BACKGROUND:The strongest genetic risk factors for atrial fibrillation (AF) are DNA variants on chromosome 4q25 near the transcription factor gene PITX2 (Pitx2:Paired-like homeodomain transcription factor 2). Mice deficient in Pitx2 (Pitx2+/-) have increased AF susceptibility, although the molecular mechanism(s) remains controversial. Pitx2 encodes a transcription factor that activates an antioxidant response to promote cardiac repair. Increased reactive oxygen species causing oxidation of polyunsaturated fatty acids generates reactive lipid dicarbonyl moieties that adduct to proteins and other macromolecules to promote cellular injury. We tested the hypothesis that oxidative stress, and specifically isolevuglandins, the most reactive lipid dicarbonyls identified, are increased in the setting of Pitx2 deficiency to promote proarrhythmic remodeling and AF.METHODS:Pitx2+/- and Pitx2+/+ wild-type littermate control mice were treated orally with vehicle, the lipid dicarbonyl scavenger 2-hydroxybenzylamine, or an inactive control compound at weaning, until study at age 16 to 18 weeks.RESULTS:Pitx2+/- mice demonstrated increased P wave duration indicative of slowed atrial conduction, as well as increased inducible AF burden and sustained AF, compared with wild type, and these abnormalities were prevented by 2-hydroxybenzylamine. Both reactive oxygen species and isolevuglandin protein adducts were elevated in Pitx2+/- atria with reduced expression of reactive oxygen species-protective genes. High-resolution respirometry demonstrated impaired mitochondrial function in Pitx2+/- atria, with disruption of mitochondrial integrity and cell-cell junctions with connexin lateralization, as well as decreased mitochondrial biogenesis gene expression. Proarrhythmic ionic current remodeling in Pitx2+/- atrial myocytes included elevated resting membrane potential, abbreviated action potential duration, and reduced maximum phase 0 upstroke velocity compared with wild type. Most of these abnormalities were ameliorated or prevented by 2-hydroxybenzylamine.CONCLUSIONS:These results demonstrate a critical role for lipid dicarbonyl mediators of oxidative stress in the proarrhythmic remodeling and AF susceptibility that occurs with Pitx2 deficiency, implying the possibility of genotype-specific therapy to prevent AF.

Aims The lymphocyte adaptor protein (LNK) is a negative regulator of cytokine and growth factor signalling. The rs3184504 variant in SH2B3 reduces LNK function and is linked to cardiovascular, inflammatory, and haematologic disorders, including stroke. In mice, deletion of Lnk causes inflammation and oxidative stress. We hypothesized that Lnk-/- mice are susceptible to atrial fibrillation (AF) and that rs3184504 is associated with AF and AF-related stroke in humans. During inflammation, reactive lipid dicarbonyls are the major components of oxidative injury, and we further hypothesized that these mediators are critical drivers of the AF substrate in Lnk-/- mice.Methods and results Lnk-/- or wild-type (WT) mice were treated with vehicle or 2-hydroxybenzylamine (2-HOBA), a dicarbonyl scavenger, for 3 months. Compared with WT, Lnk-/- mice displayed increased AF duration that was prevented by 2-HOBA. In the Lnk-/- atria, action potentials were prolonged with reduced transient outward K+ current, increased late Na+ current, and reduced peak Na+ current, pro-arrhythmic effects that were inhibited by 2-HOBA. Mitochondrial dysfunction, especially for Complex I, was evident in Lnk-/- atria, while scavenging lipid dicarbonyls prevented this abnormality. Tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) were elevated in Lnk-/- plasma and atrial tissue, respectively, both of which caused electrical and bioenergetic remodelling in vitro. Inhibition of soluble TNF-alpha prevented electrical remodelling and AF susceptibility, while IL-1 beta inhibition improved mitochondrial respiration but had no effect on AF susceptibility. In a large database of genotyped patients, rs3184504 was associated with AF, as well as AF-related stroke.Conclusion These findings identify a novel role for LNK in the pathophysiology of AF in both experimental mice and humans. Moreover, reactive lipid dicarbonyls are critical to the inflammatory AF substrate in Lnk-/- mice and mediate the pro-arrhythmic effects of pro-inflammatory cytokines, primarily through electrical remodelling. Graphical Abstract

