Yuanxiang Jin

6PPD, as an antioxidant in tire rubber, constitutes an emerging pollutant together with nanoplastics (NPs) widely present in the environment. This study explored the potential combined toxicity risk of 6PPD and 50 nm polystyrene nanoplastics (PS-NPs) to aquatic ecosystems. The study found that the presence of PS-NPs altered the physicochemical behavior of 6PPD and was associated with reduced cardiac accumulation of 6PPD and its oxidation product 6PPD-Q. The experiment showed that 6PPD activated the p53 signaling pathway by upregulating the expression of GRK5, thereby inhibiting the expression of SLC7A11 and GPX4, leading to increased ROS, iron overload, lipid peroxidation, and mitochondrial damage in zebrafish heart and rat cardiomyocytes (H9C2), thereby triggering ferroptosis. After coexposure of PS-NPs and 6PPD, physicochemical interactions between PS-NPs and 6PPD altered the colloidal state and environmental behavior of the mixture, while the cardiac levels of both 6PPD and 6PPD-Q were reduced, accompanied by weakened ferroptosis-related responses. This study revealed the cardiotoxic mechanism of 6PPD and the mitigation effect of PS-NPs after coexposure, providing a basis for environmental pollution risk assessment.

Type 2 diabetes mellitus (T2DM), a systemic metabolic network disorder, demands multiorgan intervention to restore homeostasis, posing a major global health burden. Concurrent instant glycemic control and long‐term microbiota remodeling represent an urgent scientific challenge. Herein, an inulin (INU) and hyaluronic acid (HA) double network hydrogel (IHGel) is presented to co‐deliver Bifidobacterium longum (BL) and lactoferrin (LF)‑Zn‑epigallocatechin gallate (EGCG) ternary nanoparticles (LZE NPs). The obtained LZE/BL@IHGel as an oral composite platform exhibits acid‑induced protonation to generate pH responsive pore shrinkage in the stomach, which results in protective effects of BL and sustained release of LZE NPs. Furthermore, LZE NPs maintain stable free radical scavenging activity and α ‐glucosidase inhibitory activity via metal–polyphenol coordination assembly and enhance cellular uptake through protein incorporation, thereby alleviating intestinal oxidative stress and controlling postprandial glucose. In a murine model of T2DM, 6 weeks of daily oral LZE/BL@IHGel demonstrated spatiotemporal separation of acute glycemic control and long‑term microbiota modulation by ameliorating glucolipid metabolism and multi‑organ complications, restoring intestinal homeostasis. Collectively, this study offers a versatile oral delivery strategy to bridge immediate glycemic control with long‑term gut remodeling, providing a new avenue for complex metabolic disease intervention.

Per/polyfluoroalkyl substances (PFASs) have been confirmed to have negative health effects in animal models. As a novel alternative to legacy PFASs, sodium ρ-perfluorous nonenoxybenzenesulfonate (OBS) raises growing concerns over environmental exposure and biological toxicity. Herein, colitis models were constructed for exploring the toxicity of OBS in intestinal homeostasis during the recovery period. The results verified the gut toxicity of OBS, which increased serum interleukin-1β/6/17α/22 (IL-1β, IL-6, IL-17α, IL-22) levels, decreased colonic mucus secretion, and changed gut microbiota. During colitis recovery, no statistically significant difference was observed in colonic mucus secretion and related gene expression in dextran sulfate sodium-OBS (DSS-OBS) compared with the DSS; compared with the CON group, the unchanged mucus secretion and gene expression in DSS-OBS ghad still a statistically significant difference. It indicated that the intestinal barrier disruption did not worsen after the OBS exposure, but the recovery might be delayed. Moreover, OBS exposure significantly changed gut microbiota during the recovery period, suggesting that disrupted gut microbiota might be associated with the delay of OBS-mediated inhibition of intestinal barrier repair. Additionally, network toxicology analysis identified the action targets of OBS (including Nuclear Receptor Subfamily 1 Group I Member 2 (NR1I2), Solute Carrier Family 22 Member 5 (SLC22A5), Glutathione S-Transferase Pi 1 (GSTP1), etc.), which mediate gut microbiota disorder and intestinal barrier dysfunction, and serve as potential biomarkers for OBS-induced intestinal-related diseases. Collectively, OBS exhibits definitive gut toxicity. Although short-term OBS exposure did not exacerbate the progression of colitis, it delayed the recovery of intestinal function. Among, multiple target sites, coupled with the gut microbiota, commonly mediate the gut toxicity of OBS. It suggested that the potential health risks of OBS cannot be overlooked, and the relevant departments should strengthen the management and develop next-generation alternatives.

N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPDQ), the primary oxidative metabolite of rubber antioxidant N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD), is an emerging global contaminant with multiorgan toxicity and has been detected in human breast milk and urine. Its mammary toxicity and molecular mechanisms remain poorly defined. Here, we integrated network toxicology, transcriptomics, and in vivo/in vitro validation to investigate 6PPDQ triggered mammary toxicity during adolescent exposure in mice. Network toxicology screened core targets and identified the MAPK signaling pathway as a key regulatory axis. Adolescent 6PPDQ exposure decreased mammary gland weight and length, induced pathological lesions, inhibited epithelial proliferation, and disrupted apoptotic homeostasis. Further assays confirmed that 6PPDQ caused mitochondrial dysfunction, oxidative stress, and inflammation. Mechanistically, 6PPDQ mediated mammary injury through p38 MAPK cascade activation, and p38 inhibition alleviated such adverse effects. This study elucidates a distinct p38 MAPK-dependent mechanism driving 6PPDQ-related developmental mammary toxicity, advancing the mechanistic understanding of health risks posed by rubber-derived quinone contaminants.

A collaborative intervention strategy based on probiotics represents a promising therapeutic approach against inflammatory bowel disease (IBD). However, enhancing probiotic efficacy within the IBD microenvironment while minimizing side effects remains a critical challenge. Polygonatum polysaccharide (PP), a natural plant-derived bioactive polymer, has attracted significant attention due to its ability to regulate oxidative and inflammatory stress with a favorable safety profile. Herein, PP was incorporated into calcium-alginate microgels (Mgel), resulting in enhanced mechanical strength and thermal stability. Compared to conventional calcium-alginate microgels, the PP-loaded microgels exhibited improved performance in oral delivery. In addition, PP functions as a promising microenvironmental modulator, exhibiting broad-spectrum antioxidant, anti-inflammatory, and prebiotic properties. The microgel system provides a versatile platform for probiotic oral delivery, contributing to the reshaping of the IBD microenvironment by enhancing the efficacy of Clostridium butyricum JHP6 and increasing beneficial metabolite levels in colitis. Collectively, naturally derived polysaccharide-based microspheres encapsulating probiotics offer an effective strategy to modulate the IBD microenvironment and enhance probiotic efficacy, thereby representing a collaborative intervention approach for IBD.