Oxysterol-binding protein like protein 3 (OSBPL3) has been shown involving in the development of several human cancers. However, the relationship between OSBPL3 and colorectal cancer (CRC), ...particularly the role of OSBPL3 in the proliferation, invasion and metastasis of CRC remains unclear. In this study, we investigated the role of OSBPL3 in CRC and found that its expression was significantly higher in CRC tissues than that in normal tissues. In addition, high expression of OSBPL3 was closely related to poor differentiation, advanced TNM stage and poor prognosis of CRC. Further experiments showed that over-expression of OSBPL3 promoted the proliferation, invasion and metastasis of CRC in vitro and in vivo models. Moreover, we revealed that OSBPL3 promoted CRC progression through activation of RAS signaling pathway. Furthermore, we demonstrated that hypoxia induced factor 1 (HIF-1A) can regulate the expression of OSBPL3 via binding to the hypoxia response element (HRE) in the promoter of OSBPL3. In summary, Upregulation of OSBPL3 by HIF1A promotes colorectal cancer progression through activation of RAS signaling pathway. This novel mechanism provides a comprehensive understanding of both OSBPL3 and the RAS signaling pathway in the progression of CRC and indicates that the HIF1A-OSBPL3-RAS axis is a potential target for early therapeutic intervention in CRC progression.
A simple wet-chemical method was developed for preparation of worm-like Au–Pd nanostructures uniformly supported on reduced graphene oxide (Au–Pd/rGO) with the assistance of Brij-35. The as-prepared ...nanocomposites displayed the improved analytical performance for nitrite detection.
•Worm-like Au–Pd supported on rGO was prepared by a simple wet-chemical method.•Brij-35 was used as a growth-directing agent, a stabilizing agent, and a mild reducing agent.•The as-prepared nanocomposites showed improved analytical performance for nitrite detection.•This method displayed high sensitivity, wide linear range, and low detection limit.
In this work, we developed a simple wet-chemical method for fabrication of worm-like Au–Pd nanostructures uniformly supported on reduced graphene oxide (Au–Pd/rGO), only with the assistance of polyethylene glycol monooleyl ether (Brij-35) as a growth-directing agent, a stabilizing agent, and a mild reducing agent. The as-prepared nanocomposites showed improved analytical performance for nitrite detection, which was further explored to construct a nitrite sensor with fast response, wide linear range from 0.05 to 1000.0μM, low detection limit of 0.02μM (S/N=3), good reproducibility, and long-term stability.
XTE J1810-189 underwent an outburst in 2008, and was observed over ∼100 d by RXTE. Performing a time-resolved spectral analysis on the photospheric radius expansion burst detected on 2008 May 4, we ...obtain the source distance in the range 3.5–8.7 kpc for the first time. During its outburst, XTE J1810-189 did not enter into the high/soft state, and both the soft and hard colours decreased with decreasing flux. The fractional rms remained at high values (∼30 per cent). The RXTE/PCA spectra for 3–25 keV can be described by an absorbed power-law component with an additional Gaussian component, and the derived photon index Γ increased from 1.84 ± 0.01 to 2.25 ± 0.04 when the unabsorbed X-ray luminosity at 3–25 keV dropped from 4 × 1036 to 6 × 1035 erg s−1. The relatively high flux, dense observations and broad-band spectra are strong evidence that the softening behaviour detected in the outburst of XTE J1810-189 originates from the evolution of a non-thermal component rather than the thermal component (i.e. neutron star surface emission).
Glucocorticoid (GC) hormone has been commonly used to treat systemic inflammation and immune disorders. However, the side effects associated with long-term use of high-dose GC hormone limit its ...clinical application seriously. GC hormone that can specifically target the lung might decrease the effective dosage and thus reduce GC-associated side effects. In this study, we successfully prepared human lung-targeting liposomal methylprednisolone crosslinked with nanobody (MPS-NSSLs-SPANb). Our findings indicate that MPS-NSSLs-SPANb may reduce the effective therapeutic dosage of MPS, achieve better efficacy, and reduce GC-associated side effects. In addition, MPS-NSSLs-SPANb showed higher efficacy and lower toxicity than conventional MPS.
Multiple myeloma (MM) is a cancer that occurs in plasma cells, which fall under the category of white blood cells that are in charge of antibody production. According to previous studies, ...microRNA-497 (miR-497) functions as a tumor suppressor in several types of cancer, including gastric cancer and colorectal cancer. Therefore, the present study aims to investigate the effects of miR-497 on cellular function of human MM cells through the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway by targeting Raf-1. The differentially expressed genes and miRs in MM, and the relationship between the miR and gene were verified. It was found that Raf-1 was a target gene of miR-497. The data obtained from MM tissues showed increased Raf-1 level and decreased miR-497 level. MM cells were treated with mimic, inhibitor and siRNA in order to evaluate the role of miR-497, Raf-1 and MAPK/ERK in MM. The expression pattern of miR-497, Raf-1, ERK1/2, survivin, B-cell lymphoma-2 (Bcl-2) and BCL2-Associated X (Bax) as well as the extent of ERK1/2 phosphorylation were determined. Retored miR-497 and si-Raf-1 resulted in increases in the Bax expression and cell apoptosis and decreases in the expressions of Raf-1, MEK-2, survivin, Bcl-2, along with the extent of ERK1/2 phosphorylation. In addition, the biological function evaluations of MM cells revealed that miR-497 mimic or si-Raf-1 led to suppression in cell proliferation, invasion and migration. In conclusion, our results have demonstrated that miR-497 targets Raf-1 in order to inhibit the progression of MM by blocking the MAPK/ERK signaling pathway.
