15 research outputs found
Mitofusin 2 Participates in Mitophagy and Mitochondrial Fusion Against Angiotensin II-Induced Cardiomyocyte Injury
BackgroundMitochondrial dynamics play a critical role in mitochondrial function. The mitofusin 2 (MFN2) gene encodes a mitochondrial membrane protein that participates in mitochondrial fusion to maintain and operate the mitochondrial network. Moreover, MFN2 is essential for mitophagy. In Ang II-induced cardiac remodeling, the combined effects of MFN2-mediated mitochondrial fusion and mitophagy are unclear. This study was designed to explore a novel strategy for preventing cardiomyocyte injury via modulation of mitochondrial dynamics.MethodsWe studied the function of MFN2 in mitochondrial fusion and mitophagy in Ang II-stimulated cardiomyocyte injury. Cardiomyocyte injury experiments, including reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and apoptosis rate of cardiomyocytes were performed. The mitochondrial morphology in cardiomyocytes was examined via transmission electron microscopy (TEM) and confocal microscopy. Autophagic levels in response to Ang II were examined by immunoblotting of autophagy-related proteins. Moreover, PINK1/MFN2/Parkin pathway-related proteins were examined.ResultsWith stimulation by Ang II, MFN2 expression was progressively reduced. MFN2 deficiency impaired mitochondrial quality, resulting in exacerbated mitochondrial damage induced by Ang II. The Ang II-induced increases in ROS production and apoptosis rate were alleviated by MFN2 overexpression. Moreover, MFN2 alleviated the Ang II-induced reduction in MMP. MFN2 promoted mitochondrial fusion, and MFN2 promoted Parkin translocation and phosphorylation, leading to mitochondrial autophagy. The effects of MFN2 overexpression were reversed by autophagy inhibitors.ConclusionMitofusin 2 promotes Parkin translocation and phosphorylation, leading to mitophagy to clear damaged mitochondria. However, the beneficial effects of MFN2 were reversed by autophagy inhibitors. Additionally, MFN2 participates in mitochondrial fusion to maintain mitochondrial quality. Thus, MFN2 participated in mitophagy and mitochondrial fusion against Ang II-induced cardiomyocyte injury
Deep Potential Molecular Dynamics Study of Propane Oxidative Dehydrogenation
Oxidative dehydrogenation (ODH) of light alkanes is a
key process
in the oxidative conversion of alkanes to alkenes, oxygenated hydrocarbons,
and COx (x = 1,2). Understanding
the underlying mechanisms extensively is crucial to keep the ODH under
control for target products, e.g., alkenes rather than COx, with minimal energy consumption, e.g., during the
alkene production or maximal energy release, e.g., during combustion.
In this work, deep potential (DP), a neural network atomic potential
developed in recent years, was employed to conduct large-scale accurate
reactive dynamic simulations. The model was trained on a sufficient
data set obtained at the density functional theory level. The intricate
reaction network was elucidated and organized in the form of a hierarchical
network to demonstrate the key features of the ODH mechanisms, including
the activation of propane and oxygen, the influence of propyl reaction
pathways on the propene selectivity, and the role of rapid H2O2 decomposition for sustainable and efficient ODH reactions.
The results indicate the more complex reaction mechanism of propane
ODH than that of ethane ODH and are expected to provide insights in
the ODH catalyst optimization. In addition, this work represents the
first application of deep potential in the ODH mechanistic study and
demonstrates the ample advantages of DP in the study of mechanism
and dynamics of complex systems
Finite integral transform method for analytical solutions of static problems of cylindrical shell panels
In this paper, a double finite integral transform method is developed for analytical bending solutions of non-Levy-type cylindrical shell panels without a free edge that were not obtained by classical semi-inverse methods. Three double finite integral transforms are imposed on the governing high-order partial differential equations, which, with some boundary conditions, yields the relationship between the transformed quantities and specific unknowns. Incorporating the inversions into the remaining boundary conditions leads to systems of linear algebraic equations, which determine the final analytical solutions. Comprehensive benchmark results for representative cylindrical shell panels with combinations of clamped and simply supported edges are presented, which are well validated by satisfactory agreement with other solution methods. Due to its rigorous and straightforward solution procedure, the developed method provides a solid easy-to-implement approach for exploring new analytical solutions
Bioinspired staggered-array structure design for flexible batteries
As a key component to enable future flexible and wearable electronics, flexible batteries have received great attention in recent years. While much progress has been achieved, few of these batteries have high bendability, high bulk volumetric energy density and high areal energy density simultaneously. Here, inspired by the mi-crostructures of bone and nacre, a novel staggered-array structure composed of thin sub-cells and soft adhesives is reported for flexible batteries. An analytic model, without any parameter fitting, is presented to study the mechanical behavior of the structure bent on a cylinder, which accurately captures the axial strains of the thin sub-cells and exhibits the effects of different parameters on strain reduction. Based on the results of the devel-oped model, a flexible lithium-ion battery is prepared as a demonstration, which simultaneously exhibits high bendability, high bulk volumetric energy density and high areal energy density. Owing to the thin soft adhesives, the interactions among thin sub-cells are substantially reduced, and the bulk volumetric energy density of the battery reaches as high as 92.3% of that of conventional batteries, indicating tremendous potential of the staggered-array structure for applications in flexible and wearable electronics
