Background: Microplastics (MPs) and cadmium (Cd) are widespread environmental pollutants posing significant health risks, but their combined hepatotoxic effects and underlying mechanisms remain poorly understood. Methods: Using in vivo and in vitro co-exposure models, we systematically investigated the impact of MPs on Cd-induced hepatotoxicity. The study assessed hepatic injury, oxidative stress, and inflammatory responses through transcriptomic analysis, histopathological examination, immunofluorescence, and quantitative real-time PCR. Pharmacological inhibition of endoplasmic reticulum stress with 4-phenylbutyric acid and selective blockade of IRE1α with MKC3946 were employed to dissect the signaling pathway. Results: Co-exposure to MPs and Cd significantly aggravated Cd-induced hepatic pathological damage, inflammation, and oxidative stress. Transcriptomic profiling revealed marked activation of the endoplasmic reticulum stress pathway and upregulation of pyroptosis-associated genes. Mechanistically, endoplasmic reticulum stress triggered pyroptosis via the IRE1α/TXNIP/NLRP3 signaling axis. Notably, inhibition of endoplasmic reticulum stress with 4-phenylbutyric acid, or selective blockade of IRE1α with MKC3946, effectively attenuated TXNIP/NLRP3 activation and the downstream pyroptotic response. Conclusions: MPs intensify Cd-induced hepatotoxicity by activating the IRE1α/TXNIP/NLRP3 pathway, leading to endoplasmic reticulum stress-driven pyroptosis. These findings provide a mechanistic framework for understanding the combined toxicity of microplastics and heavy metals, with important implications for environmental health risk assessment in animals and humans.

Tooth wear is a major health and welfare issue for captive giant pandas (Ailuropoda melanoleuca), but quantitative data on wear progression across different tooth types and chewing behaviors are lacking. In this study, a two-dimensional computer simulation (Processing, Java-based) was developed to model wear of giant panda canine, second premolar, and second molar teeth under two bamboo-chewing orientations (horizontal vs. vertical). Species-specific enamel hardness (344 HV), bite forces (canine: 1030 N; premolar: 1142 N; molar: 2005 N), and a stochastic chewing cycle were incorporated into the simulation. The results showed that canine wear was faster during horizontal chewing (45.68 pixel layers/100 cycles) than during vertical chewing (36.76 pixel layers/100 cycles), while premolar and molar wear were faster during vertical chewing (34.24 and 51.52 pixel layers/100 cycles, respectively) compared to horizontal chewing (10.28 and 39.40 pixel layers/100 cycles). Molars exhibited the highest overall wear rate. The predicted functional lifespan was estimated to be 47~55 years for canines; 19~34 years for premolars; and 23~29 years for molars. This study provides the first quantitative, cycle-by-cycle wear progression model for giant panda teeth.

Microplastics (MPs) can adsorb and transport heavy metals, but their influence on cadmium (Cd)-induced hepatotoxicity in mammals remains unclear. Forty-eight male Kunming mice were assigned to control, Cd, MP, and Cd + MP groups and exposed by oral gavage for 42 days. Growth performance, liver injury, oxidative stress, and inflammation were assessed, and transcriptomic and metabolomic analyses were integrated with qPCR, mitochondrial DNA (mtDNA) copy number, and ATP measurements. Compared with Cd alone, combined exposure resulted in greater reductions in body weight gain, the liver index, and antioxidant enzyme activities, together with more severe hepatic lesions and higher levels of liver injury markers and inflammatory cytokines. Co-exposure also induced broader transcriptional and metabolic disturbances than Cd alone. Integrated omics analyses converged on the dysregulation of AMPK–FOXO signaling and related energy metabolic processes. qPCR confirmed more pronounced alterations in pathway-related genes after co-exposure, while reductions in mtDNA copy number and ATP content indicated aggravated mitochondrial dysfunction and impaired energy metabolism. Collectively, these results demonstrate that MPs exacerbate Cd-induced liver injury and suggest that disruption of AMPK–FOXO-associated energy metabolism is a key molecular feature underlying the enhanced hepatotoxicity observed under combined exposure.