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, yet the cellular and molecular mechanisms underlying the AF substrate remain unclear. Isolevuglandins (IsoLGs) are highly reactive lipid dicarbonyl products that mediate oxidative stress-related injury. In murine hypertension, the lipid dicarbonyl scavenger 2-hydroxybenzylamine (2-HOBA) reduced IsoLGs and AF susceptibility. We hypothesized that IsoLGs mediate detrimental pathophysiologic effects in atrial cardiomyocytes that promote the AF substrate. Using Seahorse XFp extracellular flux analysis and a luminescence assay, IsoLG exposure suppressed intracellular ATP production in atrial HL-1 cardiomyocytes. IsoLGs caused mitochondrial dysfunction, with reduced mitochondrial membrane potential, increased mitochondrial reactive oxygen species (ROS) with protein carbonylation, and mitochondrial DNA damage. Moreover, they generated cytosolic preamyloid oligomers previously shown to cause similar detrimental effects in atrial cells. In mouse atrial and HL-1 cells, patch clamp experiments demonstrated that IsoLGs rapidly altered action potentials (AP), implying a direct effect independent of oligomer formation by reducing the maximum Phase 0 upstroke slope and shortening AP duration due to ionic current modifications. IsoLG-mediated mitochondrial and electrophysiologic abnormalities were blunted or totally prevented by 2-HOBA. These findings identify IsoLGs as novel mediators of oxidative stress-dependent atrial pathophysiology and support the investigation of dicarbonyl scavengers as a novel therapeutic approach to prevent AF.

Background: With aging, the human atrium invariably develops amyloid composed of ANP (atrial natriuretic peptide) and BNP (B-type natriuretic peptide). Preamyloid oligomers are the primary cytotoxic species in amyloidosis, and they accumulate in the atrium during human hypertension and a murine hypertensive model of atrial fibrillation susceptibility. We tested the hypothesis that preamyloid oligomers derived from natriuretic peptides cause cytotoxic and electrophysiological effects in atrial cells that promote arrhythmia susceptibility and that oligomer formation is enhanced for a mutant form of ANP linked to familial atrial fibrillation. Methods: Oligomerization was assessed by Western blot analysis. Bioenergic profiling was performed using the Seahorse platform. Mitochondrial dynamics were investigated with immunostaining and gene expression quantitated using quantitative reverse transcription polymerase chain reaction. Action potentials and ionic currents were recorded using patch-clamp methods and intracellular calcium measured using Fura-2. Results: Oligomer formation was markedly accelerated for mutant ANP (mutANP) compared with WT (wild type) ANP. Oligomers derived from ANP, BNP, and mutANP suppressed mitochondrial function in atrial HL-1 cardiomyocytes, associated with increased superoxide generation and reduced biogenesis, while monomers had no effects. In hypertensive mice, atrial cardiomyocytes displayed reduced action potential duration and maximal dV/dT of phase 0, with an elevated resting membrane potential, compared with normotensive mice. Similar changes were observed when atrial cells were exposed to oligomers. mutANP monomers produced similar electrophysiological effects as mutANP oligomers, likely due to accelerated oligomer formation, while ANP and BNP monomers did not. Oligomers decreased Na+ current, inward rectifier K+ current, and L-type Ca++ current, while increasing sustained and transient outward K+ currents, to account for these effects. Conclusions: These findings provide compelling evidence that natriuretic peptide oligomers are novel mediators of atrial arrhythmia susceptibility. Moreover, the accelerated oligomerization by mutANP supports a role for these mediators in the pathophysiology of this mutation in atrial fibrillation.

