Fig 2: Schematic overview showing lymphatic metastatic GC cell-exosomal CD44 increases FAO to confer LNM phenotype on primary GC cells via the RhoA/YAP/CPT1A signaling axis. Metastatic GC cells in LNs secrete CD44-rich exosomes, which are taken up by GC cells in primary GC tissues and upregulate its intracellular CD44 protein. CD44 then increases RhoA expression, stimulates YAP expression, de-phosphorylation and nuclear translocation. YAP and TAZ function as transcriptional co-factors to promote Prox1 transcription and protein generation. Prox1 further translocates into nuclei and increases CPT1A transcription. CPT1A protein upregulation promotes FAO reprogramming and increases cell migration and invasion, leading to acquiring LNM capacity by primary GC cells. CD44, YAP and CPT1A might be potential therapeutic targets to suppress exosome-mediated LNM phenotype transfer from lymphatic metastatic GC cells to primary GC cells. LNs, lymph nodes.

Fig 3: Changes of meningeal lymphatic drainage and related proteins of acute TBI mice. a Representative images of dCLN showing drainage of RITC-Dextran. b Graph depicting percent area of RITC-Dextran coverage of dCLN. c Representative immunofluorescence images of dorsal MLVs. d Quantification of LYVE-1 staining area of dorsal meninges. e–f Representative images of the area of LYVE-1 staining in dorsal COS, TS (contralateral), TS (ipsilateral), SSS, and basal OCCS. g–h Quantification of LYVE-1 positive area of each part of dorsal meninges and OCCS of basal meninges. i–j Western blot scans and quantitative analysis of VEGFR3, VE-cadherin, PROX-1, FOXC-2 and VEGFC protein in dorsal meninges. All data are presented as mean ± SD (n = 5–6 per group). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. ##p < 0.01 versus TBI + IL-33 group, ###p < 0.001 versus TBI + IL-33 group, ####p < 0.0001 versus TBI + IL-33 group