Automatic segmentation framework of X-Ray tomography data for multi-phase rock using Swin Transformer approach.

A thorough understanding of the impact of the 3D meso-structure on damage and failure patterns is essential for revealing the failure conditions of composite rock materials such as coal, concrete, marble, and others. This paper presents a 3D XCT dataset of coal rock with 1372 slices (each slice contains 1720 × 1771 pixels in x × y direction). The 3D XCT datasets were obtained by MicroXMT-400 using the 225/320kv Nikon Metris custom bay. The raw datasets were processed by an automatic semantic segmentation method based on the Swin Transformer (Swin-T) architecture, which aims to overcome the issue of large errors and low efficiency for traditional methods. The hybrid loss function proposed can also effectively mitigate the influence of large volume features in the training process by incorporating modulation terms into the cross entropy loss, thereby enhancing the accuracy of segmentation for small volume features. This dataset will be available to the related researchers for further finite element analysis or microstructural statistical analysis, involving complex physical and mechanical behaviors at different scales.

Alisertib exerts KRAS allele­specific anticancer effects on colorectal cancer cell lines.

The aim of the present study was to examine the effects of alisertib (ALS) on RAS signaling pathways against a panel of colorectal cancer (CRC) cell lines and engineered Flp-In stable cell lines expressing different Kirsten rat sarcoma virus (KRAS) mutants. The viability of Caco-2KRAS wild-type, Colo-678KRAS G12D, SK-CO-1KRAS G12V, HCT116KRAS G13D, CCCL-18KRAS A146T and HT29BRAF V600E cells was examined by Cell Titer-Glo assay, and that of stable cell lines was monitored by IncuCyte. The expression levels of phosphorylated (p-)Akt and p-Erk as RAS signal outputs were measured by western blotting. The results suggested that ALS exhibited different inhibitory effects on cell viability and different regulatory effects on guanosine triphosphate (GTP)-bound RAS in CRC cell lines. ALS also exhibited various regulatory effects on the PI3K/Akt and mitogen-activated protein kinase (MAPK) pathways, the two dominant RAS signaling pathways, and induced apoptosis and autophagy in a RAS allele-specific manner. Combined treatment with ALS and selumetinib enhanced the regulatory effects of ALS on apoptosis and autophagy in CRC cell lines in a RAS allele-specific manner. Notably, combined treatment exhibited a synergistic inhibitory effect on cell proliferation in Flp-In stable cell lines. The results of the present study suggested that ALS differentially regulates RAS signaling pathways. The combined approach of ALS and a MEK inhibitor may represent a new therapeutic strategy for precision therapy for CRC in a KRAS allele-specific manner; however, this effect requires further study in vivo.

MOGS promotes stemness acquisition and invasion via enhancing NOTCH1-glycosylation dependent NOTCH pathway in colorectal cancer.

Colorectal cancer (CRC) ranks as the third most prevalent cancer globally, and about half of CRC patients eventually succumb to tumor metastasis. Despite this, treatment options for metastatic colon cancer remain severely limited, reflected by a 12% 5-year overall survival rate. Increasing evidence suggests that cancer stem cells (CSCs) are pivotal in driving CRC metastasis. Our study found a significant upregulation of MOGS in metastatic colorectal cancer, with high MOGS expression inversely correlating with patient prognosis. Additionally, MOGS enhances the NOTCH pathway, thus promoting stemness in CRC cells, both in vitro and in vivo. Mechanistically, MOGS may facilitate the maturation of NOTCH1 protein by promoting NOTCH1 glycosylation. Correspondingly, silencing MOGS markedly reduced invasion and stemness of CRC cells in vivo. In summary, our findings highlight the critical role of MOGS in fostering stemness and activating the NOTCH pathway in colorectal cancer cells. Disrupting the function of the MOGS/NOTCH could represent a feasible therapeutic strategy for CRC management.

Prrx1 promotes resistance to temozolomide by upregulating ABCC1 and inducing vasculogenic mimicry in glioma.

