Al-driven analysis establishes the single base substitution signatures as personalized prognostic predictors for five-year survival of gastric cancer

Al-driven genetic engineering,as a burgeoning diagnostic tool,can offer predictive information on the five-year survival rate(FYSR)in the setup of a prognostic therapeutic schedule.This approach provides the individuality and accuracy of prognosis for FYSR of gastric cancer(GC).Unlike traditional neoplasm staging criteria,our technique ensures accuracy and individuality without relying on statistical data and empirical study.

Dicalcium silicate-induced mitochondrial dysfunction and autophagy-mediated macrophagic inflammation promotes osteogenic differentiation of BMSCs

Dicalcium silicate(Ca_(2)SiO_(4),C_(2)S)has osteogenic potential but induces macrophagic inflammation.Mitochondrial function plays a vital role in macrophage polarization and macrophagic inflammation.The mitochondrial function of C_(2)S-treated macrophages is still unclear.This study hypothesized:(i)the C_(2)S modulates mitochondrial function and autophagy in macrophages to regulate macro-phagic inflammation,and(ii)C_(2)S-induced macrophagic inflammation regulates osteogenesis.We used RAW264.7 cells as a model of macrophage.The C_(2)S(75–150μg/ml)extract was used to analyze the macrophagic mitochondrial function and macrophagemediated effect on osteogenic differentiation of mouse bone marrow-derived mesenchymal stem cells(BMSCs).The results showed that C_(2)S extract(150μg/ml)induced TNF-α,IL-1βand IL-6 production in macrophages.C_(2)S extract(150μg/ml)enhanced reactive oxygen species level and intracellular calcium level but reduced mitochondrial membrane potential and ATP production.TEM images showed reduced mitochondrial abundance and altered the mitochondrial morphology in C_(2)S(150μg/ml)-treated macrophages.Protein level expression of PINK1,Parkin,Beclin1 and LC3 was upregulated but TOMM20 was downregulated.mRNA sequencing and KEGG analysis showed that C_(2)S-induced differentially expressed mRNAs in macrophages were mainly distributed in the essential signaling pathways involved in mitochondrial function and autophagy.The conditioned medium from C_(2)S-treated macrophage robustly promoted osteogenic differentiation in BMSCs.In conclusion,our results indicate mitochondrial dysfunction and autophagy as the possible mechanism of C_(2)S-induced macrophagic inflammation.The promotion of osteogenic differentiation of BMSCs by the C_(2)S-induced macrophagic inflammation suggests the potential application of C_(2)S in developing immunomodulatory bone grafts.