Two novel alkalitolerant species Pseudalkalibacillus spartinae sp. nov. and Pseudalkalibacillus sedimenti sp. nov.

In this study, two novel alkalitolerant strains (FJAT-53046T and FJAT-53715T) were isolated from sediment samples collected in Zhangzhou, PR China. Phylogeny based on 16S rRNA gene sequences suggested that strains FJAT-53046T and FJAT-53715T were new members of the genus Pseudalkalibacillus. The two novel strains showed the highest 16S rRNA gene sequence similarity to Pseudalkalibacillus hwajinpoensis DSM 16206T, with values of 97.4 and 97.6 %, respectively. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between the two strains and the reference strain were 77.2 and 79.6 %, 20.9 and 30.2 %, respectively, which were below the prokaryotic species delineation thresholds. The ANI and dDDH values between strains FJAT-53046T and FJAT-53715T were 86.0 and 30.2 %, respectively, suggesting that they belonged to different species in the genus Pseudalkalibacillus. The major respiratory quinone in both strains was MK-7 and the major cellular fatty acids were anteiso-C15 : 0 and anteiso-C17 : 0. Diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine were the major polar lipids in both novel strains. Combined with results stemming from the determination of physical and biochemical characteristics, chemical properties, and genome analysis, strains FJAT-53046T and FJAT-53715T are proposed to represent two novel species of the genus Pseudalkalibacillus, for which the names Pseudalkalibacillus spartinae sp. nov. and Pseudalkalibacillus sedimenti sp. nov. are proposed. The type strains are FJAT-53046T (=GDMCC 1.3077T=JCM 35611T) and FJAT-53715T (=GDMCC 1.3076T=JCM 35610T), respectively.

Cytobacillus citreus sp. nov., isolated from citrus rhizosphere soil.

A Gram-stain-positive, rod-shaped and motile strain, designated FJAT-49705T, was isolated from the citrus rhizosphere soil sample. Strain FJAT-49705T grew at 20-40 °C (optimum, 30 °C) and pH 6.0-11.0 (optimum, pH 7.0) with 0-5 % (w/v) NaCl (optimum, 2 %). Strain FJAT-49705T showed high 16S rRNA gene sequence similarity to 'Bacillus dafuensis' FJAT-25496T (99.7 %) and Cytobacillus solani FJAT-18043T (98.0 %). In phylogenetic (based on 16S rRNA gene sequences) and phylogenomic trees (based on 71 bacterial single-copy genes), strain FJAT-49705T clustered with the members of the genus Cytobacillus. MK-7 was the only isoprenoid quinone present. The main polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and an unidentified phospholipid. The major fatty acids were anteiso-C15 : 0 and iso-C15 : 0. The genomic DNA G+C content was 36.9 %. The average nucleotide identity (ANI) values between FJAT-49705T and 'B. dafuensis' FJAT-25496T and C. solani FJAT-18043T were below the cut-off level (95-96 %) recommended as the ANI criterion for interspecies identity. Based on the above results, strain FJAT-49705T represents a novel species of the genus Cytobacillus, for which the name Cytobacillus citreus sp. nov. is proposed. The type strain is FJAT-49705T (=CCTCC AB 2019243T= LMG 31580T).

α- and ß-(C4H5N2O)(IO3)·HIO3: Two SHG Materials Based on Organic-Inorganic Hybrid Iodates.

Organic-inorganic hybrid nonlinear optical (NLO) materials are highly anticipated because of the integration of both merits of the organic and inorganic moieties. Herein, the 2-pyrimidinone cation (C4H5N2O)+ has been incorporated into the iodate system to form two polymorphic organic-inorganic hybrid iodates, namely, α- and ß-(C4H5N2O)(IO3)·HIO3. They crystallize in different polar space groups (Ia and Pca21), and their structures feature one-dimensional (1D) chain structures composed of (C4H5N2O)+ cations, IO3- anions, and HIO3 molecules interconnected via hydrogen bonds. α- and ß-(C4H5N2O) (IO3)·HIO3 exhibit strong and moderate second-harmonic-generation (SHG) responses of 6.4 and 0.9 × KH2PO4 (KDP), respectively, the same band gaps of 3.65 eV, and high powder laser-induced damage threshold (LIDT) values [51 and 57 × AgGaS2 (AGS)]. The results of theoretical calculations revealed that the large SHG effect of α-(C4H5N2O)(IO3)·HIO3 originated from the IO3 and HIO3 groups. This work indicates that (C4H5N2O)+ is a potential group for designing new NLO materials with brilliant optical performances.