Gliomas are the most common primary brain tumors with dismal prognoses. Temozolomide (TMZ), the frontline therapeutic agent for gliomas, has shown limited clinical benefit primarily due to the acquired chemoresistance. Although growing evidence has suggested that the multi-drug resistance phenotype and abnormal vascular microenvironment are responsible for the intrinsic and extrinsic TMZ resistance, the molecular mechanism of TMZ resistance remains to be elucidated. In this study, we found Paired-related homeobox 1 (Prrx1) was an independent prognostic factor for the efficacy of chemotherapy-based postoperative treatment. Silencing Prrx1 markedly enhanced the TMZ-induced cytotoxicity both in vitro and in vivo. We also demonstrated that Prrx1 increased the expression of ABCC1, a member of ATP-Binding Cassette (ABC) transporter protein family, through binding to the promoter region of ABCC1 gene and initiating its transcription. Silencing ABCC1 mitigated the TMZ resistance induced by Prrx1. Furthermore, Prrx1 facilitates the formation of vasculogenic mimicry (VM), a critical extrinsic mechanism for glioma TMZ resistance. Collectively, our findings supported the critical role of Prrx1 in TMZ resistance via intrinsic and extrinsic mechanism. Targeting Prrx1 might represent a feasible strategy to overcome therapeutic resistance in glioma.

The Role of Metabolic Dysfunction in T-Cell Exhaustion During Chronic Viral Infection.

T cells are important components of adaptive immunity that protect the host against invading pathogens during infection. Upon recognizing the activation signals, naïve and/or memory T cells will initiate clonal expansion, trigger differentiation into effector populations and traffic to the inflamed sites to eliminate pathogens. However, in chronic viral infections, such as those caused by human immunodeficiency virus (HIV), hepatitis B and C (HBV and HCV), T cells exhibit impaired function and become difficult to clear pathogens in a state known as T-cell exhaustion. The activation and function persistence of T cells demand for dynamic changes in cellular metabolism to meet their bioenergetic and biosynthetic demands, especially the augmentation of aerobic glycolysis, which not only provide efficient energy generation, but also fuel multiple biochemical intermediates that are essential for nucleotide, amino acid, fatty acid synthesis and mitochondria function. Changes in cellular metabolism also affect the function of effectors T cells through modifying epigenetic signatures. It is widely accepted that the dysfunction of T cell metabolism contributes greatly to T-cell exhaustion. Here, we reviewed recent findings on T cells metabolism under chronic viral infection, seeking to reveal the role of metabolic dysfunction played in T-cell exhaustion.

PRRX1 promotes colorectal cancer stemness and chemoresistance via the JAK2/STAT3 axis by targeting IL-6.

Background: Stemness acquirement is one of the hallmarks of cancer and the major reason for the chemoresistance and poor prognosis of colorectal cancer (CRC). Previous research has revealed the stimulatory role of paired related homeobox 1 (PRRX1) on CRC metastasis. However, the role of PRRX1 in stemness acquirement and chemoresistance of CRC is still not clear. Methods: A retrospective cohort study was performed to investigate the relationship between PRRX1 expression and multiple clinicopathological characteristics of CRC patients. The functional effects of PRRX1 on stemness and chemoresistance of CRC cells were validated by in vitro and in vivo assays. Gene set enrichment analysis (GSEA) and JASPAR software were performed to predict the underlying mechanisms. Enzyme-linked immunosorbent assay (ELISA), Western blot, immunofluorescence, and dual-luciferase reporter assays were used to confirm the PRRX1-mediated signaling and its downstream factors. Results: The expression of PRRX1 was up-regulated in CRC tissues and cell lines compared to normal epithelial tissues and cell lines. High expression of PRRX1 was tightly associated with the metastasis, chemoresistance, and poor prognosis of CRC patients. Additionally, PRRX1 significantly promoted the proliferation, viability, stemness, and chemoresistance of CRC cells, as well as the activation of the interleukin-6 (IL-6)/JAK2/STAT3 axis. Inhibiting the expression of IL-6 dramatically eliminated the effects of PRRX1 on CRC cell stemness and chemoresistance. Conclusions: PRRX1 plays a vital role in the stemness and chemoresistance of CRC cells via JAK2/STAT3 signaling by targeting IL-6. Further, PRRX1 may be a valid biomarker for predicting the effect of chemotherapy and prognosis of CRC patients.

