Insight-HXMT observations of Swift J0243.6+6124 during its 2017-2018 outburst

The recently discovered neutron star transient Swift J0243.6+6124 has been monitored by {\it the Hard X-ray Modulation Telescope} ({\it Insight-\rm HXMT). Based on the obtained data, we investigate the broadband spectrum of the source throughout the outburst. We estimate the broadband flux of the source and search for possible cyclotron line in the broadband spectrum. No evidence of line-like features is, however, found up to $\rm 150~keV$. In the absence of any cyclotron line in its energy spectrum, we estimate the magnetic field of the source based on the observed spin evolution of the neutron star by applying two accretion torque models. In both cases, we get consistent results with $B\rm \sim 10^{13}~G$, $D\rm \sim 6~kpc$ and peak luminosity of $\rm >10^{39}~erg~s^{-1}$ which makes the source the first Galactic ultraluminous X-ray source hosting a neutron star.Comment: publishe

Overview to the Hard X-ray Modulation Telescope (Insight-HXMT) Satellite

As China's first X-ray astronomical satellite, the Hard X-ray Modulation Telescope (HXMT), which was dubbed as Insight-HXMT after the launch on June 15, 2017, is a wide-band (1-250 keV) slat-collimator-based X-ray astronomy satellite with the capability of all-sky monitoring in 0.2-3 MeV. It was designed to perform pointing, scanning and gamma-ray burst (GRB) observations and, based on the Direct Demodulation Method (DDM), the image of the scanned sky region can be reconstructed. Here we give an overview of the mission and its progresses, including payload, core sciences, ground calibration/facility, ground segment, data archive, software, in-orbit performance, calibration, background model, observations and some preliminary results.Comment: 29 pages, 40 figures, 6 tables, to appear in Sci. China-Phys. Mech. Astron. arXiv admin note: text overlap with arXiv:1910.0443

Cinobufagin Induces Apoptosis in Osteosarcoma Cells Via the Mitochondria-Mediated Apoptotic Pathway

Background/Aims: Osteosarcoma is a common primary malignant bone tumor that mainly occurs in childhood and adolescence. Despite developments in the diagnosis and treatment of osteosarcoma, the prognosis is still very poor. Cinobufagin is an active component in the anti-tumor Chinese medicine called “Chan Su”, and we previously revealed that cinobufagin induced apoptosis and reduced the viability of osteosarcoma cells; however, the underlying mechanism remains to be elucidated. Herein, the present study was undertaken to illuminate the molecular mechanism of cinobufagin-induced apoptosis of osteosarcoma cell. Methods: U2OS and 143B cells were treated with different concentrations of cinobufagin. Cell viability, colony formation ability and morphological changes were assessed by a CCK-8 assay, a clonogenic assay and light microscopy, respectively. Cell apoptosis was detected by Hoechst 33258 and Annexin V-FITC/PI staining. Reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were determined by flow cytometry. Glutathione (GSH) levels were detected by a GSH and GSSG assay kit. The levels of apoptosis-related proteins were determined by western blotting, and 143B cells were introduced to establish a xenograft tumor model. The effect of cinobufagin on osteosarcoma was further investigated in vivo. Results: Our results showed that cinobufagin significantly reduced the viability of U2OS and 143B cells in vitro in a dose-and time-dependent manner. In addition, cinobufagin-induced apoptosis in U2OS and 143B cells was concentration-dependent. Moreover, we found that cinobufagin treatment increased the level of intracellular ROS, decreased ΔΨm, reduced GSH and inhibited GSH reductase (GR). The effects of cinobufagin on cell proliferation, apoptosis, ROS generation and ΔΨm loss were dramatically reversed when the cells were pretreated with the thiol-antioxidants NAC or GSH. Moreover, cinobufagin treatment increased the expression of the pro-apoptotic protein Bax and decreased the expression of the anti-apoptitic protein Bcl-2, thus altering the ratio of Bax to Bcl-2. Furthermore, Cinobufagin treatment caused cytochrome c release from the mitochondria to cytoplasm, thus increasing the protein levels of cleaved-caspase family members to induce apoptosis. Ac-DEVD-CHO or Z-LEHD-FMK significantly reduced cinobufagin-induced apoptosis. Finally, a subcutaneous xenograft animal study verified that cinobufagin also significantly suppressed osteosarcoma growth in vivo. Conclusions: Our present data demonstrated that cinobufagin triggered cell apoptosis in osteosarcoma cells via the intrinsic mitochondria-dependent apoptosis pathway by the accumulation of ROS and the loss of ΔΨm. In an in vivo subcutaneous xenograft model, cinobufagin exhibited excellent tumor inhibitory effects. These results suggest that cinobufagin might potentially be further developed as an anti-tumor candidate for treating osteosarcoma patients in the clinic

