PDPN/CCL2/STAT3 feedback loop alter CAF heterogeneity to promote angiogenesis in colorectal cancer.

Colorectal cancer (CRC) is one of the common clinical malignancies and the fourth leading cause of cancer-related death in the world. The tumor microenvironment (TME) plays a crucial role in promoting tumor angiogenesis, and cancer-associated fibroblasts (CAFs) are one of the key components of the tumor microenvironment. However, due to the high heterogeneity of CAFs, elucidating the molecular mechanism of CAF-mediated tumor angiogenesis remained elusive. In our study, we found that there is pro-angiogenic functional heterogeneity of CAFs in colorectal cancer and we clarified that Podoplanin (PDPN) can specifically label CAF subpopulations with pro-angiogenic functions. We also revealed that PDPN + CAF could maintain CAF heterogeneity by forming a PDPN/CCL2/STAT3 feedback loop through autocrine CCL2, while activate STAT3 signaling pathway in endothelial cells to promote angiogenesis through paracrine CCL2. We demonstrated WP1066 could inhibit colorectal cancer angiogenesis by blocking both the PDPN/CCL2/STAT3 feedback loop in CAFs and the STAT3 signaling pathway in endothelial cells. Altogether, our study suggests that STAT3 could be a potential therapeutic target for blocking angiogenesis in colorectal cancer. We provide theoretical basis and new therapeutic strategies for the clinical treatment of colorectal cancer.

Research on methods for controlling strand sag in main cables.

The accuracy of main cable construction in suspension bridges is directly influenced by the sag of the strands during the erection process. Thus, effective methods for controlling strand sag are crucial. However, the current control standards and methods are primarily based on practical engineering experience, lacking quantitative analysis and a sufficient basis. This paper aims to address this gap by summarizing four commonly used strand sag control methods and proposing a quantitative analysis model that considers the influence of random factors. The model quantifies the impact of these methods on the main cable shape and strand tension after cable tightening. To illustrate the practical application, a suspension bridge is utilized as a case study. The results of the study illustrate a linear relationship between the main cable sag and inter-strand distance, with each control method exhibiting a varying linear change rate. Moreover, the discrepancy in strand distance contributes to uneven strand tension after cable tightening. Random errors contribute to the dispersion of the main cable sag and strand tension, which are further exacerbated by cumulative errors between layers of general strands. Based on the study's results, this paper provides valuable references for the erection and control of the main cable in suspension bridges.