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Introduction: The Medium Energy X-ray telescope (ME) is a collimated X-ray telescope onboard the Insight hard X-ray modulation telescope (Insight-HXMT) satellite. It has 1728 Si-PIN pixels readout using 54 low noise application-specific integrated circuits (ASICs). ME covers the energy range of 5-30 keV and has a total detection area of 952 cm2. The typical energy resolution of ME at the beginning of the mission is 3 keV at 17.8 keV (Full Width at Half Maximum, FWHM) and the time resolution is 255 us. In this study, we present the in-orbit performance of ME in its first 5 years of operation. Methods: The performance of ME was monitored using onboard radioactive sources and astronomical X-ray objects. ME carries six 241Am radioactive sources for onboard calibration, which can continuously illuminate the calibration pixels. The long-term performance evolution of ME can be quantified using the properties of the accumulated spectra of the calibration pixels. In addition, observations of the Crab Nebula and the pulsar were used to check the long-term evolution of the detection efficiency as a function of energy. Conclusion: After 5 years of operation, 742 cm2 of the Si-PIN pixels were still working normally. The peak positions of 241Am emission lines gradually shifted to the high energy region, implying a slow increase in ME gain of 1.43%. A comparison of the ME spectra of the Crab Nebula and the pulsar shows that the E-C relations and the redistribution matrix file are still acceptable for most data analysis works, and there is no detectable variation in the detection efficiency.

Cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) are deadly malignancy with poor prognosis and limited treatment options. Endoplasmic reticulum (ER) stress plays an important role in the pathogenesis and development of malignant solid tumors which is associated with chemotherapeutic drug resistance. The therapeutic potential of targeting ER stress signaling in cancer via surface BiP/GRP78 (78-kDa glucose-regulated protein), a major role in ER stress sensing, is now under clinical trials. YUM70 is a novel inducer of ER stress that induces apoptosis in cancer by directly bound BiP and inactivated its function. In this study, we investigated the possible role of epidermal growth factor receptor (EGFR) pathway and cell death mechanisms in YUM70 induced CCA or HCC cells cytotoxicity. Although both YUM70 and HA15 as BiP inhibitors exerted the mono-therapeutic anti-proliferation effect and induced autophagy and apoptosis, YUM70 exhibited more potent anti-tumor potential by suppressing the EGFR downstream signaling: ERK1/2 and mTOR/p70(S6K) pathways at the concentration of 100 µM more effectively. At the same tested concentration, HA15 could not inhibit the phosphorylation of ERK1/2 or p70(S6K). Moreover, we discovered that YUM70 induced GSDME dependent pyroptosis by activating NF-κB pathway and inhibited EMT via inactivation of β-catenin pathway. Additionally, pharmacologic targeting of ERK signaling is usually limited by adaptive resistance, frequently mediated by feedback activation of receptor tyrosine kinases (RTKs) signaling. We observed that treatment of HuCCT1 or Huh7 cells with YUM70 resulted in increased EGFR phosphorylation. Inhibiting EGFR activation with Gefitinib or Osimertinib synergistically increased the anti-tumor activity of BiP inhibitors. Our results demonstrated novel strategy that BiP inhibitors, in combination with Gefitinib or Osimertinib, should be tested in CCA or HCC patients.

Background Disruption of the gut barrier is an essential mechanism of inflammatory bowel diseases (IBDs) contributing to the development of mucosal inflammation. A hallmark of barrier disruption is the disassembly of epithelial adherens junctions (AJs) driven by decreased expression of a major AJ protein, E-cadherin. A group of isoxazole compounds, such as E-cadherin-upregulator (ECU) and ML327, were previously shown to stimulate E-cadherin expression in poorly differentiated human cancer cells. This study was designed to examine whether these isoxazole compounds can enhance and protect model intestinal epithelial barriers in vitro. Methods The study was conducted using T84, SK-CO15, and HT-29 human colonic epithelial cell monolayers. Disruption of the epithelial barrier was induced by pro-inflammatory cytokines, tumor necrosis factor-α, and interferon-γ. Barrier integrity and epithelial junction assembly was examined using different permeability assays, immunofluorescence labeling, and confocal microscopy. Epithelial restitution was analyzed using a scratch wound healing assay. Results E-cadherin-upregulator and ML327 treatment of intestinal epithelial cell monolayers resulted in several barrier-protective effects, including reduced steady-state epithelial permeability, inhibition of cytokine-induced barrier disruption and junction disassembly, and acceleration of epithelial wound healing. Surprisingly, these effects were not due to upregulation of E-cadherin expression but were mediated by multiple mechanisms including inhibition of junction protein endocytosis, attenuation of cytokine-induced apoptosis, and activation of promigratory Src and AKT signaling. Conclusions Our data highlight ECU and ML327 as promising compounds for developing new therapeutic strategies to protect the integrity and accelerate the restitution of the intestinal epithelial barrier in IBD and other inflammatory disorders.

