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Early melatonin treatment ameliorates social and cognitive deficits in VPA-induced ASD rats. ( A ) Schematic of three-chamber social interaction. ( B ) Representative <t>heatmaps</t> depicting social patterns (E: empty cage; S1: stranger 1). ( C ) Sniffing time towards S1, comparative time allocation between S1 and empty chamber, and chamber time-derived preference index. ( D ) Representative heatmaps depicting social novelty patterns (S1: stranger 1; S2: stranger 2). ( E ) Sniffing time allocation between S1 and S2, chamber occupancy duration comparisons, and dual-modality preference index. ( F ) Behavioral protocols for novel object recognition (NOR). ( G ) Heatmaps delineating exploration patterns (“F”: familiar columnar object; “N”: novel cubic object). ( H ) Discrimination time between familiar and novel objects, preference indices (N vs. F), and total ambulatory distance traversed. ( I ) Schematic of the open field test (OFT) and (J) Representative movement tracks. ( K ) Locomotor patterns, including total distance traversed, center zone duration, and central compartment entries. ( L ) Experimental protocols for Morris water maze. ( M ) Heatmaps delineating the 4-day acquisition phase, complemented by escape latency dynamics evolution. ( N ) Trajectory heatmap illustrating probe trial patterns on day 6, with target quadrant duration and crossings. Biological replication was demonstrated through 12 independent samples per experimental cohort, and data are presented as mean ± standard error. * P < 0.05, ** P < 0.01, *** P < 0.001. CON, control; VPA, sodium valproate; MTV, melatonin + VPA
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Identification of oxidative stress-responsive genes FOS and JUN in human adrenocortical cells A . Gene set variation analysis (GSVA) of hallmark pathways in APAs and adjacent tissues based on integrated datasets ( GSE60042 , GSE64957 , and GSE156931 ). B . Oxidative stress-related pathways identified by gene set enrichment analysis (GSEA) of APAs versus adjacent tissues, based on integrated datasets ( GSE60042 , GSE64957 , and GSE156931 ). C and D . Volcano plots of RNA sequencing data showing differentially expressed genes (DEGs) in HAC15 adrenocortical cells treated with 4 μM RSL-3 (oxidative stressor via GPX4 inhibition and lipid peroxidation) or 250 μM H 2 O 2 (direct oxidant) for 3h vs. DMSO-treated controls (n = 3 biological replicates). Dashed lines: adjusted p < 0.05; |log2 fold change| > 1. E . Venn diagram identifying overlapping DEGs between RSL-3/H 2 O 2 -treated HAC15 cells and spatial <t>transcriptomics</t> (ST) data from aldosterone-producing adenomas (APAs, n = 7) vs. paired adjacent adrenal cortex. F . Gene Ontology (GO) enrichment of overlapping genes in Panel B, highlighting oxidative stress and steroidogenic pathways. NES, normalized enrichment score; FDR, false discovery rate; NS, not significant.
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Identification of oxidative stress-responsive genes FOS and JUN in human adrenocortical cells A . Gene set variation analysis (GSVA) of hallmark pathways in APAs and adjacent tissues based on integrated datasets ( GSE60042 , GSE64957 , and GSE156931 ). B . Oxidative stress-related pathways identified by gene set enrichment analysis (GSEA) of APAs versus adjacent tissues, based on integrated datasets ( GSE60042 , GSE64957 , and GSE156931 ). C and D . Volcano plots of RNA sequencing data showing differentially expressed genes (DEGs) in HAC15 adrenocortical cells treated with 4 μM RSL-3 (oxidative stressor via GPX4 inhibition and lipid peroxidation) or 250 μM H 2 O 2 (direct oxidant) for 3h vs. DMSO-treated controls (n = 3 biological replicates). Dashed lines: adjusted p < 0.05; |log2 fold change| > 1. E . Venn diagram identifying overlapping DEGs between RSL-3/H 2 O 2 -treated HAC15 cells and spatial <t>transcriptomics</t> (ST) data from aldosterone-producing adenomas (APAs, n = 7) vs. paired adjacent adrenal cortex. F . Gene Ontology (GO) enrichment of overlapping genes in Panel B, highlighting oxidative stress and steroidogenic pathways. NES, normalized enrichment score; FDR, false discovery rate; NS, not significant.
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Image Search Results


