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Colorectal cancer (CRC) remains one of the most frequent neoplasms of digestive tract worldwide. Circular RNAs (circRNAs) have been identified to serve crucial regulatory roles in the pathogenesis of human cancers. However, the role and regulatory mechanism of circ_0000467 in the progression of CRC are still unclear. The expression levels of circ_0000467, microRNA-330-5p (miR-330-5p), and tyrosine receptor kinase 3 (TYRO3) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-330-5p and circ_0000467 or TYRO3 was validated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft tumor assay and Immunohistochemistry (IHC) assay were implemented to analyze CRC tumor growth in vivo. Circ_0000467 was a stable circRNA and was highly expressed in CRC tumor tissues and cells. Silencing of circ_0000467 could inhibit the proliferation, migration, invasion, and glycolysis and accelerated the apoptosis of CRC cells in vitro and hindered tumor growth in vivo. Mechanistically, circ_0000467 directly interacted with miR-330-5p and circ_0000467 depletion inhibited CRC cell malignant progression by regulating miR-330-5p. Furthermore, TYRO3 was a target of miR-330-5p and circ_0000467 upregulated TYRO3 expression by sponging miR-330-5p. Moreover, TYRO3 overexpression counteracted the inhibitory effect of miR-330-5p overexpression or circ_0000467 knockdown on CRC cell progression. Altogether, circ_0000467 knockdown suppressed CRC cell malignant development through modulating the miR-330-5p/TYRO3 network, providing a novel molecular target of CRC therapy.

Cold metal transfer (CMT) fusion brazing technology was used to weld 6061 aluminum alloy and Q235 galvanized steel with ER4043 welding wire. The microstructure, hardness, tensile performance, and fatigue performance of the welded joint were observed and analyzed. The results show that the tensile strength of the welded joint is 110.83 MPa and the fatigue strength limit is 170 MPa. In the fatigue process, the coupon first undergoes cyclic hardening and then cyclic softening and a ratchet effect occurs. The coupon was broken at the interface layer or weld zone where the fatigue strength limit is the lowest. The fatigue crack initiation is mainly caused by: (1) inclusions and second-phase particles; and (2) porosity and incomplete fusion. When cracks encounter holes during expansion, the expansion direction will change. The fatigued coupon displays a toughness fracture in the instantaneous fracture zone.

Glioblastoma multiforme (GBM) is a fatal cancer with varying life expectancy, even for patients undergoing the same standard therapy. Identification of differentially expressed genes in GBM patients with different survival rates may benefit the development of effective therapeutic strategies. In the present study, key pathways and genes correlated with survival in GBM patients were screened with bioinformatic analysis. Included in the study were 136 eligible patients who had undertaken surgical resection of GBM followed by temozolomide (TMZ) chemoradiation and long-term therapy with TMZ. A total of 383 differentially expressed genes (DEGs) related to GBM survival were identified. Gene Ontology and pathway enrichment analysis as well as hub gene screening and module analysis were performed. As expected, angiogenesis and migration of GBM cells were closely correlated with a poor prognosis. Importantly, the results also indicated that cell dormancy was an essential contributor to the reduced survival of GBM patients. Given the lack of specific targeted genes and pathways known to be involved in tumour cell dormancy, we proposed enriched candidate genes related to the negative regulation of cell proliferation, signalling pathways regulating pluripotency of stem cells and neuroactive ligand-receptor interaction, and 3 hub genes (FTH1, GRM1 and DDIT3). Maintaining persistent cell dormancy or preventing tumour cells from entering dormancy during chemoradiation should be a promising therapeutic strategy.

Numerous studies have shown that calmodulin (CaM) is a major regulator of calcium-dependent signaling, which regulates cell proliferation, programmed cell death, and autophagy in cancer. However, limited information is available on mechanisms underlying the effect of CaM on the invasive property of glioblastoma multiforme (GBM) cells, especially with respect to invadopodia formation. In this study, we find that CaM serves as a prognostic factor for GBM, and it is strongly associated with the invasive nature of this tumor. Results of preliminary experiments indicated that CaM concentration was significantly correlated with the invasive capacity of and invadopodia formation by different GBM cell lines. CaM inhibition via a small hairpin RNA or a pharmacological inhibitor significantly disrupted invadopodia formation and MMP activity and downregulated vimentin expression. Moreover, CaM knockdown exerted a strong anti-invasive effect on GBM in vivo. Interestingly, epidermal growth factor treatment promoted CaM redistribution from the nucleus to the cytoplasm, eventually activating invadopodia-associated proteins by binding to them via their cytosolic-binding sites. Moreover, CaM inhibition suppressed the activation of invadopodia-associated proteins. Thus, our findings provide a novel therapeutic strategy to impede GBM invasion by inhibiting invadopodia formation, and shed light on the spatial organization of CaM signals during GBM invasion.

Numerous studies have shown that calmodulin (CaM) is a major regulator of calcium-dependent signaling, which regulates cell proliferation, programmed cell death, and autophagy in cancer. However, limited information is available on mechanisms underlying the effect of CaM on the invasive property of glioblastoma multiforme (GBM) cells, especially with respect to invadopodia formation. In this study, we find that CaM serves as a prognostic factor for GBM, and it is strongly associated with the invasive nature of this tumor. Results of preliminary experiments indicated that CaM concentration was significantly correlated with the invasive capacity of and invadopodia formation by different GBM cell lines. CaM inhibition via a small hairpin RNA or a pharmacological inhibitor significantly disrupted invadopodia formation and MMP activity and downregulated vimentin expression. Moreover, CaM knockdown exerted a strong anti-invasive effect on GBM in vivo. Interestingly, epidermal growth factor treatment promoted CaM redistribution from the nucleus to the cytoplasm, eventually activating invadopodia-associated proteins by binding to them via their cytosolic-binding sites. Moreover, CaM inhibition suppressed the activation of invadopodia-associated proteins. Thus, our findings provide a novel therapeutic strategy to impede GBM invasion by inhibiting invadopodia formation, and shed light on the spatial organization of CaM signals during GBM invasion.

Glioblastomas (GBMs) are the most prevalent and devastating primary intracranial malignancies and have extensive heterogeneity. Notch1 signaling is a more complex process in the development of numerous cell and tissue types, including gliomagenesis and progression, and is upregulated in glioma-initiating cells. However, the contradictory expression of Notch1 among lower grade gliomas and GBMs confounds our understanding of GBM biology and has made identifying effective therapies difficult. In this study, we validated that Notch1 and NF-κB(p65) are highly expressed in the classical and proneural subtypes of GBM using the data set from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). DAPT and shRNA targeting Notch1 decreased NF-κB(p65) expression, suppressed cell proliferation, and induced apoptosis of GBM cells in vitro and in vivo. Furthermore, we illustrated that the intracellular Notch could bind with NF-κB(p65) in GBM cells. These findings suggest that the cross-talk between Notch1 signaling and NF-κB(p65) could contribute to the proliferation and apoptosis of glioma, and this discovery could help drive the design of more effective therapies in Notch1-targeted clinical trials.