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To activate peroxymonosulfate (PMS) and degrade methylene blue (MB), cobalt and nitrogen‐doped porous carbon composite catalysts were prepared through pyrolysing zeolitic imidazolate framework ZIF‐9 and dicyandiamide (DCDA) at 700–900 °C with various mass ratios. Powder X‐ray diffraction, scanning electron microscopy, transmission electron microscopy, and Brunauer‐Emmett‐Teller results showed that Co, porous carbon and carbon nanotubes (CNTs) co‐existed in the catalyst prepared at 800 °C with a ZIF‐9/DCDA ratio of 1 : 3. Thermogravimetric analysis suggested that CNT@ZIF‐800 had a higher ratio of graphitic to turbostratic carbon than CNT@ZIF‐700. It had degraded 94.8 % MB within 30 min, which was about 1.9 times faster than its counterpart C‐ZIF‐800. It also showed faster degradation rates towards Congo red (98.5 %, 5 min) and slower rates towards rhodamine B (90.7 %, 30 min) than MB. Furthermore, XPS revealed that it had 14.5 % more Co−Nx/pyridinic‐N active sites than C‐ZIF‐800. EPR suggested that 1O2 might be the primary catalytic species whereas the SO4−⋅ and ⋅OH the secondary ones. The formation mechanism of such active species might be originated from the synergistic activation of PMS by CNTs, Co−Nx/pyridinic‐N and abundant Co sites in the CNT@ZIF‐800. This work not only provided efficient Fenton‐like catalysts for MB degradation, but also clarified the catalytic mechanism. [ABSTRACT FROM AUTHOR]

Melatonin has been proven to have antiarrhythmic potential; however, several studies have recently challenged this view. Herein, using a mouse model of obesity‐induced atrial fibrillation (AF), we tentatively explored whether exogenous melatonin supplementation could increase AF susceptibility in the context of obesity. We observed that an 8‐week drinking administration of melatonin (60 µg/ml in water) induced a greater susceptibility to AF in obese mice, although obesity‐induced structural remodeling was alleviated. An investigation of systemic insulin sensitivity showed that melatonin treatment improved insulin sensitivity in obese mice, whereas it inhibited glucose‐stimulated insulin secretion. Notably, melatonin treatment inhibited protein kinase B (Akt) signaling in the atria of obese mice and palmitate‐treated neonatal rat cardiomyocytes, thereby providing an AF substrate. Melatonin increased lipid stress in obesity, as evidenced by elevated lipid accumulation and lipolysis‐related gene expression, thus contributing to the impairment in atrial Akt signaling. Taken together, our results demonstrated that melatonin could increase AF susceptibility in obesity, probably due to increased lipid stress and resultant impairment of atrial Akt signaling. Our findings suggest that special precautions should be taken when administering melatonin to obese subjects. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical setting. Its pathogenesis was associated with metabolic disorder, especially defective fatty acids oxidation (FAO). However, whether promoting FAO could prevent AF occurrence and development remains elusive. In this study, we established a mouse model of obesity-related AF through high-fat diet (HFD) feeding, and used l-carnitine (LCA, 150 mg/kg⋅BW/d), an endogenous cofactor of carnitine palmitoyl-transferase-1B (CPT1B; the rate-limiting enzyme of FAO) to investigate whether FAO promotion can attenuate the AF susceptibility in obesity. All mice underwent electrophysiological assessment for atrial vulnerability, and echocardiography, histology and molecular evaluation for AF substrates and underlying mechanisms, which were further validated by pharmacological experiments in vitro. HFD-induced obese mice increased AF vulnerability and exhibited apparent atrial structural remodeling, including left atrial dilation, cardiomyocyte hypertrophy, connexin-43 remodeling and fibrosis. Pathologically, HFD apparently leads to defective cardiac FAO and subsequent lipotoxicity, thereby evoking a set of pathological reactions including oxidative stress, DNA damage, inflammation, and insulin resistance. Enhancing FAO via LCA attenuated lipotoxicity and lipotoxicity-induced pathological changes in the atria of obese mice, resulting in restored structural remodeling and ameliorated AF susceptibility. Mechanistically, LCA activated AMPK/PGC1α signaling both in vivo and in vitro , and pharmacological inhibition of AMPK via Compound C attenuated LCA-induced cardio-protection in palmitate-treated primary atrial cardiomyocytes. Taken together, our results demonstrated that FAO promotion via LCA attenuated obesity-mediated AF and structural remodeling by activating AMPK signaling and alleviating atrial lipotoxicity. Thus, enhancing FAO may be a potential therapeutic target for AF. [ABSTRACT FROM AUTHOR]

