The angiotensin receptor and neprilysin inhibitor, LCZ696, in heart failure: A meta-analysis of randomized controlled trials.

BACKGROUND: LCZ696 is a novel neuroendocrine inhibitor that has been widely used in heart failure (HF). However, its advantage over other neuroendocrine inhibitors, such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) has not been fully elucidated. This study aimed to provide the latest evidence regarding the efficacy and safety of LCZ696 as compared to other ACEis and ARBs with regards to the treatment of HF. METHODS: We systematically searched databases, including PubMed, Embase, and the Cochrane Library, for relevant randomized controlled trials (RCTs). The outcome measures included all-cause mortality, rate of hospitalizations for HF, rate of death from cardiovascular causes, change in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and decline of renal function. RESULTS: Five RCTs involving 19,078 patients were identified. The meta-analysis indicated that LCZ696 was associated with a significant reduction in all-cause mortality (hazard ratio [HR] = 0.84; 95% confidence interval [CI], 0.76-0.93; P = .0005), rate of hospitalizations for HF (HR = 0.80; 95% CI, 0.73-0.87; P < .00001), reduction in NT-proBNP levels (rate ratio = 0.78; 95% CI, 0.70-0.88; P < .0001), and decline in renal function (odds ratio = 0.77; 95% CI, 0.68-0.88; P < .0001) compared with ACEis and ARBs. However, there was no statistical difference in the rate of death from cardiovascular causes (HR = 0.86; 95% CI, 0.72-1.03; P = .09) between LCZ696 and ACEis and ARBs. CONCLUSION: LCZ696 is superior to ACEis and ARBs in the treatment of HF. Hence, it should be more widely used clinically.

Screening of pesticide residues in Traditional Chinese Medicines using modified QuEChERS sample preparation procedure and LC-MS/MS analysis.

A robust and high-throughput method was developed for the determination of 108 pesticide residues in Traditional Chinese Medicines (TCMs) simultaneously using a combination of UHPLC-MS/MS analysis and the modified QuEChERS method. Extraction was carried out in acetonitrile containing 0.75% (v/v) acetic acid with ultrasonication for 15 min; MgSO4 and C18 were used as the dispersive-solid phase extraction sorbents. The method exhibited good linearity (r2 > 0.9901), in addition to good selectivity, precision and repeatability. More than 92% of pesticides exhibited high rates or recovery in the 70-120% range. This method showed high sensitivity, with Limits of Quantitation in the 0.01-20 ng/mL range in Cortex Moutan, and 0.01-50 ng/mL in the other TCMs. The method was employed for the analysis of 39 real samples from different habitats, and pesticides were detected in 92.3% of the samples, with 26 pesticides being detected in these three TCMs. More than four pesticides were detected in a third of the samples. Among them, tebuconazole was detected in all the three TCMs with 0.22-22.02 µg/kg concentration, which was lower than the provisions in GB 2763-2019 (50 µg/kg). In addition, the paclobutrazol detection rate in Ophiopogon japonicus was 100%, and the detected concentrations of 9 samples exceeded the Maximum Residue Levels defined for vegetables (50 µg/kg). Considering there are no regulations that govern the limits of pesticide residues in the three TCMs in China, we recommend the acceleration of efforts to introduce appropriate regulations.

Population genomics demystifies the defoliation phenotype in the plant pathogen Verticillium dahliae.

Verticillium dahliae is a broad host-range pathogen that causes vascular wilts in plants. Interactions between three hosts and specific V. dahliae genotypes result in severe defoliation. The underlying mechanisms of defoliation are unresolved. Genome resequencing, gene deletion and complementation, gene expression analysis, sequence divergence, defoliating phenotype identification, virulence analysis, and quantification of V. dahliae secondary metabolites were performed. Population genomics previously revealed that G-LSR2 was horizontally transferred from the fungus Fusarium oxysporum f. sp. vasinfectum to V. dahliae and is exclusively found in the genomes of defoliating (D) strains. Deletion of seven genes within G-LSR2, designated as VdDf genes, produced the nondefoliation phenotype on cotton, olive, and okra but complementation of two genes restored the defoliation phenotype. Genes VdDf5 and VdDf6 associated with defoliation shared homology with polyketide synthases involved in secondary metabolism, whereas VdDf7 shared homology with proteins involved in the biosynthesis of N-lauroylethanolamine (N-acylethanolamine (NAE) 12:0), a compound that induces defoliation. NAE overbiosynthesis by D strains also appears to disrupt NAE metabolism in cotton by inducing overexpression of fatty acid amide hydrolase. The VdDfs modulate the synthesis and overproduction of secondary metabolites, such as NAE 12:0, that cause defoliation either by altering abscisic acid sensitivity, hormone disruption, or sensitivity to the pathogen.