Prrx1 promotes stemness and angiogenesis via activating TGF-ß/smad pathway and upregulating proangiogenic factors in glioma.

Glioma is one of the most lethal cancers with highly vascularized networks and growing evidences have identified glioma stem cells (GSCs) to account for excessive angiogenesis in glioma. Aberrant expression of paired-related homeobox1 (Prrx1) has been functionally associated with cancer stem cells including GSCs. In this study, Prrx1 was found to be markedly upregulated in glioma specimens and elevated Prrx1 expression was inversely correlated with prognosis of glioma patients. Prrx1 potentiated stemness acquisition in non-stem tumor cells (NSTCs) and stemness maintenance in GSCs, accompanied with increased expression of stemness markers such as SOX2. Prrx1 also promoted glioma angiogenesis by upregulating proangiogenic factors such as VEGF. Consistently, silencing Prrx1 markedly inhibited glioma proliferation, stemness, and angiogenesis in vivo. Using a combination of subcellular proteomics and in vitro analyses, we revealed that Prrx1 directly bound to the promoter regions of TGF-ß1 gene, upregulated TGF-ß1 expression, and ultimately activated the TGF-ß/smad pathway. Silencing TGF-ß1 mitigated the malignant behaviors induced by Prrx1. Activation of this pathway cooperates with Prrx1 to upregulate the expression of stemness-related genes and proangiogenic factors. In summary, our findings revealed that Prrx1/TGF-ß/smad signal axis exerted a critical role in glioma stemness and angiogeneis. Disrupting the function of this signal axis might represent a new therapeutic strategy in glioma patients.

lncRNA KCNQ1OT1 knockdown inhibits colorectal cancer cell proliferation, migration and invasiveness via the PI3K/AKT pathway.

Colorectal cancer (CRC) is one of the most common primary malignancies worldwide. Numerous studies have demonstrated that long non-coding RNAs (lncRNAs) are considered as crucial regulators of tumor progression. In particular, upregulation of the lncRNA KCNQ1OT1 was reported in various types of malignancy as a promoter of tumor progression. However, the role and underlying mechanism of KCNQ1OT1 in CRC remain unclear. Thus, the present study aimed to investigate the role of KCNQ1OT1 in colorectal cancer through GEPIA, reverse transcription-quantitative PCR (RT-qPCR) and western blot analyses, and cell assays. GEPIA analysis demonstrated that high expression levels of KCNQ1OT1 in CRC tissues predicted a poor prognosis for patients with CRC. KCNQ1OT1 was overexpressed in CRC tissues and cell lines via RT-qPCR analysis. Furthermore, the results from the cell viability assay, colony formation assay, wound healing assay, invasion assay and flow cytometric analysis demonstrated that KCNQ1OT1 knockdown significantly inhibited CRC cell proliferation, migration and invasiveness, and promoted CRC cell apoptosis, leading to cell cycle arrest. Western blot analysis demonstrated that KCNQ1OT1 knockdown inhibited the PI3K/AKT signaling pathway. These results suggest that KCNQ1OT1 may act as an oncogene through the PI3K/AKT signaling pathway in CRC.

Ethanol promotes alcohol-related colorectal cancer metastasis via the TGF-ß/RUNX3/Snail axis by inducing TGF-ß1 upregulation and RUNX3 cytoplasmic mislocalization.

