The epithelial-mesenchymal transition (EMT) is crucial to cancer progression and metastasis. Although multiple cellular miRNAs have been identified to regulate the EMT and metastasis in cancers, the ...role of viral miRNAs in cancer progression remains largely unknown. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy typically characterized by its early metastasis. In the present study, we have discovered the involvement of a viral miRNA, EBV-miR-BART7-3p, in the EMT and metastasis of NPC cells. Initially, we observed that EBV-miR-BART7-3p was highly expressed in NPC and positively correlated with lymph node metastasis and clinical stage of NPC. Subsequently, we demonstrated that EBV-miR-BART7-3p enhanced cell migration/invasion in vitro, cancer metastasis in vivo, and particularly the EMT characterized by loss of epithelial markers and gain of mesenchymal features in NPC cells. Furthermore, mechanistic studies disclosed that EBV-miR-BART7-3p targeted a major human tumor suppressor PTEN, modulating PI3K/Akt/GSK-3β signaling and eventually leading to the high expression and nuclear accumulation of Snail and β-catenin, which favor EMT. Knockdown of PTEN could phenocopy the effect of EBV-miR-BART7-3p, whereas re-expression of PTEN resulted in a phenotypic reversion. Moreover, these findings were supported by an observation of an EBV-positive cell model in which silencing of endogenous EBV-miR-BART7-3p partially attenuated cell migration/invasion and altered EMT protein expression pattern via reverting PI3K/Akt, Snail and β-catenin expression. Thus, this study suggests a novel mechanism by which EBV-miR-BART7-3p modulates the EMT and metastasis of NPC cells, and a clinical implication of EBV-miR-BART7-3p as a potential biomarker or therapeutic target.
Summary
Neopterin is primarily synthesized and released by activated macrophages/monocytes upon stimulation with interferon‐γ and is considered as a marker for macrophage activation. This study aimed ...to analyze the serum levels of neopterin in patients with dermatomyositis (DM) in association with clinical manifestations, laboratory data and patient prognosis. One hundred and eighty‐two consecutive DM patients and 30 healthy controls were retrospectively enrolled into the study. Serum levels of neopterin were significantly increased in DM patients compared to healthy controls (P < 0·001). High serum neopterin levels were associated with anti‐melanoma differentiation‐associated gene (MDA5) antibody, rapidly progressive interstitial lung disease (RP‐ILD) and characteristic DM cutaneous involvement. Longitudinal assessment of serum samples revealed that the serum neopterin levels were closely correlated with disease severity (β = 30·24, P < 0·001). In addition, a significant increase in serum neopterin concentration of non‐survivors was observed when compared to that of survivors (P < 0·001). Receiver operator characteristic curves showed that serum neopterin could distinguish non‐survivors and survivors at an optimal cut‐off level of 22·1 nmol/l with a sensitivity and specificity of 0·804 and 0·625, respectively (P < 0·001). Kaplan–Meier survival curves revealed that DM patients with serum neopterin > 22·1 nmol/l had a significantly higher mortality compared to the patient group with serum neopterin < 22·1 nmol/l (log‐rank P < 0·001). Multivariate regression analysis identified high serum neopterin concentration to be an independent risk factor for poor prognosis in DM (adjusted hazard ratio = 4·619, 95% confidence interval = 2·092–10·195, P < 0·001). In conclusion, increased serum levels of neopterin were significantly associated with RP‐ILD and reduced survival in DM patients, suggesting it as a promising biomarker in disease evaluation of DM.
Serum neopterin was significantly increased in DM, especially in patients with anti‐MDA5 and RP‐ILD. Serum neopterin seems to parallel disease severity in DM patients. High baseline level of neopterin was associated with increased mortality and was identified as an independent prognostic factor in DM.
