Laminin-integrin a6b4 interaction activates notch signaling to facilitate bladder cancer development.

BACKGROUND: Laminins are high-molecular weight (400 ~ 900 kDa) proteins in extracellular matrix, which serve as major component of the basal lamina, and play a crucial role in promoting tumor cell migration. This study aimed at characterizing the role of laminin in promoting cancer development, and elucidating the mechanism of tumor progression driven by laminin-Notch signaling in bladder cancer. METHODS: 2D collagen/laminin culture system was established and CCK-8/transwell assay was conducted to evaluate the proliferation/migration ability of Biu-87 and MB49 cells cultured on 2D gels. Activation of integrins-Notch1 signaling was determined by western blotting. Orthotopic bladder cancer mice model was established to assess the therapeutic effects of Notch inhibitor. RESULTS: Our study demonstrated that extracellular laminin can trigger tumor cell proliferation/migration through integrin α6ß4/Notch1 signaling in bladder cancer. Inhibition of Telomere repeat-binding factor 3 (TRB3)/Jagged Canonical Notch Ligand 1 (JAG1) signaling suppressed Notch signals activation induced by laminin-integrin axis. In MB49 orthotopic bladder cancer mice model, Notch inhibitor SAHM1 efficiently improved tumor suppressive effects of chemotherapy and prolonged survival time of tumor-bearing mice. CONCLUSION: In conclusion, we show that, in bladder cancer, extracellular laminin induced the activation of Notch pathway through integrin α6ß4/TRB3/JAG3, and disclosed a novel role of laminin in bladder cancer cells proliferation or migration.

A prospective cohort study of the relationship between the withdrawal time and the detection rate of colorectal adenoma.

BACKGROUND AND AIMS: The effect of colonoscopy withdrawal time (WT) beyond 6 min on colorectal adenoma detection rate (ADR) is unclear. We focused on the relationship between WT and ADR. MATERIALS AND METHODS: This study was a prospective observational study involving 437 patients who underwent colonoscopy at Tongren Hospital in Shanghai from 1 July 2020 to 31 August 2020. Patients were divided into two groups according to whether the WT was >6 min. Age, sex, body mass index (BMI), defoaming rate score, Boston bowel preparation scale (BBPS), primary colonoscopy, hypertension, diabetes mellitus, dietary preparation 1 day before the examination, and abdominal surgery history factors were analysed by univariate and multivariable logistic regression to explore the odds ratios (ORs) of ADR in two WT groups. Restricted cubic spline regression was used to further analyze the relationship between WT and the ORs of adenoma detection. RESULTS: The ADR among 437 patients was 17.16% (75/437). Multivariable regression analysis showed that in the group with WT >6 min, patients aged ≥50 years old and male could have an increased risk of adenoma detection (OR 5.80, 95% CI 2.32-14.47; p < .001; OR 2.30, 95% CI 1.19-4.43; p = .013). The cubic spline curve showed that the ADR increased with time for WT of 6-8 min, and the highest ADR was achieved when the WT was controlled at 8 min (WT = 5.997, OR = 0.997; WT = 8.240 min, OR = 3.092). CONCLUSION: The highest ADR was achieved when the WT of colonoscopy was controlled at 8 min.

Ajuba transactivates N-cadherin expression in colorectal cancer cells through interaction with Twist.

Ajuba is a multiple LIM domain-containing protein and functions as a transcriptional coregulator to modulate many gene expressions in various cellular processes. Here, we describe that the LIM domain of Ajuba interacts with Twist, and the Twist box is a pivotal motif for the interaction. Biologically, Ajuba enhances transcription of target gene N-cadherin as an obligate coactivator of Twist. The enhancement is achieved by binding to the E-box element within N-cadherin promoter as revealed by luciferase reporter and chromatin immunoprecipitation assays. Mechanistic investigation demonstrates that Ajuba recruits CBP and Twist to form a ternary complex at the Twist target promoter region and concomitantly enhances histone acetylation at these sites. These findings identify that Twist is a new interacting protein of Ajuba and Ajuba/Twist/CBP ternary complex may be a potential treatment strategy for Twist-related tumour metastasis.

