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Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia. It is unknown why fibrosis in IPF distributes in the peripheral or named sub-pleural area. Migration of pleural mesothelial cells (PMC) should contribute to sub-pleural fibrosis. Calpain is known to be involved in cell migration, but the role of calpain in PMC migration has not been investigated. In this study, we found that PMCs migrated into lung parenchyma in patients with IPF. Then using Wt1tm1(EGFP/Cre)Wtp /J knock-in mice, we observed PMC migration into lung parenchyma in bleomycin-induced pleural fibrosis models, and calpain inhibitor attenuated pulmonary fibrosis with prevention of PMC migration. In vitro studies revealed that bleomycin and transforming growth factor-β1 increased calpain activity in PMCs, and activated calpain-mediated focal adhesion (FA) turnover as well as cell migration, cell proliferation, and collagen-I synthesis. Furthermore, we determined that calpain cleaved FA kinase in both C-terminal and N-terminal regions, which mediated FA turnover. Lastly, the data revealed that activated calpain was also involved in phosphorylation of cofilin-1, and p-cofilin-1 induced PMC migration. Taken together, this study provides evidence that calpain mediates PMC migration into lung parenchyma to promote sub-pleural fibrosis in IPF.

The distribution of fibrosis in idiopathic pulmonary fibrosis (IPF) is subpleural with basal predominance. Alveolar epithelial cell was considered as the key cell in the initial phase of IPF. However, the idea of activation and damage of alveolar epithelial cells is very difficult to explain why fibrosis distributes in the subpleural area. In this study, human pleural mesothelial cell (PMC) line and primary rat PMC was used as in vitro model. Intraperitoneal injection of bleomycin was used for making a pulmonary fibrosis model. The integrity of cultured monolayer PMCs was determined by transepithelial electric resistance (TEER). Pleural permeability was estimated by measuring paracellular transport of fluorescein isothiocyanate (FITC)-conjugated dextran. Changes in lung tissue of patients with IPF were analyzed by Masson’s and immunofluorescence staining. We found bleomycin induced PMCs damage and increased PMCs permeability; increased PMCs permeability aggravated bleomycin-induced subpleural inflammation and pulmonary fibrosis. Moreover, bleomycin was found to activate VEGF/Src signaling which increased PMCs permeability. In vivo, inhibition of VEGF/Src signaling prevented bleomycin-induced subpleural pulmonary fibrosis. At last, activation of VEGF/Src signaling was confirmed in subpleural area in patients with IPF. Taken together, our findings indicate that VEGF/Src signaling mediated pleural barrier damage and increased permeability which contributes to subpleural pulmonary fibrosis.

Pleural fibrosis is defined as an excessive deposition of extracellular matrix that results in destruction of the normal pleural tissue architecture and compromised function. Tuberculous pleurisy, asbestos injury, and rheumatoid pleurisy are main causes of pleural fibrosis. Pleural mesothelial cells (PMCs) play a key role in pleural fibrosis. However, detailed mechanisms are poorly understood. Serine/arginine-rich protein SRSF6 belongs to a family of highly conserved RNA-binding splicing-factor proteins. Based on its known functions, SRSF6 should be expected to play a role in fibrotic diseases. However, the role of SRSF6 in pleural fibrosis remains unknown. In this study, SRSF6 protein was found to be increased in cells of tuberculous pleural effusions (TBPE) from patients, and decellularized TBPE, bleomycin, and TGF-β1 were confirmed to increase SRSF6 levels in PMCs. In vitro, SRSF6 mediated PMC proliferation and synthesis of the main fibrotic protein COL1A2. In vivo, SRSF6 inhibition prevented mouse experimental pleural fibrosis. Finally, activated SMAD2/3, increased SOX4, and depressed miRNA-506-3p were associated with SRSF6 upregulation in PMCs. These observations support a model in which SRSF6 induces pleural fibrosis through a cluster pathway, including SRSF6/WNT5A and SRSF6/SMAD1/5/9 signaling. In conclusion, we propose inhibition of the splicing factor SRSF6 as a strategy for treatment of pleural fibrosis.

