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BACKGROUND: In the USA, the prolonged effective survival of cancer population has brought significant attention to the rising risk of cardiometabolic morbidity and mortality in this population. This heightened risk underscores the urgent need for research into effective pharmacological interventions for cancer survivors. Notably, metformin, a well-known metabolic regulator with pleiotropic effects, has shown protective effects against cardiometabolic disorders in diabetic individuals. Despite these promising indications, evidence supporting its efficacy in improving cardiometabolic outcomes in cancer survivors remains scarce. METHODS: A prospective cohort was established using a nationally representative sample of cancer survivors enrolled in the US National Health and Nutrition Examination Survey (NHANES), spanning 2003 to 2018. Outcomes were derived from patient interviews, physical examinations, and public-access linked mortality archives up to 2019. The Oxidative Balance Score was utilized to assess participants' levels of oxidative stress. To evaluate the correlations between metformin use and the risk of cardiometabolic diseases and related mortality, survival analysis of cardiometabolic mortality was performed by Cox proportional hazards model, and cross-sectional analysis of cardiometabolic diseases outcomes was performed using logistic regression models. Interaction analyses were conducted to explore the specific pharmacological mechanism of metformin. RESULTS: Among 3995 cancer survivors (weighted population, 21,671,061, weighted mean [SE] age, 62.62 [0.33] years; 2119 [53.04%] females; 2727 [68.26%] Non-Hispanic White individuals), 448 reported metformin usage. During the follow-up period of up to 17 years (median, 6.42 years), there were 1233 recorded deaths, including 481 deaths from cardiometabolic causes. Multivariable models indicated that metformin use was associated with a lower risk of all-cause (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.47-0.81) and cardiometabolic (HR, 0.65; 95% CI, 0.44-0.97) mortality compared with metformin nonusers. Metformin use was also correlated with a lower risk of total cardiovascular disease (odds ratio [OR], 0.41; 95% CI, 0.28-0.59), stroke (OR, 0.44; 95% CI, 0.26-0.74), hypertension (OR, 0.27; 95% CI, 0.14-0.52), and coronary heart disease (OR, 0.41; 95% CI, 0.21-0.78). The observed inverse associations were consistent across subgroup analyses in four specific cancer populations identified as cardiometabolic high-risk groups. Interaction analyses suggested that metformin use as compared to non-use may counter-balance oxidative stress. CONCLUSIONS: In this cohort study involving a nationally representative population of US cancer survivors, metformin use was significantly correlated with a lower risk of cardiometabolic diseases, all-cause mortality, and cardiometabolic mortality.
Subject(s)
Cancer Survivors , Cardiovascular Diseases , Metformin , Humans , Metformin/therapeutic use , Female , Male , Cancer Survivors/statistics & numerical data , Middle Aged , United States/epidemiology , Cardiovascular Diseases/mortality , Prospective Studies , Hypoglycemic Agents/therapeutic use , Aged , Cross-Sectional Studies , Nutrition Surveys , Cohort Studies , Neoplasms/mortalityABSTRACT
BACKGROUND: Left bundle branch block (LBBB) and atrial fibrillation (AF) are commonly coexisting conditions. The impact of LBBB on catheter ablation of AF has not been well determined. This study aims to explore the long-term outcomes of patients with AF and LBBB after catheter ablation. METHODS: Forty-two patients with LBBB of 11,752 patients who underwent catheter ablation of AF from 2011 to 2020 were enrolled as LBBB group. After propensity score matching in a 1:4 ratio, 168 AF patients without LBBB were enrolled as non-LBBB group. Late recurrence and a composite endpoint of stroke, all-cause mortality, and cardiovascular hospitalization were compared between the two groups. RESULTS: Late recurrence rate was significantly higher in the LBBB group than that in the non-LBBB group (54.8% vs. 31.5%, p = .034). Multivariate analysis showed that LBBB was an independent risk factor for late recurrence after catheter ablation of AF (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.09-4.40, p = .031). LBBB group was also associated with a significantly higher incidence of the composite endpoint (21.4% vs. 6.5%, HR 3.98, 95% CI 1.64-9.64, p = .002). CONCLUSIONS: LBBB was associated with a higher risk for late recurrence and a higher incidence of composite endpoint in the patients underwent catheter ablation.
