Hedgehog signaling-related genomics signature for the accurate progress and prognosis prediction in gastric cancer.

The Hedgehog pathway is thought to be closely associated with the progression of GC; however, a specific link between the Hedgehog pathway on the prognosis and immune infiltration of gastric cancer is still lacking. This study collected Hedgehog pathway-related genes. The Hedgehog pathway-related pattern were identified by consensus cluster analysis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were used to identify the biological functions which were significantly altered between predefined Cluster1 and Cluster2 in consensus clustering. The risk model of gastric cancer based on Hedgehog signaling pathway was constructed by univariate and multivariate COX regression, and the nomogram was constructed. The results showed that there were significant differences in the expression of Hedgehog pathway-related genes between the two groups. In addition, the constructed risk model was significantly correlated with the clinical prognosis and immune cell infiltration level of patients with gastric cancer. The model effectively predicted the efficacy of chemotherapy in GC patients and the sensitivity of drug treatment between groups. We systematically revealed the mechanism of Hedgehog pathway in gastric cancer and selected biomarkers with biological significance from a new perspective, providing potential direction for the treatment of gastric cancer.

Projections of land use change and habitat quality assessment by coupling climate change and development patterns.

Exploring future land use changes and assessing the habitat quality remains a challenging topic for watershed ecological sustainability. However, most studies ignore the effects of coupled climate change and development patterns. In this study, a framework for assessing habitat quality under the influence of future land use change is constructed based on exploring the driving forces of land use change factors and integrating the system dynamics (SD) model, future land use simulation (FLUS) model and InVest model. The framework enables the projection of land use change and the assessment of habitat quality in the context of future climate change and different development strategies. Applying the framework to the Weihe River Basin, the main driving forces of land-use change in the Weihe River Basin were identified based on geographical detectors, and habitat quality assessment was realized for the Weihe River Basin under the coupled scenarios of three typical shared socioeconomic pathways and future development patterns (SSP126-EP, SSP245-ND, SSP585-EG). The results show that 1) population, precipitation, and temperature are the major driving factors for land use change. 2) The coupling model of SD and FLUS can effectively simulate the future trend of land use change, the relative error is within 2 %, and the overall accuracy is 93.58 %. 3) Significant differences in habitat quality as a result of modifications in land use patterns in different contexts. Affected by ecological protection, the habitat quality in SSP126-EP was significantly better than that in SSP245-ND and SSP585-EG. This research can provide references for future watershed ecological management decisions.

Runoff forecasting model based on variational mode decomposition and artificial neural networks.

Accurate runoff forecasting plays a vital role in water resource management. Therefore, various forecasting models have been proposed in the literature. Among them, the decomposition-based models have proved their superiority in runoff series forecasting. However, most of the models simulate each decomposition sub-signals separately without considering the potential correlation information. A neoteric hybrid runoff forecasting model based on variational mode decomposition (VMD), convolution neural networks (CNN), and long short-term memory (LSTM) called VMD-CNN-LSTM, is proposed to improve the runoff forecasting performance further. The two-dimensional matrix containing both the time delay and correlation information among sub-signals decomposing by VMD is firstly applied to the CNN. The feature of the input matrix is then extracted by CNN and delivered to LSTM with more potential information. The experiment performed on monthly runoff data investigated from Huaxian and Xianyang hydrological stations at Wei River, China, demonstrates the VMD-superiority of CNN-LSTM to the baseline models, and robustness and stability of the forecasting of the VMD-CNN-LSTM for different leading times.

Dynamic simulation of river water environmental capacity based on the subsection summation model.

There are noteworthy problems in current strategies to calculate river water environmental capacity (WEC), including the generalization of tributaries and water intakes, which results in inaccurate calculation results of the WEC, and the difficulty in adapting to dynamic changes in demands and hydrological conditions in terms of practical application. To address these flaws, the subsection summation model (SSM) was built for river WEC calculation. The SSM increases the number of control sections according to drain outlets, water intakes, and tributaries and acquires the WEC of the functional area section by section. The Wei River was taken as the study area for verification and application of the SSM. Supported by a comprehensive integration platform, the WEC simulation system of the Wei River was constructed. The results show that the SSM enhances the accuracy of the WEC calculation, and the results are closer to the actual situation. The simulation system could obtain the WEC according to the demands and changes in the hydrological conditions, thus providing technical means for policymakers. PRACTITIONER POINTS: The subsection summation model provides a more accurate water environmental capacity (WEC) calculation method considering tributaries and water intakes avoiding generalization. The simulation system should be established to make the WEC calculation adapt to the demands or changes in the hydrological conditions. The model and system could supply the basis and technical means for decision-making.

