MiR-592 Promotes Gastric Cancer Proliferation, Migration, and Invasion Through the PI3K/AKT and MAPK/ERK Signaling Pathways by Targeting Spry2

Background/Aims: Gastric cancer (GC) is one of the most prevalent digestive malignancies. MicroRNAs (miRNAs) are involved in multiple cellular processes, including oncogenesis, and miR-592 itself participates in many malignancies; however, its role in GC remains unknown. In this study, we investigated the expression and molecular mechanisms of miR-592 in GC. Methods: Quantitative real-time PCR and immunohistochemistry were performed to determine the expression of miR-592 and its putative targets in human tissues and cell lines. Proliferation, migration, and invasion were evaluated by Cell Counting Kit-8, population doubling time, colony formation, Transwell, and wound-healing assays in transfected GC cells in vitro. A dual-luciferase reporter assay was used to determine whether miR-592 could directly bind its target. A tumorigenesis assay was used to study whether miR-592 affected GC growth in vivo. Proteins involved in signaling pathways and the epithelial–mesenchymal transition (EMT) were detected with western blot. Results: The ectopic expression of miR-592 promoted GC proliferation, migration, and invasion in vitro and facilitated tumorigenesis in vivo. Spry2 was a direct target of miR-592 and Spry2 overexpression partially counteracted the effects of miR-592. miR-592 induced the EMT and promoted its progression in GC via the PI3K/AKT and MAPK/ERK signaling pathways by inhibiting Spry2. Conclusions: Overexpression of miR-592 promotes GC proliferation, migration, and invasion and induces the EMT via the PI3K/AKT and MAPK/ERK signaling pathways by inhibiting Spry2, suggesting a potential therapeutic target for GC

Research on the Performance of Pumpjet Propulsor of Different Scales

This study presents a numerical research on the open-water performance of a pumpjet propulsor at different scales. Simulations were performed by an in-house viscous CFD (Computational Fluid Dynamic) code. The Reynolds-averaged Navier–Stokes (RANS) method with SST k-ω turbulence model is employed. A dynamic overset grid is used to treat the relative motion between the rotor and other parts. The numerical results are compared with the model test data and they agree well. Comparisons for the open-water performance between the pumpjet propulsors with two scales are carried out. The results indicate that the total thrust coefficient of the large-scale pumpjet propulsor is greater than that of the small-scale one while the torque coefficient is smaller. Therefore, the efficiency of the large-scale pumpjet propulsor is about 8~10% higher than that of the small-scale pumpjet propulsor. The open-water performance of the rotor, pre-swirl stator and duct is obtained separately to estimate the discrepancies on the thrust and torque coefficients between different scales. To analyze the scale effect from different parts, the research on flow field and pressure distribution are carried out. The variation of total thrust and torque coefficient comes mainly from the rotor, which is caused by the flow field, influenced by the duct and stator

Research on the Performance of Pumpjet Propulsor of Different Scales

This study presents a numerical research on the open-water performance of a pumpjet propulsor at different scales. Simulations were performed by an in-house viscous CFD (Computational Fluid Dynamic) code. The Reynolds-averaged Navier–Stokes (RANS) method with SST k-ω turbulence model is employed. A dynamic overset grid is used to treat the relative motion between the rotor and other parts. The numerical results are compared with the model test data and they agree well. Comparisons for the open-water performance between the pumpjet propulsors with two scales are carried out. The results indicate that the total thrust coefficient of the large-scale pumpjet propulsor is greater than that of the small-scale one while the torque coefficient is smaller. Therefore, the efficiency of the large-scale pumpjet propulsor is about 8~10% higher than that of the small-scale pumpjet propulsor. The open-water performance of the rotor, pre-swirl stator and duct is obtained separately to estimate the discrepancies on the thrust and torque coefficients between different scales. To analyze the scale effect from different parts, the research on flow field and pressure distribution are carried out. The variation of total thrust and torque coefficient comes mainly from the rotor, which is caused by the flow field, influenced by the duct and stator

