Bis[hexa­amminecobalt(III)] penta­chloride nitrate

The title compound, [Co(NH3)6]2Cl5(NO3), was obtained under hydro­thermal conditions. The asymmetric unit contains three Co3+ ions, one lying on an inversion center and the other two located at 2/m positions. All Co3+ ions are six-coordinated by NH3 mol­ecules, forming [Co(NH3)6]3+ octahedra, with Co—N distances in the range 1.945 (4)–1.967 (3) Å. The nitrate N atom and one of the O atoms lie at a mirror plane. Among the Cl− anions, one lies in a general position, one on a twofold axis and two on a mirror plane. N—H⋯O and N—H⋯Cl hydrogen bonds link the cations and anions into a three-dimensional network

Application of CFD, Taguchi Method, and ANOVA Technique to Optimize Combustion and Emissions in a Light Duty Diesel Engine

Some previous research results have shown that EGR (exhaust gas recirculation) rate, pilot fuel quantity, and main injection timing closely associated with engine emissions and fuel consumption. In order to understand the combined effect of EGR rate, pilot fuel quantity, and main injection timing on the NOx (oxides of nitrogen), soot, and ISFC (indicated specific fuel consumption), in this study, CFD (computational fluid dynamics) simulation together with the Taguchi method and the ANOVA (analysis of variance) technique was applied as an effective research tool. At first, simulation model on combustion and emissions of a light duty diesel engine at original baseline condition was developed and the model was validated by test. At last, a confirmation experiment with the best combination of factors and levels was implemented. The study results indicated that EGR is the most influencing factor on NOx. In case of soot emission and ISFC, the greatest influence parameter is main injection timing. For all objectives, pilot fuel quantity is an insignificant factor. Furthermore, the engine with optimized combination reduces by at least 70% for NOx, 20% in soot formation, and 1% for ISFC, in contrast to original baseline engine

A TonB-dependent receptor regulates antifungal HSAF biosynthesis in \u3ci\u3eLysobacter\u3c/i\u3e

Lysobacter species are Gram-negative bacteria that are emerging as new sources of antibiotics, including HSAF (Heat Stable Antifungal Factor), which was identified from L. enzymogenes with a new mode of action. LesR, a LuxR solo, was recently shown to regulate the HSAF biosynthesis via an unidentified mechanism in L. enzymogenes OH11. Here, we used a comparative proteomic approach to identify the LesR targets and found that LesR influenced the expression of 33 proteins belonging to 10 functional groups, with 9 proteins belonging to the TBDR (TonB-Dependent Receptor) family. The fundamental role of bacterial TBDR in nutrient uptake motivates us to explore their potential regulation on HSAF biosynthesis which is also modulated by nutrient condition. Six out of 9 TBDR coding genes were individually in-frame deleted. Phenotypic and gene-expression assays showed that TBDR7, whose level was lower in a strain overexpressing lesR, was involved in regulating HSAF yield. TBDR7 was not involved in the growth, but played a vital role in transcribing the key HSAF biosynthetic gene. Taken together, the current lesR-based proteomic study provides the first report that TBDR7 plays a key role in regulating antibiotic (HSAF) biosynthesis, a function which has never been found for TBDRs in bacteria. Includes Supplementary materials

Identification and Characterization of the Anti-Methicillin-Resistant \u3ci\u3eStaphylococcus aureus\u3c/i\u3e WAP-8294A2 Biosynthetic Gene Cluster from \u3ci\u3eLysobacter enzymogenes\u3c/i\u3e OH11

Lysobactor enzymogenes strain OH11 is an emerging biological control agent of fungal and bacterial diseases. We recently completed its genome sequence and found it contains a large number of gene clusters putatively responsible for the biosynthesis of nonribosomal peptides and polyketides, including the previously identified antifungal dihydromaltophilin (HSAF). One of the gene clusters contains two huge open reading frames, together encoding 12 modules of nonribosomal peptide synthetases (NRPS). Gene disruption of one of the NRPS led to the disappearance of a metabolite produced in the wild type and the elimination of its antibacterial activity. The metabolite and antibacterial activity were also affected by the disruption of some of the flanking genes. We subsequently isolated this metabolite and subjected it to spectroscopic analysis. The mass spectrometry and nuclear magnetic resonance data showed that its chemical structure is identical to WAP-8294A2, a cyclic lipodepsipeptide with potent antimethicillin-resistant Staphylococcus aureus (MRSA) activity and currently in phase I/II clinical trials. The WAP- 8294A2 biosynthetic genes had not been described previously. So far, the Gram-positive Streptomyces have been the primary source of anti-infectives. Lysobacter are Gram-negative soil/water bacteria that are genetically amendable and have not been well exploited. The WAP-8294A2 synthetase represents one of the largest NRPS complexes, consisting of 45 functional domains. The identification of these genes sets the foundation for the study of the WAP-8294A2 biosynthetic mechanism and opens the door for producing new anti-MRSA antibiotics through biosynthetic engineering in this new source of Lysobacter

Biosynthesis of HSAF, a Tetramic Acid-containing Macrolactam from \u3ci\u3eLysobacter enzymogenes\u3c/i\u3e

