Epithelial Neoplasia Coincides with Exacerbated Injury and Fibrotic Response in the Lungs of \u3cem\u3eGprc5a\u3c/em\u3e-Knockout Mice Following Silica Exposure

Exposure to crystalline silica is suggested to increase the risk for a variety of lung diseases, including fibrosis and lung cancer. However, epidemiological evidences for the exposure-risk relationship are ambiguous and conflicting, and experimental study from a reliable animal model to explore the relationship is lacking. We reasoned that a mouse model that is sensitive to both lung injury and tumorigenesis would be appropriate to evaluate the exposure-risk relationship. Previously, we showed that, Gprc5a-/- mice are susceptible to both lung tumorigenesis and endotoxin-induced acute lung injury. In this study, we investigated the biological consequences in Gprc5a-/- mouse model following silica exposure. Intra-tracheal administration of fine silica particles in Gprc5a-/- mice resulted in more severe lung injury and pulmonary inflammation than in wild-type mice. Moreover, an enhanced fibrogenic response, including EMT-like characteristics, was induced in the lungs of Gprc5a-/- mice compared to those from wild-type ones. Importantly, increased hyperplasia or neoplasia coincided with silica-induced tissue injury and fibrogenic response in lungs from Gprc5a-/- mice. Consistently, expression of MMP9, TGFβ1 and EGFR was significantly increased in lungs from silica-treated Gprc5a-/- mice compared to those untreated or wild-type ones. These results suggest that, the process of tissue repair coincides with tissue damages; whereas persistent tissue damages leads to abnormal repair or neoplasia. Thus, silica-induced pulmonary inflammation and injury contribute to increased neoplasia development in lungs from Gprc5a-/- mouse model

Exploring hypotheses on karez initiation and decline in the Flaming Mountains from a photo modelling campaign

C

G9a Is Essential for EMT-Mediated Metastasis and Maintenance of Cancer Stem Cell-Like Characters in Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a particularly aggressive cancer with poor prognosis, largely due to lymph node metastasis and local recurrence. Emerging evidence suggests that epithelial-to-mesenchymal transition (EMT) is important for cancer metastasis, and correlated with increased cancer stem cells (CSCs) characteristics. However, the mechanisms underlying metastasis to lymph nodes in HNSCC is poorly defined. In this study, we show that E-cadherin repression correlates with cancer metastasis and poor prognosis in HNSCC. We found that G9a, a histone methyltransferase, interacts with Snail and mediates Snail-induced transcriptional repression of E-cadherin and EMT, through methylation of histone H3 lysine-9 (H3K9). Moreover, G9a is required for both lymph node-related metastasis and TGF-β-induced EMT in HNSCC cells since knockdown of G9a reversed EMT, inhibited cell migration and tumorsphere formation, and suppressed the expression of CSC markers. Our study demonstrates that the G9a protein is essential for the induction of EMT and CSC-like properties in HNSCC. Thus, targeting the G9a-Snail axis may represent a novel strategy for treatment of metastatic HNSCC

Autocrine Epiregulin Activates EGFR Pathway for Lung Metastasis Via EMT in Salivary Adenoid Cystic Carcinoma

Salivary adenoid cystic carcinoma (SACC) is characterized by invasive local growth and a high incidence of lung metastasis. Patients with lung metastasis have a poor prognosis. Treatment of metastatic SACC has been unsuccessful, largely due to a lack of specific targets for the metastatic cells. In this study, we showed that epidermal growth factor receptors (EGFR) were constitutively activated in metastatic lung subtypes of SACC cells, and that this activation was induced by autocrine expression of epiregulin (EREG), a ligand of EGFR. Autocrine EREG expression was increased in metastatic SACC-LM cells compared to that in non-metastatic parental SACC cells. Importantly, EREG-neutralizing antibody, but not normal IgG, blocked the autocrine EREG-induced EGFR phosphorylation and the migration of SACC cells, suggesting that EREG-induced EGFR activation is essential for induction of cell migration and invasion by SACC cells. Moreover, EREG-activated EGFR stabilized Snail and Slug, which promoted EMT and metastatic features in SACC cells. Of note, targeting EGFR with inhibitors significantly suppressed both the motility of SACC cells in vitro and lung metastasis in vivo. Finally, elevated EREG expression showed a strong correlation with poor prognosis in head and neck cancer. Thus, targeting the EREG-EGFR-Snail/Slug axis represents a novel strategy for the treatment of metastatic SACC even no genetic EGFR mutation

