Plasma metabolites as mediators in immune cell-pancreatic cancer risk: insights from Mendelian randomization.

Background: Immune cells play a crucial role in the development and progression of pancreatic cancer, yet the causal relationship remains uncertain due to complex immune microenvironments and conflicting research findings. Mendelian randomization (MR), this study aims to delineate the causal relationships between immune cells and pancreatic cancer while identifying intermediary factors. Methods: The genome-wide association study (GWAS) data on immune cells, pancreatic cancer, and plasma metabolites are derived from public databases. In this investigation, inverse variance weighting (IVW) as the primary analytical approach to investigate the causal relationship between exposure and outcome. Furthermore, this study incorporates MR-Egger, simple mode, weighted median, and weighted mode as supplementary analytical approaches. To ensure the reliability of our findings, we further assessed horizontal pleiotropy and heterogeneity and evaluated the stability of MR results using the Leave-one-out method. In conclusion, this study employed mediation analysis to elucidate the potential mediating effects of plasma metabolites. Results: Our investigation revealed a causal relationship between immune cells and pancreatic cancer, highlighting the pivotal roles of CD11c+ monocytes (odds ratio, ORIVW=1.105; 95% confidence interval, 95%CI: 1.002-1.218; P=0.045), HLA DR+ CD4+ antigen-presenting cells (ORIVW=0.920; 95%CI: 0.873-0.968; P=0.001), and HLA DR+ CD8br T cells (ORIVW=1.058; 95%CI: 1.002-1.117; P=0.041) in pancreatic cancer progression. Further mediation analysis indicated that oxalate (proportion of mediation effect in total effect: -11.6%, 95% CI: -89.7%, 66.6%) and the mannose to trans-4-hydroxyproline ratio (-19.4, 95% CI: -136%, 96.8%) partially mediate the relationship between HLA DR+ CD8br T cells and pancreatic cancer in nature. In addition, our analysis indicates that adrenate (-8.39%, 95% CI: -18.3%, 1.54%) plays a partial mediating role in the association between CD11c+ monocyte and pancreatic cancer, while cortisone (-26.6%, 95% CI: 138%, -84.8%) acts as a partial mediator between HLA DR+ CD4+ AC and pancreatic cancer. Conclusion: This MR investigation provides evidence supporting the causal relationship between immune cell and pancreatic cancer, with plasma metabolites serving as mediators. Identifying immune cell phenotypes with potential causal effects on pancreatic cancer sheds light on its underlying mechanisms and suggests novel therapeutic targets.

Numerical Investigation of Mechanical Performance and Micro-Structure Failure of Polymer-Fiber Reinforced Sand.

Natural sand has a loose and porous structure with low strength, and is prone to many geoengineering problems that cause huge losses. In this study, an organic polymer-polymer-fiber blend was used to improve the strength of sand. Using a series of laboratory and numerical simulation tests, researchers have investigated the microdamage behavior of an organic polymer and fiber-treated sand in various types of mechanical tests and explored the improvement mechanism. The results showed that the polymer- and fiber-treated sand enhanced the integrity and exhibited differential damage responses under different test conditions. The increase in polymer content induced uniform force transfer, leading to a wider range of particle motion and crack initiation, whereas the fibers adhered and confined the surrounding particles, inducing an arching force chain and dispersive/buckling cracking. Polymer- and fiber-treated sands increased their energy-carrying capacity and improved their energy release, which affected the damage characteristics. Organic polymers, fibers, and sand particles were wrapped around each other to form an effective interlocking structure, which enhances the integrity and mechanical properties of sand. This study provides novel ideas and methods in the polymer-fiber composite treatment of sand in the microscopic field.