The Role of CXCR3 in the Induction of Primary Biliary Cirrhosis

Objective. Investigate whether CXCR3 and its ligands were involved in the pathogenesis of primary biliary cirrhosis (PBC) in an autoimmune cholangitis animal model. Methods. Female C57BL/6 mice were injected with 5 mg/kg of poly I:C intraperitoneally twice a week for 24 weeks. PBC model was confirmed by liver function, serum autoantibodies and liver biopsy. Lymphocytes subsets in liver and spleen and CXCL10 serum level were tested by flow cytometry and ELISA. Liver specimens were collected to evaluate the differences in pathology between WT and CXCR3−/− mice. Results. Antimitochondrial antibody was detected in all PBC model. Numbers of infiltrates were detected in the portal areas 8 weeks after poly I:C injection, which progressed up to 24 weeks. Compared to control mice, CXCL10 serum level increased in PBC mice and the proportion of CXCR3+ cells increased in the intrahepatic infiltrates of PBC mice, chiefly on CD8+ cells, whereas the expression of CXCR3 on CD3+ and CD8+ splenocytes decreased in PBC model. Compared with WT mice, CXCR3−/− mice developed delayed and milder progression of cellular inflammation. Conculsions. CXCR3 might contribute to the development of PBC in murine model. Knockout of CXCR3 might delay and alleviate the PBC disease progression, but could not entirely block the disease development

VLBI detection of the AE Aqr twin, LAMOST J024048.51+195226.9

LAMOST J024048.51+195226.9 (J0240+1952) was recently identified as the second AE Aquarii (AE Aqr)-type cataclysmic variable, possessing the fastest known rotating white dwarf. We performed a Very Long Baseline Interferometry (VLBI) observation of J0240+1952 utilizing the European VLBI Network at 1.7\,GHz, to obtain the first view of the radio morphology on mas scale. Our high-resolution VLBI image clearly shows that the radio emission is compact on mas scale ($\lesssim2$\,AU), with no evidence for a radio jet or extended emission. The compact radio source has an average flux density of $\sim0.37$\,mJy, and its brightness temperature is given at $\gtrsim2.3\times10^{7}$\,K, confirming a non-thermal origin. The emission exhibits irregular variations on a time-scale of tens of minutes, similar to the radio flares seen in AE Aqr. The measured VLBI position of J0240+1952 is consistent with that derived from \textit{Gaia}. Our results favour the model in which the radio emission is attributed to a superposition of synchrotron radiation from expanding magnetized blobs of this system

Gene co-expression network analysis identifies BRCC3 as a key regulator in osteogenic differentiation of osteoblasts through a β-catenin signaling dependent pathway

Objective(s): The prognosis of osteoporosis is very poor, and it is very important to identify a biomarker for prevention of osteoporosis. In this study, we aimed to identify candidate markers in osteoporosis and to investigate the role of candidate markers in osteogenic differentiation. Materials and Methods: Using Weighted Gene Co-Expression Network analysis, we identified three hub genes might associate with osteoporosis. The mRNA expression of hub genes in osteoblasts from osteoporosis patients or healthy donor was detected by qRT-PCR. Using siRNA and overexpression, we investigated the role of hub gene BRCC3 in osteogenic differentiation by alkaline phosphatase staining and Alizarin red staining. Moreover, the role of β-catenin signaling in the osteogenic differentiation was detected by using β-catenin signaling inhibitor XAV939.Results: We identified three hub genes that might associate with osteoporosis including BRCC3, UBE2N, and UBE2K. UBE2N mRNA and UBE2K mRNA were not changed in osteoblasts isolated from osteoporosis patients, compared with healthy donors, whereas BRCC3 mRNA was significantly increased. Depletion of BRCC3 promoted the activation of alkaline phosphatase and formation of calcified nodules in osteoblasts isolated from osteoporosis patients and up-regulated β-catenin expression. XAV939 reversed the BRCC3 siRNA-induced osteogenic differentiation. Additionally, inhibited osteogenic differentiation was also observed after BACC3 overexpression, and this was accompanied by decreased β-catenin expression.Conclusion: BRCC3 is an important regulator for osteogenic differentiation of osteoblasts through β-catenin signaling, and it might be a promising target for osteoporosis treatment

VLBI astrometry on the white dwarf pulsar AR Scorpii

AR Scorpii (AR Sco), the only-known radio-pulsing white dwarf binary, shows unusual pulsating emission at the radio, infrared, optical, and ultraviolet bands. To determine its astrometric parameters at the radio band independently, we conducted multi-epoch Very Long Baseline Interferometry (VLBI) phase-referencing observations with the European VLBI Network at 5 GHz and the Chinese VLBI Network plus the Warkworth 30-m telescope (New Zealand) at 8.6 GHz. By using the differential VLBI astrometry, we provide high-precision astrometric measurements on the parallax (pi = 8.52(-0.07)(+0.04) mas) and proper motion (mu(alpha) = 9.48(-0.07)(+0.04) mas yr(-1), mu(delta) = -51.32(-0.38)(+0.22) mas yr (-1)). The new VLBI results agree with the optical Gaia astrometry. Our kinematic analysis reveals that the Galactic space velocities of AR Sco are quite consistent with that of both intermediate polars and polars. Combined with the previous tightest VLBI constraint on the size, our parallax distance suggests that the radio emission of AR Sco should be located within the light cylinder of its white dwarf