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SMAD-specific E3 ubiquitin proten ligase 1 (SMURF1) is involved in transforming growth factor (TGF)-β1/Smad pathway-mediated tissue fibrosis. However, its role in pulmonary fibrosis and the related molecular mechanisms are still unclear. This study aims to investigate whether SMURF1 inhibits autophagy and promotes pulmonary fibrosis via SMAD family member 7 (SMAD7) and TGF-β1/SMAD signal pathway. MRC-5 cells were treated with TGF-β1 followed by MURF1- interference. The rate of cell migration was assessed using the cell scratch test. Autophagosomes were analyzed using a transmission electron microscope. mRNA levels of SMURF1, SMAD7, TGF-β1, phosphorylated (p)-SMAD1, p-SMAD3, α-smooth muscle actin (α-SMA), matrix metallopeptidase 7 (MMP7), microtubule-associated protein light chain 3 (LC3 ) and Beclin1 were evaluated by quantitative real-time PCR (qPCR), Western blotting, and immunofluorescence. The interaction between SMURF1 and SMAD7 was investigated in a co-immunoprecipitation (Co-IP) experiment. We found that after TGF-β1 treatment, the mRNA levels of SMURF1, α-SMA, MMP7, and p-Smad1/3 were increased, and the levels of Beclin1 and LC3 were decreased. Apart from these, cell autophagy was decreased, while the migration ability was increased. After SMURF1-interference, SMURF1, α-SMA and MMP7 mRNA levels were significantly decreased, p-SMAD1 was slightly reduced, and p-Smad3 was not changed. As for Beclin1 and LC3, their transcription increased, cell autophagy increased, and migratory ability decreased. The interaction between SMURF1 and Smad7 was confirmed by Co-IP. In conclusion, SMURF1 may inhibit autophagy and promote lung fibrosis by downregulating SMAD7 and activating the TGF-β1/SMAD pathway. These results may serve as a basis for the development of new therapeutic targets in the pulmonary fibrosis clinic.

Idiopathic pulmonary fibrosis (IPF) is a serious progressive and irreversible lung disease with unknown etiology and few treatment options. This disease was once thought to be a chronic inflammatory-driven process, but it is increasingly recognized that the epithelial–mesenchymal transition (EMT) contributes to the cellular origin of fibroblast accumulation in response to injury. During the pathogenesis of pulmonary fibrotic diseases, transforming growth factor- β (TGF- β ) signaling is considered a pivotal inducer of EMT and fibroblast activation, and a number of therapeutic interventions that interfere with TGF- β signaling have been developed to reverse established fibrosis. However, efficient and well-tolerated antifibrotic agents are not currently available. Previously, we reported the identification of sorafenib to antagonize TGF- β signaling in mouse hepatocytes in vitro . In this manuscript, we continued to evaluate the antifibrotic effects of sorafenib on bleomycin (BLM)-induced pulmonary fibrosis in mice. We further demonstrated that sorafenib not only profoundly inhibited TGF- β 1-induced EMT in alveolar epithelial cells, but also simultaneously reduced the proliferation and collagen synthesis in fibroblasts. Additionally, we presented in vivo evidence that sorafenib inhibited the symptoms of BLM-mediated EMT and fibroblast activation in mice, warranting the therapeutic potential of this drug for patients with IPF.

To reduce fan noise and weight, according to the structural characteristics of a turbofan engine, a fan rotor with an ultra-low rotating speed is designed in this study by using a new concept of diffusion blade profiles in which the rotating speed of an ultra-highly loaded rotor is only 0.58 times that of a normally loaded rotor. To further examine the applicability of this rotor, its matching stator is also designed. The flow fields in the ultra-highly and normally loaded fan stages are simulated using the same numerical method to conduct an aerodynamic characteristic comparison. Compared with the normally loaded rotor, the sizes of the boundary layers on the blade surfaces, the wakes behind the blades and the flow losses of the ultra-highly loaded rotor are smaller. At the design point, the efficiency of the ultra-highly loaded fan stages is higher than that of the normally loaded stage; moreover, the surge margin of the former is evidently larger than that of the latter. The ultra-highly loaded fan could be a good candidate for use in Ultra-High Bypass Ratio Geared Turbofan (UHBRGT) technology.

