New Insight into the Function of Dopamine (DA) during Cd Stress in Duckweed (Lemna turionifera 5511).

Dopamine (DA), a kind of neurotransmitter in animals, has been proven to cause a positive influence on plants during abiotic stress. In the present study, the function of DA on plants under cadmium (Cd) stress was revealed. The yellowing of duckweed leaves under Cd stress could be alleviated by an exogenous DA (10/20/50/100/200 µM) supplement, and 50 µM was the optimal concentration to resist Cd stress by reducing root breakage, restoring photosynthesis and chlorophyll content. In addition, 24 h DA treatment increased Cd content by 1.3 times in duckweed under Cd stress through promoting the influx of Cd2+. Furthermore, the gene expression changes study showed that photosynthesis-related genes were up-regulated by DA addition under Cd stress. Additionally, the mechanisms of DA-induced Cd detoxification and accumulation were also investigated; some critical genes, such as vacuolar iron transporter 1 (VIT1), multidrug resistance-associated protein (MRP) and Rubisco, were significantly up-regulated with DA addition under Cd stress. An increase in intracellular Ca2+ content and a decrease in Ca2+ efflux induced by DA under Cd stress were observed, as well as synchrony with changes in the expression of cyclic nucleotide-gated ion channel 2 (CNGC2), predicting that, in plants, CNGC2 may be an upstream target for DA action and trigger the change of intracellular Ca2+ signal. Our results demonstrate that DA supplementation can improve Cd resistance by enhancing duckweed photosynthesis, changing intracellular Ca2+ signaling, and enhancing Cd detoxification and accumulation. Interestingly, we found that exposure to Cd reduced endogenous DA content, which is the result of a blocked shikimate acid pathway and decreased expression of the tyrosine aminotransferase (TAT) gene. The function of DA in Cd stress offers a new insight into the application and study of DA to Cd phytoremediation in aquatic systems.

Acetylcholine (ACh) enhances Cd tolerance through transporting ACh in vesicles and modifying Cd absorption in duckweed (Lemna turionifera 5511).

Acetylcholine (ACh), an important neurotransmitter, plays a role in resistance to abiotic stress. However, the role of ACh during cadmium (Cd) resistance in duckweed (Lemna turionifera 5511) remains uncharacterized. In this study, the changes of endogenous ACh in duckweed under Cd stress has been investigated. Also, how exogenous ACh affects duckweed's ability to withstand Cd stress was studied. The ACh sensor transgenic duckweed (ACh 3.0) showed the ACh signal response under Cd stress. And ACh was wrapped and released in vesicles. Cd stress promoted ACh content in duckweed. The gene expression analysis showed an improved fatty acid metabolism and choline transport. Moreover, exogenous ACh addition enhanced Cd tolerance and decreased Cd accumulation in duckweed. ACh supplement reduced the root abscission rate, alleviated leaf etiolation, and improved chlorophyll fluorescence parameters under Cd stress. A modified calcium (Ca2+) flux and improved Cd2+ absorption were present in conjunction with it. Thus, we speculate that ACh could improve Cd resistance by promoting the uptake and accumulation of Cd, as well as the response of the Ca2+ signaling pathway. Also, plant-derived extracellular vesicles (PDEVs) were extracted during Cd stress. Therefore, these results provide new insights into the response of ACh during Cd stress.

Network Pharmacology and Integrated Molecular Docking Study on the Mechanism of the Therapeutic Effect of Fangfeng Decoction in Osteoarthritis.

BACKGROUND: At present, there are no effective pharmacologic therapies for attenuating the course of osteoarthritis (OA) in humans and current therapies are geared to mitigating symptoms. Fangfeng decoction (FFD) is a traditional Chinese medicine prescribed for the treatment of OA. In the past, FFD has achieved positive clinical outcomes in alleviating the symptoms of OA in China. However, its mechanism of action has not yet been clarified. OBJECTIVE: The objective of this study is to investigate and explore the mechanism of FFD and how the compound interacts with the target of OA; network pharmacology and molecular docking methods were applied in this study. METHODS: The active components of FFD were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) database according to the inclusion criteria as oral bioactivity (OB) ≥ 30% and drug likeness (DL) ≥ 0.18. Then, gene name conversion was performed through the UniProt website. The related target genes of OA were obtained from the Genecards database. Core components, targets, and signaling pathways were obtained through compound-target-pathway (C-T-P) and protein-protein interaction (PPI) networks were built using Cytoscape 3.8.2 software. Matescape database was utilized to get gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of gene targets. The interactions of key targets and components were analyzed by molecular docking in Sybyl 2.1 software. RESULTS: A total of 166 potential effective components, 148 FFD-related targets, and 3786 OA-related targets were obtained. Finally, 89 common potential target genes were confirmed. Pathway enrichment results showed that HIF-1 and CAMP signaling pathways were considered key pathways. The screening of core components and targets was achieved through the CTP network. The core targets and active components were obtained according to the CTP network. The molecular docking results showed that quercetin, medicarpin, and wogonin of FFD could bind to NOS2, PTGS2, and AR, respectively. CONCLUSION: FFD is effective in the treatment of OA. It may be caused by the effective binding of the relevant active components of FFD to the targets of OA.

