Matrix remodeling associated 7 (MXRA7) was first noted to co-express with a group of matrix remodeling related genes, and its biological functions had remained unclear. In this study, we investigated the presumed function of MXRA7 in a carbon tetrachloride (CCl4)-induced acute liver injury model in mice. Wild-type, MXRA7−/− mice, and mice that were pulsed with hydrodynamic injection of vehicle or MXRA7-harboring plasmids were challenged with a single dose of CCl4 for injury induction. The sera, spleens, and livers were harvested from mice for assay of cytokines/chemokines expression, cellular responses, or histological features. We found that MXRA7 deficiency alleviated, and MXRA7 overexpression aggravated liver damage in CCl4-challenged mice. FACS analysis showed that MXRA7 deficiency reduced the recruitment of neutrophils through downregulation the expression of CXCL1 and CXCL2 in liver, decreased the number of CD8+ T cells in liver and spleen, suppressed the release of IFNγ and TNFα from T cells, and decreased IFNγ in serum and liver. Western blot assay demonstrated that MXRA7 deficiency suppressed the activation of MAPK pathway and AKT/NF-κB pathway, respectively. Lastly, MXRA7 deficiency or overexpression regulated the expression of two matrix remodeling-related genes (fibronectin and TIMP1) in the liver. We concluded that MXRA7 was an active player in CCl4-induced liver injury, hypothetically by mediating the inflammation or immune compartments and matrix remodeling processes. Further exploration of MXRA7 as a possible new therapeutic target for management of inflammation-mediated liver injury was discussed.
Kinesin family member 11 (KIF11) is a plus end‐directed kinesin indispensable for the formation of the bipolar spindle in metaphase, where it objects to the action of minus end‐directed molecular motors. Here, we hypothesize that KIF11 might be a therapeutic target of breast cancer and regulated by miR‐30a . Cell Counting Kit 8 assays were used to investigate cell proliferation. Invasion assays were used to survey the motility of cells. Kaplan‐Meier and Cox proportional analyses were employed for this outcome study. The prognostic significance and performance of KIF11 were validated on 17 worldwide independent microarray datasets and two The Cancer Genome Atlas‐Breast Invasive Carcinoma sets. microRNA was predicted targeting KIF11 through sequence alignment in microRNA.org and confirmed by coexpression analysis in human breast cancer samples. Dual‐luciferase reporter assays were employed to validate the interaction between miR‐30a and KIF11 further. Higher KIF11 mRNA levels and lower miR‐30a were significantly associated with poor survival of breast cancer patients. Inhibition of KIF11 by small‐hairpin RNA significantly reduced the proliferation and invasion capabilities of the breast cancer cells. Meanwhile, downregulation of KIF11 could enhance the cytotoxicity of adriamycin in breast cancer cell lines MCF‐7 and MDA‐MB‐231. A population study also validated that chemotherapy and radiotherapy significantly improved survival in early‐stage breast cancer patients with low KIF11 expression levels. Further bioinformatics analysis demonstrated that miR‐30a could interact with KIF11 and validated by dual‐luciferase reporter assays. Therefore, KIF11 is a potential therapeutic target of breast cancer. miR‐30a could specifically interact with KIF11 and suppress its expression in breast cancer.
Rendezvous on the geostationary orbit (GEO) is much more complex than that on the low earth orbit and has a higher critical requirement for safety performance. This paper presents a safe scenario design method for GEO rendezvous proximity missions where the safety Furthermore, an exhaustive analysis is performed to find the dangerous regions of the V-bar keeping positions and the appropriate semi-major axis of the fly-by ellipse, considering the safety requirements of both the target and the collocated satellite. A geometry method is then developed for designing a feasible and suboptimal safe rendezvous scenario. The method is tested by designing four rendezvous scenarios with ±V-bar approach directions respectively in the situations with and without one collocated satellite. Safety performance and velocity increments of the scenarios are compared and a conclusion is reached that the collocated satellite has a significant influence on the scenario design.
Nonlinear uncertainty propagation is of critical importance in many application fields of astrodynamics. In this paper, a framework combining the differential algebra technique and the Gaussian mixture model method is presented to accurately propagate the state uncertainty of a nonlinear system. A high-order Taylor expansion of the final state with respect to the initial deviations is firstly computed with the differential algebra technique. Then the initial uncertainty is split to a Gaussian mixture model. With the high-order state transition polynomial, each Gaussian mixture element is propagated to the final time, forming the final Gaussian mixture model. Through this framework, the final Gaussian mixture model can include the effects of high-order terms during propagation and capture the non-Gaussianity of the uncertainty, which enables a precise propagation of probability density. Moreover, the manual derivation and integration of the high-order variational equations is avoided, which makes the method versatile. The method can handle both the application of nonlinear analytical maps on any domain of interest and the propagation of initial uncertainties through the numerical integration of ordinary differential equation. The performance of the resulting tool is assessed on some typical orbital dynamic models, including the analytical Keplerian motion, the numerical J 2 perturbed motion, and a nonlinear relative motion.
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