total amount heat released while developing its fuzzy rules and membership functions for precision control. However, the detailed kinetic model of the heat released is unable to be obtained since there are several unobservable parameters during the process, such as the energy held in the reactor and jacket walls. Therefore, particle swarm optimization algorithm (PSO) is proposed as the controller to maintain the reactor temperature at the desired trajectory by manipulating the inlet jacket fluid temperature and flow rate. The simulation results show the proposed PSO produces better performances in terms of minimizing fluctuation in control actions and overshooting as compared with the conventional fuzzy logic controller.

The power output of photovoltaic array may reduce as the photovoltaic panels' connection close to each other and lead to the occurrence of partials shading. Under partial shading condition, the unshaded modules of PV array receive solar irradiation at higher level, while the shaded module of PV array receives lower irradiation. Thus, multiple maximum power point also will occur under the partial shading condition. The proposed modelling in this paper is 4×4 PV array and tested two different conditions in partial shading condition (PSC) where there are random irradiance values that had been set. Therefore, this paper aim to model more than one PV array and the platform modelling for this paper is 4×4 PV array. Besides that, explore the conventional method which is Perturb and Observe (P&O) based MPPT controller in optimizing the efficiency of the PV array. Unfortunately, the conventional method only can trap the power at the local maximum power under partial shading conditions. Thus, the proposed algorithm that used to track the maximum power is differential evolution (DE) in order to improve the power output of the PV array. The simulation results shows the proposed DE able to track the global MPP.

The emergence and persistence of methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in livestock animals have been reported as a potential risk factor for transmission to humans. In this study, we investigated the nationwide prevalence and characteristics of MRSA and MSSA in the Korean beef production system, including retail markets, slaughterhouses, and cattle farms. From a total of 1,285 samples, only 5 MRSA strains were isolated: from a farmer (1 ST72 MRSA), a carcass sample from a slaughterhouse (1 ST72 MRSA), and beef cattle (3 ST5 MRSA). In addition, 11 MSSA strains were isolated from beef cattle (n=3), humans (1 farmer, 1 slaughterhouse worker, and 4 retail market workers), and carcass samples (n=1) and slaughterhouse environment (n=1). Although the prevalence of MRSA and MSSA in beef cattle was much lower than that reported in pigs, 5/5 MRSA and 2/11 MSSA strains displayed multiple drug resistance (MDR) phenotypes. Unlike the swine-associated MRSA, no correlation was found between tetracycline/zinc resistance and MDR phenotype. However, MRSA strains had an identical set of staphylococcal enterotoxins and exhibited enhanced levels of resistance to antimicrobial peptides (PMAP-36 and LL-37) compared to the MSSA strains. In conclusion, continued and systemic surveillance of livestock, meat products, and humans in close contact with livestock/meat products is necessary to prevent the transmission of MRSA and MSSA to humans.

Helicobacter pylori is a gram-negative, microaerophilic, and spiral-shaped bacterium and causes gastrointestinal diseases in human. IL-1β is a representative cytokine produced in innate immune cells and is considered to be a key factor in the development of gastrointestinal malignancies. However, the mechanism of IL-1β production by neutrophils during H. pylori infection is still unknown. We designed this study to identify host and bacterial factors involved in regulation of H. pylori-induced IL-1β production in neutrophils. We found that H. pylori-induced IL-1β production is abolished in NLRP3-, ASC-, and caspase-1/11-deficient neutrophils, suggesting essential role for NLRP3 inflammasome in IL-1β response against H. pylori. Host TLR2, but not TLR4 and Nod2, was also required for transcription of NLRP3 and IL-1β as well as secretion of IL-1β. H. pylori lacking cagL, a key component of the type IV secretion system (T4SS), induced less IL-1β production in neutrophils than did its isogenic WT strain, whereas vacA and ureA were dispensable. Moreover, T4SS was involved in caspase-1 activation and IL-1β maturation in H. pylori-infected neutrophils. We also found that FlaA is essential for H. pylori-mediated IL-1β production in neutrophils, but not dendritic cells. TLR5 and NLRC4 were not required for H. pylori-induced IL-1β production in neutrophils. Instead, bacterial motility is essential for the production of IL-1β in response to H. pylori. In conclusion, our study shows that host TLR2 and NLRP3 inflammasome and bacterial T4SS and motility are essential factors for IL-1β production by neutrophils in response to H. pylori.