HSAF was isolated from Lysobacter enzymogenes, a bacterium used in the biological control of fungal diseases of plants. Structurally, it is a tetramic acid-containing macrolactam fused to a tricyclic system. HSAF exhibits a novel mode of action by disrupting sphingolipids important to the polarized growth of filamentous fungi. Here, we described the HSAF biosynthetic gene cluster which contains only a single-module polyketide synthase-nonribosomal peptide synthetase (PKS/ NRPS), although the biosynthesis of HSAF apparently requires two separate polyketide chains that are linked together by one amino acid (ornithine) via two amide bonds. Flanking the PKS/ NRPS are six genes, encoding a cascade of four tightly clustered redox enzymes on one side and a sterol desaturase/fatty acid hydroxylase and a ferredoxin reductase on the other side. The genetic data demonstrate that the four redox genes, in addition to the PKS/NRPS gene and the sterol desaturase/fatty acid hydroxylase gene, are required for HSAF production. The biochemical data show that the adenylation domain of the NRPS specifically activated L-ornithine and the fourdomain NRPS was able to catalyze the formation of a tetramic acid-containing product from acyl- S-ACP and ornithinyl-S-NRPS. These results reveal a previously unrecognized biosynthetic mechanism for hybrid PK/NRP in prokaryotic organisms

Biosynthesis of HSAF, a Tetramic Acid-containing Macrolactam from \u3ci\u3eLysobacter enzymogenes\u3c/i\u3e

HSAF was isolated from Lysobacter enzymogenes, a bacterium used in the biological control of fungal diseases of plants. Structurally, it is a tetramic acid-containing macrolactam fused to a tricyclic system. HSAF exhibits a novel mode of action by disrupting sphingolipids important to the polarized growth of filamentous fungi. Here, we described the HSAF biosynthetic gene cluster which contains only a single-module polyketide synthase-nonribosomal peptide synthetase (PKS/ NRPS), although the biosynthesis of HSAF apparently requires two separate polyketide chains that are linked together by one amino acid (ornithine) via two amide bonds. Flanking the PKS/ NRPS are six genes, encoding a cascade of four tightly clustered redox enzymes on one side and a sterol desaturase/fatty acid hydroxylase and a ferredoxin reductase on the other side. The genetic data demonstrate that the four redox genes, in addition to the PKS/NRPS gene and the sterol desaturase/fatty acid hydroxylase gene, are required for HSAF production. The biochemical data show that the adenylation domain of the NRPS specifically activated L-ornithine and the fourdomain NRPS was able to catalyze the formation of a tetramic acid-containing product from acyl- S-ACP and ornithinyl-S-NRPS. These results reveal a previously unrecognized biosynthetic mechanism for hybrid PK/NRP in prokaryotic organisms

Associations between Source-Specific Fine Particulate Matter and Mortality and Hospital Admissions in Beijing, China

The health effects of PM2.5 exposure have become a major public concern in developing countries. Identifying major PM2.5 sources and quantifying the health effects at the population level are essential for controlling PM2.5 pollution and formulating targeted emissions reduction policies. In the current study, we have obtained PM2.5 mass data and used positive matrix factorization to identify the major sources of PM2.5. We evaluated the relationship between short-term exposure to PM2.5 sources and mortality or hospital admissions in Beijing, China, using 441 742 deaths and 9 420 305 hospital admissions from 2013 to 2018. We found positive associations for coal combustion and road dust sources with mortality. Increased hospital admission risks were significantly associated with sources of vehicle exhaust, coal combustion, secondary sulfates, and secondary nitrates. Compared to the cool season, excess mortality risk estimates of coal combustion source were significantly higher in the warm season. Our findings show that reducing more toxic sources of PM2.5, especially coal emissions, and developing clean energy alternatives can have critical implications for improving air quality and protecting public health

Efficacy and safety of a combination of miglitol, metformin and insulin aspart in the treatment of type 2 diabetes

Purpose: To study the clinical effect of combining insulin aspart with different drugs in the treatment oftype 2 diabetes mellitus (T2DM).Methods: Two hundred and thirty-seven T2DM patients admitted to the Endocrinology Department of the Second Affiliated Hospital of Kunming Medical University from March to September 2018 were selected as subjects in this study. Miglitol and metformin were used in combination with insulin aspart in the treatment of T2DM. In addition, data on the effectiveness and safety of different treatment options,such as patient’s weight, waist circumference, blood glucose indicators, indices of heart, liver and kidney functions, and incidence of complications were recorded and compared between the two groups.Results: The use of a combination of miglitol and insulin aspart produced an excellent hypoglycaemic effect, and it significantly reduced the incidence of sensory neuropathy in the eyes and distal limbs (p < 0.05). The use of combination of metformin and insulin aspart effectively protected the heart and kidney, and prevented hypoglycaemia (p < 0.05).Conclusion: These results suggest that treatment with a combination of miglitol and insulin aspart is suitable for patients with T2DM whose blood sugar levels are out of control, while combined treatment with metformin and insulin aspart is more suited for patients who desire to reduce blood sugar and blood lipids through weight loss, and patients with cardiac and renal insufficiency