Rationale: Aldehyde accumulation is regarded as a pathognomonic feature of oxidative stress-associated cardiovascular disease. Objective: We investigated how the heart compensates for the accelerated accumulation of aldehydes. Methods and Results: Aldehyde dehydrogenase 2 (ALDH2) has a major role in aldehyde detoxification in the mitochondria, a major source of aldehydes. Transgenic (Tg) mice carrying an Aldh2 gene with a single nucleotide polymorphism (Aldh2*2) were developed. This polymorphism has a dominant-negative effect and the Tg mice exhibited impaired ALDH activity against a broad range of aldehydes. Despite a shift toward the oxidative state in mitochondrial matrices, Aldh2*2 Tg hearts displayed normal left ventricular function by echocardiography and, because of metabolic remodeling, an unexpected tolerance to oxidative stress induced by ischemia/ reperfusion injury. Mitochondrial aldehyde stress stimulated eukaryotic translation initiation factor 2␣ phosphorylation. Subsequent translational and transcriptional activation of activating transcription factor-4 promoted the expression of enzymes involved in amino acid biosynthesis and transport, ultimately providing precursor amino acids for glutathione biosynthesis. Intracellular glutathione levels were increased 1.37-fold in Aldh2*2 Tg hearts compared with wild-type controls. Heterozygous knockout of Atf4 blunted the increase in intracellular glutathione levels in Aldh2*2 Tg hearts, thereby attenuating the oxidative stress-resistant phenotype. Furthermore, glycolysis and NADPH generation via the pentose phosphate pathway were activated in Aldh2*2 Tg hearts. (NADPH is required for the recycling of oxidized glutathione.) Conclusions: The findings of the present study indicate that mitochondrial aldehyde stress in the heart induces metabolic remodeling, leading to activation of the glutathione-redox cycle, which confers resistance against acute oxidative stress induced by ischemia/reperfusion.

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Air breakdown phenomenon is generally considered as a negative effect in previous research on triboelectric nanogenerators (TENGs), which is always accompanied by air ionization. Here, by utilizing the air breakdown induced ionized air channel, we designed a direct-current triboelectric nanogenerator (DC-TENG) for harvesting contact-separation mechanical energy. During working process, the charges firstly transfer from bottom to top electrode through an external circuit in contact state, then flow back via the ionized air channel This article is protected by copyright. All rights reserved. created by air breakdown in separation process. So a unidirectional flow of electrical charges can be observed in the external circuit. With repeating contact-separation cycles, continuous pulsed DC output through external circuit can be realized. This working mechanism was verified by real time electrode potential monitoring, photocurrent signal detection and controllable discharging observation. The DC-TENG can be used for directly and continuously charging an energy storage unit and/or driving electronic devices without using a bridge rectifier. Owing to its simplicity in structure, the mechanism is further applied to fabricate the first flexible DC-TENG. This research provides a significant fundamental study for DC-TENG technology, and may expand its application in flexible electronics and flexible self-charging power systems.

To investigate the possible mechanisms of glutathione reductase (GR) in protecting against oxidative stress, we obtained transgenic tobacco (Nicotiana tabacum) plants with 30-70% decreased GR activity by using a gene encoding tobacco chloroplastic GR for the RNAi construct. We investigated the responses of wild type and transgenic plants to oxidative stress induced by application of methyl viologen in vivo. Analyses of CO(2) assimilation, maximal efficiency of photosystem II photochemistry, leaf bleaching, and oxidative damage to lipids demonstrated that transgenic plants exhibited enhanced sensitivity to oxidative stress. Under oxidative stress, there was a greater decrease in reduced to oxidized glutathione ratio but a greater increase in reduced glutathione in transgenic plants than in wild type plants. In addition, transgenic plants showed a greater decrease in reduced ascorbate and reduced to oxidized ascorbate ratio than wild type plants. However, there were neither differences in the levels of NADP and NADPH and in the total foliar activities of monodehydroascorbate reductase and dehydroascorbate reductase between wild type and transgenic plant. MV treatment induced an increase in the activities of GR, ascorbate peroxidase, superoxide dismutase, and catalase. Furthermore, accumulation of H(2)O(2) in chloroplasts was observed in transgenic plants but not in wild type plants. Our results suggest that capacity for regeneration of glutathione by GR plays an important role in protecting against oxidative stress by maintaining ascorbate pool and ascorbate redox state.

Purpose A nonparametric smooth line is usually added to spectral model to account for background signals in vivo magnetic resonance spectroscopy (MRS). The assumed smoothness of the baseline significantly influences quantitative spectral fitting. In this paper, a method is proposed to minimize baseline influences on estimated spectral parameters. Methods In this paper, the non-parametric baseline function with a given smoothness was treated as a function of spectral parameters. Its uncertainty was measured by root-mean-squared error (RMSE). The proposed method was demonstrated with a simulated spectrum and in vivo spectra of both short echo time (TE) and averaged echo times. The estimated in vivo baselines were compared with the metabolite-nulled spectra, and the LCModel-estimated baselines. The accuracies of estimated baseline and metabolite concentrations were further verified by cross-validation. Results An optimal smoothness condition was found that led to the minimal baseline RMSE. In this condition, the best fit was balanced against minimal baseline influences on metabolite concentration estimates. Conclusion Baseline RMSE can be used to indicate estimated baseline uncertainties and serve as the criterion for determining the baseline smoothness of in vivo MRS.

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AA-LT-d-rHDL could decrease the drug leakage during the remodeling behaviors induced by LCAT and fulfill efficient drug delivery.

Learning a powerful representation for a class with few labeled samples is a challenging problem. Although some state-of-the-art few-shot learning algorithms perform well based on meta-learning, they only focus on novel network architecture and fail to take advantage of the knowledge of every classification task. In this paper, to accomplish this goal, it proposes to combine the channel attention and spatial attention module (C-SAM), the C-SAM can mine deeply more effective information using samples of different classes that exist in different tasks. The residual network is used to alleviate the loss of the underlying semantic information when the network is deeper. Finally, a relation network including a C-SAM is applied to act as a classifier, which avoids learning more redundant information and compares the relation between difference samples. The experiment was carried out using the proposed method on six datasets, such as miniimagenet, Omniglot, Caltech-UCSD Birds, describable textures dataset, Stanford Dogs and Stanford Cars. The experimental results show that the C-SAM outperforms many state-of-the-art few-shot classification methods.