BACKGROUND: Alcohol intake is a well-known lifestyle risk factor for CRC, and an increasing number of studies have revealed that alcohol intake is also tightly associated with CRC metastasis. However, the effect of alcohol on CRC metastasis and its underlying mechanism remain unclear. METHODS: A retrospective cohort study was performed to investigate the characteristics of patients with alcohol-related CRC. The effects of ethanol on the biological behaviours of CRC cells were assessed through in vivo and in vitro assays using the Lieber-DeCarli ethanol liquid diet and ethanol, respectively. The ethanol-mediated signalling pathway and downstream factors were screened through ELISA, western blot, immunofluorescence and co-immunoprecipitation. FINDINGS: Most patients with alcohol-related CRC, particularly those with tumour metastasis, were characterized by a notably higher circulating ethanol level and a lower systemic acetaldehyde level. Moreover, CRC cells accumulated in ethanol, but not acetaldehyde, to notably higher levels compared with adjacent normal cells. Alcohol intake significantly promoted CRC metastasis via the ethanol-mediated TGF-ß/Smad/Snail axis, and ethanol induced the cytoplasmic mislocalization of RUNX3 and further promoted the aggressiveness of CRC by targeting Snail. Pirfenidone (PFD) significantly eliminated the effects of ethanol on CRC metastasis by specifically blocking TGF-ß signalling. INTERPRETATION: Alcohol intake plays a vital role in CRC metastasis via the ethanol-mediated TGF-ß/RUNX3/Snail axis, and PFD might be a novel therapeutic management strategy for CRC.

Overexpression of MAGT1 is associated with aggressiveness and poor prognosis of colorectal cancer.

Tumor metastasis and anticancer drug resistance are the major causes of mortality in patients with colorectal cancer (CRC). Due to the limitations of conventional biomarkers, it is urgent to identify novel and valid biomarkers to predict the progression and prognosis of CRC. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect MAGT1 expression in CRC clinical samples or cell lines. Bioinformatics analysis was used to investigate the association between MAGT1 alteration and clinicopathological features of patients with CRC. The present study revealed that the transcription levels of magnesium transporter 1 (MAGT1) were significantly increased in CRC tissues compared with matched adjacent normal tissues. Overexpression of MAGT1 was associated with advanced tumor stage, N and M classification. In addition, for patients who underwent chemotherapy, patients in the MAGT1-low expression group exhibited a longer overall survival (OS) time than patients in the high-expression group. Patients with CRC treated with chemotherapy had a longer OS time than those treated without chemotherapy in the MAGT1-low expression group but not in the MAGT1-high expression group. Furthermore, MAGT1 was a valid but not an independent prognostic factor for CRC. Therefore, the present study highlighted that MAGT1 may serve as a valid biomarker for predicting the development, progression and poor prognosis of CRC.

Tumor-secreted dickkopf2 accelerates aerobic glycolysis and promotes angiogenesis in colorectal cancer.

Angiogenesis is a fundamental process that involves in tumor progression and metastasis. Vascular endothelial growth factor (VEGF) family and their receptors are identified as the most prominent regulators of angiogenesis. However, the clinical efficacy of anti-VEGF/VEGFR therapy is not ideal, prompting the needs to further understand mechanisms behind tumor angiogenesis. Here, we found that Dickkopf associated protein 2 (DKK2), a secretory protein highly expressed in metastatic colorectal cancer tissues, could stimulate angiogenesis via a classic VEGF/VEGFR independent pathway. Methods: DKK2 was screened out from microarray data analyzing gene expression profiles of eight pairs of non-metastatic and metastatic human colorectal cancer (CRC) tissues. Immunofluorescence histochemical staining (IHC) was used to detect the expression of DKK2 and angiogenesis in CRC tissues. Chicken chorioallantoic membrane (CAM) assay and Human umbilical vein endothelial cells (HUVEC) tubule formation assay was used for in vitro and in vivo angiogenesis study, respectively. Lactate and glucose concentration in the culture medium was measured by enzyme-linked immunosorbent assay (ELISA). Luciferase reporter assay was used to verify the interaction between miR-493-5p and the 3'UTR of DKK2. Results: DKK2 could stimulate angiogenesis via accelerating the aerobic glycolysis of CRC cells, through which lactate is produced from glucose and accumulated in tumor microenvironment. Lactate functions as the final executor of DDK2 to stimulate tube formation of endothelial cells, and blockage of lactate secretion by lactate transporter (MCT) inhibitors dramatically neutralize the progression and metastasis of CRC both in vitro and in vivo. DKK2 could cooperate with lipoprotein receptor-related protein 6, which is required for glucose uptake, and activated the downstream mTOR signal pathway to accelerate lactate secretion. In addition, the expression of DKK2 is switched on via the demethylation of miR-493-5p, which allows the dissociated of miR-493-5p from the 3'-UTRs of DKK2 and initiates its stimulatory role on CRC progression in an autocrine or paracrine manner. Conclusion: DKK2 promotes tumor metastasis and angiogenesis through a novel VEGF-independent, but energy metabolism related pathway. DKK2 might be a potential anti-angiogenic target in clinical treatment for the advanced CRC patients.