The emergence of livestock-associated (LA)-methicillin-resistant Staphylococcus aureus (MRSA) in livestock animal has become a significant zoonotic concern. In the present study, we investigated nationwide prevalence of LA-MRSA across pork production chain including pig farms, slaughterhouses, and retail markets. A total of 40 MRSA strains were isolated during the investigation and the overall prevalence of MRSA was 3.4% (n = 37), 0.6% (n = 2), and 0.4% (n = 1) in pig farms, slaughterhouses, and retail markets, respectively. Multilocus sequence typing analyses revealed that the 2 most significant clonal lineages in pork production chain in Korea were ST398 (n = 25) and ST541 (n = 6). All of the 40 MRSA isolates were further characterized to investigate key genotypic and phenotypic correlates associated with the emergence and spread of clonal complex 398 (CC398; ST398, and ST541) LA-MRSA. Although the prevalence of swine-associated MRSA was still relatively low and mostly restricted to pig farms, multidrug-resistant CC398 LA-MRSA isolates with new spa types (t18102 and t18103) were identified as a major clonal lineage. The CC398 LA-MRSA strains tended to exhibit increased levels of multiple drug resistance (MDR) phenotype compared with non-CC398 MRSA strains. Of note, in comparison with non-CC398 MRSA isolates, CC398 LA-MRSA isolates exhibited significantly enhanced tetracycline (TET) and zinc resistance. These findings suggested that co-selection pressure associated with MDR phenotype, especially TET resistance, and zinc resistance may have played a significant role in the emergence and persistence of CC398 LA-MRSA in pig farms in Korea.

L-Theanine, found in green tea leaves has been shown to positively affect immunity and relaxation in humans. There have been many attempts to produce L-theanine through enzymatic synthesis to overcome the limitations of traditional methods. Among the many genes coding for enzymes in the L-theanine biosynthesis, glutamylmethylamide synthetase (GMAS) exhibits the greatest possibility of producing large amounts of production. Thus, GMAS from

A therapeutic strategy capable of skewing toward a Th1-type immune response is crucial for cancer treatment. Recently, we reported Mycobacterium paragordonae (Mpg) as a potential live vaccine for mycobacterium infections. In this study, we explored the immunotherapeutic potential of heat-killed Mpg (HK-Mpg) in a mouse tumor xenograft model and elucidated its underlying antitumor mechanisms. MC38 cells derived from murine colon adenocarcinoma were implanted by subcutaneously injecting mice. The anticancer effects of HK-Mpg therapy were compared with HK-M. bovis BCG, an effective adjuvant for cancer immunotherapy. HK-Mpg treatment enhanced tumor reduction and mouse survival. Furthermore, HK-Mpg treatment synergistically enhanced the anticancer therapeutic effect of cisplatin. In addition, HK-Mpg enhanced inflammatory cytokine production and recruitment of immune cell into tumor-infiltrating sites and splenocytes in vaccinated mice. Our mechanistic study demonstrates that HK-Mpg therapy elicits a strong antitumor immune response in mice, mainly through natural killer cell-mediated oncolytic activity via the activation of dendritic cells (DCs) and by enhancing inflammatory cytokines production such as IL-12 from DC. Hence, HK-Mpg can be a potential immunotherapy adjuvant, enhancing the effect of cancer chemotherapy.

The increase in canine skin and soft tissue infections, such as pyoderma and otitis, caused by Staphylococcus schleiferi strains, is of significant zoonotic concern. In this study, we report the first complete genome sequence for a methicillin-resistant clinical isolate of S. schleiferi (MRSS) designated as SS4, obtained from a dog with otitis externa, in Korea. The genome of SS4 strain was of 2,539,409 bp and presented high G+C content ratio (35.90%) with no plasmid. Comparative analysis of SS4 genome revealed that it is closely related to 2142-05 and 5909-02 strains isolated from the canine skin infections in the USA.

The purpose of this study is to investigate whether nicotinamide riboside (NR) can improve inflammation and cognitive function in diabetic mice. ICR male mice were fed for 14 weeks with either high-fat chow diet (HF, 60% kcal fat) or standard chow diet (CON, 10% kcal fat). HF, streptozotocin, and nicotinamide were used to induce hyperglycemia. NR or vehicle was delivered via stomach gavage for six weeks. Oral glucose tolerance test, Y-maze test, and nest construction test were conducted before and after the NR treatment period. NR treatment induced down-regulation of NLRP3, ASC, and caspase-1. NR reduced IL-1 expression significantly by 50% in whole brains of hyperglycemic mice. Other inflammatory markers including TNF-&alpha, and IL-6 were also attenuated by NR. Brain expression of amyloid-&beta, precursor protein and presenilin 1 were reduced by NR. In addition, NR induced significant reduction of amyloid-&beta, in whole brains of diabetic mice. NR treatment restored hyperglycemia-induced increases in brain karyopyknosis to the levels of controls. Nest construction test showed that NR improved hippocampus functions. Spatial recognition memory and locomotor activity were also improved by NR supplementation. These findings suggest that NR may be useful for treating cognitive impairment by inhibiting amyloidogenesis and neuroinflammation.

