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Background Pydiflumetofen, as a new succinate dehydrogenase inhibitor (SDHI) chiral fungicide, has been used in crop production because of its broad-spectrum and high-efficiency antifungal activity. However, little literature is known about pydiflumetofen at the chiral level. Therefore, the stereoselective bioactivity and degradation of pydiflumetofen enantiomers were investigated. Results Pydiflumetofen presented effective bioactivity against the eight tested phytopathogens, and its enantiomers showed significant difference in activity. The bioactivity of R-pydiflumetofen was 9.0 ~ 958.8 times higher than that of S-enantiomer. Treatment with R-pydiflumetofen increased the cell membrane permeability of Sclerotinia sclerotiorum and decreased more exopolysaccharide and oxalic acid production more than treatment with S-pydiflumetofen. Furthermore, R-pydflumetofen exhibited better inhibitory activity against the succinate dehydrogenase (SDH) enzyme of S. sclerotiorum than S-pydiflumetofen by 584-folds. According to homology modeling and molecular docking studies, the binding affinities of the R-enantiomer and S-enantiomer were - 7.0 kcal mol-1 and -5.3 kcal mol-1 , respectively. Additionally, the degradation half-lives of S- and R-pydiflumetofen in three vegetables (cucumber, eggplant, and cowpea) under field conditions were 2.56 ~ 3.12 d and 2.48 ~ 2.76 d, respectively, which revealed that R-pydiflumetofen degraded faster than S-pydiflumetofen. Conclusion Based on the results obtained, R-pydiflumetofen not only exhibited a higher bactericidal activity, but also posed fewer residual risks in the environment. The mechanism of the stereoselective bioactivity was correlated with the stereoselective inhibition activity of the target enzyme and then effected the cell membrane permeability and the production of exopolysaccharide and oxalic acid. This research could provide a foundation for the systematic evaluation of pydiflumetofen from an enantiomeric view. This article is protected by copyright. All rights reserved.

As a forceful nematicide, fosthiazate has been largely applied in the management of root-knot nematodes and other herbivorous nematodes. However, the toxicity of fosthiazate to nontarget nematodes is unclear. To explore the toxicity and the mechanisms of fosthiazate in nontarget nematodes, Caenorhabditis elegans was exposed to 0.01-10 mg/L fosthiazate. The results implied that treatment with fosthiazate at doses above 0.01 mg/L could cause injury to the growth, locomotion behavior, and reproduction of the nematodes. Moreover, L1 larvae were more vulnerable to fosthiazate exposure than L4 larvae. Reactive oxygen species (ROS) production and lipofuscin accumulation were fairly increased in 1 mg/L fosthiazate-exposed nematodes. Treatment with 0.1 mg/L fosthiazate significantly inhibited the activity of acetylcholinesterase (p0.01). Furthermore, subacute exposure to 10 mg/L fosthiazate strongly influenced the expression of genes related to oxidative stress, reproduction, and nerve function (e.g., gst-1, sod-1, puf-8, wee-1.3, and ace-1 genes). These findings suggested that oxidative stress, reproduction and nerve disorders could serve as key endpoints of toxicity induced by fosthiazate. The cyp-35a family gene was the main metabolic fosthiazate in C. elegans, and the cyp-35a5 subtype was the most sensitive, with a change in expression level of 2.11-fold compared with the control. These results indicate that oxidative stress and neurological and reproductive disorders played fundamental roles in the toxicity of fosthiazate in C. elegans and may affect the abundance and function of soil nematodes.

Cyproconazole (CPZ), representing the chiral triazole fungicides, is widely used in the pharmaceutical and agricultural fields. To clarify its potential adverse effects on the generalized CYP-mediated processes within mammalian, a comparative experimental and computational approach was employed to investigate the CYP-mediated metabolism processes of CPZ stereoisomers in rat liver microsomes (RLMs). The depletion rate of CPZ stereoisomers in vitro incubation system with RLMs followed the order RR-> SS-> SR-> RS-CPZ. The results of kinetic assays were in line with the depletion rate results. Further inhibition assay confirmed the stereo selective metabolism of CPZ stereoisomers by different CYP isoforms. Molecular dynamics (MD) simulation revealed the stereoselective metabolism mechanism. Several hydrogen bonds and pi-stacking restrict the position of CPZ isomers in the active cavity of CYPs so that the 4'-nitrogen on the triazole ring can bind closely to the heme of CYP, which results in the metabolism of CPZ isomers. By combining the computational and experimental approaches, the structure-activity relationship of CPZ and CYP was elucidated, and this method can be further applied to predict the degree of uncertainty in the process of xenobiotic biotransformation of triazole fungicides and serve as a basis for risk assessment.

Pydiflumetofen is a novel and efficient broad-spectrum chiral fungicide consisting of a pair of enantiomers. A simple and sensitive chiral analytical method was established to determine the enantiomers of this chiral fungicide in food and environmental samples by ultra-high-performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-MS/MS) using QuEChERS method coupled with octadecylsilane-dispersive solid-phase extraction (C18-dSPE) as extraction procedure. The specific optical rotation and the absolute configuration of the enantiomers were identified by polarimetry and electronic circular dichroism (ECD). The elution order of the pydiflumetofen enantiomers on Lux Cellulose-2 was S-(−)-pydiflumetofen and R-(+)-pydiflumetofen. The average recoveries of eleven matrices ranged from 71.3% to 107.4%. The intraday relative standard deviations (RSDs) were less than 11.8%, and the interday RSDs were less than 12.6% for the two enantiomers. Stereoselective dissipation in pakchoi and soil were observed: S-(−)-pydiflumetofen was degraded faster than R-(+)-pydiflumetofen in pakchoi, causing the enantiomer fraction (EF) of the enantiomers to change from 0.50 to 0.42 in 7 days. However, R-(+)-pydiflumetofen was degraded faster than S-(−)-pydiflumetofen in soil, causing the EF of the enantiomers to change from 0.49 to 0.52 in 21 days. This study provides a method for monitoring pydiflumetofen enantiomer residues, which is crucial for improving risk assessments and the development of chiral pesticides.

