Prevention and Reversal of Atrial Fibrillation Inducibility and Autonomic Remodeling by Low-Level Vagosympathetic Nerve Stimulation

ObjectivesWe hypothesized that autonomic atrial remodeling can be reversed by low-level (LL) vagosympathetic nerve stimulation (VNS).BackgroundPreviously, we showed that VNS can be antiarrhythmogenic.MethodsThirty-three dogs were subjected to electrical stimulation (20 Hz) applied to both vagosympathetic trunks at voltages 10% to 50% below the threshold that slowed sinus rate or AV conduction. Group 1 (n = 7): Programmed stimulation (PS) was performed at baseline and during 6-h rapid atrial pacing (RAP). PS allowed determination of effective refractory period (ERP) and AF inducibility measured by window of vulnerability (WOV). LL-VNS was continuously applied from the 4th to 6th hours. Group 2 (n = 4): After baseline ERP and WOV determinations, 6-h concomitant RAP+LL-VNS was applied. Sustained AF was induced by injecting acetylcholine (ACh) 10 mM into the anterior right ganglionated plexus (Group 3, n = 10) or applying ACh 10 mM to right atrial appendage (Group 4, n = 9).ResultsGroup 1: The ERP progressively shortened and the ΣWOV (sum of WOV from all tested sites) progressively increased (p < 0.05) during 3-h RAP then returned toward baseline during 3-h RAP+LL-VNS (p < 0.05). Group 2: 6-h concomitant RAP+LL-VNS did not induce any significant change in ERP and ΣWOV. Group 3 and Group 4: AF duration (AF-D) and cycle length (AF-CL) were markedly altered by 3-h LL-VNS (Group 3: baseline: AF-D = 389 ± 90 s, AF-CL = 45.1 ± 7.8 ms; LL-VNS: AF-D = 50 ± 15 s, AF-CL = 82.0 ± 13.7 ms [both p < 0.001]; Group 4: baseline: AF-D = 505 ± 162 s, AF-CL = 48.8 ± 6.6 ms; LL-VNS: AF-D = 71 ± 21 s, AF-CL = 101.3 ± 20.9 ms [both p < 0.001]).ConclusionsLL-VNS can prevent and reverse atrial remodeling induced by RAP as well as suppress AF induced by strong cholinergic stimulation. Inhibition of the intrinsic cardiac autonomic nervous system by LL-VNS may be responsible for these salutary results

KLF15 and PPAR α

The metabolic myocardium is an omnivore and utilizes various carbon substrates to meet its energetic demand. While the adult heart preferentially consumes fatty acids (FAs) over carbohydrates, myocardial fuel plasticity is essential for organismal survival. This metabolic plasticity governing fuel utilization is under robust transcriptional control and studies over the past decade have illuminated members of the nuclear receptor family of factors (e.g., PPARα) as important regulators of myocardial lipid metabolism. However, given the complexity of myocardial metabolism in health and disease, it is likely that other molecular pathways are likely operative and elucidation of such pathways may provide the foundation for novel therapeutic approaches. We previously demonstrated that Kruppel-like factor 15 (KLF15) is an independent regulator of cardiac lipid metabolism thus raising the possibility that KLF15 and PPARα operate in a coordinated fashion to regulate myocardial gene expression requisite for lipid oxidation. In the current study, we show that KLF15 binds to, cooperates with, and is required for the induction of canonical PPARα-mediated gene expression and lipid oxidation in cardiomyocytes. As such, this study establishes a molecular module involving KLF15 and PPARα and provides fundamental insights into the molecular regulation of cardiac lipid metabolism

High-resolution record of temporal change in organic matter burial over the past ∼8,600 years on the northwestern continental slope of the South China Sea

Sedimentary organic matter (SOM) on continental slopes in marine regions can sensitively record climatic and environmental changes. In this study, total organic carbon content (TOC), total nitrogen content (TN), and their stable isotope compositions (δ13C and δ15N) for sediments of core G02 were investigated (at ∼24.2-year resolution) to reveal the temporal variations in organic matter sources and the main controls on the sources and distribution of buried organic matter on the northwestern continental slope of the South China Sea over the last ∼8600 years. Results of a δ13C binary mixing model reveal that ∼82.3 ± 3% of SOM is derived from marine autochthonous sources. We suggest that the carbon and nitrogen contents and compositions of SOM are governed by distinct factors. The more positive δ15N values before the Pulleniatina Minimum Event occurrence are ascribed to stronger subsurface water intrusion by the Kuroshio Current, which led to enhanced subsurface denitrification and in turn counteracted the effect of mixing with surface water caused by the East Asian winter monsoon. Sedimentary δ13C values show a fluctuant decrease during ca. 8.6–3.0 cal kyr BP and a conspicuous increase during ca. 3.0–1.4 cal kyr BP. These changes are attributed to the decrease of marine productivity induced by the continuous weakening East Asian monsoon effect and the decrease of terrigenous organic carbon input induced by the weakened Indian summer monsoon precipitation, respectively. Since ca. 1.4 cal kyr BP, human activities have become the dominant factor in controlling the production and distribution of organic carbon. The results provide an important basis for understanding of source-sink processes of organic matter and the factors influencing these processes on continental slopes in low-latitude marginal seas