Abstract
Characterizing the long-term variability of AGNs is a key legacy of RXTE. We carry out a spectral analysis on a sample of 20 Seyfert 1 galaxies, which had been observed by the RXTE for at ...least 100 times. All 18,335 spectra are fitted in a uniform way using a power-law component plus an additional Gaussian line when necessary. For any source in our sample, we confirm that the spectrum softens or the photon index, Γ, increases with increasing the 2–10 keV luminosity, LX. However, different source holds distinct Γ − LX/LEdd relation, rather than a common one. We also fit the correlation with a function of Γ = C + β × log (flux), where C is a constant and parameter β is the slope of the correlation. In this way, the increase speed of the Γ − LX/LEdd relation can be depicted with the parameter β. Since our sample contains a large sample of long-term monitored sources, it allows us to explore the second order effect of spectral evolution. We find that there is an anti-correlation between β and the X-ray Eddington ratio, LX/LEdd. That is, the increasing tendency of Γ with increasing X-ray luminosity becomes slower when the source has a larger X-ray Eddington ratio. Our results may indicate changes in the geometry and/or the viscosity parameter of the accretion disc at different Eddington ratios.
Swift J1357.2−0933 underwent an episodic accretion in 2011 and provided very regular temporal and spectral evolution, making it an ideal source for exploring the nature of very faint X-ray ...transients. In this work, we present a detailed analysis on both X-ray and near-ultraviolet (NUV) light curves. The fluxes at all wavelengths display a near-exponential decays in the early phase and transit to a faster decay at late times. The e-folding decay time-scales monotonically decrease with photon energies, and the derived viscous time-scale is
$\tau _{\rm \dot{M}} \sim 60$
d. The time-scale in the late faster decay stage is about a few days. The high ratio of NUV luminosity to X-ray luminosity indicates that the irradiation is unimportant in this outburst, while the near-exponential decay profile and the long decay time-scales conflict with the disc thermal–viscous instability model. We thus suggest that the disc is thermally stable during the observations. Adopting the truncated disc model, we obtain a lower limit of peak accretion rate of
$0.03 \dot{M}_{\rm Edd}$
and the X-ray radiative efficiency η < 5 × 10−4, which decreases as the luminosity declines. The low X-ray radiative efficiency is caused by the combined action of advection and outflows, and naturally explains that the X-ray reprocessing is overwhelmed by the viscous radiation of the outer standard disc in the NUV regime. We also propose a possibility that the outer standard disc recedes from the central black hole, resulting in the faster decay at late times.
During the course of screening natural sesquiterpenoids for new antitumor agents, two novel compounds, fischerisin A (1) and fischerisin B (2), were isolated from the roots of Ligularia fischeri. ...Their structures were elucidated by interpretation of their IR, high resolution-mass spectrometry (HR-MS), 1D- and 2D-NMR data. Fischerisin A and B are the first representatives of a novel sesquiterpenoid-geranylhydroquinone hybrid, and both compounds exhibited in vitro cytotoxicity against cultured human oral epidermoid carcinoma (KB) and human breast cancer (MCF-7) cell lines with IC50 values of 9.7 and 10.2 μM, and 9.8 and 17.8 μM, respectively.
ABSTRACT III Zw 2 is the prototype of radio-intermediate quasars. Although there is the evidence of possessing strong jet, significant γ-ray emission has not been reported before. In this work, we ...carry out a detailed analysis of the latest Fermi-LAT Pass 8 data. No significant γ-ray signal has been detected in the time-averaged 7-year Fermi-LAT data of III Zw 2; however, we have identified two distinct γ-ray flares with isotropic luminosities of ∼1045 erg s−1. Multiwavelength data analysis (also including the optical photometric observations from Yunnan Observatories) are presented and the main finding is simultaneous optical and γ-ray flares of III Zw 2 appearing in 2009 November. Violent γ-ray variability with a doubling timescale of 2.5 hr was detected in another γ-ray flare in May 2010, for which the 3-hr γ-ray peak flux is ∼250 times of the average flux in 7 years. Rather similar behaviors are observed in blazars and the blazar model can reasonably reproduce the spectral energy distribution of III Zw 2 in a wide energy range, strongly suggesting that its central engine resembles that of blazars. In view of its core, which shares radio similarities with young radio sources, together with weak extended radio lobe emission, we suggest that III Zw 2 harbors a recurrent activity core and thus serves as a valuable target for investigating the fueling and triggering of the activity in radio-loud active galactic nuclei.
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