Identification and drug metabolic characterization of four new CYP2C9 variants CYP2C9*72-*75 in the Chinese Han population

Cytochrome 2C9 (CYP2C9), one of the most important drug metabolic enzymes in the human hepatic P450 superfamily, is required for the metabolism of 15% of clinical drugs. Similar to other CYP2C family members, CYP2C9 gene has a high genetic polymorphism which can cause significant racial and inter-individual differences in drug metabolic activity. To better understand the genetic distribution pattern of CYP2C9 in the Chinese Han population, 931 individuals were recruited and used for the genotyping in this study. As a result, seven synonymous and 14 non-synonymous variations were identified, of which 4 missense variants were designated as new alleles CYP2C9*72, *73, *74 and *75, resulting in the amino acid substitutions of A149V, R150C, Q214H and N418T, respectively. When expressed in insect cell microsomes, all four variants exhibited comparable protein expression levels to that of the wild-type CYP2C9 enzyme. However, drug metabolic activity analysis revealed that these variants exhibited significantly decreased catalytic activities toward three CYP2C9 specific probe drugs, as compared with that of the wild-type enzyme. These data indicate that the amino acid substitution in newly designated variants can cause reduced function of the enzyme and its clinical significance still needs further investigation in the future

The gut microbiome in atherosclerotic cardiovascular disease

The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Effect of Preheating Temperature on the Microstructure and Tensile Properties of 6061 Aluminum Alloy Processed by Hot Rolling-Quenching

The present work investigates the microstructure and tensile properties of a hot rolled 6061 alloy quenched by cold rolls (RQ) at different preheating temperatures. The preheating temperature strongly affects microstructure evolution and mechanical properties. Low preheating temperature (490 °C) resulted in both low strength and low elongation. The RQ alloy preheated at 540 °C exhibited improved ductility compared to those subjected to T6 and T8 temper, and comparable strength to that after T8 temper. The dynamic recovery during hot rolling contributed to the improved tensile elongation and retained work hardening. High preheating temperature also led to pronounced ageing hardening during short-term ageing

Soil Organic Nitrogen Indirectly Enhances Pepper-Residue-Mediated Soil Disease Suppression through Manipulation of Soil Microbiome

Banana Fusarium wilt-suppressive soils are effective against pathogen invasion, yet soil physicochemical factors responsible for conducive or suppressive behavior have not been reported. Here, we investigated the changes in banana biomass, disease incidence (DI), soil culturable microbes and physicochemical properties by incorporating pepper and banana residues into conducive and suppressive soils. Before the incorporation of any residues, the suppressive soil significantly increased banana biomass and decreased DI compared to the conducive soil. The biomass of the suppressive soil was significantly higher than that of the conducive soil after the incorporation of either pepper or banana residues. Compared with the control (CK), the incorporation of pepper residues to both soils significantly reduced DI, while banana residues had the opposite effect. Additionally, both conducive and suppressive soils supplemented with pepper residues significantly reduced the amounts of culturable Fusarium oxysporum and increased the amounts of beneficial Pseudomonas and Bacillus. The pepper residue extracts significantly inhibited the growth of F. oxysporum mycelium. Soil alkali-hydrolyzable nitrogen (AN) responded most strongly to residue application to suppressive soil. The AN factor was significantly and positively correlated with banana biomass; however, there was no direct and significant negative correlation with DI. Further analysis of the results showed that elevated AN content could stimulate the amounts of culturable Bacillus in the soil, and Bacillus antagonized the proliferation of pathogen and thus indirectly and effectively reduced banana DI. In conclusion, soil AN content can indirectly improve the disease suppression ability of pepper-residue-mediated suppressive soil by manipulating the soil microbiome

Chemical constituents and biological activities against Tribolium castaneum (Herbst) of the essential oil from Citrus wilsonii leaves

The essential oil obtained from Citrus wilsonii Tanaka leaves with hydrodistillation was investigated by GC and GC-MS. The main components of the essential oil were identified to be citronellol (16.94%), nerol acetate (10.35%), γ-terpinen (9.85%), citronellal (9.36%) and β-pinene (6.72%). Among them, the four active constituents, predicted with a bioactivity-test, were isolated and identified as citronellol, γ-terpinene, nerol (neryl) acetate and β-pinene. It was found that the essential oil of C. wilsonii leaves and isolated compounds possessed fumigant and contact toxicity against Tribolium castaneum adults. The essential oil and γ-terpinen showed strong fumigant toxicity against T. castaneum (LC50 = 8.18 and 4.09 mg L-1). Repellency of the crude oil and active compounds was also determined. Citronellol, neryl acetate and β-pinene were strongly repellent (100%, 86% and 92%, respectively, at 78.63 nL cm-2, after 2 h treatment) against T. castaneum. The essential oil and citronellol exhibited the same level of repellency compared with the positive control, DEET. The results indicate that the essential oil of C. wilsonii leaves and its active compounds had the potential to be developed as natural fumigants, insecticides and repellents for control of T. castaneum