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The catenin beta 1 gene (CTNNB1) plays a crucial role in the malignant progression of various cancers. Emerging studies have suggested that its hyperactivation is closely related to the occurrence and development of bladder cancer(BCa). Here, we report that UCHL3(Ubiquitin C-terminal hydrolase L3), a deubiquitinating enzyme promotes the development of bladder cancer through Wnt signaling pathway by interacting with and stabilizing CTNNB1 in vitro and in vivo. GSEA analysis showed that UCHL3 was highly associated with Wnt signaling pathway, and it was validated by luciferase reporter assays and RT-PCR, which found that its functions depend on its deubiquitinating activity. We also found that the overexpression of UCHL3 boosted the bladder cancer cells proliferation, invasion and migration, while the depletion of UCHL3 in bladder cancer cells delayed the tumor tumorigenesis in vitro and in vivo. Especially, Uchl3-deficient mice were less susceptible to bladder tumorigenesis. Additionally, UCHL3 was highly expressed in bladder cancer and associated with advanced clinicopathological parameters. These findings provided direct insight into the molecular mechanism of the functions of UCHL3 in bladder cancer, and provided new target for therapeutic approach against bladder cancer.

MAPK/JNK signaling is pivotal in carcinogenesis. However, ubiquitin-mediated homeostasis of JNK remains to be verified. Here, with results from RNA sequencing (RNA-seq) and luciferase reporter pathway identification, we show that USP14 orchestrates MAPK/JNK signaling and identify USP14 as a deubiquitinase that interacts and stabilizes JNK. USP14 is elevated in colorectal cancer patients and is positively associated with JNK protein and downstream gene expression. USP14 ablation clearly inhibits colorectal tumorigenesis by targeting the MAPK/JNK signaling cascade in vitro and in vivo. Moreover, USP14 expression is induced by TNF-α, forming a feedback loop with JNK and leading to tumor amplification. Our study suggests that elevated expression of USP14 promotes MAPK/JNK signaling by stabilizing JNK, which in turn augments colorectal carcinogenesis, indicating a potential therapeutic target for colorectal cancer patients with increased USP14 expression.

Circular RNAs (circRNAs) belong to a novel class of noncoding RNA that gained more attention in human cancer pathogenesis. The role of circRNA in esophageal squamous cell carcinoma (ESCC) is largely unclear. Present investigation was to characterize new circRNAs regulating ESCC progression and explore the regulatory mechanisms in ESCC. In this study, circRNAs differentially expressed in ESCC and adjacent normal tissues were characterized via high-throughput sequencing. Then the differentially expressed circRNA between ESCC and adjacent normal tissues were investigated using Rt-qPCR. The role of circ-ARAP2 expression on tumor progression were detected in both in vivo and in vitro. Luciferase reporter assays were used to identify the relationships among circ-ARAP2, microRNA (miR)-761 and the cell cycle regulator Forkhead Box M1 (FOXM1). The result of the expression profile analyses regarding human circRNAs in ESCC demonstrated that circ-ARAP2 was up-regulated significantly in both ESCC tissues and cell lines. Downregulation circ-ARAP2 suppressed ESCC proliferation, tumor growth and metastasis inboth in vivo and in vitro. The data also suggested that miR-761 and FOXM1 were circ-ARAP2 downstream targets which were confirmed through luciferase reporter analysis. Overexpression of FOXM1 or inhibiting miR-761 restored ESCC cell proliferation and invasion ability after silencing circ-ARAP2. The study also found that circ-ARAP2 influenced the endothelial-mesenchymal transition (EMT) and cancer stem cells differently by regulating miR-761/FOXM1. In one word, the results demonstrated that abnormal circ-ARAP2 expression promoted ESCC progression by regulating miR-761/FOXM1 axis-mediated stemness and EMT.

The scientific evaluation and identification of the relationship between urban comprehensive carrying capacity (UCC) and urbanization in Northeast China under serious urban shrinkage is an important basis for realizing the all-around revitalization of the region. Using a panel data set of 34 prefecture-level cities with six nonshrinking cities and 28 shrinking cities in Northeast China from 2003 to 2019, this study constructs an ordinary panel data model and a static and dynamic spatial econometric model, the spatial Durbin model (SDM), to identify the relationship between the UCC and urbanization and to empirically investigate the impacts of the key control variables on UCC improvement. The results show a significant U-shaped curve relationship between the UCC and urbanization for the shrinking cities and a significant inverted U-shaped curve relationship for the nonshrinking cities, and the spillover effect of the urbanization is not significant. Moreover, social urbanization has a significant negative spatial effect on the local and neighborhood UCC of the nonshrinking cities, while demographic and spatial urbanization have significant positive spatial effects on the local and neighborhood UCC of the shrinking cities. In addition, fixed asset investment significantly promotes the UCC of the nonshrinking and shrinking cities and has significant positive spillover effects on the neighboring regions. R&D investment has a significant positive spatial effect on only the local and neighborhood UCC of the shrinking cities, while it has a significant positive effect on only the local UCC of the nonshrinking cities. New-type urbanization, industrial structure adjustment, new infrastructure construction and technological innovation are effective measures for improving and enhancing the comprehensive carrying capacity of cities in Northeast China.

