Objectives This study sought to evaluate the safety and efficacy of rosuvastatin in preventing contrast-induced acute kidney injury (CI-AKI) in patients with diabetes mellitus (DM) and chronic kidney ...disease (CKD). Background CI-AKI is an important complication after contrast medium injection. While small studies have shown positive results with statin therapy, the role of statin therapy in prevention of CI-AKI remains unknown. Methods We randomized 2,998 patients with type 2 DM and concomitant CKD who were undergoing coronary/peripheral arterial angiography with or without percutaneous intervention to receive rosuvastatin, 10 mg/day (n = 1,498), for 5 days (2 days before, and 3 days after procedure) or standard-of-care (n = 1,500). Patients' renal function was assessed at baseline, 48 h, and 72 h after exposure to contrast medium. The primary endpoint of the study was the development of CI-AKI, which was defined as an increase in serum creatinine concentration ≥0.5 mg/dl (44.2 μmol/l) or 0.25% above baseline at 72 h after exposure to contrast medium. Results Patients randomized to the rosuvastatin group had a significantly lower incidence of CI-AKI than controls (2.3% vs. 3.9%, respectively; p = 0.01). During 30 days' follow-up, the rate of worsening heart failure was significantly lower in the patients treated with rosuvastatin than that in the control group (2.6% vs. 4.3%, respectively; p = 0.02). Conclusions Rosuvastatin significantly reduced the risk of CI-AKI in patients with DM and CKD undergoing arterial contrast medium injection. (Rosuvastatin Prevent Contrast Induced Acute Kidney Injury in Patients With Diabetes TRACK-D; NCT00786136 )
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The insecticide imidacloprid (IMI), which is used worldwide, pollutes environments and has significant ecotoxicological effects. Microbial metabolism and photolysis are the major pathways of IMI ...degradation in natural environments. Several studies have reported that the metabolites of IMI nitroreduction are more toxic to some insects and mammals than IMI itself. Thus, environmental degradation of IMI may enhance the ecotoxicity of IMI and have adverse effects on non-target organisms. Here, we report that an actinomycete—Gordonia alkanivorans CGMCC 21704—transforms IMI to a nitroreduction metabolite, nitroso IMI. Resting cells of G. alkanivorans at OD600 nm = 10 transformed 95.7% of 200 mg L−1 IMI to nitroso IMI in 4 d. Nitroso IMI was stable at pH 4–9. However, it rapidly degraded under sunlight via multiple oxidation, dehalogenation, and oxidative cleavage reactions to form 10 derivatives; the half-life of nitroso IMI in photolysis was 0.41 h, compared with 6.19 h for IMI. Acute toxicity studies showed that the half maximal effective concentration (EC50) values of IMI, nitroso IMI, and its photolytic metabolites toward the planktonic crustacean Daphnia magna for immobilization (exposed to the test compounds for 48 h) were 17.70, 9.38, 8.44 mg L−1, respectively. The half-life of nitroso IMI in various soils was also examined. The present study reveals that microbial nitroreduction accelerates IMI degradation and the nitroso IMI is easily decomposed by sunlight and in soil. However, nitroso IMI and its photolytic products have higher toxicity toward D. magna than the parent compound IMI, and therefore increase the ecotoxicity of IMI.
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•A new isolate Gordonia alkanivorans effectively transformed IMI to nitroso derivate.•The genome of G. alkanivorans CGMCC 21704 has been determined.•The nitroso IMI is easily degraded by photolysis and in soils.•10 derivates were produced under photolysis by sunlight.•Nitroso IMI and its photolytic products were more toxic to D. magna than IMI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We sought to investigate the characteristics, survival and risk factors for mortality in Chinese patients with connective tissue disease (CTD)-associated pulmonary arterial hypertension (APAH) in ...modern therapy era. 129 consecutive adult patients who visited one of three referral centres in China with a diagnosis of CTD-APAH confirmed by right heart catheterisation during the previous 5 years were enrolled. The end-point was all-cause death or data censoring. Systemic lupus erythematosus was the most common underlying CTD (49%) and systemic sclerosis just accounted for 6% in this cohort. The overall survival at 1 and 3 years was 92% and 80%, respectively. Pericardial effusion, a shorter 6-min walk distance, lower mixed venous oxygen saturation, higher pulmonary vascular resistance (PVR) and alkaline phosphatase (ALP), and lower total cholesterol levels were all associated with a higher risk of death among the study population. Higher PVR and ALP were independent predictors of mortality. In conclusion, unlike in western patients, systemic lupus erythematosus is the most common underlying disease in Chinese patients with CTD-APAH. The survival of Chinese patients with CTD-APAH in the modern treatment era is similar to that in western countries. Elevated PVR and ALP are independent risk factors for poor outcomes.
