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Mesothelin, a secreted protein, is overexpressed in some cancers, including pancreatic cancer. Rescent studies have shown that overexpression of mesothelin significantly increased tumor cell proliferation, and downregulation of mesothelin inhibited cell proliferation in pancreatic cancer cells, but its exact function and mechanism remains unclear. The aim of the present study was to evaluate the effects of mesothelin on proliferation and apoptosis in pancreatic cancer cells with different p53 status and to explore its signal pathway. Mesothelin levels were detected by western blot and RT-PCR assay in human pancreatic cancer AsPC-1, HPAC and Capan-2, Capan-1 and MIA PaCa-2 cell lines. Mesothelin was slienced by shRNA in AsPC-1, Capan-2 and Capan-1 cells with rich mesothelin level, and mesothelin was overexpressed in the HPAC and Capan-2 cells with less mesothelin level. We observed that in the AsPC-1 and Capan-1cells with mt-p53, and Capan-2 cells with wt-p53, shRNA mediated sliencing of the mesothelin significantly increased PUMA and Bax expression and caspase-3 activity, and decreased bcl-2 expression, followed by the reduced proliferation and colony forming capability and increased cell apoptosis. When PUMA was slienced by siRNA in the stable mesothelin shRNA transfected cells, proliferative capability was significantly increased, and apoptosis was decreased. However, in the Capan-2 cells with wt-p53, suppression of the mesothelin significantly increased wt-p53 levels. When p53 was blocked by siRNA in the stable mesothelin shRNA transfected Capan-2 cells, PUMA was inhibited, followed by increased proliferative capability and decreased cell apoptosis. In the HPAC and Capan-2 cells with wt-p53 and in the MIA PaCa-2 cells with mt-p53, overexpression of the mesothelin significantly decreased bax levels and increased bcl-2 levels, followed by increased proliferative and colony forming capability. Furthermore, mesothelin-shRNA-transfected cells exhibited a reduced rate of tumor growth under in vivo conditions. However, mesothelin-transfected cells exhibited a increased rate of tumor growth under in vivo conditions. Our data demonstrated that mesothelin promotes proliferation and inhibited apoptosis through p53-dependent pathway in pancreatic cancer cells with wt-p53, and p53-independent pathway in pancreatic cancer cells with mt-p53. Targeting mesothelin by shRNA is the important method for pancreatic cancer therapy.

The relationship between product pricing and product packaging plays an important role in the buying behavior of consumers, whereas customer satisfaction plays a mediating role. To test these hypotheses, research was conducted on university students in China. Questionnaire-based convenience sampling was conducted on 500 students for data collection using online and offline sources. A total of 367 (73%) students responded, and 17 questionnaires were rejected due to missing information. SPSS and AMOS software were used for the data analysis. Product pricing and product information were independent variables in this study, whereas consumer buying behavior was a dependent variable. Customer satisfaction is mediated by one dependent and two independent variables. Confirmatory factor analysis, path analysis, and discriminant validity in structural equation modeling revealed that product pricing and packaging had a statistically significant relationship with the buyer decision process. The introduction of satisfaction as a mediating variable led to the observation of full mediation in the case of product pricing and partial mediation in product packaging. Given the results of this research, product managers should adopt pricing tactics along with product packaging to influence the buying intentions of consumers.