To conduct genetic diagnosis for a family affected with hamophilia A.Potential mutations of the F8 gene were analyzed with PCR and Sanger sequencing. Carriers of the mutation were identified through linkage analysis using short tandem repeat (STR) markers. Suspected mutations were verified among 100 healthy controls to rule out genetic polymorphism. Prenatal diagnosis was provided based on the above results.Sequencing analysis has identified two mutations, c.1 AT and c.4 CT, which have replaced the start codon (ATG) with leucine (TTG) and glutamine (GAA) with the stop codon (TAA), respectively. The same mutations were not found among the 100 healthy controls. The patient's mother and sister were heterozygous for the same mutations. Upon prenatal diagnosis, the fetus was determined as a male and did not harbor the above mutations. Linkage analysis also confirmed that the fetus has inherited the non-risk X chromosome from his maternal grandfather.Detection of pathogenic mutations can enable prenatal diagnosis for the disease.

To use combined G-banding and array-comparative genomic hybridization (aCGH) for the prenatal diagnosis of a fetus with 5q35 deletion syndrome.Chromosomal karotypes of the fetus and parents were analyzed with G-banding analysis. aCGH was performed to detect minor chromosomal structural abnormalities.The karyotype of the fetus was ascertained as 46, XY, t(5;10)(q35;p13), and the karyotypes of the parents were normal. aCGH has identified a de novo 1.68 Mb deletion at 5q35.2q35.3 and a 1.44 Mb duplication at 10p14p13.aCGH has a higher resolution and greater accuracy for mapping chromosomal aberrations and is a useful supplement for G banding karyptyping analysis.

Background Alcohol contributes to approximately 30% of all serious crashes. While the majority of drivers acknowledge the risks associated with drink-driving, a significant proportion of the population continue to engage in this behaviour. Attitudes towards drink-driving as well as personal alcohol consumption patterns are likely to underpin a driver’s decision to drink-drive. These associations were explored in the current study. Methods A large (N = 2994) cross-sectional online survey of a representative sample of drivers in Australia was conducted. Participants provided information about their own alcohol consumption patterns, drink-driving behaviour as well as attitudes towards drink-driving (own and others) and enforcement strategies. Results Alcohol consumption patterns differed according to age, gender and work status. Drivers who reported drink-driving behaviour and had high risk alcohol consumption patterns were less likely to agree that drink-driving leads to increased crash risk and more likely to agree they drink and drive when they believed they could get away with it. In contrast, drivers who did not report drink-driving and had low risk consumption patterns were more likely to report that the enforcement strategies are too lenient. Binary logistic regression showed that high risk alcohol consumption patterns and agreement from drivers that they drink and drive when they believe they can get away with it had the strongest associations with drink-driving. These findings highlight the relationships between one’s drinking patterns, drink-drive behaviour and attitudes towards drink-driving and drink-driving enforcement Conclusions and implications The patterns of associations that emerged suggest that drink-driving is the expression of a broader health issue for the most “at-risk” cohort of drinkers. The decision to drink and drive may result from a need borne from an alcohol dependent lifestyle exacerbated by a social acceptability of the behaviour and positive attitudes towards one’s ability to drink-drive with few adverse consequences. Therefore, the broader alcohol consumption patterns of drink-drivers needs to be considered when targeting drink-drive reductions.

The traditional methods to solve the PV mismatch problem are using diodes and photovoltaic cells in series and in parallel to compensate voltage and current. Considering the cost of production, it is unrealistic that each photovoltaic cell parallels with one bypass diode. One bypass diode may parallels with dozen or more solar cells. Therefore, the connection of the photovoltaic cells in parallel with bypass diodes is very important. This paper proposes the traditional connection may reduce the whole PV modules output power when the shadow covers partial modules. A new photovoltaic cells connection, named "door-connection", is proposed to solve this problem. The paper analyses the characteristics of the door-connection output power in three typical shadow cases. It is proved that the new connection can improve the output power obviously compared with the traditional connection.

This paper presents an improved Particle Swarm Optimization algorithm (IPSO) for solving the flexible load dispatch problem (FLD) which relates to renewable energy power generation and three types of load composed of electric vehicle (EV), ice-storage central air conditioning and smart household appliance. The objective of the FLD problem is to utilize aggregators of the three types of load to deal with the unpredictability and intermittence of the renewable energy power generation. Facing premature convergence of PSO, the proposed method divides the search process into two stages. In the first stage, every particle selects one particle randomly to learn. The second stage is the conventional PSO algorithm. The total length the optimal particle flights for, the average velocity and the distance of every iteration are used to evaluate performance of PSO and IPSO. The results of a 12-unit system show that the IPSO is more stable and effective than PSO.