Integrated Serum Pharmacochemistry, Network Pharmacology, and Molecular Docking to Study the Mechanism of Rhubarb against Atherosclerosis.

BACKGROUND: Atherosclerosis (AS) is a chronic inflammatory disease characterized by the accumulation of lipids, the formation of lesion plaques, and the narrowing of arterial lumens. Rhubarb has significant effects against AS, but there is a lack of analysis and exploration of the mechanism of action of the transitional components in serum containing rhubarb. OBJECTIVE: This work aims to combine serum pharmacochemistry, network pharmacology, and molecular docking to explore active ingredients and mechanism of rhubarb against AS. METHOD: Firstly, the components of rhubarb in blood samples were identified using HPLC-QTOF/MS. The ingredients-targets-disease interaction network of rhubarb was constructed through network pharmacology. Then, molecular docking between the ingredients and the core targets was carried out using the Autodock Vina software. RESULTS: Eleven active ingredients and five metabolites were preliminarily identified. The network pharmacology results showed that chrysophanol, resveratrol, and emodin might have potential pharmacological effects on AS. The PPI network showed that the key proteins were PTGS2, ESR1, PTGS1, and ELANE. GO analysis revealed that genes were mainly enriched in the inflammatory response and response to exogenous stimuli. Moreover, these genes were related to IL-17 signaling pathways, lipid and atherosclerosis, and other pathways. Molecular docking analyses showed that chrysophanol and emodin have strong binding affinities with the target proteins PTGS2 and PTGS1. CONCLUSION: A comprehensive strategy combining serum pharmacochemistry with network pharmacology and molecular docking was employed to investigate the active ingredients and the mechanism of rhubarb in treating AS, which provided a basis for studying the pharmacological effects and action mechanisms of rhubarb.

Transcriptomic and Metatranscriptomic Analyses Provide New Insights into the Response of the Pea Aphid Acyrthosiphon pisum (Hemiptera: Aphididae) to Acetamiprid.

Acetamiprid is a broad-spectrum neonicotinoid insecticide used in agriculture to control aphids. While recent studies have documented resistance to acetamiprid in several aphid species, the underlying mechanisms are still not fully understood. In this study, we analyzed the transcriptome and metatranscriptome of a laboratory strain of the pea aphid, Acyrthosiphon pisum (Harris, 1776), with reduced susceptibility to acetamiprid after nine generations of exposure to identify candidate genes and the microbiome involved in the adaptation process. Sequencing of the transcriptome of both selected (RS) and non-selected (SS) strains allowed the identification of 14,858 genes and 4938 new transcripts. Most of the differentially expressed genes were associated with catalytic activities and metabolic pathways involving carbon and fatty acids. Specifically, alcohol-forming fatty acyl-CoA reductase (FAR) and acyl-CoA synthetase (ACSF2), both involved in the synthesis of epidermal wax layer components, were significantly upregulated in RS, suggesting that adaptation to acetamiprid involves the synthesis of a thicker protective layer. Metatranscriptomic analyses revealed subtle shifts in the microbiome of RS. These results contribute to a deeper understanding of acetamiprid adaptation by the pea aphid and provide new insights for aphid control strategies.

Joint extremes in precipitation and infectious disease in the USA: A bivariate POT study.

Mounting heavy precipitation events (HPEs) caused by the climate change have drawn wide attention. Increased incidences of infectious diseases are known as the common following health impact, while little has been studied about the extremal relationship in between. Therefore, this study aims to investigate the joint extremes of precipitation and infectious disease mortality rate in the USA, using publicly accessible data from the National Centers for Environmental Information and the Centers for Disease Control and Prevention. The study reveals the positive association between heavy precipitations and infectious diseases with slight national and regional differences using multivariate Peaks-Over-Threshold modelling. The strength of extremal dependence is measured by the extreme parameter α from a logistic dependence model in multivariate extreme value theory. The Midwestern USA shows an excessive impact of HPEs on infectious disease mortality (α=0.7524), while the other regions show similar extremal dependence strength with the national one (α values all approximate 0.77). The study also discovered spatial disparities in the extremal dependences for five sub-categories of infectious diseases in each census region, among which mycoses show the strongest extremal dependence with precipitation in almost all regions. These spatial differences of extremal dependence may be attributed to geographic, social-economic factors and the self-inherited characteristics of certain diseases. The findings are expected to assist in developing strategies counteracting extreme risks resulting from weather events and health issues as well. The cutting-edge multivariate Peaks-Over-Threshold (POT) approach employed herein also shows promise for a wide range of extreme risk assessment topics.

miR-92a-1-p5 Modulated Expression of the flightin Gene Regulates Flight Muscle Formation and Wing Extension in the Pea Aphid, Acyrthosiphon pisum (Hemiptera: Aphidoidea).

Aphids exhibit wing polyphenism. Winged and wingless aphid morphs are produced by parthenogenesis depending on population density and host plant quality. Recent studies showed that microRNAs in alate and apterous individuals have differential expression and are involved in wing dimorphism of Acyrthosiphon pisum. From which miR-92a-1-p5 can target the mRNA of flight muscle gene flightin in vitro, but what effect they have on wing development of aphid is unclear. Here with the nanocarrier-delivered RNA interference (RNAi) method, flightin gene was knocked down in winged nymphs of A. pisum. Results showed that the majority (63.33%) of adults had malformed wings, the shape of dorsal longitudinal muscle (DLM) was deformed severely, the dorsoventral flight muscle (DVM) became wider and looser in aphids with flightin reduction compared with the negative control. Overexpression of miR-92a-1-p5 caused decreased expression of flightin and malformed wings of aphids, with a mutant ratio of 62.50%. Morphological analysis of flight musculature showed the consistent result as that with flightin knockdown. These results suggest that flightin is essential for flight musculature formation and wing extension in A. pisum, which can be modulated by miR-92a-1-p5.