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We confirmed that Lactobacillus paracasei (L. paracasei) strains (KBL382, 384, 385) exhibited strong protective effects in an in vivo dextran sodium sulfate-induced colitis model. L. paracasei treatment significantly improved colitis symptoms. Among tested strains, L. paracasei KBL382-treated mice exhibited significantly lower levels of cytokines interferon gamma, interleukin (IL)-4, IL-6, tumor necrosis factor, and IL-17A. On the other hand, higher levels of anti-inflammatory cytokine IL-10 and CD4 + CD25 + Foxp3+ T regulatory cell populations in mesenteric lymph nodes were observed in mice group with L. paracasei. L. paracasei treatment clearly increased zonula occluden-1, claudin 3, and mucin 4 levels, which improved the tight junction and mucus thickness. L. paracasei-treated mice showed significantly higher bacterial diversity and changed the composition of cecal microbiota. Therefore, we suggest that L. paracasei could be a useful tool in the treatment of inflammatory bowel diseases via immunomodulation and the improvement of gut microbiota.

An obligately anaerobic, Gram-stain-positive and spore-forming strain, SNUG30386T was isolated from a faecal sample of a healthy Korean subject. The strain formed a round ivory-coloured colony and cells were chained rods with tapered ends, approximately 2.0–2.5×0.6–0.8 μm in size. The taxonomic analysis indicated that strain SNUG30386T was within the family Lachnospiraceae . According to the 16S rRNA gene sequence similarity, the closest species to strain SNUG30386T was Clostridium symbiosum (95.6 %), followed by Enterocloster asparagiformis (94.8 %), Enterocloster clostridioformis (94.8 %) and Enterocloster lavalensis (94.6 %). The evolutionary tree based on 16S rRNA gene sequences demonstrated that strain SNUG30386T had split apart at a unique branch point far from other close relatives. Its DNA G+C content was 48.3 mol% calculated from the whole genome sequence. The major cellular fatty acids were C16 : 0 and C14 : 0. Compared to those of the closely related species, strain SNUG30386T showed distinct biochemical activities such as being unable to utilize most of carbon sources except d-glucose and l-arabinose. As a result, based on its unique phylogenetic clade and taxonomic characteristics, we conclude that strain SNUG30386T represents a novel species within the genus Clostridium , for which the name Clostridium fessum sp. nov. is proposed. The type strain of the novel species is SNUG30386T (=KCTC 15633T= JCM 32258T).

Background Elements, including essential minerals and metals, play an important role in human biological functions. Some studies have suggested that exposure to certain elements such as arsenic and cadmium can disturb gut microbiota and result in metabolic disorders. Despite considerable evidence that exposure to toxic heavy metals is significantly associated with host metabolic disorder, few studies have investigated the relationships between fecal elements, gut microbiota, and host metabolism. In order to gain a deeper understanding of the impact of various fecal elements on gut microbiota and metabolic disorder, we have to investigate fecal elements from human stools for association study and demonstrate that certain elements have the causal effect on metabolic disease and changes in gut microbiota. Results We analyzed 28 elements from 304 feces of human twins and evaluated the effects of fecal elements on both gut microbiota and metabolic disorder. Fecal beryllium content was found significantly correlated with biomarkers of metabolic disease and metabolic disease-related gut microbiota such as Akkermansia and Bifidobacterium . In vitro human fecal culture showed marked reduction of species evenness and Bifidobacterium abundance after beryllium treatment. Notably, in mice fed a high-fat diet, 30 ppb of beryllium exposure resulted in significant body weight gain and increased plasma biomarkers for metabolic disorder with an altered microbial community. Beryllium exposure also affected cecal short chain fatty acid profiles, colonic function, and inflammation. Conclusions Our findings indicate that low doses of beryllium, almost similar to the current criteria for beryllium in drinking water, perturb the gut microbiota and worsen metabolic disorders, which is significant implication in public health.

An intramolecular rhodium-catalyzed transannulation of readily available cyanothiadiazoles containing an ester, amide, or ether as a linker is described. It provides a wide range of bicyclic isothiazoles in good to excellent yields together with the release of molecular nitrogen. These results indicate that the carbon atom in the α-thiavinyl carbene is nucleophilic and that the sulfur atom is electrophilic.

