Identification of a pool of non-pumping Na/K-ATPase

Recent studies have ascribed many non-pumping functions to the Na/K-ATPase. Here, we present experimental evidence demonstrating that over half of the plasma membrane Na/KATPase in LLC-PK1 cells is performing cellular functions other than ion pumping. This “non-pumping” pool of Na/K-ATPase, like the pumping pump, binds ouabain. Depletion of either cholesterol or caveolin-1 moves some of the “non-pumping” Na/KATPase into the pumping pool. Graded knock-down of the 1 subunit of the Na/K-ATPase eventually results in loss of this “non-pumping” pool while preserving the pumping pool. Our prior studies indicate that a loss of the non-pumping pool is associated with a loss of receptor function as evidenced by the failure of ouabain administration to induce the activation of Src and/or ERK. Therefore, our new findings suggest that a substantial amount of surface-expressed Na/K-ATPase, at least in some types of cells, may function as non-canonical ouabain-binding receptors

Regulation of caveolin-1 membrane trafficking by the Na/K-ATPase

Here, we show that the Na/K-ATPase interacts with caveolin-1 (Cav1) and regulates Cav1 trafficking. Graded knockdown of Na/K-ATPase decreases the plasma membrane pool of Cav1, which results in a significant reduction in the number of caveolae on the cell surface. These effects are independent of the pumping function of Na/K-ATPase, and instead depend on interaction between Na/K-ATPase and Cav1 mediated by an N-terminal caveolin-binding motif within the ATPase α1 subunit. Moreover, knockdown of the Na/K-ATPase increases basal levels of active Src and stimulates endocytosis of Cav1 from the plasma membrane. Microtubule-dependent long-range directional trafficking in Na/K-ATPase–depleted cells results in perinuclear accumulation of Cav1-positive vesicles. Finally, Na/K-ATPase knockdown has no effect on processing or exit of Cav1 from the Golgi. Thus, the Na/K-ATPase regulates Cav1 endocytic trafficking and stabilizes the Cav1 plasma membrane pool

The global progress on the non-point source pollution research from 2012 to 2021: a bibliometric analysis

Background: With effective control of point source pollution, non-point source (NPS) pollution has been widely concerned as the primary reason for the improvement of global water environmental quality. Some bibliometric analysis related to NPS pollution has been carried out before the mid-2010s. Analyzing the research status and hot issues of NPS pollution in the past decade is important for guiding the control and management of NPS pollution in the future. Results: A bibliometric analysis was conducted based on 3407 publications retrieved from the Web of Science during 2012–2021. China, USA and UK were the most productive countries. Sci. Total Environ, Environ. Sci. Pollut. Res, and Water were the most productive journals. The NPS pollutant, pollution types, driving forces, technology and the research object were retrieved from the keywords analysis. The common NPS pollutants of nitrogen, phosphorus, and heavy metals grabbed the highest attention, while the emerging contaminants have attracted increased attention. The migration and transformation of agricultural NPS pollution and urban NPS pollution driven by climate change and land use change were hot issues related to NPS pollution studies. Technologies related to the combination of 3S technology (RS, GIS, and GPS) and NPS pollution models, the sustainable control technologies, the technology of accurate traceability and automatic monitoring, and the comprehensive management plan were the important research areas related to NPS pollution. Although the research locations were mostly concentrated in the surface water and groundwater, the ocean and drinking water have great potential for future research. Conclusions: This study illustrates the global focuses related to NPS pollution during 2012–2021 according to analyzing the publication outputs, source journals, source country, author, institution and the high-frequency keywords. Results demonstrated that the migration and transformation mechanism and ecological risk assessment for heavy metals and emerging pollutants, accurate traceability techniques, sustainable ecological restoration control techniques, and marine pollution have attracted rising attention. Additionally, developing countries will have a higher interest in NPS pollution in the future, because developed countries have already made great progress in controlling NPS pollution

Involvement of Reactive Oxygen Species in a Feed-Forward Mechanism of Na/K-ATPase Mediated Signaling

Cardiotonic steroids (such as ouabain) signaling through Na/K-ATPase regulate sodium reabsorption in the renal proximal tubule. We report here that reactive oxygen species are required to initiate ouabain-stimulated Na/K-ATPase·c-Src signaling. Pretreatment with the antioxidant N-acetyl-L-cysteine prevented ouabain-stimulated Na/K-ATPase·c-Src signaling, protein carbonylation, redistribution of Na/K-ATPase and sodium/proton exchanger isoform 3, and inhibition of active transepithelial 22Na+ transport. Disruption of the Na/K-ATPase·c-Src signaling complex attenuated ouabain-stimulated protein carbonylation. Ouabain-stimulated protein carbonylation is reversed after removal of ouabain, and this reversibility is largely independent of de novo protein synthesis and degradation by either the lysosome or the proteasome pathways. Furthermore, ouabain stimulated direct carbonylation of two amino acid residues in the actuator domain of the Na/K-ATPase α1 subunit. Taken together, the data indicate that carbonylation modification of the Na/K-ATPase α1 subunit is involved in a feed-forward mechanism of regulation of ouabain-mediated renal proximal tubule Na/K-ATPase signal transduction and subsequent sodium transport

