Abstract The discovery of coherent pulsations from several ultraluminous X-ray pulsars (ULXPs) has provided direct evidence of a supercritical accretion flow. However, the geometrical structure of ...such an accretion flow onto the central neutron star remains poorly understood. NGC 5907 ULX1 is one of the most luminous ULXPs, with a luminosity exceeding 10 41 erg s −1 . Here we present a broadband X-ray study of this ULXP using the data from simultaneous observations with XMM-Newton and NuSTAR conducted in 2014 July. The phase-resolved spectra are well reproduced by a model consisting of a multicolor disk blackbody emission with a temperature gradient of p = 0.5 ( T ∝ r − p ) and a power law with an exponential cutoff. The disk component is phase-invariant and has an innermost temperature of ∼ 0.3 keV. Its normalization suggests a relatively low inclination angle of the disk, in contrast to the previous claims in other literature. The power-law component, attributed to the emission from the accretion flow inside the magnetosphere of the neutron star, indicates phase-dependent spectral shape changes; the spectrum is slightly harder in the pre-peak phase than in the post-peak phase. This implies that the magnetosphere has an asymmetric geometry around the magnetic axis and that hotter regions close to the magnetic pole become visible before the pulse peak.
ABSTRACT
Here, we present results from over 500 ksChandra and XMM–Newton observations of the cool core of the Centaurus cluster. We investigate the spatial distributions of the O, Mg, Si, S, Ar, Ca, ...Cr, Mn, Fe, and Ni abundances in the intracluster medium with CCD detectors, and those of N, O, Ne, Mg, Fe, and Ni with the Reflection Grating Spectrometer (RGS). The abundances of most of the elements show a sharp drop within the central 18 arcsec, although different detectors and atomic codes give significantly different values. The abundance ratios of the above elements, including Ne/Fe with RGS, show relatively flat radial distributions. In the innermost regions with the dominant Fe–L lines, the measurements of the absolute abundances are challenging. For example, AtomDB and SPEXACT give Fe = 0.5 and 1.4 solar, respectively, for the spectra from the innermost region. These results suggest some systematic uncertainties in the atomic data and response matrices at least partly cause the abundance drop rather than the metal depletion into the cold dust. Except for super-solar N/Fe and Ni/Fe, sub-solar Ne/Fe, and Mg/Fe, the abundance pattern agrees with the solar composition. The entire pattern is challenging to reproduce with the latest supernova nucleosynthesis models. Observed super-solar N/O and comparable Mg abundance to stellar metallicity profiles imply that the mass-loss winds dominate the intracluster medium in the brightest cluster galaxy. The solar Cr/Fe and Mn/Fe ratios indicate a significant contribution of near- and sub-Chandrasekhar mass explosions of Type Ia supernovae.
Abstract
Chemical elements in the hot medium permeating early-type galaxies, groups, and clusters make such objects an excellent laboratory for studying metal enrichment and cycling processes on the ...largest scales of the universe. Here, we report the analysis by the XMM-Newton Reflection Grating Spectrometer of 14 early-type galaxies, including the well-known brightest cluster galaxies of Perseus, for instance. The spatial distribution of the O/Fe, Ne/Fe, and Mg/Fe ratios is generally flat in the central 60″ regions of each object, irrespective of whether or not a central Fe abundance drop has been reported. Common profiles between noble gas and normal metal suggest that the dust depletion process does not work predominantly in these systems. Therefore, observed abundance drops are possibly attributed to other origins, such as systematics in the atomic codes. Giant systems with a high ratio of gas mass to luminosity tend to hold a hot gas (∼2 keV) yielding the solar N/Fe, O/Fe, Ne/Fe, Mg/Fe, and Ni/Fe ratios. Contrarily, light systems in a sub-keV temperature regime, including isolated or group-centered galaxies, generally exhibit supersolar N/Fe, Ni/Fe, Ne/O, and Mg/O ratios. We find that the latest supernova nucleosynthesis models fail to reproduce such a supersolar abundance pattern. Possible systematic uncertainties contributing to these high abundance ratios of cool objects are also discussed in tandem with the crucial role of future X-ray missions.