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Background: Cyclophosphamide is a common tumor chemotherapy drug used to treat various cancers. However, the resulting immunosuppression leads to leukopenia, which is a serious limiting factor in clinical application. Therefore, the introduction of immunomodulators as adjuvant therapy may help to reduce the hematological side effects of cyclophosphamide. Lvjiaobuxue granule has been widely used in the clinical treatment of gynecological diseases such as anemia and irregular menstruation. Recently, it has been found to increase the function of white blood cells, but its mechanism of action is still unclear. We aimed to reveal the mechanisms of Lvjiaobuxue granule against acute leukopenia by an integrated strategy combining metabolomics with network pharmacology.Methods: Subcutaneously inoculated 4T1 breast cancer cells to prepare tumor-bearing mice, intraperitoneal injection of cyclophosphamide to establish a 4T1 tumor-bearing mice leukopenia animal model, using pharmacodynamic indicators, metabolomics, network pharmacology and molecular biology and other technical methods. To comprehensively and systematically elucidate the effect and mechanism of Lvjiaobuxue granule in improving cyclophosphamide-induced leukopenia in 4T1 tumor-bearing mice.Results: Lvjiaobuxue granule can improve the blood routine parameters and organ index levels of the leukopenia model of 4T1 tumor-bearing mice. Metabolomics studies revealed that 15 endogenous metabolites in the spleen of mice were considered as potential biomarkers of Lvjiaobuxue granule for their protective effect. Metabonomics and network pharmacology integrated analysis indicated that Lvjiaobuxue granule exerted the leukocyte elevation activity by inhibiting the branched-chain amino acids (BCAAs) degradation pathway and increasing the levels of valine, leucine and isoleucine. The results of molecular biology also showed that Lvjiaobuxue granule can significantly regulate the key enzymes in the catabolism of BCAAs, which further illustrates the importance of BCAAs in improving leukopenia.Conclusion: Lvjiaobuxue granule exerts obvious pharmacological effects on the leukopenia model of 4T1 tumor-bearing mice induced by cyclophosphamide, which could be mediated by regulating the branched-chain amino acid degradation pathway and the levels of valine, leucine and isoleucine.

Aim and Objective:: Despite the prevalence and burden of major depressive disorder (MDD), our current understanding of the pathophysiology is still incomplete. Therefore, this paper aims to explore genes and evaluate their diagnostic ability in the pathogenesis of MDD. Methods:: Firstly, the expression profiles of mRNA and microRNA were downloaded from the gene expression database and analyzed by the GEO2R online tool to identify differentially expressed genes (DEGs) and differentially expressed microRNAs (DEMs). Then, the DAVID tool was used for functional enrichment analysis. Secondly, the comprehensive protein- protein interaction (PPI) network was analyzed using Cytoscape, and the network MCODE was applied to explore hub genes. Thirdly, the receiver operating characteristic (ROC) curve of the core gene was drawn to evaluate clinical diagnostic ability. Finally, mirecords was used to predict the target genes of DEMs. Results:: A total of 154 genes were identified as DEGs, and 14 microRNAs were identified as DEMs. Pathway enrichment analysis showed that DEGs were mainly involved in hematopoietic cell lineage, PI3K-Akt signaling pathway, cytokinecytokine receptor interaction, chemokine signaling pathway, and JAK-STAT signaling pathway. Three important modules are identified and selected by the MCODE clustering algorithm. The top 12 hub genes including CXCL16, CXCL1, GNB5, GNB4, OPRL1, SSTR2, IL7R, MYB, CSF1R, GSTM1, GSTM2, and GSTP1 were identified as important genes for subsequent analysis. Among these important hub genes, GSTM2, GNB4, GSTP1 and CXCL1 have good diagnostic ability. Finally, by combining these four genes, the diagnostic ability of MDD can be improved to 0.905, which is of great significance for the clinical diagnosis of MDD. Conclusion:: Our results indicate that GSTM2, GNB4, GSTP1 and CXCL1 have potential diagnostic markers and are of great significance in clinical research and diagnostic application of MDD. This result needs a large sample study to further confirm the pathogenesis of MDD.

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This paper attempts to evaluate the click efficiency of different graphic designs of the virtual reality (VR) system for shipbuilding in a shipyard. For this purpose, a prediction method for the completion time of pointing tasks in a VR was proposed based on the probabilistic Fitts' law, and a selection model was constructed for targets in arbitrary shape in VR. According to the design requirements of VR interfaces, the authors considered the influence of target shape on task completion time, constructed the relationship between hit probability and the index of difficulty (ID) of the task, and took the target center as the center point of the function to be integrated, thus defining the probabilistic Fitts' model in VR scenes. Next, Experiment 1 was designed to compute the constant terms of probability function P(HIT) in the improved probabilistic Fitts' model; Experiment 2 was designed to calculate the constant terms of prediction function in the improved model. Int his way, the improved probabilistic Fitts' model was completed. Finally, our model was validated and evaluated by the actual pointing task of the shipbuilding VR system of a shipyard. The results show that our model can predict the task completion time well under VR scenes. The research provides effective guidance for designers to optimize the interface layout in a VR environment, and optimize the user experience of interface interaction.