Intelligent Diagnosis of Rolling Bearings Fault Based on Multisignal Fusion and MTF-ResNet.

Existing diagnosis methods for bearing faults often neglect the temporal correlation of signals, resulting in easy loss of crucial information. Moreover, these methods struggle to adapt to complex working conditions for bearing fault feature extraction. To address these issues, this paper proposes an intelligent diagnosis method for compound faults in metro traction motor bearings. This method combines multisignal fusion, Markov transition field (MTF), and an optimized deep residual network (ResNet) to enhance the accuracy and effectiveness of diagnosis in the presence of complex working conditions. At the outset, the acquired vibration and acoustic emission signals are encoded into two-dimensional color feature images with temporal relevance by Markov transition field. Subsequently, the image features are extracted and fused into a set of comprehensive feature images with the aid of the image fusion framework based on a convolutional neural network (IFCNN). Afterwards, samples representing different fault types are presented as inputs to the optimized ResNet model during the training phase. Through this process, the model's ability to achieve intelligent diagnosis of compound faults in variable working conditions is realized. The results of the experimental analysis verify that the proposed method can effectively extract comprehensive fault features while working in complex conditions, enhancing the efficiency of the detection process and achieving a high accuracy rate for the diagnosis of compound faults.

Knockout of TRPA1 exacerbates angiotensin II-induced kidney injury.

Macrophage-mediated inflammation plays a critical role in hypertensive kidney disease. Here, we investigated the role of transient receptor potential ankyrin 1 (TRPA1), a sensor of inflammation, in angiotensin II (ANG II)-induced renal injury. Subcutaneous infusion of ANG II (600 ng·min-1·kg-1) for 28 days was used to induce hypertension and renal injury in mice. The results showed that ANG II-induced hypertensive mice have decreased renal Trpa1 expression (P < 0.01), whereas ANG II receptor type 1a-deficient hypotensive mice have increased renal Trpa1 expression (P < 0.05) compared with their normotensive counterparts. ANG II induced similar elevations of systolic blood pressure in Trpa1-/- and wild-type (WT) mice but led to higher levels of blood urea nitrogen (P < 0.05), serum creatinine (P < 0.05), and renal fibrosis (P < 0.01) in Trpa1-/- mice than WT mice. Similarly, ANG II increased both CD68+/inducible nitric oxide synthase+ M1 and CD68+/arginase 1+ M2 macrophages in the kidneys of both Trpa1-/- and WT mice (all P < 0.01), with higher extents in Trpa1-/- mice (both P < 0.01). Compared with WT mice, Trpa1-/- mice had significantly increased expression levels of inflammatory cytokines and their receptors in the kidney. Cultured murine macrophages were stimulated with phorbol 12-myristate 13-acetate, which downregulated gene expression of TRPA1 (P < 0.01). A TRPA1 agonist, cinnamaldehyde, significantly inhibited phorbol 12-myristate 13-acetate-stimulated expression of IL-1ß and chemokine (C-C motif) ligand 2 in macrophages, which were attenuated by pretreatment with a TRPA1 antagonist, HC030031. Furthermore, activation of TRPA1 with cinnamaldehyde induced apoptosis of macrophages. These findings suggest that TRPA1 may play a protective role in ANG II-induced renal injury, likely through inhibiting macrophage-mediated inflammation.

TRPA1 Promotes Cardiac Myofibroblast Transdifferentiation after Myocardial Infarction Injury via the Calcineurin-NFAT-DYRK1A Signaling Pathway.