Proinflammatory cytokines have been shown to induce oxidative stress and electrical remodeling. Mice lacking the lymphocyte adaptor protein (Lnk-/-), a negative regulator of cytokine signaling, display systemic and atrial inflammation, oxidative stress, and atrial fibrillation (AF) susceptibility in the absence of structural abnormalities. Previously, we found highly reactive products of lipid peroxidation, isolevuglandins (IsoLGs), to be key mediators of AF susceptibility in Lnk-/- mice.

Background: Hypertension is one of the most common risk factors for atrial fibrillation (AF), although the precise cellular and molecular mechanism(s) by which hypertension leads to AF are not well understood. Isolevuglandins (IsoLGs) are highly reactive dicarbonyl products of lipid peroxidation responsible for a major component of oxidative stress-related injury. In a mouse model of hypertension, we recently demonstrated that IsoLGs are elevated in hypertensive mouse atria and that an IsoLG scavenger reduced both IsoLG burden and AF susceptibility. Hypothesis: In this study, we hypothesized that IsoLGs can promote AF by inducing proarrhythmic metabolic and electrophysiologic (EP) changes in atrial cardiomyocytes. Methods and Results: Using standard patch clamp methods, we found significant changes in action potential properties of isolated mouse atrial cardiomyocytes exposed to IsoLGs (1μM, n=15 cells), including elevation of resting membrane potential, shortening of APD and reduction of V max . Acute IsoLG treatment led to a reduction of intracellular ATP production in atrial HL-1 cardiomyocytes, as measured by using a luminescence assay. Employing TMRM and Mitotracker Green staining for confocal and high-throughput screening (HTS) live-cell imaging assays, we also found that IsoLGs decreased mitochondrial membrane potential (compared to control, TMRM fluorescence decreased by 23%, 28%, 36% and 42%, respectively, when exposed to 0.01, 0.1, 0.5 and 1μM concentrations of IsoLG) accompanied by increased apoptosis (Cell Event Caspase-3/7 Green Detection Reagent) in a concentration-dependent manner, suggesting a prolonged mitochondrial transition pore opening. Moreover, cell metabolism assays performed using Agilent’s Seahorse XF96 extracellular flux analyzer revealed that IsoLGs exert a concentration dependent decrease in basal oxygen consumption rate and ATP production in HL-1 atrial cardiomyocytes. Conclusion: Together, these findings indicate that IsoLGs promote proarrhythmic EP and mitochondrial effects in atrial cells and thus may provide a novel therapeutic target for AF.

Introduction: Inflammation and oxidative stress are linked to multiple risk factors for atrial fibrillation (AF), and to AF itself in the setting of sterile injury (e.g. after catheter ablation or cardiac surgery). However, anti-inflammatory therapies and conventional antioxidants cause adverse effects or are ineffective to prevent AF. Highly reactive mediators of lipid peroxidation such as isolevuglandins (IsoLGs) have been identified as a major component of oxidative stress-related injury. We hypothesized that during AF promoted by cardiac inflammation, a scavenger of IsoLG will decrease AF susceptibility. Methods: We studied mice with a systemic inflammatory phenotype due to deficiency in the lymphocyte adaptor protein ( Lnk -/- ), a negative regulator of cytokine signaling. At weaning, Lnk -/- mice and their wild-type (WT) littermates received either vehicle or a potent IsoLG scavenger, 2-hydroxybenzylamine (2-HOBA), by oral administration. At age 14 weeks, animals underwent transesophageal burst pacing, echocardiography, and tissue harvest or flow cytometry to measure atrial inflammation and IsoLG-adducts. Results: Cardiac histology and echocardiography revealed no major histologic or structural abnormalities in Lnk -/- mice. Nevertheless, Lnk -/- mice demonstrated a significant increase in AF burden compared to WT controls (124.8±43.3 vs 6.8±3 sec, respectively [mean±SEM, n=28, 12; P<0.05]), as well as increased sustained AF (> 30 sec; 48.1% vs 0%; P<0.01]). Leukocyte infiltration was present in the atria of Lnk -/- mice, with a significant increase in CD3, CD19, NK1.1, and CD11b/MHCII positive cells, compared to atria from WT control mice. Furthermore, there was a 2 to 4-fold increase in IsoLG-adducts for Lnk -/- atrial immune cells positive for CD3, CD19, NK1.1 and CD11b/MHCII, compared to cells from WT atria. Lnk -/- mice treated with 2-HOBA had significantly reduced AF burden (4.7±4.5 sec, n=7; P<0.05) with a trend towards reduction in sustained AF (0%, n=7; P=0.057). Conclusions: IsoLGs play a critical role in the pathogenesis of inflammation-mediated AF, and 2-HOBA, a scavenger of IsoLGs, represents a potentially novel therapeutic strategy for AF in this clinical setting.