Transition metals can catalyse the stereoselective synthesis of cyclic organic molecules in a highly atom-efficient process called cycloisomerization. Many diastereoselective (substrate ...stereocontrol), and enantioselective (catalyst stereocontrol) cycloisomerizations have been developed. However, asymmetric cycloisomerizations where a chiral catalyst specifies the stereochemical outcome of the cyclization of a single enantiomer substrate--regardless of its inherent preference--are unknown. Here we show how a combined theoretical and experimental approach enables the design of a highly reactive rhodium catalyst for the stereoselective cycloisomerization of ynamide-vinylcyclopropanes to 5.3.0-azabicycles. We first establish highly diastereoselective cycloisomerizations using an achiral catalyst, and then explore phosphoramidite-complexed rhodium catalysts in the enantioselective variant, where theoretical investigations uncover an unexpected reaction pathway in which the electronic structure of the phosphoramidite dramatically influences reaction rate and enantioselectivity. A marked enhancement of both is observed using the optimal theory-designed ligand, which enables double stereodifferentiating cycloisomerizations in both matched and mismatched catalyst-substrate settings.
The perfluorooctanoic acid (PFOA)-degrading strain YAB1 was isolated from the soil near a perfluorinated compound production plant through acclimation and enrichment culture, using PFOA as the sole ...carbon source. This strain was preliminarily identified as Pseudomonas parafulva based on colony morphology, physiological and biochemical features, and 16S rRNA gene sequencing. Using shaking flask fermentation, the maximum tolerable concentration of YAB1 on PFOA was found to be 1000 mg/L. The optimal conditions for bacterial growth and PFOA degradation were 30°C, pH 7, 2% inoculum, and an initial PFOA concentration of 500 mg/L. After 96 h of culture, the PFOA degradation rate determined by GC-MS analysis was 32.4%. When 1 g/L glucose was added to the inorganic salt culture medium, the degradation rate increased to 48.1%. Glucose was the best exogenous carbon source for the degradation of PFOA. This study reports the degradation performance of PFOA-degrading bacteria.
This experiment was conducted to assess the comparative effects of dietary antibiotics and oregano essential oil (OEO) addition on growth performance, antioxidant status and intestinal health of ...broilers. A total of 384 one-day-old broilers were randomly allocated to 4 treatments with 6 replicates of 16 broilers each. The 4 treatments were: an antibiotic-free control diet (control), control + 20 mg/kg colistin sulfate and 20 mg/kg virginiamycin (antibiotics), control + 200 mg/kg natural oregano essential oil (NOEO), and control + 200 mg/kg synthetic oregano essential oil (SOEO). The experiment lasted for 42 d. Results showed that birds fed with OEO had greater (P < 0.05) average daily gain (ADG) and lower (P < 0.05) feed conversion ratio (FCR) than those fed with control diet during d 1 to 21. Besides, birds fed with NOEO had the greatest (P < 0.05) ADG in the four groups during d 22 to 42. The serum oxidative stress parameters showed that OEO improved (P < 0.05) the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and glutathione reductase (GR) of birds on day 21 and the activity of total antioxidant capacity (T-AOC) of birds on d 42. Relative to control, NOEO increased (P < 0.05) the activity of T-AOC in jejunum and decreased (P < 0.05) the level of malondialdehyde (MDA) in serum and jejunum. Moreover, OEO supplementation increased (P < 0.05) the concentrations of sIgA in duodenum and jejunum, Lactobacillus and total anaerobes in cecum, as well as activities of trypsin, chymotrypsin, lipase and amylase in duodenum, but restrained (P < 0.05) the amount of Escherichia coli. The NOEO supplementation increased (P < 0.05) total anaerobes of broilers on d 42 and the villus height to crypt depth ratio (VH/CD) of ileum. These results suggest that OEO improved antioxidant status and intestinal health of broilers which contributed to the growth performance improvement of broilers. Dietary OEO supplementation can be a promising alternative to antibiotic growth promoters for improving poultry production.