Mesenchymal stem cell transplantation worsens intestinal inflammation and microenvironment in PI3Kγ-knockout mice.

Considering the possible interaction between mesenchymal stem cells (MSCs) and PI3Kγ-associated drugs, we evaluated the efficacy and action mechanism of MSCs in the treatment of colitis in PI3Kγ-/- mice. Trinitro-benzene-sulfonic acid enema was used to create a colitis model, and MSCs were transplanted through the caudal vein to treat colitis in wild-type and PI3Kγ-/- mice. We sequenced microbial 16S rRNA genes in the colonic mucosa of PI3Kγ-/- and wild-type mice and quantified colonic IgA, IL-2, IL-10, IL-17A, occludin, and serum IgA. MSC transplantation led to a more serious reduction in the weight of trinitro-benzene-sulfonic acid-administered PI3Kγ-/- mice than that in wild-type mice. The disease activity index, pathological scoring, number of taxa in the colon, Berger-Parker index, I-index, proportion of Proteobacteria, and IgA level in the blood were higher in PI3Kγ-/- mice than in wild-type mice after MSC transplantation. The occludin and IL-10 levels in the colon tissues decreased before and after MSC transplantation in PI3Kγ-/- mice, whereas they were increased in wild-type mice The IL-17 level decreased in both wild-type and PI3Kγ-/- mice, with knockout mice showing a greater decrease. Therefore, MSC transplantation in PI3Kγ-/- mice led to increased numbers of exogenous pathogenic microorganisms and enhanced colitis that was difficult to relieve.

Neobacillus rhizophilus sp. nov. and Neobacillus citreus sp. nov., isolated from the citrus rhizosphere soil.

Two Gram-staining positive strains, FJAT-49825T and FJAT-50051T were isolated from a citrus rhizosphere soil sample. Strains FJAT-49825T and FJAT-50051T showed the highest 16S rRNA gene sequence similarity with the type strain of Neobacillus cucumis (98.4-98.5%). The 16S rRNA gene sequence similarity between strains FJAT-49825T and FJAT-50051T was 99.8%. Strain FJAT-49825T optimally grew at 35 °C, pH 6.0 in the absence of NaCl while strain FJAT-50051T grew at 40 °C, pH 7.0 and in presence of 2% NaCl (w/v). Both strains contained meso-2,6-diaminopimelic acid as the cell-wall diamino acid. The respiratory quinone of strains FJAT-49825T and FJAT-50051T was MK-7. The polar lipids of strain FJAT-49825T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, unidentified aminolipid and unidentified lipid whereas strain FJAT-50051T polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, unidentified phospholipid and unidentified lipid. The major fatty acids (> 10%) in both strains were iso-C15:0 and anteiso-C15:0. The genomic DNA G + C content of strains FJAT-49825T and FJAT-50051T were 40.8 and 41.1%, respectively. The average nucleotide identity and digital DNA-DNA hybridization value between strains FJAT-49825T and FJAT-50051T and with other members of the genus Neobacillus were lower than the cut-off value (95-96/70%) for interspecies identity. Based on the results, strains FJAT-49825T and FJAT-50051T represent two novel species of the genus Neobacillus, for which the names Neobacillus rhizophilus sp. nov. and Neobacillus citreus sp. nov. are proposed. The type strains are FJAT-49825T (= GDMCC 1.2592T = JCM 34834T) and FJAT-50051T (= GDMCC 1.2593T = JCM 34835T).

Evansella halocellulosilytica sp. nov., an alkali-halotolerant and cellulose-dissolving bacterium isolated from bauxite residue.