Background— The widely used macrolide antibiotic azithromycin increases risk of cardiovascular and sudden cardiac death, although the underlying mechanisms are unclear. Case reports, including the one we document here, demonstrate that azithromycin can cause rapid, polymorphic ventricular tachycardia in the absence of QT prolongation, indicating a novel proarrhythmic syndrome. We investigated the electrophysiological effects of azithromycin in vivo and in vitro using mice, cardiomyocytes, and human ion channels heterologously expressed in human embryonic kidney (HEK 293) and Chinese hamster ovary (CHO) cells. Methods and Results— In conscious telemetered mice, acute intraperitoneal and oral administration of azithromycin caused effects consistent with multi-ion channel block, with significant sinus slowing and increased PR, QRS, QT, and QTc intervals, as seen with azithromycin overdose. Similarly, in HL-1 cardiomyocytes, the drug slowed sinus automaticity, reduced phase 0 upstroke slope, and prolonged action potential duration. Acute exposure to azithromycin reduced peak SCN5A currents in HEK cells (IC 50 =110±3 μmol/L) and Na + current in mouse ventricular myocytes. However, with chronic (24 hour) exposure, azithromycin caused a ≈2-fold increase in both peak and late SCN5A currents, with findings confirmed for I Na in cardiomyocytes. Mild block occurred for K + currents representing I Kr (CHO cells expressing hERG; IC 50 =219±21 μmol/L) and I Ks (CHO cells expressing KCNQ1+KCNE1; IC 50 =184±12 μmol/L), whereas azithromycin suppressed L-type Ca ++ currents (rabbit ventricular myocytes, IC 50 =66.5±4 μmol/L) and I K1 (HEK cells expressing Kir2.1, IC 50 =44±3 μmol/L). Conclusions— Chronic exposure to azithromycin increases cardiac Na + current to promote intracellular Na + loading, providing a potential mechanistic basis for the novel form of proarrhythmia seen with this macrolide antibiotic.

BACKGROUND:The widely used macrolide antibiotic azithromycin increases risk of cardiovascular and sudden cardiac death, although the underlying mechanisms are unclear.Case reports, including the one we document here, demonstrate that azithromycin can cause rapid, polymorphic ventricular tachycardia in the absence of QT prolongation, indicating a novel proarrhythmic syndrome.We investigated the electrophysiological effects of azithromycin in vivo and in vitro using mice, cardiomyocytes, and human ion channels heterologously expressed in human embryonic kidney (HEK 293) and Chinese hamster ovary (CHO) cells. METHODS AND RESULTS:In conscious telemetered mice, acute intraperitoneal and oral administration of azithromycin caused effects consistent with multi-ion channel block, with significant sinus slowing and increased PR, QRS, QT, and QTc intervals, as seen with azithromycin overdose.Similarly, in HL-1 cardiomyocytes, the drug slowed sinus automaticity, reduced phase 0 upstroke slope, and prolonged action potential duration.Acute exposure to azithromycin reduced peak SCN5A currents in HEK cells (IC 50 =110±3 μmol/L) and Na + current in mouse ventricular myocytes.However, with chronic (24 hour) exposure, azithromycin caused a ≈2-fold increase in both peak and late SCN5A currents, with findings confirmed for I Na in cardiomyocytes.Mild block occurred for K + currents representing I Kr (CHO cells expressing hERG; IC 50 =219±21 μmol/L) and I Ks (CHO cells expressing KCNQ1+KCNE1; IC 50 =184±12 μmol/L), whereas azithromycin suppressed L-type Ca ++ currents (rabbit ventricular myocytes, IC 50 =66.5±4μmol/L) and I K1 (HEK cells expressing Kir2.1, IC 50 =44±3 μmol/L). CONCLUSIONS:Chronic exposure to azithromycin increases cardiac Na + current to promote intracellular Na + loading, providing a potential mechanistic basis for the novel form of proarrhythmia seen with this macrolide antibiotic.