Hepatocellular carcinoma (HCC) is the second leading cause of cancer‐related death. High recurrence rates after curative resection and the lack of specific biomarkers for intrahepatic metastases are ...major clinical problems. Recently, exosomal microRNAs (miRNAs) have been reported to have a role in the formation of the pre‐metastatic niche and as promising biomarkers in patients with malignancy. Here we aimed to clarify the molecular mechanisms of intrahepatic metastasis and to identify a novel biomarker miRNA in patients with HCC. A highly intrahepatic metastatic cell line (HuH‐7M) was established by in vivo selection. HuH‐7M showed increased proliferative ability and suppression of apoptosis and anoikis. HuH‐7M and the parental cell (HuH‐7P) showed the similar expression of epithelial‐mesenchymal transition markers and cancer stem cell markers. In vivo, mice treated with exosomes derived from HuH‐7M showed increased tumorigenesis of liver metastases. Exosomes from HuH‐7M downregulated endothelial cell expression of vascular endothelial‐cadherin (VE‐cadherin) and zonula occludens‐1 (ZO‐1) in non‐cancerous regions of liver and increased the permeability of FITC‐dextran through the monolayer of endothelial cells. The miRNAs (miR‐638, miR‐663a, miR‐3648, and miR‐4258) could attenuate endothelial junction integrity by inhibiting VE‐cadherin and ZO‐1 expression. In patients with HCC, higher serum exosomal miR‐638 expression was associated with tumor recurrence. In conclusion, the miRNAs secreted from a highly metastatic cancer cell can promote vascular permeability via downregulation of endothelial expression of VE‐cadherin and ZO‐1. Serum exosomal miR‐638 expression holds potential for serving as a significant and independent prognostic marker in HCC.
miR‐638, miR‐663a, miR‐3648, and miR‐4258 downregulate VE‐cadherin and ZO‐1 expression in HUVECs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
A phase-resolved analysis on the X-ray spectrum of ultraluminous X-ray pulsar (ULXP) NGC 300 ULX-1 is performed with data taken with XMM-Newton and NuSTAR on 2016 December 16. In addition to ...the classical phase-restricting analysis, a method developed in active galactic nuclei studies is newly employed for ULXP. It has revealed that the pulsation cycle of the source can be divided into two intervals in terms of X-ray variability. This suggests the rotating flow consists of at least two representative emission regions. Furthermore, the new method successfully decomposed the spectrum into an independent pair in each interval. One is an unchanging-component spectrum that can be reproduced by a standard disk model with a
720
−
120
+
220
km inner radius and a 0.25 ± 0.03 keV peak temperature. The other is the spectrum of the component that coincides with the pulsation. This was explained with a Comptonization of a
0.22
−
0.1
+
0.2
keV blackbody and exhibited a harder photon index in the brighter phase interval of two. The results are consistent with a picture that the pulsating emission originates from a funnel-like flow formed within the magnetosphere, and the inner flow exhibiting a harder continuum is observed exclusively when the opening cone points to the observer.
ABSTRACT
Using archival data from Suzaku, XMM–Newton, and NuSTAR, nine representative ultra-luminous X-ray sources (ULXs) in nearby galaxies were studied. Their X-ray spectra were all reproduced with ...a multicolour disc emission model plus its Comptonization. However, the spectral shapes of individual sources changed systematically depending on the luminosity, and defined three typical spectral states. These states differ either in the ratio between the Comptonizing electron temperature and the innermost disc temperature, or in the product of Compton y-parameter and fraction of the Comptonized disc photons. The luminosity range at which a particular state emerges was found to scatter by a factor of up to 16 among the eight ULXs. By further assuming that the spectral state is uniquely determined by the Eddington ratio, the sample ULXs are inferred to exhibit a similar scatter in their masses. This gives a model-independent support to the interpretation of ULXs in terms of relatively massive black holes. None of the spectra showed noticeable local structures. Especially, no Fe K-shell absorption/emission lines were detected, with upper limits of 30–40 eV in equivalent width from the brightest three among the sample: NGC 1313 X-1, Holmberg IX X-1, and IC 342 X-1. These properties disfavour ordinary mass accretion from a massive companion star, and suggest direct Bondi–Hoyle accretion from dense parts of the interstellar medium.
Although the tumor microenvironment plays an important role in tumor growth, it is not fully understood what role hepatic stellate cells (HSCs) play in the hepatocellular carcinoma (HCC) ...microenvironment.
A high-fat diet after streptozotocin was administered to HSC-specific Atg7-deficient (GFAP-Atg7 knockout KO) or growth differentiation factor 15 (GDF15)-deficient (GFAP-GDF15KO) mice. LX-2 cells, a human HSC cell line, were cultured with human hepatoma cells.