α-Ketoglutarate improves cardiac insufficiency through NAD+-SIRT1 signaling-mediated mitophagy and ferroptosis in pressure overload-induced mice
Abstract Background In heart failure (HF), mitochondrial dysfunction and metabolic remodeling lead to a reduction in energy productivity and aggravate cardiomyocyte injury. Supplementation with α-ketoglutarate (AKG) alleviated myocardial hypertrophy and fibrosis in mice with HF and improved cardiac insufficiency. However, the myocardial protective mechanism of AKG remains unclear. We verified the hypothesis that AKG improves mitochondrial function by upregulating NAD+ levels and activating silent information regulator 2 homolog 1 (SIRT1) in cardiomyocytes. Methods In vivo, 2% AKG was added to the drinking water of mice undergoing transverse aortic constriction (TAC) surgery. Echocardiography and biopsy were performed to evaluate cardiac function and pathological changes. Myocardial metabolomics was analyzed by liquid chromatography‒mass spectrometry (LC‒MS/MS) at 8 weeks after surgery. In vitro, the expression of SIRT1 or PINK1 proteins was inhibited by selective inhibitors and siRNA in cardiomyocytes stimulated with angiotensin II (AngII) and AKG. NAD+ levels were detected using an NAD test kit. Mitophagy and ferroptosis levels were evaluated by Western blotting, qPCR, JC-1 staining and lipid peroxidation analysis. Results AKG supplementation after TAC surgery could alleviate myocardial hypertrophy and fibrosis and improve cardiac function in mice. Metabolites of the malate-aspartate shuttle (MAS) were increased, but the TCA cycle and fatty acid metabolism pathway could be inhibited in the myocardium of TAC mice after AKG supplementation. Decreased NAD+ levels and SIRT1 protein expression were observed in heart of mice and AngII-treated cardiomyocytes. After AKG treatment, these changes were reversed, and increased mitophagy, inhibited ferroptosis, and alleviated damage in cardiomyocytes were observed. When the expression of SIRT1 was inhibited by a selective inhibitor and siRNA, the protective effect of AKG was suppressed. Conclusion Supplementation with AKG can improve myocardial hypertrophy, fibrosis and chronic cardiac insufficiency caused by pressure overload. By increasing the level of NAD+, the SIRT-PINK1 and SIRT1-GPX4 signaling pathways are activated to promote mitophagy and inhibit ferroptosis in cardiomyocytes, which ultimately alleviates cardiomyocyte damage
Spatio-Temporal Distribution of Total Nitrogen and Phosphorus in Dianshan Lake, China: The External Loading and Self-Purification Capability
Dominant negative mutation of the TGF-β receptor blocks hypoxia-induced pulmonary vascular remodeling
Hesperetin, a Promising Dietary Supplement for Preventing the Development of Calcific Aortic Valve Disease
Background: No effective therapeutic agents for calcific aortic valve disease (CAVD) are available currently. Dietary supplementation has been proposed as a novel treatment modality for various diseases. As a flavanone, hesperetin is widely abundant in citrus fruits and has been proven to exert protective effects in multiple diseases. However, the role of hesperetin in CAVD remains unclear. Methods: Human aortic valve interstitial cells (VICs) were isolated from aortic valve leaflets. A mouse model of aortic valve stenosis was constructed by direct wire injury (DWI). Immunoblotting, immunofluorescence staining, and flow cytometry were used to investigate the roles of sirtuin 7 (Sirt7) and nuclear factor erythroid 2-related factor 2 (Nrf2) in hesperetin-mediated protective effects in VICs. Results: Hesperetin supplementation protected the mice from wire-injury-induced aortic valve stenosis; in vitro, hesperetin inhibited the lipopolysaccharide (LPS)-induced activation of NF-κB inflammatory cytokine secretion and osteogenic factors expression, reduced ROS production and apoptosis, and abrogated LPS-mediated injury to the mitochondrial membrane potential and the decline in the antioxidant levels in VICs. These benefits of hesperetin may have been obtained by activating Nrf2–ARE signaling, which corrected the dysfunctional mitochondria. Furthermore, we found that hesperetin could directly bind to Sirt7 and that the silencing of Sirt7 decreased the effects of hesperetin in VICs and potently abolished the ability of hesperetin to increase Nrf2 transcriptional activation. Conclusions: Our work demonstrates that hesperetin plays protective roles in the aortic valve through the Sirt7–Nrf2–ARE axis; thus, hesperetin might be a potential dietary supplement that could prevent the development of CAVD
Facile H<sub>2</sub>O‑Contributed O<sub>2</sub> Activation Strategy over Mn-Based SCR Catalysts to Counteract SO<sub>2</sub> Poisoning
Mn-based catalysts preferred in low-temperature selective
catalytic
reduction (SCR) are susceptible to SO2 poisoning. The stubborn
sulfates make insufficient O2 activation and result in
deficient reactive oxygen species (ROS) for activating reaction molecules.
H2O has long been regarded as an accomplice to SO2, hastening catalyst deactivation. However, such a negative impression
of the SCR reaction was reversed by our recent research. Here, we
reported a H2O contribution over Mn-based SCR catalysts
to counteract SO2 poisoning through accessible O2 activation, in which O2 was synergistically activated
with H2O to generate ROS for less deactivation and more
expected regeneration. The resulting ROS benefited from the energetically
favorable route supported by water-induced Ea reduction and was actively involved in the NH3 activation and NO oxidation process. Besides, ROS maintained high
stability over the SO2 + H2O-deactivated γ-MnO2 catalyst throughout the mild thermal treatment, achieving
complete regeneration of its own NO disposal ability. This strategy
was proven to be universally applicable to other Mn-based catalysts