Herein, a processing method is proposed for accurate microdisplacement measurements from a 2D Fabry–Perot (F-P) fringe pattern. The core of the processing algorithm uses the F-P interference imaging ...concentric ring pattern to accurately calculate the centre coordinates of the concentric ring. The influencing factors of measurement were analysed, and the basic idea of data processing was provided. In particular, the coordinate rotation by the 45-degree method (CR) was improved; consequently, the virtual pixel interval was reduced by half, and the calculation accuracy of the circle centre coordinate was improved. Experiments were conducted to analyse the influence of the subdivision and circle fitting methods. The results show that the proposed secondary coordinate rotation (SCR) by 45 degrees method can obtain higher accuracy of the centre coordinate than the CR method, and that the multichord averaging method (MCAM) is more suitable for calculation of the centre coordinate than the circular regression method (CRM). Displacement measurement experiments were performed. The results show that the standard experimental deviation of the centre of the circle is approximately 0.009 µm, and the extended uncertainty of the displacement measurement in the range of 5 mm is approximately 0.03 μm. The data processing method studied in this study can be widely used in the field of F-P interferometry.
Hazardous material road transport accidents pose a serious threat to public life, property and the environment. Therefore, studying the factors influencing road transport accidents involving ...hazardous materials can help identify the main causes behind them and contribute to the adoption of specific and targeted measures to reduce casualty rates and improve traffic safety. However, most existing research either adopted methods based on statistical analysis or neglected to further evaluate the spatial relationships. This study aims to use the eXtreme Gradient Boosting (XGBoost) algorithm to analyze hazardous material road transport accident data from seven regions of China. Considering the rarity of these events, the classification performance of different methods is compared based on precision, recall, F-score and Area Under Curve (AUC). The results indicate that the proposed XGBoost method has the best modeling performance. There is some variation between regions in the features that have a significant impact on accident severity. The influence of the same feature on the severity of an accident even varies from region to region. The aforementioned results provide a theoretical basis for exploring the issues, sustainability, challenges, and tasks of safe transportation activities for hazardous materials in the future. These results can help regions develop targeted prevention and response policies to efficiently reduce the incidence and severity of accidents.
This paper examines the effects and mechanism of the financialization of manufacturing enterprises on total factor productivity (TFP). Thus, it provides evidence of the economic consequences of ...corporate financialization from the perspective of productivity. Using the panel data of China's listed manufacturing companies from 2007 to 2018, the level of corporate financialization is measured using the proportion of financial assets in the total assets. The results show that the deepening of the financialization of manufacturing enterprises significantly reduces TFP and the magnitude of the impacts of different types of financial assets variates. In addition, the effects of corporate financialization on TFP are heterogeneous in terms of their significance and degrees in different types of enterprises as well as in different levels of enterprises' TFP. The further analysis of the influencing mechanism shows that corporate financialization has different effects on the TFP of manufacturing enterprises through technological innovation and resource allocation efficiency.
In brain imaging segmentation, precise tumor delineation is crucial for diagnosis and treatment planning. Traditional approaches include convolutional neural networks (CNNs), which struggle with ...processing sequential data, and transformer models that face limitations in maintaining computational efficiency with large-scale data. This study introduces MambaBTS: a model that synergizes the strengths of CNNs and transformers, is inspired by the Mamba architecture, and integrates cascade residual multi-scale convolutional kernels. The model employs a mixed loss function that blends dice loss with cross-entropy to refine segmentation accuracy effectively. This novel approach reduces computational complexity, enhances the receptive field, and demonstrates superior performance for accurately segmenting brain tumors in MRI images. Experiments on the MICCAI BraTS 2019 dataset show that MambaBTS achieves dice coefficients of 0.8450 for the whole tumor (WT), 0.8606 for the tumor core (TC), and 0.7796 for the enhancing tumor (ET) and outperforms existing models in terms of accuracy, computational efficiency, and parameter efficiency. These results underscore the model's potential to offer a balanced, efficient, and effective segmentation method, overcoming the constraints of existing models and promising significant improvements in clinical diagnostics and planning.
