Abstract Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue disease (CTD), causing death in systemic sclerosis (SSc). The past decade has yielded many scientific ...insights into microRNA (miRNAs) in PAH and SSc. This growth of knowledge has well-illustrated the complexity of microRNA (miRNA)-based regulation of gene expression in PAH. However, few miRNA-related SSc-PAH were elucidated. This review firstly discusses the role of transforming growth factor-beta (TGF-β) signaling and bone morphogenetic protein receptor type II (BMPR2) in PAH and SSc. Secondly, the miRNAs relating to TGF-β and BMPR2 signaling pathways in PAH and SSc or merely PAH were subsequently summarized. Finally, future studies might develop early diagnostic biomarkers and target-oriented therapeutic strategies for SSc-PAH and PAH treatment.
The railway rivet is one of the most important and easily damaged parts of the connection. If rivets develop cracks during the production process, their load-bearing capacity will be reduced, thereby ...increasing the risk of failure. Fluorescent magnetic particle flaw detection (FMPFD) is a widely used inspection method for train fasteners. Manual inspection is not only time-consuming but also prone to miss detection, therefore intelligent detection system has important application value. However, the fluorescent crack images obtained by FMPFD present challenges for intelligent detection, such as the dense, multi-scaled and uninstantiated cracks. In addition, there is limited research on fluorescent rivet crack detection. This paper adopts instance segmentation to achieve automatic cracks detection of rivets. A decentralized target center and low overlap rate labeling method is proposed, and a Gaussian-weighted correction post-processing method is introduced to improve the recall rate in the areas of dense cracks. An efficient channel spatial attention mechanism for feature extraction is proposed in order to enhance the detection of multi-scale cracks. For uninstantiated cracks, an improvement of crack detection in uninstantiated regions based on multi task feature learning is proposed, thoroughly utilizing the semantic and spatial features of the fluorescent cracks. The experimental results show that the improved methods are better than the baseline and some cutting-edge algorithms, achieving a recall rate and mAP
of 86.4% and 90.3%. In addition, a single coil non-contact train rivet composite magnetization device is built for rivets that can magnetize different shapes of rivets and has universality.
Interference-fit is getting increasing attentions in the aerospace field owing to its excellent enhancement on the sealing and fatigue life of composites assembly, but the severe damage around the ...hole caused by installation is still a huge challenge. In this paper, a three-dimensional anisotropic non-linear progressive damage model based on continuum damage mechanics was developed to reveal the damage mechanism of carbon fiber reinforced plastic (CFRP) composites interference bolting with sleeve. The proposed model adopted strain-based failure criteria and non-linear damage evolution law to predict damage initiation and propagation of composite laminates. A cohesive model taking into account the traction-separation constitutive response was employed to capture the delamination behavior between the composite plies. The elastoplastic model was utilized to characterize the sleeve's deformation behavior. Numerical simulations of different installation modes are performed and compared with experiments. The inserting load, damage modes and damage positions predicted by the proposed model agree well with the experimental results. Moreover, it is also verified that the interference installation of sleeved fasteners can remarkably reduce the intra-laminar damage and avoid the inter-laminar delamination of composite laminates compared to the conventional bolt.
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•A 3D anisotropic non-linear PDM was developed to reveal the damage mechanism of composites interference bolting with sleeve.•The model adopted strain-based failure criteria and non-linear damage evolution law to predict damage of composites.•Interference installation experiments were conducted to verify the damage behavior of composites under different modes.
Deformation of the gear shaft in transmission is inevitable after case hardened heat treatment. Straightening is the normal way to ensure the straightness requirement. During the straightening ...process, cracks often appear and result in scrapped parts. Based on the situation of high rejection rate of straightening crack of the internal input shaft of a dual-clutch automobile transmission, this paper makes an in-depth analyses of the pressure straightening process theory, the crack generation mechanism, the working process of the automatic straightening machine and the crack detection system, etc., and establishes the relationship between the ram increment, the total displacement and the crack rate during multi-step progressive straightening, proposes a way to quickly judge the straightening performance of the parts. Finally, after optimizing the pressure position by finite element analysis, optimizing the straightening procedure by adjusting ram increment and adopting vector straightening method, optimizing the parts martial properties by heat treatment improvement, the straightening crack rate of internal input shaft was reduced from 1.95 % to 0.14 %.
Gout is a common form of inflammatory arthritis where urate crystals deposit in joints and surrounding tissues. With the high prevalence of gout, the standardized and effective treatment of gout is ...very important, but the long-term treatment effect of gout is not satisfied because of the poor adherence in patients to the medicines. Recently, advanced imaging modalities, including ultrasonography (US), dual-energy computed tomography (DECT), and magnetic resonance imaging (MRI), attracted more and more attention for their role on gout as intuitive and non-invasive tools for early gout diagnosis and evaluation of therapeutic effect. This review summarized the role of US, DECT, and MRI in the management of gout from four perspectives: hyperuricemia, gout attacks, chronic gout, and gout complications described the scoring systems currently used to quantify disease severity and discussed the challenges and limitations of using these imaging tools to assess response to the gout treatment.