Subject(s)
Atrial Fibrillation , Catheter Ablation , Stroke , Humans , Bundle-Branch Block/etiology , Risk Factors , Stroke/etiology , Catheter Ablation/adverse effects , Treatment Outcome , RecurrenceABSTRACT
In animal studies, sodium-glucose co-transporter-2 inhibitors-such as empagliflozin-have been shown to improve heart failure and impaired cardiac contractility induced by anthracyclines-including doxorubicin-although the therapeutic mechanism remains unclear. Moreover, abnormalities in Ca2+ handling within ventricular myocytes are the predominant feature of heart failure. Accordingly, this study aimed to investigate whether empagliflozin can alleviate Ca2+ handling disorders induced by acute doxorubicin exposure and elucidate the underlying mechanisms. To this end, ventricular myocytes were isolated from C57BL/6 mice. Contraction function, Ca2+ handling, and mitochondrial reactive oxygen species (ROS) generation were then evaluated using IonOptix or confocal microscopy. Ca2+ handling proteins were detected by western blotting. Results show that incubation with 1 µmol/L of doxorubicin for 120-min impaired cardiac contractility in isolated myocytes, which was significantly alleviated by pretreatment with 1 µmol/L of empagliflozin. Doxorubicin also markedly induced Ca2+ handling disorders, including decreased Ca2+ transients, prolonged Ca2+ transient decay time, enhanced frequency of Ca2+ sparks, and decreased Ca2+ content in the sarcoplasmic reticulum. These dysregulations were improved by pretreatment with empagliflozin. Moreover, empagliflozin effectively inhibited doxorubicin-induced mitochondrial ROS production in isolated myocytes and rescued doxorubicin-induced oxidation of Ca2+/calmodulin-dependent protein kinase II (ox-CaMKII) and CaMKII-dependent phosphorylation of RyR2. Similarly, preincubation with 10 µmol/L Mito-TEMPO mimicked the protective effects of empagliflozin. Collectively, Empagliflozin ameliorated the doxorubicin-induced contraction malfunction and Ca2+-handling disorders. These findings suggest that empagliflozin alleviates Ca2+-handling disorders by improving ROS production in the mitochondria and alleviating the enhanced oxidative CaMKII signaling pathway induced by doxorubicin.
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BACKGROUND & AIMS: The individual effect of working schedule on survival in the hypertensive population has not been adequately studied. Shiftworkers are also prone to unhealthy lifestyles like pro-inflammatory diet. Therefore, we assessed the effect of shift work and its joint association with dietary inflammatory potential on mortality risk among the large US nationally representative sample of adult hypertensive population. METHODS: Data were from a nationally representative prospective cohort among US hypertensive population (n = 3680; weighted population, 54,192,988). The participants were linked to the 2019 public-access linked mortality archives. The working schedule were self-reported using the Occupation Questionnaire Section. Dietary inflammatory index (DII) scores were equally calculated using the 24-hour dietary recall (24 h) interviews. Multivariable Cox proportional hazards regression models were used to estimate hazard ratio and 95% confidence intervals (95%CI) for survival of hypertension individuals by work schedule and dietary inflammatory potential. The joint effect of work schedule and dietary inflammatory potential was then examined. RESULTS: Among the 3680 hypertension individuals (39.89% female [n = 1479] and 71.42% white [n = 1707]; weighted mean [SE] age, 47.35 [0.32] years), 592 individuals reported shift work status. 474 (10.76%) reported shift work status with pro-inflammatory dietary pattern (DII scores > 0). 118 (3.06%) reported shift work status with anti-inflammatory dietary pattern (DII scores < 0). 646 (19.64%) reported a non-shift working schedule with anti-inflammatory dietary pattern, while 2442 (66.54%) reported non-shift working schedule with pro-inflammatory dietary pattern. After a median follow-up of 11.67 years (140 months), 317 deaths (cardiovascular diseases (CVD), 65; cancer, 104) were registered. Cox regression analysis showed that shift work was associated with higher risk of all-cause mortality (hazard ratio [HR], 1.48; 95% CI, 1.07-2.06) compared with non-shift workers. In the joint analysis, shift work status combined with pro-inflammatory dietary pattern was associated with the highest all-cause mortality risk. Moreover, adopting the anti-inflammatory diet significantly attenuates the deleterious effect of shift work on mortality risk. CONCLUSIONS: In this large representative sample of adults with hypertension in the U.S., the combination of shift work status with pro-inflammatory dietary pattern was highly prevalent and was associated with the highest risks of death from all causes.
