Pancreatic ductal adenocarcinoma (PDAC) has prominent extracellular matrix (ECM) that compromises treatments yet cannot be nonselectively disrupted without adverse consequences. ECM of PDAC, despite the recognition of its importance, has not been comprehensively studied in patients. In this study, we used quantitative mass spectrometry (MS)-based proteomics to characterize ECM proteins in normal pancreas and pancreatic intraepithelial neoplasia (PanIN)- and PDAC-bearing pancreas from both human patients and mouse genetic models, as well as chronic pancreatitis patient samples. We describe detailed changes in both abundance and complexity of matrisome proteins in the course of PDAC progression. We reveal an early up-regulated group of matrisome proteins in PanIN, which are further up-regulated in PDAC, and we uncover notable similarities in matrix changes between pancreatitis and PDAC. We further assigned cellular origins to matrisome proteins by performing MS on multiple lines of human-to-mouse xenograft tumors. We found that, although stromal cells produce over 90% of the ECM mass, elevated levels of ECM proteins derived from the tumor cells, but not those produced exclusively by stromal cells, tend to correlate with poor patient survival. Furthermore, distinct pathways were implicated in regulating expression of matrisome proteins in cancer cells and stromal cells. We suggest that, rather than global suppression of ECM production, more precise ECM manipulations, such as targeting tumor-promoting ECM proteins and their regulators in cancer cells, could be more effective therapeutically.

The prognosis for pancreatic ductal adenocarcinoma (PDAC) remains poor despite decades of effort. The abundant extracellular matrix (ECM) in PDAC comprises a major fraction of the tumor mass and plays various roles in promoting resistance to therapies. However, nonselective depletion of ECM has led to poor patient outcomes. Consistent with that observation, we previously showed that individual matrisome proteins derived from stromal cells correlate with either long or short patient survival. In marked contrast, those derived from cancer cells correlate strongly with poor survival. Here, we studied three cancer cell-derived matrisome proteins that are significantly overrepresented during PDAC progression, AGRN (agrin), SER-PINB5 (serine protease inhibitor B5), and CSTB (cystatin B). Using both overexpression and knockdown experiments, we demonstrate that all three are promoters of PDAC metastasis. Furthermore, these proteins operate at different metastatic steps. AGRN promoted epithelial-to-mesenchymal transition in primary tumors, whereas SERPINB5 and CSTB enhanced late steps in the metastatic cascade by elevating invadopodia formation and in vivo extravasation. All three genes were associated with a poor prognosis in human patients and high levels of SERPINB5, secreted by cancer cells and deposited in the ECM, correlated with poor patient prognosis. This study provides strong evidence that cancer cell-derived matrisome proteins can be causal in promoting tumorigenesis and metastasis and lead to poor patient survival. Therefore, compared with the bulk matrix, mostly made by stromal cells, precise interventions targeting cancer cell-derived matrisome proteins, such as AGRN, SERPINB5, and CSTB, may represent preferred potential therapeutic targets.Significance: This study provides insights into the biological roles of cancer cell-derived matrisome proteins in PDAC and supports the notion that these proteins are protumorigenic and better therapeutic targets.

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Superhydrophobic surfaces are conventionally prepared employing two steps: roughening a surface and lowering their surface energy. In the present work, a direct voltage (DC) is applied between two copper plates immersed in a dilute ethanolic stearic acid solution. The surface of the anodic copper electrode transforms to superhydrophobic due to a reaction between copper and stearic acid solution. The fabrication process of superhydrophobic copper surfaces is simplified in just one-step.The surface of the anodic copper is found to be covered with flower-like low surface energy copper stearate films providing the water contact angle of 153 ± 2° with the rolloff properties.

