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This paper reports a study on the flexural performance of prestressed high strength steel reinforced concrete (PHSSRC) beams and proposes machine learning (ML) models for predicting the flexural bearing capacity of steel reinforced concrete (SRC) beams. Seven prestressed steel reinforced concrete (PSRC) beams were tested under a four-point bending load to investigate the effect of steel strength grade, steel ratio, and longitudinal reinforcement ratio on the flexural load capacity of beams. The test results indicated that increasing the steel strength grade and steel ratio significantly enhanced the bearing capacity of PSRC beams. A database consisting of 112 sets of experimental data on the flexural performance of SRC beams, including the test data in this study, was established for training and validating the ML models. Artificial Neural Network (ANN) model and eXtreme Gradient Boosting (XGBoost) model were respectively developed to predict the flexural load capacity of SRC beams, and the accuracy of the flexural load capacity values predicted by the design specification, the ANN model and the XGBoost model were compared. The results show that the XGBoost model has the best prediction performance. Finally, the sensitivity analysis of the parameters was performed using the Shapley Additivity (SHAP) interpretation method.

Abstract Background Osteoarthritis is a degenerative joint disease. Cartilage degeneration is the earliest and most important pathological change in osteoarthritis, and persistent inflammation is one of the driving factors of cartilage degeneration. Cucurbitacin E, an isolated compound in the Cucurbitacin family, has been shown to have anti-inflammatory effects, but its role and mechanism in osteoarthritic chondrocytes are unclear. Methods For in vitro experiments, human chondrocytes were stimulated with IL-1β, and the expression of inflammatory genes was measured by Western blotting and qPCR. The expression of extracellular matrix proteins was evaluated by immunofluorescence staining, Western blotting and saffron staining. Differences in gene expression between cartilage from osteoarthritis patients and normal cartilage were analysed by bioinformatics methods, and the relationship between Cucurbitacin E and its target was analysed by a cellular thermal shift assay, molecular docking analysis and molecular dynamics simulation. For in vivo experiments, knee osteoarthritis was induced by DMM in C57BL/6 mouse knee joints, and the effect of Cucurbitacin E on knee joint degeneration was evaluated. Results The in vitro experiments confirmed that Cucurbitacin E effectively inhibited the production of the inflammatory cytokine interleukin-1β(IL-1β) and cyclooxygenase-2 (COX-2) by IL-1β-stimulated chondrocytes and alleviates extracellular matrix degradation. The in vivo experiments demonstrated that Cucurbitacin E had a protective effect on the knee cartilage of C57BL/6 mice with medial meniscal instability in the osteoarthritis model. Mechanistically, bioinformatic analysis of the GSE114007 and GSE117999 datasets showed that the PI3K/AKT pathway was highly activated in osteoarthritis. Immunohistochemical analysis of PI3K/Akt signalling pathway proteins in pathological slices of human cartilage showed that the level of p-PI3K in patients with osteoarthritis was higher than that in the normal group. PI3K/Akt were upregulated in IL-1β-stimulated chondrocytes, and Cucurbitacin E intervention reversed this phenomenon. The cellular thermal shift assay, molecular docking analysis and molecular dynamics experiment showed that Cucurbitacin E had a strong binding affinity for the inhibitory target PI3K. SC79 activated Akt phosphorylation and reversed the effect of Cucurbitacin E on IL-1β-induced chondrocyte degeneration, demonstrating that Cucurbitacin E inhibits IL-1β-induced chondrocyte inflammation and degeneration by inhibiting the PI3K/AKT pathway. Conclusion Cucurbitacin E inhibits the activation of the PI3K/AKT pathway, thereby alleviating the progression of OA. In summary, we believe that Cucurbitacin E is a potential drug for the treatment of OA.