Subject(s)
Cardiovascular Diseases , Hypertension , Shift Work Schedule , Adult , Humans , Female , Middle Aged , Male , Risk Factors , Inflammation , Prospective Studies , Diet , Hypertension/epidemiology , Hypertension/complicationsABSTRACT
OBJECTIVE: This study aimed to evaluate the feasibility of real-time visualization and mapping of the right phrenic nerve (RPN) by using intracardiac echocardiography (ICE) during atrial fibrillation (AF) ablation. BACKGROUND: RPN injury is a complication associated with the ablation of AF. Multiple approaches are currently being used to prevent and detect RPN injuries. However, none of these approaches can directly visualize the RPN in real-time during the ablation procedure. METHODS AND RESULTS: The RPN was detected using ICE. The RPN and its adjacent structures were analysed. The relationship between the RPN's distance from the superior vena cava (SVC) and its pacing capture threshold was quantified. The safety of SVC isolation guided by the ICE-visualized RPN was evaluated. Thirty-eight people were enrolled in this study. The RPN was visualized by ICE in 92% of patients. It ran through the space between the SVC and the mediastinal pleura and had a 'straw'-like appearance upon ICE imaging. The course of the RPN was close to the SVC (minimum 1.0 ± 0.4 mm) and the right superior pulmonary vein (minimum 14.1 ± 7.3 mm). There was a positive linear correlation between the RPN's capture threshold and its distance from the SVC (Spearman's correlation coefficient = 0.728, < 0.001). SVC isolation was guided by the RPN; none of the patients developed an RPN injury. CONCLUSIONS: RPN can be visualized by ICE in most patients, thus providing a novel approach for the real-time detection of RPN during AF ablation.
Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Humans , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/surgery , Phrenic Nerve/injuries , Vena Cava, Superior/diagnostic imaging , Vena Cava, Superior/surgery , Catheter Ablation/adverse effects , Catheter Ablation/methods , Echocardiography , Pulmonary Veins/diagnostic imaging , Pulmonary Veins/surgeryABSTRACT
AIMS: Heart failure (HF) is one of the leading causes of the global burden of disability and mortality. However, the comprehensive epidemic status of HF in China is unclear. Notably, the gender-specific survey for HF prevalence is lacking. The present study aimed to analyse the gender-specific prevalence and temporal trend of HF in China and explore the attributable aetiology and risk factors. METHODS AND RESULTS: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 was used to evaluate the age-standardized prevalence and years lived with disability of HF in China by gender. The temporal trend of HF and attributable risk factors were analysed by Joinpoint regression models from 1990 to 2019. The total age-standardized prevalence rate of HF steadily decreased over the past two decades from 1079.4 to 1032.8 per 100 000 individuals. Since 2017, the prevalence trend of HF has significantly increased [annual percentage change (APC) of 2.72 for females and 0.61 for males, P < 0.05]. In 2019, the age-standardized rate of HF prevalence in females surpassed that of males, and hypertensive heart disease was the leading cause of HF for females (42.65% of cases) and males (41.19% of cases). From 2017 to 2019, high systolic pressure contributed to most cases of HF-related hypertensive heart disease, with an APC of 2.68 for females and 0.48 for males (P < 0.05). CONCLUSIONS: Although HF prevalence has steadily decreased over the past two decades, an increasing trend has occurred since 2017, especially for females. The leading cause of HF was hypertensive heart disease. Metabolic risks, particularly high systolic pressure, consistently contribute to the prevalence of heart diseases leading to HF. Promoting HF screening and controlling metabolic risks at the population level are imperative. Gender differences in HF prevalence should be considered.