A rhodium-catalyzed cyclization reaction of sulfoximines with 3-diazoindolin-2-imines is described. This protocol provides a wide range of indolo-1,2-benzothiazines in moderate to excellent yields together with the release of molecular nitrogen and p-toluenesulfonamide. The present method involves the N–H/C–H activation of S-aryl sulfoximines and has the advantages of a broad substrate scope.

An efficient synthetic method for the selective preparation of dihydrophosphaisocoumarins and their derivatives was developed through a palladium-catalyzed oxidative cyclization reaction of a wide range of arylphosphonic acid monoethyl esters with activated and unactivated 1,3-dienes, including 1-aryl-substituted 1,3-dienes and 1-alkyl-substituted 1,3-dienes, thus opening a new avenue for the synthesis of phosphaheterocyclic compounds.

Gut microbiota play an important role in immune responses and energy metabolism. In this study, we evaluated whether administration of Lactobacillus fermentum (L. fermentum) KBL375 isolated from healthy Korean feces improves the atopic dermatitis using the house dust mite (Dermatophagoides farinae)-induced atopic dermatitis (AD) mouse model. Administration of L. fermentum KBL375 significantly decreased dermatitis score, ear and dorsal thickness, and serum immunoglobulin E level in AD-induced mice. Significant reductions in mast cells and eosinophils were discovered in skin tissues from L. fermentum KBL375-treated mice. T helper 2 cell-related cytokines interleukin (IL)-4, IL-5, IL-13, and IL-31 significantly decreased, and anti-inflammatory cytokine IL-10 or transforming growth factor-β increased in skin tissues from L. fermentum KBL375-treated mice. In addition to phenotypic changes in skin tissues, L. fermentum KBL375 treatment induced an increase in the CD4+CD25+Foxp3+ cell population in mesenteric lymph nodes. Taxonomic and functional analyses of gut microbiota showed significantly higher cecum bacterial diversities and abundances including genus Bilophila, Dorea, and Dehalobacterium in L. fermentum KBL375-treated mice. Metabolic analysis of the cecum also showed significant changes in the levels of various amino acids including methionine, phenylalanine, serine, and tyrosine, as well as short chain fatty acids such as acetate, butyrate, and propionate in AD-induced mice due to L. fermentum KBL375 treatment. These altered metabolites in AD-induced mice returned to the levels similar to those in control mice when treated with L. fermentum KBL375. Therefore, L. fermentum KBL375 could be useful for AD treatment by modulating the immune system and inducing various metabolites.

Two long-rod-shaped, Gram-stain-positive, obligately anaerobic and non-spore-forming strains, SNUG30099T and SNUG30370T, were isolated from faecal samples of healthy Korean subjects. The strains formed circular ivory-coloured colonies on Brain-heart infusion medium supplemented with 0.5% Difco yeast extract (YBHI) agar and cells were approximately 3.5–4.5×0.3–0.4 µm in size. Taxonomic analyses based on 16S rRNA gene sequences distinguished the strains from other species within the family Erysipelotrichaceae . The closest relative of strains SNUG30099T and SNUG30370T was Longibaculum muris (92.9 % and 93.6 % similarity, respectively), followed by Clostridium saccharogumia (92.3 % and 92.2 %). Phylogenetic inference also divided the strains into a unique branch that differed from other related strains that belong to the family Erysipelotrichaceae . DNA G+C contents based on the whole genome sequences of strains SNUG30099T and SNUG30370T were 29.2 and 30.2 mol%, respectively. Both novel strains possessed meso-diaminopimelic acid as the peptidoglycan, and phosphatidylethanolamine was observed as one of the major polar lipids. The major cellular fatty acid composition was different from those of other related taxa. In addition, the profile of biochemical activities advocated that the strains have distinct characteristics in comparison to other strains. Taken together, a novel genus, named Faecalibacillus gen. nov., is proposed, which includes the type species Faecalibacillus intestinalis sp. nov. for strain SNUG30099T and Faecalibacillus faecis sp. nov. for strain SNUG30370T. The type strains of these novel species are SNUG30099T (=KCTC 15631T=JCM 32256T) and SNUG30370T (=KCTC 15632T=JCM 32257T).