A bi-level multiobjective optimization model for waste load allocation in rivers.

It is often difficult to apply existing waste load allocation (WLA) models to management institutions at all levels of the river basin because the existing WLA models do not consider the principles of fairness and efficiency at each management level of the basin. The implementation of environmental protection tax law has also greatly impacted WLA. This paper proposes the bi-level multiobjective allocation model under an environmental protection tax law to solve the WLA problem for different management levels. The upper allocation targets the minimal environmental Gini coefficient and the minimal unit pollutant emission cost. The impact of the environmental protection tax is also considered. The targets of the lower-level allocation are the maximal industrial output value and the minimal unevenness of reduction rates. The proposed model was applied to the case of the Wei River basin, and the results demonstrated that the bi-level multiobjective allocation model could solve the problem of WLA under an environmental protection tax law. Each level of the bi-level multiobjective allocation model considers the principles of fairness and efficiency to distribute the load in the basin, thereby offering a better reference for decision-makers at both levels.

miR-618 Suppresses Metastasis in Gastric Cancer by Downregulating the Expression of TGF-ß2.

Recent studies have demonstrated that microRNAs regulate gene expression and are related to cancer progression. Increasing evidence shows that miR-618 plays an important role in a variety of tumors, including thyroid carcinomas, breast cancer and lymphoma cancer. However, no studies have examined the expression or function of miR-618 in gastric cancer (GC). In this study, we examined the effects and molecular mechanisms of miR-618 in GC. We compared the expression levels of miR-618 in 90 paired GC tissues and adjacent noncancerous tissues. Cell cycle, apoptosis and transwell assays were performed in GC cells with miR-618 mimic or inhibitor in vitro. We first used quantitative PCR(qPCR) to show that miR-618 expression levels were downregulated in GC tissues, which showed statistical significance. Next we used transwell assays to prove that miR-618 suppressed the invasion and migration capacity of GC cells. Furthermore, screening of the miRDB and Target Scan Human databases indicated TGF-ß2 as a downstream target of miR-618. In further research, we identified TGF-ß2 as a target gene of miR-618 by the luciferase reporter assay. Western blot analysis confirmed that TGF-ß2 expression was inversely correlated with miR-618 expression. In situ hybridization showed that miR-618 expression level was downregulated in GC tissues. In conclusion, our findings suggest that miR-618 may function as a tumor suppressor in GC and suppresses metastasis in GC by negatively regulating the transcriptional level of TGF-ß2. Anat Rec, 302:931-940, 2019. © 2019 Wiley Periodicals, Inc.

Overexpression of MYC binding protein promotes invasion and migration in gastric cancer.

Gastric cancer (GC) is the second leading cause of cancer-associated mortality worldwide. Although the mortality rate of patients with GC has improved, it remains a significant health issue. The MYC proto-oncogene protein serves key roles in cellular proliferation, differentiation, transformation and apoptosis. Previous studies have identified the abnormal expression of MYC-binding protein (MYCBP) during tumorigenesis in multiple types of cancer. Furthermore, evidence demonstrates that the abnormal expression of MYCBP contributes to the invasion and migration of human cancer types, including colon cancer and glioma; however, its influence on GC remains unclear. In the present study, the expression of MYCBP in GC cells and tissues was analyzed by reverse transcription-quantitative polymerase chain reaction. Additionally, GC cell lines were transfected with small interfering RNAs against MYCBP or lymphoid enhancer-binding factor 1 (LEF-1) and assessed by in vitro transwell migration and invasion assays. The results indicated that the expression of MYCBP in GC cells and tissues was markedly increased compared with a normal gastric epithelial cell line and adjacent normal gastric mucosal tissues, respectively. Furthermore, MYCBP downregulation notably inhibited the metastatic capacity of GC cells, and LEF-1 knockdown was found to downregulate the expression of MYCBP. On the basis of the findings of the present study, MYCBP may be a direct target of the ß-catenin/LEF-1 pathway via binding LEF-1, and could potentially be used as a biomarker for the diagnosis and prognosis of GC.