Accumulating evidence has shown that type 2 diabetes (T2D) and coronary artery disease (CAD) may stem from a 'common soil'. The aim of our study was to examine the association between genetic ...predisposition to T2D and the risk of severe CAD among patients with acute coronary syndromes (ACS) undergoing angiography.
The current case-control study included 1414 ACS patients with at least one major epicardial vessel stenosis > 50% enrolled in the ACS Genetic Study. The severity of CAD was quantified by the number of coronary arteries involved. Genetic risk score (GRS) was calculated using 41 common variants that robustly associated with increased risk of T2D in East Asians. Logistic regression models were used to estimate the association between GRS and the severity of CAD.
In the age-, sex- and BMI-adjusted model, each additional risk allele was associated with a 6% increased risk of multi-vessel disease (OR = 1.06, 95% CI 1.02-1.09). The OR was 1.43 (95% CI 1.08-1.89) for the risk of severe CAD when comparing the extreme tertiles of T2D-GRS. The association was not reduced after further adjustment for conventional cardiovascular risk factors. Additional adjustment for T2D status in our regression model attenuated the association by approximately one quarter. In subgroup analysis, the strengths of the associations between GRS and the severity of CAD were broadly similar in terms of baseline demographic information and disease characteristics.
Our data indicated that genetic predisposition to T2D is associated with elevated risk of severe CAD. This association revealed a possible causal relationship and is partially mediated through diabetic status.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nitrile hydratases have received significant interest both in the large-scale industrial production of acrylamide and nicotinamide, and the remediation of environmental contamination with ...nitrile-containing pollutants. Almost all known nitrile hydratases include an α-subunit (AnhA) and β-subunit (AnhB), and a specific activator protein is crucial for their maturation and catalytic activity. Many studies exist on nitrile hydratase characteristics and applications, but few have reported their metal insertion and post-translational maturation mechanism. In this study, we investigated the cobalt insertion and maturation mechanism of nitrile hydratase from
Streptomyces canus
CGMCC 13662 (
Sc
NHase) bearing three subunits (AnhD, AnhE, and AnhA).
Sc
NHase subunits were purified, and the cobalt content and nitrile hydratase activity of the
Sc
NHase subunits were detected. We discovered that cobalt could insert into the cobalt-free AnhA of
Sc
NHase in the absence of activator protein under reduction agent DL-dithiothreitol (DTT) environment. AnhD not only performed the function of AnhB of NHase, but also acted as a metal ion chaperone and self-subunit swapping chaperone, while AnhE did not act as similar performance. A cobalt direct-insertion under reduction condition coordinated self-subunit swapping mechanism is responsible for
Sc
NHase post-translational maturation. Molecular docking of
Sc
NHase and substrates suggested that the substrate specificity of
Sc
NHase was correlated with its structure.
Sc
NHase had a weak hydrophobic interaction with IAN through protein–ligand interaction analysis and, therefore, had no affinity with indole-3-acetonitrile (IAN). The post-translational maturation mechanism and structure characteristics of
Sc
NHase could help guide research on the environmental remediation of nitrile-containing waste contamination and three-subunit nitrile hydratase.
Microvirga flocculans CGMCC 1.16731 can degrade many cyano group-containing neonicotinoid insecticides. Here, its genome was sequenced, and a novel nitrile hydratase gene cluster was discovered in a ...plasmid. The NHase gene cluster (pnhF) has gene structure β-subunit 1, α-subunit, and β-subunit 2, which is different from previously reported NHase gene structures. Phylogenetic analysis of α-subunits indicated that NHases containing the three subunit (β1αβ2) structure are independent from NHases containing two subunits (αβ). pnhF was successfully expressed in Escherichia coli, and the purified PnhF could convert the nitrile-containing insecticide flonicamid to N-(4-trifluoromethylnicotinoyl)glycinamide. The enzymatic properties of PnhF were investigated using flonicamid as a substrate. Homology models revealed that amino acid residue β1-Glu56 may strongly affect the catalytic activity of PnhF. This study expands our understanding of the structures and functions of NHases and the enzymatic mechanism of the environmental fate of flonicamid.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
Thiacloprid is a widely-used neonicotinoid insecticide, but its enzymatic conversion and the toxicity of the amide metabolite are poorly understood. Here, a N2-fixing bacterium, Microvirga flocculans ...CGMCC 1.16731, was reported to metabolize thiacloprid via hydration and hydroxylation to thiacloprid amide and 4-hydroxy thiacloprid respectively. M. flocculans transformed 90.5% of 0.63 mmol/L thiacloprid in 30 h with a half-life of 9.0 h. In soil, the bacterium transformed 92.4% of 80 μmol/kg soil thiacloprid in 9 d. A cobalt-type nitrile hydratase (NHase) composed of an α-subunit (TnhA) and a β-subunit (TnhB) converted thiacloprid to thiacloprid amide. Co-expression of activator (TnhC) with NHase could improve the TnhA solubility and therefore enhanced 4-folds higher NHase activity. The NHase produced recombinantly in Escherichia coli transformed 97% of 0.76 mmol/L thiacloprid in 10 min. M. flocculans NHase had a Km value of 0.63 mmol/L and Vmax of 10.2 μmol/min/mg toward thiacloprid. Thiacloprid amide has higher toxic effect on growth of M. flocculans than thiacloprid, whereas lower toxic on the aquatic invertebrate Daphnia magna. Both thiacloprid and thiacloprid amide inhibited tnhA transcription. This increases our understanding of the enzymatic mechanism of environmental fate of thiacloprid and toxicity of its amide metabolite toward soil microbes and aquatic organisms.
