Yi Huang

Platelet activating factor (PAF) is a phospholipid with proinflammatory and thrombogenic properties, which has been implicated in inflammatory disorders including vasculitis and asthma. PAF-like compounds are present in oxidized LDL (oxLDL), which has been detected in the atherosclerotic lesion, where it may activate monocytes, macrophages, and T cells. OxLDL may therefore both initiate and perpetuate inflammatory reactions in the artery wall. Herein we demonstrate that PAF has the capacity to induce enhanced interferon gamma (IFN-gamma) secretion in peripheral blood mononuclear leukocytes (PBMCs), as does oxLDL. Both oxLDL- and PAF-induced IFN-gamma secretions were inhibited by a specific PAF-receptor antagonist, WEB 2170. PAF-like lipids in oxLDL could thus be responsible for oxLDL-induced activation of immune-competent cells. The effects of PAF and oxLDL were inhibited by antibodies to major histocompatibility complex class II and thus depend on accessory cells like monocytes. Both PAF and oxLDL induced tumor necrosis factor-alpha (TNF-alpha) synthesis in peripheral blood. PAF-mediated TNF-alpha production was inhibited by WEB 2170, whereas oxLDL-induced TNF-alpha was only partially inhibited. These findings indicate that both PAF and oxLDL have the capacity to induce TNF-alpha, which may increase atherogenesis due to its pleiotropic proinflammatory effects. Our findings suggest that the PAF receptor plays an important role in the inflammatory component of atherosclerosis.

The early stages of atherosclerosis are characterized by penetration into the arterial intima by both T lymphocytes and monocytes. Some of these T lymphocytes show signs of activation, though the mechanisms by which they become activated are not known. The monocytes develop into macrophages and subsequently into foam cells filled with oxidized LDL (oxLDL)-derived lipids. OxLDL has been found to exert several proinflammatory effects, including enhanced adhesiveness of endothelial cells and monocytes, chemotaxis of monocytes and T cells, and T-cell activation. The enzyme-linked immunospot (ELISPOT) assay has been shown to be a sensitive method for detection of single cells secreting antibodies or cytokines. Here we have used this method to characterize the T-cell cytokine secretion pattern after exposure to oxLDL in vitro. In peripheral blood mononuclear cells from healthy donors (n = 27), a significantly enhanced number of INF-gamma-producing cells was detected by ELISPOT (P < .001) after stimulation with 5 micrograms/mL oxLDL. In contrast, production of interleukin-4 was not significantly enhanced after stimulation with oxLDL. OxLDL-induced IFN-gamma secretion and T-cell proliferation were completely inhibited by major histocompatibility complex (MHC) class II antibodies. Furthermore, oxLDL was found to enhance the antibody secretion, indicating B-cell activation. Our results indicate that oxLDL activates T cells by an MHC class II-dependent mechanism. In healthy individuals, oxLDL induces IFN-gamma, which is produced by T helper type 1-like cells. These findings demonstrate that oxLDL induces a cell-dependent immune reaction, which may play an important role in the development of atherosclerosis.

Surface defect detection of crane wire rope is very important for safe operations of crane. However, the surface defect characteristics of crane wire rope are varied, there is no standardized data and tiny-size, which makes the universal surface defect detection models ineffective. Therefore, a surface defect detection model named TBi-YOLOv5 is proposed in this article. First, a random augment method is used to search the optimal data augment strategy automatically and enforce the generalization ability of the surface defect detection model. Then, in order to enhance the feature extraction ability on both the local and global views, a Bottleneck Transformer (BOT) module is added in YOLOv5, which makes effective fusion of convolutional neural network (CNN) and multi-head self-attention mechanism (MHSA). After that, inspired by the idea of bidirectional feature pyramid network (BiFPN), a small target detection layer (STPL) is added in the neck part of YOLOv5 to detect the tiny-size surface defect on the wire rope. Experiments on the surface defect detection of crane wire rope show the effectiveness of the proposed TBi-YOLOv5. Compared with YOLOv5s, the mean average precision (mAP) of TBi-YOLOv5 has been increased by nearly 4%.

CONTEXT: Malignant thyroid tumor with distant metastasis is associated with poor outcome. Early detection of distant metastasis is of great clinical importance. OBJECTIVE: Thyroid tumor infiltrated with T cells can serve as a biomarker for monitoring metastasis. DESIGN: A retrospective analysis was performed of patient clinical samples collected between 2012 to 2018, using T-cell receptor sequencing (TCR-seq) for clinical exploration. SETTING: This study took place at Zhejiang Cancer Hospital. PATIENTS: Sixty-eight patients with papillary thyroid cancer (PTC) (distinct metastatic status) and 21 patients with benign nodules were enrolled. All patients had not received any treatment before surgery. MAIN OUTCOME MEASURE: The characteristics of TCRβ complementary-determining region 3 (CDR3) for each patient were determined by high-throughput sequencing. RESULTS: The TCRβ diversity of malignant tumors is significantly higher than benign nodules both in blood and tumor samples (Shannon index, blood, P < .01; tumor, P < .001). The malignant tumors with distant metastasis or invasiveness showed lower TCRβ diversity than nonmetastasis (Shannon index, P < .01) or noninvasive (Shannon index, P < .01) malignant tumors. Analysis of the Morisita-Horn similarity index indicated significant TCRβ repertoire similarity between tumor and blood in distant-metastatic patients (comparison with nonmetastasis, P < .05). According to the discrepancy of the CDR3 among patients with different clinicopathological status, the classifier was constructed to discriminate distant-metastatic individuals. A promising area under the curve value of 83.8% was obtained with the number of overlapping CDR3 clonotypes. CONCLUSION: The availability and reliability of TCR-seq render it prospective to translate these intrinsic attributes into clinical practice for monitoring distant metastasis in PTC patients.