Grape ripe rot, a globally significant fungal disease caused by Colletotrichum spp., severely threatens grape yield and quality. This study systematically investigated the pathogen species, biological characteristics, and fungicide sensitivity through multiregional sampling (2022 to 2024, covering seven districts across four provinces), morphological analysis, molecular identification, and EC50 assays. The results revealed that 125 isolates were obtained and classified into five species, namely, Colletotrichum aenigma, C. conoides, C. viniferum, C. gloeosporioides, and C. fructicola, based on morphological traits and multilocus phylogenetic analysis (ITS, CHS, GAPDH, TUB2, and ACT). Among these, C. viniferum was identified as the dominant species responsible for grape ripe rot, with an isolation rate of 74.4%, and C. conoides represents a new species isolated from grape ripe rot in China. Biological assays revealed that the optimal temperature and pH for mycelial growth on PDA were 25 to 30°C and pH 5 to 6, respectively, and the pathogenicity significantly increased at 30°C following wound inoculation. Fungicide sensitivity tests indicated that prochloraz exhibited the highest inhibitory efficacy against all the species (EC50 ≤ 0.03 mg/liter). This study elucidates the geographical distribution patterns of Colletotrichum spp. in China and their differential responses to fungicides, providing critical theoretical and practical insights for optimizing integrated management strategies against grape ripe rot.
Introduction and Objective: Bofanglutide is a bi-weekly GLP-1 analog being developed for the treatment of type 2 diabetes and overweight or obesity. This trial evaluated the pharmacokinetic (PK) and safety profile of bofanglutide in participants with varying degrees of renal impairment compared with those with normal renal function. Methods: Participants were enrolled and classified into four groups based on eGFR: normal renal function, mild, moderate, and severe renal impairment (n=8 per group). Each participant received a single subcutaneous dose of 3 mg bofanglutide. Plasma concentrations were measured up to 840 h post-dose. Primary endpoints included maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC0-last) and infinity (AUC0-inf). Results: Bofanglutide exposure was comparable across renal impairment groups and the normal renal function group. The geometric least-squares mean ratios for Cmax, AUC0-last, and AUC0-inf were all close to 1, with the upper bounds of the 90% confidence intervals slightly exceeding the predefined 1.25 equivalence limit (up to 1.28) in five comparisons. No serious adverse events related to bofanglutide were reported, and most adverse events were gastrointestinal-related. Conclusion: There were no clinically relevant effects of renal impairment on bofanglutide PK. Dose adjustment is not required for participants with renal impairment. Disclosure W. Zhao: None. H. Shen: None. J. Pan: None. L. Shao: None. J. Zhao: None. M. Ding: None. T. Xie: None. Y. Li: None. J. Wang: None. X. Yang: None. H. Wu: None. W. Chen: None.
Hepatic fibrosis progression involves complex multicellular crosstalk, highlighting the critical need to identify key therapeutic targets. In this study, we identify insulin-like growth factor binding protein 6 (IGFBP6) as a marker specifically enriched in hepatic stellate cells (HSCs) and upregulated in viral hepatitis-associated fibrosis. Using thioacetamide (TAA)-induced mouse models and transforming growth factor-β (TGF-β)-stimulated cell models, we demonstrate the pro-fibrotic role of IGFBP6. Through network pharmacology screening, pantothenic acid (PA) is identified as a potent compound targeting IGFBP6. PA administration significantly reduces collagen deposition, attenuates HSCs' activation, and decreases hepatic fibrosis-related markers. Notably, PA maintains efficacy in mouse models with established fibrosis. Mechanistically, PA directly interacts with IGFBP6, inducing ubiquitin-dependent degradation and inhibiting TGF-β/SMADs signaling. This study identifies IGFBP6 as a driver of hepatic fibrosis and validates PA as a potent therapeutic agent. Therefore, targeting IGFBP6 with PA offers a potential clinical treatment strategy for hepatic fibrosis.