Subject(s)
Disabled Persons , Heart Failure , Hypertension , Male , Female , Humans , Prevalence , Risk Factors , Heart Failure/epidemiologyABSTRACT
PURPOSE: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of glucose-lowering agents that have improved clinical outcomes in patients with heart failure; however, their therapeutic mechanisms remain elusive. Although contradictory results have been reported, it has been proposed that improving Na+ homeostasis may be the underlying mechanism of action of SGLT2 inhibitors in heart failure treatment. This study explored whether empagliflozin ameliorates Na+ and Ca2+ handling disorders induced by ouabain in an Na+-dependent manner. METHODS: Isolated ventricular myocytes of mice were incubated with ouabain to establish a cellular model of Na+ overload. Effects of empagliflozin on Na+ and Ca2+ handling were evaluated using an ionOptix system and a confocal microscope. Distinct cytosolic Na+ levels were established by incubating different ouabain concentrations (10, 50, and 100 µmol/L). RESULTS: In the absence of ouabain, 1 µmol/L empagliflozin had a negligible impact on Na+ and Ca2+ handling in ventricular myocytes. Ouabain (50 µmol/L) significantly enhanced cytosolic Na+ levels and dysregulated Ca2+ handling, including an increased Ca2+ transient amplitude, elevated Ca2+ content in the sarcoplasmic reticulum, and enhanced spontaneous Ca2+ release normalized by treatment with 1 µmol/L empagliflozin within 10 min. All Na+ and Ca2+ handling abnormalities induced by ouabain were reversed by 1 µmol/L empagliflozin. The efficacy of empagliflozin was more potent at higher cytosolic Na+ levels. Pretreatment with the Na+/H+ exchanger (NHE) inhibitor (1 µmol/L cariporide) abolished the effects of empagliflozin. CONCLUSION: Empagliflozin ameliorates ouabain-induced Na+ and Ca2+ handling disorders in a cytosolic Na+-dependent manner, potentially by inhibiting the NHE.
Subject(s)
Heart Failure , Ouabain , Mice , Animals , Ouabain/pharmacology , Myocytes, Cardiac , Sodium/pharmacology , Glucose/pharmacology , Calcium/pharmacologyABSTRACT
Cardiotoxicity is the major side effect of anthracyclines (doxorubicin, daunorubicin, epirubicin, and idarubicin), though being the most commonly used chemotherapy drugs and the mainstay of therapy in solid and hematological neoplasms. Advances in the field of cardio-oncology have expanded our understanding of the molecular mechanisms underlying anthracycline-induced cardiotoxicity (AIC). AIC has a complex pathogenesis that includes a variety of aspects such as oxidative stress, autophagy, and inflammation. Emerging evidence has strongly suggested that the loss of mitochondrial quality control (MQC) plays an important role in the progression of AIC. Mitochondria are vital organelles in the cardiomyocytes that serve as the key regulators of reactive oxygen species (ROS) production, energy metabolism, cell death, and calcium buffering. However, as mitochondria are susceptible to damage, the MQC system, including mitochondrial dynamics (fusion/fission), mitophagy, mitochondrial biogenesis, and mitochondrial protein quality control, appears to be crucial in maintaining mitochondrial homeostasis. In this review, we summarize current evidence on the role of MQC in the pathogenesis of AIC and highlight the therapeutic potential of restoring the cardiomyocyte MQC system in the prevention and intervention of AIC.