A synthetic method for obtaining a wide variety of isothiazoles by the Rh-catalyzed transannulation of 1,2,3-thiadiazoles with alkyl, aryl, and heteroaryl nitriles, which proceeds via an α-thiavinyl Rh-carbenoid intermediate, was developed. The results suggest that during its reaction with nitriles, the α-thiavinyl carbene acts as an umpolung 1,3-dipole equivalent, in contrast to its behavior during its reaction with alkynes. The developed method was successfully employed to synthesize pentaoligomeric arylene compounds consisting of three benzene and two isothiazole rings.

A Gram-stain-positive and obligately anaerobic bacterial strain, BR72T, forming ivory yellow colonies was isolated from a faecal sample of a healthy Korean woman. 16S rRNA gene sequence analysis indicated that strain BR72T belongs to Clostridium cluster XIVa and represents a distinct phyletic line within the family Lachnospiraceae. The most closely related strains were Clostridium nexile DSM 1787T (94.1 % 16S rRNA gene sequence similarity), Coprococcus comes ATCC 27758T (93.5 %), Ruminococcus torques ATCC 27756T (93.5 %), Ruminococcus lactaris ATCC 29176T (93.5 %), Clostridium aerotolerans DSM 5434T (93.1 %) and Eubacterium fissicatena DSM 3598T (92.9 %). The DNA G+C content of strain BR72T based on its genome sequence was 45.3 mol%. The major cellular fatty acids were C16 : 0, C14 : 0, and iso-C17 : 1 I and/or anteiso-C17 : 1 B. Acetic acid was produced from glucose fermentation. Other physiological and biochemical comparisons allowed the phenotypic differentiation of strain BR72T from the members of the family Lachnospiraceae. Based on the phylogenetic and phenotypic findings, this strain is considered to represent a novel species of a new genus belonging to the family Lachnospiraceae and the name Sellimonas intestinalis gen. nov., sp. nov. is proposed. The type strain of Sellimonas intestinalis is BR72T ( = KCTC 15479T = JCM 30749T).

Sequential copper-catalyzed [3+2] cycloaddition, rhodium-catalyzed OH insertion, intramolecular 1,8-addition, and rearrangement starting from 1-alkynes, N-sulfonyl azides, and tropolones is demonstrated for the synthesis of the 2-functionalized aminotropones in one pot. These results indicate that sequential functionalization of OH and C(sp2)O bonds smoothly occurs in the C(sp2)OH bonds of tropolone

Summary Although a link between the gut microbiota and alcohol-related liver diseases (ALDs) has previously been suggested, the causative effects of specific taxa and their functions have not been fully investigated to date. Here, we analyze the gut microbiota of 410 fecal samples from 212 Korean twins by using the Alcohol Use Disorders Identification Test (AUDIT) scales to adjust for host genetics. This analysis revealed a strong association between low AUDIT scores and the abundance of the butyrate-producing genus Roseburia. When Roseburia spp. are administered to ALD murine models, both hepatic steatosis and inflammation significantly improve regardless of bacterial viability. Specifically, the flagellin of R. intestinalis, possibly through Toll-like receptor 5 (TLR5) recognition, recovers gut barrier integrity through upregulation of the tight junction protein Occludin and helps to restore the gut microbiota through elevated expression of IL-22 and REG3γ. Our study demonstrates that Roseburia spp. improve the gut ecosystem and prevent leaky gut, leading to ameliorated ALDs.

Alkenylation of phosphacoumarins is developed from the reaction of phosphacoumarins with a variety of activated as well as nonactivated alkenes via aerobic oxidative Heck reactions. In addition, 3-alkenylphosphacoumarins undergo an inverse electron demand Diels-Alder reaction (IEDDA) with enamines in situ generated from ketone and pyrrolidine followed by 1,2-elimination and a dehydrogenation, producing fluorescent benzophosphacoumarins.