The Discovery of Natural Typing Annotations: User-produced Potential Chinese Word Delimiters

Human labeled corpus is indispensable for the training of supervised word segmenters. However, it is time-consuming and labor-intensive to label corpus manually. During the process of typing Chinese text by Pingyin, people usually need to type "space " or nu-meric keys to choose the words due to homo-phones, which can be viewed as a cue for segmentation. We argue that such a process can be used to build a labeled corpus in a more natural way. Thus, in this paper, we in-vestigate Natural Typing Annotations (NTAs) that are potential word delimiters produced by users while typing Chinese. A detailed analysis on over three hundred user-produced texts containing NTAs reveals that high-quality NTAs mostly agree with gold seg-mentation and, consequently, can be used for improving the performance of supervised word segmentation model in out-of-domain. Experiments show that a classification model combined with a voting mechanism can reli-ably identify the high-quality NTAs texts that are more readily available labeled corpus. Furthermore, the NTAs might be particularly useful to deal with out-of-vocabulary (OOV) words such as proper names and neo-logisms.

Detection of Nanoscale Soil Organic Matter by Middle Infrared Spectrum for Forensic Science

Soil is useful as a kind of trace evidence for forensic science. Thus it is very crucial to identify sources of soil. The nanoscale soil organic matter (NSOMs) can be used to differentiate soil sources because their constituents and contents are relatively stable with time but variant by location. In this study, NSOMs from eighteen regions of Shandong Province in China were examined by middle infrared spectrum (4000–400 cm−1). The results showed that the constituents and contents of NSOMs in eighteen samples were dramatically different; a NSOM fingerprint for each sample was drawn based on these characteristics. This suggests that a national or global NSOM fingerprint database could be rapidly established by the one-step middle infrared spectrum analysis for different soil samples, which will be helpful to determine crime scenes by comparing the middle infrared spectrum of forensic soil with the NSOMs fingerprint database

circCAPRIN1 interacts with STAT2 to promote tumor progression and lipid synthesis via upregulating ACC1 expression in colorectal cancer

Abstract Background Circular RNAs (circRNAs) generated by back‐splicing of precursor mRNAs (pre‐mRNAs) are often aberrantly expressed in cancer cells. Accumulating evidence has revealed that circRNAs play a critical role in the progression of several cancers, including colorectal cancer (CRC). However, the current understandings of the emerging functions of circRNAs in CRC lipid metabolism and the underlying molecular mechanisms are still limited. Here, we aimed to explore the role of circCAPRIN1 in regulating CRC lipid metabolism and tumorigenesis. Methods circRNA microarray was performed with three pairs of tumor and non‐tumor tissues from CRC patients. The expression of circRNAs were determined by quantitative PCR (qPCR) and in situ hybridization (ISH). The endogenous levels of circRNAs in CRC cells were manipulated by transfection with lentiviruses overexpressing or silencing circRNAs. The regulatory roles of circRNAs in the occurrence of CRC were investigated both in vitro and in vivo using gene expression array, RNA pull‐down/mass spectrometry, RNA immunoprecipitation assay, luciferase reporter assay, chromatin immunoprecipitation analysis, and fluorescence in situ hybridization (FISH). Results Among circRNAs, circCAPRIN1 was most significantly upregulated in CRC tissue specimens. circCAPRIN1 expression was positively correlated with the clinical stage and unfavorable prognosis of CRC patients. Downregulation of circCAPRIN1 suppressed proliferation, migration, and epithelial‐mesenchymal transition of CRC cells, while circCAPRIN1 overexpression had opposite effects. RNA sequencing and gene ontology analysis indicated that circCAPRIN1 upregulated the expressions of genes involved in CRC lipid metabolism. Moreover, circCAPRIN1 promoted lipid synthesis by enhancing Acetyl‐CoA carboxylase 1 (ACC1) expression. Further mechanistic assays demonstrated that circCAPRIN1 directly bound signal transducer and activator of transcription 2 (STAT2) to activate ACC1 transcription, thus regulating lipid metabolism and facilitating CRC tumorigenesis. Conclusions These findings revealed the oncogenic role and mechanism of circCAPRIN1 in CRC. circCAPRIN1 interacted with STAT2 to promote CRC tumor progression and lipid synthesis by enhancing the expression of ACC1. circCAPRIN1 may be considered as a novel potential diagnostic and therapeutic target for CRC patients

