Background: Angelicae Dahuricae Radix (ADR) is used as both a traditional Chinese medicine and a food ingredient in China and East Asian countries. ADR is generally sun-dried post-harvest but is sometimes sulfur-fumigated to prevent decay and rot. Although there are some studies on the effect of sulfur fumigation on ADR, they are not comprehensive. Methods: This study used HPLC fingerprinting, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), in vitro anti-inflammatory assays, and metabolite analysis in blood based on UPLC-MS/MS to assess the impact of sulfur fumigation on the active ingredients of ADR. Results: There were significant decreases in specific coumarins and amino acids, particularly byakangelicol, oxypeucedanin, L-proline, and L-arginine, following sulfur fumigation. Among the 185 metabolites in blood, there were 30 different compounds, and oxypeucedanin was the most obvious component to decrease after sulfur fumigation. ADR showed anti-inflammatory activity regardless of sulfur fumigation. However, the effects on the production of cytokines in LPS-induced RAW264.7 cells were different. Conclusions: Chemometric analysis and in vitro anti-inflammatory studies suggested that byakangelicol and oxypeucedanin could serve as potential quality markers for identifying sulfur-fumigated ADR. These findings provide a chemical basis for comprehensive safety and functional evaluations of sulfur-fumigated ADR, supporting further research in this field.

A rapid classification method was developed for the malignant and benign thyroid nodules with ultrasound guided-fine needle aspiration biopsy (FNAB) samples. With probe electrospray ionization mass spectrometry, the mass-scan data of FNAB samples were used as datasets for machine learning. The patients were marked as malignant (98 patients), benign (110 patients) or undetermined (42 patients) by experienced doctors in terms of ultrasound, the B-Raf (BRAF) gene, and cytopathology inspections. Pairwise coupling was performed on 163 ions to generate 3630 ion ratios as new features for classifier training. With the new features, the performance of the multilayer perception (MLP) classifier is much better than that with the 163 ions as features directly. After training, the accuracy of the MLP classifier is as high as 92.0%. The accuracy of the single-blind test is 82.4%, which proved the good generalization ability of the MLP classifier. The overall concordance is 73.0% between prediction and six-month follow-up for patients in the undetermined group. Especially, the classifier showed high accuracy for the undetermined patients with suspicious for papillary carcinoma diagnosis (90.9%). In summary, the machine learning method based on FNAB samples has potential for real clinical applications.

The distribution of environmental pollutants and their associated metabolic perturbations within tissues is essential for understanding toxicological mechanisms. However, whether hexafluoropropylene oxide tetramer acid (HFPO-TeA), an emerging alternative to legacy PFASs, induces spatially heterogeneous metabolic disruption in aquatic organisms remains unclear. Here, adult zebrafish were exposed to HFPO-TeA to investigate hepatic phospholipid spatial distribution and gut microbial dysfunction. Matrix-assisted laser desorption/ionization quadrupole time-of-flight mass spectrometry imaging (MALDI-QTOF-MSI) revealed marked spatial perturbation of 14 putatively annotated lipid features, mainly including phosphatidylcholines (PCs), phosphatidylglycerols (PGs), phosphatidylethanolamines (PEs), diacylglycerols (DAGs), and phosphatidylinositols (PIs). Notably, these phospholipids exhibited region-specific down- or up-regulation, suggesting localized phospholipid remodeling within hepatic microdomains rather than spatially uniform disruption. These spatially resolved phospholipid alterations provide mechanistically relevant evidence for HFPO-TeA-induced hepatotoxicity and phospholipids with annotated spatial perturbation as candidate lipid-feature biomarkers for future validation. Moreover, HFPO-TeA reduced gut microbial diversity and reshaped the intestinal community, including decreases in Firmicutes at the phylum level and increases in Shewanella and Aeromonas at the genus level, taxa linked to lipid metabolism and phospholipid remodeling. Functional prediction further indicated suppressed microbial metabolic potential, with relative enrichment of genetic information processing and cellular maintenance functions. Together, the microbiome shift toward phospholipid remodeling-associated taxa and the spatially resolved hepatic perturbation of specific phospholipids provide convergent evidence that targeted phospholipid metabolic remodeling within tissue microregions may underlie HFPO-TeA-induced metabolic toxicity. This study provides a spatially resolved perspective on the multilevel metabolic toxicity of HFPO-TeA and demonstrates significant potential for revealing the health impacts of emerging PFAS alternatives.