摘要：In order to find novel antifungal agents with good activity and aqueous solubility, a series of SYN-2869 analogues containing a pyridine ring were synthesized and evaluated for their in vitro antifungal activity and water solubility. The results indicated that some compounds showed potent activity against six pathogenic fungi. In particular, the analogue 17a having an isobutyl substitution on the triazolone exhibited significant broad spectrum antifungal activity. In addition, the water solubility of compound l？a was sufficiently improved over SYN-2869.

摘要：A series of novel pleuromutilin derivatives with 4H-pyran-4-one and pyridin-4-one substitution in the C-14 side chain have been designed and synthesized. In vitro antibacterial activity evaluation showed that most of the derivatives exhibited potent antibacterial activity against drug resistant Gram-positive strains. Compounds 12 a, 12 d, and 28 are the most active derivatives in this series, displaying activity comparable to that of retapamulin and BC-3781. As the metabolic stability of this series is not satisfactory, further modifications are going on to improve their pharmacokinetic profile.

摘要：A series of novel bis（trifluoroethyl）phosphonomethyl ether derivatives of acyclovir was synthesized and their in vitro anti-HBV activity was evaluated in HepG2 2.2.15 cells. In contrast to acyclovir, most of the described phosphonates emerged as potent inhibitors of HBV replication. Especially, the most active compound 11 with IC50 value of 2.92 μmol/L was 33 times more potent than acyclovir with ICso value of 100 μmol/L.

摘要：A series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates was synthesized and their anti-HBV activity was evaluated in HepG2 2.2.15 cells. Compound 1d exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with EC50 and CC50 values of 0.207 μmol/L and 2530 μmol/L, respectively.

摘要：GPR40 has emerged as an attractive drug target for the treatment of type 2 diabetes due to its role in the enhancement of insulin secretion with glucose dependency. With the aim to improve the metabolic and safety profiles, a series of novel phenylpropionic acid derivatives were synthesized. Extensive structural optimization led to identification of compounds 22 g and 23 e as potent GPR40 agonists with moderate liver microsomal stability. All the discovery supported further exploration surrounding this scaffold.

摘要：A series of novel triazole derivatives containing y-lactam were designed and synthesized, and their structures were confirmed by IH NMR, 13C NMR and HRMS, The in vitro antifungal activities of the target compounds were evaluated, The results showed that all of the compounds exhibited stronger activity against the six clinically important fungi tested than fluconazole. 3D and 3E showed comparative activity against the fungi tested except for Candida glabrata and Aspergillus fumigatus as voriconazole. In addition, the docking model for 2A and CYP51 was investigated.

摘要：In order to develop novel LpxC inhibitors with good activities and metabolic stability, two series of compounds with hydrophilic terminus have been synthesized and their in vitro antibacterial activities against Escherichial coil and Pseudomonas aemginosa were evaluated. Especially, compounds 22b and c exhibited comparable antibacterial activities to CHIR-090 and better metabolic stability than CHIR-090 and LPC-011 in liver microsomes （rat and mouse）, which indicated the terminal methylsulfone may be a preferred structure in the design of LpxC inhibitors and worthy of further investigations.

摘要：麦什扎黄河大桥主桥为一孔246 m下承式提篮钢箱—组合梁系杆拱桥,引桥为一孔40 m预应力混凝土异形现浇箱梁。主桥主拱为钢箱截面,拱轴线为二次抛物线,平面与铅垂线夹角为9°,面内矢跨比为1/5;主梁为钢混组合梁,钢结构部分为钢格构梁体系;主桥施工采用斜拉扣挂配合缆索吊法施工,先拱后梁。受桥梁设计理念、资金来源、分离式墩柱和未来水平系杆索更换等多种因素影响,该桥主引桥衔接位置设计为140 cm纵桥向牛腿,引桥小桩号侧端横梁设计为类似于门式框架墩盖梁的异形端横梁。纵桥向牛腿采用了加粗门字形骨架钢筋,引桥主梁预应力钢束从牛腿正中穿过等创新设计。异形端横梁采用了减小靠近张拉端横向预应力间距,优化横向预应力布置线形,改变张拉槽口形状和锚下钢筋网等诸多设计。

摘要：随着都市圈一体化进程的持续深化,城市交通体系的互联互通已成为推动区域协调发展的重要力量。在此背景下,高效整合各类交通资源,满足不同出行者的多样化出行需求,对于提升都市圈一体化出行服务的品质至关重要。智慧出行服务作为利用数据分析与处理技术优化服务质量的前沿领域,展现出巨大的潜力。文章从数据赋能的视角出发,深入探讨南京都市圈在数字化和一体化建设方面的需求,在此基础上创新性地提出出行服务助手成熟度模型,并设计面向都市圈乘客的出行服务助手,旨在构建一个全面覆盖南京都市圈的乘客信息服务体系,实现多模式交通服务的一站式整合。同时,文章提出构建碳普惠平台的构想,以促进南京地铁官方APP从单一的城市轨道交通出行服务工具向都市圈综合服务门户的转变,从而显著提升都市圈乘客的服务体验。

摘要：目前对横幅广告视觉注意和记忆效果的研究出现了“独特性观”和“盲视观”两种矛盾的观点。本研究从任务驱动的视角出发,引入计算神经科学的视觉注意计算模型,借助眼动追踪技术,探讨不同任务驱动下横幅广告的视觉显著性对消费者的注意和记忆效果的影响。结果表明:在不同任务驱动下,横幅广告的视觉显著性对消费者的注意及记忆效果的影响具有显著差异。具体而言,在浏览任务中,视觉显著性高的横幅广告比视觉显著性低的横幅广告能带来更好的广告注意及记忆效果;在搜索任务中,不同视觉显著性水平的横幅广告对消费者的注意和记忆效果的影响没有显著差异。本研究丰富了计算神经科学在营销领域的运用,为企业选择合适的网络广告策略提供借鉴。