TGF-ß1 promotes human breast cancer angiogenesis and malignant behavior by regulating endothelial-mesenchymal transition.

Background: Endothelial-mesenchymal transition (EndMT) is an important process of angiogenesis, which plays a significant role in in tumor invasion and metastasis, while its regulatory mechanisms in breast cancer remain to be fully elucidated. We previously demonstrated that tumor-associated macrophages (TAMs) can induce EndMT in endothelial cells by secreting CCL18 through the activation of the TGF-ß and Notch signaling pathways in breast cancer. This study was designed to study the role of EndMT in breast cancer angiogenesis and progression in order to explore the underlying mechanism. Methods: Immunohistochemistry (IHC) was used to evaluate the expression of microvascular density (MVD) and EndMT markers in breast cancer. TGF-ß1 was used to induce EndMT models of differentiated-endothelial breast cancer stem-like cells (BCSLCs). In vitro cell migration, proliferation and matrigel tube-formation assays, as well as in vivo nude mouse tumor-bearing model and nude mouse dorsal skinfold window chamber (DSWC) model, were utilized to investigate the effects in order to explore the mechanism of EndMT induced by TGF-ß1 on breast cancer progression. Results: In this study, we demonstrated that the EndMT markers were positively associated with MVD indicating unfavorable prognosis of invasive ductal carcinoma (IDC) patients. Functionally, TGF-ß1 promoted migration, proliferation and angiogenesis of differentiated-endothelial BCSLCs by inducing EndMT in vitro and promoted tumor growth and angiogenesis in vivo. Mechanically, we revealed TGF-ß1 induced EndMT by activation of TGF-ß and Notch signaling pathways with increase of p-Smad2/3 and Notch1 expression. Moreover, we found Snail and Slug were key factors of TGF-ß and Notch signaling pathways. Conclusion: Our findings elucidated the mechanism of TGF-ß1 in the promotion of angiogenesis and progression by EndMT in breast cancer.

Imaging damage in plate waveguides using frequency-domain multiple signal classification (F-MUSIC).

Earlier, an ameliorated MUSIC (Am-MUSIC) algorithm is developed by the authors [1], aimed at expanding conventional MUSIC algorithm from linear array-facilitated nondestructive evaluation to in situ health monitoring with a sparse sensor network. Yet, Am-MUSIC leaves a twofold issue to be improved: i) the signal representation equation is constructed at each pixel across the inspection region, incurring high computational cost; and ii) the algorithm is applicable to monochromatic excitation only, ignoring signal features scattered out of the excitation frequency band which also carry information on structural integrity. With this motivation, a multiple-damage-scattered wavefield model is developed, with which the signal representation equation is constructed in the frequency domain, avoiding computationally expensive pixel-based calculation - referred to as frequency-domain MUSIC (F-MUSIC). F-MUSIC quantifies the orthogonal attributes between the signal subspace and noise subspace inherent in signal representation equation, and generates a full spatial spectrum of the inspected sample to visualize damage. Modeling in the frequency domain endows F-MUSIC with the capacity to fuse rich information scattered in a broad band and therefore enhance imaging precision. Both simulation and experiment are performed to validate F-MUSIC when used for imaging single and multiple sites of damage in an isotropic plate waveguide with a sparse sensor network. Results accentuate that effectiveness of F-MUSIC is not limited by the quantity of damage, and imaging precision is not downgraded due to the use of a highly sparse sensor network - a challenging task for conventional MUSIC algorithm to fulfil.

Corrigendum: TGF-ß1 promotes human breast cancer angiogenesis and malignant behavior by regulating endothelial-mesenchymal transition.

[This corrects the article DOI: 10.3389/fonc.2022.1051148.].

High BTBD7 expression positive is correlated with SLUG-predicted poor prognosis in hormone receptor-negative breast cancer.

BACKGROUND: Hormone receptor-negative breast cancer (HRNBC), which includes triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER-2) overexpressing breast cancer, is prone to metastasis and has a poor prognosis. BTB/POZ domain-containing protein 7 (Btbd7) is thought to regulate SLUG and the epithelial-mesenchymal transition (EMT) process. However, the role of Btbd7 in HRNBC is unclear. METHODS: Expression of BTBD7 and SLUG in HRNBC tumor tissue and normal adjacent tissue (NAT) as well as breast cancer cells were characterized by immunohistochemistry and immunofluorescence. MDA-MA-231 cells was transfected with BTBD7 siRNA and detected by qRT-PCR and western blot. Expression levels of Slug and EMT related proteins were detected western blot analysis. cell invasion assays were used to analyse cell invasion ability of MDA-MA-231. GO and KEGG analyses was used to analysis the gene function. RESULTS: The total positive rate of BTBD7 expression in HRNBC tumor tissue was 66.7%, which was higher than that in NAT (52.1%) and benign breast lesion tissues (20%). Co-expression of SLUG and BTBD7 proteins could be found in HRNBC tissue and MDA-MA-231 cells. BTBD7 silencing significantly up-regulated the epithelial marker E-cadherin, down-regulated the mesenchymal markers α-SMA and SLUG and suppressed the invasion abilities of MDA-MA-231 cells. GO and KEGG analyses based on 322 DEGs showed that BTBD7 may be associated with generic transcription in breast cancer. CONCLUSIONS: The study data indicated that BTBD7 was inversely associated with SLUG expression. Higher BTBD7 was associated with poor clinicopathologic features and prognosis in HRNBC patients. BTBD7 silencing inhibited EMT through regulation of SLUG expression. BTBD7 might act as a potential molecular target for gene therapy in HRNBC patients.

