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Slope reliability analyses considering spatially variable soil properties generally necessitate a discretization of a slope region into disjoint zones called random field elements (RFEs). Few efforts have been devoted to investigating the effect of RFE size on the assessment of reliabilities and risks of slopes possibly due to the huge computational burdens associated with a small RFE size. This study systematically investigates the influence of RFE size on statistics of factor of safety (FS) and sliding mass (SM), distribution of critical slip surfaces, reliability, and risk of slopes. As the size of RFE is small, a stepwise covariance matrix decomposition method (CMDM) is used to effectively simulate the random field of the shear strength parameter. This stepwise CMDM is justified using a simple and straightforward method. Monte Carlo simulation (MCS) is employed to estimate the probability of failure and risk of slopes. Three cohesive slopes are adopted to investigate the effect of RFE size on the statistics of FS and SM, distribution of critical slip surfaces, system reliability, and risk of the slope. It is shown that the RFE size has a relatively larger influence on the distribution of SM than that of FS. A relatively larger size of RFE tends to overestimate the slope failure probability and risk. The critical size of RFE required for an accurate evaluation of the statistics of FS and SM is smaller than that required for the evaluation of failure probability and risk.

Hypoxia, the most common feature in the tumor microenvironment, is closely related to tumor malignant progression and poor patient’s prognosis. Exosomes, initially recognized as cellular “garbage dumpsters”, are now known to be important mediums for mediating cellular communication in tumor microenvironment. However, the mechanisms of hypoxic tumor cell-derived exosomes facilitate colorectal cancer progression still need further exploration. In the present study, we found that exosomes from hypoxic colorectal cancer cells (H-Exos) promoted G1-S cycle transition and proliferation while preventing the apoptosis of colorectal cancer cells by transmitting miR-210-3p to normoxic tumor cells. Mechanistic investigation indicated that miR-210-3p from H-Exos elicited its protumoral effect via suppressing CELF2 expression. A preclinical study further confirmed that H-Exos could promote tumorigenesis in vivo. Clinically, the expression of miR-210-3p in circulating plasma exosomes was markedly upregulated in colorectal cancer patients, which were closely associated with multiple unfavorable clinicopathological features. Taken together, these results suggest that hypoxia may stimulate colorectal cancer cells to secrete miR-210-3p-enriched exosomes in tumor microenvironment, which elicit protumoral effects by inhibiting CELF2 expression. These findings provide new insights on the mechanism of colorectal cancer progression and potential therapeutic targets for colorectal cancer.

Understanding the interaction between complicated geophysical flows and barriers remains a critical challenge for hazards countermeasures in engineering design. In this study, the impact of geophysical flows on a rigid barrier is studied numerically using coupled computational fluid dynamics and discrete element method (CFDDEM). Three types of fluid: Bingham, Herschel-Bulkley, and water are chosen as the fluid phase to mix with particles in the simulation, corresponding to Case B-P, Case HB-P, Case W-P, respectively. The results of twophase simulations are then compared with initial volume controlled dry granular flow (Case P) under the same Froude condition. Two impact mechanisms, namely pileup and runup mechanisms, are recognised in flowbarrier interaction. The effects of fluid properties including viscosity and density on the impact force against the flume base and barrier and inter-particle contacts are also systematically examined. In addition, the dynamic pressure coefficient alpha is also predicted by a newly proposed analytical model, which has been validated by the data from experimental and numerical tests. Findings indicate that the new model may provide a useful reference to calculate the impact force for the design of a rigid barrier in intercepting hazardous geophysical flows.