Association of pro-inflammatory diet with increased risk of gallstone disease: a cross-sectional study of NHANES January 2017-March 2020.

Background and aim: Gallstone disease (GSD) is a major public health problem worldwide. The dietary inflammatory index (DII) and the energy-adjusted DII (E-DII) have been used to describe dietary inflammatory potential. The current study sought to investigate the pro-inflammatory role of diet on GSD among outpatients in the United States. Methods: Cross-sectional data from 7,334 individuals older than 20 years who participated in the National Health and Nutrition Examination Survey (NHANES) from January 2017 to March 2020 were obtained. The relationship between GSD and DII was assessed using self-reported data. An association between DII and the risk of GSD was determined using sample-weighted logistic regression and restricted cubic splines (RCS). Subgroup analyzes were conducted to assess the interaction between DII and related factors. Sensitivity analysis was further used to confirm the stability of the relationship. To control for the effect of total energy intake, E-DII was calculated and analyzed. Results: A total of 10.5% of the study participants had GSD. The DII ranged from -5.52 to 5.51, and the median DII was significantly higher for participants with GSD than those without (1.68 vs. 1.23, p < 0.001). There was a significant and stable positive relationship between DII and GSD in adjusted models (OR 1.10, 95% CI 1.00-1.20). In the fully adjusted model, subjects with DII scores in the highest tertile were more likely to have GSD than those in the lowest tertile (OR 1.52, 95% CI 1.19-1.93). An apparent dose-response association between DII and GSD was detected. The association between E-DII and GSD remained stable. Conclusion: Higher DII/E-DII scores linked to the intake of a pro-inflammatory diet were positively associated with a higher risk of GSD. These findings suggest that pro-inflammatory dietary patterns can promote the formation of gallstones.

Experimental Study on the Dynamic Tensile Characteristics of Coal Samples.

As coal mines continue deep mining, the frequency of coal and rock dynamic disasters has also gradually increased. In this paper, dynamic tensile strength deformation, energy evolution, and crack development under an impact test were studied on Brazilian coal samples, using a split Hopkinson pressure bar (SHPB) test device. A high-speed camera was adopted to capture the failure process of the coal specimens. The research results demonstrate that when the impact velocity is greater than 4.75 m/s, the dynamic tensile strength of the vertical bedding direction is higher than that of the parallel bedding direction of the coal samples. With the increase in the impact velocity, the dynamic strain and ultimate strain rate of two types of coal samples are increased, and the average value of the first and second dynamic deformation moduli of coal samples shows decreasing characteristics. As the incident energy increases, the sum of reflected and transmitted energy increases, and the absorbed energy also increases in the two types of coal samples. The two types of Brazilian disc coal samples mainly showed tensile and shear failure characteristics. The dynamic tensile deformation characteristics of the two types of coal specimens are less affected by the impact angles. However, the crack propagation of coal samples was mainly influenced by the impact angles. The test results can be used for the prediction of coal and rock outburst in deep underground coal excavation.

Experimental Study on the Determinant Factors and Energy Criterion of Coal and Gas Outbursts.

A series of coal and gas outburst tests were conducted on coal seams in north China to determine the important order of gas pressure, in situ stress, and coal strength during coal and gas outbursts. And the typical phenomena of coal and gas outbursts were investigated. In addition, improved outburst energy equations were built to study the coal energy evolution process during coal and gas outbursts. The results show that the coal strength has the strongest influence on coal and gas outbursts, followed by the gas pressure and the in situ stress. The weights of pulverized coal with a particle size of less than 0.28 mm are consistent with the changing trend of the total weights of the pulverized coal particles in the corresponding outburst interval. Furthermore, the results suggest that the gas pressure monitored by the sensors close to the outburst hole begins to drop first and lasts for the longest time. The outburst coal presents obvious fracture and pulverization damage characteristics, and the pulverization damage features of the coal near the outburst hole are more obvious. In addition, the improved outburst energy equation was established, and the rationality of the improved outburst energy equation was verified by using the outburst orthogonal simulation experimental data and the on-site outburst accident cases. The results of this experiment have important guiding significance for preventing and controlling the occurrence of coal and gas outbursts and ensuring safe and efficient mining of coal mines.