Here we report the spectral-timing results of the black hole X-ray binary 4U 1630–47 during its 2021 outburst using observations from the Hard X-ray Modulation Telescope (Insight-HXMT). Type C quasi-periodic oscillations (QPOs) in ∼1.6–4.2 Hz and quasi-regular modulation (QRM) near 60 mHz are detected during the outburst. The mHz QRM has a fractional rms of ∼10%–16% in the 8–35 keV energy band with a Q factor (frequency/width) of ∼2–4. Benefiting from the broad energy band of Insight-HXMT, we study the energy dependence of the ∼60 mHz QRM in 1–100 keV for the first time. We find that the fractional rms of the mHz QRM increases with photon energy, while the time lags of the mHz QRM are soft and decrease with photon energy. Fast recurrence of the mHz QRM, in a timescale of less than 1 hr, has been observed during the outburst. During this period, the corresponding energy spectra moderately change when the source transitions from the QRM state to the non-QRM state. The QRM phenomenon also shows a dependence with the accretion rate. We suggest that the QRM could be caused by an unknown accretion instability aroused from the corona.

Background and purpose: Ginsenoside Rg1 (GS Rg1), as an important active substance of Panax ginseng, has been proven to have elaborate cardioprotective effects. The purpose of this study was to detect that GS Rg1 attenuates cardiac oxidative stress and inflammation in streptozotocin (STZ)-induced diabetic rats (DM). Methods: Cardiac function was assessed by heart rate and blood pressure. Markers relevant to myocardial oxidative stress and antioxidant capacity, and inflammatory reaction factors were detected. The mRNA and protein expression were detected by RT-qPCR and Western blot, respectively. Results: GS Rg1 treatment significantly reduced the symptoms of cardiac hypertrophy and hypertension, and also decreased oxidative stress, inflammation response, NF-κB expression and NLRP3 inflammasome expression. GS Rg1 enhanced mitochondrial biogenesis by increasing PGC-1α, complex III and complex Ⅳ expression. GS Rg1 treatment significantly increased the expression of AMPK, Nrf2 and HO-1 in cardiac tissues. Conclusion: GS Rg1 exhibited protective effect against STZ-induced cardiac dysfunction, which is potentially associated with AMPK/Nrf2/HO-1 signal pathway.

The Medium Energy X-ray telescope (ME) is one of the three main telescopes on board the Insight Hard X-ray Modulation Telescope (Insight-HXMT) astronomy satellite. ME contains 1728 pixels of Si-PIN detectors sensitive in 5-30 keV with a total geometrical area of 952 cm2. Application Specific Integrated Circuit (ASIC) chips, VA32TA6, is used to achieve low power consumption and low readout noise. The collimators define three kinds of field of views (FOVs) for the telescope, 1{\deg}{\times}4{\deg}, 4{\deg}{\times}4{\deg}, and blocked ones. Combination of such FOVs can be used to estimate the in-orbit X-ray and particle background components. The energy resolution of ME is ~3 keV at 17.8 keV (FWHM) and the time resolution is 255 {\mu}s. In this paper, we introduce the design and performance of ME., Comment: 18 pages with 36 figures