Background Interleukin (IL)-6, an important proinflammatory cytokine, plays a potential pathological role in systemic lupus erythematosus (SLE). Studies on the relationship of IL-6 gene polymorphisms with SLE are inconclusive. The aim of this study was to estimate the relationship more precisely. Methods The databases of PubMed and Web of Science updated to 30 August 2014 were retrieved. Meta-analysis was conducted using allelic contrast, dominant, recessive and homozygote contrast models. Fifteen studies were included in this study and ethnicity-specific meta-analysis was performed on European, Iranian and Asian populations. Results Analysis for the IL-6-174 G/C polymorphism under all models except the homozygote contrast model indicated an association in the overall population (allelic contrast model: odds ratio (OR) 1.428, 95% confidence interval (CI) 1.124–1.812, dominant model: OR 1.382, 95% CI 1.037–1.842, recessive model: OR 1.610, 95% CI 1.158–2.240, homozygote contrast model: OR 1.759, 95% CI 0.989–3.127), as well as in European individuals under all four genetic models (allelic contrast model: OR 1.557, 95% CI 1.155–2.098, dominant model: OR 1.699, 95% CI 1.203–2.400, recessive model: OR 1.506, 95% CI 1.176–1.930, homozygote contrast model: OR 2.118, 95% CI 1.103–4.065). Analysis for the IL-6-572 G/C polymorphism indicated significant association in overall ethnicities under the recessive model (OR 1.491, 95% CI 1.104–2.014), but not under other models or in Asian individuals. In addition, significant association between the IL-6-174 G/C polymorphism and discoid skin lesions and antinuclear antibodies (ANAs) were found under the allelic contrast model and recessive model, respectively (discoid skin lesions: OR 2.271, 95% CI 1.053–4.895; ANAs: OR 2.244, 95% CI 1.141–4.416). Conclusion This meta-analysis provides evidence of the association between the IL-6 polymorphism and the risk of SLE, hinting that the IL-6-174 G/C and IL-6-572 G/C polymorphisms may play a role in SLE susceptibility.

For InAs/GaAs quantum dot system, the evolution of the wetting layer (WL) with the InAs deposition thickness has been studied by reflectance difference spectroscopy (RDS). Two transitions related to the heavy- and light-hole in the WL have been distinguished in RD spectra. Taking into account the strain and segregation effects, a model has been presented to deduce the InAs amount in the WL and the segregation coefficient of the indium atoms from the transition energies of heavy- and light-holes. The variation of the InAs amount in the WL and the segregation coefficient are found to rely closely on the growth modes. In addition, the huge dots also exhibits a strong effect on the evolution of the WL. The observed linear dependence of In segregation coefficient upon the InAs amount in the WL demonstrates that the segregation is enhanced by the strain in the WL.

This study examines the microtubular cytoskeleton during megasporogenesis in the Nun orchid, Phaius tankervilliae. The subepidermal cell located at the terminal end of the nucellar filament differentiates first into an archesporial cell and then enlarges to become the megasporocyte. The megasporocyte undergoes the first meiotic division, giving rise to two dyad cells of unequal size. Immunostaining reveals that microtubules become more abundant as the megasporocyte increases in size. Microtubules congregate around the nucleus forming a distinct perinuclear array and many microtubules radiate directly from the nuclear envelope. In the megasporocyte, prominent microtubules are readily detected at the chalazal end of the cell cytoplasm. After meiosis I, the chalazal dyad cell expands in size at the expense of the micropylar dyad cell. At this stage, new microtubule organizing centres can be found at the corners of the cells. The appearance of these structures is stage-specific and they are not found at any other stages of megasporogenesis. The functional dyad cell undergoes the second meiotic division, resulting in the formation of two megaspores of unequal size. The chalazal megaspore enlarges and eventually gives rise to the embryo sac. As the functional megaspore expands, the microtubules again form a distinct perinuclear array with many microtubules radiating from the nuclear envelope. A defined cortical array of microtubules has not been found in P. tankervilliae during the course of megasporogenesis.