Excitotoxicity represents the primary cause of neuronal death following spinal cord injury (SCI). While autophagy plays a critical and intricate role in SCI, the specific mechanism underlying the ...relationship between excitotoxicity and autophagy in SCI has been largely overlooked. In this study, we isolated primary spinal cord neurons from neonatal rats and induced excitotoxic neuronal injury by high concentrations of glutamic acid, mimicking an excitotoxic injury model. Subsequently, we performed transcriptome sequencing. Leveraging machine learning algorithms, including weighted correlation network analysis (WGCNA), random forest analysis (RF), and least absolute shrinkage and selection operator analysis (LASSO), we conducted a comprehensive investigation into key genes associated with spinal cord neuron injury. We also utilized protein-protein interaction network (PPI) analysis to identify pivotal proteins regulating key gene expression and analyzed key genes from public datasets (GSE2599, GSE20907, GSE45006, and GSE174549). Our findings revealed that six genes-Anxa2, S100a10, Ccng1, Timp1, Hspb1, and Lgals3-were significantly upregulated not only in vitro in neurons subjected to excitotoxic injury but also in rats with subacute SCI. Furthermore, Hspb1 and Lgals3 were closely linked to neuronal autophagy induced by excitotoxicity. Our findings contribute to a better understanding of excitotoxicity and autophagy, offering potential targets and a theoretical foundation for SCI diagnosis and treatment.
With the development of advanced metering infrastructure (AMI), electrical data are collected frequently by smart meters. Consequently, the load data volume and length increase dramatically, which ...aggravates the data storage and transmission burdens in smart grids. On the other hand, for event detection or market-based demand response applications, load service entities (LSEs) want smart meter readings to be classified in specific and meaningful types. Considering these challenges, a stacked auto-encoder (SAE)-based load data mining approach is proposed. First, an innovative framework for smart meter data flow is established. On the user side, the SAEs are utilized to compress load data in a distributed way. Then, centralized classification is adopted at remote data center by softmax classifier. Through the layer-wise feature extracting of SAE, the sparse and lengthy raw data are expressed in compact forms and then classified based on features. A global fine-tuning strategy based on a well-defined labeled subset is embedded to improve the extracted features and the classification accuracy. Case studies in China and Ireland demonstrate that the proposed method is more capable to achieve the minimum of error and satisfactory compression ratios (CR) than benchmark compressors. It also significantly improves the classification accuracy on both appliance and house level datasets.
Background: Acute kidney injury (AKI) refers to a sudden loss of renal function. This study was performed to identify the key RNAs acting in the mechanism of sepsis-induced AKI.
Methods: Microarray ...dataset GSE94717 (including six sepsis-induced AKI samples and three control samples) was downloaded from Gene Expression Omnibus database. Differentially expressed miRNAs (DE-miRNAs) were identified. The miRNA targets were predicted and enrichment analysis was performed. Protein-protein interaction (PPI) and competing endogenous RNA (ceRNA) regulatory networks were constructed. Mouse podocytes were treated with lipopolysaccharide (LPS), following by cell viability and PCR analysis. Cellular apoptosis and the ceRNA network were validated.
Results: Thirty-one common DE-miRNAs (two up-regulated and 29 down-regulated) by AKI versus control and male AKI versus control were identified. We found the targets of miR-15a-5p, miR-15b-5p, and miR-16-5p were involved in mTOR signaling pathway, and those of miR-29b-3p and miR-16-5p were enriched in PI3K-Akt signaling pathway. RNAs including miR-15b-5p, miR-15a-5p, miR-107, XIST, miR-16-5p, and cullin 3 gene (CUL3) were included in the ceRNA regulatory network. The downregulation of miR-15a-5p and miR-15b-5p and the upregulation of lncRNA XIST and CUL3 gene were validated using qPCR. The miR-15a-5p-XIST-CUL3 regulatory axis was identified and was validated. We confirmed that LPS inhibited the growth of mouse podocytes and seven of the ten miRNAs, but upregulated XIST and CUL3. Transfection analysis showed XIST siRNA enhanced LPS-induced MPC5 cell apoptosis and miR-15a-5p inhibitor reserved it, so did as CUL3 overexpression for miR-15a-5p mimics.
Conclusion: The miR-15a-5p-XIST-CUL3 regulatory axis was related to the pathogenesis of sepsis-induced AKI.
Highlights
Totally, 31 miRNAs were dysregulated between disease and control groups.
MiR-15a-5p, miR-15b-5p, and miR-16-5p were involved in mTOR signaling pathway.
MiR-16-5p and miR-29b-3p were implicated in PI3K-Akt signaling pathway.
The miR-15a-5p-XIST-CUL3 axis was critical for sepsis-induced AKI.
Dental pulp stem cells (DPSCs) were the most widely used seed cells in the field of neural regeneration and bone tissue engineering, due to their easily isolation, lack of ethical controversy, low ...immunogenicity and low rates of transplantation rejection. The purpose of this study was to investigate the role of basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) on neural differentiation of DPSCs in vitro. DPSCs were cultured in neural differentiation medium containing NGF and bFGF alone or combination for 7 days. Then neural genes and protein markers were analyzed using western blot and RT-PCR. Our study revealed that bFGF and NGF increased neural differentiation of DPSCs synergistically, compared with bFGF and NGF alone. The levels of Nestin, MAP-2, βIII-tubulin and GFAP were the most highest in the DPSCs + bFGF + NGF group. Our results suggested that bFGF and NGF signifiantly up-regulated the levels of Sirt1. After treatment with Sirt1 inhibitor, western blot, RT-PCR and immunofluorescence staining showed that neural genes and protein markers had markedly decreased. Additionally, the ERK and AKT signaling pathway played a key role in the neural differentiation of DPSCs stimulated with bFGF + NGF. These results suggested that manipulation of the ERK and AKT signaling pathway may be associated with the differentiation of bFGF and NGF treated DPSCs. Our date provided theoretical basis for DPSCs to treat neurological diseases and repair neuronal damage.
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