Early melatonin treatment ameliorates social and cognitive deficits in VPA-induced ASD rats. ( A ) Schematic of three-chamber social interaction. ( B ) Representative heatmaps depicting social patterns (E: empty cage; S1: stranger 1). ( C ) Sniffing time towards S1, comparative time allocation between S1 and empty chamber, and chamber time-derived preference index. ( D ) Representative heatmaps depicting social novelty patterns (S1: stranger 1; S2: stranger 2). ( E ) Sniffing time allocation between S1 and S2, chamber occupancy duration comparisons, and dual-modality preference index. ( F ) Behavioral protocols for novel object recognition (NOR). ( G ) Heatmaps delineating exploration patterns (“F”: familiar columnar object; “N”: novel cubic object). ( H ) Discrimination time between familiar and novel objects, preference indices (N vs. F), and total ambulatory distance traversed. ( I ) Schematic of the open field test (OFT) and (J) Representative movement tracks. ( K ) Locomotor patterns, including total distance traversed, center zone duration, and central compartment entries. ( L ) Experimental protocols for Morris water maze. ( M ) Heatmaps delineating the 4-day acquisition phase, complemented by escape latency dynamics evolution. ( N ) Trajectory heatmap illustrating probe trial patterns on day 6, with target quadrant duration and crossings. Biological replication was demonstrated through 12 independent samples per experimental cohort, and data are presented as mean ± standard error. * P < 0.05, ** P < 0.01, *** P < 0.001. CON, control; VPA, sodium valproate; MTV, melatonin + VPA

Journal: Cellular and Molecular Life Sciences: CMLS

Article Title: Melatonin ameliorates autistic-like behaviors by restoring gut microbiota-derived tryptophan metabolites

doi: 10.1007/s00018-026-06163-8

Figure Lengend Snippet: Early melatonin treatment ameliorates social and cognitive deficits in VPA-induced ASD rats. ( A ) Schematic of three-chamber social interaction. ( B ) Representative heatmaps depicting social patterns (E: empty cage; S1: stranger 1). ( C ) Sniffing time towards S1, comparative time allocation between S1 and empty chamber, and chamber time-derived preference index. ( D ) Representative heatmaps depicting social novelty patterns (S1: stranger 1; S2: stranger 2). ( E ) Sniffing time allocation between S1 and S2, chamber occupancy duration comparisons, and dual-modality preference index. ( F ) Behavioral protocols for novel object recognition (NOR). ( G ) Heatmaps delineating exploration patterns (“F”: familiar columnar object; “N”: novel cubic object). ( H ) Discrimination time between familiar and novel objects, preference indices (N vs. F), and total ambulatory distance traversed. ( I ) Schematic of the open field test (OFT) and (J) Representative movement tracks. ( K ) Locomotor patterns, including total distance traversed, center zone duration, and central compartment entries. ( L ) Experimental protocols for Morris water maze. ( M ) Heatmaps delineating the 4-day acquisition phase, complemented by escape latency dynamics evolution. ( N ) Trajectory heatmap illustrating probe trial patterns on day 6, with target quadrant duration and crossings. Biological replication was demonstrated through 12 independent samples per experimental cohort, and data are presented as mean ± standard error. * P < 0.05, ** P < 0.01, *** P < 0.001. CON, control; VPA, sodium valproate; MTV, melatonin + VPA

Article Snippet: Taxon-resolved heatmaps (Fig. E) delineated VPA-associated blooms of Erysipelotrichia ( log2FC = + 2.03, vs. CON, FDR = 0.032) and Clostridia ( log2FC = + 2.01, vs. CON, FDR = 0.028), alongside depletion of Ruminococcaceae ( log2FC = − 4.13, vs. CON, FDR < 0.001), Bacteroides ( log2FC = − 1.50, vs. CON, FDR = 0.028), Lachnospiraceae ( log2FC = − 1.53, vs. CON, FDR = 0.012), and Butyricimonas ( log2FC = − 1.32, vs. CON, FDR = 0.011), all counteracted by melatonin (e.g., Clostridia log2FC = -1.39, Ruminococcaceae log2FC = + 1.14, Bacteroides log2FC = + 1.22).

Techniques: Derivative Assay, Control

Identification of oxidative stress-responsive genes FOS and JUN in human adrenocortical cells A . Gene set variation analysis (GSVA) of hallmark pathways in APAs and adjacent tissues based on integrated datasets ( GSE60042 , GSE64957 , and GSE156931 ). B . Oxidative stress-related pathways identified by gene set enrichment analysis (GSEA) of APAs versus adjacent tissues, based on integrated datasets ( GSE60042 , GSE64957 , and GSE156931 ). C and D . Volcano plots of RNA sequencing data showing differentially expressed genes (DEGs) in HAC15 adrenocortical cells treated with 4 μM RSL-3 (oxidative stressor via GPX4 inhibition and lipid peroxidation) or 250 μM H 2 O 2 (direct oxidant) for 3h vs. DMSO-treated controls (n = 3 biological replicates). Dashed lines: adjusted p < 0.05; |log2 fold change| > 1. E . Venn diagram identifying overlapping DEGs between RSL-3/H 2 O 2 -treated HAC15 cells and spatial transcriptomics (ST) data from aldosterone-producing adenomas (APAs, n = 7) vs. paired adjacent adrenal cortex. F . Gene Ontology (GO) enrichment of overlapping genes in Panel B, highlighting oxidative stress and steroidogenic pathways. NES, normalized enrichment score; FDR, false discovery rate; NS, not significant.

