Amb a 1-Specific IgE in Heart Failure: A Translational Framework for Seasonal Risk, Endotyping, and Patient-Centered Management.

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most prevalent chronic liver disorder globally, characterized by excessive lipid accumulation within hepatocytes accompanied by oxidative stress, chronic low-grade inflammation, and gut-liver axis dysfunction (). Without timely intervention, it may progress to non-alcoholic steatohepatitis, cirrhosis (, ), or even hepatocellular carcinoma (). The pathogenesis of NAFLD is closely linked to energy excess and ectopic lipid deposition (). Key drivers of disease progression include gut microbiota dysbiosis, intestinal mucosal barrier damage, and endotoxemia induced by long-term high-sugar, high-fat diets. High-fat diets disrupt gut microbiota homeostasis, reducing the abundance of beneficial bacteria producing short-chain fatty acids (SCFAs) while promoting the proliferation of pro-inflammatory bacteria (, ). This damages intestinal tight junctions, allowing toxic metabolites like lipopolysaccharide (LPS) to enter the bloodstream. Currently, no specific drugs for NAFLD exist clinically. Bioactive compounds derived from natural foods, however, have gained attention in NAFLD prevention and treatment research due to their high safety profile and multi-target regulatory advantages (, ). Mulberry fruit, a widely cultivated fruit with both medicinal and edible uses, is rich in active components such as polysaccharides, flavonoids, and anthocyanins (). Among these, mulberry fruit polysaccharides (MP), as water-soluble heteropolysaccharides, have been demonstrated to possess antioxidant, anti-inflammatory, and glucose-lipid metabolism-regulating bioactivities (). Ai employed an enzyme-assisted extraction (EAE) method using pectinase and pectin lyas, achieving yields of 7.7 and 8.3%, respectively (). Li utilized a high-shear-assisted hot water extraction method, yielding 9.95% (). Recent studies indicate that MP can alleviate metabolic diseases by reshaping gut microbiota structure, increasing SCFA production, and repairing the intestinal mucosal barrier (). However, systematic research on MP’s role in improving NAFLD and its mechanism of exerting hepatoprotective effects through gut microbiota regulation remains scarce. Its potential as a functional ingredient in NAFLD prevention and treatment warrants further exploration. The extraction efficiency and quality of MP directly determine its biological activity and application value. Traditional hot water extraction suffers from low yield, time-consuming processes, high energy consumption, and susceptibility to polysaccharide structural degradation (, ). Enzyme-Assisted Ultrasound Extraction (EAUE) is a highly efficient, eco-friendly extraction technique. It employs enzymatic digestion to disrupt mulberry fruit cell walls and utilizes ultrasound to accelerate mass transfer, significantly enhancing polysaccharide extraction yield and activity (, ). Response Surface Methodology (RSM) efficiently optimizes extraction processes involving multiple interacting factors, providing scientific basis for MP’s large-scale production (). Meanwhile, Genetic Algorithm-optimized Back Propagation (GA-BP) neural networks, with their strong ability to model high-order nonlinear relationships and avoid local optima, offer a complementary approach to RSM for refining extraction parameter prediction and global optimization (, ). To date, no studies have reported the use of RSM and GA-BP to optimize the EAUE process for MP or investigated its potential to improve NAFLD through gut microbiota regulation.