Background: In recent years, it is proved that the immune system contributes a lot to the pathogenesis and progression of endometriosis (EM). Identifying the signature of immune cell infiltration, the immune related diagnostic biomarkers, and even the potential therapeutic targets in endometriosis patients will aid the early diagnosis and treatment of EM. Methods: Firstly, the microarray expression dataset was downloaded from the gene expression omnibus (GEO) database. Subsequently, the signature of immune cell infiltration of endometrium tissues was calculated through the xCell algorithm. The hub module most relevant to immune cells was selected through the weighted gene co-expression network (WGCNA). The differentially expressed genes (DEGs) were identified by the limma package of R. The immune-related hub genes were further selected. Finally, the validation and clinical characteristics of hub genes were performed.Results: In our study, it was showed that macrophages and neutrophils were the main infiltrating immune cells in the endometrium tissue and 4 hub genes related to immune infiltration in ectopic lesions of EM were identified through multi-bioinformatic analysis. The expression of those hub genes (TNFSF13B, IL7R, CSF1R, LEP) in other validated datasets was consistent with our results. Each hub gene had significantly correlation with most of immune cells, and the area under the ROC curves (AUC) of those hub genes for disease diagnosis were all higher than 0.8. We also find that those hub genes were connectively concerned with the common complication infertility of EM.Conclusions: It is proved that the dysfunction of the immune system is connectively associated with the ectopic lesions of EM. And the immune related biomarkers (TNFSF13B, IL7R, CSF1R, LEP) may be helpful in the development of the pathogenesis, diagnosis and even the potential therapeutic targets of EM.

1.1 Background Slug as a member of the epithelial-mesenchymal transition(EMT) leads to the decrease of adhesion between cancer cells and the increase of cell migration. Many studies have been reported the relationship between prognosis and slug expression in patients with breast cancer, yet the results are controversial. Therefore, it is necessary to conclude the relationship between slug and breast cancer by a meta-analysis. 1.2 Methods We looked for studies on breast cancer and slug via PubMed, Scopus and Web of Science .A total of 1458 patients from the final eight studies were included in this meta-analysis. Overall survival (OS) and Disease-free survival (DFS) were the primary endpoints. Pooled hazard ratio (HR), pooled odds ratio (OR), and 95% confidence interval (CI) were calculated to assess the association between slug, prognosis, and clinicopathological parameters (age, tumor size, histological grade, axillary lymph nodes status(LN),TNM stage, ER(estrogen receptor) status, PR(progesterone receptor) status, HER-2(human epidermal growth factor receptor 2)status). Data analysis was carried out by using STATA version 14.0. (Stata Corporation, TX, USA)software. 1.3 Results This meta-analysis included 1458 patients from eight studies. The final results show that high slug expression leads to poor OS（pooled HR = 2.21;95%CI=1.47-3.33;p＜0.001) and DFS （pooled HR = 2.03;95%CI=1.26-3.28; P=0.004) in breast cancer. In terms of clinicopathological parameters, the results show that breast cancer patients with high slug expression have higher TNM stage(I-II/III-IV; pooled OR=0.42;95%CI=0.25-0.70;P=0.001), more prone to axillary lymph node metastasis(N+/N0;pooled OR =2.16; 95%CI =1.31-3.56; P=0.003) and more severe ER deficiency (positive /negative; pooled OR=0.67;95%CI=0.45-0.99; P=0.042).However, slug is not related to age, histological grade, tumor size, PR status and Her-2 status. 1.4 Conclusion This meta-analysis results show that high slug expression in breast cancer is associated with poor OS, DFS and axillary lymph node status, TNM stage and ER status, but not related to age, histological grade, tumor size, PR status and Her-2 status.