Hepatitis B virus infection is a serious global health problem and causes life-threatening liver disease. In particular, genotype C shows high prevalence and severe liver disease compared with other genotypes. However, the underlying mechanisms regarding virological traits still remain unclear. This study investigated the clinical factors and capacity to modulate Type I interferon (IFN-I) between two HBV polymerase polymorphisms rt269L and rt269I in genotype C. This report compared clinical factors between rt269L and rt269I in 220 Korean chronic patients with genotype C infections. The prevalence of preC mutations between rt269L and rt269I was compared using this study's cohort and the GenBank database. For in vitro and in vivo experiments, transient transfection using HBV genome plasmid and HBV virion infection using HepG2-hNTCP-C4 and HepaRG systems and hydrodynamic injection of HBV genome into mice tails were conducted, respectively. This report's clinical data indicated that rt269I vs. rt269L was more significantly related to HBV e antigen (HBeAg) negative serostatus, lower levels of HBV DNA and HBsAg, and disease progression. Our epidemiological study showed HBeAg negative infections of rt269I infections were attributed to a higher frequency of preC mutations at 1896 (G to A). Our in vitro and in vivo studies also found that rt269I could lead to mitochondrial stress mediated STING dependent IFN-I production, resulting in decreasing HBV replication via the induction of heme-oxygenase-1. In addition, we also found that rt269I could lead to enhanced iNOS mediated NO production in an IFN-I dependent manner. These data demonstrated that rt269I can contribute to HBeAg negative infections and liver disease progression in chronic patients with genotype C infections via mitochondrial stress mediated IFN-I production.

Thymic regulatory T cells (tT

OBJECTIVES: The aim of this study is to compare dietary intakes and dietary inflammatory index (DII) between normal subjects and patients with schizophrenia. METHODS: Total 306 subjects (139 controls and 167 patients with recent-onset schizophrenia spectrum disorder) were participated in this analysis. Dietary intakes of nutrients were analyzed from responses of a 76-items semi-quantitative food frequency questionnaire using CAN-Pro 5.0 software, and DII scores were estimated based on the analyzed results of dietary intakes. The total DII scores were calculated from dietary intakes of nutrients unadjusted or adjusted by energy contents. Then, dietary habit, nutritional intakes, and the DII score were compared between controls and schizophrenia group. Odds ratios (ORs) for schizophrenia and correlation between DII and related clinical data were analyzed by logistic regression analysis and Pearson's correlation test, respectively. RESULTS: There was a significant difference in body mass index between controls (22.49 ± 3.07 kg/m(2)) and schizophrenia subjects (24.27 ± 5.18 kg/m(2)) (P = 0.001). Schizophrenia group had remarkably higher energy intake and lower dietary intakes in omega-6 polyunsaturated fatty acids (PUFAs), linoleic acids, niacin, and vitamin E compared with control group (P

Rhodococcus sp. YHY01 was studied to utilize various lignin derived aromatic compounds. It was able to utilize p-coumaric acid, cresol, and 2,6 dimethoxyphenol and resulted in biomass production i.e. 0.38 g dcw/L, 0.25 g dcw/L and 0.1 g dcw/L, and lipid accumulation i.e. 49%, 40%, 30%, respectively. The half maximal inhibitory concentration (IC50) value for p-coumaric acid (13.4 mM), cresol (7.9 mM), and 2,6 dimethoxyphenol (3.4 mM) was analyzed. Dimethyl sulfoxide (DMSO) solubilized barley straw lignin fraction was used as a carbon source for Rhodococcus sp. YHY01 and resulted in 0.130 g dcw/L with 39% w/w lipid accumulation. Major fatty acids were palmitic acid (C16:0) 51.87%, palmitoleic acid (C16:l) 14.90%, and oleic acid (C18:1) 13.76%, respectively. Properties of biodiesel produced from barley straw lignin were as iodine value (IV) 27.25, cetane number (CN) 65.57, cold filter plugging point (CFPP) 14.36, viscosity (υ) 3.81, and density (ρ) 0.86.

Staphylococcus pseudintermedius is considered a primary pathogen of canine skin and soft tissue infections, and the rapid emergence of methicillin-resistant S. pseudintermedius worldwide is a major issue. In the current study, genotypic and phenotypic correlates associated with S. pseudintermedius causing canine otitis externa were evaluated using 41 S. pseudintermedius strains isolated from dogs with otitis externa (n = 26) and healthy dogs (n = 15). The S. pseudintermedius strains were subjected to a comparative analysis of (i) genotypes (multilocus sequence typing, agr, and spa types), (ii) methicillin resistance and SCCmec types, (iii) multidrug resistance (MDR), (iv) biofilm formation, and (v) susceptibility to canine cathelicidin (K9CATH). A high degree of genetic diversity was observed in both groups of S. pseudintermedius strains, regardless of methicillin resistance. Almost all methicillin-resistant strains (>95%) harbored SCCmec V and displayed MDR. Although there was no difference in biofilm formation, S. pseudintermedius strains derived from otitis externa exhibited enhanced resistance to cationic antimicrobial peptide (K9CATH) compared with strains from healthy dogs. The high degree of heterogeneity in MLST, agr, and spa types prevented the identification of correlations between any specific genotype and virulence phenotype in otitis externa caused by S. pseudintermedius, These findings provide an important basis for monitoring and treating canine skin and soft tissue infections in Korea.