Abstract Background Aortic dissection (AD) is a macrovascular disease which is pathologically characterized by aortic media degeneration.This experiment aims to explore how iron deficiency (ID) ...affects the function of vascular smooth muscle cell (VSMC) and participates in the occurrence and development of AD by regulating gene expression. Methods The relationship between iron and AD was proved by Western-blot (WB) and immunostaining experiments in human and animals. Transcriptomic sequencing explored the transcription factors that were altered downstream. WB, flow cytometry and immunofluorescence were used to demonstrate whether ID affected HIF1 expression through oxygen transport. HIF1 signaling pathway and phenotypic transformation indexes were detected in cell experiments. The use of the specific HIF1 inhibitor PX478 further demonstrated that ID worked by regulating HIF1. Results The survival period of ID mice was significantly shortened and the pathological staining results were the worst. Transcriptomic sequencing indicated that HIF1 was closely related to ID and the experimental results indicated that ID might regulate HIF1 expression by affecting oxygen balance. HIF1 activation regulates the phenotypic transformation of VSMC and participates in the occurrence and development of AD in vivo and in vitro.PX478, the inhibition of HIF1, can improve ID-induced AD exacerbation.
COVID-19 is a highly contagious respiratory disease, which mainly affects the lungs. Critically ill patients are easily complicated by cytokine storms, acute respiratory distress syndrome (ARDS), and ...respiratory failure, which seriously threaten their lives. Pulmonary fibrosis (PF) is a common interstitial lung disease, and its pathogenesis may involve the participation of a variety of immune cells and inflammatory factors. Current studies have shown that patients with COVID-19 may be complicated by pulmonary fibrosis, and patients with pulmonary fibrosis may also be at higher risk of contracting COVID-19 than healthy people. Pulmonary fibrosis is an important risk factor leading to the aggravation of COVID-19 disease. COVID-19 complicated by cytokine storm and ARDS mechanism pathways are similar to the pathogenesis of pulmonary fibrosis. The potential interaction between pulmonary fibrosis and COVID-19 can cause acute exacerbation of the patient's condition, but the potential mechanism between the two has not been fully elucidated. Most of the drug treatment programs for COVID-19-related pulmonary fibrosis are currently formulated about the relevant guidelines for idiopathic pulmonary fibrosis (IPF), and there is no clear drug treatment program recommendation. This article aims to summarize the relevant mechanism pathways of COVID-19 and pulmonary fibrosis, explore the interrelationships and possible mechanisms, and discuss the value and risks of existing and potential COVID-19-related pulmonary fibrosis treatment drugs, to provide reference for anti-fibrosis treatment for patients.
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The balance between T helper 17 (Th17) cells and regulatory T (Treg) cells, plays a critical role in rheumatoid arthritis (RA). The differentiation of Th17 cells requires the ...activation of STAT3, which determines the balance of Th17/Treg. Here, we investigated the therapeutic effect of Cryptotanshinone (CTS) on collagen induced mouse arthritis and explored the underlying mechanisms.
Arthritis was induced in DBA/1 mice with bovine collagen type II and complete Freund’s adjuvant. CTS was given at 20mgkg−1d−1 or 60mgkg−1d−1 by gavage for 6weeks. The immuno-inflammation and joint destruction were evaluated and the balance of Th17/Treg was determined. STAT3 acetylation and phosphorylation were detected by western blotting, and the involvement of p300 was investigated by siRNA and plasmid overexpression.
CTS at a dose of 60mgkg−1d−1 ameliorated the inflammation and joint destruction in CIA mice. It improved Th17/Treg imbalance, and inhibited both acetylation and phosphorylation of STAT3. CTS reduced p300 expression and its binding to STAT3, but increased phosphorylated AMPK. Knockdown of p300 mimicked the inhibitory effect of CTS on STAT3 acetylation and phosphorylation, which could be partially rescued by overexpression of p300-WT, but not p300-dominant negative (DN) construct.