In Cymbidium sinense, the pattern of embryo development is unusual in that oblique cell divisions result in the formation of several suspensor cells prior to the development of the embryo proper. Characteristic changes in microtubular distribution can be found within the zygote and the proembryo during their development. After fertilization, the ellipsoid-shaped zygote has randomly distributed micro tubules within its cytoplasm. As the zygote takes on a more rounded appearance, microtubules organize into a dense meshwork. Furthermore, microtubule bundles appear at the chalazal region of the cell prior to the first mitotic division of the zygote. At the preprophase stage of mitosis, a preprophase band of microtubules appears in the cytoplasm of the zygote. The zygote divides obliquely and unequally and gives rise to an apical cell and a slightly larger basal cell. Many randomly-aligned microtubules can be found in the cortex of the basal cell. The increase in the abundance of microtubules coincides with the isotropic expansion of the basal cell. The early division of the basal cell and subsequent division of the apical cell results in the formation of a four-celled embryo, of which three cells near the micropylar pole develop as suspensor cells. In the suspensor cells, the microtubules tend to orient in the same direction as the long axis of the cell. In addition, prominent microtubules can also be found near the adjoining cell walls of the four-celled embryo. The terminal cell is highly cytoplasmic with abundant microtubules within the cell. Subsequent divisions of the terminal cell give rise to additional suspensor cells and the embryo proper. In the mature embryo, five suspensor cells are usually present; one eventually grows through the micropyle of the inner integument and four grow towards the chalazal pole. The cortical microtubules of suspensor cells redistribute from a longitudinal to a transverse direction as they grow towards their respective poles.

Anthers of rice (Oryza sativa L.) at different stages of development were cryofixed, freeze-substituted, and embedded in methacrylate. Sections were then cut and immuno-labeled with anti-tubulin to localize microspore microtubules. Changes in microtubule distribution pattern were followed by confocal fluorescence microscopy. To facilitate description, pollen development has been divided into four developmental stages (twenty-four phases). (i) The young-microspore stage (phases 1-5) is characterized by the formation of a vacuole. When the vacuole enlarges, the nucleus moves to the periphery of the cell. Afterwards the nucleus migrates to a site opposite the germ pore. Between the germ pore and the nucleus there is a strand of cytoplasm which contains some microtubules that run in parallel to the pore-nucleus axis. (ii) At the first-mitosis stage (phases 6-12) a perinuclear band of tubules appears which eventually girdles the nucleus. (iii) At the generative-cell development stage (phases 13-20), after the first mitosis a generative cell forms at a site opposite the germ pore. It is initially lens-shaped and part of its wall is appressed closely to the plasma membrane of the microspore. The wall of the generative cell contains cellulose and callose. Later the generative cell detaches from the microspore wall and migrates into the cytoplasm of the vegetative cell. In the vegetative cytoplasm the generative cell becomes spherical. (iv) At the second-mitosis and sperm formation stage (phases 21-24) the mitotic division is symmetrical. Before division, the shape of the generative cell changes from spherical to spindle-shaped. After cell division two sperm cells form, although they do not detach from each other. Later, cytoplasmic processes containing microtubules develop at the two ends of the sperm cells. These long processes remain linked to each other to form a paired unit.[PUBLICATION ABSTRACT]

Embryo development in Cymbidium sinenseis characterized by two consecutive oblique divisions resulting in the formation of a four-celled embryo. Three of the four cells towards the micropyle begin to vacuolate while the remaining cell located at the terminus remains cytoplasmic. The three cells towards the base become suspensor cells, and they continue to elongate and expand by the process of vacuolation. The terminal cytoplasmic cell continues to divide and give rise to the embryo proper and additional suspensor cells. Nile red staining indicates the absence of cuticular material in the walls of the suspensor cells. A positive reaction towards nile red can be detected in the embryo proper after periclinal divisions have ceased in the surface layer. In the mature embryo, storage protein and lipid are present in the cells of the embryo proper.