The widely-used macrolide antibiotic azithromycin (AZ) increases risk of cardiovascular and sudden cardiac death. Case reports indicate that AZ can cause polymorphic ventricular tachycardia in the absence and presence of QT prolongation, implying a novel proarrhythmic syndrome. We investigated the electrophysiologic effects of AZ in vivo and in vitro using mice, cardiomyocytes, and heterologously-expressed human ion channels. After implanting an ECG telemeter, conscious adult mice received intraperitoneal injection of AZ (50 mg/kg, followed in 60 min by 100 mg/kg; n=7). With both doses of AZ, heart rate declined (from 685±24 to 489±20 and 481±21 bpm, for baseline, 50 and 100 mg/kg, respectively [mean±SEM]; P<0.001). In addition, AZ increased the PR interval (32.7±0.9 ms to 39.4±0.7 and 39.8±0.9 ms, respectively; P<0.001), QRS interval (10.2±0.4 ms to 12.5±0.4 and 13.3±0.5 ms, respectively; P<0.001), and QT interval (37.4±4 ms to 48.0±5 and 51.2±4 ms, respectively; P<0.01). In spontaneously-beating HL-1 cardiomyocytes, AZ (100 μM) significantly slowed beat rate (from 215±7 to 180±7 bpm; n=14; P<0.01), while increasing action potential rise time (23.0±3.0 to 36.2±3.8 ms; P<0.01) and duration (at 90% repolarization, 118.3±8 to 137.8±8.7ms; P<0.01). In HEK cells stably expressing SCN5A, AZ reduced Na+ currents (IC50 110±3 μM; n=14), while similar results were obtained using mouse ventricular myocytes (IC50 117±4 μM; n=6). In addition, AZ suppressed K+ currents recorded from HEK cells expressing hERG (IC50 219±21 μM; n=5) and CHO cells expressing KCNQ1 and KCNE1 (IC50 184±12 μM; n=6), as well as L-type Ca++ current in rabbit ventricular myocytes (IC50 67±4 μM; n=5). We conclude that azithromycin blocks multiple cardiac ion channels to prolong the PR, QRS, and QT interval in vivo, at concentrations achievable within the heart based on intracellular drug accumulation. These effects likely contribute to its novel proarrhythmic effect in humans.

Al/C composite foil of less than 10 μm thickness carbon layer with excellent interfacial bonding and sheet resistivity of 9.75×10-8 Ω·m was prepared by resin pyrolysis. Its microstructure, phase composition and interfacial structure were systematically investigated by using scanning electron microscope (SEM), X-ray diffraction (XRD) and transmission electron microscope (TEM), respectively. The effect of Al/C composite foil on solid aluminum electrolytic capacitor as cathode collector was studied. The results show that Al/C composite foil has dense cross section structure and porous surface structure. The generation of Al4C3 in Al/C composite foil is confirmed by XRD pattern. Rectangular Al4C3 needle is observed to grow in the interface between carbon layer and aluminum foil by TEM, which strengthens the interfacial bond of carbon layer and aluminum foil. The prepared Al/C composite foil is used as cathode foil of solid-aluminum electrolytic capacitor with designed voltage of 4V and designed capacity of (560±20) μF, resulting in capacity of 565 μF, equivalent series resistance (ESR) of 4.5 mΩ, dissipation factor (DF) of 1.05%, while the same performance parameter for solid aluminum electrolytic capacitor made by common etched aluminum foil are 420 μF of capacity, 7.4 mΩ of ESR, 30% of DF. The Al/C composite foil show better performance than etched aluminum foil as cathode foil.