Kruppel-like Factor 15 Is a Critical Regulator of Cardiac Lipid Metabolism

Background: Metabolic homeostasis is central to normal cardiac function. The molecular mechanisms underlying metabolic plasticity in the heart remain poorly understood. Results: Kruppel-like factor 15 (KLF15) is a direct and independent regulator of myocardial lipid flux. Conclusion: KLF15 is a core component of the transcriptional circuitry that governs cardiac metabolism. Significance: This work is the first to implicate the KLF transcription factor family in cardiac metabolism. The mammalian heart, the body\u27s largest energy consumer, has evolved robust mechanisms to tightly couple fuel supply with energy demand across a wide range of physiologic and pathophysiologic states, yet, when compared with other organs, relatively little is known about the molecular machinery that directly governs metabolic plasticity in the heart. Although previous studies have defined Kruppel-like factor 15 (KLF15) as a transcriptional repressor of pathologic cardiac hypertrophy, a direct role for the KLF family in cardiac metabolism has not been previously established. We show in human heart samples that KLF15 is induced after birth and reduced in heart failure, a myocardial expression pattern that parallels reliance on lipid oxidation. Isolated working heart studies and unbiased transcriptomic profiling in Klf15-deficient hearts demonstrate that KLF15 is an essential regulator of lipid flux and metabolic homeostasis in the adult myocardium. An important mechanism by which KLF15 regulates its direct transcriptional targets is via interaction with p300 and recruitment of this critical co-activator to promoters. This study establishes KLF15 as a key regulator of myocardial lipid utilization and is the first to implicate the KLF transcription factor family in cardiac metabolism

Cd0.9Co0.1S Nanorods with an Internal Electric Field and Photothermal Effect Synergistically for Boosting Photocatalytic H2 Evolution

The paper reports a strategy to synthesize Cd0.9Co0.1S nanorods (NRs) via a one-pot solvothermal method. Remarkably, the pencil-shaped Cd0.9Co0.1S NRs with a large aspect ratio and good polycrystalline plane structure significantly shorten the photogenerated carrier transfer path and achieve fast separation. An appropriate amount of Co addition enhances visible light-harvesting and generates a photothermal effect to improve the surface reaction kinetics and increases the charge transfer rate. Moreover, the internal electric field facilitates the separation and transfer of carriers and effectively impedes their recombination. As a result, the optimized Cd0.9Co0.1S NRs yield a remarkable H2 evolution rate of 8.009 mmol·g−1·h−1, which is approximately 7.2 times higher than that of pristine CdS. This work improves the photocatalytic hydrogen production rate by tuning and optimizing electronic structures through element addition and using the photothermal synergistic effect

Development and Protection of Geological Resources in Datong Volcanic Cluster National Geopark

Volcanic resources are a kind of special tourism resources, with its unique geomorphologic features and geological structure, attracting a large number of tourists for sightseeing and visiting. Based on the development status of Datong Volcanic Cluster National Geopark, this paper analyzes the advantages, disadvantages, opportunities and challenges of the development of Datong Volcanic Cluster National Geopark, and puts forward some suggestions on the development and protection of volcanic Cluster geological resources

A Method for Safety Evaluation of Train Braking System Considering Multiple Types of Preventive Maintenance Cycles

The train braking system with redundant components has an essential effect on driver safety. In this paper, we consider the failure of K-out-of-N brake motors during operation and the redundant recovery by preventive maintenance. Two Continuous Time Markov Chains (CTMC) are used to model the working process and the preventive maintenance process of the braking system corresponding to the real situation of the train. Considering the maintenance effect of intermittent daily and cyclical overhaul with nested relationships, a new operation risk assessment model of the K-out-of-N system is developed to evaluate the effectiveness of the preventive maintenance of the train. Some safety parameters are solved based on the two coupled preventive maintenance periods, which conveniently design the safety of the train braking system. Finally, a case study illustrates the effectiveness of the safety evaluation method. The results show that we can trade off the effects of the multiple PM intervals on train safety considering the redundancy structure of the braking system by the proposed model