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Background: In recent years, the number of people infected with the hepatitis C virus (HCV) is increasing rapidly. This has become a major threat to global health, therefore, new anti- HCV drugs are urgently needed. HCV NS5B polymerase is an RNA-dependent RNA polymerase (RdRp), which plays an important role in virus replication, and can effectively prevent the replication of HCV sub-genomic RNA in daughter cells. It is considered a very promising HCV therapeutic target for the design of anti-HCV drugs. Methods: In order to explore the relationship between the structure of benzimidazole derivative and its inhibitory activity on NS5B polymerase, holographic quantitative structure-activity relationship (HQSAR) and Topomer comparative molecular field analysis (CoMFA) were used to establish benzimidazole QSAR model of derivative inhibitors. Results: The results show that for the Topomer CoMFA model, the cross-validation coefficient q2 value is 0.883, and the non-cross-validation coefficient r2 value is 0.975. The model is reasonable, reliable, and has a good predictive ability. For the HQSAR model, the cross-validated q2 value is 0.922, and the uncross-validated r2 value is 0.971, indicating that the model data fit well and has a high predictive ability. Through the analysis of the contour map and color code diagram, 40 new benzimidazole inhibitor molecules were designed, and all of them have higher activity than template molecules, and the new molecules have significant interaction sites with protein 3SKE. Conclusion: The 3D-QSAR model established by Topomer CoMFA and HQSAR has good prediction results and the statistical verification is valid. The newly designed molecules and docking results provide theoretical guidance for the synthesis of new NS5B polymerase inhibitors and for the identification of key residues that the inhibitors bind to NS5B, which helps to better understand their inhibitory mechanism. These findings are helpful for the development of new anti-HCV drugs.

This paper measures the performance of taxi operators using data envelopment analysis (DEA) and the improvement of performance based on benchmarks. This includes basic DEA models and a cros...

Shuai Bian,1 Hongfei Cai,1 Youbin Cui,1,* Wanguo Liu,2,* Chunsheng Xiao3 1Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 2Department of Orthopedic Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, People’s Republic of China; 3Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Youbin CuiDepartment of Thoracic Surgery, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of ChinaEmail cuiyb@jlu.edu.cnWanguo LiuDepartment of Orthopedic Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, People’s Republic of ChinaEmail liuwanguo6016@jlu.edu.cnAbstract: Acute lung injury (ALI) or its aggravated stage acute respiratory distress syndrome (ARDS) may lead to a life-threatening form of respiratory failure, resulting in high mortality of up to 30– 40% in most studies. Although there have been decades of research since ALI was first described in 1967, the clinical therapeutic alternatives for ALI are still in a state of limited availability. Supportive treatment and mechanical ventilation still have priority. Despite some preclinical studies demonstrating the benefit of pharmacological interventions, none of these has been proved completely effective to date. Recent advances in nanotechnology may shed new light on the pharmacotherapy of ALI. Nanomedicine possesses targeting and synergistic therapeutic capability, thus boosting pharmaceutical efficacy and mitigating the side effects. Currently, a variety of nanomedicine with diverse frameworks and functional groups have been elaborately developed, in accordance with their lung targeting ability and the pathophysiology of ALI. The in-depth review of the current literature reveals that liposomes, polymers, inorganic materials, cell membranes, platelets, and other nanomedicine approaches have conferred attractive therapeutic benefits for ALI treatment. In this review, we explore the recent progress in the study of the nanomedicine-based therapy of ALI, presenting various nanomedical approaches, drug choices, therapeutic strategies, and outcomes, thereby providing insight into the trends.Keywords: acute lung injury, acute respiratory distress syndrome, drug delivery, nanoparticle, nanomedicine