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Safeguard China's karst cavern habitats.
Furthermore, LRP5 was co-immunoprecipitated with TβRI and TβRII, and its extracellular domain was essential for interacting with TβRs and for its pro-fibrotic activity. In addition to stabilizing TβRs, LRP5 increased the basal membrane presentation and TGF-β1-induced internalization of these receptors. Notably, TGF-β1 also induced LRP5 internalization. These findings indicate that LRP5 promotes tubulointerstitial fibrosis, at least partially, via direct modulation of TGF-β/Smad signaling, a novel, Wnt-independent function.γδT cells have been reported to exert immunosuppressive functions in multiple solid malignant diseases, but their immunosuppressive functional subpopulation in breast cancer (BC) is still undetermined. Here, we collected 40 paired BC and normal tissue samples from Chinese patients for analysis. First, we showed that γδT1 cells comprise the majority of CD3+ T cells in BC; next, we found that CD73+γδT1 cells were the predominant regulatory T-cell (Treg) population in BC, and that their prevalence in peripheral blood was also related to tumour burden. In addition, CD73+γδT1 cells exert an immunosuppressive effect via adenosine generation. We also found that BC could modulate CD73 expression on γδT cells in a non-contact manner. The microarray analysis and functional experiments indicated that breast tumour cell-derived exosomes (TDEs) could transmit lncRNA SNHG16, which upregulates CD73 expression, to Vδ1 T cells. Regarding the mechanism, SNHG16 served as a ceRNA by sponging miR-16-5p, which led to the derepression of its target gene SMAD5 and resulted in potentiation of the TGF-β1/SMAD5 pathway to upregulate CD73 expression in Vδ1 T cells. Our results showed that the BC-derived exosomal SNHG16/miR-16-5p/SMAD5-regulatory axis potentiates TGF-β1/SMAD5 pathway activation, thus inducing CD73 expression in Vδ1 T cells. Our results first identify the significance of CD73+Vδ1 Tregs in BC, and therapy targeting this subpopulation or blocking TDEs might have potential for BC treatment in the future.APC/CCdh1 is a ubiquitin ligase with roles in numerous diverse processes, including control of cellular proliferation and multiple aspects of the DNA damage response. Precise regulation of APC/CCdh1 activity is central to efficient cell-cycle progression and cellular homeostasis. Here, we have identified Cdh1 as a direct substrate of the replication stress checkpoint effector kinase Chk1 and demonstrate that Chk1-mediated phosphorylation of Cdh1 contributes to its recognition by the SCFβTRCP ubiquitin ligase, promotes efficient S-phase entry, and is important for cellular proliferation during otherwise unperturbed cell cycles. We also find that prolonged Chk1 activity in late S/G2 inhibits Cdh1 accumulation. In addition to promoting control of APC/CCdh1 activity by facilitating Cdh1 destruction, we find that Chk1 also antagonizes activity of the ligase by perturbing the interaction between Cdh1 and the APC/C. Overall, these data suggest that the rise and fall of Chk1 activity contributes to the regulation of APC/CCdh1 activity that enhances the replication process.BACKGROUND Circumferential decompression (CD) is an essential treatment option for myelopathy associated with thoracic-ossification of the posterior longitudinal ligament (T-OPLL) when laminectomy cannot achieve sufficient ventral decompression. find more Although intraoperative neurophysiological monitoring (IONM) is widely used, the operation has a relatively high risk. This study is the first to describe the use of contrast-enhanced ultrasound (CEUS) to evaluate the spinal cord blood flow (SCBF) during thoracic spine surgery in humans. The objective of this study was to compare clinical outcomes between intraoperative CEUS and IONM during CD. MATERIAL AND METHODS Sixty-eight T-OPLL patients who received CD from 2007 to 2014 were reviewed. All patients underwent IONM. CEUS was used on the following 2 occasions on 18 patients to evaluate SCBF the first measurement was performed after laminectomy and the second after ventral decompression. Outcomes were evaluated by the Hirabayashi recovery rate (HRR). RESULTS The overall HRR of all patients was 56.7%. Regarding CEUS, the HRR was 20.0% in Group A (SCBF decreased) and 63.6% in Group B (SCBF increased), indicating a significantly poorer neurological outcome in Group A (P less then 0.01). Regarding IONM, the HRR did not significantly differ between Groups C (no meaningful change in potential), D (potential changed up to alert criteria), and E (potential improved). CONCLUSIONS IONM is relatively effective in detecting impending spinal cord dysfunction. Intraoperative CEUS is a safe and reliable method for assessing SCBF changes, which may be used as a supplement to IONM, thus reducing the incidence of false-negative results.BACKGROUND Tumor embolism is a rare neoplastic complication that occurs when there is intravenous invasion by a benign or malignant tumor. We present the case of an asymptomatic patient with an incidentally discovered leiomyosarcoma tumor emboli, which was initially misdiagnosed as "thrombus in transit." CASE REPORT The patient was a 58-year-old woman who was incidentally found on echocardiogram to have a large tubular mass within the inferior vena cava and right atrium. Although initially characterized as "thrombus in transit", this mobile right atrial mass was present without clinical, echocardiographic, or radiographic evidence of pulmonary embolism or increased pulmonary arterial impedance. Given that a thrombus in transit is nearly always associated with submassive or massive pulmonary emboli and their attendant right heart sequelae, these pertinent negative findings led us to seek an alternative diagnosis. After a trial of conservative management with anticoagulation and attempted removal of the mass with the AngioVac system, the patient ultimately underwent median sternotomy and surgical embolectomy on cardiopulmonary bypass to remove the mass, which was later identified on pathology as a leiomyosarcoma. CONCLUSIONS With rare exceptions, "thrombus in transit" is accompanied by large pulmonary emboli and the presence of increased pulmonary artery pressure and right heart strain. The absence of clinical, echocardiographic, or radiographic evidence of these hemodynamic sequelae should raise suspicion for an alternative diagnosis. Tumor embolism should be considered in the differential diagnosis of any patient with a history of malignancy who presents with evidence of intracardiac mass or embolism.
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