Reduction of Na/K-ATPase potentiates marinobufagenin-induced cardiac dysfunction and myocyte apoptosis

Background: Na/K-ATPase decrease has been reported in patients with heart failure and is related to cardiac dysfunction. Results: Reducing Na/K-ATPase activates caspase 9 and induces cardiac dilation when treated with marinobufagenin. Conclusion: Reduction of Na/K-ATPase potentiates marinobufagenin-induced cardiac myocyte apoptosis. Significance: Decreased Na/K-ATPase content together with increased cardiotonic steroids levels is a novel mechanism that may account for cardiac dysfunction

Pharmacokinetic Interaction between Magnolol and Piperine in Rats

Purpose: To investigate the pharmacokinetic mechanism of interaction between magnolol and piperine when co-administered to rats.Methods: The rats were divided into five groups as follows: magnolol group (625 mg/kg); low dose of piperine group (20 mg/kg); high dose of piperine group (40 mg/kg); low dose of piperine + magnolol group; or high dose of piperine + magnolol group. Plasma samples were collected at regular time intervals after administration of a single dose of magnolol (625 mg/kg, p.o.) alone or piperine (20 or 40 mg/kg, p.o.) in the presence or absence of magnolol (625 mg/kg, p.o.). The concentrations of magnolol and piperine in plasma were measured by a validated high performance liquid chromatography (HPLC) method.Results: Compared with control, the groups given magnolol alone, concomitant administration of piperine and magnolol resulted in significant decrease (p < 0.01) in the AUC and Cmax of magnolol. Interestingly, compared with administration of piperine alone (20 mg/kg), co-administration with magnolol did not significantly (p > 0.05) alter the pharmacokinetic parameters of piperine. However, at high dose (40 mg/kg) of piperine, Cmax of piperine significantly decreased from 4.30 ± 1.47 to 2.50 ± 0.78 μg/mL (p < 0.05).Conclusion: Co-administration of magnolol and piperine decreases plasma concentration of either drug in rats, suggesting that concurrent use of magnolol with piperine or piperine-containing diets would require close monitoring for potential interactions.Keywords: Magnolol, Piperine, Pharmacokinetic interaction, Co administratio

Broadband enhancement of spontaneous emission in a photonic-plasmonic structure

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Phylogenetic and Genome Analysis of 17 Novel Senecavirus A Isolates in Guangdong Province, 2017

Senecavirus A (SVA), an emerging RNA virus, is considered to be associated with porcine idiopathic vesicular disease (PIVD). From February to September 2017, 17 novel SVA strains were isolated from samples with the vesicular disease from Guangdong Province, China. Full-length genomes and individual genes of the 17 new SVA isolates were genetically and phylogentically analyzed. Results showed that complete genomes, VP1, 3C, and 3D genes of these 17 novel SVA isolates revealed 96.5–99.8%, 95.1–99.9%, 95.6–100%, and 96.9–99.7% nucleotides identities, respectively. Phylogenetic analyses based on sequences of full-length genomes, VP1, 3C, and 3D genes indicated that 17 novel SVA isolates separated to three well-defined groups. Meanwhile, phylogenetic analysis for all available Chinese SVA strains demonstrated that 45 Chinese SVA strains clustered into five distinct groups with no significant relationship between strains from different provinces and/or years, including a newly emerging branch in China. This is the first comprehensive study of phylogenetic analysis for all available Chinese SVA strains, indicating the appearance of a new type of SVA strains and the complicated circulations with at least five different types of SVA strains in pigs in China

A multinode quantum network over a metropolitan area

Towards realizing the future quantum internet, a pivotal milestone entails the transition from two-node proof-of-principle experiments conducted in laboratories to comprehensive, multi-node setups on large scales. Here, we report on the debut implementation of a multi-node entanglement-based quantum network over a metropolitan area. We equipped three quantum nodes with atomic quantum memories and their telecom interfaces, and combined them into a scalable phase-stabilized architecture through a server node. We demonstrated heralded entanglement generation between two quantum nodes situated 12.5 km apart, and the storage of entanglement exceeding the round-trip communication time. We also showed the concurrent entanglement generation on three links. Our work provides a metropolitan-scale testbed for the evaluation and exploration of multi-node quantum network protocols and starts a new stage of quantum internet research.Comment: 21 pages in total, 4 figures and 1 table in the main text, 5 figures and 8 tables in the supplementary materia