Swimming Impedes Intestinal Microbiota and Lipid Metabolites of Tumorigenesis in Colitis-Associated Cancer.

Background: Accumulating data support that regular physical activity potentially inhibits chronic colitis, a risk factor for colitis-associated cancer (CAC). However, possible effects of physical activity on CAC and the underlying mechanisms remain poorly understood. Methods: A pretreatment of swimming on azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CAC mice was implemented to determine its protective effect. Inflammation and tumorigenesis were assessed using colorectums from C57BL/6 mice. In order to determine how swimming alters colonic lipid metabolism and gene expression, a comparative analysis was conducted. Meanwhile, alterations in intestinal microbiota and short-chain fatty acids (SCFAs) were detected and analyzed. Finally, an integration analysis of colonic lipid metabolism with gene expression and intestinal microbiota was performed respectively. Result: Swimming pretreatment relieved bowel inflammation and minimized tumor formation. We demonstrated that prostaglandin E2 (PGE2)/PGE2 receptor 2 subtype (EP2) signaling as a potential regulatory target for swimming induces colonic lipid metabolites. Swimming-induced genera, Erysipelatoclostridium, Parabacteroides, Bacteroides, and Rikenellaceae_RC9_gut_group, induced intestinal SCFAs and affected the function of colonic lipid metabolites enriched in glycerophospholipid metabolism and choline metabolism in cancer. Conclusion: According to our experiments, swimming pretreatment can protect mice from CAC by intervention in the possible link between colonic lipid metabolites and PGE2/EP2 signaling. Further, swimming-induced genera and probiotics promoted glycerophospholipid metabolism and choline metabolism in cancer, the major constituents of colonic lipid metabolites, and increased SCFAs, which were also important mechanisms for the anti-inflammatory and anti-tumorigenic effects of swimming.

Analysis of transcript-wide profile regulated by microsatellite instability of colorectal cancer.

Background: Microsatellite instability-high (MSI-H) is a form of genomic instability present in 15% of colorectal cancer (CRC) cases. Several differential gene analyses have been conducted on CRC; however, none have specifically explored the differentially expressed genes in MSI-H CRC. Research on the different gene expressions between MSI-H CRC and microsatellite stable (MSS) CRC, and their different patterns of metastasis will provide invaluable insights for diagnosis, prognosis, and treatment. Methods: In this study, the differential expression of 46,602 genes were analyzed across 613 different tissue samples from The Cancer Genome Atlas (TCGA)-colon adenocarcinoma (COAD) and TCGA-rectum adenocarcinoma (READ) as part of a gene association analysis. R package TCGAbiolinks (version 2.18.0) was used to download the data set, and DESeq2 (version 1.30.1) was used for the differential gene analysis. The resulting genes were then analyzed for shared pathways with R package clusterProfiler (version 3.0.4). Results: A total of 237 significantly differentially expressed genes (Padj<0.05) were found between MSI-H and MSS CRC. Differentially expressed genes include insulin like growth factor 2 (IGF2) and fibroblast growth factor 3 (FGF3), and the enriched pathways mostly involve hearing, digestive regulation, and neurogenesis.463 differentially expressed genes were found between metastatic and non-metastatic CRC. Notably differentially expressed genes in metastatic CRC include DEAD-box helicase 53 (DDX53) and adiponectin, C1Q and collagen domain containing (ADIPOQ), and enriched pathways include the immune system, cell adhesion, and cell signaling. For MSI-H CRC, a total of 34 genes were significantly differently expressed between metastatic and non-metastatic CRC. These include notum, palmitoleoyl-protein carboxylesterase (NOTUM), serpin family B member 2 (SERPINB2), and several keratin (KRT) genes, and the pathway analysis showed the major enrichment of the hormonal and secretion and regulation pathways. Of the differentially expressed genes in metastatic CRC, 25 were immunity related and include fatty acid binding protein 4 (FABP4), and the pathway analysis showed the enrichment of humoral immunity and lymphocyte regulation. Conclusions: Of the biologically plausible differentially expressed genes, the most notable were NOTUM, KRT6A, KRT14, SERPINB2, and serum amyloid A1 (SAA1). NOTUM, KRT6A, and KRT14 are active in the Wnt pathway. All five are also involved in various inflammation pathways.