A reverse time migration-based multistep angular spectrum approach for ultrasonic imaging of specimens with irregular surfaces.

We develop a new ultrasonic imaging framework for non-destructive testing of an immersed specimen featuring an irregular top surface and demonstrate its capability of accurately depicting the lower surfaces of multiple damages hidden in the specimen. Central to the framework is a multistep angular spectrum approach (ASA), via which the forward propagation wavefields of wave sources and backward propagation wavefields of the received wave signals are calculated. Upon applying a zero-lag cross-correlation imaging condition of reverse time migration (RTM) to the obtained forward and backward wavefields, the image of the specimen with an irregular surface can be reconstructed, in which hidden damages, if any and regardless of quantity, are visualized. The effectiveness and accuracy of the framework are examined using numerical simulation, followed with experiment, in both of which multiple side-drilled holes, at different locations in aluminum blocks with various irregular surfaces, are characterized. Results have proven that multiple damages in a specimen with an irregular surface can be individually localized, and the lower surface of each damage can further be imaged accurately, thanks to the RTM-based algorithm in which multiple wave reflections from the specimen bottom are taken into wavefield extrapolation. The proposed imaging approach presents higher computational efficiency, compared to conventional RTM, and enhanced imaging contrast over prevailing total focusing methods.

Analysis of Lung Adenocarcinoma Subtypes Based on Immune Signatures Identifies Clinical Implications for Cancer Therapy.

Lung cancer is the most common cause of cancer deaths worldwide, and lung adenocarcinoma (LUAD) is the most common histological subtype. However, the prognostic and predictive outcomes differ because of this cancer type heterogeneity. LUAD subtypes were identified on the basis of the immunogenomic profiling of 29 immune signatures. We named three LUAD subtypes: Immunity High, Immunity Medium, and Immunity Low. The Immunity High subtype was characterized by immune activation, e.g., increased immune scores, elevated stromal scores and the highest infiltration of CD8+ T cells, and decreased tumor purities. Activated expressions of human leukocyte antigen (HLA) genes, immune checkpoint molecules, and T helper 1 (Th1)/interferon-gamma (IFNγ) gene signature were also observed in the Immunity High subtype. N 6-methyladenosine (m6A) RNA methylation, associated with cancer initiation and progression, was reduced in the Immunity High subtype. Functional and signaling pathway enrichment analysis further showed that differentially expressed genes between the Immunity High subtype and the other subtypes mainly participated in immune response and some cancer-associated pathways. In addition, the Immunity High subtype exhibited more sensitivity to immunotherapy and chemotherapy. Finally, candidate compounds that aimed at LUAD subtype differentiation were identified. Comprehensively characterizing the LUAD subtypes based on immune signatures may help to provide potential strategies for LUAD treatment.

Diffuse ultrasonic wave-based structural health monitoring for railway turnouts.

Real-time damage evaluation is a critical step to warrant the integrity of turnout systems in railway industry. Nevertheless, existing structural health monitoring (SHM) approaches, despite their proven effectiveness in laboratory demonstration, are restricted from in-situ implementation in engineering practice. Based upon the continued endeavors of the authors in developing SHM approaches and exploring real world applications, an in-situ SHM approach, exploiting active diffuse ultrasonic waves (DUW) and a benchmark-less method, has been developed and implemented in a marshalling station in China. When trains passing a railway turnout, the train-induced loads on the rail track can lead to the growth of defects in the rail, and such growth disturbs the ultrasound traversing at the defect and gives rise to discrepancies between the DUW signals acquired before and after the train's passage. On this basis, a damage index, making use of the defect growth-induced changes in DUW signals, is proposed to identify the presence of defect. The probability of defect growth induced by the train-related load can be used to assess the severity of the defect. Via an online diagnosis system, conformance tests are implemented in Chengdu North Marshalling Station, in which defects in switch rails are identified and the health status of in-service rail tracks are continuously monitored. The results have demonstrated the effectiveness and reliability of DUW-driven SHM towards real world railway turnout applications.

A Spray-on, Nanocomposite-Based Sensor Network for in-Situ Active Structural Health Monitoring.

A new breed of nanocomposite-based spray-on sensor is developed for in-situ active structural health monitoring (SHM). The novel nanocomposite sensor is rigorously designed with graphene as the nanofiller and polyvinylpyrrolidone (PVP) as the matrix, fabricated using a simple spray deposition process. Electrical analysis, as well as morphological characterization of the spray-on sensor, was conducted to investigate percolation characteristic, in which the optimal threshold (~0.91%) of the graphene/PVP sensor was determined. Owing to the uniform and stable conductive network formed by well-dispersed graphene nanosheets in the PVP matrix, the tailor-made spray-on sensor exhibited excellent piezoresistive performance. By virtue of the tunneling effect of the conductive network, the sensor was proven to be capable of perceiving signals of guided ultrasonic waves (GUWs) with ultrahigh frequency up to 500 kHz. Lightweight and flexible, the spray-on nanocomposite sensor demonstrated superior sensitivity, high fidelity, and high signal-to-noise ratio under dynamic strain with ultralow magnitude (of the order of micro-strain) that is comparable with commercial lead zirconate titanate (PZT) wafers. The sensors were further networked to perform damage characterization, and the results indicate significant application potential of the spray-on nanocomposite-based sensor for in-situ active GUW-based SHM.