An alkali and salt-tolerating strain FJAT-44876T was isolated from the bauxite residue sample. The 16S rRNA gene sequence and phylogenetic analysis suggest that strain FJAT-44876T was a member of the genus Evansella. It grew at 15-45 â„ƒ (optimum 20-25 â„ƒ) and pH 6.5-11.0 (optimum pH 8.0-9.0) with 0-20% (w/v) NaCl (optimum 6-8%). The major fatty acids were anteiso-C15:0, iso-C15:0, anteiso-C17:0, iso-C17:0, and C16:0. The cell wall peptidoglycan contained meso-diaminopimelic acid and MK-7 as the menaquinone. The major polar lipids were diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, and phosphatidylglycerol. The genomic DNA G+C content was 38.2%. The average nucleotide identity values between strain FJAT-44876T and closely related members were below the cutoff level for species delineation. Thus, based on the above results, strain FJAT-44876T represents a novel species of the genus Evansella, for which the name Evansella halocellulosilytica sp. nov., is proposed. The type strain is FJAT-44876T (=CCTCC AB 2016264T = DSM 104633T).

Prognostic value of a nomogram based on peripheral blood immune parameters in unresectable hepatocellular carcinoma after intensity-modulated radiotherapy.

BACKGROUND: For patients with unresectable hepatocellular carcinoma (uHCC), intensity-modulated radiotherapy (IMRT) has become one of the options for clinical local treatment. Immune parameters, including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic immune inflammatory (SII), predict survival in various cancers. This study aimed to determine whether peripheral immune parameters can predict survival in patients with uHCC undergoing IMRT and establish a clinically useful prognostic nomogram for survival prediction. METHODS: The clinical data of 309 HCC patients were retrospectively analyzed and randomly divided into training (n = 216) and validation (n = 93) cohorts. PLR, NLR and SII were collected before and after IMRT. Univariate and multivariate Cox analyses were performed to identify independent prognostic factors affecting survival, which were used to generate a nomogram. RESULTS: The median survival was 16.3 months, and significant increases in PLR, NLR, and SII were observed after IMRT (P < 0.001). High levels of immune parameters were associated with poor prognosis (P < 0.001); enlarged spleen, Barcelona clinic liver cancer stage (B and C), post-SII, and delta-NLR were independent risk factors for survival and were included in the nomogram, which accurately predicted 3- and 5-year survival. The nomogram was well verified in the validation cohort. CONCLUSIONS: High levels of immune parameters are associated with poor prognosis in uHCC patients receiving IMRT. Our nomogram accurately predicts the survival of patients with uHCC receiving IMRT.

Lederbergia citri sp. nov., and Lederbergia citrisecundus sp. nov., isolated from citrus rhizosphere.

Two Gram-positive, rod-shaped, motile, endospore-forming strains, FJAT-49780T and FJAT-49732T were isolated from a citrus rhizosphere soil sample. The optimal growth temperatures for strains FJAT-49780T and FJAT-49732T were 45 and 35-40 °C, respectively. The optimal growth pH for strains FJAT-49732T and FJAT-49780T were pH 8.0 and pH 6.0, respectively. The 16S rRNA gene sequence similarity between FJAT-49780T and FJAT-49732T was 98.6%. Strains FJAT-49780T and FJAT-49732T shared 97.9-98.4% 16S rRNA gene sequence similarities to the type strain of Lederbergia wuyishanensis. In phylogenetic trees (based on 16S rRNA gene sequence), strains FJAT-49732T and FJAT-49780T clade with Lederbergia members. Both strains contained meso-diaminopimelic acid in their cell-wall peptidoglycan and MK-7 was the only isoprenoid quinone detected. The major fatty acids of strains FJAT-49732T and FJAT-49780T were anteiso-C15:0 and iso-C15:0. The polar lipids of strain FJAT-49780T were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, an unidentified aminophospholipid, unidentified phospholipid and unidentified lipids while strain FJAT-49732T contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, an unidentified glycolipid, unidentified aminolipid and unidentified phospholipid. The genomic DNA G+C content of strains FJAT-49780T and FJAT-49732T were 37.0 and 36.7%, respectively. The digital DNA-DNA hybridization and average nucleotide identity values between strains FJAT-49780T and FJAT-49732T and with other members of the genus Lederbergia were below the cut-off level for species delineation. Thus, based on the above results, strains FJAT-49780T and FJAT-49732T represent two novel species of the genus Lederbergia, for which the names Lederbergia citri sp. nov., and Lederbergia citrisecundus sp. nov., are proposed. The type strains are FJAT-49780T (= CCTCC AB 2019242T = LMG 31583T) and FJAT-49732T (= CCTCC AB 2019246T = LMG 31584T).