A non-orthogonal constitutive model is developed to characterize the anisotropic material behavior of woven composite fabrics under large deformation. A convected coordinate system, whose in-plane ...axes are coincident with the weft and warp yarns of woven fabrics, are embedded in the shell elements. Contravariant stress components and covariant strain components in a constitutive relation are introduced into the convected coordinate system. The transformations between the contravariant/covariant components and the Cartesian components of the stress and strain tensors provide an approach for deriving the global non-orthogonal constitutive relations for woven composite fabrics. By taking advantage of the tensile–shear decoupling in the constitutive equation under the convected coordinate system, the material characterization of woven fabrics is simplified. As an essential part for these transformations, a fiber orientation model is developed, by using some fundamental continuum mechanics concepts, to trace the yarn reorientation of woven fabrics during deformation. The proposed material characterization approach is demonstrated on a balanced plain weave composite fabric. The equivalent material properties are obtained by matching with experimental data of tensile and bias extension tests on the woven composite fabric. Model validation is provided by comparing numerical results with experimental data of bias extension test and shear test. The development of this non-orthogonal model is critical to the ultimate goal, i.e. using numerical simulations to optimize the forming of woven composite fabric sheets.
Ethanol sensing has important applications, including breath alcohol checkers. A highly selective and stable ethanol sensor—see Figure—based on single‐crystalline divanadium pentoxide nanobelts is ...described, representing a new strategy for the design of novel practicable gas sensors. Potential problems caused by changes of relative humidity or the presence of other gases are ruled out.
Summary
Complement activation has a deep pathogenic influence in immunoglobulin (Ig)A nephropathy (IgAN). C3a and C5a, small cleavage fragments generated by complement activation, are key mediators ...of inflammation. The fragments exert broad proinflammatory effects by binding to specific receptors (C3aR and C5aR, respectively). However, no studies thus far have investigated the effects of C3a, C5a and their receptors on IgAN. We observed that C3aR and C5aR antagonists repressed IgA‐induced cell proliferation and interleukin (IL)‐6 and monocyte chemotactic protein 1 (MCP‐1) production in cultured human mesangial cells (HMCs). Furthermore, an IgAN mouse model induced by Sendai virus infection was employed to investigate the effects of C3aR and C5aR on IgAN in vivo for the first time. Wild‐type (WT) and several knock‐out mouse strains (C3aR–/– or C5aR–/–) were immunized intranasally with increasing doses of inactivated virus for 14 weeks and were subjected to two intravenous viral challenges during the time‐period indicated. In the Sendai virus‐induced IgAN model, C3aR/C5aR‐deficient mice had significantly reduced proteinuria, lower renal IgA and C3 deposition, less histological damage and reduced mesangial proliferation compared with WT mice. Both C3aR deficiency and C5aR deficiency, especially C3aR deficiency, inhibited renal tumour necrosis factor (TNF)‐α, transforming growth factor (TGF)‐β, IL‐1β, IL‐6 and MCP‐1 expression significantly. However, C3aR/C5aR‐deficient and WT mice with IgAN did not differ with respect to their blood urea nitrogen (BUN) and serum creatinine levels. Our findings provide further support for the idea that C3aR and C5aR are crucially important in IgAN, and suggest that pharmaceutically targeting C3aR/C5aR may hold promise for the treatment of IgAN.
In the Sendai virus‐induced IgAN model, C3aR/C5aR‐deficient mice had significantly reduced proteinuria, lower renal IgA and C3 deposition, less histologic damage and reduced mesangial proliferation compared with WT mice.
ABSTRACT
In the caviar software package, a standard tool for astrometry of images from the Cassini imaging science subsystem (ISS), Gaussian fitting is used to measure the centre of point-like ...objects, achieving a typical precision of about 0.2 pixels. In this work, we consider how alternative methods may improve on this. We compare three traditional centroiding methods: two-dimensional Gaussian fitting, median, and modified moment. Results using 56 selected images show that the centroiding precision of the modified moment method is significantly better than the other two methods, with standard deviations for all residuals in sample and line of 0.065 and 0.063 pixels, respectively, representing a factor of over 2 improvement compared to Gaussian fitting. Secondly, a comparison of observations using Cassini ISS images of Anthe is performed. Anthe results show a similar improvement. The modified moment method is then used to reduce all ISS images of Anthe during the period 2008–2017. The observed-minus-calculated residuals relative to the JPL SAT393 ephemeris are calculated. In terms of α × cos(δ) and δ in the Cassini-centred international celestial reference frame, mean values of all residuals are close to 0 km, and their standard deviations are less than 1 km for narrow angle camera images, and about 4 km for wide angle camera images.
PDF