Background In December 2019, novel coronavirus (SARS-CoV-2) pneumonia (COVID-19) was reported in Wuhan and has since rapidly spread throughout China. We aimed to clarify the characteristics and clinical significance of peripheral lymphocyte subset alteration in COVID-19. Methods The levels of peripheral lymphocyte subsets were measured by flow cytometry in 60 hospitalized COVID-19 patients before and after treatment, and their association with clinical characteristics and treatment efficacy was analyzed. Results Total lymphocytes, CD4+ T cells, CD8+ T cells, B cells, and natural killer (NK) cells decreased in COVID-19 patients, and severe cases had a lower level than mild cases. The subsets showed a significant association with inflammatory status in COVID-19, especially CD8+ T cells and CD4+/CD8+ ratio. After treatment, 37 patients (67%) showed clinical response, with an increase in CD8+ T cells and B cells. No significant change in any subset was detected in nonresponsive cases. In multivariate analysis, posttreatment decrease in CD8+ T cells and B cells and increase in CD4+/CD8+ ratio were indicated as independent predictors of poor efficacy. Conclusions Peripheral lymphocyte subset alteration was associated with clinical characteristics and treatment efficacy of COVID-19. CD8+ T cells tended to be an independent predictor for COVID-19 severity and treatment efficacy., Peripheral lymphocyte subset alteration showed a clear association with the clinical characteristics of COVID-19, especially in relation to disease severity assessment and treatment efficacy prediction, which could help to indicate timely interventions to be provided by physicians.

Background: Since December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCP) occurred in Wuhan, and rapidly spread throughout China We aimed to clar

Additional file 1: Supplyment 1: Supplementary Text 1. Review protocol.

Additional file 2: Supplyment 2: Supplementary Table 1. Quality of cohort studies according to the Newcastle-Ottawa Scale (NOS). Supplementary Table 2. Quality of cross-sectional studies according to the JBI Critical Appraisal Checklist.

Background Circular RNAs (circRNAs) are a class of newly discovered RNAs that attach great importance to modulate gene expression and biological function. Nonetheless, in gastric cancer (GC), the expression and function of circRNA are much less explored. In this study, circ_0000267 expression in GC was investigated and the function and mechanism of circ_0000267 was probed. Materials and Methods Quantitative real‐time PCR (qRT‐PCR) was employed to detect circ_0000267, miR‐503‐5p, and HMGA2 expression. Immunohistochemistry and western blot were adopted to detect HMGA2 and epithelial–mesenchymal transition (EMT)‐related proteins (E‐cadherin and N‐cadherin) expression in GC tissues and cells, respectively. GC cell lines with circ_0000267 overexpressed and knocked down were constructed, and CCK‐8 assay, BrdU assay, scratch healing assay, and transwell assay were employed to assess the effect of circ_0000267 on the proliferation and metastasis of GC cells. Besides, dual‐luciferase reporter gene assay was adopted to verify the targeting relationship between circ_0000267 and miR‐503‐5p. Results Circ_0000267 showed a significant upregulation in GC tissues and cell lines, and its high expression level was extremely linked to the increased tumor diameter and local lymph node metastasis. Circ_0000267 overexpression accelerated GC cell proliferation, metastasis, and EMT processes, while knocking down circ_0000267 led to the opposite effect. From the perspective of mechanism, circ_0000267 promoted the progression of GC through adsorbing miR‐503‐5p and upregulating HMGA2 expression. Conclusion Circ_0000267 is an oncogenic circRNA that affects the progression of GC, which participates in promotion of GC proliferation, migration, invasion, and EMT via modulating the miR‐503‐5p/HMGA2 axis., In this study, we demonstrated that circ_0000267 is an oncogenic circRNA that affects the progression of gastric cancer, which participates in promotion of gastric cancer cells proliferation, migration, invasion, and EMT via modulating the miR‐503‐5p/HMGA2 axis.

Ulcerative colitis (UC) is a chronic inflammatory disease and its involvement area in colon is influenced by a complex network of gene interactions. We analyzed the weighted gene co-expression networks in microarray dataset from colonic mucosa of patients with UC and identified one gene co-expression module that was highly associated with the progression of involved area in UC colon (Pearson coefficient=0.81, P