Journal: Redox Biology

Article Title: FOS and JUN regulate oxidative stress and steroidogenesis in human aldosterone-producing adenomas

doi: 10.1016/j.redox.2025.103982

Figure Lengend Snippet: Identification of oxidative stress-responsive genes FOS and JUN in human adrenocortical cells A . Gene set variation analysis (GSVA) of hallmark pathways in APAs and adjacent tissues based on integrated datasets ( GSE60042 , GSE64957 , and GSE156931 ). B . Oxidative stress-related pathways identified by gene set enrichment analysis (GSEA) of APAs versus adjacent tissues, based on integrated datasets ( GSE60042 , GSE64957 , and GSE156931 ). C and D . Volcano plots of RNA sequencing data showing differentially expressed genes (DEGs) in HAC15 adrenocortical cells treated with 4 μM RSL-3 (oxidative stressor via GPX4 inhibition and lipid peroxidation) or 250 μM H 2 O 2 (direct oxidant) for 3h vs. DMSO-treated controls (n = 3 biological replicates). Dashed lines: adjusted p < 0.05; |log2 fold change| > 1. E . Venn diagram identifying overlapping DEGs between RSL-3/H 2 O 2 -treated HAC15 cells and spatial transcriptomics (ST) data from aldosterone-producing adenomas (APAs, n = 7) vs. paired adjacent adrenal cortex. F . Gene Ontology (GO) enrichment of overlapping genes in Panel B, highlighting oxidative stress and steroidogenic pathways. NES, normalized enrichment score; FDR, false discovery rate; NS, not significant.

Article Snippet: B . Spatial transcriptomics heatmaps of FOS, JUN, CYP11B2, and KCNJ5 across APA-adrenal cortex pairs (n = 7).

Techniques: RNA Sequencing, Inhibition

Validation of FOS and JUN expression and oxidative stress activity in APAs and paired adjacent adrenal tissues A. Boxplots showing the expression levels of CYP11B2 , FOS , and JUN across APAs and paired adjacent adrenal tissues, integrating data from GSE60042 , GSE64957 , and GSE156931 . B . Spatial transcriptomics heatmaps of FOS, JUN, CYP11B2, and KCNJ5 across APA-adrenal cortex pairs (n = 7). C . Representative Spatial transcriptomics expression maps of CYP11B2 , FOS , and JUN in KCNJ5 -mutant ( KCNJ5 MUT ) vs. wild-type APAs ( KCNJ5 WT ) and adjacent tissues. D . Integrated UMAP embedding and boxplot showing the distribution of oxidative stress scores in seven APAs and their paired adjacent tissues. E . Representative spatial feature plots of oxidative stress scores projected onto H&E-stained APA and paired adjacent tissue sections. F and G . Gene expression analysis of FOS and JUN in APAs and paired adjacent adrenal tissues from 10 KCNJ5 -mutant and 10 wild-type APA patients. *P < 0.05, **P < 0.01, ***P < 0.001.

Journal: Redox Biology

Article Title: FOS and JUN regulate oxidative stress and steroidogenesis in human aldosterone-producing adenomas

doi: 10.1016/j.redox.2025.103982

Figure Lengend Snippet: Validation of FOS and JUN expression and oxidative stress activity in APAs and paired adjacent adrenal tissues A. Boxplots showing the expression levels of CYP11B2 , FOS , and JUN across APAs and paired adjacent adrenal tissues, integrating data from GSE60042 , GSE64957 , and GSE156931 . B . Spatial transcriptomics heatmaps of FOS, JUN, CYP11B2, and KCNJ5 across APA-adrenal cortex pairs (n = 7). C . Representative Spatial transcriptomics expression maps of CYP11B2 , FOS , and JUN in KCNJ5 -mutant ( KCNJ5 MUT ) vs. wild-type APAs ( KCNJ5 WT ) and adjacent tissues. D . Integrated UMAP embedding and boxplot showing the distribution of oxidative stress scores in seven APAs and their paired adjacent tissues. E . Representative spatial feature plots of oxidative stress scores projected onto H&E-stained APA and paired adjacent tissue sections. F and G . Gene expression analysis of FOS and JUN in APAs and paired adjacent adrenal tissues from 10 KCNJ5 -mutant and 10 wild-type APA patients. *P < 0.05, **P < 0.01, ***P < 0.001.

Article Snippet: B . Spatial transcriptomics heatmaps of FOS, JUN, CYP11B2, and KCNJ5 across APA-adrenal cortex pairs (n = 7).

Techniques: Biomarker Discovery, Expressing, Activity Assay, Mutagenesis, Staining, Gene Expression