Journal: Bioactive Materials

Article Title: A foam cell-targeted lipophagy restoration strategy stabilizes vulnerable atherosclerotic plaques

doi: 10.1016/j.bioactmat.2026.02.041

Figure Lengend Snippet: Schematic of the anti-atherosclerotic mechanism of OPN-HMCN@MLT. ( A ) The study commenced with the synthesis of mesoporous carbon nanospheres (MCN) functionalized with an OPN-binding peptide and hyaluronic acid to construct the OPN-HMCN nanoplatform. The OPN-binding peptide was designed to recognize OPN enriched in the extracellular matrix and on the surface of foam cells, thereby enabling selective accumulation in OPN-rich pathological regions. Following OPN recognition, OPN-HMCN@MLT undergoes CD44-dependent endocytosis. Melatonin (MLT), a lipid autophagy–promoting agent, was subsequently encapsulated within the nanocarrier to form OPN-HMCN@MLT. Firstly, the released MLT can bind to and upregulate the expression of PPARα and PPARγ, which then promote the expression of downstream genes (ABCA1, ABCG1, ACOX-1, and CTP1A) and trigger the lipophagy. ( B ) Subsequently, its lipophagy-enhancing effects, including ABCA1/G1-mediated cholesterol efflux and CTP1A/ACOX-1-mediated mitochondrial fatty acid oxidation, were studied to confirm the reversal of foam cell formation. ( C ) These effects eventually promote foam cells to reverse into macrophages. Abbreviations: MCN, mesoporous carbon nanoparticle; OPN, osteopontin; MLT, melatonin; LDL, low-density lipoprotein; ox-LDL, oxidized low-density lipoprotein; PA, Photoacoustic.

Article Snippet: To block nonspecific binding, membranes were incubated with 5% skim milk for 1 h. Thereafter, membranes were incubated overnight at 4 °C with primary antibodies against ABCA1, ABCG1, ACOX1, CPT1A, LC3 (ab192890, 1:2000, abcam), LAMP1 (84658-5-RR, 1:8000, Proteintech), PPARα (66826-1-Ig, 1:3000, Proteintech), PPARγ (66936-1-Ig, 1:10000, Proteintech), P62 (18420-1-AP, 1:10000, Proteintech), MCAD (55210-1-AP, 1:3000, Proteintech), LCAD (17526-1-AP, 1:10000, Proteintech), tubulin (80762-1-RR, 1:10000, Proteintech), GAPDH (60004-1-Ig, 1:50000, Proteintech), and β-actin (66009-1-Ig, 1:20000, Proteintech).

Techniques: Binding Assay, Construct, Expressing

Journal: bioRxiv

Article Title: BAT protects against hepatic oxidative stress by remodeling the circulating metabolome

doi: 10.64898/2026.05.12.722834

Figure Lengend Snippet: A. Schematic overview of the strategy we used to study how BAT affects systemic metabolite and lipid profiles in vivo. Step 1, generating the BAT ablation mouse model ( Ucp1 -Cre; Pparg flox/flox , herein BAT-mice) and littermate control ( Pparg flox/flox , herein BAT+ mice); Step 2, collecting the serum samples from these mice under acute cold (6 °C for 1 and 3 h), chronic cold (6 °C for 3 days), and thermoneutrality (28 °C for 3 days), with ad libitum feeding; Step 3, quantifying the dynamic profiles of metabolites and lipids across different temperature conditions by LC-MS; Step 4, selecting the metabolites and lipids altered by BAT ablation and clustering them based on their profile similarity. The altered molecules included those accumulated in BAT-ablated mice, which might be cleared by BAT, and those elevated in mice with intact BAT, which might be derived from BAT. N = 8 for BAT-ablated mice and N = 10 for littermate controls. B-C. Correlation clustering of circulating metabolites ( B ) and lipids ( C ) altered by BAT ablation. An unpaired t-test was used to determine the significance of each circulating metabolite or lipid between BAT+ and BAT- mice under each temperature condition. A total of 206 metabolites and 249 lipids with p < 0.05 in at least one condition were included for correlation clustering. Clustering analysis was performed using Mfuzz package in R software, and pairwise Pearson correlation coefficients between molecules were used to generate heatmaps. Table S1 lists the p values and fold changes between the BAT+ and BAT- groups for these metabolites and lipids. N = 8 for BAT-ablated mice and N = 10 for littermate controls. BAT- > BAT+, molecules were accumulated in BAT-ablated mice. BAT+ > BAT-, molecules were elevated in littermate controls with intact BAT. BAT-, BAT-ablated mice; BAT+, littermate controls. C-1h, 6 °C for 1 hour; C-3h, 6 °C for 3 hours; C-3d, 6 °C for 3 days; TN-3d, 28 °C for 3 days. Mice were provided with ad libitum access to food and water throughout the experiment. AMP, adenosine monophosphate; γ-Glu-Glu, glutamyl-glutamic acid; Pyro-Glu, pyroglutamic acid, SAM, S-adenosylmethionine; GSSG, oxidized glutathione; GSH, reduced glutathione; GABA, γ-aminobutyric acid; TG, triglyceride; DG, diglyceride; PE, phosphatidylethanolamine; PC, phosphatidylcholine; SM, sphingomyelin; Cer, ceramide; EtherPE, ether-linked phosphatidylethanolamine; EtherPC, ether-linked phosphatidylcholine; CE, cholesterol ester; LPE, lysophosphatidylethanolamine; LPC, lysophosphatidylcholine; LNAPE, N-acyl-lysophosphatidylethanolamine; HexCer, hexosylceramide; CAR, acylcarnitine; OHFA, hydroxy fatty acid; DiOHFA, dihydroxy fatty acid; DHA, docosahexaenoic acid. D-E. Representative quantitative profiles of known BAT-regulated metabolites ( D ) and lipids ( E ). Relative units: quantitative peak areas from LC-MS normalized to the average. N = 8 for BAT-ablated mice and N = 10 for littermate controls. Statistic: unpaired t-test, ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001. Ad libitum conditions. C-1h, 6 °C for 1 hour; C-3h, 6 °C for 3 hours; C-3d, 6 °C for 3 days; TN-3d, 28 °C for 3 days. F. Representative quantitative profiles of metabolites and lipids newly identified as BAT-regulated in this study. Relative units: quantitative peak areas from LC-MS normalized to the average. N = 8 for BAT-ablated mice and N = 10 for littermate controls. Statistic: unpaired t-test, ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001. Ad libitum conditions. C-1h, 6 °C for 1 hour; C-3h, 6 °C for 3 hours; C-3d, 6 °C for 3 days; TN-3d, 28 °C for 3 days. G. Relative quantitative profiles of indicated fatty acids and 12, 13-diHOME in serum from BAT-ablated mice and littermate controls. Relative units: quantitative peak areas from LC-MS normalized to the average. N = 8 for BAT-ablated mice and N = 10 for littermate controls. Statistic: unpaired t-test. ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001. Ad libitum conditions. C-1h, 6 °C for 1 hour; C-3h, 6 °C for 3 hours; C-3d, 6 °C for 3 days; TN-3d, 28 °C for 3 days.

Article Snippet: PPARg flox/flox (Stock No. 004584), and Ucp1 -Cre (Stock No. 024670) mice were obtained from the Jackson Laboratory.

Techniques: In Vivo, Control, Liquid Chromatography with Mass Spectroscopy, Derivative Assay, Software