// Fan Wang 1, 3, * , Pai-Lan Peng 2, 4, * , Xue Lin 5 , Ying Chang 1, 3 , Jing Liu 1, 3 , Rui Zhou 1, 3 , Jia-Yan Nie 1, 3 , Wei-Guo Dong 2 , Qiu Zhao 1, 3 and Jin Li 1, 3 1 Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China 2 Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, China 3 Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, China 4 Department of Gastroenterology, The Central Hospital of Enshi Autonomous Prefecture, Enshi 445000 China 5 Department of Critical Care Medicine, The People’s Hospital of Huangshan, Huangshan 245000 China * These authors have contributed equally to this work Correspondence to: Jin Li, email: 18207118835@163.com Wei-Guo Dong, email: dwg@whu.edu.cn Qiu Zhao, email: zhaoqiuwhu@163.com Keywords: intestinal lamina propria; NKG2D; natural killer cells; ulcerative colitis Received: June 16, 2017 Accepted: August 26, 2017 Published: October 30, 2017 ABSTRACT The role of intestinal lamina propria (LP) NKG2D+ NK cells is unclear in regulating Th1/Th2 balance in ulcerative colitis (UC). In this study, we investigated the frequency of LP NKG2D+ NK cells in DSS-induced colitis model and intestinal mucosal samples of UC patients, as well as the secretion of Th1/Th2/Th17 cytokines in NK cell lines after MICA stimulation. The role of Th1 cytokines in UC was validated by bioinformatics analysis. We found that DSS-induced colitis in mice was characterized by a Th2-mediated process. In acute phrase, the frequency of LP NKG2D+ lymphocytes increased significantly and decreased in remission, while the frequency of LP NKG2D+ NK cells decreased significantly in acute phase and increased in remission. No obvious change was found in the frequency of total LP NK cells. Similarly, severe UC patients had a higher expression of mucosal NKG2D and a lower number of NKG2D+ NK cells than mild to moderate UC. In NK cell lines, the MICA stimulation could induce a predominant secretion of Th1 cytokines (TNF, IFN-γ). Furthermore, in bioinformatics analysis, mucosal Th1 cytokine of TNF, showed a double-edged role in UC when compared to the Th1-mediated disease of Crohn’s colitis. In conclusion, LP NKG2D+ NK cells partially played a regulatory role in UC through secreting Th1 cytokines to regulate the Th2-predominant Th1/Th2 imbalance, despite of the concomitant pro-inflammatory effects of Th1 cytokines.

Hypoxia represents one of the most pervasive microenvironmental stresses in HCC due to the overwhelming growth and inadequate blood supply. HIF1α as an important transcription factor participates in the regulation of various biological behaviors of HCC cells under hypoxia. Our previous study indicated that miR-375 is a hypoxia-associated miRNA. However, the interaction between miR-375 and HIF1α remains unclear. Bioinformatic analysis was performed for miRNA screening. qRT-PCR, western blotting, and immunohistochemical staining were used to detect the expression of related molecules. Bioinformatic analysis and dual luciferase assay were used to predict and further confirm the target association. Transwell chamber assay and flow cytometry were, respectively, used to detect migration, invasion and apoptosis of hepatoma cells. MiR-375 presented an obviously differential expression in human HCCs versus background livers (BLs) and HCCs versus normal liver tissues (NLTs). In rat models, miR-375 was gradually declined during hepatocarcinogenesis. HIF1α was remarkably upregulated at protein level rather than at mRNA level in human HCCs versus BLs, HCCs versus NLTs, BLs versus NLTs, and in rat fibrotic livers versus NLTs. HIF1α was determined to be a target of miR-375. MiR-375 inhibitor induced the migration and invasive capabilities and attenuated apoptosis of hepatoma cells under hypoxia. Depriving HIF1α by siRNA could partially reverse the function of miR-375 inhibitor under hypoxia. MiR-375 impairs the invasive capabilities of HCC cells by targeting HIF1α under hypoxia.

Sandstone usually disintegrates into gap-graded granular materials with a matrix-sustained structure due to weathering factors. This paper presents an investigation on the small strain stiffness of this type of granular materials based on Discrete Element Method (DEM) simulations. Our numerical results indicate the percentage of sliding contact is negligibly small within the small strain range, and the small strain stiffness of fines is well consistent with the widely recognized Hardin’s equation. Both findings confirm the validity of DEM simulations on the study of small strain response of granular materials. The simulation results are further analyzed based on mixture theory. A structure variable is introduced to correlate with the evolution of inter-aggregates structure. This variable is found to increase with the volume fraction of coarse aggregates but is rather independent of the confining stress and the initial void ratio of the fine matrix. Based on the insights drawn from DEM simulations, a homogenization equation is proposed for the small strain stiffness of gap-graded granular soils to reproduce the small strain stiffness of gap-gaped materials observed in our numerical simulations and is further validated by laboratory test data from the literature. The equation can be conveniently incorporated into classical elastoplastic models to model gap-graded granular materials.

