αO-Conotoxin GeXIVA[1,2] Suppresses In Vivo Tumor Growth of Triple-Negative Breast Cancer by Inhibiting AKT-mTOR, STAT3 and NF-κB Signaling Mediated Proliferation and Inducing Apoptosis.

Breast cancer is one of the leading causes of cancer mortality worldwide, and triple-negative breast cancer (TNBC) is the most problematic subtype. There is an urgent need to develop novel drug candidates for TNBC. Marine toxins are a valuable source for drug discovery. We previously identified αO-conotoxin GeXIVA[1,2] from Conus generalis, which is a selective antagonist of α9 nicotinic acetylcholine receptors (nAChRs). Recent studies indicated that α9 nAChR expression is positively correlated with breast cancer development; thus, α9 nAChR could serve as a therapeutic target for breast cancer. In this study, we aimed to investigate the in vivo antitumor effects of GeXIVA[1,2] on TNBC and to elucidate its underlying anticancer mechanism. Our data showed that GeXIVA[1,2] effectively suppressed 4T1 tumor growth in vivo at a very low dose of 0.1 nmol per mouse. Our results uncovered that the antitumor mechanism of GeXIVA[1,2] simultaneously induced apoptosis and blocked proliferation. Further investigations revealed that GeXIVA[1,2]-induced Caspase-3-dependent apoptosis was achieved through regulating Bax/Bcl-2 balance, and GeXIVA[1,2]-inhibited proliferation was mediated by the downregulation of the AKT-mTOR, STAT3 and NF-κB signaling pathways. Our study provides valuable arguments to demonstrate the potential of GeXIVA[1,2] as a novel marine-derived anticancer drug candidate for the treatment of TNBC.

Antidepressants as Autophagy Modulators for Cancer Therapy.

Cancer is a major global public health problem with high morbidity. Depression is known to be a high-frequency complication of cancer diseases that decreases patients' life quality and increases the mortality rate. Therefore, antidepressants are often used as a complementary treatment during cancer therapy. During recent decades, various studies have shown that the combination of antidepressants and anticancer drugs increases treatment efficiency. In recent years, further emerging evidence has suggested that the modulation of autophagy serves as one of the primary anticancer mechanisms for antidepressants to suppress tumor growth. In this review, we introduce the anticancer potential of antidepressants, including tricyclic antidepressants (TCAs), tetracyclic antidepressants (TeCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs). In particular, we focus on their autophagy-modulating mechanisms for regulating autophagosome formation and lysosomal degradation. We also discuss the prospect of repurposing antidepressants as anticancer agents. It is promising to repurpose antidepressants for cancer therapy in the future.

A Rapid Method of the Rock Mass Surface Reconstruction for Surface Deformation Detection at Close Range.

Characterizing the surface deformation during the inter-survey period could assist in understanding rock mass progressive failure processes. Moreover, 3D reconstruction of rock mass surface is a crucial step in surface deformation detection. This study presents a method to reconstruct the rock mass surface at close range in a fast way using the improved structure from motion-multi view stereo (SfM) algorithm for surface deformation detection. To adapt the unique feature of rock mass surface, the AKAZE algorithm with the best performance in rock mass feature detection is introduced to improve SfM. The surface reconstructing procedure mainly consists of image acquisition, feature point detection, sparse reconstruction, and dense reconstruction. Hereafter, the proposed method was verified by three experiments. Experiment 1 showed that this method effectively reconstructed the rock mass model. Experiment 2 proved the advanced accuracy of the improved SfM compared with the traditional one in reconstructing the rock mass surface. Eventually, in Experiment 3, the surface deformation of rock mass was quantified through reconstructing images before and after the disturbance. All results have shown that the proposed method could provide reliable information in rock mass surface reconstruction and deformation detection.

Accuracy Improvement of Binocular Vision Measurement System for Slope Deformation Monitoring.

This paper studies the limitations of binocular vision technology in monitoring accuracy. The factors affecting the surface displacement monitoring of the slope are analyzed mainly from system structure parameters and environment parameters. Based on the error analysis theory, the functional relationship between the structure parameters and the monitoring error is studied. The error distribution curve is obtained through laboratory testing and sensitivity analysis, and parameter selection criteria are proposed. Corresponding image optimization methods are designed according to the error distribution curve of the environment parameters, and a large number of tests proved that the methods effectively improved the measurement accuracy of slope deformation monitoring. Finally, the reliability and accuracy of the proposed system and method are verified by displacement measurement of a slope on site.

LINC01140 Alleviates the Oxidized Low-Density Lipoprotein-Induced Inflammatory Response in Macrophages via Suppressing miR-23b.

