RESUMEN
The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and other coronaviruses and thus is a target for coronavirus drug discovery. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors. Here, we report the development of specific, noncovalent inhibitors of 3CLpro. The most potent one, WU-04, effectively blocks SARS-CoV-2 replications in human cells with EC50 values in the 10-nM range. WU-04 also inhibits the 3CLpro of SARS-CoV and MERS-CoV with high potency, indicating that it is a pan-inhibitor of coronavirus 3CLpro. WU-04 showed anti-SARS-CoV-2 activity similar to that of PF-07321332 (Nirmatrelvir) in K18-hACE2 mice when the same dose was administered orally. Thus, WU-04 is a promising drug candidate for coronavirus treatment. A novel oral noncovalent inhibitor of 3C-like protease, named WU-04, was developed as a promising drug candidate for COVID-19 treatment.
RESUMEN
With the impact of the COVID-19 pandemic, global container freights have increased dramatically since the second half of 2020, which has significantly hampered the booking activities of fragmented transportation space for small and medium-sized import and export enterprises (SMIEEs). To provide SMIEEs with an effective tool for controlling shipping costs, we propose the design principles of index microinsurance under fragmented scenarios and design the container freight index microinsurance (CFIM) based on a comprehensive analysis of the term, compensation and share structures. We further establish the pricing model for the CFIM and selection procedure for product optimization, and illustrate the framework with a case study based on the data of the China Containerized Freight Index Europe Service, which demonstrates the good performance of the designed product even under extreme market conditions. The design principles proposed can shed light on the innovation of index microinsurance product that meets fragmented needs and the newly designed CFIM, along with the pricing and optimization procedure, provides practitioners with useful tools for cost control.
RESUMEN
Introduction: Traumatic spinal cord injuries (TSCI) are worldwide public health problems. There has been a lack of extensive multi-center study of TSCI epidemiology in Northwest China in pre- and post-pandemic period of COVID-19. Materials: and Methods: A multi-center retrospective study of 14 hospitals of Northwest China was conducted on patients with TSCI between 2017 and 2020. Variables assessed included patient demographics, etiology, segmental distribution, treatment, waiting time for treatment and outcomes. Results: : The number of patients with TSCI showed an increasing trend from 2017 to 2019 while there were fewer patients in 2020 than in 2019. The male-to-female ratio was 3.67:1 and the mean age was 48±14.9. The major cause of TSCI was high fall (38.8%), low fall (27.7%), traffic accidents (23.9%), sports (2.6%) and others (7.0%). The segmental distribution showed a bimodal pattern, peak segments were C6 and Tl1, L1(14.7%) was the most frequently injured segments. Incomplete injury (72.8%) occurred more often than complete injury (27.2%). ASIA scale of most patients did not change before and after treatment both in operational or conservative group. 975 patients from urban and 1646 patients from rural areas were conducted, most urban residents could rush to get treatment after injured immediately (<1 h), whereas most rural patients get treatment spend several hours since injured. The rough annual incidence from 2017-2020 are 112.4, 143.4,152.2 and 132.6 per million people calculated by the population-coverage-rate. Conclusion: The incidence of TSCI in Northwest China is high and growing. However, under the pandemic policy reasons, it has decreased in 2020. The promotion of online work may be an effective primary prevention measures for trauma. Also, due to the distance from the hospitals with proper conditions, rural patients need to spend long time to there, the timely treatment of them should be paid attention.