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Laryngeal squamous cell carcinoma (LSCC) is a common malignancy among men in the anatomical position of head and neck. Hoarseness, pharyngalgia, and dyspnea are common symptoms. LSCC is a complex polygenic carcinoma that is caused by many factors involving polygenic alteration, environmental pollution, tobacco, and human papillomavirus. Classical protein tyrosine phosphatase nonreceptor type 12 (PTPN12) has been extensively studied to decipher its mechanism as a tumor suppressor gene in various human carcinomas; however, there is no comprehensive elucidation of the PTPN12 expression and its regulatory mechanisms in LSCC. As such, we expect to provide new insights for finding new biomarkers and effective therapeutic targets in LSCC. Immunohistochemical staining, western blot (WB), and quantitative real-time RT-PCR (qRT-PCR) were used for the messenger RNA (mRNA) and protein expression analyses of PTPN12, respectively. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, clone formation, transwell migration, and transwell invasion assays were used to assess the proliferation, migration, and invasion ability of LSCC cells. Online prediction and design software tools (http://www.targetscan.org/ and http://www.microRNA.org) were used to predict associated miRNA. Studying the targeted regulatory relationship between miR-146b-3p and PTPN12 was based on dual luciferase reporter gene analysis. qRT-PCR was used to assess miR-146b-3p expression in LSCC. miR-146b-3p inhibitor and mimic were transfected, followed by qRT-PCR and WB assays to detect the expression of PTPN12. The gain and loss functional experiments were used to investigate the effects of miR-146b-3p transfection on the proliferation, migration, and invasion of tumor cells. Online bioinformatics prediction software (https://cn.string-db.org/ and https://www.genecards.org/) was used to determine potential downstream target genes of PTPN12. qRT-PCR and WB analyses were used to assess the mRNA and protein expression levels of target genes. Our study showed significantly decreased mRNA and protein expression levels of PTPN12 in LSCC compared with the adjacent normal tissues. The lower PTPN12 mRNA expression was correlated with pathological differentiation, and lower PTPN12 protein expression was correlated with the TNM stage in LSCC tissues. The subsequent in vitro functional analyses showed the inhibitory effect of PTPN12 over-expression on the proliferation, migration, and invasiveness abilities of LSCC cell line. Using online prediction and design software, miR-146b-3p was searched to target PTPN12. The miR-146b-3p was expressed at a high level in LSCC tissues and cell lines. Luciferase reporter assay exhibited that miR-146b-3p inhibited the luciferase activity of PTPN12 markedly. The functional analyses showed the tumor-promoting role of miR-146b-3p on the proliferation, migration, and invasiveness abilities of LSCC cell. Furthermore, co-transfection of cells with miR-146b-3p and PTPN12 significantly restored the inhibitory effect of PTPN12 on LSCC cell growth, migration, and invasiveness. This phenomenon unveiled that miR-146b-3p regulated the proliferation, migration, and invasion of LSCC cells by targeting PTPN12. EGFR and ERBB2 were selected as the downstream-regulation target genes. Up-regulation of PTPN12 significantly suppressed EGFR expression. Accordingly, the miR-146b-3p mimic significantly up-regulated the EGFR expression. However, up-regulation of PTPN12 and miR-146b-3p mimic suppressed ERBB2 protein expression but induced its gene expression. Down-regulation of PTPN12 is associated with up-regulation of miR-146b-3p in LSCC. Moreover, PTPN12 serves as a tumor suppressor gene through regulating the proliferation, migration, and invasion of LSCC cells. miR-146b-3p/PTPN12 axis is expected to be a novel therapeutic target in LSCC.

We present a new 3-D radially anisotropic seismic velocity model EARA2024 of the crust and mantle beneath East Asia and the northwestern Pacific using adjoint full-waveform inversion tomography. We construct the EARA2024 model by iteratively minimizing the waveform similarity misfit between the synthetic and observed waveforms from 142 earthquakes recorded by about 2000 broad-band stations in East Asia. Compared to previous studies, this new model renders significantly improved images of the subducted oceanic plate in the upper mantle, mantle transition zone, and uppermost lower mantle along the Kuril, Japan, Izu-Bonin and Ryukyu Trenches. Complex slab deformation and break-offs are observed at different depths. Moreover, our model provides new insights into the origins of intraplate volcanoes in East Asia, including the Changbaishan, Datong-Fengzhen, Tengchong and Hainan volcanic fields. [ABSTRACT FROM AUTHOR]

The understanding of the velocity structure and basement morphology within the basin is crucial for seismic hazard mitigation and the study of basin evolution. To explore the intricate structure of the Binchuan Basin in western Yunnan, China, we deployed a linear dense array in the northern region of the Binchuan Basin, with inter‐station distance ranging from 50 to 100 m. We propose a novel receiver function processing workflow. Initially, we extracted coherent receiver functions based on the dense array, followed by a inversion of basement morphology, S‐wave velocities, and sedimentary layer's average Vp/Vs ratio jointly with frequency‐dependent teleseismic apparent shear velocity and receiver function waveforms. The results show that S‐wave velocity anomalies correspond to the unconsolidated sediments. The thickness of the sedimentary layer ranges from ∼0.5 to ∼0.75 km. The basement morphology suggests the basin is controlled by normal faults. Additionally, intra‐basin faults displayed higher fault displacement to length ratios (∼0.27) than most isolated normal faults (10−3–10−1), which may result from accumulated fault displacement due to interactions between fault segments. These results emphasize the significant role of N–S trending intra‐basin faults in basin evolution, suggesting that micro‐block rotations and transitional movements within the Northwestern Yunnan Rift Zone are primary mechanisms shaping the Binchuan Basin. We further proposed a multi‐stage model for the evolution of the Binchuan Basin. The robustness testing validates that the proposed processing flow is an effective approach to comprehensively image the basin velocity structure and the basement morphology. Plain Language Summary: Our study focused on imaging the fine structure of the Binchuan Basin in western Yunnan, China, which is crucial for seismic hazard evaluation and understanding the basin's evolution. We proposed a new workflow to examine the basin's structure and characteristics. By setting up a linear dense seismometer array in the northern region of the Binchuan Basin, we gathered valuable data. Our findings showed a connection between areas with lower seismic velocity and sedimentary layers. Basement depth ranges from 0.5 to 0.75 km. Intra‐basin faults, with a higher ratio of maximum fault displacement to length compared to typical faults, suggest their crucial role in basin evolution due to accumulated fault displacement. The basement morphology suggests the evolution of the basin is controlled by normal faults. Our results also suggest micro‐block rotations and rift zone movements as key factors in shaping the Binchuan Basin. These findings establish a detailed model for the basin's evolution. Additionally, our synthetic tests confirmed the effectiveness of our newly proposed method in understanding basin structures comprehensively. Key Points: We proposed a new workflow using teleseismic signals to study basin sediment layers and basement morphologyS‐wave velocity, Vp/Vs ratio, and sediment layer thickness structures of the Binchuan Basin were inverted using the proposed methodA geological model for the evolution of the Binchuan Basin was proposed to explain the high fault displacement to length ratio [ABSTRACT FROM AUTHOR]