Ethnopharmacological relevance The root of Panax notoginseng is traditionally used as an anti-hemorrhagic agent to promote blood circulation without causing “congealed” blood. Furthermore, the flower of P. notoginseng is a popular, traditional medicine taken daily for the preventing of hypertension and for reducing blood cholesterol profiles. Besides, the flower of P. notoginseng contains a higher level of saponins, particularly protopanaxadiol-type ginsenosides, as compared to the root. However, detailed pharmacological studies on this flower have rarely been conducted. Material and methods In this study, the saponins extracted from the flower of P. notoginseng (FS) were examined on the endothelial cell migration assay, chemically induced vascular insufficiency model in zebrafish larvae and myocardial infraction (MI) model in rats, for determination of their pro-angiogenic and therapeutic effects on MI treatment. Results Our results demonstrate that FS significantly promoted VEGF-induced migration of human umbilical vein endothelial cells (HUVECs) and partially restored defective intersegmental vessels (ISV) in a chemically induced vascular insufficiency model of zebrafish larvae. When compared to MI group, two weeks post-treatment of FS (25–50 mg/kg/day) induced approximately 3-fold upregulation of VEGF mRNA expression and a concomitant increase in blood vessel density in the peri-infarct area of the heart. Moreover, TUNEL analysis indicates a reduction in the mean apoptotic nuclei per field in peri-infarct myocardium upon FS treatment. Conclusions The pro-angiogenic effects of FS demonstrated in in vitro and in vivo experimental models suggest that the purified saponin preparation from flowers of P. notoginseng may potentially provide preventive and therapeutic agent for cardiovascular diseases.

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive and fibrosing interstitial pneumonia of unknown cause. The main feature of IPF is a heterogeneous appearance with areas of sub-pleural fibrosis. However, the mechanism of sub-pleural fibrosis was poorly understood. In this study, our in vivo study revealed that pleural mesothelial cells (PMCs) migrated into lung parenchyma and localized alongside lung fibroblasts in sub-pleural area in mouse pulmonary fibrosis. Our in vitro study displayed that cultured-PMCs-medium induced lung fibroblasts transforming into myofibroblast, cultured-fibroblasts-medium promoted mesothelial-mesenchymal transition of PMCs. Furthermore, these changes in lung fibroblasts and PMCs were prevented by blocking TGF-β1/Smad2/3 signaling with SB431542. TGF-β1 neutralized antibody attenuated bleomycin-induced pulmonary fibrosis. Similar to TGF-β1/Smad2/3 signaling, wnt/β-catenin signaling was also activated in the process of PMCs crosstalk with lung fibroblasts. Moreover, inhibition of CD147 attenuated cultured-PMCs-medium induced collagen-I synthesis in lung fibroblasts. Blocking CD147 signaling also prevented bleomycin-induced pulmonary fibrosis. Our data indicated that crosstalk between PMC and lung fibroblast contributed to sub-pleural pulmonary fibrosis. TGF-β1, Wnt/β-catenin and CD147 signaling was involved in the underling mechanism.

Idiopathic pulmonary fibrosis (IPF) is a fatal fibrosing interstitial lung disease with limited therapeutic options and a median survival of 3 years after diagnosis. Dysregulated epithelial regeneration is key event involved in initiating and sustaining IPF. The type II alveolar epithelial cells (AECIIs) play a crucial role for epithelial regeneration and stabilisation of alveoli. Loss of cell apical-basal polarity contributes to fibrosis. AECII has apical-basal polarity, but it is poorly understood whether AECII apical-basal polarity loss is involved in fibrosis. Bleomycin is a traditional inducer of pulmonary fibrosis. Here firstly we observed that bleomycin induced apical-basal polarity loss in cultured AECIIs. Next, cell polarity proteins lethal (2) giant larvae 1 (Lgl1), PAR-3A, aPKC and PAR-6B were investigated. We found bleomycin induced increases of Lgl1 protein and decreases of PAR-3A protein, and bleomycin-induced PAR-3A depression was mediated by increased-Lgl1. Then Lgl1 siRNA was transfected into AECIIs. Lgl1 siRNA prevented apical-basal polarity loss in bleomycin-treated AECIIs. At last, Lgl1-conditional knockout mice were applied in making animal models. Bleomycin induced pulmonary fibrosis, but this was attenuated in Lgl1-conditional knockout mice. Together, these data indicated that bleomycin mediated AECII apical-basal polarity loss which contributed to experimental pulmonary fibrosis. Inhibition of Lgl1 should be a potential therapeutic strategy for the disease.

