Luye Pharma (China)

The utilization of Baijiu distiller's grains (BDGs), commonly used as a feed ingredient, remains limited due to challenges such as elevated levels of anti-nutritional factors (ANFs), high fiber content, and low protein concentration. Microbial fermentation has been recognized as an effective strategy to improve the nutritional quality of feed substrates. However, its efficacy is highly dependent on process parameters such as temperature. Despite its significance, the effect of temperature on the interaction between microbial communities and the physicochemical properties of BDGs during fermentation remains poorly understood. To address this gap, BDGs were fermented using Bacillus subtilis, Candida utilis, and Geotrichum candidum under varying temperatures. Comprehensive physicochemical analyses combined with high-throughput sequencing of microorganisms were performed to investigate the dynamic changes in both fermentation products and microbial kinetics. The results revealed that the optimal fermentation performance was achieved at 34°C. At this temperature, compared to untreated BDGs, phytic acid, tannin, and crude fiber levels were significantly reduced by 65.18%, 30.69%, and 15.34% respectively, whereas crude protein and amino acid contents increased by 15.5% and 7.13%. Furthermore, temperature was found to play a crucial role in shaping the dynamics of microbial community succession, with Stenotrophomonas, Bacillus, Pseudomonas, Paenibacillus, and Pediococcus identified as key bacterial genera influencing the nutritional composition of BDGs. Temperature variations drive shifts in microbial communities and consequently affect the nutritional quality during fermentation. These findings provide valuable experimental evidence and support the potential of fermented BDGs as a viable protein ingredient substitute in animal feed.

In metabolic dysfunction-associated steatotic liver disease (MASLD), exosome-encapsulated miRNAs mediate intercellular signaling pathways that drive dysregulated lipid metabolism, inflammation, and fibrosis. However, the cell-of-origin specificity and disease-modifying mechanisms of these microRNAs (miRNAs) remain poorly characterized. Here, we aimed to define the exosomal miRNA signatures originating from key MASLD microenvironments (liver and adipose tissue) and evaluate their causal roles in promoting hepatic steatosis and cellular damage. Plasma exosomes from patients with MASLD (n = 6) and healthy control volunteers (n = 6) were isolated, characterized, and profiled for miRNA expression. Subjects were enrolled from the Department of Gastroenterology at the First Affiliated Hospital of Shandong First Medical University. Oleic acid (OA)-treated HepG2 and Bel-7404 cells were used to model MASLD in vitro. Identified miRNAs were transfected into HepG2 and Bel-7404 cells to assess effects on triglyceride (TG) accumulation, reactive oxygen species (ROS), and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activity. Protein levels of key metabolic regulators-acyl-coenzyme A synthetase short-chain family member 2 (ACSS2), matrix metalloproteinase-12 (MMP12), fatty acid synthase (FASN), stearoyl-CoA desaturase-1 (SCD1), and sterol regulatory element-binding transcription factor 1 (SREBF1)-were evaluated using enzyme-linked immunosorbent assay, Oil Red O staining, Western blotting, and quantitative real-time polymerase chain reaction. Engineered exosomes-overexpressing miRNA mimics were used to validate target interactions. Exosomal miR-122-3p and miR-3614-5p were significantly upregulated in patients with MASLD compared with healthy volunteers (P <0.05). Transfection of miR-122-3p-but not miR-3614-5p-into OA-treated HepG2 and Bel-7404 cells led to increased TG accumulation and ROS production, suppressed AMPK activity, and upregulated the expression of lipid metabolism genes ACSS2, FASN, SCD1, and SREBF1. These phenotypic effects were replicated using engineered exosomes-overexpressing miR-122-3p, with successful cellular uptake confirmed by luciferase assay. Mechanistically, fibroblast growth factor receptor 4 (FGFR4) was identified as a direct target of exosomal miR-122-3p: treatment with miR-122-3p-enriched exosomes reduced FGFR4 expression in wild-type hepatocytes but not in FGFR4-mutant models, confirming target specificity. Exosomal miR-122-3p drives the progression of nonalcoholic fatty liver disease by promoting lipid accumulation, oxidative stress, and suppression of AMPK signaling, primarily through targeting FGFR4. These results identify the miR-122-3p/FGFR4 axis as a potential therapeutic target for treating this condition.

Overexpression of cyclooxygenase-2 (COX-2) and associated reactive species, specifically hypochlorous acid (HClO) and peroxynitrite (ONOO⁻), in the tumor microenvironment are critical hallmarks for early cancer diagnosis. In this work, we designed and synthesized two fluorescent probes,S1andS2, for the targeted imaging of HClO and ONOO⁻, respectively. Both probes integrate a celecoxib ligand for COX-2 targeting with a naphthalimide fluorophore. The probes operate via a photoinduced electron transfer (PET) mechanism, producing a distinct fluorescence turn-on response with excellent linearity against analyte concentration (R2 = 0.9902forS1with HClO;R2 = 0.9897forS2with ONOO⁻). This mechanism was theoretically validated through DFT calculations. In vitro cellular imaging demonstrated that both probes exhibit low cytotoxicity and achieve superior tumor cell selectivity, showing significantly higher fluorescence intensity in COX-2 overexpressing MCF-7 cancer cells than in normal HUVEC cells. The molecular basis for targeting was rigorously investigated using molecular docking and 100ns molecular dynamics simulations. MM/PBSA calculations revealed favorable binding enthalpies for bothS1(-80.05 ± 7.19kcal/mol) andS2(-83.76 ± 3.88kcal/mol) with COX-2, confirming stable and specific complex formation. This integrated experimental and computational strategy yields highly sensitive and selective probes, positioningS1andS2as promising tools for studying cancer-related biomarkers at the cellular level.

Fresh wet tuber-based vermicelli is prized for its soft and elastic texture, which relies on high moisture content. However, this leads to water exudation and texture hardening during storage, limiting industrial application. This study employed immersion as a moisture regulation strategy, analyzing changes in water distribution, hardness, microstructure, and reheating quality during immersion and storage. Results indicated that moisture content increased rapidly within the first 20 min and stabilized after 40 min, accompanied by a significant reduction in hardness and gelatinization enthalpy. Microstructural analysis revealed that an immersion time of 30-40 min (62-63% moisture) was optimal, preserving suitable hardness and structural integrity. During storage, these samples achieved stable water distribution by day 35. In contrast, samples immersed for 50-60 min (64-65% moisture) showed markedly increased free water and notable structural damage. Reheating tests further confirmed that immersion for 30-40 min helped maintain moderate hardness post-storage. Therefore, controlling immersion to 30-40 min effectively balances texture, storage stability, and reheating quality.