DLC1 inhibits colon adenocarcinoma cell migration by promoting secretion of the neurotrophic factor MANF.

DLC1 (deleted in liver cancer-1) is downregulated or deleted in colorectal cancer (CRC) tissues and functions as a potent tumor suppressor, but the underlying molecular mechanism remains elusive. We found that the conditioned medium (CM) collected from DLC1-overexpressed SW1116 cells inhibited the migration of colon adenocarcinoma cells HCT116 and SW1116, but had no effect on proliferation, which suggested DLC1-mediated secretory components containing a specific inhibitor for colon adenocarcinoma cell migration. Analysis by mass spectrometry identified mesencephalic astrocyte-derived neurotrophic factor (MANF) as a candidate. More importantly, exogenous MANF significantly inhibited the migration of colon adenocarcinoma cells HCT116 and SW1116, but did not affect proliferation. Mechanistically, DLC1 reduced the retention of MANF in ER by competing the interaction between MANF and GRP78. Taken together, these data provided new insights into the suppressive effects of DLC1 on CRC, and revealed the potential of MANF in the treatment of CRC.

A python code for automatic construction of Fischer plots using proxy data.

Fischer plots are widely used in paleoenvironmental research as graphic representations of sea- and lake-level changes through mapping linearly corrected variation of accumulative cycle thickness over cycle number or stratum depth. Some kinds of paleoenvironmental proxy data (especially subsurface data, such as natural gamma-ray logging data), which preserve continuous cyclic signals and have been largely collected, are potential materials for constructing Fischer Plots. However, it is laborious to count the cycles preserved in these proxy data manually and map Fischer plots with these cycles. In this paper, we introduce an original open-source Python code "PyFISCHERPLOT" for constructing Fischer Plots in batches utilizing paleoenvironmental proxy data series. The principle of constructing Fischer plots based on proxy data, the data processing and usage of the PyFISCHERPLOT code and the application cases of the code are presented. The code is compared with existing methods for constructing Fischer plots.

Circular RNA circ_0002138 is down-regulated and suppresses cell proliferation in colorectal cancer.

Circular RNAs (circRNAs) have been recently identified as widespread and diverse endogenous noncoding RNAs that may harbor vital functions in humans. However, the role of circRNAs in the process of tumorigenesis and development of colorectal cancer (CRC) remains hitherto vague. In this study, we investigated the expression level of circ_0002138 in 35 paired CRC tissues by quantitative real-time polymerase chain reaction (qRT-PCR) and found that circ_0002138 was stably down-regulated in CRC tissues compared to paired adjacent normal tissues (P < 0.001). Fisher's exact test was further conducted to analyze the relationship between circ_0002138 expression level and clinico pathological factors of CRC patients. Circ_0002138 expression was significantly correlated with age. To evaluate the diagnostic value of circ_0002138, a receiver operating characteristic (ROC) curve was used and the area under the ROC curve was 0.7249. Additionally, functional analysis demonstrated that circ_0002138 significantly inhibited CRC cell proliferation in vitro. Overall, our data suggest that circ_0002138 may become a novel potential biomarker for diagnosis and treatment target of CRC.

