The Zhaoshan long-baseline Atom Interferometer Gravitation Antenna (ZAIGA) is a new type of underground laser-linked interferometer facility, and is currently under construction. It is in the 200-meter-on-average underground of a mountain named Zhaoshan which is about 80 km southeast to Wuhan. ZAIGA will be equipped with long-baseline atom interferometers, high-precision atom clocks, and large-scale gyros. ZAIGA facility will take an equilateral triangle configuration with two 1-km-apart atom interferometers in each arm, a 300-meter vertical tunnel with atom fountain and atom clocks mounted, and a tracking-and-ranging 1-km-arm-length prototype with lattice optical clocks linked by locked lasers. The ZAIGA facility will be used for experimental research on gravitation and related problems including gravitational wave detection, high-precision test of the equivalence principle of micro-particles, clock based gravitational red-shift measurement, rotation measurement and gravito-magnetic effect. arXiv:1903.09288v4 [physics.atom-ph]
TianQin is a planned space-based gravitational wave (GW) observatory consisting of three Earth-orbiting satellites with an orbital radius of about $10^5 \, {\rm km}$. The satellites will form an equilateral triangle constellation the plane of which is nearly perpendicular to the ecliptic plane. TianQin aims to detect GWs between $10^{-4} \, {\rm Hz}$ and $1 \, {\rm Hz}$ that can be generated by a wide variety of important astrophysical and cosmological sources, including the inspiral of Galactic ultra-compact binaries, the inspiral of stellar-mass black hole binaries, extreme mass ratio inspirals, the merger of massive black hole binaries, and possibly the energetic processes in the very early universe and exotic sources such as cosmic strings. In order to start science operations around 2035, a roadmap called the 0123 plan is being used to bring the key technologies of TianQin to maturity, supported by the construction of a series of research facilities on the ground. Two major projects of the 0123 plan are being carried out. In this process, the team has created a new-generation $17 \, {\rm cm}$ single-body hollow corner-cube retro-reflector which was launched with the QueQiao satellite on 21 May 2018; a new laser-ranging station equipped with a $1.2 \, {\rm m}$ telescope has been constructed and the station has successfully ranged to all five retro-reflectors on the Moon; and the TianQin-1 experimental satellite was launched on 20 December 2019—the first-round result shows that the satellite has exceeded all of its mission requirements.
Thus, our results suggest the paradigm that graft rejection versus tolerance is determined by a balance between the activation of effector T cells versus immune suppression by regulatory T cells, and that after transplantation, IL-6 functions as a systemic danger signal that overcomes constitutive immune suppression mediated by regulatory T cells and promotes the activation of effector T cells.
The TianQin-1 satellite (TQ-1), which is the first technology demonstration satellite for the TianQin project, was launched on
Chromosomal aberrations at 12q13 are frequent in nonsmall-cell lung cancer (NSCLC). Here, we examined mRNA expression of 20 genes within chromosome band 12q13 by quantitative real-time polymerase chain reaction in NSCLC. Of the 20 genes, nine were upregulated, while two genes were downregulated. Among the nine upregulated genes, mRNA values of RACGAP1, MCRS1, EIF4B, WNT1, and PTGES3 were significantly higher in NSCLCs compared with normal lung tissues. Subsequently, overexpressions of RACGAP1 and MCRS1 were confirmed at the protein level in tissues and cultured cells of lung cancer by immunostaining and Western blot. RACGAP1 was labeled in the nucleus of tumor cells in 89% of the tumor specimens. In the cultured cells, RACGAP1 was present principally in the nucleus of nonmitotic cells, but showed a diffuse distribution in the cytoplasm of mitotic cells (metaphase) and at the contractile ring between two separating daughter cells (telophase). Furthermore, RACGAP1 downregulation by RNA interference caused cytokinesis defects, indicating that RACGAP1 is required for cytokinesis. MCRS1 was stained in all tumor specimens and strongly stained in 31% of cases. Interestingly, MCRS1 exhibits different localization in the mitotic cells of cultured immortalized human bronchial epithelial cells and cultured lung cancer cells. In vitro, downregulation of MCRS1 in lung cancer cells inhibited cell proliferation, increased apoptosis, and induced cell cycle arrest at the G1 phase. These findings indicate that RACGAP1 and MCRS1 may be cancer-related genes in NSCLC.