An ivory/yellow, Gram-stain-negative, short-rod-shaped, aerobic bacterial strain, designated JC2948T, was isolated from a soil sample taken from Gwanak Mountain, Republic of Korea. 16S rRNA gene sequence analysis indicated that strain JC2948T belongs to the genus Burkholderia . The test strain showed highest sequence similarities to Burkholderia tropica LMG 22274T (97.6 %), Burkholderia acidipaludis NBRC 101816T (97.5 %), Burkholderia tuberum LMG 21444T (97.5 %), Burkholderia sprentiae LMG 27175T (97.4 %), Burkholderia terricola LMG 20594T (97.3 %) and Burkholderia diazotrophica LMG 26031T (97.1 %). Based on average nucleotide identity (ANI) values, the new isolate represents a novel genomic species as it shows less than 90 % ANI values with other closely related species. Also, other phylosiological and biochemical comparisons allowed the phenotypic differentiation of strain JC2948T from other members of the genus Burkholderia . Therefore, we suggest that this strain should be classified as the type strain of a novel species of the genus Burkholderia . The name Burkholderia monticola sp. nov. (type strain, JC2948T = JCM 19904T = KACC 17924T) is proposed.

An efficient synthetic method of fluorenes having an enamine moiety at C-9 methylene bridge is developed from N-sulfonyl-4-biaryl-1,2,3-triazole derivatives via Rh-catalyzed denitrogenative cyclization in a 5-exo mode. Rh-catalyzed denitrogenative cyclization followed by catalytic hydrogenation produces N-tosylaminomethyl-substituted fluorenes in one pot. Moreover, fluorenes are synthesized via tandem Cu-catalyzed [3 + 2] cycloaddition and Rh-catalyzed denitrogenative cyclization in a 5-exo mode starting from 2-ethynylbiaryls and N-sulfonyl azides in one pot.

The Cu-catalyzed, formal aza-[3 + 2] cycloaddition reaction of pyridine derivatives with α-diazo oxime ethers in trifluoroethanol was used to synthesize imidazopyridines via the release of molecular nitrogen and elimination of alcohol. These methods enabled modular synthesis of a wide range of N-heterobicyclic compounds such as imidazopyridazines, imidazopyrimidines, and imidazopyrazines with an α-imino Cu-carbenoid generated from the α-diazo oxime ethers and copper.

A strictly anaerobic Gram-stain-positive, non-motile and non-spore-forming bacterial strain, BR31T, was isolated from a faecal sample of a healthy human. Bacterial colonies were ivory-coloured on GAM agar and composed of rod-shaped cells with rounded ends approximately 1.4–2.1×0.5–0.6 µm in size. According to comparative analysis based on 16S rRNA gene sequences, strain BR31T formed a distinct phylogenetic lineage that reflects a new genus within Clostridium cluster XIVa in the family Lachnospiraceae , with highest similarity to Eubacterium contortum DSM 3982T (94.6 %). The DNA G+C content was calculated to be 47.0 mol% from whole genome sequencing. Predicted genes associated with synthesis of teichuronic acid, polyamines, polar lipids and diaminopimelic acid were detected. The peptidoglycan contained meso-diaminopimelic acid and the main polar lipid detected was phosphatidylglycerol. The major metabolic end product of glucose was acetic acid, which was in agreement with those of most members of the family. However, the profile of major cellular fatty acids (C16 : 0, C14 : 0, summed feature 4 and C13 : 0) and overall enzyme activity demonstrated phenotypic differentiation of strain BR31T from other closely related genera. Thus, based on distinct phenotypic, phylogenetic, genotypic and chemotaxonomic characteristics, strain BR31T is considered to represent a novel species of a new genus, for which the name Merdimonas faecis gen. nov., sp. nov. is proposed. The type strain of Merdimonas faecis is BR31T (=KCTC 15482T=JCM 30748T).