Subject(s)
Anthracyclines , Cardiotoxicity , Anthracyclines/toxicity , Antibiotics, Antineoplastic/pharmacology , Calcium/metabolism , Cardiotoxicity/metabolism , Daunorubicin/metabolism , Daunorubicin/pharmacology , Doxorubicin/pharmacology , Epirubicin/metabolism , Epirubicin/pharmacology , Humans , Idarubicin/metabolism , Idarubicin/pharmacology , Mitochondria/metabolism , Mitochondrial Proteins/metabolism , Myocytes, Cardiac/metabolism , Reactive Oxygen Species/metabolismABSTRACT
Background: The impact of elevated resting heart rate on early-stage renal dysfunction, manifesting as microalbuminuria, in hypertension is unclear. This study aimed to analyze the association between resting heart rate and microalbuminuria in patients with hypertension according to their blood pressure status. In addition, the effect of antihypertensive agents on this relationship was evaluated. Methods and Results: We searched the National Health and Nutrition Examination Survey for eligible participants from 2009 to 2018. Data on key parameters such as age, sex, blood pressure, heart rate, albumin creatinine ratio, and medication were collected for analysis. Subsequently, participants were classified according to the heart rate quartile and blood pressure status for subgroups assessment. A total of 5,692 participants were enrolled in this study. After adjusting the confounding factors, there was a linear association between resting heart rate and microalbuminuria in patients with hypertension (OR 1.184 [per 1 SD]; 95% CI: 1.101, 1.274; P < 0.001). However, the association between elevated resting heart rate and microalbuminuria was not significant in patients with uncontrolled hypertension (OR 1.092 [per 1 SD]; 95% CI: 0.935, 1.275; P = 0.269). The OR of the indirect effect of ß-blockers on the risk of microalbuminuria incidence through heart rate was 0.926 (95% CI: 0.895, 0.956), while the direct effect was 1.374 (95% CI: 1.138, 1.662, P = 0.010). Similarly, dihydropyridine calcium channel blockers were associated with a higher prevalence of microalbuminuria (OR 1.300, 95% CI: 1.058, 1.597, P = 0.013), but the association between non-dihydropyridine calcium channel blockers and microalbuminuria was not significant (OR 1.207, 95% CI: 0.737, 1.978, P = 0.454). Conclusion: Elevated resting heart rate is associated with a high risk of microalbuminuria in untreated patients and patients with controlled hypertension. Although there is a linear association between heart rate and microalbuminuria, the use of ß-blockers exhibits a significantly increase in the prevalence of microalbuminuria in hypertension. Likewise, dihydropyridine calcium channel blockers may increase the risk of microalbuminuria in hypertension.
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Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe yet rare inherited arrhythmia disorder. The cornerstone of CPVT medical therapy is the use of ß-blockers; 30% of patients with CPVT do not respond well to optimal ß-blocker treatment. Studies have shown that flecainide effectively prevents life-threatening arrhythmias in CPVT. Flecainide is a class IC antiarrhythmic drug blocking cardiac sodium channels. RyR2 inhibition is proposed as the principal mechanism of antiarrhythmic action of flecainide in CPVT, while it is highly debated. In this article, we review the current progress of this issue.
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This study investigated the developmental cascades of marital quality, harsh discipline, and child externalizing behavior in a Chinese sample of 976 father-mother dyads and their children (initial Mage = 7.63 years, 52.2% boys). Marital quality, harsh discipline, and child externalizing behavior were assessed at three annual measurement occasions. Cascade models indicated the unidirectional rather than bidirectional relations between the variables over and above within-time covariance and across-time stability. Both increased maternal and paternal marital quality in a given year predicted decreases in child externalizing behavior in the next year. Child externalizing behavior in a given year predicted increases in both maternal and paternal harsh discipline in the next year. Moreover, increased paternal but not maternal marital quality in a given year predicted decreases in psychological aggression rather than corporal punishment in the next year. Moreover, the indirect effect of marital quality on child externalizing behavior through harsh discipline was not found. In addition, the potential indirect effect of marital quality on harsh discipline through child externalizing behavior was observed. These findings highlight the importance of examining developmental cascades across family subsystems and efforts to improve marital relationship to promote child adjustment as well as parent-child interaction during middle childhood in Chinese society.