Polyhydroxybutyrate (PHB), the most well-known polyhydroxyalkanoate, is a bio-based, biodegradable polymer that has the potential to replace petroleum-based plastics. Lignocellulose hydrolysate, a non-edible resource, is a promising substrate for the sustainable, fermentative production of PHB. However, its application is limited by the generation of inhibitors during the pretreatment processes. In this study, we investigated the feasibility of PHB production in

9049 Background: ROS1 fusions are oncogenic drivers in various cancers types, including 1-3% of non-small cell lung cancers (NSCLCs). Immunotherapy approvals for NSCLC include ROS1-rearranged carcinomas, but the activity of immune checkpoint inhibition (ICI) as monotherapy or in combination with chemotherapy (chemo-ICI) therapy, as well as the immunophenotypic characteristics of these tumors, have not been described in a large data set. Methods: In this multi-institutional study, patients with ROS1-rearranged NSCLC were identified retrospectively. Tumor PD-L1 expression and tumor mutational burden (TMB) were assessed as part of routine clinical care. In patients who received ICI monotherapy or chemo-ICI in the metastatic setting, time to treatment discontinuation (TTD) and objective response rate (ORR; RECIST v. 1.1) were calculated. TTD was assessed with Kaplan-Meier methods; patients remaining on treatment were censored at last follow up. Results: 184 patients with ROS1-rearranged NSCLC were identified. Among 146 PD-L1 evaluable cases, PD-L1 expression was < 1% in 60 (41%), 1-49% in 35 (24%) and ≥50% in 51 (35%) tumors. Ninety-two of 100 (92%) TMB-evaluable tumors had < 10 mutations/megabase (mut/Mb). TMB was significantly lower for ROS1-rearranged NSCLCs (n = 97) vs. ROS1-wild type tumors (n = 5,380) evaluated with next-generation sequencing using MSK-IMPACT (median 2.6 vs. 5.9 mut/Mb, p < 0.001). Twenty-eight patients received ICI monotherapy and 11 patients received chemo-ICI. The median TTD was 2.1 months (95% CI: 1.0-4.2; n = 28) for single-agent ICI therapy and 10 months (95% CI: 4.7-14.1; n = 11) for chemo-ICI therapy. The ORR was 13% (2/16 RECIST-evaluable; 95% CI: 2-38%) for ICI monotherapy and 83% (5/6 RECIST-evaluable; 95% CI: 36-100%) for chemo-ICI therapy. There was no difference in PD-L1 tumor expression (p = 0.9) or TMB (p = 0.8) between responders and non-responders and no correlation between PD-L1 tumor expression (rho = 0.16, p = 0.6) or TMB (rho = 0.03, p = 0.9) and maximum change in sum of target lesions. Conclusions: Most ROS1-rearranged NSCLCs have low or no PD-L1 expression and low TMB. The activity of checkpoint inhibitor monotherapy is disappointing in ROS1-driven NSCLC. In contrast, combination chemoimmunotherapy can achieve clinically meaningful activity.

Adoptive transfer of regulatory T cells (Tregs) is therapeutic in T1D mouse models. Notably, Tregs specific for pancreatic islets were shown more potent than polyclonal Tregs in blocking disease. However, the frequency of antigen-specific Tregs is extremely low and ex vivo expansion has the potential risk to destabilize Tregs leading to an effector phenotype. Here, we developed methods to generate durable, antigen-specific engineered Tregs (EngTregs) from primary human CD4+ T cells using a combination of lentiviral TCR transduction and FOXP3 homology-directed repair (HDR)-editing. Using TCRs derived from clonally expanded islet-reactive CD4+ T cells in T1D, we generated islet-specific EngTregs that exhibit a Treg-like phenotype. Islet-specific EngTregs effectively suppress proliferation and cytokine production by islet-specific effector T cells (Teff). Notably, EngTregs suppress Teff recognizing the identical peptide as well as bystander Teff recognizing alternative islet antigens. Importantly, islet-specific EngTregs suppress polyclonal endogenous islet-specific T cells derived from PBMC of individuals with T1D. To directly assess the capacity of EngTregs to modulate diabetes in vivo, we established an identical HDR-editing strategy in islet-specific murine cells. Following adoptive transfer, islet-specific mu-EngTregs homed to the pancreas and blocked diabetes triggered by islet-specific Teff in recipient mice. Collectively, our approach enables the production of EngTregs specific to pancreatic islets with the capacity to efficiently suppress islet specific responses. This approach has the capacity to deliver targeted islet specific therapy to treat or prevent T1D.

Ag processing in the endoplasmic reticulum (ER) by the ER aminopeptidase associated with Ag processing (ERAAP) is central to presentation of a normal peptide–MHC class I (MHC I) repertoire. Alternations in ERAAP function cause dramatic changes in the MHC I–presented peptides, which elicit potent immune responses. An unusual subset of CD8+ T cells monitor normal Ag processing by responding to a highly conserved FL9 peptide that is presented by Qa-1b, a nonclassical MHC Ib molecule (QFL) in ERAAP-deficient cells. To understand the structural basis for recognition of the conserved ligand, we analyzed the αβ TCRs of QFL-specific T cells. Individual cells in normal wild-type and TCRβ-transgenic mice were assessed for QFL-specific TCR α- and β-chains. The QFL-specific cells expressed a predominant semi-invariant TCR generated by DNA rearrangement of TRAV9d-3–TRAJ21 α-chain and TRBV5–TRBD1–TRBJ2-7 β-chain gene segments. Furthermore, the CDR3 regions of the α- as well as β-chains were required for QFL ligand recognition. Thus, the αβ TCRs used to recognize the peptide–Qa-1 ligand presented by ERAAP-deficient cells are semi-invariant and likely reflect a conserved mechanism for monitoring the fidelity of Ag processing in the ER.