Cardiac fibroblasts (CFs) are a critical cell population responsible for myocardial extracellular matrix homeostasis. After stimulation by myocardial infarction (MI), CFs transdifferentiate into cardiac myofibroblasts (CMFs) and play a fundamental role in the fibrotic healing response. Transient receptor potential ankyrin 1 (TRPA1) channels are cationic ion channels with a high fractional Ca2+ current, and they are known to influence cardiac function after MI injury; however, the molecular mechanisms regulating CMF transdifferentiation remain poorly understood. TRPA1 knockout mice, their wild-type littermates, and mice pretreated with the TRPA1 agonist cinnamaldehyde (CA) were subjected to MI injury and monitored for survival, cardiac function, and fibrotic remodeling. TRPA1 can drive myofibroblast transdifferentiation initiated 1 week after MI injury. In addition, we explored the underlying mechanisms via in vitro experiments through gene transfection alone or in combination with inhibitor treatment. TRPA1 overexpression fully activated CMF transformation, while CFs lacking TRPA1 were refractory to transforming growth factor ß- (TGF-ß-) induced transdifferentiation. TGF-ß enhanced TRPA1 expression, which promoted the Ca2+-responsive activation of calcineurin (CaN). Moreover, dual-specificity tyrosine-regulated kinase-1a (DYRK1A) regulated CaN-mediated NFAT nuclear translocation and TRPA1-dependent transdifferentiation. These findings suggest a potential therapeutic role for TRPA1 in the regulation of CMF transdifferentiation in response to MI injury and indicate a comprehensive pathway driving CMF formation in conjunction with TGF-ß, Ca2+ influx, CaN, NFATc3, and DYRK1A.

Activation of transient receptor potential vanilloid 1 accelerates re-endothelialization and inhibits neointimal formation after vascular injury.

OBJECTIVE: Transient receptor potential vanilloid 1 (TRPV1) is an important regulator of endothelial function, but the effects of TRPV1 on endothelial recovery and neointimal formation after vascular injury remain elusive. We tested the effects of activating TRPV1 using capsaicin on re-endothelialization and neointimal formation after wire-induced injury of the carotid artery in mice. METHODS: The human umbilical vein endothelial cells (HUVECs) were treated with the TRPV1 agonist capsaicin, its antagonist capsazepine, intracellular calcium chelator BAPTA, or mitofusin 2 (Mfn2)-specific short interfering RNA (siRNA). The migration, proliferation, mitochondrial morphology, membrane potential, and adenosine triphosphate production were measured. The carotid artery wire injury procedure was performed in male TRPV1 knockout mice and C57BL/6J wild-type (WT) mice that were then treated with or without Mfn2 siRNA. The re-endothelialization and neointimal formation were evaluated. RESULTS: Capsaicin significantly enhanced the migration and proliferation of HUVECs. Both capsazepine and BAPTA abolished capsaicin-induced migration and proliferation of HUVECs. In addition, capsaicin stimulated the formation of reticular mitochondria, augmented mitochondrial membrane potential, increased adenosine triphosphate production, and upregulated Mfn2. However, these effects were attenuated by knockdown of Mfn2 with specific siRNA. Dietary capsaicin markedly accelerated re-endothelialization and inhibited neointimal formation in WT mice but not in TRPV1 knockout mice. Moreover, Mfn2 siRNA also attenuated capsaicin-induced enhancement of endothelial recovery and suppression of neointimal hyperplasia in WT mice. CONCLUSIONS: Activation of TRPV1 with capsaicin attenuates neointimal formation by accelerating re-endothelialization through upregulation of Mfn2.

Apolipoprotein E-deficient rats develop atherosclerotic plaques in partially ligated carotid arteries.

BACKGROUND: The goal of this study was to establish an apolipoprotein E-deficient (ApoE(-/-)) rat model. METHODS: The ApoE(-/-) rat was created by TALEN-mediated gene targeting in the genetic background of Sprague Dawley rat. Six-to eight-week-old male rats were used in the experiments (n = 10 in each group). RESULTS: After fed with high-cholesterol diet (HCD) for 12 weeks, the ApoE(-/-) rats displayed typical dyslipidemia. In contrast, HCD failed to induce hypercholesterolemia in wild-type rats. However, there was no obvious atherosclerotic lesion in oil red O-stained en face aortas and the aortic root sections in both genetic types of rats. Interestingly, partial ligation caused the formation of plaques consist of lipid and macrophages in carotid arteries from ApoE(-/-) rats, but induced the neointimal hyperplasia in wild-type rats. Additionally, we found that HCD slightly increased the expression of adhesion molecules, while partial ligation dramatically upregulated these molecules. CONCLUSIONS: The ApoE(-/-) rat is a novel model for dyslipidemia and could also be used in the research of atherosclerosis.