Subject(s)
Child Behavior , Marriage , Parent-Child Relations , Punishment , Child , Child Behavior/psychology , China , Female , Humans , Male , Punishment/psychologyABSTRACT
We demonstrate a widely applicable method to alter the adsorption configuration of multi-carbon containing reactants by no catalyst engineering but simply adjusting the local reaction environment of the catalyst surface. Using electrocatalytic acetone to propane hydrogenation (APH) as a model reaction and common commercial Pt/Pt-based materials as catalysts, we found local H+ concentration can significantly influence the adsorption mode of acetone reactant, for example, in vertical or flat mode, and target product selectivity. Electrocatalytic measurement combined with in situ spectroscopic characterizations reveals that the vertically adsorbed acetone is favorable for propane production while the flatly adsorbed mode suppresses the reaction. DFT calculations indicate that the H coverage on catalyst surface plays a decisive role in the adsorption configuration of acetone. The increased local acidity can facilitate the adsorption configuration of acetone from flat to vertical mode and suppress the competing hydrogen evaluation reaction, which consequently enhances the APH selectivity.
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Background: Post-cardiac procedure atrial fibrillation (PCP-AF) is a significant medical problem. Inflammation is one of the key factors in the pathogenesis of PCP-AF. As a classical anti-inflammatory drug, colchicine may prevent the occurrence of PCP-AF. This meta-analysis of 12 randomized controlled trials (RCTs) analyzed the feasibility and safety of colchicine for the prevention of PCP-AF. Methods: PubMed, EMBASE, Web of Science, the Cochrane Library, and Google Scholar were retrieved for RCTs on the efficacy of colchicine in preventing atrial fibrillation. The primary endpoint was the diagnosis of PCP-AF, which includes cardiac surgery or pulmonary vein isolation. Evaluation was performed with estimated odds ratios (OR) and 95% confidence intervals (CI). Results: In this meta-analysis, 12 RCTs were selected and a total of 2297 patients were included. Colchicine therapy was associated with a reduced incidence of PCP-AF both in post-cardiac surgery (OR: 0.62; 95% CI: 0.49-0.78, p < 0.0001, I 2 = 0%), and in post-pulmonary vein isolation (OR: 0.43; 95% CI: 0.30-0.62, p < 0.0001, I 2 = 0%). Colchicine therapy was associated with increased side effects (OR: 2.81; 95% CI: 1.96-4.03, p < 0.00001, I 2 = 26%). Conclusion: Colchicine can effectively prevent post-cardiac operative atrial fibrillation and relapse of atrial fibrillation after pulmonary vein isolation (PVI). However, colchicine can also increase the incidence of side effects, mainly gastrointestinal adverse events. More studies are needed to find a more appropriate treatment dose and time.
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BACKGROUND: Green tea has been one of the most popular beverages in China since ancient times. Mixed results concerning the effect of green tea consumption on the incidence of hypertension have been published over the past decades. However, no previous studies have focused on longevous individuals in China and the sex differences in the association between habitual green tea intake and hypertension. METHODS: The data extracted from the database of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2018 were used for a secondary analysis. Logistic regression models were employed to examine the odds ratio (OR) of daily green tea consumption on the incidence of hypertension by sex. RESULTS: A total of 9277 individuals were included in the analysis (39.8% were men). The included individuals had a mean age of 80.9 and 84.8 years for those who drank green tea daily and those who had never, respectively (p < 0.001). The incidence of hypertension varied at baseline according to green tea drinking habit and sex. For women who had a habitual green tea intake or had never drunk green tea, the incidence of hypertension was 47.3 and 43.9%, respectively (p = 0.241), whereas it was 51.6 and 39.7% for men (p < 0.001). After adjusting for potential confounders, a 38% increase in the risk of hypertension was observed in men who consumed green tea daily (OR, 1.38; 95% CI, 1.15-1.67; p < 0.001). CONCLUSIONS: Chinese longevous men had a 38% higher risk of developing hypertension when drinking green tea daily. However, no effect of green tea consumption on the incidence of hypertension in women was found. More attention should be paid to the lifestyle of longevous individuals for health promotion, and a sex-specific approach to deliver care for very elderly people is warranted.
