Fig 2: PUFA ω-3 alleviates sodium nitrite exposure-induced cerebral cortical tissue damage in fetal rats via the NRF1/HMOX1 pathway.(A) TNF and IL-1B concentrations were detected by ELISA, n = 3 rats/group. (B-C) The mRNA and protein expression levels of Tnf, Nos2, and Il1b were detected by qRT-PCR and western blot, n = 3 rats/group. Original blots are presented in S2A Fig. (D) Expression levels of SOX2, ENO2, and TUBB3 in the brain cortical tissue of each group were detected by IF, n = 3 rats/group. (E) IOD data statistics of SOX2, ENO2, and TUBB3 expression in the brain cortical tissue of each group were analyzed by Image-Pro-Plus, n = 3 rats/group. (F-H) Nrf1 and Hmox1 mRNA and protein expression levels were analyzed by qRT-PCR and western blot, n = 3 rats/group. Original blots are presented in S2B Fig. *P < 0.05. IF, immunofluorescence; IL-1B, interleukin-1 beta; IOD, integrated optical density; qRT-PCR, quantitative real-time PCR; TNF, tumor necrosis factor.

Fig 3: The effect of F. necrophorum on apoptosis and inflammatory factors of macrophages was detected by RT-qPCR. Bax (A), Bcl-2 (B), cyto-c (C), AIF (D), caspase-3 (E), caspase-8 (F), caspase-12 (G), caspase-9 (H), TNF- α (I), IL-1 β (J) and IL-6 (K) gene expression with F. necrophorum stimulation (MOIs of 0 and 100) from 0 to 6 h (n = 3). ***P<0.001, ns, not significant.

Fig 4: The inflammation level of liver in CCl4-induced ALF mice and the angiogenesis in grafts. (A–C) The TNF-a, IL-6, and DHE staining images of liver tissues and quantitative analysis of mean fluorescence intensity (MFI). Scale bar: 200 µm. (D–I) The mRNA expression levels of TNFA, IL-6, COX2, Pro-IL 1, INOS, and IL 10. (J) Immunofluorescence staining images of CD31 in the liver tissue sections of “fiber/dECM” and “Cu NZs@fiber/dECM” groups on day 1. (K) The immunofluorescence staining images of CD31 and HLA in the liver tissue sections of “HLCs/Cu NZs@fiber/dECM” group on day 1 and 3. Blue: DAPI-labelled cell nuclei; Red: Cy3-labelled CD31, ROS-reacted DHE; Green: Alexa Fluor 488-labelled TNF-a, IL-6, HLA. Scale bar: 100 µm. All data are presented as mean ± SD, n = 3. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 versus control, ns means no significance versus control, #P < 0.05, ##P < 0.01 for Cu NZs@fiber/dECM and hADMSCs/Cu NZs@fiber/dECM versus HLCs/Cu NZs@fiber/dECM.

Fig 5: MNPs@PLX suppresses the pro‐inflammatory reaction by modulating MAOA in female Cntnap4+/− mice. A) Hierarchical clustering of differential metabolites among wild‐type (WT), Cntnap4+/− and Cntnap4+/− +MNPs@PLX mice. B) The expression levels of Dodecanoic acid, Pantothenic acid, and 5‐HIAA in the hippocampus from the metabonomic results. C) The expression levels of 5‐HIAA in the hippocampus were examined by ELISA. D) Schematic illustration of tryptophan metabolism to produce 5‐Hydroxyindoleacetic acid (5‐HIAA). MAOA (highlighted in red) catalyzes the last step. E) The mRNA expression level of Maoa in hippocampi of Cntnap4+/− mice treated with NPs@PLX, MNPs, or MNPs@PLX. n = 3 per group. F) Experimental design for clorgyline administration in Cntnap4+/− mice. G,H) The mRNA expression levels of Il‐1b, Il‐6, Tnfa, Ifng, Tgfb, Cx3cr1, Tmem119, and Csf1r in hippocampi of Cntnap4+/− mice treated with clorgyline. n = 3 per group. I,J) Representative blots and quantification showing MAOA, TMEM119, CX3CR1, CSF1R, IL‐1β, and TNF‐α expression in hippocampi of Cntnap4+/− mice treated with clorgyline. n = 3 per group. K) Immunofluorescence staining of Iba1‐positive cells in hippocampi of Cntnap4+/− mice treated with clorgyline. Scale bars, 40 µm. Magnified images are shown in the middle row, and skeletal diagrams of Iba1‐positive cells are shown in the bottom row. Scale bars, 10 µm. L) Quantification of endpoint voxels, branch length and volume of Iba1‐positive cells. n = 6−7. M) The mRNA expression level of Maoa in LPS‐treated cells with different concentrations of GABA (50, 100, 500, and 1000 µM). n = 3 per group. N) The mRNA expression levels of Il‐1b, Il‐6, and Tnfa in LPS‐treated cells with different concentrations of clorgyline (10, 50, and 100 µM). n = 3 per group. O,P) Representative blots and quantification showing TLR4, p‐NF‐κB, and NF‐κB expression in cells treated with LPS and/or 10 µM clorgyline. n = 3 per group. Q) Cellular supernatant levels of IL‐1β, IL‐6, and TNF‐α in cells treated with LPS and/or 10 µM clorgyline. n = 6 per group. Results are expressed as the mean ± SEM. ** p < 0.01, * p < 0.05 versus WT or control; ## p < 0.01, # p < 0.05 versus Cntnap4+/− + MNPs@PLX or Cntnap4+/− + clorgyline or LPS + clorgyline; && p < 0.01 versus Cntnap4+/− + NPs@PLX. Statistical significance was determined using one‐way ANOVA and Tukey's tests for post hoc comparisons.