Prognostic value of Muc5AC in gastric cancer: A meta-analysis.

AIM: To assess the correlation between decreased Muc5AC expression and patients' survival and clinicopathological characteristics by conducting a meta-analysis. METHODS: Literature searches were performed in PubMed and EMBASE, and 11 studies met our criteria. Summary hazard ratios or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the effect. For the pooled analysis of the correlation between decreased Muc5AC expression and clinicopathological characteristics (tumour invasion depth, lymph node metastasis, tumour-node-metastasis stage, tumour size, venous invasion and lymphatic invasion), ORs and their variance were combined to estimate the effect. RESULTS: Eleven retrospective cohort studies comprising 2135 patients were included to assess the association between Muc5AC expression and overall survival and/or clinicopathological characteristics. Decreased Muc5AC expression was significantly correlated with poor overall survival of gastric cancer patients (pooled HR = 1.35, 95%CI: 1.08-1.7). Moreover, decreased Muc5AC expression was also significantly associated with tumour invasion depth (pooled OR = 2.12, 95%CI: 1.56-2.87) and lymph node metastasis (pooled OR = 1.56, 95%CI: 1.00-2.44) in gastric cancer. CONCLUSION: Decreased Muc5AC expression might be a poor prognostic predictor for gastric cancer.

Expression, purification, crystallization and preliminary X-ray analysis of the HER3-9E12 Fab complex.

9E12 is a fully human immunoglobulin G1/κ monoclonal antibody that is specific for the epidermal growth factor receptor 3 (HER3), the overexpression of which has been detected in many tumour types and is associated with poor survival outcomes. To date, knowledge of the molecular mechanism for targeted antibodies that directly inhibit HER3 signalling is limited. Because knowledge of such therapeutic antibodies would help basic immunological therapeutics, structural insights into the HER3-9E12 Fab complex are important. Recombinant human HER3 and Fab fragments of the 9E12 antibody were cloned, expressed and crystallized, and crystallographic data sets were collected. The crystals belonged to space group P1, with unit-cell parameters a=74.4, b=98.6, c=99.6 Å, α=106.0, ß=95.0, γ=102.5° and diffracted to a resolution of 2.1 Å.

Long-lasting complete regression of established mouse tumors by counteracting Th2 inflammation.

Mice with intraperitoneal ID8 ovarian carcinoma or subcutaneous SW1 melanoma were injected with monoclonal antibodies (mAbs) to CD137PD-1CTLA4 7-15 days after tumor initiation. Survival of mice with ID8 tumors tripled and >40% of mice with SW1 tumors remained healthy >150 days after last treatment and are probably cured. Therapeutic efficacy was associated with a systemic immune response with memory and antigen specificity, required CD4 cells and involved CD8 cells and NK cells to a less extent. The 3 mAb combination significantly decreased CD19 cells at tumor sites, increased IFN-γ and TNF-α producing CD4 and CD8 T cells and mature CD86 dendritic cells (DC), and it increased the ratios of effector CD4 and CD8 T cells to CD4Foxp3 regulatory T (Treg) cells and to CD11bGr-1 myeloid suppressor cells (MDSC). This is consistent with shifting the tumor microenvironment from an immunosuppressive Th2 to an immunostimulatory Th1 type and is further supported by PCR data. Adding an anti-CD19 mAb to the 3 mAb combination in the SW1 model further increased therapeutic efficacy. Data from ongoing experiments show that intratumoral injection of a combination of mAbs to CD137PD-1CTLA4CD19 can induce complete regression and dramatically prolong survival also in the TC1 carcinoma and B16 melanoma models, suggesting that the approach has general validity.