We describe the timing system and the timing calibration results of the three payloads on-board the Insight-Hard X-ray Modulation Telescope (Insight-HXMT). These three payloads are the High Energy X-ray telescope (HE, 20-250 keV), the Medium Energy X-ray telescope (ME, 5-30 keV) and the low Energy X-ray telescope (LE, 1-10 keV). We present a method to correct the temperature-dependent period response and the long-term variation of the on-board crystal oscillator, especially for ME that does not carry a temperature-compensated crystal oscillator. The time of arrivals (ToAs) of the Crab pulsar are measured to evaluate the accuracy of the timing system. As the ephemeris of the Crab pulsar given by Jodrell Bank observatory has systematic errors around 40 {\mu}s (Rots et al. 2014), we use the quasi-simultaneous observations of the X-ray Timing Instrument (XTI) on-board the Neutron star Interior Composition Explorer (NICER) to produce the Crab ephemerides and to verify the timing system of Insight-HXMT. The energy-dependent ToAs' offsets relative to the NICER measurements including physical and instrumental origins are about 24.7{\mu}s, 10.1{\mu}s and 864.7{\mu}s, and the systematic errors of the timing system are determined as 12.1{\mu}s, 8.6{\mu}s, and 15.8{\mu}s, for HE, ME and LE respectively., Comment: 29 pages, 14 figures, accepted for publication in ApJS

Septins are GTP-binding proteins that self-assemble into high-order cytoskeletal structures, filaments, and rings. The septin cytoskeleton has a number of cellular functions, including regulation of cytokinesis, cell migration, vesicle trafficking, and receptor signaling. A plant cytokinin, forchlorfenuron (FCF), interacts with septin subunits, resulting in the altered organization of the septin cytoskeleton. Although FCF has been extensively used to examine the roles of septins in various cellular processes, its specificity, and possible off-target effects in vertebrate systems, has not been investigated. In the present study, we demonstrate that FCF inhibits spontaneous, as well as hepatocyte growth factor-induced, migration of HT-29 and DU145 human epithelial cells. Additionally, FCF increases paracellular permeability of HT-29 cell monolayers. These inhibitory effects of FCF persist in epithelial cells where the septin cytoskeleton has been disassembled by either CRISPR/Cas9-mediated knockout or siRNA-mediated knockdown of septin 7, insinuating off-target effects of FCF. Biochemical analysis reveals that FCF-dependent inhibition of the motility of control and septin-depleted cells is accompanied by decreased expression of the c-Jun transcription factor and inhibited ERK activity. The described off-target effects of FCF strongly suggests that caution is warranted while using this compound to examine the biological functions of septins in cellular systems and model organisms.

In this paper we present the enhanced X-ray Timing and Polarimetry mission - eXTP. eXTP is a space science mission designed to study fundamental physics under extreme conditions of density, gravity and magnetism. The mission aims at determining the equation of state of matter at supra-nuclear density, measuring effects of QED, and understanding the dynamics of matter in strong-field gravity. In addition to investigating fundamental physics, eXTP will be a very powerful observatory for astrophysics that will provide observations of unprecedented quality on a variety of galactic and extragalactic objects. In particular, its wide field monitoring capabilities will be highly instrumental to detect the electro-magnetic counterparts of gravitational wave sources. The paper provides a detailed description of: (1) the technological and technical aspects, and the expected performance of the instruments of the scientific payload; (2) the elements and functions of the mission, from the spacecraft to the ground segment., Accepted for publication on Sci. China Phys. Mech. Astron. (2019)

Geometric calibration is critical to the accurate SPECT reconstruction. In this paper, a geometric calibration method was developed for a dedicated breast SPECT system with a tilted parallel beam (TPB) orbit. The acquisition geometry of the breast SPECT was firstly characterized. And then its projection model was established based on the acquisition geometry. Finally, the calibration results were obtained using a nonlinear optimization method that fitted the measured projections to the model. Monte Carlo data of the breast SPECT were used to verify the calibration method. Simulation results showed that the geometric parameters with reasonable accuracy could be obtained by the proposed method.