Subject(s)
Hypertension , Tea , Aged , Aged, 80 and over , China/epidemiology , Female , Humans , Hypertension/diagnosis , Hypertension/epidemiology , Incidence , Male , Risk Factors , Sex CharacteristicsABSTRACT
A single cardiomyocyte is a vital tool in the cellular and subcellular level studies of cardiac biology and diseases as a fundamental unit of contraction and electrical activity. Hence, isolating viable, high-quality cardiomyocytes from the heart is the initial and most crucial experimental step. Comparing the various protocols for isolating the cardiomyocytes of adult mice, the Langendorff retrograde perfusion is the most successful and reproducible method reported in the literature, especially for isolating ventricular myocytes. However, isolating quality atrial myocytes from the perfused heart remains challenging, and few successful isolation reports are available. Solving this complicated problem is extremely important because apart from ventricular disease, atrial disease accounts for a large part of heart diseases. Therefore, further investigations on the cellular level to reveal the mechanisms are warranted. In this paper, a protocol based on the Langendorff retrograde perfusion method is introduced and some modifications in the depth of aorta cannulation and the steps that may affect the digestion process to isolate atrial and ventricular myocytes were simultaneously made. Moreover, the isolated cardiomyocytes are confirmed to be amenable to patch clamp investigation.
Subject(s)
Heart Atria , Heart Ventricles , Myocytes, Cardiac , Animals , Cell Separation , Mice , PerfusionABSTRACT
Present one-step N2 fixation is impeded by tough activation of the N≡N bond and low selectivity to NH3 . Here we report fixation of N2 -to-NH3 can be decoupled to a two-step process with one problem effectively solved in each step, including: 1)â facile activation of N2 to NOx - by a non-thermal plasma technique, and 2)â highly selective conversion of NOx - to NH3 by electrocatalytic reduction. Importantly, this process uses air and water as low-cost raw materials for scalable ammonia production under ambient conditions. For NOx - reduction to NH3 , we present a surface boron-rich core-shell nickel boride electrocatalyst. The surface boron-rich feature is the key to boosting activity, selectivity, and stability via enhanced NOx - adsorption, and suppression of hydrogen evolution and surface Ni oxidation. A significant ammonia production of 198.3â µmol cm-2 h-1 was achieved, together with nearly 100 % Faradaic efficiency.
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Electrocatalytic production of hydrogen from seawater provides a route to low-cost and clean energy conversion. However, the hydrogen evolution reaction (HER) using seawater is greatly hindered by the lack of active and stable catalysts. Herein, an unsaturated nickel surface nitride (Ni-SN@C) catalyst that is active and stable for the HER in alkaline seawater is prepared. It achieves a low overpotential of 23 mV at a current density of 10 mA cm-2 in alkaline seawater electrolyte, which is superior to Pt/C. Compared to conventional transition metal nitrides or metal/metal nitride heterostructures, the Ni-SN@C has no detectable bulk nickel nitride phase. Instead, unsaturated NiN bonding on the surface is present. In situ Raman measurements show that the Ni-SN@C performs like Pt with the ability to generate hydronium ions in a high-pH electrolyte. The catalyst operation is then demonstrated in a two-electrode electrolyzer system, coupling with hydrazine oxidation at the anode. Using this system, a cell voltage of only 0.7 V is required to achieve a current density of 1 A cm-2 .