Eicosapentaenoic and docosahexaenoic acids attenuate hyperglycemia through the microbiome-gut-organs axis in db/db mice.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been suggested to prevent the development of metabolic disorders. However, their individual role in treating hyperglycemia and the mechanism of action regarding gut microbiome and metabolome in the context of diabetes remain unclear. RESULTS: Supplementation of DHA and EPA attenuated hyperglycemia and insulin resistance without changing body weight in db/db mice while the ameliorative effect appeared to be more pronounced for EPA. DHA/EPA supplementation reduced the abundance of the lipopolysaccharide-containing Enterobacteriaceae whereas elevated the family Coriobacteriaceae negatively correlated with glutamate level, genera Barnesiella and Clostridium XlVa associated with bile acids production, beneficial Bifidobacterium and Lactobacillus, and SCFA-producing species. The gut microbiome alterations co-occurred with the shifts in the metabolome, including glutamate, bile acids, propionic/butyric acid, and lipopolysaccharide, which subsequently relieved ß cell apoptosis, suppressed hepatic gluconeogenesis, and promoted GLP-1 secretion, white adipose beiging, and insulin signaling. All these changes appeared to be more evident for EPA. Furthermore, transplantation with DHA/EPA-mediated gut microbiota mimicked the ameliorative effect of DHA/EPA on glucose homeostasis in db/db mice, together with similar changes in gut metabolites. In vitro, DHA/EPA treatment directly inhibited the growth of Escherichia coli (Family Enterobacteriaceae) while promoted Coriobacterium glomerans (Family Coriobacteriaceae), demonstrating a causal effect of DHA/EPA on featured gut microbiota. CONCLUSIONS: DHA and EPA dramatically attenuated hyperglycemia and insulin resistance in db/db mice, which was mediated by alterations in gut microbiome and metabolites linking gut to adipose, liver and pancreas. These findings shed light into the gut-organs axis as a promising target for restoring glucose homeostasis and also suggest a better therapeutic effect of EPA for treating diabetes. Video abstract.

Polyunsaturated fatty acids intake, omega-6/omega-3 ratio and mortality: Findings from two independent nationwide cohorts.

BACKGROUND & AIMS: Polyunsaturated fatty acids (PUFA) have been reported to exert pleiotropic protective effects against various chronic diseases. However, epidemiologic evidence linking specific PUFA intake to mortality has been limited and contradictory. We aim to assess the associations between specific dietary PUFA and mortality among adults in China and America, respectively. METHODS: Participants from China Health and Nutrition Survey (CHNS, n = 14,117) and National Health and Nutrition Examination Survey [NHANES (n = 36,032)] were prospectively followed up through the year 2011. Cox regression models were used to investigate hypothesized associations. RESULTS: A total of 1007 and 4826 deaths accrued over a median of 14 and 9.1 years of follow-up in CHNS and NHANES, respectively. Dietary marine omega-3 PUFA was robustly associated with a reduced all-cause mortality [Hazard ratio (HR) comparing extreme categories: 0.74, 95% CI: 0.61-0.89; P < 0.001 for trend] in CHNS. Nevertheless, this inverse relationship was not observed in NHANES. The overall mortality was positively associated with the intake of α-linolenic acid (ALA) (HR comparing extreme quartiles: 1.23, 95% CI: 1.01-1.50; P = 0.054 for trend) in CHNS, whereas weak inverse associations of ALA (P = 0.035 for trend) and LA (P = 0.027 for trend) with all-cause mortality were found in NHANES. Increased dietary intake of arachidonic acid was consistently linked with reduced all-cause mortality both in NHANES and CHNS. Importantly, consuming PUFA at an omega-6/omega-3 ratio of 6-10 was associated with a lower risk of death in CHNS. CONCLUSIONS: Intakes of different specific PUFA show distinct associations with mortality and these relationships also vary between Chinese and US populations. These findings suggest maintaining an omega-6/omega-3 balance diet for overall health promotion outcomes (NCT03155659).

Detection of resistance to fungicides, mating types and fitness of Phytophthora infestans in Hebei, China.

In vitro, isolates resistant to metalaxyl (M) and oxadixyl (O) of Phytophthora infestans were 11.2% of 62 isolates from potato and tomato in Hebei Province, mean resistance factor was 15,022 fold and 24,733 fold, respectively, no isolates resistant either to cymoxanil (C) or to dimethomorph (D) were detected. On the other hand, in vivo, isolates resistant to M and O were 29.0% and 32.7%, respectively, among 217 isolates from potato plants in Weichang and Chongli, Hebei, only one isolate resistant to M and O was found among 88 isolates from tomato plants in Xushui, Hebei. Among 73 isolates from potato in Weichang and Chongli, 6 isolates with A2 mating type were 8.2%, 3 A2 isolates resistant to metalaxyl and oxadixyl. 3 A2 isolates were 6.8% of 44 isolates from tomato in Xushui. Cross resistance in Phytophthora infestans was confirmed between M and O, but no cross resistance between C or D and M or O. The field isolates resistant to M and O were outstandingly fitter than sensitive or intermediate ones, mainly due to stronger sporulation capacity of the field isolates.

Synergism in mixtures of cymoxanil and mancozeb on Phytophthora infestans in vivo.

The preventive activity of 1:8 mixture of cymoxanil and mancozeb against Phytophthora infestans was higher than that of either the two single ingredients or the other nine mixtures. The synergistic interaction existed (synergy ratio 2.01) between the two at the mixing ratio of 1:8, whereas additive interaction (synergy ratios ranged from 0.73 to 1.34) existed at the mixing ratios ranging from 1:1 to 1:7, from 1:9 to 1:10, 1:8 was the optimal ratio. The preventive activity of 1:8 mixture was higher than the curative and the eradicative. In addition, the eradicative synergism of inhibiting sporangia production on lesions was stronger than the eradicative synergism of inhibiting lesion extension and suppressing infection of sporangia, and than the curative synergism of inhibiting lesion sporulation on detached potato leaflets.