FUNDC1: a key mediator of adenosine A2BR activation-induced inhibition of cardiac mitophagy under ischemia/reperfusion conditions.

Background: Mitophagy is an essential factor in mitochondrial quality control and myocardial ischaemia/reperfusion (I/R) injury protection. Because adenosine A2B receptor (A2BR) activation exerts a major role in reducing myocardial I/R injury, the effects of adenosine A2BR activation on cardiac mitophagy under reperfusion conditions were investigated. Methods: 110 adult Wistar rats (7-10 w), weighing 250-350 grams, were cultured in specific-pathogen-free (SPF) conditions before experiments. All hearts were removed and reperfused by Langendorff device. Six hearts with coronary flow (CF) values >28 or <10 mL/min were excluded. Others were arbitrarily divided into the following groups: sham operation group, I/R group, BAY60-6583 (BAY) (1-1,000 nM) + I/R group, PP2 + BAY + I/R group. After ischemia in rats, reperfusion was performed. H9c2 cells were placed in an imitated ischemic environment followed by Tyrode's solution to stimulate hypoxia/reoxygenation (H/R) injury. The mitochondrial fluorescence indicator MitoTracker Green and lysosomal fluorescence indicator LysoTracker Red were used to examine mitochondria and lysosomes, respectively. Colocalization of mitochondrial and autophagy marker proteins was determined by immunofluorescence. Autophagic flow currents were tested by Ad-mCherry-GFP-LC3B. Protein-protein interactions were predicted using a database and analyzed by co-immunoprecipitation. Autophagy marker protein, mitophagy marker protein, and mitophagy protein FUNDC1 were detected by immunoblotting. Results: Compared with those in the I/R group, myocardial autophagy and mitophagy were suppressed by the selective adenosine A2BR agonist BAY, and this effect was inhibited by the selective Src tyrosine kinase inhibitor PP2, indicating that adenosine A2BR activation could inhibit myocardial autophagy and mitophagy by activating Src tyrosine kinase. In support, in H9c2 cells, the selective Src tyrosine kinase inhibitor PP2 inhibited the effect of BAY on TOM20 with LC3 or mitochondria with lysosomes colocalization and autophagy flow. Here, we showed that mitochondrial FUNDC1 co-precipitated with Src tyrosine kinase after BAY was added. Consistently, the immunofluorescence and western blotting results demonstrated that compared to that in the H/R group, the expression of mitochondrial FUNDC1 was reduced by BAY, but this effect was reversed by PP2. Conclusions: Adenosine A2BR activation may inhibit myocardial mitophagy by downregulating expression of the mitochondrial FUNDC1 by activating Src tyrosine kinase under I/R conditions and could increase the interaction between Src tyrosine kinase and FUNDC1.

Fast Terahertz Imaging Model Based on Group Sparsity and Nonlocal Self-Similarity.

In order to solve the problems of long-term image acquisition time and massive data processing in a terahertz time domain spectroscopy imaging system, a novel fast terahertz imaging model, combined with group sparsity and nonlocal self-similarity (GSNS), is proposed in this paper. In GSNS, the structure similarity and sparsity of image patches in both two-dimensional and three-dimensional space are utilized to obtain high-quality terahertz images. It has the advantages of detail clarity and edge preservation. Furthermore, to overcome the high computational costs of matrix inversion in traditional split Bregman iteration, an acceleration scheme based on conjugate gradient method is proposed to solve the terahertz imaging model more efficiently. Experiments results demonstrate that the proposed approach can lead to better terahertz image reconstruction performance at low sampling rates.

Hybrid Sparsity Model for Fast Terahertz Imaging.

In order to shorten the long-term image acquisition time of the terahertz time domain spectroscopy imaging system while ensuring the imaging quality, a hybrid sparsity model (HSM) is proposed for fast terahertz imaging in this paper, which incorporates both intrinsic sparsity prior and nonlocal self-similarity constraints in a unified statistical model. In HSM, a weighted exponentiation shift-invariant wavelet transform is introduced to enhance the sparsity of the terahertz image. Simultaneously, the nonlocal self-similarity by means of the three-dimensional sparsity in the transform domain is exploited to ensure high-quality terahertz image reconstruction. Finally, a new split Bregman-based iteration algorithm is developed to solve the terahertz imaging model more efficiently. Experiments are presented to verify the effectiveness of the proposed approach.