The aim of this study was to compare the sequence of the astA gene found in 8 Korean and 11 Japanese Escherichia coli isolates. Conventional PCR was used to amplify the astA gene from the chromosomal and plasmid DNA preparation samples of each isolate using commercial DNA extraction kits. Cloning of the PCR products, sequence analysis, and pulse field gel electrophoresis (PFGE) were sequentially performed. An identical copy of astA in each isolate were found for 8 Korean and 8 Japanese E. coli strains isolated from bovine, porcine, and healthy human carriers. Among these, 1 Korean and 4 Japanese isolates carried a stop mutation at residue 16. Three Japanese outbreak strains (V199, V638, and 96-127-23) carried multiple clones of astA gene with multiple amino acids changes at residues 11, 16, 20, 23, 30, 33, and 34. Compared with the non-diarrheal isolates, clonal diversity and sequence variations of the astA gene in outbreak isolates may be associated with virulence potential of EAST1.

국민안전처가 개발 주체가 되어 재난 피해자를 위한 재난심리 치료를 위해 기능성 게임을 제안하고 운영할 수 있을까? 재난 회복력을 위한 기능성 게임 활용 가능성에 대한 연구 사례는 찾아보기 힘들다. 이러한 가능성을 논의하기 위해 재난 회복력과 기능성 게임과 관련된 주제어 검색으로 나타난 선행 연구들이 그러한 가능성을 언급하고 있는지 또는 관련 선행 연구들이...

Delayed wound healing is one of the major diabetic complications. During wound healing process, the early inflammatory stage is important for better prognosis. One of antioxidant nutrient, gamma-tocopherol (GT) is considered to regulate inflammatory conditions. This study investigated the effect of GT supplementation on mechanism associated with inflammation, oxidative stress, and apoptosis during early cutaneous wound healing in diabetic mice. Diabetes was induced by alloxan injection in ICR mice. All mice were divided into three groups: non-diabetic control mice (CON), diabetic control mice (DMC), and diabetic mice supplemented with GT (GT). After two weeks of GT supplementation, excisional wounds were made by biopsy punches (4 mm). Diabetic mice showed increases in fasting blood glucose (FBG) level, hyper-inflammatory response, oxidative stress, and delayed wound closure rate compared to non-diabetic mice. However, GT supplementation reduced FBG level and accelerated wound closure rate by regulation of inflammatory response-related proteins such as nuclear factor kappa B, interleukin-1β, tumor necrosis factor-α, and c-reactive protein, and oxidative stress-related markers including nuclear factor (erythroid derived 2)-like 2, NAD(P)H dehydrogenase quinone1, heme oxygenase-1, manganese superoxide dismutase, catalase and glutathione peroxidase and apoptosis-related markers such as sirtuin-1, peroxisome proliferator-activated receptor gamma coactivator 1- α, and p53 in diabetic mice. Taken together, GT would be a potential therapeutic to prevent diabetes-induced delayed wound healing by regulation of inflammatory response, apoptosis, and oxidative stress. Impact statement Gamma tocopherol has shown ameliorative effect on diabetic wound healing by regulation of inflammation, oxidative stress, and apoptosis demonstrated by nuclear factor kappa B, nuclear factor (erythroid derived 2)-like 2, and sirtuin-1.

Antimicrobial-resistant (AR) enterococci have emerged as leading nosocomial pathogens. Transmission of AR Enterococci from animals to humans has been demonstrated. However, there is limited information on the transmission of enterococci from horses to humans. To address this issue, we characterized 260 enterococci isolated from horse-associated samples in Korea in 2013 based on their AR profiles and virulence traits. AR profiling revealed an average ratio of AR enterococci of 23.8%. Seven isolates (2.7%) were multidrug-resistant Enterococcus faecalis. Most tetracycline-resistant enterococci harbored either tetM or tetL or both genes; genes conferring resistance to other antimicrobials were detected at low rates. Biofilm formation and gelatinase activity were observed in 51.1% and 47.7% of isolates, respectively; most were E. faecalis harboring the gelE gene. Evidence of transmission of AR enterococci between horses and their environments was provided by pulsed-field gel electrophoresis, and highlights the risk of AR enterococcus transmission to horse riders and handlers through close contact.

