Fig 2: The mechanism of how taurine relieves S. uberis infection by activating autophagy. From the above results, we infer that taurine enters the cells through transporters (TauT and PAT 1) to improve PTEN activity, promote the conversion of PIP3 to PIP2, and inhibit PI3K/Akt/mTOR signaling pathway, thereby attenuating the phosphorylation of ULK1 and ATG13 by mTOR, promoting the formation of ULK1-ATG13-FIP200 complex, and activating autophagy of MAC-T cells. S. uberis is recognized by both TLR2 and TLR4, internalizes into cells and may be ubiquitinated. Then, it is mediated by related receptor proteins into autophagosomes and fused with lysosomes to form autolysates. Finally, S. uberis is degraded and eliminated by proteases and hydrolases, which attenuates the stimulation to cells and reduces the activation of NF-?B, inhibits the secretion of inflammatory factors (such as TNF-a, IL-1ß, and IL-6), and alleviates the excessive inflammatory response and damage caused by S. uberis infection.

Fig 3: Breast cancer (TCGA cohort) PI3K signaling and stemness scores form a common cluster with proliferative and metabolic processes.As in Fig 6 except based on data from the TCGA breast cancer cohort as indicated.

Fig 4: Effects of atorvastatin and gefitinib alone or in combination on the growth and apoptosis of KRAS mutant NSCLC cells. (a) A549, Calu1, H157, and H460 cells were treated with the indicated concentrations of gefitinib or in the presence of 1 or 5 µM atorvastatin. (b–e) A549 (b and c) and Calu1 (d and e) cells were transfected with p110a E545K or control vector (b and d), or PTEN or control shRNA (c and e). After 24 h, cells were treated with indicated doses of atorvastatin or gefitinib, and their combinations for 3 days, then proliferation was measured by MTT assay. (f and k) A549 (f) and Calu1 (k) cells were treated with indicated doses of atorvastatin or gefitinib, and their combinations for 48 h, cell apoptosis was evaluated by FCM assay. (g–o) The apoptosis of A549 (g–j) and Calu1 (l–o) PIK3CA mutant (g, i, l, n) or PTEN (h, j, m, o) mutant cells were also evaluated by FCM assay (g, h, l, m) and caspase 3/7 activity assay (i, j, n, o), respectively. Bars are mean±S.D. from three independent experiments. **P<0.01; ***P<0.001

Fig 5: Effects of atorvastatin and gefitinib alone or in combination on the biomarkers of the growth and apoptosis of A549 or its PIK3CA and PTEN mutant tumor in vivo. (a) The positive staining of Ki67 expression per field from paraffin-embedded sections of A549 and its PIK3CA or PTEN mutant tumor treated with either atorvastatin or gefitinib alone or in combination was determined by immunohistochemistry and morphometric quantification. (b) Apoptotic nuclei with fragmented DNA were detected by TUNEL staining, and further analyzed by morphometric quantification. The final statistical graphs represent 10 non-overlapping images of each tumor specimen from five animals per group. All scale bars represent 50 µm. *P<0.05; **P<0.01; ***P<0.001