Highlights• Superhydrophobic copper surfaces by a one-step electrochemical modification process in an ethanolic stearic acid solution.• Analysis of the corrosion properties of as-received, hydrophobic and superhydrophobic copper surfaces.• The corrosion resistance of the superhydrophobic surface is found to be 1220 kΩ cm 2 as compared to as-received bare copper surface 1 kΩ cm 2 . AbstractSuperhydrophobic copper surfaces have been prepared by a one-step electrochemical modification process in an ethanolic stearic acid solution. In this work, the corrosion properties of hydrophobic copper surface and superhydrophobic copper surfaces were analyzed by means of electrochemical analyses and compared with that of as-received bare copper substrate. The decrease of corrosion current density (icorr) as well as the increase of polarization resistance (Rp) obtained from potentiodynamic polarization curves revealed that the superhydrophobic film on the copper surfaces improved the corrosion resistance performance of the copper substrate.Graphical Abstract

This study investigated the significant influence of HCO3 – on the degradation of contaminants of emerging concern (CECs) during nitrate photolysis at 254 nm for water reuse applications. The second-order rate constants for the reactions between selected contaminants with carbonate radical (CO3 •–) were determined at pH 8.8 and T = 20 °C: estrone ((5.3 ± 1.1) × 108 M–1 s–1), bisphenol A ((2.8 ± 0.2) × 108 M–1 s–1), 17α-ethynylestradiol ((1.6 ± 0.3) × 108 M–1 s–1), triclosan ((4.2 ± 1.4) × 107 M–1 s–1), diclofenac ((2.7 ± 0.7) × 107 M–1 s–1), atrazine ((5.7 ± 0.1) × 106 M–1 s–1), carbamazepine ((4.2 ± 0.01) × 106 M–1 s–1), and ibuprofen ((1.2 ± 1.1) × 106 M–1 s–1). Contributions from UV, reactive nitrogen species (RNS), hydroxyl radical (•OH), and CO3 •– to the CEC decomposition in UV/NO3 – in the presence and absence of HCO3 – were investigated. In addition, possible transformation products and degradation pathways of triclosan, diclofenac, bisphenol A, and estrone in UV/NO3 –/HCO3 – were proposed based on the mass (MS) and MS2 spectra. Significant reduction in the cytotoxicity of bisphenol A was observed after the treatment with UV/NO3 –/HCO3 –.

Infection of H5N1 influenza virus causes the highest mortality among all influenza viruses. The mechanisms underlying such high viral pathogenicity are incompletely understood. Here, we report that the H5N1 influenza virus encodes a microRNA-like small RNA, miR-HA-3p, which is processed from a stem loop-containing viral RNA precursor by Argonaute 2, and plays a role in enhancing cytokine production during H5N1 infection. Mechanistic study shows that miR-HA-3p targets poly(rC)-binding protein 2 (PCBP2) and suppresses its expression. Consistent with PCBP2 being an important negative regulator of RIG-I/MAVS-mediated antiviral innate immunity, suppression of PCBP2 expression by miR-HA-3p promotes cytokine production in human macrophages and mice infected with H5N1 virus. We conclude that miR-HA-3p is the first identified influenza virus-encoded microRNA-like functional RNA fragment and a novel virulence factor contributing to H5N1-induced 'cytokine storm' and mortality.

The deficient osseointegration and implant-associated infections are pivotal issues for the long-term clinical success of endosteal Ti implants, while development of functional surfaces that can simultaneously overcome these problems remains highly challenging. This study aimed to fabricate sophisticated Ti implant surface with both osteogenic inducing activity and inherent antibacterial ability simply via tailoring surface topographical features. Micro/submciro/nano-scale structure was constructed on Ti by three cumulative subtractive methods, including sequentially conducted sandblasting as well as primary and secondary acid etching treatment. Topographical features of this hierarchical structure can be well tuned by the time of the secondary acid treatment. Ti substrate with mere micro/submicro-scale structure (MS0-Ti) served as a control to examine the influence of hierarchical structures on surface properties and biological activities. Surface analysis indicated that all hierarchically structured surfaces possessed exactly the same surface chemistry as that of MS0-Ti, and all of them showed super-amphiphilicity, high surface free energy, and high protein adsorption capability. Biological evaluations revealed surprisingly antibacterial ability and excellent osteogenic activity for samples with optimized hierarchical structure (MS30-Ti) when compared with MS0-Ti. Consequently, for the first time, a hierarchically structured Ti surface with topography-induced inherent antibacterial capability and excellent osteogenic activity was constructed.