Oligosaccharide (OS) is used as a sugar replacement as well as an ingredient in functional foods because of its beneficial effects, mainly on reducing calorie content and promoting intestinal health. By contrast, the effects of OS on inflammation are less well investigated. The purpose of this study was to investigate the effects of sucrose-derived OS on glucose control and inflammation in high fat (HF) diet-fed mice. Male C57BL6 mice were randomly assigned to six treatment groups (n = 10-14 mice per group): 1) lean control (CON), 2) HF control, 3) HF-low sucrose (LS, 100 mg/kg/day), 4) HF-high sucrose (HS, 1000 mg/kg/day), 5) HF-low OS (LOS, 100 mg/kg/day), and 6) HF-high OS (HOS, 1000 mg/kg/day). PBS (vehicle), sucrose, and OS were administered by stomach gavage. Body weight, food intake, and markers of liver function (activities of aspartate aminotransferase and alanine aminotransferase) were not affected by the treatments. HOS treatment decreased levels of serum glucose, insulin, and homeostasis model assessment-insulin resistance compared with sucrose treatment. However, serum adiponectin levels of the HOS group were higher than those of the sucrose groups. Serum levels of the pro-inflammatory cytokines interleukin-6 (IL-6) and fetuin-A were lower in the HOS group than in the sucrose groups. Hepatic gene expression levels of pro-inflammatory cytokines and related factors (fetuin-A, NF-κB, TLR4, TNF-alpha, and IL-6) were decreased and the levels of insulin signaling-related molecules (sirtuin 1, insulin receptor, and Akt) were increased in HOS-treated mice as compared with sucrose-treated mice. These results demonstrate that OS treatment is effective in improving glucose control and inflammation in high fat diet-fed mice.

Analysis of nutritional compositions of soybean sprouts cultivated with bamboo ash was carried out. Bamboo ash was utilized as sprouting water of soybeans and adjusted to 0.2, 0.6, 1.0, 1.4, 2.0, 6.0 and 10.0 g/L. Stem length and contents of isoflavone (daidzin, glycitin, genestin, daidzein, glycitein, and genestein) and vitamin C in soybean sprouts cultivated with 0.2 g/L were higher than those in soybean sprouts cultivated with only water. Potassium, magnesium, and calcium of all cultivation methods were detected in higher contents than others. In particular, potassium showed a high absorption rate in the soybean sprouts. The major amino acid was asparagine (616.05~849.15 mg/100 g, soybean eq.), and contents of lysine, leucine, and ornithine in soybean sprouts cultivated at 0.2 g/L were higher than those of methods by only water and addition of 6-benzylaminopurine. According to the results, soybean sprouts cultivated with 0.2 g/L of bamboo ash were effective for increasing nutritional compositions.

Many countries have taken an interest in small and medium sized nuclear power plants. SMART, which was developed by Korea Atomic Energy Research Institute (KAERI), is a small sized integral type pressurized water reactor with a rated thermal power of 330 MW. In order to analyze thermal hydraulic characteristics of the SMART design, the TASS/SMR code has been developed. The code was validated using the results of basic and separate effect tests including small scale experiments for the SMART special components. To enhance an analysis capability of the TASS/SMR code for an integral type PWR, the KAERI has constructed the VISTA-ITL facility, and several integral effect tests have been performed at the VISTA-ITL facility. The TASS/SMR code is validated using the results of a loss of coolant flow transient, which is one of the integral effect tests performed at the VISTA-ITL. According to the evaluation results, the code predicts well the overall thermal hydraulic behaviors including the system pressure, fluid temperature, and mass flow rate. The main coolant pump model is important in order to simulate well the primary coolant flow behavior at an early transient.

Limited information is available regarding horse-associated antimicrobial resistant (AR) Escherichia (E.) coli. This study was designed to evaluate the frequency and characterize the pattern of AR E. coli from healthy horse-associated samples. A total of 143 E. coli (4.6%) were isolated from 3,078 samples collected from three national racetracks and 14 private horse-riding courses in Korea. Thirty of the E. coli isolates (21%) showed antimicrobial resistance to at least one antimicrobial agent, and four of the AR E. coli (13.3%) were defined as multi-drug resistance. Most of the AR E. coli harbored AR genes corresponding to their antimicrobial resistance phenotypes. Four of the AR E. coli carried class 1 integrase gene (intI1), a gene associated with multi-drug resistance. Pulsed-field gel electrophoretic analysis showed no genetic relatedness among AR E. coli isolated from different facilities; however, cross-transmissions between horses or horses and environments were detected in two facilities. Although cross-transmission of AR E. coli in horses and their environments was generally low, our study suggests a risk of transmission of AR bacteria between horses and humans. Further studies are needed to evaluate the risk of possible transmission of horse-associated AR bacteria to human communities through horse riders and horse-care workers.

BACKGROUND In small series or individual reports, SNPs within the mprF ORF and dysregulation of its expression in Staphylococcus aureus have been linked to daptomycin resistance (DAP-R) via a proposed gain-in-function mechanism. Similarly, dysregulation of dltABCD has also been associated with DAP-R. METHODS Using 22 well-characterized, isogenic daptomycin-susceptible (DAP-S)/DAP-R clinical MRSA strain pairs, we assessed potential relationships of the DAP-R phenotype with: (i) regulation of mprF transcription; (ii) regulation of dltABCD transcription; (iii) expression of the two-component regulatory system, graRS (upstream regulator for both mprF and dltABCD transcription); (iv) SNPs within the graRS promoter or its ORF; and (v) altered mprF transcription and lysyl-phosphatidylglycerol (L-PG) synthesis. RESULTS Enhanced expression of mprF occurred with SNPs in highly distinct and well-chronicled MprF domain 'hot spots' and rarely occurred without such mutations. Increased expression and/or dysregulation of mprF and dltABCD were not uncommon in DAP-R strains, occurring in 27% of strains for each gene. In these latter strains, neither graRS expression profiles nor polymorphic sequences within the graRS promoter or ORF could be significantly linked to altered transcription of mprF or dlt. CONCLUSIONS Although graRS can co-regulate mprF and dltABCD expression, loci outside of this regulon appear to be involved in dysregulation of these latter two genes and the DAP-R phenotype. Finally, DAP-R strains exhibiting significantly altered mprF transcription profiles produced significantly increased levels of L-PG.