Duodenojejunal Bypass Plus Sleeve Gastrectomy Reduces Infiltration of Macrophages and Secretion of TNF-α in the Visceral White Adipose Tissue of Goto-Kakizaki Rats.

BACKGROUND: Current studies indicate that inflammation of white adipose tissue (WAT) is a pathogenic characteristic of insulin resistance. However, the significance of visceral WAT inflammation after bariatric surgery remains unclear. METHODS: Duodenojejunal bypass plus sleeve gastrectomy (DJB-SG) was performed on Goto-Kakisaki rats. Weight, fasting blood glucose (FBG), and homeostatic model assessment of insulin resistance (HOMA-IR) in the DJB-SG group were compared to those in a sham surgery (SHAM) group every 2 weeks. The results of an oral glucose tolerance test (OGTT) and the volume of visceral adipose tissue (Visc.Fat) were compared before and 8 weeks postsurgery. Eight weeks after surgery, the rats were sacrificed and visceral WAT collected from the greater omentum. Tumor necrosis factor-α (TNF-α) and cluster of differentiation 68 (CD68) expression in the WAT were evaluated in paraffin-embedded sections by immunohistochemistry. RESULTS: Compared with the SHAM group, the DJB-SG group demonstrated a significant reduction in weight, FBG, and HOMA-IR (P < 0.05), with elevation of insulin levels (P < 0.05) from 4 weeks after surgery. OGTT and the quantity of Visc.Fat were significantly reduced (P < 0.05) 8 weeks after surgery. Moreover, the expression of TNF-α and CD68 in the visceral white adipose tissue was significantly lower 8 weeks after surgery (P < 0.05). CONCLUSIONS: The DJB-SG model established in Goto-Kakisaki rats achieved anticipated efficacy. Reduced TNF-α-related inflammation in visceral WAT may result in improved insulin resistance.

Sphingomyelin synthase 2 promotes an aggressive breast cancer phenotype by disrupting the homoeostasis of ceramide and sphingomyelin.

Breast cancer is the most common type of carcinoma in women worldwide, but the mechanisms underlying tumour development and progression remain unclear. Sphingomyelin synthase 2 (SGMS2) is a crucial regulator involved in ceramide (Cer) and sphingomyelin (SM) homoeostasis that is mostly studied for its role in lipid metabolism. Our primary study indicated that high SGMS2 expression is associated with breast cancer metastasis. Gain- and loss-of-function assays in vitro and in vivo revealed that SGMS2 promotes cancer cell proliferation by suppressing apoptosis through a Cer-associated pathway and promotes cancer cell invasiveness by enhancing epithelial-to-mesenchymal transition (EMT) initiation through the TGF-ß/Smad signalling pathway. Further study determined that SGMS2 activated the TGF-ß/Smad signalling pathway primarily by increasing TGF-ß1 secretion, which was likely associated with aberrant expression of SM. Thus, our findings indicate that SGMS2-mediated activation of the TGF-ß/Smad signalling pathway is important in breast cancer progression, which provides new insight into the mechanisms underlying breast cancer metastasis and suggests a possible anticancer therapy for breast cancer.

