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Human trophoblast cell apoptosis may induce miscarriage. Trophoblast cells are sensitive to environmental BaP-7,8-dihydrodiol-9,10-epoxide (BPDE). However, how BPDE induces human trophoblast cell apoptosis is still largely elusive. In this work, we used BPDE-treated human trophoblast cells and villous tissues collected from recurrent miscarriage and health control groups to explore the underlying mechanism of BPDE-induced human trophoblast cell apoptosis. Continued with our recent work, we found that lncRNA HZ01 (lnc-HZ01) could induce human trophoblast cell apoptosis. In mechanism, lnc-HZ01 up-regulated p53 expression level by suppressing its MDM2-mediated proteasomal degradation. Meanwhile, we found that p53 acted as lnc-HZ01 transcription factor and promoted lnc-HZ01 transcription. Thus, lnc-HZ01 and p53 composed a positive feedback loop in human trophoblast cells. In normal trophoblast cells, relatively low levels of lnc-HZ01 and p53 suppressed p53/caspase-3 apoptosis pathway, giving normal pregnancy. Upon BPDE exposure, BPDE up-regulated the expression levels of lnc-HZ01 and p53, triggered this positive feedback loop, activated the p53/caspase-3 apoptosis pathway, and then induced miscarriage. Collectively, we discovered new mechanism by which lnc-HZ01 regulated BPDE-induced human trophoblast cell apoptosis, providing scientific basis for the diagnosis and treatment of unexplained recurrent miscarriage. • Lnc-HZ01 activates p53/caspase-3 pathway and induces human trophoblast cell apoptosis. • Lnc-HZ01 and p53 compose a positive feedback loop in human trophoblast. • BPDE up-regulates lnc-HZ01 and p53 expression and triggers this positive feedback loop. • Human trophoblast cell apoptosis may induce miscarriage. [ABSTRACT FROM AUTHOR]

Human trophoblast cells play important role in embryo-fetal development. However, trophoblast cells are sensitive to environmental carcinogens. Recently, we have discovered that BPDE inhibits trophoblast cell migration, invasion and proliferation, and also increases trophoblast cell apoptosis. Ferroptosis is a newly identified iron-dependent non-apoptotic programmed cell death. Whether BPDE might induce trophoblast cell ferroptosis is completely unknown. In this work, we have discovered that ferroptosis does occur in BPDE-treated human trophoblast cells. Iron metabolism up-regulates intracellular free Fe2+ level, produces excessive ROS (reactive oxygen species), and accelerates lipid peroxidation. GPX4 efficiently eliminates ROS and inhibits lipid peroxidation. Thus, ferroptosis is well suppressed due to the balance of these two pathways in healthy trophoblast cells. However, BPDE exposure could promote iron metabolism, increase intracellular free Fe2+ level, produce excessive ROS, and result in lipid peroxidation. Meanwhile, BPDE also down-regulates GPX4 expression level by promoting its proteasomal degradation, which eventually produces excessive ROS and induces lipid peroxidation. Thus, BPDE exposure induces trophoblast cell ferroptosis by unbalancing these two pathways, providing new insight in understanding BPDE-induced dysfunctions of human trophoblast cells. • BPDE exposure induces human trophoblast cell ferroptosis. • BPDE exposure increases intracellular free Fe2+ level and ROS level. • BPDE promotes GPX4 proteasomal degradation and reduces its protein level. • BPDE produces excessive ROS and induces lipid peroxidation. [ABSTRACT FROM AUTHOR]

Keypoint-based object detection achieves better performance without positioning calculations and extensive prediction. However, they have heavy backbone, and high-resolution is restored using upsampling that obtain unreliable features. We propose a self-constrained parallelism keypoint-based lightweight object detection network (SCPNet), which speeds inference, drops parameters, widens receptive fields, and makes prediction accurate. Specifically, the parallel multi-scale fusion module (PMFM) with parallel shuffle blocks (PSB) adopts parallel structure to obtain reliable features and reduce depth, adopts repeated multi-scale fusion to avoid too many parallel branches. The self-constrained detection module (SCDM) has a two-branch structure, with one branch predicting corners, and employing entad offset to match high-quality corner pairs, and the other branch predicting center keypoints. The distances between the paired corners' geometric centers and the center keypoints are used for self-constrained detection. On MS-COCO 2017 and PASCAL VOC , SCPNet's results are competitive with the state-of-the-art lightweight object detection. https://github.com/mengdie-wang/SCPNet.git. • SCPNet can speed inference, drop parameters, and obtain more accurate boundary boxes. • PMFM for feature extraction can maintain high-resolution and widen receptive field. • SCDM proposes the distance constraint between geometric centers and center keypoints. [ABSTRACT FROM AUTHOR]