Ha S Y, Lee C H, Chang H K, Chang S, Kwon K Y, Lee E H, Roh M S & Seo B (2012) Histopathology 60, 731–739 Differential expression of forkhead box M1 and its downstream cyclin-dependent kinase inhibitors p27kip1 and p21waf1/cip1 in the diagnosis of pulmonary neuroendocrine tumours Aims: Pulmonary neuroendocrine (NE) tumours represent a spectrum of phenotypically distinct entities with different biological behaviours. Difficulties in classifying these tumours are frequently encountered in clinical practice. Forkhead box M1 (FoxM1) is essential for the development of various cancers and is a proliferation-specific transcription factor that regulates transcription of cell cycle genes, including cyclin-dependent kinase inhibitors p27kip1 and p21waf1/cip1. This study was performed to determine the utility of FoxM1, p27kip1 and p21waf1/cip1 as immunomarkers for subtyping pulmonary NE tumours. Methods and results: FoxM1, p27kip1 and p21waf1/cip1 expression was evaluated by immunohistochemistry in 60 pulmonary NE tumours [19 typical carcinoids (TCs), six atypical carcinoids (ACs), 17 large cell neuroendocrine carcinomas (LCNECs) and 18 small cell lung cancers (SCLCs)]. The frequencies of FoxM1 and p21waf1/cip1 expression were significantly different between TCs and ACs (each P = 0.009), and those of FoxM1 and p27kip1 expression were significantly different between LCNECs and SCLCs (P = 0.012 and P = 0.002, respectively). The combined FoxM1(−)/p21waf1/cip1(−) and FoxM1(+)/p27kip1(high) phenotypes had the best diagnostic accuracy for distinguishing TCs from ACs, and SCLCs from LCNECs, respectively. Conclusions: FoxM1, p27kip1 and p21waf1/cip1 showed distinct immunoreactivity according to histological subtype, which may be of value as an ancillary test in the differential diagnosis of pulmonary NE tumours.

A variety of activated as well as nonactivated alkenes react with the title compounds via aerobic oxidative Heck reactions to 3-alkenylphosphacoumarins.

An efficient synthetic method of fluorenes having an enamine moiety at C-9 methylene bridge is developed from N-sulfonyl-4-biaryl-1,2,3-triazole derivatives via Rh-catalyzed denitrogenative cyclization in a 5-exo mode. Rh-catalyzed denitrogenative cyclization followed by catalytic hydrogenation produces N-tosylaminomethyl-substituted fluorenes in one pot. Moreover, fluorenes are synthesized via tandem Cu-catalyzed [3 + 2] cycloaddition and Rh-catalyzed denitrogenative cyclization in a 5-exo mode starting from 2-ethynylbiaryls and N-sulfonyl azides in one pot.

Diethyl bromoalkylphosphonates are coupled with a broad variety of aryl iodides via intermediate alkylindium species to give the corresponding arylalkylphosphonates in moderate to good yields.

A Gram-stain negative, rod-shaped, non-spore-forming, obligate aerobic bacterial strain, JC2949T, was isolated from grassland soil in Gwanak Mountain, Seoul, Republic of Korea. Phylogenetic analysis, based on 16S rRNA sequences, indicated that strain JC2949T belongs to the genus Burkholderia , showing highest sequence similarities with Burkholderia grimmiae R27T (98.8 %), Burkholderia cordobensis LMG 27620T (98.6 %), Burkholderia jiangsuensis MP-1TT (98.6 %), Burkholderia zhejiangensis OP-1T (98.5 %), Burkholderia humi LMG 22934T (97.5 %), Burkholderia terrestris LMG 22937T (97.3 %), Burkholderia telluris LMG 22936T (97.2 %) and Burkholderia glathei ATCC 29195T (97.0 %). The major fatty acids of strain JC2949T were C18 : 1ω7c, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. Its predominant polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and an unknown amino phospholipid. The dominant isoprenoid quinone was ubiquinone Q-8. The pairwise average nucleotide identity values between strain JC2949T and the genomes of 30 other species of the genus Burkholderia ranged from 73.4–90.4 %, indicating that the isolate is a novel genomic species within this genus. Based on phenotypic and chemotaxonomic comparisons, it is clear that strain JC2949T represents a novel species of the genus Burkholderia . We propose the name for this novel species to be Burkholderia megalochromosomata sp. nov. The type strain is JC2949T ( = KACC 17925T = JCM 19905T).

Phosphoryl alkylindium reagents are generated in situ from the direct insertion of indium with bromoalkyl phosphonates in the presence of CuCl, and their synthetic application to arylalkyl phosphonates is reported via a Pd-catalyzed cross-coupling reaction with tolerance of a diversity of functional groups including ester, ketone, aldehyde, nitrile, nitro, trifluoromethyl, chloride, methoxy, hydroxy, and amino.