In the steatohepatitis-based tumorigenesis model, GFAP-Atg7KO mice formed fewer and smaller liver tumors than their wild-type littermates. Mixed culture of LX-2 cells and hepatoma cells promoted LX-2 cell autophagy and hepatoma cell proliferation, which were attenuated by Atg7 KO in LX-2 cells. Hepatoma cell xenograft tumors grew rapidly in the presence of LX-2 cells, but Atg7 KO in LX-2 cells abolished this growth. RNA-sequencing revealed that LX-2 cells cultured with HepG2 cells highly expressed GDF15, which was abolished by Atg7 KO in LX-2 cells. GDF15 KO LX-2 cells did not show a growth-promoting effect on hepatoma cells either in vitro or in the xenograft model. GDF15 deficiency in HSCs reduced liver tumor size caused by the steatohepatitis-based tumorigenesis model. GDF15 was highly expressed and GDF15-positive nonparenchymal cells were more abundant in human HCC compared with noncancerous parts. Single-cell RNA sequencing showed that GDF15-positive rates in HSCs were higher in HCC than in background liver. Serum GDF15 levels were high in HCC patients and increased with tumor progression.
In the HCC microenvironment, an increase of HSCs that produces GDF15 in an autophagy-dependent manner may be involved in tumor progression.
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Background
CD36, a multi-ligand scavenger receptor, has been associated with several cancers. Many studies have revealed that CD36 contributed to cancer malignancy. This study aimed to reveal the ...function of CD36 expression in pancreatic ductal adenocarcinoma (PDAC).
Methods
CD36 expression was characterized using immunohistochemistry in 95 clinical specimens resected from patients with PDAC. We divided patients into two groups, with different CD36 expression levels, and analyzed and compared their prognoses. CD36 expression was also assessed in PDAC cell lines. Gemcitabine-resistant (GR) PDAC cell lines were transfected with small interfering RNA (siRNA) that specifically targeted CD36 to evaluate chemoresistance and apoptosis.
Results
In resected PDAC samples, CD36 expression was significantly correlated with microinvasion into the venous system (
p
= 0.0284). Patients with high CD36 expression had significantly lower overall survival (OS) and recurrence-free survival (RFS) rates than patients with low expression; thus, CD36 was an independent prognostic factor for OS and RFS. In subgroup analyses, CD36 was an independent risk factor for OS and RFS in 59 patients treated with gemcitabine adjuvant chemotherapy. CD36 expression was upregulated in PDAC–GR cell lines compared with the PDAC parent cell line. Transduction with siRNA downregulated CD36, which reduced PDAC cell resistance to gemcitabine and inhibited anti-apoptosis proteins.
Conclusion
CD36 expression influenced gemcitabine resistance by regulating anti-apoptosis proteins. High CD36 expression was a significant, unfavorable prognostic factor in PDAC. Anti-CD36 treatment might serve as an optional treatment for lowering resistance to gemcitabine.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
CXCL9, an IFN‐γ inducible chemokine, has been reported to play versatile roles in tumor‐host interrelationships. However, little is known about its role in intrahepatic cholangiocarcinoma (iCCA). ...Here, we aimed to elucidate the prognostic and biological implications of CXCL9 in iCCA. Endogenous CXCL9 expression and the number of tumor‐infiltrating lymphocytes were immunohistochemically assessed in resection specimens. These data were validated in mice treated by silencing CXCL9 with short hairpin RNA. In addition, the induction of endogenous CXCL9 and the effects of CXCL9 on tumor biological behaviors were evaluated in human cholangiocarcinoma cell lines. Immunohistochemical analyses revealed that high CXCL9 expression was closely correlated with prolonged postoperative survival and a large number of tumor‐infiltrating natural killer (NK) cells. In fact, due to the trafficking of total and tumor necrosis factor‐related apoptosis‐inducing ligand‐expressing NK cells into tumors, CXCL9‐sufficient cells were less tumorigenic in the liver than CXCL9‐deficient cells in mice. Although CXCL9 involvement in tumor growth and invasion abilities differed across cell lines, it did not exacerbate these abilities in CXCL9‐expressing cell lines. We showed that CXCL9 was useful as a prognostic marker. Our findings also suggested that CXCL9 upregulation might offer a therapeutic strategy for treating CXCL9‐expressing iCCA by augmenting anti–tumor immune surveillance.
CXCL9, an IFN‐γ inducible chemokine, plays versatile roles in the tumor‐host interrelationship. In this study, we demonstrated that elevated intratumoral CXCL9 expression was associated with a large number of tumor‐infiltrating NK cells, leading to favorable postoperative survival in patients with intrahepatic cholangiocarcinoma. Upregulation of CXCL9 might be an immunotherapeutic approach for treating intrahepatic cholangiocarcinoma.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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