Predictive value of serum VEGF, IL-1 and TNF-α in the treatment of thromboangiitis obliterans by revascularization.

Effect of revascularization in the treatment of thromboangiitis obliterans (TAO) and the predictive value of serum vascular endothelial growth factor (VEGF), interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) of risk factors of amputation were investigated. From April 2012 to August 2015, a total of 117 patients with TAO admitted to the First Hospital of Lanzhou University were selected. Patients treated with revascularization combined with prostaglandin sodium and cilostazol were enrolled in group A (67 patients), and patients treated with sodium and cilostazol were enrolled in group B (50 patients). The clinical efficacy was evaluated by calculating the intermittent claudication distance and the ankle brachial index (ABI) of patients. The occurrence probability of nausea and vomiting, skin pruritus, abdominal pain, coagulation abnormalities and amputation were recorded. The concentration of serum VEGF, IL-1 and TNF-α were measured using enzyme-linked immunosorbent assay (ELISA). After treatment, the intermittent claudication distance, ABI and efficiency of group A was markedly higher than that of group B (P<0.05). After treatment, serum VEGF concentration in group A was clearly higher than that in group B (P<0.05), and IL-1 and TNF-α levels were much lower than those in group B (P<0.05). The amputation rate in group A was significantly lower than that in group B (P<0.05). Patients with amputation in both groups were enrolled in the study group (24 cases), and those without amputation were included in the control group (93 cases). The serum VEGF concentration in the study group before treatment was significantly lower than that in the control group (P<0.05), while IL-1 and TNF-α levels were significantly higher than those of the control group (P<0.05). In conclusion, pretreatment serum VEGF, IL-1 and TNF-α had a positive diagnostic value for poor prognosis of patients with amputation, and low concentration of VEGF and higher concentration of IL-1 and TNF-α are the risk factors for amputations in patients with TAO.

The Effects of Different Fluorescent Indicators in Observing the Changes of the Mitochondrial Membrane Potential during Oxidative Stress-Induced Mitochondrial Injury of Cardiac H9c2 Cells.

We evaluated the ability of different fluorescent indicators by various analytical instruments, including a laser scanning confocal microscope (LSCM), fluorescence plate reader, and flow cytometer (FCM), to measure the mitochondrial membrane potential (ΔΨm) of cardiac H9c2 cells during oxidative stress-induced mitochondrial injury. The mitochondrial oxygen consumption rate and a transmission electron microscope were used to detect changes in mitochondrial functions and morphology, respectively. Cardiac H9c2 cells were exposed to H2O2 (500, 750, 1000, and 1250 µM) to induce mitochondrial oxidative stress injury, and fluorescent indicators including tetramethyl rhodamine ethyl ester (TMRE), 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine iodide (JC-1), and rhodamine 123 (R123) were used to detect changes in ΔΨm using an LSCM, fluorescence plate reader, and FCM. The decrease in ΔΨm caused by H2O2 was determined by endpoint and dynamic analyses after staining with JC-1 or TMRE. With the R123 probe, the LSCM could only detect the change in ΔΨm caused by 1000 µM H2O2. Moreover, R123 was less effective than JC-1 and TMRE for measurement of ΔΨm by the LSCM. Our data indicated that an LSCM is the most suitable instrument to detect dynamic changes in ΔΨm, whereas all three instruments can detect ΔΨm at the endpoint.

Ab Initio Screening of Doped Mg(AlH4)2 Systems for Conversion-Type Lithium Storage.

In this work, we have explored the potential applications of pure and various doped Mg(AlH4)2 as Li-ion battery conversion electrode materials using density functional theory (DFT) calculations. Through the comparisons of the electrochemical specific capacity, the volume change, the average voltage, and the electronic bandgap, the Li-doped material is found to have a smaller bandgap and lower average voltage than the pure system. The theoretical specific capacity of the Li-doped material is 2547.64 mAhg-1 with a volume change of 3.76% involving the electrode conversion reaction. The underlying reason for property improvement has been analyzed by calculating the electronic structures. The strong hybridization between Lis-state with H s-state influences the performance of the doped material. This theoretical research is proposed to help the design and modification of better light-metal hydride materials for Li-ion battery conversion electrode applications.