IntroductionHigh-altitude pulmonary edema (HAPE) is a severe complication of rapid exposure to high-altitude hypoxia, but its molecular mechanisms remain incompletely understood. This study aimed to characterize lung proteomic alterations in HAPE and identify candidate proteins associated with its pathophysiological processes.MethodsMale Wistar rats were randomly allocated to control and HAPE model groups (n = 20/group). The HAPE model was induced by exposure to simulated altitude (7,000 m) under hypobaric hypoxia combined with treadmill exercise for 48 h. Pulmonary edema was evaluated by lung wet-to-dry (W/D) weight ratio, bronchoalveolar lavage fluid (BALF) protein concentration, inflammatory cytokine measurement, and histopathological examination. Lung proteomic profiling was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), followed by GO, KEGG, and PPI network analyses. Candidate proteins were further validated using Western blotting, immunohistochemistry, and RT-qPCR.ResultsHAPE rats exhibited prominent pulmonary edema characterized by increased lung W/D ratios, elevated BALF protein leakage, enhanced production of inflammatory cytokines, and marked interstitial edema. Proteomic analysis identified 5,250 proteins, among which 288 DEPs were detected, including 160 upregulated and 128 downregulated proteins. Functional enrichment analysis revealed that these DEPs were primarily associated with immune and inflammatory responses, extracellular matrix organization, glycerophospholipid metabolism, phosphatidylinositol signaling, and cell adhesion pathways. Multi-level validation confirmed increased expression of MMP9, MMP8, Serpine1 (PAI-1), MPO, HK3, and MAP3K6 at both protein and transcriptional levels. PPI network analysis indicated that MMP9 represented a central hub protein with the highest interaction connectivity.ConclusionThis study provides a comprehensive proteomic profile of HAPE lung tissue and highlights the involvement of neutrophil-associated inflammation, extracellular matrix remodeling, fibrinolytic regulation, and metabolic adaptation in HAPE progression. The identified proteins, particularly MMP9, may serve as potential biomarkers and candidates for further mechanistic investigation.
ObjectiveTo explore the feasibility of constructing a prediction model for vascular recanalization in cervical artery dissection (CeAD) based on high-resolution vessel wall imaging (HR-VWI) radiomics features combined with clinical risk factors.MethodsA total of 110 patients with CeAD were retrospectively enrolled. Clinical baseline data and HR-VWI images were collected. The Radiomics Intelligent Analysis Software (RIAS) was used for image preprocessing, ROI segmentation, and radiomics feature extraction and screening. Combined with clinical factors, multiple prediction models including random forest, gradient boosting decision tree, and logistic regression (LR) were constructed. Model performance was evaluated using AUC, calibration, Brier score, and decision curve analysis (DCA).ResultsA total of 11 features (6 radiomics + 5 clinical) were selected through a multi-step workflow (ICC filtering → t-test → LASSO → backward AIC selection). The LR model achieved the best performance, with an AUC of 0.757 (95% CI: 0.531–0.983) and average precision of 0.95 in the independent test set. The model showed acceptable calibration (Brier score = 0.129; intercept = 0.913; slope = 0.896) and favorable clinical utility by DCA. Hyperuricemia, hyperlipidemia, smoking, headache, stenosis degree, and specific radiomics features were independent predictors of recanalization. Wavelet-HLH_glszm_Small Area High Gray Level Emphasis and wavelet-LHH_glcm_SumEntropy showed the most significant predictive effects. However, given the limited sample size and few events, these results should be interpreted as preliminary.ConclusionThe combined LR model shows moderate discriminative ability for predicting vascular recanalization in CeAD. As a proof-of-concept study, it provides preliminary reference for prognostic assessment, while external validation in larger multi-center cohorts is warranted before clinical implementation.
Ricinine, a plant-derived alkaloid, exhibits potent insecticidal activity; however, the molecular mechanisms underlying its differential toxicity among insect species remain largely elusive. This study employed integrated metabolomics and transcriptomics to investigate the adaptation strategies of three lepidopteran insects with distinct host plant ranges—Bombyx mori (B. mori), Spodoptera litura (S. litura), and Samia cynthia ricini (S. cynthia ricini) to ricinine. The three species exhibited sharply divergent toxicological responses: ricinine caused acute lethality in B. mori, severely inhibited the growth of S. litura, but induced no significant adverse effects in S. cynthia ricini. Untargeted metabolomics and transcriptomics revealed that ricinine treatment provoked the most severe metabolic disruption in B. mori, followed by S. litura, while the impact on S. cynthia ricini was minimal. Moreover, the species showed largely species-specific pathway-enrichment patterns, indicating fundamentally different adaptive mechanisms. Integrated analysis identified decreased normalized relative abundances of key metabolites (e.g., adenine, flavin mononucleotide) and significant downregulation of genes associated with NAD/NADH-linked energy metabolism (e.g., nicotinate phosphoribosyltransferase (NPH), malate dehydrogenase (MDH), acetyl-CoA synthetase (ACS)) in susceptible species. These molecular changes were associated with β-nicotinamide adenine dinucleotide (β-NAD) metabolism and oxidative phosphorylation-related pathways. Exogenous β-NAD supplementation alleviated ricinine toxicity in S. litura, supporting the involvement of β-NAD-related metabolism. In contrast, S. cynthia ricini, despite accumulating the highest levels of ricinine, displayed only marginal metabolic and transcriptional perturbations, signifying the evolution of robust innate tolerance mechanisms. Finally, the combined treatment with ricinine and nucleopolyhedrovirus (NPV) produced greater growth inhibition and mortality in S. litura than either treatment alone, which was associated with the marked inhibition of cytochrome P450 detoxification enzyme activity. These findings elucidate evolutionary strategies insects employ to cope with plant alkaloids and provide a molecular basis for developing novel, selective pest control agents.
