Synergistic antifungal effect and potential mechanism of Dimethomorph combined with Pyrimethanil against Phytophthora capsici.

Synergistic effect of dimethomorph (DIM) and pyrimethanil (PYM) was evaluated using the Wadley method and the molecular mechanism of the antifungal effects of the combined treatment was systematically investigated. DIM+PYM had a synergistic effect on Phytophthora capsici, with the synergistic effect being observed at 5:1, at which the synergy coefficient was 1.8536. The mycelia of the pathogen treated with DIM+PYM were branched, uneven in thickness, and swollen. Moreover, scanning electron microscopy (SEM) revealed that DIM+PYM caused mycelium breaks, swelling, and apex enlargement, while transmission electron microscopy (TEM) revealed structural damage, cavities, and cell membrane morphological abnormalities. DIM+PYM inhibited the growth of mycelia, destroyed the cell membrane, interfered with energy metabolism, reduced protein and sugar content. Additionally, the transcriptome and metabolome of fungi treated with DIM+PYM changed significantly; specifically, there were 1571 differentially expressed genes and 802 differential metabolites. DIM+PYM may mainly damage the cell membrane, energy, protein, soluble sugar pathways.

Integrated histopathology and transcriptome metabolome profiling reveal the toxicity mechanism of phenazine-1-carboxylic acid in zebrafish.

Phenazine-1-carboxylic acid (PCA) is a new type of agrochemical used to prevent plant diseases, but its effects on aquatic organisms are unclear. To comprehensively assess the impacts of PCA for aquatic organisms and its associated environmental risks, this study investigated, taking zebrafish as the research object, the toxicological mechanism of PCA by means of optical microscopy, hematoxylin and eosin (HE) staining, ultrastructural observation, physiological and biochemical testing, transcriptome sequencing, metabolome analysis, fluorescence quantitative PCR and molecular simulation. The results indicated that PCA was detrimental to zebrafish embryos, larvae and adults, with LC50 values at 96 h of 3.9093 mg/L, 8.5075 mg/L, and 13.6388 mg/L, respectively. PCA caused abnormal spontaneous movement, slowed the heart rate, delayed hatching, shortened the body length, slowed growth, and caused malformations. PCA mainly affected the brain, liver, heart, and ovaries. PCA distorted cell morphology, damaged mitochondrial membranes, disintegrated mitochondrial ridges, and dissociated nuclear membranes. PCA inhibited the enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX), decreased the malondialdehyde (MDA) content and disrupted antioxidant effects. The results of omics studies confirmed that PCA interfered with the transcriptional and metabolic network of zebrafish, downregulating most genes and metabolites. PCA mainly affected functions related to mitochondrial steroids, lipids, sterols, oxidoreductase activity and pathways involving cofactors, steroids, porphyrin, cytochromes, which specifically bound to targets such as panx3, agmat, and ace2. PCA was moderately toxic to zebrafish, and its usage should be strictly controlled to reduce toxic effects on aquatic organisms. The results of this study provide a new insights for ecotoxicology research.

Risk management and provider liabilities in infantile cerebral palsy based on malpractice litigation cases.

AIM: Infantile cerebral palsy (CP) severely affects the survival and quality of life of infants. CP is typically caused by multiple factors, leading to causal uncertainty of the role of medical errors in CP and resulting in frequent medical disputes. No relevant research exists on risk management and malpractice liabilities in CP, including in China. METHOD: A retrospective analysis of 400 CP malpractice litigation cases from 18th June 1999 to 23rd November 2017, collected from China Judgments Online, included basic case information, CP risk factors, medical errors, medical malpractice liability determination, and compensation. RESULTS: Up to 63.5% of infants with CP were affected by asphyxia, followed by hypoxic-ischemic encephalopathy (63.3%), neonatal infection (52.3%) and intracranial hemorrhage (36.0%). Most (89.1%) of civil judgments resulted in liability for medical errors, with the highest proportion of ultimate liability. The three most frequent medical errors were failure of completing delivery in time (30.2%), incomplete assessment of birth process detection (28.8%), and nonstandard medical records (25.3%). Each case involved 2.5 medical errors on average. No difference in the distribution of medical errors between premature and full-term CP infants (P > 0.05) was found. Compensation for damage was awarded in 91.4% of claims, and the mean value of compensation was $73,506. The mean value of the total actual loss of the family was $128,198. INTERPRETATION: Contradictions between the doctors and patients were prominent in malpractice CP litigation cases, with a total loss of $3.97 billion attributable to new CP cases in China in 2017. Asphyxia was the most frequent risk factor for CP since it may easily draw the attention of the sufferer's family. Medical service providers did not pay attention to risk management in preterm infants. The importance of fetal monitoring and standardized medical record writing should be emphasized.