Squalene epoxidase promotes the chemoresistance of colorectal cancer via (S)-2,3-epoxysqualene-activated NF-κB

Abstract Background While de novo cholesterol biosynthesis plays a crucial role in chemotherapy resistance of colorectal cancer (CRC), the underlying molecular mechanism remains poorly understood. Methods We conducted cell proliferation assays on CRC cells with or without depletion of squalene epoxidase (SQLE), with or without 5-fluorouracil (5-FU) treatment. Additionally, a xenograft mouse model was utilized to explore the impact of SQLE on the chemosensitivity of CRC to 5-FU. RNA-sequencing analysis and immunoblotting analysis were performed to clarify the mechanism. We further explore the effect of SQLE depletion on the ubiquitin of NF-κB inhibitor alpha (IκBα) and (S)-2,3-epoxysqualene on the binding of IκBα to beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) by using immunoprecipitation assay. In addition, a cohort of 272 CRC patients were selected for our clinical analyses. Results Mechanistically, (S)-2,3-epoxysqualene promotes IκBα degradation and subsequent NF-κB activation by enhancing the interaction between BTRC and IκBα. Activated NF-κB upregulates the expression of baculoviral IAP repeat containing 3 (BIRC3), sustains tumor cell survival after 5-FU treatment and promotes 5-FU resistance of CRC in vivo. Notably, the treatment of terbinafine, an inhibitor of SQLE commonly used as antifungal drug in clinic, enhances the sensitivity of CRC to 5-FU in vivo. Additionally, the expression of SQLE is associated with the prognosis of human CRC patients with 5-FU-based chemotherapy. Conclusions Thus, our finding not only demonstrates a new role of SQLE in chemoresistance of CRC, but also reveals a novel mechanism of (S)-2,3-epoxysqualene-dependent NF-κB activation, implicating the combined potential of terbinafine for 5-FU-based CRC treatment

Table_1_Incidence, predictors and prognostic implications of positive circumferential resection margin in colon cancer: A retrospective study in a Chinese high-volume cancer center.docx

Positive circumferential resection margin (CRM) was associated with a higher recurrence rate and worse survival in rectal cancer. Predictors of CRM in rectal cancer have widely been investigated. Our study aims to determine the incidence, predictors and prognostic implications of positive CRM following colon cancer (CC) surgery in a Chinese high-volume cancer center. The clinicopathological features and oncological outcomes of CC patients undergoing surgery between January 2008 and December 2018 were identified from Fudan University Shanghai Cancer Center database. Positive CRM was defined as resection margin ≤1 mm. A total of 5268 stage I-IV CC patients were identified in our study, 108 (2.05%) of whom had positive CRM. Multivariate logistic analysis found that advanced N stage, distant metastases and poorly differentiated tumor had increased risk of positive CRM. After propensity score matching, the 5-year overall survival rates of the patients with positive and negative CRM were 33.2% and 39.8% (P=0.005), respectively. Multivariable COX regression model showed that positive CRM was an independent prognostic factor for OS in CC patients. The overall rate of positive CRM in our center is lower than that in western population. Several adverse pathological parameters deserve more attention to identify CC patients at a high risk of positive CRM. Adoption of appropriate surgical techniques and multidisciplinary treatment planning are expected to improve oncological outcomes for high selected CC patients with “high-risk” CRM involvement.</p