SummaryToll-like receptor 4 (TLR4) is a member of the Toll-like receptor family, which can bridge innate and adaptive immune responses. Activation of the TLR4 signalling pathway may induce the release of proinflammatory cytokines such as tumour necrosis factor (TNF)-a and interleukin (IL)-12, which was considered to play an important role in pathogenesis of immune-mediated diseases. Ankylosing spondylitis (AS) is an immune-mediated disease whose aetiology remains unknown. The aim of the study was to investigate the expression of TLR4 and serum TNF-a, IL-12 and soluble tumour necrosis factor-related apoptosis-inducing ligand (sTRAIL) level in AS patients. The results indicated that TLR4 protein and mRNA levels were significantly higher in AS patients than in healthy controls; however, there was no significant difference between human leucocyte antigen (HLA)-B27-positive and -negative AS patients, as well as serum levels of TNF-a, IL-12 and sTRAIL. In addition, in HLA-B27-positive AS patients, TLR4 level showed close associations with the cytokines and laboratory parameters of disease activity [erythrocyte sedimentation rate (ESR) and plasma C-reactive protein (CRP)], respectively. Similarly, the strong associations between the cytokines or between IL-12 and ESR or CRP were observed in HLA-B27-positive AS patients. Interestingly, in HLA-B27-positive AS patients, TNF-a correlated significantly with ESR, but did not with CRP. In contrast, sTRAIL correlated with CRP, but did not with ESR. Among HLA-B27-negative patients, no close correlation was found. In our study, it was suggested that the abnormal activation of TLR4 signalling and serum TNF-a, IL-12 and sTRAIL may play a key role in the development and progression of AS, which may be dependent on the status of HLA-B27 antigen.
Background:Surgical resection is generally considered the main curative treatment for intrahepatic biliary cystadenocarcinoma (IBCA) or suspected IBCAs, but controversy exists regarding the prognosis for IBCAs. This study aimed to describe the clinicopathological characteristics of IBCA and identify prognostic factors that may influence the survival of patients treated with surgical procedures.Methods:Thirty-four patients with histologically confirmed IBCA treated between January 2000 and June 2014 were included. The clinical characteristics of patients with IBCA were compared with those of 41 patients with intrahepatic biliary cystadenoma (IBC); factors that significant difference were analyzed for prognosis analysis of IBCA using multivariate/univariate Cox proportional hazards regression models. Survival curves were constructed using the Kaplan–Meier method and compared using the log-rank test.Results:IBCAs had a strong female predominance, and the most common presenting symptoms were abdominal pain or discomfort. Compared with IBCs, IBCAs occurred in older patients, in more male patients, and were associated statistically significant abnormal increase in alanine aminotransferase (P = 0.01) and total bilirubin (P = 0.04). Mural nodules were more frequently seen with IBCAs and may associate with malignancy. It was difficult to differentiate between IBC and IBCA based on laboratory examination and imaging findings. Although complete resection is recommended, enucleation with negative margins also achieved good outcomes. Median overall patient survival was 76.2 months; survival at 1, 3, and 5 years was 88.0%, 68.7%, and 45.8%, respectively. Radical resection and noninvasive tumor type were independent prognostic factors for overall survival.Conclusions:It remains difficult to distinguish between cystadenomas and cystadenocarcinomas based on laboratory examination and image findings. Complete resection is recommended for curative treatment, and patients should be closely followed postoperatively, particularly those with invasive tumors.
Toll-like receptor 2 (TLR2) and TLR4 signaling may induce differential secretion of T helper 1 (Th1) and Th2 cytokines, potentially influencing the development of autoimmune or atopic diseases. To date, the influence of the type of stimulus, timing, and dose of TLR2 and TLR4 ligands on cytokine secretion has not been well established. We tested whether the innate stimuli peptidoglycan (Ppg, TLR2 agonist) and lipid A (LpA, TLR4 agonist) differentially affect the secretion of interleukin-13 (IL-13) (Th2) and interferon-gamma (IFN-gamma) (Th1). Further, we examined the influence of the maturity of the immune system, species, dose, and timing of stimuli in human cord and adult peripheral blood mononuclear cells (PBMC) and murine cells in vitro and in vivo. Stimulation with Ppg induced the secretion of both IL-13 and IFN-gamma, influenced by time and dose in neonates, adults, and mice. In contrast, stimulation with LpA induced primarily time-independent and dose-independent production of IFN-gamma. Pulmonary administration of Ppg in vivo in mice resulted in secretion of IL-13, whereas administration of LpA resulted in secretion of IFN-gamma in bronchoalveolar lavage (BAL). Therefore, TLR2 and TLR4 stimuli differentially influence IL-13 and IFN-gamma secretion in neonates, adults, and mice, supporting a critical role for innate stimuli in the modulation of cytokine responses.
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