Colorectal cancer (CRC) is a common human malignant tumor, and the fourth most common cause of cancer‑associated mortality in China. However, the pathogenesis of CRC is not yet fully understood. The present study aimed to investigate the expression and clinical significance of microRNA (miR)‑126 and insulin receptor substrate‑1 (IRS‑1), as well as the role of miR‑126 in the prognosis of patients with CRC. A total of 86 colorectal tissue specimens, including 40 CRC and adjacent normal tissue, 26 colorectal adenoma tissue and 20 normal colorectal tissue samples, were collected for the present study. Reverse transcription‑quantitative PCR analysis was performed to determine miR‑126 and IRS‑1 mRNA expression levels, while western blotting and immunohistochemistry (IHC) analyses were performed to determine IRS‑1 protein expression levels. The correlation between miR‑126 and IRS‑1 expression, as well as the association between altered miR‑126 and IRS‑1 expression levels and clinicopathological characteristics, and the overall survival time of patients with CRC were assessed. The results demonstrated that miR‑126 expression was significantly downregulated, while IRS‑1 protein expression was upregulated in CRC tissues compared with that in adjacent normal tissues, colorectal adenoma tissues and normal colorectal tissues, respectively. IHC analysis exhibited strong positive staining of IRS‑1 protein in CRC tissues, while absent or weak staining of IRS‑1 protein was detected in adjacent normal tissues, colorectal adenoma tissues and normal colorectal tissues. miR‑126 expression was inversely correlated with IRS‑1 protein expression in CRC tissues (r=‑0.420; P<0.05). Furthermore, downregulated miR‑126 expression was associated with advanced clinicopathological characteristics of the disease and a shorter overall survival time in patients with CRC. Taken together, the results of the present study suggest that miR‑126 downregulation may be a candidate molecular marker predictive of poor prognosis of patients with CRC.
Objectives In this study, we aimed to clarify the relationship between physical activity (PA) and diabetes mellitus (DM), as well as the mediating role of Systemic Immune-Inflammatory Index (SII) in the relationship. Design A cross-sectional study. Setting National Health and Nutrition Examination Survey (NHANES) data collection took place in the USA at participants’ homes and mobile examination centres with specialised equipment. Participants The study population consisted of 9493 American adults aged 20 and above from the NHANES 2005 to 2018. Primary and secondary outcome measures Information on the specific PA was reported through self-administered questionnaire by participants and we used this information to calculate a metabolic equivalent score for the particular PA. The calculation of SII follows a standard formula: SII=P (platelets)×N (neutrophils)/L (lymphocytes). Results A total of 9493 participants were included, with 1672 diagnosed with DM. The participants with DM were more inclined to have lower levels of PA while having higher levels of SII. In all three models, high levels of PA were significantly negatively associated with the risk of DM compared with moderate levels of PA, and a non-linear association between natural logarithm-physical activity (Ln-PA) and DM was observed. Furthermore, there was a significant reduction in DM risk for Ln-PA >6.71 in all models. Mediation analysis showed that SII mediated the relationship between PA and DM, as well as between Ln-PA and DM, with respective mediation proportions of 4.32% and 12.141%, as well as 3.12% and 10.46% after adjusting for covariates. Conclusion This study investigated the relationship among PA, SII and DM. We provide robust evidence supporting the inverse association between PA and DM risk while highlighting the mediating role of inflammation, as reflected by SII. These findings contribute valuable insights to inform public health strategies and clinical interventions aimed at reducing the global burden of DM.
The Petrov-Galerkin finite-element method is used to solve the unified Kadomtsev-Petviashvili equation [Chen and Liu, J. Fluid Mech. 288 (1995) 383]. Numerical experiments have been focused on studying the effect of slowly varying topography on the propagation of surface solitary waves in a stationary channel and Kelvin solitary waves in a rotating channel. We find that in the absence of rotation, an oblique incident solitary wave propagating over a three-dimensional shelf in a straight wide channel will eventually develop into a series of uniform straight-crested solitary waves, together with a train of small oscillatory waves moving upstream. With proper phase shifts, the shapes of these final two-dimensional solitary waves coincide with those of solitary waves emerging from a corresponding normal incident solitary wave propagating over the corresponding two-dimensional shelf. In a two-layered rotating channel, the variation of topography does not have much effect on the propagation of a Kelvin solitary wave of depression, whereas it can have a significant influence on the propagation of a Kelvin solitary wave of elevation. Explanations for these numerical findings are given.