Neuraminidase 1 is a driver of experimental cardiac hypertrophy.

AIMS: Despite considerable therapeutic advances, there is still a dearth of evidence on the molecular determinants of cardiac hypertrophy that culminate in heart failure. Neuraminidases are a family of enzymes that catalyze the cleavage of terminal sialic acids from glycoproteins or glycolipids. This study sought to characterize the role of neuraminidases in pathological cardiac hypertrophy and identify pharmacological inhibitors targeting mammalian neuraminidases. METHODS AND RESULTS: Neuraminidase 1 (NEU1) was highly expressed in hypertrophic hearts of mice and rats, and this elevation was confirmed in patients with hypertrophic cardiomyopathy (n = 7) compared with healthy controls (n = 7). The increased NEU1 was mainly localized in cardiomyocytes by co-localization with cardiac troponin T. Cardiomyocyte-specific NEU1 deficiency alleviated hypertrophic phenotypes in response to transverse aortic constriction or isoproterenol hydrochloride infusion, while NEU1 overexpression exacerbated the development of cardiac hypertrophy. Mechanistically, co-immunoprecipitation coupled with mass spectrometry, chromatin immunoprecipitation, and luciferase assays demonstrated that NEU1 translocated into the nucleus and interacted with GATA4, leading to Foetal gene (Nppa and Nppb) expression. Virtual screening and experimental validation identified a novel compound C-09 from millions of compounds that showed favourable binding affinity to human NEU1 (KD = 0.38 µM) and effectively prevented the development of cardiac remodelling in cellular and animal models. Interestingly, anti-influenza drugs zanamivir and oseltamivir effectively inhibited mammalian NEU1 and showed new indications of cardio-protection. CONCLUSIONS: This work identifies NEU1 as a critical driver of cardiac hypertrophy and inhibition of NEU1 opens up an entirely new field of treatment for cardiovascular diseases.

[o-C5 H4 NHOH]2 [I7 O18 (OH)]⋠3 H2 O: An Organic-Inorganic Hybrid SHG Material Featuring an [I7 O18 (OH)] ∞ 2 - Branched Polyiodate Chain.

An organic-inorganic hybrid polyiodate, namely, [o-C5 H4 NHOH]2 [I7 O18 (OH)]⋅3 H2 O (I), featuring a novel branched polyiodate chain has been obtained by evaporation method. [o-C5 H4 NHOH]2 [I7 O18 (OH)]⋅3 H2 O (I) crystalizes in the polar space group Ia and features an [I7 O18 (OH)] ∞ 2 - branched polyiodate chain in which [I3 O9 ]3- trimers are grafted on the same side of the one-dimensional (1D) chain based on [I4 O11 (OH)]3- tetramers. The asymmetric organic amine groups are beneficial to the polymerization of iodate groups and inducing the formation of the non-centrosymmetric (NCS) structure. Compound I exhibits a rather large Second-Harmonic- Generation (SHG) signal of 8.5×KH2 PO4 (KDP) upon 1064 nm laser radiation, a moderate band gap of 3.90 eV and a high laser-induced-damage-threshold (LIDT) of 182.34 MW cm-2 , hence it is a promising new SHG material. The relationship between the structures of the organic amine groups and the overall structures has been also analyzed.

Degeneration of the intestinal microbial community in PI3Kγ-knockout mice.

