Interstitial lung disease (ILD) comprises diverse chronic inflammatory and fibrotic disorders with poorly understood mechanisms and limited diagnostic biomarkers. Growing evidence implicates lipid metabolic reprogramming in ILD pathogenesis, yet integrated metabolomic-transcriptomic analyses remain scarce. We performed combined metabolomic and transcriptomic analysis using publicly available datasets. Plasma metabolite profiles of ILD and lobar pneumonia (LOB) patients were analyzed by NMR-based metabolomics. Multivariate analyses (PCA, PLS-DA, OPLS-DA) identified discriminatory metabolites. KEGG enrichment revealed associated pathways. Transcriptomic data from lung tissue were analyzed for differentially expressed genes, identifying 345 differentially expressed genes (|log2FC| > 0.585, adjusted p < 0.05), integrated with metabolomic data to identify shared pathways. ROC curves evaluated diagnostic performance of key metabolites. To validate the bioinformatic findings, we established a bleomycin (BLM)-induced ILD mouse model with or without high-cholesterol diet (HCD) intervention. RT-qPCR, Western blotting, H&E staining, and Masson's trichrome staining were performed to assess gene expression and histopathological changes in lung tissue. Metabolomic profiling showed clear separation between ILD and LOB samples, driven by alterations in triglyceride-rich lipoproteins, phospholipids, and cholesterol fractions. Seven metabolites were significantly increased in ILD (p < 0.05). Integrated multi-omics identified "lipid and atherosclerosis" as a key shared pathway, encompassing six differential genes (CD36, NFKBIA, PIK3R1, SELP, CCL2, VCAM1) and one differential metabolite (Cholesterol [HDL4]). ROC analysis showed a combined metabolite model achieved AUC of 0.810. Experimental validation confirmed SELP, CCL2, and VCAM1 were upregulated while NFKBIA was downregulated in BLM-treated mice. HCD further aggravated BLM-induced pulmonary fibrosis and markedly elevated the expression of inflammatory cytokines (TNF-α, IL-6, IL-1β) as well as key pathway proteins (SELP, CCL2, VCAM1). This integrated multi-omics analysis reveals a strong link between lipid dysregulation and ILD pathogenesis. Cholesterol fractions, triglycerides, and phospholipids may serve as potential non-invasive biomarkers for ILD, while the lipid and atherosclerosis pathway represents a promising target for therapeutic intervention. Animal experiments further validated that HCD exacerbates ILD via the lipid and atherosclerosis pathway, reinforcing the clinical relevance of cholesterol dysregulation in ILD progression. Our findings provide new insights into the metabolic mechanisms of ILD and establish a foundation for future diagnostic and therapeutic development.

Mayonnaise is a popular condiment, but its consumption is concerning, especially for people suffering from high blood lipid levels and overweight. In this study, we aimed to formulate reduced-fat and cholesterol-free (without egg) mayonnaise samples with chia seed mucilage (0.5%-1%) and whey protein (5%-10%) similar to full-fat mayonnaise in organoleptic and technical properties. Interestingly, the light mayonnaise samples showed higher emulsion stability (98.91%-99.08% vs. 57.42%), viscosity (8185-9657 vs. 8610 cp), consistency (0.73 vs. 0.65), firmness (147.8-198.2 vs. 110), and adhesiveness (1991-2170 vs. 1850 mJ), with more than a 22% calorie reduction compared to the control. The higher viscosity, along with the increased moisture content (27.95%-29.56% vs. 15.21%), resulted in a better sensory score by the panelists (4.45-4.55 vs. 3.85), likely due to the perceived creaminess and freshness. The better rheology attributes were related to the electrostatic interactions in protein-polysaccharide complex which provide similar to or better texture than the control. The new formula showed lower brightness (due to higher light scattering), yellowness (due to lower oil content), and redness (due to egg yolk removal) compared to the control in the Hunter Lab assay. Interestingly, a lower peroxide value (3.3-3.74 vs. 5.86 meq O2/kg) was observed in the egg-free and reduced-fat samples. Furthermore, slightly more fungal growth was seen in the new formula due to its higher moisture content. However, the fungal growth remained below the maximum permitted level of 102 CFU/g until the end of storage. In conclusion, the new formula containing 5% whey protein and 0.5%-1% chia mucilage can be used as light mayonnaise with appropriate technical and health promotion properties.