α-Imino rhodium carbenes generated in situ from 1-sulfonyl-1,2,3-triazoles react with alkenyl alkyl ethers followed by an elimination reaction to produce pyrroles.

A method for synthesis of substituted pyrroles has been developed. 1-Sulfonyl-1,2,3-triazoles generated from terminal alkynes gave α-imino rhodium carbene complexes, which when reacted with alkenyl alkyl ethers afforded substituted pyrroles. The method can be efficiently applied to a one-pot sequential reaction starting from terminal alkynes.

Rhodium-catalyzed oxidative coupling reactions via C–H activation and annulation directed by phosphonamide and phosphinamide groups were developed under aerobic conditions, which produced benzazaphosphole 1-oxides and phosphaisoquinolin-1-oxides.

A tyrosinase inhibitor was isolated from the whole plant of Barbarea orthocerus Led. (Brassicaceae) by activity-guided fractionation, and identified as (R)-5-phenyl-2-oxazolidinethione (barbarin) by structural analysis followed by comparison with reported spectral data. The compound exhibited significant inhibitory effects on mushroom and murine tyrosinases at more than 1.6 × 10 -5 M. Barbarin exhibited IC 50 values of 4.2 × 10 -5 M on mushroom tyrosinase and of 4.8 × 10 -5 M on murine tyrosinase. Kojic acid as a positive control exhibited IC 50 values of 3.4 × 10 -5 M and 6.0 × 10 -5 M on mushroom and murine tyrosinases, respectively. Therefore, barbarin exhibited a similar level of inhibitory potency with kojic acid used as a positive control. In a kinetic study with various concentrations of L-dopa as the substrate, barbarin was identified as an uncompetitive inhibitor and kojic acid as a mixed inhibitor of both mushroom and murine tyrosinases. Barbarin exhibited K EIS values of 3.3 × 10 -5 M and 3.6 × 10 -5 M on mushroom and murine tyrosinases, respectively. Kojic acid exhibited K EIS and K EI values of 2.4 × 10 -5 M and 2.2 × 10 -5 M on mushroom tyrosinase and those of 8.9 × 10 -5 M and 7.2 × 10 -5 M on murine tyrosinase, respectively.

Pulmonary neuroendocrine (NE) tumours represent a spectrum of phenotypically distinct entities with different biological behaviours. Difficulties in classifying these tumours are frequently encountered in clinical practice. Forkhead box M1 (FoxM1) is essential for the development of various cancers and is a proliferation-specific transcription factor that regulates transcription of cell cycle genes, including cyclin-dependent kinase inhibitors p27(kip1) and p21(waf1/cip1) . This study was performed to determine the utility of FoxM1, p27(kip1) and p21(waf1/cip1) as immunomarkers for subtyping pulmonary NE tumours.FoxM1, p27(kip1) and p21(waf1/cip1) expression was evaluated by immunohistochemistry in 60 pulmonary NE tumours [19 typical carcinoids (TCs), six atypical carcinoids (ACs), 17 large cell neuroendocrine carcinomas (LCNECs) and 18 small cell lung cancers (SCLCs)]. The frequencies of FoxM1 and p21(waf1/cip1) expression were significantly different between TCs and ACs (each P = 0.009), and those of FoxM1 and p27(kip1) expression were significantly different between LCNECs and SCLCs (P = 0.012 and P = 0.002, respectively). The combined FoxM1((-)) /p21(waf1/cip1(-)) and FoxM1((+)) /p27(kip1(high)) phenotypes had the best diagnostic accuracy for distinguishing TCs from ACs, and SCLCs from LCNECs, respectively.FoxM1, p27(kip1) and p21(waf1/cip1) showed distinct immunoreactivity according to histological subtype, which may be of value as an ancillary test in the differential diagnosis of pulmonary NE tumours.

Rhodium-catalyzed oxidative coupling reactions via C-H activation and annulation directed by phosphonamide and phosphinamide groups were developed under aerobic conditions, which produced benzazaphosphole 1-oxides and phosphaisoquinolin-1-oxides.

Based on the fact that a decision feedback equaliser (DFE) can be divided into a linear equaliser and a prediction error filter with feedback, a new blind adaptation method for the DFE is proposed. The proposed method provides reliable convergence and the resulting symbol error rate is very close to that of the DFE using a training sequence