Necroptosis, a novel programmed cell death, plays a critical role in the development of fibrosis, yet its role in atrial fibrillation (AF) remains elusive. Mounting evidence demonstrates that aerobic exercise improves AF‐related symptoms and quality of life. Therefore, we explored the role of necroptosis in AF pathogenesis and exercise‐conferred cardioprotection. A mouse AF model was established either by calcium chloride and acetylcholine (CaCl2‐Ach) administration for 3 weeks or high‐fat diet (HFD) feeding for 12 weeks, whereas swim training was conducted 60 min/day, for 3‐week duration. AF susceptibility, heart morphology and function and atrial fibrosis were assessed by electrophysiological examinations, echocardiography and Masson's trichrome staining, respectively. Both CaCl2‐Ach administration and HFD feeding significantly enhanced AF susceptibility (including frequency and duration of episodes), left atrial enlargement and fibrosis. Moreover, protein levels of necroptotic signaling (receptor‐interacting protein kinase 1, receptor‐interacting protein kinase 3, mixed lineage kinase domain‐like protein and calcium/calmodulin‐dependent protein kinase II or their phosphorylated forms) were markedly elevated in the atria of AF mice. However, inhibiting necroptosis with necrostatin‐1 partly attenuated CaCl2‐Ach (or HFD)‐induced fibrosis and AF susceptibility, implicating necroptosis as contributing to AF pathogenesis. Finally, we found 3‐week swim training inhibited necroptotic signaling, consequently decreasing CaCl2‐Ach‐induced AF susceptibility and atrial structural remodeling. Our findings identify necroptosis as a novel mechanism in AF pathogenesis and highlight that aerobic exercise may confer benefits on AF via inhibiting cardiac necroptosis. [ABSTRACT FROM AUTHOR]

Myocardial ischemia/reperfusion (I/R) injury is a major determinant of morbidity and mortality in patients undergoing treatment for cardiac disease. A variety of treatments are reported to have benefits against reperfusion injury, yet their cardioprotective effects seem to be diminished in obesity, and the underlying mechanism remains elusive. In this study, we found that db/db mice exhibit cardiac hyper- O -GlcNAcylation. In parallel, palmitate treatment (200 mM; 12 h) in H9c2 cells showed an increase in global protein O -GlcNAcylation, along with an impaired insulin response against reperfusion injury. To investigate whether O -GlcNAcylation underlies this phenomenon, glucosamine was used to increase global protein O -GlcNAc levels. Interestingly, histological staining, electrophysiological studies, serum cardiac markers and oxidative stress biomarker assays showed that preischemic treatment with glucosamine attenuated insulin cardioprotection against myocardial infarction, arrhythmia and oxidative stress. Mechanistically, glucosamine treatment decreased insulin-stimulated Akt phosphorylation, a key modulator of cell survival. Furthermore, inhibition of O -GlcNAcylation via 6-diazo-5-oxo- l -norleucine (DON) apparently increased insulin-induced Akt phosphorylation and restored its cardioprotective response against reperfusion injury in palmitate-induced insulin-resistant H9c2 cells. Our findings demonstrated that obesity-induced hyper- O -GlcNAcylation might contribute to the attenuation of insulin cardioprotection against I/R injury. Proposed mechanisms by which hyper- O -GlcNAcylation impairs the insulin response against reperfusion-induced myocardial injury and arrhythmias in obesity. Akt O -GlcNAcylation decreased insulin-stimulated phosphorylation, thus resulting in an impaired insulin response against reperfusion injury. [Display omitted] • Increased O-GlcNAcylation via GlcN attenuated insulin-induced cardioprotection. • Glucosamine treatment decreased insulin-stimulated Akt phosphorylation. • Inhibition of O-GlcNAcylation via DON resensitized insulin response. [ABSTRACT FROM AUTHOR]