Myeloperoxidase Modulates Hydrogen Peroxide Mediated Cellular Damage in Murine Macrophages

Myeloperoxidase (MPO) is involved in the development of many chronic inflammatory diseases, in addition to its key role in innate immune defenses. This is attributed to the excessive production of hypochlorous acid (HOCl) by MPO at inflammatory sites, which causes tissue damage. This has sparked wide interest in the development of therapeutic approaches to prevent HOCl-induced cellular damage including supplementation with thiocyanate (SCN−) as an alternative substrate for MPO. In this study, we used an enzymatic system composed of glucose oxidase (GO), glucose, and MPO in the absence and presence of SCN−, to investigate the effects of generating a continuous flux of oxidants on macrophage cell function. Our studies show the generation of hydrogen peroxide (H2O2) by glucose and GO results in a dose- and time-dependent decrease in metabolic activity and cell viability, and the activation of stress-related signaling pathways. Interestingly, these damaging effects were attenuated by the addition of MPO to form HOCl. Supplementation with SCN−, which favors the formation of hypothiocyanous acid, could reverse this effect. Addition of MPO also resulted in upregulation of the antioxidant gene, NAD(P)H:quinone acceptor oxidoreductase 1. This study provides new insights into the role of MPO in the modulation of macrophage function, which may be relevant to inflammatory pathologies

Double Forward Propagation for Memorized Batch Normalization

Batch Normalization (BN) has been a standard component in designing deep neural networks (DNNs). Although the standard BN can significantly accelerate the training of DNNs and improve the generalization performance, it has several underlying limitations which may hamper the performance in both training and inference. In the training stage, BN relies on estimating the mean and variance of data using a single mini-batch. Consequently, BN can be unstable when the batch size is very small or the data is poorly sampled. In the inference stage, BN often uses the so called moving mean and moving variance instead of batch statistics, i.e., the training and inference rules in BN are not consistent. Regarding these issues, we propose a memorized batch normalization (MBN), which considers multiple recent batches to obtain more accurate and robust statistics. Note that after the SGD update for each batch, the model parameters will change, and the features will change accordingly, leading to the Distribution Shift before and after the update for the considered batch. To alleviate this issue, we present a simple Double-Forward scheme in MBN which can further improve the performance. Compared to related methods, the proposed MBN exhibits consistent behaviors in both training and inference. Empirical results show that the MBN based models trained with the Double-Forward scheme greatly reduce the sensitivity of data and significantly improve the generalization performance

Intra-Cluster Federated Learning-Based Model Transfer Framework for Traffic Prediction in Core Network

Accurate prediction of cellular traffic will contribute to efficient operations and management of mobile network. With deep learning, many studies have achieved exact cellular traffic prediction. However, the reality is that quite a few subnets in the core network do not have sufficient computing power to train their deep learning model, which we call subnets (LCP-Nets) with limited computing power. In order to improve the traffic prediction efficiency of LCP-Nets with the help of deep learning and the subnets (ACP-Nets) with abundant computing power under the requirement of privacy protection, this paper proposes an intra-cluster federated learning-based model transfer framework. This framework customizes models for LCP-Nets, leveraging transferring models trained by ACP-Nets. Experimental results on the public dataset show that the framework can improve the efficiency of LCP-Nets traffic prediction

The role of the myeloperoxidase-derived oxidant hypothiocyanous acid (HOSCN) in the induction of mitochondrial dysfunction in macrophages

A host of chronic inflammatory diseases are accelerated by the formation of the powerful oxidant hypochlorous acid (HOCl) by myeloperoxidase (MPO). In the presence of thiocyanate (SCN-), the production of HOCl by MPO is decreased in favour of the formation of a milder oxidant, hypothiocyanous acid (HOSCN). The role of HOSCN in disease has not been fully elucidated, though there is increasing interest in using SCN- therapeutically in different disease settings. Unlike HOCl, HOSCN can be detoxified by thioredoxin reductase, and reacts selectively with thiols to result in reversible modifications, which could potentially reduce the extent of MPO-induced damage during chronic inflammation. In this study, we show that exposure of macrophages, a key inflammatory cell type, to HOSCN results in the reversible modification of multiple mitochondrial proteins, leading to increased mitochondrial membrane permeability, decreased oxidative phosphorylation and reduced formation of ATP. The increased permeability and reduction in ATP could be reversed by pre-treatment of the macrophages with cyclosporine A, implicating a role for the mitochondrial permeability transition pore. HOSCN also drives cells to utilise fatty acids as an energetic substrate after the inhibition of oxidative phosphorylation. Raman imaging studies highlighted the ability of HOSCN to perturb the electron transport chain of mitochondria and redistribute these organelles within the cell. Taken together, these data provide new insight into the pathways by which HOSCN can induce cytotoxicity and cellular damage, which may have relevance for the development of inflammatory disease, and therapeutic strategies to reduce HOCl-induced damage by supplementation with SCN-

Study on properties of SLM-NiTi shape memory alloy under the same energy density

In recent years, selective laser melting (SLM)-NiTi had developed rapidly due to the ability to achieve the complex shape and internal features, as well as high dimensional accuracy. The choice of parameters was particularly critical to the forming and performance of SLM-NiTi. In this work, we had designed and prepared five sets of SLM-NiTi shape memory alloys with the same energy density (range of 40–90 J/mm3). The microstructure, phase transition characteristic, mechanical properties and shape memory effect of SLM-NiTi shape memory alloys were investigated through various characterization methods of X-ray diffraction, scanning electron microscopy, differential scanning calorimetry and stress-controlled cyclic tensile tests, etc. The results showed that the surface forming quality of SLM-NiTi was not only related to the energy density, but also related to the value of P/V, which higher than 0.3 or lower than 0.1 would lead to the formation of surface pores. Interestingly, the SLM-NiTi showed ultrahigh failure strength of 735 MPa and elongation of 10.88% under room temperature tensile conditions. In addition, stress-controlled cyclic tensile tests under 400 MPa indicated that the SLM-NiTi had excellent shape memory effect of 76.1% recovery ratio and 3.95% recoverable strain after ten times loading–unloading cycles. The design of multi-parameter variables can not only optimize the surface quality, but also provide a basis for the prediction of SLM-NiTi phase transition temperature

MnASI1 Mediates Resistance to Botrytis cinerea in Mulberry (Morus notabilis)

Six α-amylase/subtilisin inhibitor genes (MnASIs) were identified from mulberry (Morus notabilis). In this study, bioinformatics and expression pattern analysis of six MnASIs were performed to determine their roles in resistance to B. cinerea. The expression of all six MnASIs was significantly increased under Botrytis cinerea infection. MnASI1, which responded strongly to B. cinerea, was overexpressed in Arabidopsis and mulberry. The resistance of Arabidopsis and mulberry overexpressing MnASI1 gene to B. cinerea was significantly improved, the catalase (CAT) activity was increased, and the malondialdehyde (MDA) content was decreased after inoculation with B. cinerea. At the same time, H2O2 and O2− levels were reduced in MnASI1 transgenic Arabidopsis, reducing the damage of ROS accumulation to plants. In addition, MnASI1 transgenic Arabidopsis increased the expression of the salicylic acid (SA) pathway-related gene AtPR1. This study provides an important reference for further revealing the function of α-amylase/subtilisin inhibitors