Peng-fei Chen,1–3,* Fan Wang,1,2,* Zi-xiong Zhang,4,* Jia-yan Nie,1,2 Lan Liu,1,2 Jue-rong Feng,1,2 Rui Zhou,1,2 Hong-ling Wang,1,2 Jing Liu,1,2 Qiu Zhao1,2 1Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; 2Hubei Clinical Center & Key Lab of Intestinal & Colorectal Diseases, Wuhan 430071, China; 3Department of Gastroenterology, The Central Hospital of Enshi Autonomous Prefecture, Enshi 445000, China; 4Department of Otolaryngology, The Central Hospital of Enshi Autonomous Prefecture, Enshi 445000, China *These authors contributed equally to this work Background: Colon cancer (CC) patients with early relapse usually have a poor prognosis. In this study, we aimed to identify a novel signature to improve the prediction of relapse-free survival (RFS) in CC. Methods: Four microarray datasets were merged into a training set (n=1,045), and one RNA-sequencing dataset was used as a validation set (n=384). In the training set, microarray meta-analysis screened out 596 common RFS-related genes across datasets, which were used to construct 177,310 gene pairs. Then, the LASSO penalized generalized linear model identified 16 RFS-related gene pairs, and a risk score was calculated for each sample according to the model coefficients.Results: The risk score demonstrated a good ability in predicting RFS (area under the curve [AUC] at 5 years: 0.724; concordance index [C-index]: 0.642, 95% CI: 0.615–0.669). High-risk patients showed a poorer prognosis than low-risk patients (HR: 3.519, 95% CI: 2.870–4.314). Subgroup analysis reached consistent results when considering multiple confounders. In the validation set, the risk score had a similar performance (AUC at 5 years: 0.697; C-index: 0.696, 95% CI: 0.627–0.766; HR: 2.926, 95% CI: 1.892–4.527). When compared with a 13-gene signature, a 15-gene signature, and TNM stage, the score showed a better performance (P5 years (n=314), the score demonstrated an excellent performance (C-index: 0.869, 95% CI: 0.816–0.922; HR: 13.55, 95% CI: 7.409–24.78). Conclusion: Our study identified a novel gene-pair signature for prediction of RFS in CC. Keywords: colon cancer, relapse-free survival, gene pair, prognosis

Peng-Fei Chen,1–3,* Fan Wang,1,2,* Jia-Yan Nie,1,2,* Jue-Rong Feng,1,2 Jing Liu,1,2 Rui Zhou,1,2 Hong-Ling Wang,1,2 Qiu Zhao1,2 1Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China; 2Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan, China; 3Department of Gastroenterology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, China *These authors contributed equally to this work Background and aims: Gastric cancer (GC) is one of the most common cancers worldwide, and its pathogenesis is related to a complex network of gene interactions. The aims of our study were to find hub genes associated with the progression and prognosis of GC and illustrate the underlying mechanisms.Methods: Weighted gene co-expression network analysis (WGCNA) was conducted using the microarray dataset and clinical data of GC patients from Gene Expression Omnibus (GEO) database to identify significant gene modules and hub genes associated with TNM stage in GC. Functional enrichment analysis and protein–protein interaction network analysis were performed using the significant module genes. We regarded the common hub genes in the co-expression network and protein–protein interaction (PPI) network as “real” hub genes for further analysis. Hub gene was validated in another independent dataset and The Cancer Genome Atlas (TCGA) dataset.Results: In the significant purple module (R2=0.35), a total of 12 network hub genes were identified, among which six were also hub nodes in the PPI network of the module genes. Functional annotation revealed that the genes in the purple module focused on the biological processes of system development, biological adhesion, extracellular structure organization and metabolic process. In terms of validation, CDH11 had a higher correlation with the TNM stage than other hub genes and was strongly correlated with biological adhesion based on GO functional enrichment analysis. Data obtained from the Gene Expression Profiling Interactive Analysis (GEPIA) showed that CDH11 expression had a strong positive correlation with GC stages (P