Although normally absent, spontaneous pacemaker activity can develop in human atrium to promote tachyarrhythmias. HL-1 cells are immortalized atrial cardiomyocytes that contract spontaneously in culture, providing a model system of atrial cell automaticity. Using electrophysiologic recordings and selective pharmacologic blockers, we investigated the ionic basis of automaticity in atrial HL-1 cells. Both the sarcoplasmic reticulum Ca++ release channel inhibitor ryanodine and the sarcoplasmic reticulum Ca++ ATPase inhibitor thapsigargin slowed automaticity, supporting a role for intracellular Ca++ release in pacemaker activity. Additional experiments were performed to examine the effects of ionic currents activating in the voltage range of diastolic depolarization. Inhibition of the hyperpolarization-activated pacemaker current, If, by ivabradine significantly suppressed diastolic depolarization, with modest slowing of automaticity. Block of inward Na+ currents also reduced automaticity, whereas inhibition of T- and L-type Ca++ currents caused milder effects to slow beat rate. The major outward current in HL-1 cells is the rapidly activating delayed rectifier, IKr. Inhibition of IKr using dofetilide caused marked prolongation of action potential duration and thus spontaneous cycle length. These results demonstrate a mutual role for both intracellular Ca++ release and sarcolemmal ionic currents in controlling automaticity in atrial HL-1 cells. Given that similar internal and membrane-based mechanisms also play a role in sinoatrial nodal cell pacemaker activity, our findings provide evidence for generalized conservation of pacemaker mechanisms among different types of cardiomyocytes.

Indium sulfide nanomaterials of different frameworks and morphologies have been prepared ionothermally using indium chloride and sodium sulfide as raw materials and different ionic liquids as solvent.The morphology and framework of indium sulfide nanomaterials were characterized by XRD,SEM,TEM.The results show that: prepared at constant temperature of 150 ℃ for 24 h,the sample in the ionic liquid,1-Ethyl-3-methylimidazolium bromide was tetragonal β-In2S3 with hexagonal flake morphology,while in 1-Butyl-3-methylimidazolium tetrafluoroborate,the sample was cubic β-In2S3 with flower like morphology.The FTIR result indicated that ionic liquids have a strong act on the reaction process.Ultraviolet-visible optical Absorption spectrum and photoluminescence spectrum of the nanoflakes have also been characterized.

During atrial fibrillation (AF), rapid stimulation causes atrial remodeling that increases arrhythmia susceptibility. Using an established atrial (HL-1) myocyte model, we investigated the transcriptional profile associated with early atrial myocyte remodeling. Spontaneously contracting HL-1 cells were cultured in the absence and presence of rapid stimulation for 24 h and RNA harvested for microarray analysis. We identified 758 genes that were significantly altered with rapid stimulation (626 up- and 132 down-regulated). Results were confirmed using real-time quantitative RT-PCR for selected genes based on physiological relevance in human AF and/or experimental atrial tachycardia (AT), and regulation in the microarray results. In some cases, transcriptional changes were rapid, occurring within 3 h. For a selected group of genes, results were validated for the expressed protein, with findings that correlated with observed transcriptional changes. Significantly regulated genes were classified using the Gene Ontology Database to permit direct comparison of our findings with previously published myocardial transcriptional profiles. For broad functional categories, there was strong concordance between rapidly stimulated HL-1 myocytes and human AF, but not for other remodeling paradigms (cardiomyopathy and exercise). Many individual gene changes were conserved with AF/AT, with marked up-regulation of genes encoding brain and atrial natriuretic peptide precursors, and heat shock proteins. For the conserved genes, both a cellular stress and survival response was evident. Our results demonstrate similarities with human AF/experimental AT with respect to large-scale patterns of transcriptional remodeling, as well as regulation of specific individual genes. Importantly, we identified novel pathways and molecules that were concordantly regulated in vivo.