The analysis and application of granular backfill material to reduce surface subsidence in China's northwest coal mining area.

In China's northwest coal mining area, the excavation of shallow buried thick coal seams has caused serious damage to the phreatic water layer and induced deterioration of the ecological environment. Backfilling is a basic method of controlling the loss of groundwater and reducing surface subsidence. In order to reduce the porosity of the backfill material and control the compression ratio of the backfill body, the grain gradation of the local aeolian sand was studied based on the geological conditions of the shallow buried coal seam in the Yulin mining area, Shaanxi province. Subsequently, aeolian sand was selected as the backfilling aggregate, and tests were implemented. The optimum proportion and slurry concentration of the backfill material were then obtained. The engineering application shows that the strength and stability of the backfill body based on the close packing theory can satisfy the requirements of supporting the overlying strata, and the integrity of overburden strata is competent. The maximum accumulated surface subsidence was measured to be 38mm, indicating that the aeolian sand-based backfill material in shallow and thick underground coal seam mining is able to protect the eco-environment and control the geo-environmental hazards, which are critical for the sustainable development of the mining industry and economic growth.

Smad1 promotes colorectal cancer cell migration through Ajuba transactivation.

SMAD family member 1 (Smad1) have been involved in metastatic progression of many cancer types. However, the detailed molecular signalling pathway underlying the regulatory link between Smad1 and metastasis remains elusive. Here, we demonstrate that Smad1 promotes migration of colorectal cancer (CRC) cells by inducing Snail and Ajuba expression simultaneously, but no apparent effect on Twist1 expression. Remarkably, E-cadherin, the best known Snail/Ajuba target gene is downregulated by Smad1 expression. Further, depletion of Ajuba in HCT116 cells significantly dampens the cell migration capability induced by Smad1 overexpression, suggesting that Ajuba is required for Smad1 to induce cell migration. Moreover, clinical analysis shows a significant positive correlation between the level of Smad1 and Ajuba in CRC samples. Together, our data provides the first evidence of the regulatory network of Smad1/Snail/Ajuba axis in CRC migration, suggesting that Smad1 and Ajuba are potential new therapeutic targets and prognostic factors for CRC.

Role of B7-H4 siRNA in Proliferation, Migration, and Invasion of LOVO Colorectal Carcinoma Cell Line.

OBJECTIVES: Colorectal cancer is one of the most common malignancies. Recent studies investigated that B7-H4 is highly expressed in various cancers. We aimed at exploring the effect of B7-H4 siRNA on proliferation, invasion, and migration of LOVO cells which expressed B7-H4 notably. DESIGN AND METHODS: Colon adenocarcinoma dataset was downloaded from The Cancer Genome Atlas. 35 colorectal cancer patients admitted to Shanghai Tongren Hospital were enrolled in this study. Cell proliferation and cell cycle distribution were identified by CCK8 and flow cytometry, respectively. Transwell assay was performed to detect the invasion and migration of LOVO cells. CXCL12/CXCR4 expression and JAK2/STAT3 phosphorylation were determined by real-time PCR and western blot. RESULTS: B7-H4 expressed is elevated in colorectal cancer tissues than in the adjacent normal tissues. B7-H4 siRNA effectively inhibited the proliferation at 24 h and 48 h, arrested cell cycle at G0/G1, and suppressed cell invasion and migration. Gene set enrichment analysis showed that CXCL12/CXCR4 and JAK/STAT were correlative with the B7-H4 expression. Additionally, CXCL12/CXCR4 expression and JAK2/STAT3 phosphorylation were reduced. CONCLUSIONS: B7-H4 siRNA can effectively inhibit proliferation, invasion, and migration of LOVO cells by targeting CXCL12/CXCR4 and JAK2/STAT3 signaling, which can serve as a new target for colorectal carcinoma treatment.

A survival predictive model in patients undergoing radical resection of ampullary adenocarcinoma.