Increased microRNA (miR)‑32 expression in colorectal cancer (CRC) tissues enhances CRC cell proliferation, migration, invasion and attenuates CRC cell apoptosis by repressing the expression of phosphatase and tensin homolog (PTEN). Forkhead box K1 (FOXK1) was identified as a potential interacting transcription factor using DNA pull‑down assays and mass spectrometry. The present study aimed to elucidate the role of FOXK1 in regulating miR‑32 expression in CRC. The expressions of FOXK1, miR‑32, transmembrane protein 245 gene (TMEM245) and PTEN were compared between CRC and normal colonic tissues. Levels of miR‑32, TMEM245, PTEN and the proliferation and apoptosis of CRC cells were studied using FOXK1‑overexpression or knockdown, or by simultaneously interfering with FOXK1 and miR‑32 expression. Direct FOXK1 binding to the miR‑32 promoter was verified using chromatin immunoprecipitation (ChIP) and dual‑luciferase reporter assays. The results showed elevated FOXK1, miR‑32 and TMEM245 expression, and significantly decreased PTEN expression in CRC, compared with normal colonic tissues. Correlations between the expressions of TMEM245 and miR‑32, FOXK1 and miR‑32, and FOXK1 and TMEM245 were positive and significant. FOXK1‑knockdown led to decreased miR‑32 and TMEM245 expression and increased PTEN expression, whereas FOXK1‑overexpression had the opposite effect. Overexpressed FOXK1 promoted the malignancy of CRC cells in vitro by stimulating proliferation and reducing apoptosis; whereas FOXK1‑depletion suppressed such malignancy and a miR‑32 inhibitor partially reversed the effects of FOXK1. The results of ChIP and dual‑luciferase reporter assays indicated that FOXK1 directly binds to the promoter of TMEM245/miR‑32. Thus, the FOXK1‑miR‑32‑PTEN signaling axis may play a crucial role in the pathogenesis and development of CRC.
Two–dimensional depth–integrated model equations describing nonlinear water waves propagating over a permeable bed are developed. These model equations are expressed in terms of the free–surface displacement and representative horizontal velocity components, which could be the velocity components evaluated at certain elevation or the depth–averaged velocity components. Each set of model equations invokes different approximations and therefore imposes different limitations on the vorticity field. The frequency–dispersion properties of the linearized model equations are investigated and are compared with those of small amplitude waves over a permeable bed. Based on these comparisons, an optimal model is suggested. To check the validity of the model equations, a laboratory experiment of a wave train propagating over a submerged triangular permeable bar is performed. Numerical results of the model equations show very good agreement with experimental data. The effects of the submerged permeable bar on the wave evolution are also discussed.
Asymmetric cell division (ACD) gives rise to two daughter cells with different fates after mitosis and is a fundamental process for generating cell diversity and for the maintenance of the stem cell population. The cancer stem cell (CSC) theory suggests that CSCs with dysregulated self-renewal and asymmetric cell division serve as a source of intra-tumoral heterogeneity. This heterogeneity complicates the diagnosis and treatment of cancer patients, because CSCs can give rise to aggressive clones that are metastatic and insensitive to multiple drugs, or to dormant tumor cells that are difficult to detect. Here, we review the regulatory mechanisms and biological significance of asymmetric division in tumor cells, with a focus on ACD-induced tumor heterogeneity in early tumorigenesis and cancer progression. We will also discuss how dissecting the relationship between ACD and cancer may help us find new approaches for combatting this heterogeneity.
In this paper, the propagation of interfacial waves in a two-layered fluid system is investigated. The interfacial waves are weakly nonlinear and dispersive and propagate in a slowly rotating channel with varying topography and sidewalls, and a weak steady background current field. An evolution equation for the interfacial displacement is derived for waves propagating predominantly in the longitudinal direction of the channel. This new evolution equation is called the unified Kadomtsev–Petviashvili (uKP) equation because most of the KP-type equations existing in the literature for both surface water waves and interfacial waves are special cases of the new evolution equation. The Painlevé PDE test is used to find the conditions under which the uKP equation can be solved by the inverse scattering transform. When these conditions are satisfied, elementary transformations are found to reduce the uKP equation to one of the completely integrable equations: the KP, the Korteweg–de Vries (KdV) or the cylindrical KdV equations. The integral invariants associated with the uKP equation for waves propagating in a varying channel are obtained and their relations with the conservation of mass and energy are discussed.
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