Background/Objectives: Ejiao, a macromolecular protein complex derived from donkey hide, is a traditional Chinese medicine with clinically demonstrated efficacy against ulcerative colitis (UC). Due to its large molecular size and poor absorbability, its therapeutic effects are presumed to depend on gut microbiota. We hypothesized that specific gut bacteria capable of degrading Ejiao might also mediate its biological functions. Methods: To test this hypothesis, a systematic investigation was conducted by integrating culturomics, proteomics, metabolomics, 16S rRNA gene amplicon high-throughput sequencing, and animal disease models. Results: A total of 134 human gut bacterial strains capable of utilizing Ejiao as a nutrient source were isolated. Among them, Ligilactobacillus salivarius D3-8 exhibited the strongest growth in Ejiao-based medium. Genomic analysis identified 63 protease/peptidase genes, and peptidomic profiling confirmed its degradation activity, which released 50 novel peptides. Notably, administration of L. salivarius D3-8 alone significantly alleviated dextran sodium sulfate (DSS)-induced colitis, concurrently increasing the abundance of beneficial bacterium Dubosiella newyorkensis and elevating the anti-inflammatory metabolite indole-3-carbinol via upregulated tryptophan metabolism. Conclusions: Our findings identify L. salivarius D3-8 as both a dedicated Ejiao-degrader and a protective probiotic against colitis. This work provides direct evidence that gut bacteria can utilize Ejiao and proposes a potential novel mechanistic framework in which the biological effects of Ejiao may be mediated through its interaction with specific, functionally potent degraders such as L. salivarius D3-8.

Chronic UVB exposure drives extrinsic skin aging through oxidative stress, inflammation, and collagen degradation. Although oral collagen peptides are promising photoprotective agents, most preparations lack defined composition and mechanistic validation. Here, we characterized CCAP1, a type I collagen-derived oligopeptide fraction (~1.7 kDa; 94.69% collagen-related components) prepared from Colla Corii Asini by dual-enzymatic hydrolysis and membrane fractionation. In UVB-irradiated mice, oral CCAP1 (100 and 200 mg/kg/d, 28 days) markedly alleviated UVB-induced epidermal hyperplasia, restored skin hydration and dermal collagen types I/III/IV, and suppressed MMP1. Untargeted skin metabolomics nominated AMPK signaling as the central node; Western blotting confirmed that CCAP1 activated the AMPK/Nrf2 axis while suppressing NF-κB phosphorylation, with elevated SOD activity and reduced MDA content. In UVB-injured HaCaT keratinocytes, CCAP1 restored cell viability and reduced intracellular ROS, and both effects were abolished by the AMPK inhibitor Compound C, establishing AMPK as a functionally required mediator. Collectively, CCAP1 is a composition-defined, orally bioavailable collagen peptide fraction that attenuates UVB-induced photoaging via an AMPK-dependent Nrf2/NF-κB regulatory program.

Overexploitation of groundwater resources poses a critical challenge in major agricultural regions worldwide, yet how confined and unconfined aquifers respond differentially to governance interventions remains poorly understood. This study presents a comparative assessment of hydrochemical evolution and nitrate contamination dynamics in the Weishan Irrigation District, Shandong Province, China, contrasting pre-governance conditions (2011) with post-governance status (2022–2023) following comprehensive overexploitation control. By integrating hydrochemical characterization with stable isotope tracers (δ¹⁸O, δD, δ¹⁵N-NO₃⁻, δ¹⁸O-NO₃⁻) and Bayesian mixing models (MixSIAR), we reveal fundamentally contrasting aquifer responses to regulation. The unconfined aquifer exhibited continued degradation under persistent agricultural influence, characterized by elevated sodium, nitrate, and bicarbonate concentrations. In sharp contrast, the confined aquifer demonstrated substantial recovery, with major ion concentrations declining markedly, hydrochemical facies restored toward a pristine state, and overall water quality improving significantly to achieve full compliance with the highest-quality standards by 2023. These divergent trajectories indicate that regulatory interventions effectively restored aquitard barrier integrity, thereby shielding the confined aquifer from surface contamination, whereas the unconfined aquifer remained vulnerable to agricultural pollution. Isotope-constrained Bayesian modeling identified soil organic nitrogen, chemical fertilizers, manure/sewage, and industrial wastewater as dominant nitrate sources, with isotopic evidence confirming that the unconfined aquifer receives mixed recharge from Yellow River water and precipitation under contemporary contamination, while the confined aquifer maintains independent, pollution-free recharge. These findings demonstrate that overexploitation control can effectively rehabilitate confined aquifer systems by reestablishing natural hydrogeological barriers, but unconfined aquifers require targeted agricultural pollution mitigation. The contrasting responses highlight the necessity of aquifer-specific management strategies in irrigation-dependent regions, advancing theoretical understanding of how regulatory measures differentially affect multi-layered groundwater systems and providing a scientific basis for precision groundwater governance.