Our study suggested that the anti-arthritis effects of CTS were attained through suppression of p300-mediated STAT3 acetylation. Our data suggest that CTS might be a potential immune modulator for RA treatment.
Legubicin, a novel prodrug based on doxorubicin, has both albumin-binding and legumain-activating properties. The aim of this study was to develop and validate a UHPLC-MS/MS method for investigating ...the in vivo pharmacokinetics and tissue distribution profiles of legubicin in rats and tumor-bearing mice following intravenous administration, and to compare this prodrug with the positive control drug doxorubicin. The study employed a UHLC-MS/MS method to determine the levels of albumin-bound of legubicin and two metabolites (free Leu-DOX and DOX) in plasma, tumor, and tissue samples. This method was validated for good selectivity, high sensitivity, excellent extraction recovery, and short run time. The results showed that legubicin was present in the circulation in vivo mainly in a protein-bound form with larger AUC values and lower clearance and distribution, and essentially released small amounts of doxorubicin. Compared to administration of equimolar doses of doxorubicin, legubicin showed increased exposure of the active drug in the tumor and decreased the level of the active drug in the heart and kidney. This study provides valuable information on the pharmacokinetics and tissue distribution of legubicin, implicating its potential as a novel and effective drug candidate for anti-cancer therapies.
Our previous study found that deletion of Sorting nexin 10 (SNX10) can protect against colonic inflammation and pathological damage induced by dextran sulfate sodium (DSS). This inspired us that ...modulation of SNX10 expression in colonic epithelial cells might represent a promising therapeutic strategy for inflammatory bowel disease (IBD).
Effective delivery of siRNA/shRNA to silence genes is a highly sought-after means in the treatment of multiple diseases. Here, we encapsulated SNX10-shRNA plasmids (SRP) with polylactide-polyglycolide (PLGA) to make oral nanoparticles (NPs), and then applied them to acute and chronic IBD mice model, respectively. The characteristics of the nanoparticles were assayed and the effects of SRP-NPs on mouse IBD were evaluated.
High-efficiency SNX10-shRNA plasmids were successfully constructed and coated with PLGA to obtain nanoparticles, with a particle size of 275.2 ± 11.4mm, uniform PDI distribution, entrapment efficiency of 87.6 ± 2.5%, and drug loading of 13.11 ± 1.38%, displayed dominant efficiency of SNX10 RNA interference in the colon. In both acute and chronic IBD models, SRP-NPs could effectively reduce the loss of mice body weight, relieve the intestinal mucosal damage and inflammatory infiltration, inhibit the expression of inflammatory cytokines IL-1β, IL-23, TNF-α, and down-regulate the expression of toll-like receptors (TLRs) 2 and 4.
Oral nanoparticles of SNX10-shRNA plasmid displayed dominant efficiency of SNX10 RNA interference in the colon and ameliorate mouse colitis via TLR signaling pathway. SNX10 is a new target for IBD treatment and nanoparticles of SNX10-shRNA plasmid might be a promising treatment option for IBD.
Abstract Icotinib, one of the leading compounds selected from our compound library, was found to be a potent and specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with ...an IC50 of 5 nM. When profiled with 88 kinases, Icotinib only showed meaningful inhibitory activity to EGFR and its mutants. Icotinib blocked EGFR-mediated intracellular tyrosine phosphorylation (IC50 = 45 nM) in the human epidermoid carcinoma A431 cell line and inhibits tumor cell proliferation. In vivo studies demonstrated that Icotinib exhibited potent dose-dependent antitumor effects in nude mice carrying a variety of human tumor-derived xenografts. The drug was well tolerated at doses up to 120 mg/kg/day in mice without mortality or significant body weight loss during the treatment. A head to head randomized, double blind phase III trial using Gefitinib as an active control for patients with advanced non-small cell lung cancer (NSCLC) was finished recently (Trial registration ID: NCT01040780 ). The data shows that Icotinib was non-inferior to Gefitinib in terms of median progression free survival (PFS) and safety superior favor to Icotinib compared to Gefitinib.
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