Panax notoginseng is often used to promote blood circulation for the intervention of cardiovascular diseases (CVDs), while the flower of Panax notoginseng (PF) is used in folk remedies for the amelioration of hypertension in the Yunnan Province of China as a tea and is increasing in popularity throughout Asia. Previous studies on the Panax notoginseng were mainly focused on the root such that limited research on the flower cannot feed the need of increasing consumption and the products quality and pharmacological profile remains to be well characterized. In this study, chromatographic fingerprints and angiogenesis activities of different batches of commercial PF decoction were determined and then multiple regression analysis was performed to analyze their spectrum-effect relationships. The results of chromatographic fingerprints and zebrafish angiogenesis bioassay indicated the significant heterogeneities in the twelve batches of commercial PF products. Multiple regression analysis on the spectrums-activi...

Transparent Electrowetting display (EWD) has been considered as one of the promising technologies for transparent display application. The performance and reliability of transparent EWD were studied and improved in this research. The surface modified of rib structure was implemented to inhibit oil overflow and patternable hydrophobic layer was also developed to deal with oil non-recovery issue.

The rmtB gene, one of the 16S rRNA methylase genes whose products confer high-level resistance to aminoglycosides, is most prevalent among Enterobacteriaceae strains. In this study, eight non-duplicate rmtB-carrying avian Escherichia coli strains from a farm in China were isolated and characterized, and further examined by phylogenetic grouping, conjugation experiments and PCR-based replicon typing. In addition, the genetic environment of rmtB was investigated by cloning and sequencing. Six rmtB-carrying E. coli were identified as phylogroup A, sequence type (ST) 156 (A-ST156), with two assigned to D-ST117; however, all of them carried the same IncI1 ST136 plasmid. The genetic environment of the rmtB gene in these eight plasmids was the same, as shown by PCR mapping. A multidrug-resistant region carrying blaTEM-1, rmtB, a class 1 integron cassette array (intI1-dfrA12-orfF-aadA2-qacEΔ1-sul1) and aacC2 was characterized on the conjugative IncI1 ST136 plasmid. Co-location of the rmtB gene with a class 1 integron cassette array and aacC2 on the conjugative plasmid will facilitate its maintenance and dissemination.

Smart window is an emerging application for display industry. It can control the sunlight penetration and display information. In this paper, we had made 6-inch color smart window prototype by electrowetting-based technique. The ink jet process is adopted to dose various colored oil into sub-pixel to achieve color device. Without color filter, the transmittance of the device can be improved. Further, to evaluate the practicability of using the smart window device in the night, we had added luminescence substances into the colored oils and designed the cladding structure to achieve a luminous smart window.

Transparent display is currently an interesting topic in the display technologies for mobile device, monitor, shopping window or smart window application. This paper described the large area (14 inch) transparent electrowetting display (EWD) by using two-layer hydrophilic rib structure and manufacturing process is proposed as well. This work included two parts: structure and process development of large area transparent electrowetting display and the implementation of two-layer hydrophilic rib structure and plasma treatment in the manufacturing process for electrowetting display. The two-layer structure material and plasma treatment is implemented to modify the manufacturing process and improve the panel performance. The development of this study realized the concept of transparent electrowetting display with large size display area.

70% to 90% diseases are caused from mixture of emotions and sensory pleasures and pressure. To contemporary people, the pressure is omnipresent. According to World Health Organization (WHO) recognizing, there are more than 80 types of physical and psychological diseases, most of them are related to psychology. In recent years more and more people believe and research on music therapy.

For outdoor multimedia device, electrowetting display (EWD) is one of the potential technologies. In this paper, we evaluated the single layer multi-color EW device by using various colored oils without adopting color filter. The oils were dosed into the pixel by using ink-jet printing (UP) technique. for colored oils, in order to improve the color saturation of EWD panel, we used mixed solvent to increase the solubility of dyes. Then, by using UP technique, a single layer multi-color EW device was successfully fabricated and the optical property had been evaluated. Also, to improve the reliability of fluid motion, a simulation named FLUENT was first adopted to predict and realize the fluid behavior under different electric force.