Wuyang Huang

Emerging evidence suggests that inflammaging contributes significantly to male reproductive senescence and oxidative stress, yet safe, non‐invasive interventions that act on the upstream regulatory circuitry of the spermatogonial niche remain elusive. Here we investigated the restorative potential of a high‐anthocyanin Blueberry Anthocyanin Extract (BAE) in a middle‐aged murine model, integrating physiological monitoring, histopathology, and paired testicular transcriptomics and metabolomics to resolve the molecular logic of BAE‐mediated rejuvenation. BAE prevented age‐associated physiological deterioration without detectable toxicity, reversed seminiferous tubule degeneration, and restored sperm kinematics. Mechanistically, multi‐omics integration converged on three coordinated regulatory modules rather than a single pathway. First, BAE engaged adenylyl cyclase–cAMP–PKA signaling to license canonical Wnt /β‐catenin activity, driving spermatogonial proliferation (PLZF, PCNA, c‐Myc , Ccnd1 ). Second, BAE suppressed ROS‐dependent IKK/NF‐κBNF (p65) activation, lowering testicular and systemic TNF‐α and IL‐6 and resolving the pro‐inflammatory niche. Third, BAE reprogrammed the methionine cycle and elevated NAD ⁺ , activating the AMPK–SIRT1–PGC1α axis while restraining leucine‐ and methionine‐driven mTORC1 signaling, thereby coupling redox balance to cell‐cycle re‐entry. Collectively, these data identify BAE as a dual‐action, immunometabolic modulator that simultaneously reactivates the spermatogonial proliferative program and dismantles the inflammaging circuit. By concurrently targeting the cAMP–Wnt, ROS–NF‐κB, and methionine–NAD ⁺ axes, high‐anthocyanin BAE offers a mechanism‐based functional‐food strategy to delay male reproductive aging and preserve fertility.

With the increasing prevalence of diabetic retinopathy (DR), there is an urgent need for interventions offering both metabolic and ocular benefits. This initial clinical exploration investigated the intervention effects of blueberry anthocyanins in elderly type 2 diabetic patients over six months. Supplementation with blueberry anthocyanin extract (BAE, 400 mg/day) showed favorable changes in ocular functions, with improved visual acuity (as reflected by negative ΔlogMAR values), reduced intraocular pressure (IOP∼8%, P < 0.05), and restored retinal structural integrity, which was evidenced by decreased macular edema and retinal thickness via optical coherence tomography (OCT) imaging. Furthermore, patients reported a notable alleviation of visual fatigue symptom, such as eye soreness (P < 0.05) and lacrimation (P < 0.01). Correlating with the observed ocular protection, BAE also improved systemic metabolic parameters such as fasting blood glucose and glycated hemoglobin (HbA1c) (P < 0.01), insulin resistance (triglyceride-glucose index), and inflammation markers (such as neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio). These findings should be interpreted as preliminary associations, as concurrent medications were not systematically controlled. Nonetheless, they tentatively indicated the dual action of blueberry anthocyanins for simultaneously targeting metabolic dysregulation and DR-associated visual impairment, providing clinical evidence for its development as a promising functional food used in adjunct therapy for diabetic patients.

Luteolin is a plant-derived flavone widely distributed in edible plants and medicinal herbs, attracting attention due to its antioxidant and anti-inflammatory properties. However, efficient biosynthesis of specific luteolin glycosides, particularly luteolin-5-O-xyloside, remains challenging due to low donor specificity, limited catalytic efficiency of natural glycosyltransferases, and the high cost of UDP-xylose (UDP-Xyl). In this study, a novel 5-O-xylosyltransferase and an engineered Escherichia coli whole-cell system were developed for luteolin-5-O-xyloside production. Structure-guided engineering identified Thr142 as a key residue for UDP-sugar recognition. The mutant ZmDo-T142 V showed enhanced catalytic efficiency toward UDP-Xyl (k_cat/K_m = 1302.8 s^–1 M^–1), 2.3-fold higher than the wild type. A de novo UDP-Xyl biosynthetic pathway was constructed, enabling intracellular cofactor regeneration. Under optimized conditions, a titer of 4451 mg/L with an 87% conversion rate was achieved.

