By applying ferrite-martensite microstructural control, high-deformability linepipes of grade X70 have been developed. The steel with an acicular ferrite microstructure was intercritically heat-treated at 8208C for 10 min, followed by rapidly water cooling, in order to get a ferrite/martensite dual-phase microstructure. After aging at 200-2508C for 5-15 min, the microstructure and mechanical properties of the ferrite-martensite microstructural steel were studied. The pipe with a ferrite/martensite dual-phase microstructure exhibited a superior strain aging resistance aging at 200-2508C for 5-15 min. The yield ratios were below 0.77 and the pipe still exhibited continuous yielding behavior, meanwhile tensile strength, uniform elongation and impact toughness did not experience significant change. By intercritical annealing, carbides and carbonitride containing Nb and Ti precipitated out of the ferrite phase further, at the same time, solute carbon atoms could adequately diffused from the ferrite to the uniformly distributed austenite derived from the acicular ferrite initial microstructures, leading to the reduction of the amount of free carbon and nitrogen to pin the mobile dislocations in the ferrite phase, therefore, strain aging effects were not pronounced in the temperature and time range investigated.
Background Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers. The two major lethal causes of ESCC are diagnosis at an advanced stage and lymph node metastasis (LNM). Circular RNAs (circRNAs) play critical regulatory roles in cancer progression, though, largely through unclear mechanisms. However, the character of circRNAs in the malignant progression of ESCC remains unclear. Methods The circRNA microarray was used to explore the circRNAs that were differentially expressed between ESCC and paired adjacent normal tissues. The function of circIMMP2L was validated by gain or loss of function assays. Pull‐down, RNA immunoprecipitation assays were used to demonstrate the biological mechanism of circIMMP2L. Tissue microarray (TMA), specimen, and paired plasma were investigated to evaluate the clinical significance of circIMMP2L. Results CircIMMP2L, commonly upregulated in tumor and plasma from advanced‐stage ESCC patients and LNM patients, predicts poorer patient survival. CircIMMP2L was also found to be a significant indicator for LNM, even in the T1 stage of ESCC. CircIMMP2L depletion suppressed the malignant progression of ESCC both in vitro and in vivo. Mechanistically, cytoplasmic circIMMP2L interacted with CtBP1 and facilitated the nuclear retention of CtBP1 in a CtBP2‐independent manner. Moreover, circIMMP2L promoted the interaction of CtBP1 with HDAC1 in the nucleus, which is essential for epigenetic remodeling and transcriptional suppression of E‐cadherin and p21. Conclusions These findings demonstrated that circIMMP2L promotes the malignant progression of ESCC mediated by CtBP1 nuclear retention and is a robust biomarker for the diagnosis, prognosis, and LNM in ESCC. Further, the findings extend our knowledge about the mechanism of circRNA regulation of gene transcription through epigenetics.
Tertiary lymphoid structures (TLSs) are considered to have a good prognosis in multiple solid tumors. However, the prognostic value of TLS in esophageal squamous cell carcinoma (ESCC) is unknown. In this study, we retrospectively enrolled 185 ESCC patients who underwent surgical resection. Hematoxylin and eosin staining was performed to investigate the presence, the abundance, the maturation, and the location of TLSs. We explored the cellular composition of TLSs using traditional immunohistochemistry in serial sections. The prognostic value of TLSs was investigated by univariate and multivariate analyses. A nomogram was constructed to predict the prognosis. TLS‐positive tumors were infiltrated with more CD45 + leukocytes, CD20 + B cells, CD4 + and CD8 + T cells, and CD11c + dendritic cells(DCs) compared with negative tumors. Kaplan–Meier curves showed that the presence and the abundance of TLSs were associated with longer disease‐free survival (DFS) ( p = 0.0130) and overall survival (OS) ( p = 0.0164). In addition, patients with tumors containing more CD20 + B cell infiltration had longer DFS ( p = 0.0105) and OS ( p = 0.0341). Multivariate analyses demonstrated that the presence of TLSs was an independent prognostic factor for DFS (hazard ratio [HR] = 0.384, p < 0.001) and OS (HR = 0.293, p < 0.001). The nomogram that integrated the tumor stage, histologic grade, and TLS presence had higher prognostic accuracy. Our study suggests that ESCC‐related TLSs can be used as a new biomarker for the prognosis of ESCC patients, and further understanding of their formation and mechanism of induction can provide a possible direction and target for immunotherapy of ESCC.
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