Low FAT4 expression is associated with a poor prognosis in gastric cancer patients.

In this study, we investigated the role of Fat atypical cadherin 4 (FAT4) in gastric cancer (GC) progression. Immunohistochemical analysis showed lower FAT4 expression in tumor tissues from GC patients than in normal gastric epithelium. Lower FAT4 expression was associated with poor prognosis, tumor size and invasion, and lymph node and distant metastases. Multivariate analysis showed that TNM stage, lymph node and distant metastases, Lauren classification, and FAT4 expression were independent prognostic factors in GC. Methylation-specific PCR analysis showed increased FAT4 promoter methylation in GC tumor tissues and cell lines. Higher FAT4 promoter methylation was associated with low FAT4 expression and a poor prognosis. BGC-823 cells showed increased FAT4 expression upon treatment with 5-azacytidine, demethylating agent. FAT4 knockdown in BGC-823 cells led to increased cell proliferation, migration and invasiveness. Moreover, xenografts of BGC-823 cells with FAT4 knockdown showed enhanced tumor growth and metastasis in nude mice. These findings demonstrate that low FAT4 expression is associated with a poor prognosis in GC patients.

PHD3 affects gastric cancer progression by negatively regulating HIF1A.

Prolyl hydroxylase 3 (PHD3) is widely accepted as a tumor suppressor; however, the expression of PHD3 in various cancer types remains controversial. The present study aimed to investigate the association between PHD3 expression and the clinicopathological features of gastric cancer using reverse transcription­quantitative polymerase chain reaction and immunohistochemistry. The effects of PHD3 in gastric cancer cell lines were assessed using western blot analysis and transwell migration assays. The present results revealed that PHD3 expression was increased in adjacent non­cancerous tissue compared with in gastric cancer tissue, and PHD3 overexpression was correlated with the presence of well­differentiated cancer cells, early cancer stage classification and the absence of lymph node metastasis. In vitro experiments demonstrated that PHD3 may act as a negative regulator of hypoxia­inducible factor­1α and vascular endothelial growth factor, both of which participate in tumor angiogenesis. In conclusion, the present results suggested that PHD3 may act as a tumor suppressor in gastric cancer. Therefore, the targeted regulation of PHD3 may have potential as a novel therapeutic approach for the treatment of patients with gastric cancer.

MicroRNA-145-5p inhibits gastric cancer invasiveness through targeting N-cadherin and ZEB2 to suppress epithelial-mesenchymal transition.

MicroRNA (miR)-145-5p has been reported to function as a suppressor of cancer and plays an important role in cancer invasiveness. Epithelial-mesenchymal transition (EMT) is an important process in cancer invasion and migration. However, the involvement of miR-145-5p in EMT in human gastric cancer (GC) remains unclear. In this study, we aimed to investigate the molecular mechanisms by which miR-145-5p regulates EMT in GC invasiveness. We used quantitative real-time polymerase chain reaction to investigate the miR-145-5p expression level in GC and matched normal tissues. The effects of miR-145-5p on GC cell invasion and migration abilities were evaluated using Transwell models. The relationships among miR-145-5p and zinc-finger E-box binding homeobox 2 (ZEB2), E-cadherin, and N-cadherin were analyzed by quantitative real-time polymerase chain reaction and Western blot analyses. miR-145-5p levels in primary GC tissues obtained from 60 patients were significantly downregulated, compared to those in paired normal tissues. Lauren classification, depth of tumor invasion, lymph node metastasis, lymphatic invasion, and tumor-node-metastasis stage were associated with miR-145-5p expression. miR-145-5p inhibits the expression of the candidate target gene ZEB2 to delay the invasion and migration of GC cells. ZEB2 acts as transcriptional repressor of E-cadherin, while miR-145-5p is known to suppress N-cadherin directly to regulate EMT. Therefore, we concluded that miR-145-5p may target N-cadherin and ZEB2 directly to influence EMT.