Blueberry anthocyanins may modulate the gut microbiota and improve glucose metabolism in T2DM.

The intestinal barrier undergoes profound changes with age, impacting local immunity and systemic health, yet the mechanisms coordinating immune and microbial dynamics across the lifespan remain incompletely understood. Toll-like receptor 4 (TLR4) serves as a key mediator of host–microbiota interactions. This study investigated age-related changes in barrier function and the role of TLR4 using C57BL/6J and TLR4 knockout (TLR4^−/−) mice across key developmental stages: pups (postnatal day 9), adults (2–4 months), middle-aged (7–9 months), and old (16–19 months). Through a multi-layered approach integrating histology, microbiome profiling, short-chain fatty acid (SCFA) analysis, cytokine quantification, ex vivo functional assays, and transcriptomics, we identified a multi-phase process of intestinal remodeling. Pup-P9 mice exhibited immature colonic structure, a simple microbiota dominated by Firmicutes and Proteobacteria, and undetectable acetic acid level. Adults reached peak diversity and SCFA concentrations, marked by a rise in Bacteroidota and the emergence of Akkermansia. In middle and old age, pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) increased, Bacteroidota declined while Firmicutes, Actinobacteria, and Turicibacter expanded, and aged colons showed blunted ex vivo responses to IL-1β. This age-associated functional decline phenotype was absent in TLR4^−/− mice, supporting the involvement of TLR4 signaling. Transcriptomics further revealed biphasic PI3K/Akt activation in both pups-P9 and old mice. Together, these findings suggest a systemic rewiring of host metabolic and immune signaling pathways in response to an aging microbiota, highlighting this dynamic, lifespan-wide microbiota–host signaling axis as a potential intervention target.

Hulless barley grass (HBG) is rich in bioactive compounds such as phenolics, polysaccharides, and lipids, and consequently possesses antioxidant, anti‐inflammatory, and anti‐tumor properties. However, which components contribute to its potential palliative effect on acute ulcerative colitis (AUC) is unknown. In this study, phenolics, polysaccharides, and lipids were extracted separately from HBG, and their antioxidant activities and effects on AUC in vivo were investigated. Compared to the polysaccharide/lipid extracts, phenolic extracts (HBGPE) had much higher antioxidant capacity, with 1,1‐diphenyl‐2‐picrylhydrazyl radical (DPPH·) scavenging capacity of 1.34 ± 0.02 mmol Trolox/100 g. The HBGPE also significantly decreased the body weight loss and colonic condition of dextran sodium sulfate (DSS)‐induced AUC mice. The strong anti‐inflammatory effects of HBGPE led to a significant reduction in the degree of inflammatory cell infiltration, crypt structure disruption, and mucosal damage, and down‐regulated the mRNA expression of tumor necrosis factor ( Tnfα ), interleukin‐6 ( Il6 ), and Il1b . In addition, HBGPE could reduce intestinal flora disorders. Both polysaccharide and lipid extracts led to little reduction in the colon inflammatory condition. This study confirmed that HBG extracts could inhibit inflammatory response, oxidative stress, and gut microbial imbalance, especially HBGPE, which indicated that HBG may have potential for application in dietary prevention of AUC.

Astaxanthin (AST) has been widely studied for its potential antioxidant and anti‐inflammatory effects; however, its application is limited by poor water solubility and low bioavailability. To address this, zein and chito‐oligosaccharides composite nanoparticles (ZCNps) were constructed using antisolvent precipitation for efficient AST delivery. At a zein to COS mass ratio of 10:1, AST‐loaded ZCNps (ZCANps) achieved an encapsulation efficiency of 81.23% and drug loading of 4.18 mg/g. Structural characterization confirmed that AST was successfully encapsulated in an amorphous state, stabilized by hydrophobic interactions and hydrogen bonding. ZCANps demonstrated stability under a wide range of conditions, including pH levels of 2–8, NaCl concentrations of up to 50 mmol/L, temperatures of up to 80°C, and storage for 8 weeks at 4°C. Additionally, ZCANps provided 62% UV‐light protection for AST. Compared to free AST, the encapsulated form showed significantly enhanced antioxidant activity and bioaccessibility. These results highlight ZCNps as a delivery system for improving the stability, bioavailability, and functional properties of AST in food applications.