BACKGROUND AND AIM: PI3Kγ is closely related to inflammation and cardiovascular diseases and thus, PI3Kγ inhibitors are candidate drugs for the treatment of these disorders. Considering the potential effect of the intestinal microbiome on inflammation and cardiovascular diseases, this study aimed to identify characteristics of the intestinal microbial community under PI3Kγ deficiency, to help reveal the potential influence of PI3Kγ inhibitors mediated by the microbial community. METHODS: Exon 2 of the PI3Kγ gene was knocked out in a Balb/c mouse by using single-guide RNAs. Homozygous PI3Kγ-knockout (PI3Kγ-/-) mice were obtained by embryo transfer and hybridization. PI3Kγ-/- and wild-type (WT) mice were raised in the same specific pathogen-free conditions until 8 weeks of age. Then, colonic tissues and feces from the middle segment of the colon were collected and analyzed by Illumina MiSeq sequencing. Differences in intestinal microbial community between the PI3Kγ-/- and WT mice were detected by bioinformatics analysis. RESULTS: The richness and alpha diversity of the colonic microbial community were decreased in PI3Kγ-/- mice. The alpha diversity of the microbial community in feces did not differ between PI3Kγ-/- and WT mice. The beta diversity of the microbial community in feces of PI3Kγ-/- mice was obviously different from that in WT mice, whereas the within-group variation in Bray-Curtis distances of the mucosal microbial community was significantly decreased in PI3Kγ-/- mice. The topological structure of the species-related network of the colonic microbial community in PI3Kγ-/- mice was more polarized. Finally, we predicted that PI3Kγ deficiency might affect the synthesis of some antibiotics, bile acid, and thiamine through effects on the microbial community. CONCLUSIONS: PI3Kγ dysfunction led to degeneration of the intestinal microbial community and might alter the synthesis of some antibiotics, bile acids, and thiamine. The usage of PI3Kγ inhibitors for inflammation and cardiovascular diseases might lead to knock-on effect on our organism through intestinal microbiota.

Deciphering the toxic effects of antibiotics on denitrification: Process performance, microbial community and antibiotic resistance genes.

The extensive application of antibiotics, and the occurrence and spread of antibiotic resistance genes (ARGs) shade health risks to human and animal. The long-term effects of sulfamethoxazole (SMX) and tetracycline (TC) on denitrification process were evaluated in this study, with the focus on nitrogen removal performance, microbial community and ARGs. Results showed that low-concentration SMX and TC (<0.2 mg L-1) initially caused a deterioration in nitrogen removal performance, while higher concentrations (0.4-20 mg L-1) of both antibiotics had no further inhibitory influences. The abundances of ARGs in both systems generally increased during the whole period, and most of them had significant correlations with intI1, especially efflux-pump genes. Castellaniella, which was the dominant genus under antibiotic pressure, might be potential resistant bacteria. These findings provide an insight into the toxic effects of different antibiotics on denitrification process, and guides future efforts to control antibiotics pollution in ecosystems.

Functional Metabolomics Characterizes a Key Role for N-Acetylneuraminic Acid in Coronary Artery Diseases.

BACKGROUND: As new biomarkers of coronary artery diseases (CAD) emerge via metabolomics, the underlying functional mechanisms remain to be elucidated. Functional metabolomics aims to translate metabolomics-derived biomarkers to disease mechanisms. METHODS: A cohort of 2324 patients who underwent coronary angiography from 4 independent centers was studied. A combination of ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry in the negative ion mode was used for untargeted analysis of metabolites in plasma. Significant differential metabolites were identified by cross-comparisons with and within CAD types, including normal coronary artery, nonobstructvie coronary atherosclerosis, stable angina, unstable angina, and acute myocardial infarction. A tandem liquid chromatography-mass spectrometry-based approach using isotope-labeled standard addition was subsequently performed for targeted analysis of the metabolic marker N-acetylneuraminic acid (Neu5Ac). A functional metabolomics strategy was proposed to investigate the role of Neu5Ac in the progression of CAD by using in vitro and in vivo models. RESULTS: We identified a total of 36 differential metabolites, 35 of which were confirmed with reference compounds. Elevation of Neu5Ac was observed in plasma during CAD progression in center 1 (P=4.0e-64, n=2019) and replicated in 3 independent centers (n=305). The increased level of Neu5Ac in plasma was confirmed by accurate targeted quantification. Mechanistically, Neu5Ac was able to trigger myocardial injury in vitro and in vivo by activation of the Rho/Rho-associated coiled-coil containing protein kinase signaling pathway through binding to RhoA and Cdc42, but not Rac1. Silencing neuraminidase-1, the enzyme that regulates Neu5Ac generation, ameliorated oxygen-glucose deprivation-induced injury in cardiomyocytes and ligation/isoprenaline-induced myocardial ischemia injury in rats. Pharmacological inhibition of neuraminidase by anti-influenza drugs, oseltamivir and zanamivir, also protected cardiomyocytes and the heart from myocardial injury. CONCLUSIONS: Functional metabolomics identified a key role for Neu5Ac in acute myocardial infarction, and targeting neuraminidase-1 may represent an unrecognized therapeutic intervention for CAD.