Our previous study has demonstrated that miR-23b enhances oxidized low-density lipoprotein (oxLDL)-induced inflammatory response of macrophages through the A20/NF-κB signaling pathway, thus contributing to atherosclerosis. This study aims to further investigate the upstream regulators of miR-23b in mediating oxLDL-induced inflammatory response. Human monocyte cell line THP1 was induced to differentiate into macrophages followed by the oxLDL stimulation of inflammatory response. The expression of miR-23b, LINC01140, and p53 mRNA was detected by quantitative PCR. The combination of miR-23b and LINC01140 was confirmed by luciferase reporter assay and RNA immunoprecipitation. The binding of p53 and LINC01140 promoter was determined by luciferase reporter assay. The level of inflammatory cytokines, including MCP-1, TNF-α, and IL-1ß, was assessed by enzyme-linked immunosorbent assay. LINC01140 was downregulated, while p53 and miR-23b were upregulated in oxLDL-induced inflammatory response of macrophages. Overexpression of LINC01140 reduced NF-κB activity by reducing miR-23b and increasing A20. The transcription of LINC01140 was inhibited by binding of p53 and the LINC01140 promoter region. Knockdown of p53 significantly reduced NF-κB activity and level of inflammatory cytokines by promoting LINC01140 expression. Our findings demonstrated that LINC01140 acts as an anti-inflammatory factor through negatively regulating miR-23/A20 axis. In addition, p53 is identified as a transcriptional repressor of LINC01140.

Abnormally expressed miR-23b in Chinese Mongolian at high cardiovascular risk may contribute to monocyte/macrophage inflammatory reaction in atherosclerosis.

Background: The prevalence of coronary heart disease (CHD) appears to be high among Chinese Mongolians. MiR-23b has been proven to play a key role in atherosclerosis. The expression and role of miR-23b in the Mongolians at high cardiovascular risk were explored in the present study.Methods: Forty cases of blood samples from the Mongolians at high cardiovascular risk were enrolled in the present study. The expression of miR-23b was quantified by quantitative real-time PCR. To induce monocytes differentiation into macrophages, HP-1 cells were cultured with phorbol 12-myristate 13-acetate. The level of inflammatory markers was determined by the enzyme-linked immunosorbent assay. The interaction between miR-23b and A20 was explored by the dual luciferase reporter assay.Results: The expression of miR-23b in the Mongolian at high cardiovascular risk was higher than that in healthy Mongolian volunteers. Decrease in ATP-binding cassette transporter A1 caused by miR-23b is responsible for TC accumulation in the Mongolian at high cardiovascular risk. MiR-23b enhanced the oxidized low-density lipoprotein (oxLDL)-induced inflammatory response of THP-1 derived macrophage. MiR-23b regulated nuclear factor-κB (NF-κB) pathway through targeting A20. MiR-23b mediated oxLDL-induced inflammatory response of peripheral blood mononuclear cell in the Mongolian at high cardiovascular risk.Conclusion MiR-23b enhanced oxLDL-induced inflammatory response of macrophages in the Mongolian at high cardiovascular risk through the A20/NF-κB signaling pathway, and thus contributing to atherosclerosis.

Non-Contact Measurement of the Surface Displacement of a Slope Based on a Smart Binocular Vision System.

The paper presents an intelligent real-time slope surface deformation monitoring system based on binocular stereo-vision. To adapt the system to field slope monitoring, a design scheme of concentric marking point is proposed. Techniques including Zernike moment edge extraction, the least squares method, and k-means clustering are used to design a sub-pixel precision localization method for marker images. This study is mostly focused on the tracking accuracy of objects in multi-frame images obtained from a binocular camera. For this purpose, the Upsampled Cross Correlation (UCC) sub-pixel template matching technique is employed to improve the spatial-temporal contextual (STC) target-tracking algorithm. As a result, the tracking accuracy is improved to the sub-pixel level while keeping the STC tracking algorithm at high speed. The performance of the proposed vision monitoring system has been well verified through laboratory tests.

An extended Hilbert's integral inequality in the whole plane with parameters.

By introducing independent parameters and interval variables, applying the weight functions and the technique of real analysis, an extended Hilbert's integral inequality in the whole plane with parameters and a best possible constant factor is provided. The equivalent forms, the reverses, and the related homogeneous forms with particular parameters are considered. Meanwhile, an extended Hilbert's integral operator in the whole plane is defined, and the operator expressions for the equivalent inequalities are obtained.

A High-Speed Target-Free Vision-Based Sensor for Bus Rapid Transit Viaduct Vibration Measurements Using CMT and ORB Algorithms.

Bus Rapid Transit (BRT) has become an increasing source of concern for public transportation of modern cities. Traditional contact sensing techniques during the process of health monitoring of BRT viaducts cannot overcome the deficiency that the normal free-flow of traffic would be blocked. Advances in computer vision technology provide a new line of thought for solving this problem. In this study, a high-speed target-free vision-based sensor is proposed to measure the vibration of structures without interrupting traffic. An improved keypoints matching algorithm based on consensus-based matching and tracking (CMT) object tracking algorithm is adopted and further developed together with oriented brief (ORB) keypoints detection algorithm for practicable and effective tracking of objects. Moreover, by synthesizing the existing scaling factor calculation methods, more rational approaches to reducing errors are implemented. The performance of the vision-based sensor is evaluated through a series of laboratory tests. Experimental tests with different target types, frequencies, amplitudes and motion patterns are conducted. The performance of the method is satisfactory, which indicates that the vision sensor can extract accurate structure vibration signals by tracking either artificial or natural targets. Field tests further demonstrate that the vision sensor is both practicable and reliable.