We aimed to examine the association between insulin resistance (IR) and target organ damage (TOD) in patients with hypertension. Three indices of IR (Triglyceride-Glucose index: TyG; triglyceride-to-HDL ratio: TG/HDL-C; Metabolic Score for Insulin Resistance: METS-IR) were examined for their association with TOD in 614 newly diagnosed patients with hypertension. Left ventricular mass index (LVMI), the intima-media thickness of the common carotid artery (IMT-CCA) and estimated Glomerular Filtration Rate (eGFR) were used as indices of cardiac, artery and renal damage. Receiver Operating Characteristic (ROC) analysis performed to estimate optimal cut-off for each index, while simple and multiple logistic regression models were applied to examine the indices as binary predictors of organ damage. Linear and non-linear associations were examined with continuous variables using linear regression and restricted cubic splines (RCS) models. After adjusting for confounders, logistic regression showed that high TG/HDL-C (OR:1.50, 95%CI:1.03-2.18) and METS-IR (OR:2.17, 95%CI:1.50-3.13) were associated with increased risk of left ventricular hypertrophy, while only high METS-IR was associated with increased risk of carotid plaque (OR:2.07, 95%CI:1.17-3.68) and only high TG/HDL-C was associated with renal damage (OR:2.33, 95%CI:1.02-5.36). Adjusted linear regression showed that none of the indices were significantly associated with LVMI. However, all indices were associated with CCA-IMT (p < 0.05), but none with eGFR (p > 0.05). Adjusted RCS models showed a significant non-linear association between TyG and CCA-IMT (p for non-linearity = 0.009). In conclusion, IR biomarkers are of clinical value in newly diagnosed patients with hypertension.

Biallelic isoleucyl-tRNA synthetase 1 (IARS1) variants are associated with an IARS1-related phenotype characterized by growth retardation, intellectual disability, muscular hypotonia, infantile hepatopathy, and interstitial lung disease. This rare, early-onset disorder is often lethal. Although several variants have been identified in recent years, their pathogenicity and underlying molecular mechanisms remain poorly understood. In this study, we generated Iars1Y148C/R444* compound heterozygous mice, which exhibited pulmonary alveolar proteinosis - like lesions, growth retardation, and muscular hypotonia. Lipid metabolomic profiling of these mice revealed dysregulation of cholesterol metabolism pathways. Furthermore, the Iars1 mutation increased surfactant deposition in alveolar macrophages by impairing lysosomal degradation and disrupting lysosome-autophagosome fusion. We also found that partial loss of IARS1 activity interfered with the post-translational processing of cathepsin Z by inhibiting its ubiquitin-mediated degradation. Importantly, exogenous expression of cathepsin Z improved surfactant clearance in macrophages with partial loss of Iars1 activity. Collectively, our findings demonstrate that partial loss of IARS1 activity induces lysosomal dysfunction in alveolar macrophages and promotes pulmonary surfactant accumulation in the alveoli, thereby contributing to the development of pulmonary alveolar proteinosis.

Atherosclerosis is the main pathological basis of cardiovascular disease and urgently requires more effective and targeted therapies. Here, we present a cholesterol-modulated macrophage membrane-mimetic nanoplatform for rapamycin delivery, in which β-cyclodextrin is employed to selectively deplete cholesterol from donor cell membranes. Cholesterol depletion significantly improves nanoparticle uptake by inflammatory macrophages, potentially through enhanced membrane fluidity and preserved key receptor-ligand interactions. In vitro, the cholesterol-depleted nanomedicines promote foam cell cholesterol efflux and suppress pro-inflammatory cytokine secretion, with therapeutic efficacy increasing as membrane cholesterol content decreases. In vivo, the resulting "slimming" membrane-coated nanoparticles exhibit enhanced immune evasion, prolonged systemic circulation, and improved plaque targeting, while maintaining excellent biosafety. In atherosclerotic mice, treatment with these nanoparticles reduces plaque area and lipid accumulation while increasing collagen content in a membrane cholesterol-dependent manner, indicating therapeutic effects and enhanced plaque stability. Notably, these benefits are achieved without altering systemic lipid levels, suggesting a primarily lesion-localized mechanism of action. Collectively, this study demonstrates that the "slimming" membrane-mimetic nanoplatform offers a promising approach for precise, inflammation-targeted therapy of atherosclerosis and may be extended to other chronic inflammatory vascular disorders.