IP3R-dependent mitochondrial dysfunction mediates C5b-9-induced ferroptosis in trichloroethylene-caused immune kidney injury

Patients with occupational medicamentose-like dermatitis due to trichloroethylene often suffer from immune kidney injury. Our previous study reveals that C5b-9-dependent cytosolic Ca2+ overload-induced ferroptosis is involved in trichloroethylene sensitized kidney injury. However, how C5b-9 causes cytosolic Ca2+ rise and the specific mechanism whereby overloaded Ca2+ induces ferroptosis remain unknown. The purpose of our study was to explore the role of IP3R-dependent mitochondrial dysfunction in C5b-9 mediated ferroptosis in trichloroethylene sensitized kidney. Our results showed that IP3R was activated, and mitochondrial membrane potential was decreased in the renal epithelial cells of trichloroethylene-sensitized mice, and these changes were antagonized by CD59, a C5b-9 inhibitory protein. Moreover, this phenomenon was reproduced in a C5b-9-attacked HK-2 cell model. Further investigation showed that RNA interference with IP3R not only alleviated C5b-9-induced cytosolic Ca2+ overload and mitochondrial membrane potential loss but also attenuated C5b-9-induced ferroptosis in HK-2 cells. Mechanistically, IP3R-dependent cytosolic Ca2+ overload activated the mitochondrial permeability transition pore, resulting in the loss of mitochondrial membrane potential and ferroptosis of HK-2 cells. Finally, cyclosporin A, a mitochondrial permeability transition pore inhibitor, not only ameliorated IP3R-dependent mitochondrial dysfunction but also blocked C5b-9-induced ferroptosis. Taken together, these results suggest that IP3R-dependent mitochondrial dysfunction plays an important role in trichloroethylene sensitized renal tubular ferroptosis

AC loss comparison between multifilament and nonstriated YBCO coils designed for HTS propulsion motors

In this paper, the properties of current capacity and ac transport loss of striated high temperature superconductor (HTS) coil is compared with ordinary HTS coil by using both experimental and simulation methods. The measurements were carried out by transporting a sinusoidal varying current at 77 K, with an amplitude range of 10-50 A in frequency from 70 up to 300 Hz. Measurement facilities and methods are explained in more detail in the paper. The critical current of the 4-mm width multifilament coil made with four filaments at a spacing 0.03 mm was found to be lower than that of the nonstriated coil. The frequency dependent characteristics agreed well in both experimental and simulated results. Reducing ac loss of HTS is one enabling factor for widespread adoption of the technology, and therefore, understanding its characteristics is important and discussed in this paper. Future plans based on this preliminary work are the testing of multifilament tapes in an axial flux motor field environment

Fast Adaptive Character Animation Synthesis Based on Greedy Algorithm

On the premise of ensuring the animation effect and real-time performance, it is of great significance and value for large-scale group character animation synthesis how to reduce the disaster coincidence degree among various models of fast adaptive character animation synthesis. The realization method of object-oriented finite state machine is studied in detail. Finite state machine (FSM) is an efficient behavior modeling method, which can describe the behavioral decisions of fast adaptive character animation synthesis in a complex virtual environment. Based on the implementation defects of the finite state machine in the traditional structure, using object-oriented thinking, combined with the state design mode, we further studied a finite state machine implementation method based on object-oriented technology. This achieves code reuse and simple program maintenance. The effect is extensible and effectively overcomes the shortcomings of traditional character animation synthesis. Secondly, the multipath matching tracking algorithm of the greedy algorithm is studied to generate multiple candidate sets through multiple paths, and finally, the candidate set with the minimum residual error is selected as the estimated support set, so as to improve the reconstruction performance. Further, based on the idea of multipath, using the regularization method of the ROMP algorithm, the regularized multipath matching tracking RMSP algorithm is proposed. It uses the regularized subset method to generate multiple paths and chooses the path with the fastest residual reduction as the support set of this iteration. The simulation results show that the RMSP algorithm has better reconstruction performance than the SP algorithm

Molecular dynamics study on the mechanical properties of nanocrystalline Ni-W alloys with bimodal structure

In order to study the effects of coarse grain size and Ni content on the mechanical properties, the molecular dynamics (MD) simulation of nanocrystalline (NC) Ni-W alloys with bimodal structure is carried out. The bimodal NC Ni-W alloys samples are established by embedding coarse grain into the fine grain matrix. The solute Ni atoms in the alloys are segregated in the grain boundary affected zone (GBAZ) through severe plastic deformation (SPD). The uniaxial tensile simulation of the samples shows that the coarse grain size and Ni content have obvious effects on the mechanical properties of bimodal NC Ni-W alloys. The dislocation activities and deformation mechanism of the NC Ni-W alloys are discussed in detail by observing the atomic configurations and strain evolutions diagrams obtained by MD simulation. At the same time, the phenomenon of Hall-Petch relationship and inverse Hall-Petch relationship is also observed in the research process

Bisphenol A promotes macrophage proinflammatory subtype polarization via upregulation of IRF5 expression in vitro