Buckwheat (Fagopyrum esculentumMoench; 2n= 2x= 16) is a nutritionally dense annual crop widely grown in temperate zones. To accelerate molecular breeding programmes of this important crop, we generated a draft assembly of the buckwheat genome using short reads obtained by next-generation sequencing (NGS), and constructed the Buckwheat Genome DataBase. After assembling short reads, we determined 387, 594 scaffolds as the draft genome sequence (FES_r1.0). The total length of FES_r1.0 was 1, 177, 687, 305 bp, and the N50 of the scaffolds was 25, 109 bp. Gene prediction analysis revealed 286, 768 coding sequences (CDSs; FES_r1.0_cds) including those related to transposable elements. The total length of FES_r1.0_cds was 212, 917, 911 bp, and the N50 was 1, 101 bp. Of these, the functions of 35, 816 CDSs excluding those for transposable elements were annotated by BLAST analysis. To demonstrate the utility of the database, we conducted several test analyses using BLAST and keyword searches. Furthermore, we used the draft genome as a reference sequence for NGS-based markers, and successfully identified novel candidate genes controlling heteromorphic self-incompatibility of buckwheat. The database and draft genome sequence provide a valuable resource that can be used in efforts to develop buckwheat cultivars with superior agronomic traits., 世界初となるソバの全ゲノム解読に成功 －ソバの安全性、高品質性、収量安定性の鍵となる遺伝情報の発見－. 京都大学プレスリリース. 2016-04-13.

Soft tissues such as blood vessels possess mechanical behavior characterized by a ‘J-shaped’ stress-strain curve with a low-stiffness and a highly elastic zone. These biomechanical characteristics result in rapid endothelialization, smooth muscle cell regeneration, and aneurysm inhibition. The objective of this study was to fabricate biodegradable vascular grafts mimicking the mechanical properties of native arteries. Vascular grafts (inner diameter = 5.0 mm, length = 2.0 cm) were fabricated by dip coating poly(L-lactide-co-e-caprolactone) (PLCL) copolymers on polydioxanone (PDO) fibers. We used PDO fibers of different diameters to yield vascular grafts with a range of mechanical properties. Biomechanical properties, microstructure, and biocompatibility of the grafts were assessed using circumferential tensile testing, burst pressure measurement, scanning electron microscopy, and subcutaneous implantation, respectively. Vascular grafts possessed circumferential tensile strength and strain in the range of 4.07 to 5.98 MPa and 2.83 to 3.47 MPa, respectively, and were circumferentially stronger than expanded polytetrafluoroethylene (ePTFE) grafts. Burst pressure was physiologically relevant in the range of 1323.0 to 1736 kPa and water entry pressure was between 102.66 to 257.33 kPa. Mechanical properties of the grafts were also assessed in vivo after subcutaneous implantation in Sprague-Dawley rats for up to 8 weeks. Examination of the retrieved grafts indicated that the ‘J-shaped’ strain/stress curve was maintained for up to 3 week in PDO/PLCL vascular grafts. In contrast, ePTFE grafts did not maintain ‘J-shaped’ stress-strain behavior after in vivo implantation. Histological analysis demonstrated cellularization within PDO/PLCL grafts, whereas, PTFE grafts showed cellularization and neotissues mainly at the outer side. Our results suggest a new methodology for the fabrication of biodegradable vascular grafts with mechanical behaviour comparable to the native arteries that might avoid failure due to mechanical mismatch between the graft and native arteries.

Estimation of the National Marrow Donor Program's Be The Match Registry 8/8 (HLA-A, -B, -C, and -DRB1) high-resolution (HR) unrelated donor (URD) match rate was determined in a prior study for each of the 4 most frequent patient race/ethnic groups in the United States: white (WH), Hispanic (HIS), Asian/Pacific Islander (API), and African American (AFA). For patients without an 8/8 HLA-matched URD, a 7/8 match, with a single allele or antigen mismatch, is often accepted by many transplant centers. A follow-up study was designed to determine the 7/8 or better match rate among the 4 major race/ethnic groups, using the same study cohort. Of previously HR tested URDs in the Be The Match Registry, 1344 were randomly selected and treated as pseudo-patients where HR testing was performed to identify a 7/8-matched URD; 98% of WH and over 80% of non-WH race/ethnic groups (HIS, API, and AFA) had at least a 7/8 match identified. In most cases after first testing to identify an 8/8-matched URD, a 7/8-matched URD was identified after typing just 1 URD. Extending criteria to identify a 9/10 match (included HLA-DQB1) showed the 9/10 absolute match rate decreased between 14% and 21% from the 7/8 match rate for the non-WH groups. This study provides a baseline 7/8 and 9/10 or better HLA match rate that can be further supplemented using the additional worldwide URD inventory. URD match rate information can equip centers in clinical planning and the education of patients seeking a life-saving therapy.