•A novel N2-fixing bacterium Microvirga flocculans efficiently transformed thiacloprid.•M. flocculans transformed thiacloprid via hydrolysis and hydroxylation pathways.•A thermally stable nitrile hydratase converted thiacloprid to amide metabolite.•Co-expression of TnhC with NHase enhanced 4-folds higher NHase activity.•Thiacloprid amide inhibited the growth of M. flocculans and tnhA transcription.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sulfoxaflor (SUL), a novel sulfoximine insecticide, causes environmental contamination and poses potential risks to animals. However, there are few reports of SUL degradation by pure microbes. In ...this study, a novel isolated bacterium, Pseudomonas stutzeri CGMCC 22915, rapidly degraded SUL to SUL-amide via hydration. P. stutzeri CGMCC 22915 degraded 58.2% of SUL (814.28 μmol/L) within 2 h with a half-life of 1.6 h. P. stutzeri CGMCC 22915 effectively facilitated SUL degradation in soil and surface water. The nitrile hydratase PsNHase with a different gene orientation of <β-subunit> <α-subunit> <accessory protein> was responsible for the formation of SUL-amide from SUL and transformed other nitrile-containing insecticides thiacloprid and acetamiprid to their amides. Nitrile hydratases with this gene orientation have never been reported to degrade nitrile-containing insecticides. E. coli expressing PsNHase degraded 90.4% of SUL (798.29 μmol/L) within 5 min with a half-life of just 0.59 min. PsNHase showed the highest activity in SUL degradation among reported NHases (Vmax 21.69 U/mg, Km 1.62 mmol/L). Modeling of PsNHase suggested that β-His62 was important for its highest enzymatic activity toward SUL. P. stutzeri CGMCC 22915 is promising for application in the bioremediation of SUL in contaminated soil and surface water.
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•P. stutzeri CGMCC 22915 rapidly degraded SUL via a hydration pathway.•P. stutzeri CGMCC 22915 effectively degraded SUL in surface water and soil.•The nitrile hydratase PsNHase transformed SUL to SUL-amide.•PsNHase showed the highest activity in SUL degradation among reported NHases.•PsNHase with a different gene orientation degraded nitrile-containing insecticides.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The aim of the present study was to examine the association between peripheral differential leukocyte counts and dyslipidemia in a Chinese hypertensive population. A total of 10,866 patients with ...hypertension were enrolled for a comprehensive assessment of cardiovascular risk factors using data from the China Stroke Primary Prevention Trial. Plasma lipid levels and total leukocyte, neutrophil, and lymphocyte counts were determined according to standard methods. Peripheral differential leukocyte counts were consistently and positively associated with serum total cholesterol (TC), LDL cholesterol (LDL-C), and TG levels (all P < 0.001 for trend), while inversely associated with HDL cholesterol levels (P < 0.05 for trend). In subsequent analyses where serum lipids were dichotomized (dyslipidemia/normolipidemia), we found that patients in the highest quartile of total leukocyte count (≥7.6 × 109 cells/l) had 1.64 times the risk of high TG 95% confidence interval (CI): 1.46, 1.85, 1.34 times the risk of high TC (95% CI: 1.20, 1.50), and 1.24 times the risk of high LDL-C (95% CI: 1.12, 1.39) compared with their counterparts in the lowest quartile of total leukocyte count. Similar patterns were also observed with neutrophils and lymphocytes. In summary, these findings indicate that elevated differential leukocyte counts are directly associated with serum lipid levels and increased odds of dyslipidemia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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