Genome-based reclassification of Bacillus okuhidensis as a later heterotypic synonym of Bacillus halodurans.

The present study was carried out to clarify the taxonomic relationship between two closely related Bacillus species, Bacillus okuhidensis Li et al. 2002 and Bacillus halodurans (ex Boyer 1973) Nielsen et al. 1995. The maximum-likelihood tree based on the 16S rRNA gene sequence and the phylogenomic tree based on concatenation of 16 protein-marker genes showed that these species were similar. Average nucleotide identity (ANIm 99.25 %, ANIb 98.2 %) and digital DNA-DNA hybridization values (93.5 %) between B. okuhidensis DSM 13666T and B. halodurans DSM 497T were greater than the threshold values for bacterial species delineation, indicating that they belong to the same species. Therefore, B. okuhidensis Li et al. 2002 should be reclassified as a later heterotypic synonym of B. halodurans (ex Boyer 1973) Nielsen et al. 1995.

Genome-based reclassification of Bacillus plakortidis Borchert et al. 2007 and Bacillus lehensis Ghosh et al. 2007 as a later heterotypic synonym of Bacillus oshimensis Yumoto et al. 2005; Bacillus rhizosphaerae Madhaiyan et al. 2011 as a later heterotypic synonym of Bacillus clausii Nielsen et al. 1995.

In the present study, phylogenetic and genome-based comparison was carried out to clarify the taxonomic positions of alkaliphilic Bacillus species, Bacillus plakortidis, Bacillus lehensis, Bacillus oshimensis, Bacillus rhizosphaerae and Bacillus clausii. Phylogenetic trees based on 16S rRNA gene sequences and concatenated protein marker genes were constructed. Average nucleotide identity (ANI) values were calculated to compare genetic relatedness. In phylogenetic trees, B. plakortidis DSM 19153T, B. lehensis DSM 19099T, and B. oshimensis DSM 18940T; B. rhizosphaerae DSM 21911T and B. clausii DSM 8716T clade together. The average nucleotide identity (ANI) values between B. oshimensis DSM 18940T, B. plakortidis DSM 19153T and B. lehensis DSM 19099T ranged from 98.7-98.8%, while the ANI values between B. rhizosphaerae DSM 21911T and B. clausii DSM 8716T were 95.2-95.5%. The ANI values were higher than the recognized threshold value for bacterial species delineation. Based on phylogenetic and genome comparison we propose reclassification of B. plakortidis and B. lehensis as a later heterotypic synonym of B. oshimensis; B. rhizosphaerae as a later heterotypic synonym of B. clausii.

Enantioselective Cross-Exchange between C-I and C-C σ†Bonds.

A palladium-catalyzed enantioselective intramolecular σ-bond cross-exchange between C-I and C-C bonds is realized, providing chiral indanones bearing an alkyl iodide group and an all-carbon quaternary stereocenter. Pd/TADDOL-derived phosphoramidite is found to be an efficient catalytic system for both C-C bond cleavage and alkyl iodide reductive elimination. In addition to aryl iodides, aryl bromides can also be used for this transformation in the presence of KI. Density-functional theory (DFT) calculation studies support the ring-opening of cyclobutanones occuring through an oxidative addition/reductive elimination process involving PdIV species.

Exploring the Antitumor Mechanism of High-Dose Cytarabine through the Metabolic Perturbations of Ribonucleotide and Deoxyribonucleotide in Human Promyelocytic Leukemia HL-60 Cells.