γ-Aminobutyric acid (GABA) is an amino acid not present in proteins. GABA participates in a variety of physiological functions and has received significant attention in the medical and food industries. In this study, GABA production was investigated using Lactobacillus plantarum. We designed a synthetic medium consisting of the simplest medium components such as yeast extract (nitrogen source), glucose (carbon source), and monosodium l -glutamate (MSG; substrate for GABA) and optimized their proportions to efficiently produce GABA. As a result, 19.8 g/L GABA was obtained under an optimal synthetic medium composition of 100 g/L yeast extract, 10 g/L glucose, and 2.25% MSG, which is the highest among previous studies using L. plantarum. Interestingly, 159.7% of theoretical maximum yield based on initial MSG content was obtained since yeast extract acts as a secondary source of substrate. By proper optimization with the simplest medium using L. plantarum, it can produce a high titer of GABA as well as might help various functional foods containing GABA to develop.

Recently, we reported a 6-mer hepatitis B virus (HBV)-derived peptide, Poly6, that exerts antiviral effects against human immunodeficiency virus type 1 (HIV-1). Here, we explored the immunotherapeutic potential of Poly6 via its administration into dendritic cells (DCs) in a mouse model. Our data revealed that Poly6 treatment led to enhanced production of tumor necrosis factor alpha (TNF-&alpha, ) and inducible nitric oxide synthase (iNOS)-producing DCs (Tip-DCs) in a type 1 interferon (IFN-I)-dependent manner via the induction of mitochondrial stress. Poly6 treatment in mice implanted with MC38 cells, a murine colon adenocarcinoma line, led to attenuated tumor formation, primarily due to direct cell death induced by Tip-DC mediated nitric oxide (NO) production and indirect killing by Tip-DC mediated cluster of differentiation 8 (CD8) cytotoxic T lymphocyte (CTL) activation via CD40 activation. Moreover, Poly6 treatment demonstrated an enhanced anticancer effect with one of the checkpoint inhibitors, the anti PD-L1 antibody. In conclusion, our data reveal that Poly6 treatment elicits an antitumor immune response in mice, possibly through NO-mediated oncolytic activity via Tip-DC activation and Tip-DC mediated CTL activation. This suggests that Poly6 represents a potential adjuvant for cancer immunotherapy by enhancing the anticancer effects of immune checkpoint inhibitors.

Introduction For patients with advanced NSCLC, cytologic samples may be the only diagnostic specimen available for molecular profiling. Although both rapid and comprehensive assessment are essential in this setting, an integrated multitest approach remains an important strategy in many laboratories, despite the risks and challenges when working with scant samples. In this study, we describe our experience and high success rate in using a multitest approach, focusing on the clinical validation and incorporation of ultrarapid EGFR testing using the Idylla system followed by comprehensive next-generation sequencing (NGS). Methods Cytology samples received for routine molecular testing were included in this study. The performance characteristics of the EGFR Idylla assay were assessed; tissue suitability parameters and interpretation criteria to supplement automated mutation calling were established. The assay performance was monitored for 1 year, comparing the results with those of concurrent NGS testing by MSK-IMPACT (primarily) or MSK-AmpliSeq and MSK-Fusion solid panel in a subset of cases. Results Overall, 301 samples were studied; 83 samples were included in validation (60.2% [50 of 83] were positive for EGFR mutations). Concordance with the reference method was 96.4% (80 of 83) of the samples with excellent reproducibility. The limit of detection was variable depending on the total tissue input and the specific mutation tested. Unextracted tissue inputs that maintained total EGFR cycle of quantification at less than 23 allowed all mutations to be detected if present at greater than 5% variant allele frequency. Mutations could be detected at 1% variant allele frequency with total EGFR cycle of quantification of 18. During the clinical implementation phase, 218 NSCLC samples were tested by Idylla (24.3% [53 of 218] were EGFR mutation positive). Concurrent NGS testing was requested on 165 samples and successfully performed on 96.4% (159 of 165) of the samples. The Idylla automated results were concordant with those obtained by NGS in 96.2% (153 of 159) of cases and improved to 98.7% (157 of 159) after incorporation of manual review criteria to supplement automated calling, resulting in a diagnostic sensitivity of 95.6% (95% confidence interval: 84.9%–99.5%). In general, 9% (14 of 159) of the cases tested by NGS had EGFR mutations not covered by the Idylla assay, primarily insertions in exon 19 and 20 and minor mutations co-occurring with canonical sensitizing mutations. Conclusions Comprehensive molecular testing is feasible and has a high success rate in NSCLC cytology samples when using a multitest approach. Testing with the Idylla system enables rapid and accurate determination of the EGFR status without compromising subsequent NGS testing.