Both epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) are linked to metastasis via their ability to increase invasiveness and enhance tumor-initiating capacity. Growth factors, cytokines, and chemotherapies present in the tumor microenvironment (TME) are capable of inducing EMT, but the role of the extracellular matrix (ECM) in this process remains poorly understood. Here, a novel tessellated three-dimensional (3D) polymer scaffolding is used to produce a fibrillar fibronectin matrix that induces an EMT-like event that includes phosphorylation of STAT3 and requires expression of β1 integrin. Consistent with these findings, analysis of the METABRIC dataset strongly links high-level fibronectin (FN) expression to decreased patient survival. In contrast, analysis of the MCF-10A progression series indicated that intracellular FN expression was associated with nonmetastatic cells. Therefore, differential bioluminescent imaging was used to track the metastasis of isogenic epithelial and mesenchymal cells within heterogeneous tumors. Interestingly, mesenchymal tumor cells do not produce a FN matrix and cannot complete the metastatic process, even when grown within a tumor containing epithelial cells. However, mesenchymal tumor cells form FN-containing cellular fibrils capable of supporting the growth and migration of metastatic-competent tumor cells. Importantly, depletion of FN allows mesenchymal tumor cells to regain epithelial characteristics and initiate tumor growth within a metastatic microenvironment. In contrast to the tumor-promoting functions of fibronectin within the ECM, these data suggest that autocrine fibronectin production inhibits the metastatic potential of mesenchymal tumor cells. .

Highlights d Severe Na V 1.2 deficiency results in enhanced neuronal excitability in adult mice d Increased excitability is accompanied by a higher voltage threshold in striatal MSNs d Hyperexcitability related to Na V 1.2 deficiency is reversible and autonomous d Multiple K + channels, including K V 1.1, have a compensatory reduction in expression

Probiotic bacteria reduce the intestinal colonization of pathogens. Yet, their use in preventing fatal infection caused by foodborne Listeria monocytogenes (Lm), is inconsistent. Here, we bioengineered Lactobacillusprobiotics (BLP) to express the Listeria adhesion protein (LAP) from a non-pathogenic Listeria (L. innocua) and a pathogenic Listeria (Lm) on the surface of Lactobacillus casei. The BLP strains colonize the intestine, reduce Lm mucosal colonization and systemic dissemination, and protect mice from lethal infection. The BLP competitively excludes Lm by occupying the surface presented LAP receptor, heat shock protein 60 and ameliorates the Lm-induced intestinal barrier dysfunction by blocking the nuclear factor-κB and myosin light chain kinase-mediated redistribution of the major epithelial junctional proteins. Additionally, the BLP increases intestinal immunomodulatory functions by recruiting FOXP3+T cells, CD11c+ dendritic cells and natural killer cells. Engineering a probiotic strain with an adhesion protein from a non-pathogenic bacterium provides a new paradigm to exclude pathogens and amplify their inherent health benefits.

However, surfaces with a high contact angle (CA > 150°) can also exhibit "sticky" behavior characterized by high CAH; such surfaces are termed parahydrophobic. [7] A rose petal is a prime example exhibiting such parahydrophobic behavior; this socalled petal effect [8] has attracted significant research attention [7] in an attempt to understand this somewhat puzzling wetting state.Research over the last two decades has led to noteworthy progress in the synthesis of functional surfaces inspired by nature. [9] Self-cleaning surfaces inspired by the lotus leaf [10] have potential applications in enhancing the efficiency of solar cells, reducing surface drag, enhancing fluidic transport, and preventing water corrosion of batteries and fuel cells. [5] Surfaces exhibiting the petal effect have been proposed for separation processes [11] and collection of water via directional liquid transport. [12][13][14] It has also been recently demonstrated that parahydrophobic surfaces are ideal for facilitating bubble nucleation and departure during boiling. [15,16] Models of the wetting state are typically used to design surface topologies that provide the desired wetting characteristics. [17] Unlike the lotus leaf, for which the wetting state has been confirmed and is well accepted, [4] a recent review of the current understanding of parahydrophobic surfaces reveals a lack of experimental evidence to confirm the postulated wetting states on the rose petal. [7] As the surface morphology of natural surfaces is typically complex, and the features themselves delicate, it is difficult to obtain an accurate characterization of the microscopic wetting state. The existing explanation of the petal effect is based on a partially wetting "Cassie-impregnating" state. [7] The Cassieimpregnating wetting state is adapted to the dual-scale surface features of the rose petal, [18] namely, microscale papillae (bumps) with nanoscale striae (folds) [18] on top of each micropapilla. [19] Water droplets on the petal are thought to penetrate the gap between micro-papillae but not wet the nanoscale features. Although it was postulated that high apparent CA and high adhesion exhibited by surfaces could be explained by a mixed wetting state, [20] there has been no direct experimental evidence or visualization of these hypothesized wetting states on a rose petal. One recent study visualized the wetting state on a rose petal using top-down optical microscopy, [21] and postulated the trapping of air at the surface; however, it is difficult to view the liquid-air and liquid-solid interfaces underneath the droplet using this technique. Progress has been made on visualizing the liquid-air and liquid-solid interfaces between and below condensing droplets [22,23] and moving droplets [24] on microstructured surfaces using scanning electron microscopy (SEM).The rose petal features surface structures that offer unique wetting properties. A water droplet placed on a rose petal forms a high contact angle but exhibits significant contact angle hysteresis, such that re...