[ADAM17 knockdown increases sensitivity of SW480 cells to cetuximad].

OBJECTIVE: To explore the association between expression of ADAM17 and cetuximad resistance in human colorectal cancer SW480 cells. METHODS: The expression of ADAM17 was detected using Western blotting in different human colorectal cancer cell lines, and the cells highly expressing ADAM17 were selected as the target cells. SW480 cells were transfected with ADAM17-siRNA 1 and ADAM17-siRNA 2 and the changes in the expression of ADAM17 protein were detected using Western blotting. SW480 cells were exposed to cetuximad for 24 h and the cell apoptosis was analyzed using flow cytometry. Transwell assay was used to examine the migration ability of SW480 cells with different expression levels of ADAM17; Western blotting was used to analyze the changes in the expressions of AKT signaling pathway-related proteins in the treated cells. RESULTS: The baseline expressions of ADAM17 were significantly higher in SW480 cells than in the other human colorectal cancer cell lines tested (P < 0.05). Both ADAM17-siRNA 1 and 2 effectively reduced the expression of ADAM17 protein in SW480 cells. Knockdown of ADAM17 with siRNA 1 significantly increased the sensitivity of SW480 cells to tocetuximad (P < 0.05), obviously inhibited the cell proliferation, migration and invasion, and significantly reduced the expressions of p-EGFR and p-AKT in the cells (P < 0.001). CONCLUSIONS: ADAM17 knockdown obviously inhibits EGFR-AKT signaling pathway and increases the sensitivity of SW480 cells to tocetuximad.

MicroRNA-661 expression is upregulated in pancreatic ductal adenocarcinoma and promotes cell proliferation.

Deregulation of microRNA (miRNA/miR) expression has been implicated in the development of pancreatic ductal adenocarcinoma (PDAC). However, the role of miR-661 in PDAC remains unknown. In the present study, it was revealed that miR-661 expression was significantly upregulated in PDAC tissues compared with that in adjacent normal tissues by using reverse transcription-quantitative polymerase chain reaction assays. Higher miR-661 expression revealed a positive association with lymph node metastasis, an advanced T stage and a poor prognosis in patients with PDAC. Furthermore, ectopic expression of miR-661 significantly promoted the cell proliferation ability in PDAC cell lines, and simultaneously promoted Wnt signaling pathway-related protein expression of ß-catenin, transcription factor 4 and cyclin D1 in vitro. However, the downregulation of miR-661 revealed reverse effects. Thus, the results of the present study indicated that miR-661 may function as a prognostic marker and provide insight for pancreatic cancer treatment.

[Structural changes of gut microbiota after gastric bypass in obese patients with type 2 diabetes].

OBJECTIVE: To investigate the structural changes inintestinal flora and metabolic changes in type 2 diabetic patients with obesity(BMI≥40 kg/m2)by sequencing the 16S rRNA genes. METHODS: Stool samples were collected from 4 diabetic patients before and after gastric bypass surgery for extraction of the total DNA. The diversity of the intestinal flora in the samples was investigated by 16S rRNA sequencing. After surgery, the changes in glucose and lipid metabolism were evaluated in the patients, and the changesin body mass index (BMI) and waist to hip ratio were assessed at 3 month intervals. RESULTS: After gastric bypass, the patient's BMI, waist to hip ratio, glucose metabolism and lipid metabolism gradually recovered the normal levels. The proportion of Bacteroidetesis increased and the proportions of Firmicutes and Proteobacteria decreased in the intestinal bacteria after the surgery. CONCLUSION: Gastric bypass surgery can effectively alleviate the condition of obese patients with type 2 diabetes and improve the composition of the intestinal flora.

