Fig 2: Colocalization of expression. Representative in situ hybridization (ISH) images merged with differential interference contrast (DIC) of the same field, showing Sema3A (green) and S100B (red) mRNA expression after cardiotoxin injury (day 6 (D6)) (i,ii) and after muscle-crush injury (D8, iii,iv, and D10, v,vi) without pretreatment (i,iii,v) and with 2 days of ISDN pretreatment (ii,iv,vi). Areas of Sema3A (green) and S100B (red) mRNA expression colocalized with P75 protein (white fluorescence) in terminal Schwann cells are indicated by white circles. Nuclei are counterstained with 4',6-diamidino-2-phenylindole (blue) in all fields. Bars indicate 10 µm.

Fig 3: Schematic for EV phenotyping by EPAC.(A) A melanoma cell with a BRAF V600E mutation secretes EVs into circulation or cell culture medium. (B) The sample is directly injected into EPAC, where the applied nanomixing fluid flow increases EV collisions with the capture antibody and SERS nanotags and shears off nontarget molecules (e.g., protein aggregates and apoptotic bodies) and free SERS nanotags. (C) The characterization of EV phenotypes is performed by SERS mapping. The false-color SERS spectral images are established on the basis of the characteristic peak intensities of SERS nanotags (MCSP-MBA, red; MCAM-TFMBA, blue; ErbB3-DTNB, green; LNGFR-MPY, yellow). (D) EV phenotypes defined by the relative expression levels of four biomarkers are extracted from the average signal spectra of false-color SERS spectral images. EV phenotypes are unique to each EV subpopulation. By analyzing EV samples before, during, and after BRAF inhibitor treatment, the phenotypic evolution can be tracked to provide information on treatment responses and early signs of drug resistance.

Fig 4: p75NTR knockdown reduces PM-induced brain injury. Ad-shp75NTR-mediated knockdown of p75NTR. One week after virus infusion, all rats were inoculated with S. pneumoniae in the lateral ventricle. a, b p75NTR protein levels in the cortex and hippocampus were measured by Western blot analysis 24 h post-infection. c Representative images of the sections with inflammatory cells in the cavum subarachnoidale. Scale bar = 100 µm. d, e Western blot analysis of inflammation-related transcription factors in the cortex and hippocampus from rats treated with shp75NTR or shSCR at 24 h after PM induction. Data are presented as the mean ± SEM (n = 5 rats). *p < 0.05, **p < 0.01

Fig 5: Mapping of the expression of NGF and its receptors, TrkA and p75NTR, by histochemical analysis of the spinal cord tissue during the EAE course. a1–a5 Images of NGF expression in the white matter of the spinal cord among the groups of the EAE model and its representative graph. b1–b5 Images of NGF expression in the grey matter of the spinal cord among the groups of the EAE model and its representative graph. c1–c5 Images of TrkA expression in the white matter of the spinal cord among the groups of the EAE model and its graphical representation. d1–d5 Images of TrkA expression in the grey matter of the spinal cord among the groups of the EAE model and its graphical representation. e1–e5 Images of p75NTR expression in the white matter of the spinal cord among the groups of the EAE model and its representative graph. f1–f5 Images of p75NTR expression in the grey matter of the spinal cord among the groups of the EAE model and its representative graph. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Scale bar = 100 µm