Evaluating the Sustainability of Microfinance Institutions Considering Macro-Environmental Factors: A Cross-Country Study

Microfinance institutions (MFIs) have attracted great attention, due to their significant role in poverty reduction. Given the features of MFIs, this paper proposes a novel hybrid model of soft set theory, and an improved order preference by similarity to ideal solution (HMSIT) to evaluate the sustainability of MFIs, considering accounting ratios, corporate governance factors, and macro-environmental factors, from a cross-country perspective. This setting enables the examination of the role of macro-environmental factors in the sustainability of MFIs. For this purpose, soft set theory is adopted to select optimal criteria. An improved order preference by similarity to ideal solution method, in which the weight of each criterion is determined by soft set theory, is proposed to rank the sustainability of MFIs. This algorithm enables HMSIT to make full use of various types of information. The case study uses cross-country samples. Results indicate that macro-environmental factors are significant in evaluating the sustainability of MFIs from a cross-country perspective. Particularly, they can play a key role in distinguishing MFIs with low sustainability. The results also indicate that HMSIT has strong robustness. Ranked results, produced from the proposed HMSIT are reliable enough to provide some managerial suggestions for MFIs and help stakeholders make decisions

On robust approximate optimal solutions for fractional semi-infinite optimization with uncertainty data

Abstract This paper provides some new results on robust approximate optimal solutions of a fractional semi-infinite optimization problem under uncertainty data in the constraint functions. By employing conjugate analysis and robust optimization approach (worst-case approach), we obtain some necessary and sufficient optimality conditions for robust approximate optimal solutions of such a fractional semi-infinite optimization problem. In addition, we state a mixed type approximate dual problem to the reference problem and obtain some robust duality properties between them. The results obtained in this paper improve the corresponding results in the literature

A Novel Soft Ensemble Model for Financial Distress Prediction with Different Sample Sizes

This work presents a novel soft ensemble model (ANSEM) for financial distress prediction with different sample sizes. It integrates qualitative classifiers (expert system method, ES) and quantitative classifiers (convolutional neural network, CNN) based on the uni-int decision making method of soft set theory (UI). We introduce internet searches indices as new variables for financial distress prediction. By constructing a soft set representation of each classifier and then using the optimal decision on soft sets to identify the financial status of firms, ANSEM inherits advantages of ES, CNN, and UI. Empirical experiments with the real data set of Chinese listed firms demonstrate that the proposed ANSEM has superior predicting performance for financial distress on accuracy and stability with different sample sizes. Further discussions also show that internet searches indices can offer additional information to improve predicting performance

Influence of Al Addition on the Microstructure and Wear Behavior of Laser Cladding FeCoCrNiAl<i>_x</i> High-Entropy Alloy Coatings

In order to improve the wear properties of FeCoCrNi high entropy alloy (HEA), laser cladding was applied to fabricate FeCoCrNiAlx HEA coatings with different Al additions. The Al-modified coatings exhibited excellent metallurgical bonding interfaces with the substrates. The microstructure of FeCoCrNiAl0.5 coating was the same as of the FeCoCrNi coating: face-centered cubic (FCC). However, the microstructure of FeCoCrNiAl was different: body-centered cubic (BCC) with more Al atoms distributed inside the grains. As the Al content in the coating was increased, the hardness increased as well from 202 to 546 HV0.2, while CoF and wear rate decreased from 0.62 to 0.1 and from 8.55 × 10−7 to 8.24 × 10−9 mm3/(Nm), respectively. The wear mechanisms changed from the mixture of abrasive, adhesive, and oxidative wear patterns to the mixture of abrasive and oxidative patterns. Such a change indicates that the Al addition indeed improved the wear resistance of FeCoCrNiAlx HEA coatings. Our results expand knowledge on HEA coating applications as wear-resistant materials in various applied industrial fields