Aims: Arrhythmogenesis of chronic myocardial infarction (MI) is associated with the prolongation of action potential, reduction of inward rectifier potassium (I-K1, Kir) channels and hyper-activity of Calcium/calmodul...
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Aims: Arrhythmogenesis of chronic myocardial infarction (MI) is associated with the prolongation of action potential, reduction of inward rectifier potassium (I-K1, Kir) channels and hyper-activity of Calcium/calmodulin-dependent kinase II (CaMKII) in cardiomyocytes. Zacopride, a selective I-K1 agonist, was applied to clarify the cardioprotection of I-K1 agonism via a CaMKII signaling on arrhythmias post-MI. Methods: Male SD rats were implanted wireless transmitter in the abdominal cavity and subjected to left main coronary artery ligation or sham operation. The telemetric ECGs were monitored per day throughout 4 weeks. At the endpoint, isoproterenol (1.28 mg/kg, i.v.) was administered for provocation test. The expressions of Kir2.1 (dominant subunit of I-K1 in ventricle) and CaMKII were detected by Western-blotting. Key findings: In the telemetric rats post-MI, zacopride significantly reduced the episodes of atrioventricular conduction block (AVB), premature ventricular contraction (PVC), ventricular tachycardia (VT) and ventricular fibrillation (VF), without significant effect on superventricular premature contraction (SPVC). In provocation test, zacopride suppressed the onset of ventricular arrhythmias in conscious PMI or sham rats. The expression of Kir2.1 was significantly downregulated and p-CaMKII was upregulated post-MI, whereas both were restored by zacopride treatment. Significance: I-K1/Kir2.1 might be an attractive target for pharmacological controlling of lethal arrhythmias post MI.
Organic and inorganic sedimentary parameters in and off the Changjiang Estuary have been analyzed to reconstruct historical trends in eutrophication and hypoxia over the last century. The lipid biomarker concentration...
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Organic and inorganic sedimentary parameters in and off the Changjiang Estuary have been analyzed to reconstruct historical trends in eutrophication and hypoxia over the last century. The lipid biomarker concentrations in the Changjiang Estuary mud area,(CEMA) indicated eutrophication accelerated after the 1970s. Meanwhile, Mo/Al indicated hypoxia has increased since 1960s. Eutrophication and hypoxia in the CEMA are primarily a result of the dramatically increased load of terrestrial nutrients from the Changjiang to the East China Sea. The lipid biomarker concentrations in the southwest Cheju Island mud area (SCIMA) showed primary production is controlled mainly by changes in regional climate and marine current. No significant hypoxia occurred in the SCIMA over the past century as indicated by Mo/Al. Therefore, geochemical indicators of eutrophication and hypoxia revealed different patterns between the CEMA and SCIMA, suggesting the role of river-derived nutrients in sustaining eutrophication and hypoxia in the CEMA since the 1960s. (C) 2015 Elsevier Ltd. All rights reserved.
Camptothecin (CPT) has been shown to block disassembly of the topoisomerase I (Topo I)/DNA cleavable complex. However, the poor aqueous solubility, intrinsic instability, and severe toxicity of CPTs have limited their...
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Camptothecin (CPT) has been shown to block disassembly of the topoisomerase I (Topo I)/DNA cleavable complex. However, the poor aqueous solubility, intrinsic instability, and severe toxicity of CPTs have limited their clinical applications. Herein, we report the design and synthesis of H2O-soluble and orally bioavailable hexacyclic CPT derivatives. By analysis of a virtual chemical library and cytotoxicity screening in vitro, 9 and 11 were identified as potential prodrugs and chosen for further characterization in vivo. Both compounds exhibited remarkable anticancer and anti-inflammation efficacies in animals and improved drug-like profiles.
In order to obtain high resolution inverse synthetic aperture radar (ISAR) sparse images, a block sparse signal recovery ISAR imaging algorithm is proposed by considering the cluster characteristics of target in this ...
In order to obtain high resolution inverse synthetic aperture radar (ISAR) sparse images, a block sparse signal recovery ISAR imaging algorithm is proposed by considering the cluster characteristics of target in this paper. Firstly, the ISAR sparse imaging model is established, the imaging is converted to L0 norm optimization problem. Secondly, one negative exponential function sequence is used as smoothed function to approach the block L0 norm. Finally, the revised step is added to ensure solving the optimization problem along the steepest descent gradient direction and the cost function is updated for the next loop. Simulation results verify the proposed algorithm is effective.
Currently in China, porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine rotavirus (PoRV), and porcine deltacoronavirus (PDCoV) are the major causes of porcine viral diarrhea, an...
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Currently in China, porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine rotavirus (PoRV), and porcine deltacoronavirus (PDCoV) are the major causes of porcine viral diarrhea, and mixed infections in clinics are common, resulting in significant economic losses in pig industry. Here, a dual priming oligonucleotide (DPO)-based multiplex real-time SYBR Green RT-PCR assay were developed for accurately differentiating PEDV, TGEV, PoRV, and PDCoV in clinical specimens targeting the N gene of TGEV, PEDV, and PDCoV, and the VP7 gene of PoRV. Results showed that the DPO primer allowed a wider annealing temperature range (40-65 degrees C) and had a higher priming specificity compared to conventional primer, in which more than 3 nucleotides in the 3'- or 5'-segment of DPO primer mismatched with DNA template, PCR amplification efficiency would decrease substantially or extension would not proceed. DPO-based multiplex real-time RT-PCR method had analytical detection limit of 8.63 x 10(2) copies/mu L, 1.92 x 10(2) copies/mu L, 1.74 x 10(2) copies/mu L, and 1.76 x 10(2) copies/mu L for PEDV, TGEV, PoRV, and PDCoV in clinical specimens, respectively. A total of 672 clinical specimens of piglets with diarrhea) symptoms were collected in Northeastern China from 2017 to 2018 followed by analysis using the assay, and epidemiological investigation results showed that PEDV, TGEV, PoRV, and PDCoV prevalence was 19.05%, 5.21%, 4.32%, and 3.87%, respectively. The assay developed in this study showed higher detection accuracy than conventional RT-PCR method, suggesting a useful tool for the accurate differentiation of the four major viruses causing porcine viral diarrhea in practice.
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