Despite the apparent clinical benefits of high-dose cytarabine (Ara-C) over lower dose Ara-C in acute myeloid leukemia (AML) therapy, the mechanism behind high-dose Ara-C therapy remains uncertain. In this study, a LC-MS-based method was carried out to investigate the metabolic alteration of ribonucleotide and deoxyribonucleotide in human promyelocytic leukemia cells (HL-60) after treatment with Ara-C to reveal its antitumor mechanism. The metabolic results revealed that four nucleotides (ATP, ADP, CDP, and dCTP) could be used as potential biomarkers indicating the benefit of high-dose Ara-C over lower dose Ara-C treatment. Combining metabolic perturbation and cell cycle analysis, we conjectured that, apart from the acknowledged mechanism of Ara-C on tumor inhibition, high-dose Ara-C could present a specific action pathway. It was suggested that the pronounced rise in AMP/ATP ratio induced by high-dose Ara-C can trigger AMP-activated protein kinase (AMPK) and subsequently Forkhead Box, class O (FoxO), to promote cell cycle arrest. Moreover, the significant decrease in CDP pool induced by high-dose Ara-C might further accelerate the reduction of dCTP, which then aggravates DNA synthesis disturbance. As a result, all of these alterations led to heightened tumor inhibition. This study provides new insight in the investigation of potential mechanisms in the clinical benefits of high-dose Ara-C in therapy for AML.

Bacillus gobiensis sp. nov., isolated from a soil sample.

A Gram-stain-positive, rod-shaped, endospore-forming, aerobic bacterium designated FJAT-4402T, was isolated from the weed rhizosphere soil of the Gobi desert in the Xinjiang Autonomous Region in the north-west of China. Isolate FJAT-4402T grew at 15-40 °C (optimum 30 °C), pH 5-10 (optimum pH 7) and in 0-3 % (w/v) NaCl (optimum 0 %). Phylogenetic analyses, based on 16S rRNA gene sequences, showed that isolate FJAT-4402T was a member of the genus Bacillus and was most closely related to Bacillus licheniformis DSM 13T (96.2 %). The isolate showed 33.3 % DNA-DNA relatedness to the closest reference isolate, B. licheniformis DSM 13T. The diagnostic diamino acid of the peptidoglycan of isolate FJAT-4402T was meso-diaminopimelic acid and the predominant isoprenoid quinone was MK-7. The major cellular fatty acids were anteiso-C15 : 0 (28.5 %), iso-C15 : 0 (20.1 %), anteiso-C17 : 0 (14.3 %), iso-C16 : 0 (9.6 %), C16 : 0 (8.4 %), iso-C17 : 0 (6.2 %) and iso-C14 : 0 (4.7 %) and the DNA G+C content was 42.0 mol%. The phenotypic, chemotaxonomic and genotypic properties indicated that strain FJAT-4402T represents a novel species within the genus Bacillus, for which the name Bacillus gobiensis sp. nov. is proposed. The type strain is FJAT-4402T ( = DSM 29500T = CGMCC 1.12902T).

Bacillus loiseleuriae sp. nov., isolated from rhizosphere soil from a loiseleuria plant.

A Gram-stain-positive, rod-shaped, endospore-forming, aerobic bacterium, designated strain FJAT-27997T, was isolated from the rhizosphere soil of a Loiseleuria plant collected from Sichuan province in China. Growth was observed aerobically between 20 and 35 °C (optimum 30 °C), between 0 and 3.0 % (w/v) NaCl (optimum at 0 %) concentration and pH in the range 6.0-9.0 (optimum at pH 7.0). The cell-wall peptidoglycan contained meso-diaminopimelic acid and the major isoprenoid quinone was menaquinone MK-7. The main fatty acids were iso-C15 : 0, anteiso-C15 : 0, iso-C14 : 0, C16 : 0 and C14 : 0. The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Phylogenetic analyses based on 16S rRNA gene sequences showed that isolate FJAT-27997T was a member of the genus Bacillus and was related most closely to Bacillus simplex DSM 1321T (97.95 % similarity), followed by Bacillushuizhouensis GSS03T (97.9 %). The average nucleotide identity value between strain FJAT-27997T and the most closely related species, B. simplex DSM 1321T, was 71.60 % (JSpecies), less than the previously proposed cut-off value of 96 % for differentiating species within the genus. The in silico DNA-DNA hybridization values between strain FJAT-27997T and its most closely related species were <70 %, again indicating they belong to different taxa. The main fatty acids were iso-C15 : 0 and anteiso-C15 : 0. The novel strain could be differentiated from other known Bacillus species on the basis of several phenotypic characters and fatty acid profiles. This taxononomic/genomic study revealed that strain FJAT-27997T represents a novel Bacillus species, for which the name Bacillus loiseleuriae sp. nov. (type strain FJAT-27997T =CCTCC AB 2015285T=DSM 101776T) is proposed.