TRIM26 inhibited osteosarcoma progression through destabilizing RACK1 and thus inactivation of MEK/ERK signaling

Abstract Osteosarcoma is a highly aggressive malignant tumor that is common in the pediatric population and has a high rate of disability and mortality. Recent studies have suggested that the tripartite motif-containing family genes (TRIMs) play critical roles in oncogenesis in several cancers. TRIM26, one of the TRIMs family genes, was more frequently reported to exert a tumor-suppressive role, while its detailed functional roles in the osteosarcoma progression were still unknown and require further investigation. Herein, we found that TRIM26 was markedly downregulated in osteosarcoma tissues and cells. Survival analysis revealed that higher expression of TRIM26 was associated with better prognosis and its expression was an independent protective factor in osteosarcoma. Functional analysis demonstrated that overexpression of TRIM26 inhibited osteosarcoma cell proliferation and invasion via inhibiting the EMT process and MEK/ERK signaling. In contrast, the silence of TRIM26 caused the opposite effect. RACK1, a member of the Trp-Asp repeat protein family, was identified as a novel target of TRIM26. TRIM26 could interact with RACK1 and accelerate the degradation of RACK1, thus inactivation of MEK/ERK signaling. Overexpression of RACK1 could attenuate the inhibitory effect of TRIM26 overexpression on p-MEK1/2 and p-ERK1/2, and silence of RACK1 could partly impair the effect of TRIM26 knockdown-induced upregulation of p-MEK1/2 and p-ERK1/2. Further, a series of gain- and loss-of-function experiments showed that decreased malignant behaviors including cell proliferation and invasion in TRIM26-upregulated cells were reversed when RACK1 was overexpressed, whereas RACK1 knockdown diminished the increased malignant phenotypes in TRIM26-silenced osteosarcoma cells. In conclusion, our study indicated that TRIM26 inhibited osteosarcoma progression via promoting proteasomal degradation of RACK1, thereby resulting in inactivation of MEK/ERK signaling, and impeding the EMT process

Exploring the Osteogenic Potential of Zinc-Doped Magnesium Phosphate Cement (ZMPC): A Novel Material for Orthopedic Bone Defect Repair

In orthopedics, the repair of bone defects remains challenging. In previous research reports, magnesium phosphate cements (MPCs) were widely used because of their excellent mechanical properties, which have been widely used in the field of orthopedic medicine. We built a new k-struvite (MPC) cement obtained from zinc oxide (ZnO) and assessed its osteogenic properties. Zinc-doped magnesium phosphate cement (ZMPC) is a novel material with good biocompatibility and degradability. This article summarizes the preparation method, physicochemical properties, and biological properties of ZMPC through research on this material. The results show that ZMPC has the same strength and toughness (25.3 ± 1.73 MPa to 20.18 ± 2.11 MPa), that meet the requirements of bone repair. Furthermore, the material can gradually degrade (12.27% ± 1.11% in 28 days) and promote osteogenic differentiation (relative protein expression level increased 2–3 times) of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. In addition, in vivo confirmation revealed increased bone regeneration in a rat calvarial defect model compared with MPC alone. Therefore, ZMPC has broad application prospects and is expected to be an important repair material in the field of orthopedic medicine