Loss of the 14-3-3σ is essential for LASP1-mediated colorectal cancer progression via activating PI3K/AKT signaling pathway.

LIM and SH3 protein 1 (LASP1) can promote colorectal cancer (CRC) progression and metastasis, but the direct evidence that elucidates the molecular mechanism remains unclear. Here, our proteomic data showed that LASP1 interacted with 14-3-3σ and decreased the expression of 14-3-3σ in CRC. Deletion of 14-3-3σ was required for LASP1-mediated CRC cell aggressiveness. In vitro gain- and loss-of-function assays showed that 14-3-3σ suppressed the ability of cell migration and decreased the phosphorylation of AKT in CRC cells. We further observed clearly co-localization between AKT and 14-3-3σ in CRC cells. Treatment of PI3K inhibitor LY294002 markedly prevented phosphorylation of AKT and subsequently counteract aggressive phenotype mediated by siRNA of 14-3-3σ. Clinically, 14-3-3σ is frequently down-regulated in CRC tissues. Down-regulation of 14-3-3σ is associated with tumor progression and poor prognosis of patients with CRC. Multivariate analysis confirmed low expression of 14-3-3σ as an independent prognostic factor for CRC. A combination of low 14-3-3σ and high LASP1 expression shows a worse trend with overall survival of CRC patients. Our research paves the path to future investigation of the LASP1-14-3-3σ axis as a target for novel anticancer therapies of advanced CRC.

Epigenetic silencing of miR-490-3p promotes development of an aggressive colorectal cancer phenotype through activation of the Wnt/ß-catenin signaling pathway.

The Wnt/ß-catenin pathway is known to contribute to colorectal cancer (CRC) progression, although little is known about the contribution of ß-catenin on this process. We investigated the role of miR-490-3p, which was recently reported to suppress tumorigenesis through its effect on Wnt/ß-catenin signaling. We found that hypermethylation of the miR-490-3p promoter down-regulates miR-490-3p expression in CRC tissue. Gain- and loss-of-function assays in vitro and in vivo reveal that miR-490-3p suppresses cancer cell proliferation by inducing apoptosis and inhibits cell invasiveness by repressing the initiation of epithelial-to-mesenchymal transition (EMT), a key mechanism in cancer cell invasiveness and metastasis. The frequently rearranged in advanced T-cell lymphomas (FRAT1) protein was identified as a direct target of miR-490-3p and contributes to its tumor-suppressing effects. miR-490-3p appears to have an inhibitory effect on ß-catenin expression in nuclear fractions of CRC cells, whereas FRAT1 expression is associated with the accumulation of ß-catenin in the nucleus of cells, which could be weakened by transfection with miR-490-3p. Our findings suggest that the miR-490-3p/FRAT1/ß-catenin axis is important in CRC progression and provides new insight into the molecular mechanisms underlying CRC. They may help to confirm the pathway driving CRC aggressiveness and serve for the development of a novel miRNA-targeting anticancer therapy.

Multi-Sensor Data Fusion Identification for Shearer Cutting Conditions Based on Parallel Quasi-Newton Neural Networks and the Dempster-Shafer Theory.

In order to efficiently and accurately identify the cutting condition of a shearer, this paper proposed an intelligent multi-sensor data fusion identification method using the parallel quasi-Newton neural network (PQN-NN) and the Dempster-Shafer (DS) theory. The vibration acceleration signals and current signal of six cutting conditions were collected from a self-designed experimental system and some special state features were extracted from the intrinsic mode functions (IMFs) based on the ensemble empirical mode decomposition (EEMD). In the experiment, three classifiers were trained and tested by the selected features of the measured data, and the DS theory was used to combine the identification results of three single classifiers. Furthermore, some comparisons with other methods were carried out. The experimental results indicate that the proposed method performs with higher detection accuracy and credibility than the competing algorithms. Finally, an industrial application example in the fully mechanized coal mining face was demonstrated to specify the effect of the proposed system.