Ordered mesoporous carbon-SiO2 compound was prepared via co-assembly method,wherein resol was used as carbon precursor,tetraethyl orthosilicate was used as SiO2 precursor,and triblock copolymer Pluronic F127 was used as template.Carbonization was carried out in a tubular furnace at 900℃ for 3 h under N2 flow and mesoporous carbon with secondary pore structure was obtained after removal of SiO2.The as-prepared sample was characterized by transmission electron microscopy,nitrogen isotherm adsorption-desorption measurement,cyclic voltammetry and constant current charge-discharge.The results indicated that ordered mesoporous carbon possessed a high BET specific surface area of 1657.6m2·g-1 and a specific capacitance of about 161.3F·g-1.The electrochemical performance was enhanced much more than the common mesoporous carbon material.Compared with the mesoporous carbon material with the single pore channel,the cyclic voltammetry curve of mesoporous carbon with secondary pore structure was closer to rectangular,the specific capacitance value was greatly improved and the decreasing rate of the capacitance was lower with increasing the discharge current capacitance.

Zinc hydroxide fluoride (Zn(OH)F) with novel flower-like morphology has been prepared via a microwave-assisted ionic liquid route. The flower-like Zn(OH)F particle has six petals and every petal is composed of lots of acicular nano-structure. Nanoporous ZnO is obtained by thermal decomposition of as-prepared Zn(OH)F in air, and the flower-like morphology is well retained. In the process of synthesis, ionic liquid 1-Butyl-3-methylimidazolium tetrafluoroborate is used as both the reactant and the template.

Ni(OH)(2) and Co(OH)(2) with a nanostructure were synthesized by an easy hydrothermal method without using any organic reagent. NiO and Co3O4 were obtained via heat-treatment of the hydrates at 250 degrees C and characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and N-2 adsorption-desorption analysis. The characterization results indicate that the metal oxides have a disordered mesoporous structure and high BET surface area. The results of electrochemical tests show that the mesoporous metal oxides have fine supercapacitive behaviors and their specific capacitance values at the discharging current of 5 mA are 176 and 298 F center dot g(-1), respectively.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The arrhythmia is associated with electrical (reduced action potential duration [APD] and ICa) and structural remodeling that increases future AF susceptibility. The time course of the molecular events that initiate this remodeling are not currently known, and is the focus of this investigation using rapidly stimulated atrial myocytes. In rapidly stimulated isolated canine atrial strips, APD90 was reduced within 1.5hr (APD90, ?24.3%, P(0.05) indicative of remodeling. This time course was confirmed in atrial myocytes (HL‐1 cells) subjected to rapid stimulation in culture (APD90, ?36.1%, P(0.01), with an associated reduction in ICa‐L and ICa‐T. Real time quantitative RT‐PCR results revealed no significant change in Ca2+ channel (‐subunit mRNA at this time point, indicating that proteolysis was most likely responsible for reduced ICa. The time course of transcriptional remodeling was variable, with some genes regulated very early (0–3hr: Hspa1a, Aqp4 & Prkci), others gradually over 18hr (Map2k3 & Gucy1a3), and others much later (18hr: Nppa, Nppb & Tgfb1). Thus, the remodeling produced by rapid stimulation of atrial myocytes is complex. Electrical remodeling is achieved within 90 min, while the time course of transcriptional remodeling is highly variable and likely pathway‐specific.