Uric acid(UA)-lowering bioactive peptides have emerged as promising alternatives to synthetic drugs owing to their favorable safety profile,efficacy,and bioavailability.This study investigated the anti-hyperuricemic(H...Uric acid(UA)-lowering bioactive peptides have emerged as promising alternatives to synthetic drugs owing to their favorable safety profile,efficacy,and bioavailability.This study investigated the anti-hyperuricemic(HUA)mechanisms of xanthine oxidase(XOD)-inhibitory peptides derived from Harpadon nehereus hydrolysate(HNPH).Three potent uric acid(UA)-reducing peptides were identified:FLH(FH3),FGKF(FF4),and IWHHTF(IF6).These peptides altered the secondary structure of XOD and bind to it through hydrogen bonding and hydrophobic interactions,thereby inhibiting XOD catalytic activity.Compared with FH3 and IF6,FF4 showed the strongest XOD inhibitory activity after in vitro digestion and was selected for further in vivo experiments.FF4 reduced UA levels by inhibiting hepatic UA-synthesizing enzymes,upregulating UA transporter ABCG2,and downregulating GLUT9.It alleviated inflammation and oxidative stress in HUA mice livers/kidneys,reducing pathological damage and inflammatory infiltration.FF4 also mitigated UA-induced HK-2 cell damage by regulating ROS and NLRP3 inflammatory pathways.These findings support marine-derived peptides as novel HUA therapeutics,offering alternatives to conventional drugs.展开更多
针对现有保序加密(order-preserving encryption,OPE)方案中客户端与服务端多轮交互导致的较大通信开销问题,提出一种基于本地临时缓存表和自平衡二叉搜索树的保序加密方案。在数据插入阶段通过客户端临时缓存表对插入数据预处理确定初...针对现有保序加密(order-preserving encryption,OPE)方案中客户端与服务端多轮交互导致的较大通信开销问题,提出一种基于本地临时缓存表和自平衡二叉搜索树的保序加密方案。在数据插入阶段通过客户端临时缓存表对插入数据预处理确定初始交互节点,避免从根节点开始交互,降低算法的通信开销;并使用平衡因子为k的AVL(Adelson-Velsky and Landis)树作为编码树,避免频繁的编码更新带来的较大计算开销。此外,采用格式保留加密算法FF1-SM4对数据进行加密,不仅能够提高存储效率,而且无需对数据库表结构进行大幅修改,也无需对应用程序进行修改以适应密文的变化。实验结果表明,当插入5000条数据时,该方案相较gmOPE加密效率提升约13.91%,单次插入的平均交互次数下降约69.81%。展开更多
采用差速离心、膜包超滤浓缩和Sepharose 4 Fast Flow(4FF)凝胶层析相结合的策略纯化猪繁殖与呼吸综合征病毒(PRRSV),建立了一种温和纯化PRRSV的方法。通过SDS-PAGE、Western-blot和检测病毒含量、蛋白含量等方法分析纯化效果。用纯化...采用差速离心、膜包超滤浓缩和Sepharose 4 Fast Flow(4FF)凝胶层析相结合的策略纯化猪繁殖与呼吸综合征病毒(PRRSV),建立了一种温和纯化PRRSV的方法。通过SDS-PAGE、Western-blot和检测病毒含量、蛋白含量等方法分析纯化效果。用纯化后的病毒免疫BALB/c雌性小鼠,通过免疫过氧化物酶单层细胞试验(IPMA)检测其免疫原性,并与超速离心沉淀病毒的纯化方法相比较,评估纯化病毒的免疫效果。结果显示,4FF纯化后的病毒TCID_(50)提高了50倍,与超离方法相比,4FF纯化法将病毒原液杂蛋白的去除比率由97.51%提高到99.68%,SDS-PAGE显示未见明显杂蛋白条带,IPMA结果显示4FF纯化病毒的免疫原性较好,特异性较强,消除了免疫后小鼠血清与Marc-145细胞蛋白的非特异性反应。结果表明,4FF纯化方法优于超离纯化方法,前者的建立为制备单克隆抗体和规模化纯化PRRSV疫苗的工艺开发奠定基础。展开更多
基金supported by Zhejiang Provincial Natural Science Foundation of China under Grant No.LQN25C200011.
文摘Uric acid(UA)-lowering bioactive peptides have emerged as promising alternatives to synthetic drugs owing to their favorable safety profile,efficacy,and bioavailability.This study investigated the anti-hyperuricemic(HUA)mechanisms of xanthine oxidase(XOD)-inhibitory peptides derived from Harpadon nehereus hydrolysate(HNPH).Three potent uric acid(UA)-reducing peptides were identified:FLH(FH3),FGKF(FF4),and IWHHTF(IF6).These peptides altered the secondary structure of XOD and bind to it through hydrogen bonding and hydrophobic interactions,thereby inhibiting XOD catalytic activity.Compared with FH3 and IF6,FF4 showed the strongest XOD inhibitory activity after in vitro digestion and was selected for further in vivo experiments.FF4 reduced UA levels by inhibiting hepatic UA-synthesizing enzymes,upregulating UA transporter ABCG2,and downregulating GLUT9.It alleviated inflammation and oxidative stress in HUA mice livers/kidneys,reducing pathological damage and inflammatory infiltration.FF4 also mitigated UA-induced HK-2 cell damage by regulating ROS and NLRP3 inflammatory pathways.These findings support marine-derived peptides as novel HUA therapeutics,offering alternatives to conventional drugs.
文摘针对现有保序加密(order-preserving encryption,OPE)方案中客户端与服务端多轮交互导致的较大通信开销问题,提出一种基于本地临时缓存表和自平衡二叉搜索树的保序加密方案。在数据插入阶段通过客户端临时缓存表对插入数据预处理确定初始交互节点,避免从根节点开始交互,降低算法的通信开销;并使用平衡因子为k的AVL(Adelson-Velsky and Landis)树作为编码树,避免频繁的编码更新带来的较大计算开销。此外,采用格式保留加密算法FF1-SM4对数据进行加密,不仅能够提高存储效率,而且无需对数据库表结构进行大幅修改,也无需对应用程序进行修改以适应密文的变化。实验结果表明,当插入5000条数据时,该方案相较gmOPE加密效率提升约13.91%,单次插入的平均交互次数下降约69.81%。
文摘采用差速离心、膜包超滤浓缩和Sepharose 4 Fast Flow(4FF)凝胶层析相结合的策略纯化猪繁殖与呼吸综合征病毒(PRRSV),建立了一种温和纯化PRRSV的方法。通过SDS-PAGE、Western-blot和检测病毒含量、蛋白含量等方法分析纯化效果。用纯化后的病毒免疫BALB/c雌性小鼠,通过免疫过氧化物酶单层细胞试验(IPMA)检测其免疫原性,并与超速离心沉淀病毒的纯化方法相比较,评估纯化病毒的免疫效果。结果显示,4FF纯化后的病毒TCID_(50)提高了50倍,与超离方法相比,4FF纯化法将病毒原液杂蛋白的去除比率由97.51%提高到99.68%,SDS-PAGE显示未见明显杂蛋白条带,IPMA结果显示4FF纯化病毒的免疫原性较好,特异性较强,消除了免疫后小鼠血清与Marc-145细胞蛋白的非特异性反应。结果表明,4FF纯化方法优于超离纯化方法,前者的建立为制备单克隆抗体和规模化纯化PRRSV疫苗的工艺开发奠定基础。