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Most fundamental studies of electrocatalysis are based on the experimental and simulation results obtained for bulk model materials. Some of these mechanistic understandings are inapplicable for more active nanostructured electrocatalysts. Herein, considering the simplest and most typical electrocatalytic process, the hydrogen evolution reaction, an alternative reaction mechanism is proposed for nanomaterials based on the identification of a new intermediate, which differs from those commonly known for the bulk counterparts. In-situ Raman spectroscopy and electrochemical thermal/kinetic measurements were conducted on a series of nanomaterials under different conditions. In high-pH electrolytes with negligible hydronium (H3O+) concentration in bulk phase, massive H3O+ intermediates are found generating on the catalytic surface during water dissociation and hydrogen adsorption processes. These H3O+ intermediates create a unique acid-like local reaction environment on nanostructured catalytic surfaces and cut the energy barrier of the overall reaction. Such phenomena on nanostructured electrocatalysts explain their widely observed anomalously high activity under high-pH conditions.
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Since first being reported as possible electrocatalysts to substitute platinum for the oxygen reduction reaction (ORR), carbon-based metal-free nanomaterials have been considered a class of promising low-cost materials for clean and sustainable energy-conversion reactions. However, beyond the ORR, the development of carbon-based catalysts for other electrocatalytic reactions is still limited. More importantly, the intrinsic activity of most carbon-based metal-free catalysts is inadequate compared to their metal-based counterparts. To address this challenge, more design strategies are needed in order to improve the overall performance of carbon-based materials. Herein, using water splitting as an example, some state-of-the-art strategies in promoting carbon-based nanomaterials are summarized, including graphene, carbon nanotubes, and graphitic-carbon nitride, as highly active electrocatalysts for hydrogen evolution and oxygen evolution reactions. It is shown that by rationally tuning the electronic and/or physical structure of the carbon nanomaterials, adsorption of reaction intermediates is optimized, consequently improving the apparent electrocatalytic performance. These strategies may facilitate the development in this area and lead to the discovery of advanced carbon-based nanomaterials for various applications in energy-conversion processes.
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BACKGROUND: Chemokine (C-C) ligand-2 (CCL2), also named monocyte chemoattractant protein 1 (MCP-1), is an important chemotactic factor involved in a wide range of diseases. Recent studies have shown that CCL2/MCP-1 plays crucial roles in the osteoclastogenic process. The current study was performed to measure serum CCL2 levels in postmenopausal osteoporotic patients and investigate the relationship between CCL2 concentrations in serum and disease severity in postmenopausal osteoporotic patients. METHODS: A total of 62 postmenopausal osteoporotic female patients (PMOP group), 68 postmenopausal non-osteoporotic female patients (PMNOP group), and 65 healthy women of childbearing age (Control group) were enrolled in the study. The calcaneal quantitative ultrasound was utilized to conduct bone mineral density (BMD) measurements, confirmed at the left femoral neck, greater trochanter, total hip, and L1 - L4 lumbar spine by dual energy X-ray absorptiometry (DXA). Serum CCL2, TNF-α as well as IL-6 levels were measured with enzyme-linked immunosorbent assay. Estrogen-2 (E2) was measured with radioimmunoassay. The Visual Analogue Scores (VAS) was utilized to assess the extent of pain in PMOP. RESULTS: We demonstrated for the first time that CCL2 levels were increased in postmenopausal women compared with controls. We also found that elevated CCL2 levels were linked with decreased BMD and attenuated E2 concentrations. In addition, CCL2 levels were positively correlated with inflammation markers TNF-α, IL-6, and VAS scores. CONCLUSIONS: CCL2 in serum serves as a potential biomarker for reflecting disease severity in postmenopausal osteoporotic patients. Therapeutic interventions that target CCL2 and its related signaling pathways in order to delay osteoporosis development deserve further study.