Landslide deformation is the most intuitive and effective characterization of the evolution of landslides and reveals their inherent risk. Considering the inadequacy of existing deformation monitoring data in the early warning of landslide hazards, resulting in insufficient disaster response times, this paper proposes a time-domain correlation model. Based on a regional rainfall-landslide deformation response analysis method, a time-domain correlation measure between regional rainfall and landslide deformation and a calculation method based on impulse response functions are proposed for prevalent rainfall-induced landslide areas, and the correlation with the rainfall-triggered landslide deformation mechanism is quantitatively modeled. Furthermore, using rainfall monitoring data to optimize the indicator system for landslide deformation monitoring and early warning significantly improves the preliminary warning based on landslide deformation. The feasibility of the method proposed in this paper is verified by analyzing the historical monitoring data of rainfall and landslide deformation at 15 typical locations in 5 landslide hidden hazard areas in Fengjie County, Chongqing city. (1) The correlation models for the XP landslide and XSP landslide involve a 5-day lagged correlation under a 56-day cycle and a 18-21-day lagged correlation under a 49-52-day cycle, which means that the deformation in the above areas can be modeled cyclically according to monitoring data, and early landslide warnings can be provided in advance with a lag time. (2) The correlation models for the TMS landslide and OT landslide show consistent correlations under a 48-50-day cycle and a 58-day cycle, which means that the deformation in the above areas can be predicted based on rainfall accumulation, and real-time warnings of future landslide deformation and displacement can be obtained. (3) The HJWC landslide presents a disorderly correlation pattern, which means that a preliminary landslide deformation warning cannot be provided based on rainfall alone; other monitoring data need to be supplemented and analyzed.

Background The ketogenic diet has been widely used in the treatment of various nervous system and metabolic-related diseases. Our previous research found that a ketogenic diet exerts a protective effect and promotes functional recovery after spinal cord injury. However, the mechanism of treatment is still unclear. In this study, different dietary feeding methods were used to detect myelin expression and gene level changes between different groups.Result We established 15 RNA-Seq cDNA libraries and divided them into 4 groups (SCI_KD, SCI_SD, Sham_KD and Sham_SD), and a total of 32,883 genes were detected by RNA-seq. First, KEGG pathway enrichment of upregulated differentially expressed genes (DEGs) in the SCI_KD and SCI_SD groups and GSEA analysis of the two groups found that a ketogenic diet significantly improved the steroid anabolic pathway in rats with spinal cord injury. Through cluster analysis, PPI analysis and visualization of iPath metabolic pathways, Sqle, Sc5d, Cyp51, Dhcr24, Msmo1, Hsd17b7, and Fdft1 changed significantly in the pathway. Second, through WGCNA analysis, all samples are placed in a gene network to analyse the correlation between gene modules and phenotypes. After module analysis, GO function and KEGG analysis showed that rats fed a ketogenic diet showed significantly reduced immune-related pathways, including those associated with immune and infectious diseases.Conclusion A ketogenic diet may improve the immune microenvironment and myelin growth in rats with spinal cord injury through reprogramming of steroid metabolism.

Background Metformin, which is cheap and easy to get, is a first-line anti-hyperglycemia drug. Recently, its anti-tumor effect has been revealed. Here we performed a meta-analysis to summarize previous studies and a narrative review to gather the mechanisms involved in the potential relationship. Methods We searched related articles in database of Pubmed, EMbase, Web of science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), the Wanfang and Sinomed and obtained 8 clinic trials that investigated the connection between metformin and breast cancer metastasis, containing 2 randomized controlled trials (RCTs) and 6 retrospective cohort studies. We evaluated each retrospective cohort study by Newcastle-Ottawa Scale (NOS), while RCT by Chcorane Risk of Bias tool. Pooled hazard ratios (HRs), risk ratios (RRs) and we calculated associated 95% confidence intervals (CIs) with a random-effect, generic inverse variance method. We also collected the possible mechanisms of cancer metastasis inhibition from metformin. Results A total of 8 studies containing 13919 breast cancer patients without distant metastasis before they got anticancer treatment. The result showed that adjuvant metformin in treatment of local breast cancer facilitated to suppress metastasis (HR = 0.69, 95% CI = 0.57–0.82, p I2 = 0%), and the result was consistent with the subgroup of breast cancer patients with type 2 diabetes mellitus (T2DM) (HR = 0.68, 95% CI = 0.57–0.82, p I2 = 0%). Conclusion The meta-analysis suggested metformin might repress the metastasis and be benefit to distant metastasis-free survival (DMFS) when added to systemic breast cancer therapy, supporting anti-tumor effects of metformin on breast cancer.