A high resolution solar soft X-ray spectrometer (SOX) payload onboard a satellite is developed. A silicon drift detector (SDD) is adopted as the detector of the SOX spectrometer. The spectrometer consists of the detectors and their readout electronics, a data acquisition unit and a payload data handling unit. A ground test system is also developed to test SOX. The test results show that the design goals of the spectrometer system have been achieved.

Th17 cells producing IL-17 are involved in the pathogenesis of atherosclerosis, but the underlying mechanisms remain unclear. In this study, we investigated the effects of IL-17 on human vascular endothelial cells and showed that IL-17 induced cell death of the vascular endothelial cells, which played a pivotal role in plaque destabilization triggering acute coronary syndrome (ACS). We showed that circulating Th17 cells and IL-17 increased in patients with ACS compared to the patients with stable angina or health individuals; the plasma levels of IL-6 increased but TGF-β decreased in ACS patients, exhibiting a positive and negative correlation with that of IL-17, respectively. Importantly, we uncovered that IL-17 promoted the production of von Willebrand factor by endothelial cells and induced endothelial apoptosis by activating caspase-3, caspase-9 and up-regulating the ratio of Bax/Bcl-2, indicating the function of IL-17 in vascular endothelial damage as a potential mechanism for the pathogenesis of human ACS.

Background Tumor invasion and metastasis are the major reasons for leading death of patients with hepatocellular carcinoma (HCC). Therefore, to identify molecules that can suppress invasion and metastasis of tumor will provide novel targets for HCC therapies. Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2, TIPE2, is a novel immune negative molecule and an inhibitor of the oncogenic Ras in mice but its function in human is unclear. Our previous research has shown that TIPE2 is downregulated in human primary HCC compared with the paired adjacent non-tumor tissues. Results In present study, we provide evidence that TIPE2 inhibits effectively human hepatocellular carcinoma metastasis. The forced expression of TIPE2 in HCC-derived cell lines markedly inhibits tumor cell growth, migration and invasion in vitro and suppresses growth and metastasis of HCC in vivo. Clinical information from a cohort of 112 patients reveals that loss or reduced expression of TIPE2 in primary HCC tissues is significantly associated with tumor metastasis. Mechanically, TIPE2 inhibits the migration and invasion through targeting Rac1 and then reduces F-actin polymerization and expression of matrix metallopeptidase 9 (MMP9) and urokinase plasminogen activator (uPA). Conclusion Our results indicate that human TIPE2 is endogenous inhibitor of Rac1 in HCC by which it attenuates invasion and metastasis of HCC. The data suggest that TIPE2 will be a new target for HCC therapy.

SPECT (Single-photon Emission Computerized Tomography) and PET (Positron Emission Tomography) are essential medical imaging tools, for which the sampling angle number, scan time should be chosen carefully to compromise between image quality and the radiopharmaceutical dose. In this study, the image quality of different acquisition protocol was evaluated via varied angle number and count number per angle with Monte Carlo simulation data. It was shown that when similar imaging counts were used, the factor of acquisition counts was more important than that of the sampling number in ECT (Emission Computerized Tomography). To further reduce the activity requirement and the scan duration, an iterative image reconstruction algorithm for limited-view and low-dose tomography based on compressed sensing theory has been developed. The total variation regulation was added in the reconstruction process to improve SNR (Signal to Noise Ratio) and reduce the artifacts caused by the limited angle sampling. Maximization of maximum likelihood of the estimated image and the measured data and minimization of the total variation of the image are alternative implemented. By using this advanced algorithm, the reconstruction process is able to achieve image quality matching or exceeding that of normal scan with only half of the injection radiopharmaceutical dose., 6 pages, 5 figures

The Lunar Orbital X-ray Fluorescence Imaging Spectrometer (LOXIA) designed and constructed at the Institute of High Energy Physics of the Chinese Academy of Sciences to perform chemical composition analysis of the Moon surface will operate on-board the Chang'E-1 mission, the first Chinese lunar spacecraft to be launched in 2007. We report the main results of the calibration measurements that we have performed using the X-ray beamline of the XACT facility of INAFOsservatorio Astronomico di Palermo G.S. Vaiana to determine the quantum efficiency of the XRS detector in the soft X-rays as a function of photon energy and angle of incidence.