Exposure to environmental endocrine-disrupting chemical Bisphenol-A (BPA) is closely associated with an imbalance of immune homeostasis, but the underlying mechanisms are not fully understood. In the present study, the effects of BPA on the polarization of mouse peritoneal macrophages were investigated in vitro. Environmentally relevant low concentrations of BPA treatment under M1 type polarization conditions increased the number of M1 subtype macrophages, the gene expression of M1 phenotypic marker CD11c and the activity and gene expression of M1 functional marker iNOS, as well as the production of pro-inflammatory cytokines. However, The same dose BPA treatment under M2 type polarization conditions reduced the number of M2 subtype macrophages, the gene expression of M2 phenotypic marker CD206 and the activity and gene expression of M2 functional marker Arg-1, along with the production of anti-inflammatory cytokines. We also identified that the expression of transcription factor IRF5 was upregulated by BPA exposure in M1 macrophages under M1 type polarization conditions. Our results demonstrate that BPA promotes macrophage polarization toward proinflammatory M1 subtype and M1 activity, associated with upregulated expression of IRF5, while BPA inhibits macrophage toward anti-inflammatory M2 subtype polarization. These findings provide new insight into the link between exposure to BPA and impairment of immune functions

Small extracellular vesicles derived from Nrf2-overexpressing human amniotic mesenchymal stem cells protect against lipopolysaccharide-induced acute lung injury by inhibiting NLRP3

Abstract Background Acute lung injury (ALI) is a major cause of respiratory failure in critically ill patients that results in significant morbidity and mortality. Recent studies indicate that cell-based therapies may be beneficial in the treatment of ALI. We recently demonstrated that Nrf2-overexpressing human amniotic mesenchymal stem cells (hAMSCs) reduce lung injury, fibrosis and inflammation in lipopolysaccharide (LPS)-challenged mice. Here we tested whether small extracellular vesicles (sEVs) derived from Nrf2-overexpressing hAMSCs (Nrf2-sEVs) could protect against ALI. sEVs were isolated from hAMSCs that overexpressed (Nrf2-sEVs) or silenced (siNrf2-sEVs) Nrf2. We examined the effects of sEVs treatment on lung inflammation in a mouse model of ALI, where LPS was administered intratracheally to mice, and lung tissues and bronchoalveolar lavage fluid (BALF) were analyzed 24 h later. Methods Histological analysis, immunofluorescence microscopy, western blotting, RT-PCR and ELISA were used to measure the inflammatory response in the lungs and BALF. Results We found that sEVs from hAMSCs are protective in ALI and that Nrf2 overexpression promotes protection against lung disease. Nrf2-sEVs significantly reduced lung injury in LPS-challenged mice, which was associated with decreased apoptosis, reduced infiltration of neutrophils and macrophages, and inhibition of pro-inflammatory cytokine expression. We further show that Nrf2-sEVs act by inhibiting the activation of the NLRP3 inflammasome and promoting the polarization of M2 macrophages. Conclusion Our data show that overexpression of Nrf2 protects against LPS-induced lung injury, and indicate that a novel therapeutic strategy using Nrf2-sEVs may be beneficial against ALI

Early Smoke Detection Based on Improved YOLO-PCA Network

Early detection of smoke having indistinguishable pixel intensities in digital images is a difficult task. To better maintain fire surveillance, early smoke detection is crucial. To solve the problem, we have integrated the principal component analysis (PCA) as a pre-processing module with the improved version of You Only Look Once (YOLOv3). The ordinary YOLOv3 structure has been improved after inserting one extra detection scale at stride-4 specifically to detect immense small smoke instances in the wild. The improved network design establishes a sequential relation between feature maps of lower spatial information and fine-grained semantic information in up-sampled maps via skip connections and concatenation operations. The testing of the improved model is carried out on self-prepared smoke datasets. In digital images, the smoke instances are captured in various complicated environments, for example, the mountains and fog in the background. A principal component analysis (PCA) helps in useful features selection and abandons the involvement of redundant features in the testing of the trained network hence, overcoming the latency at inference stage. In addition, to process small smoke images as positive samples during training, new sizes of anchors are calculated on small smoke data at a specified Intersection over Union (IoU) threshold. The experimental results show the improvement in precision rate, recall rate, and mean harmonic (F1-score) by 2.67, 3.06, and 5.59 percentages. The respective improvements in average precision (AP) and mean average precision (mAP) are 1.66 and 2.78 percentages

Early Smoke Detection Based on Improved YOLO-PCA Network

Early detection of smoke having indistinguishable pixel intensities in digital images is a difficult task. To better maintain fire surveillance, early smoke detection is crucial. To solve the problem, we have integrated the principal component analysis (PCA) as a pre-processing module with the improved version of You Only Look Once (YOLOv3). The ordinary YOLOv3 structure has been improved after inserting one extra detection scale at stride-4 specifically to detect immense small smoke instances in the wild. The improved network design establishes a sequential relation between feature maps of lower spatial information and fine-grained semantic information in up-sampled maps via skip connections and concatenation operations. The testing of the improved model is carried out on self-prepared smoke datasets. In digital images, the smoke instances are captured in various complicated environments, for example, the mountains and fog in the background. A principal component analysis (PCA) helps in useful features selection and abandons the involvement of redundant features in the testing of the trained network hence, overcoming the latency at inference stage. In addition, to process small smoke images as positive samples during training, new sizes of anchors are calculated on small smoke data at a specified Intersection over Union (IoU) threshold. The experimental results show the improvement in precision rate, recall rate, and mean harmonic (F1-score) by 2.67, 3.06, and 5.59 percentages. The respective improvements in average precision (AP) and mean average precision (mAP) are 1.66 and 2.78 percentages