New Hope Liuhe (China)

CRISPR technology has profoundly transformed both genome editing and the next generation of nucleic acid detection. In this study, we characterized a Cas12a ortholog, Gs12-9 (EsoCas12a), which recognizes a broad PAM motif (NYYN, where Y denotes C or T) and maintains robust cis- and trans-cleavage activity across a wide temperature range (16–60 ℃), outperforming established Cas12a variants such as LbCas12a. Leveraging Gs12-9, we established a rapid, highly sensitive, and temperature-tolerant nucleic acid detection platform that enables precise genotyping without stringent thermal control. By integrating recombinase polymerase amplification (RPA) with CRISPR/Gs12-9-mediated detection, we accurately discriminated myostatin (MSTN) knockout pigs from wild-type individuals, achieving a detection limit of 40 copies per reaction with 100% accuracy. While the MSTN knockout (KO) pig served as a proof-of-concept model in this work, the versatility of Gs12-9 supports its broader application in CRISPR-based diagnostics, including pathogen screening and genetic variant detection.

Hyperuricemia (HUA), a metabolic disorder associated with inflammatory and gut microbiota dysbiosis, demands effective intestinal-targeted therapies. Herein, a novel intestinal-targeted delivery system was designed based on quercetin nanorods coated Lactobacillus paracasei MC1 encapsulated within manganese-crosslinked Mesona chinensis polysaccharide microgels (MCPM-QUE-MC1). The MC1 strain, isolated from the traditional fermented food "Jiangshui", exhibits potent uric acid-degrading activity. The quercetin nanocoating enhances mucosal adhesion and antioxidative capacity through a prebiotic nanointerface, while manganese ions impart nanozyme-like catalytic activity, scavenging hydrogen peroxide (H2O2) and modulating the intestinal microenvironment. This synergistic assembly protects probiotics from gastric acidity and promotes intestinal colonization, as validated in mouse and pig models. In HUA mice, oral administration of MCPM-QUE-MC1 significantly reduced serum uric acid levels to 101.83 ± 6.88µmol L-1, increased MC1 abundance by 8.37-fold, improved renal function, suppressed inflammatory cytokines, and restored gut microbial homeostasis by notably enriching short-chain fatty acid-producing bacteria. Mechanistically, the therapeutic effect arises from enhanced uric acid degradation, inhibition of hepatic xanthine oxidase, reduction of intestinal permeability, and systemic endotoxemia. Overall, this study establishes a promising probiotic-polyphenol prebiotic-microgel composite platform for HUA alleviation, offering a new insight into gut microbiota-targeted therapies for metabolic diseases.

The microstructure and properties of gray cast iron are closely related. For gray cast iron with pearlite matrix, adjusting graphite characteristics to improve casting performance is the most effective method. It is of great significance to analyze the relationship between graphite characteristics and properties of gray cast iron for the development of gray cast iron with high tensile strength and high thermal conductivity. Regression models of graphite characteristics and properties of gray cast iron was established, including tensile strength and thermal conductivity. By calculating the coefficients of the two models, the different effects of graphite characteristics on the properties of gray cast iron were obtained. By testing the regression models, the feasibility of the regression analysis method in the performance analysis of gray iron castings was determined. According to the analysis results, some improvement schemes are put forward to improve the performance of castings.