BACKGROUND/AIMS: Radical resection with either pancreaticoduodenectomy or pylorus-preserving pancreaticoduodenectomy is considered to be the standard treatment for most ampullary carcinomas, but the prognostic predictive model has not yet been developed. METHODOLOGY: The pretreatment, treatment, and follow-up variables of data of 47 patients undergoing radical resection for the ampullary carcinoma were analyzed to determine the favorable prognostic variables. Employing the Kaplan-Meier method, the cumulative survival rates of the ampullary carcinoma were calculated. By Cox regression model, a stepwise multivariate analysis was performed to analyze the contributing factors of the survival rate, and a predictive survival equation was obtained. RESULTS: With the results of the univariate analysis, the variables significantly associated with favorable prognosis were younger age (<63 years), TNM stage (stage I or II or III), and the degree of tumor differentiation (well or moderately differentiated). When the above three variables were examined as covariates by Cox regression in multivariate analysis, the TNM stage and the degree of tumor differentiation were independently correlated with the survival. A predictive survival equation obtained with the beta-coefficients of the above three variables was as follows: S (t) = [So (t)] P, P = exp (0.0234 x age - 1.8744 x tumor differentiation + 1.1576 x TNM stage) CONCLUSIONS: This predictive survival equation can predict the survival and the favorable outcome of patients treated with radical resection of ampullary carcinoma.

Cryosurgery for pancreatic cancer.

The procedure of pancreatic cryosurgery is performed with intraoperative or percutaneous approaches. Based on current data and our initial experience, cryoablation appears to be a feasible, potentially safe and promising option in patients with locally advanced and unresectable pancreatic cancer. It is suggested that there are almost no known contraindications to the use of cryosurgery for pancreatic cancer. For most patients with pancreatic cancer, cryosurgery can substitute conventional surgery.

Two case reports of pilot percutaneous cryosurgery in familial multiple endocrine neoplasia type 1.

We report 2 cases of familial multiple endocrine neoplasia type 1 syndrome (MEN 1) in related Malaysian Chinese individuals: the son had simultaneous primary lesions in the pancreatic tail, parathyroid, adrenal gland, and hypophysis, with metastatic tumors in the left lung, mediastinum and spine; his mother had simultaneous primary lesions in the pancreatic head, parathyroid, and hypophysis, with metastatic tumors in the liver, spine, ilium, chest wall, and rib. Genetic testing of the 2 patients showed the same mutation in exon 9 of MEN1 (c.1288G>T, Glu430, encoding a stop codon). The tumors with the poorest prognosis and clinical sequelae were in the pancreas of both patients, and these were treated by percutaneous cryoablation. The number of hypoglycemic episodes in the son improved for more than 120 days, and the abdominal space occupying lesion resolved in his mother.

[Cryosurgery combined with Iodine-125 seed implantation in the treatment of unresectable lung cancer.].

BACKGROUND: As many lung cancer patients lose surgical possibility, it is important to explore new treatments to improve prognosis. The study is to observe adverse reactions and therapeutic effects of cryosurgery combined iodine-125 seeds implantation in treating advanced lung cancer patients. METHODS: One hundred forty unresectable pulmonary cancer patients received percutaneous cryosurgery and iodine-125 implantation under CT guidance. Patients were followed-up 1 year, with CT scan, therapeutic effect, complications and survival time monitoriy. RESULTS: The one hundred forty patients successfully received cryosurgery combined with iodine-125 seed implantation and one-year follow-up. The patients with 6 m posttreatment had complete remission (CR) of 93.4%, partial remission (PR) of 70.1%, stable disease (SD) of 7.4%, and progressive disease (PD) of 5.7%. The half-year and one-year survival rates were 94.3% and 65.7% respectively. The average KPS was improved from 66.9 to 76.3. CONCLUSIONS: Cryosurgery combined with iodine-125 seed implantation is effective in treating unresectable lung cancer, providing a promising treatment protocol for unresectable lung cancer patients.