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: Effects of atorvastatin and gefitinib alone or in combination on the activation of AKT and ERK of A549 or its PIK3CA and PTEN mutant tumors in vivo. (a and b) pAKT (a) and pERK (b) expression levels were analyzed for immunohistochemistry and the ratio of pAKT and total AKT (c) or pERK and total ERK (d) by using ELISA assay. Scatterplots represented five independent experiments in per group. All scale bars represent 50 µm. n.s, no significant difference. *P<0.05; **P<0.01; ***P<0.001

Fig 4: Effects of atorvastatin (ATV) on antitumor activity of gefitinib in nude mice bearing human lung cancer A549 and its PIK3CA or PTEN mutant xenografts. (a) Kaplan–Meier curves for illustration of the survival periods of xenograft-bearing mice treated with atorvastatin (1 mg/kg/day, p.o.) and gifitinib (100 mg/kg, thrice a week, p.o.), atorvastatin (10 mg/kg/day, p.o.) and gifitinib (100 mg/kg, thrice a week, p.o.) and each agents alone. The day 0 was used to represent the starting of treatment. (b) Representative A549 or its PIK3CA and PTEN mutant xenograft tumors resected on day 21 showing the difference in tumor volumes between individual agents and their combinations. The lower panel of b, tumor size was measured every 2 days for the indicated period. The treatment period was 21 days. Control mice received the vehicle. P-value was determined by log-rank test. Ten mice per group, mean±S.D. Also see Supplementary Tables 1 and 2, respectively

Fig 5: Model of promoter methylation-mediated SALL2 reduction confers tamoxifen resistance in ER+ breast cancerIn SALL2-hypomethylated ER+ breast cancer, SALL2 activates ER signaling via transcriptional upregulation of ESR1 and inhibits Akt/mTOR signaling via transcriptional upregulation of PTEN (left), leading to an estrogen-dependent growth and tamoxifen sensitivity. In SALL2-hypermethylated ER+ breast cancer, promoter methylation-mediated SALL2 reduction represses ERa and PTEN expression and activates Akt/mTOR signaling, resulting in estrogen-independent tumor growth and tamoxifen-resistant phenotype. DNMT inhibitor-induced SALL2 restoration resensitizes tamoxifen-resistant breast cancer to endocrine therapy (right).