Fig 2: Regulators of mRNA translation in B cells.a Total content of ribosomal proteins was calculated as sum of CN x MW / NA, where CN is protein copy number, MW is protein molecular weight, and NA is Avogadro’s constant. Graph depicts ribosomal proteins as a proportion to total protein content in T1, T2, MZ and FoB cells. b, c Graphs display copy numbers of key components of the eIF4F mRNA translation initiation complex (eIF4A1, eIF4B, eIF4E, eIF4G1). Overlay histogram represents flow cytometric detection of eIF4A1 in MZ and FoB cells. d PDCD4 protein amounts detected by mass spectrometry (left) or flow cytometry (right). e Ratio between EIF4A1 and PDCD4 copy numbers was calculated in each B cell subset. Graphs display mean ± SD (n = 4 mice). Source data are provided as Source Data file.

Fig 3: Knockdown of PDCD4 suppresses KA-induced oxidative stress in HT22 cells. (A) Dichlorodihydrofluorescein diacetate staining was used to assess reactive oxygen species levels. Original magnification, x200. (B) Levels of MDA, SOD and GSH-Px were detected using kits. Data are presented as the means ± SD. ***P<0.001 vs. Control; ###P<0.001 vs. KA + sh-NC. GSH-Px, glutathione peroxidase; KA, kainic acid; MDA, malondialdehyde; NC, negative control; PDCD4, human programmed cell death 4; sh, short hairpin; SOD, superoxide dismutase.

Fig 4: Expression of programmed cell death 4 (PDCD4) and miR-16 in atherosclerosis. (A) Mouse model of atherosclerosis. According to the results of hematoxylin and eosin staining, large plaques (indicated by arrows) were induced by a high-fat diet in the thoracic aorta of the ApoE−/− mice, which indicated that the mouse model of atherosclerosis was successfully developed. (B) PDCD4 mRNA expression in the mice with atherosclerosis was detected by RT-qPCR. (C and D) PDCD4 protein expression in mice with atherosclerosis was detected by (C) western blot analysis and (D) immunohistochemistry. (E) miR-16 expression in mice with atherosclerosis detected by stem-loop RT-qPCR. (F–H) Expression levels of PDCD4 (F) mRNA and (G) protein, as well as (H) miR-16 expression in foam cells derived from oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages. Difference between 2 groups was analyzed using a t-test. ***P<0.001 compared with the control. AS, atherosclerosis.

Fig 5: Combined treatment of Trametinib and Osimertinib effectively inhibited the growth of P_AZDR1 (Osimertinib resistant) cells in vivo. (A) The flow chart for in vivo experimental design and treatment schedule. (B) Tumor curve over time shows that the combination of Trametinib and Osimertinib suppressed the tumor growth the most followed by the Trametinib alone group as compared to the vehicle and Osimertinib groups (no significant difference between these two groups). (C) Bodyweight over time curve demonstrated no apparent systematic toxicity in the mice receiving combined treatment. (D) Kaplan-Meier survival curve shows that the mice that received the combined treatment exhibited the highest survival ratio as compared to the rest. (E) Real-time PCR results of the tumor samples revealed that the miR-21-5p level was most significantly suppressed in the combined treatment followed by the Trametinib group while no significant difference was observed between vehicle and Osimertinib groups. (F) Immunostaining analysis of PDX tumor sections showed that the combined treatment most prominently suppressed the expression of MEK, ERK, STAT3 and PDCD4 but an increased E-cadherin was observed, compared to other sections. * p < 0.05; ** p < 0.01; *** p < 0.001. NS, not significantly different. PDX: patient-derived xenograft.