Protease-activated receptor-2 (PAR-2) has shown strong pro-angiogenesis activity physiologically and pathologically. This study aimed to explore PAR-2 regulation of pro-angiogenesis gene expression and the underlying molecular pathways in gastric cancer cells. MKN28 human gastric cancer cells were treated with trypsin, a PAR-2 activator, and subjected to real-time reverse transcription polymerase chain reaction (qRT-PCR), western blotting and ELISA for gene expression analyses. ERK1/2 phosphorylation and p38 MAP kinase inhibitors (PD98059 and SB203580, respectively) were used to block their gene activities. PAR-2 mRNA and protein were expressed in MKN-28 cells and activated by trypsin treatment. Trypsin-activated PAR-2 protein significantly enhanced expression of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) mRNA and protein in gastric cancer cells in a dose- and time-dependent manner. PAR-2 activation also induced the phosphorylation of ERK1/2 and p38 MAP kinase, but the ERK1/2 and p38 inhibitors blocked the activated PAR-2-induced VEGF and COX-2 expression in gastric cancer cells. PAR-2-induced expression of VEGF and COX-2 mRNA and protein in gastric cancer MKN28 cells was mediated by activation of an ERK1/2- and p38 MAP kinase-dependent pathway. Thus, PAR-2 may serve as a promising target for anti-angiogenesis therapy to treat gastric cancer.

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Choosing a suitable cross-border logistics mode is the foundation for cross-border e-commerce enterprises to achieve sustainable development. Based on an analysis of the literature, the cross-border logistics modes are summarized as postal parcel, international express, overseas warehouse, and special line logistics modes. Using the multi-value set qualitative comparative analysis (mvQCA) method to explore the factors and formation paths of logistics mode selection of cross-border e-commerce enterprises, the results include the following: (1) The choice of logistics mode is the result of multiple condition variables, and the formation paths of different logistics mode selection vary. (2) The postal parcel mode is most selected by small and medium-sized B2C cross-border e-commerce enterprises; the overseas warehouse and special line modes are most selected by large and medium-sized ones with high logistics service capacity. (3) The international express mode is selected by B2C cross-border e-commerce enterprises of all sizes, and there is no typical formation path. The results indicate that cross-border e-commerce enterprises should have clear positioning and select the most suitable logistics mode, as only in this way can cross-border e-commerce and logistics enterprises jointly achieve sustainable development.

Background Colorectal cancer (CRC) is a malignant tumor of the digestive system that contains high levels of immune cells. Lactic acid, a major metabolite, plays a crucial role in tumor development, maintenance, and therapeutic response. However, the prognostic potential and therapeutic biomarker potential of lactate‐related genes (LRGs) in CRC patients remain to be elucidated. Methods We collected the mRNA expression profile and clinical data of CRC patients from the Cancer Genome Atlas (TCGA) database and the GSE59382 cohort. Univariate Cox regression, Lasso regression and multivariate Cox regression analysis were used to construct the prognosis model. Combined with the risk score and important clinicopathological features, the nomogram was established. In addition, the relationship between risk score and immune infiltration, immune checkpoint gene expression, and drug sensitivity was investigated. Results We constructed lactate‐related gene signatures (LRGS) based on four LRGs, which independently predicted the prognosis of CRC. Patients with different risk scores are found to have distinct immune status, tumor mutation load, immune response, and drug sensitivity. In addition, nomogram results determined by risk scores and clinical factors have higher predictive performance. Conclusion We found that LRGS is a reliable biomarker for predicting clinical outcomes, evaluating immune infiltration and efficacy, and predicting the sensitivity to drugs in patients with CRC.