The COVID-19 pandemic caused by the SARS-CoV-2 virus continually poses serious threats to global public health. The main protease (Mpro) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing Mpro inhibitors derived from either Boceprevir or Telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 Mpro activity in vitro with IC50 values ranging from 7.6 to 748.5 nM. The co-crystal structure of Mpro in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a SARS-CoV-2 infection transgenic mouse model, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats.
Background Digital health technologies (ie, the integration of digital technology and health information) aim to increase the efficiency of health care delivery; they are rapidly adapting to health care contexts to provide improved medical services for citizens. However, contrary to expectations, their rapid adoption appears to have led to health inequities, with differences in health conditions or inequality in the distribution of health care resources among different populations. Objective This scoping review aims to identify and describe the inequities of health care services brought about by the adoption of digital health technologies. The factors influencing such inequities, as well as the corresponding countermeasures to ensure health equity among different groups of citizens, were also studied. Methods Primary studies and literature, including articles and reviews, published in English between 1990 and 2020 were retrieved using appropriate search strategies across the following three electronic databases: Clarivate Analytics’ Web of Science, PubMed, and Scopus. Data management was performed by two authors (RY and WZ) using Thomson Endnote (Clarivate Analytics, Inc), by systematically screening and identifying eligible articles for this study. Any conflicts of opinion were resolved through discussions with the corresponding author. A qualitative descriptive synthesis was performed to determine the outcomes of this scoping review. Results A total of 2325 studies were collected during the search process, of which 41 (1.76%) papers were identified for further analysis. The quantity of literature increased until 2016, with a peak in 2020. The United States, the United Kingdom, and Norway ranked among the top 3 countries for publication output. Health inequities caused by the adoption of digital health technologies in health care services can be reflected in the following two dimensions: the inability of citizens to obtain and adopt technology and the different disease outcomes found among citizens under technical intervention measures. The factors that influenced inequities included age, race, region, economy, and education level, together with health conditions and eHealth literacy. Finally, action can be taken to alleviate inequities in the future by government agencies and medical institutions (eg, establishing national health insurance), digital health technology providers (eg, designing high-quality tools), and health care service recipients (eg, developing skills to access digital technologies). Conclusions The application of digital health technologies in health care services has caused inequities to some extent. However, existing research has certain limitations. The findings provide a comprehensive starting point for future research, allowing for further investigation into how digital health technologies may influence the unequal distribution of health care services. The interaction between individual subjective factors as well as social support and influencing factors should be included in future studies. Specifically, access to and availability of digital health technologies for socially disadvantaged groups should be of paramount importance.
OBJECTIVERecent genome-wide association studies (GWAS) revealed that a 9p21.3 locus was associated with type 2 diabetes. In this study, we carried out a large-scale case-control study in the GeneID Chinese Han population to 1) further replicate the association of 9p21.3 type 2 diabetes GWAS single nucleotide polymorphisms (SNPs) and 2) assess the association of these SNPs with coronary artery disease.RESEARCH DESIGN AND METHODSThree SNPs (rs2383208, rs10811661, and rs10757283) were genotyped in two GeneID cohorts of 3,167 Chinese Han individuals. Case-control association design was used to determine the association of the SNPs with type 2 diabetes and coronary artery disease. Gensini scores were calculated in the coronary artery disease subjects and were tested for association with the variants. Multivariate logistic regressions were performed on association studies.RESULTSThe association between two of the three SNPs and type 2 diabetes was replicated in the GeneID population (rs2383208, P = 0.936; rs10811661-T, P = 0.02, odds ratio [OR] = 1.23; rs10757283-C, P = 0.003, OR = 1.30). The same two SNPs also contributed to the risk of coronary artery disease (CAD) (rs10811661-T, P = 0.002, OR = 1.19; rs10757283-C, P = 0.003, OR = 1.18). In addition, rs10757283 was associated with severity of coronary atherosclerosis estimated by the Gensini scoring system (risk allele C, quantitative-trait regression adjusted P = 0.002).CONCLUSIONSFor the first time to our knowledge, our results indicated that the same 9p21.3 locus, represented by SNPs rs10811661 and rs10757283, contributed to the risk of type 2 diabetes and coronary artery disease in our GeneID Chinese Han population.
The COVID-19 is currently spreading around the world, which has posed significant threats to global health and economy. Convalescent plasma is confirmed effective against the novel corona virus in preliminary studies.In this paper, we first described the therapeutic schedule, antibody detection method, indications, contraindications of the convalescent plasmas, and reported the operability of the treatment by case study.
Three isostructural lanthanide metal−organic frameworks (Ln-MOFs, Ln = Eu 3+ , Tb 3+ , Dy 3+ ) containing Pterphenyl-2,2″,4,4″-tetracarboxylate ligand (H 4 L) with red, green, and blue luminescence were solvothermally synthesized. Thus, a series of mixed Ln-MOFs, (Eu x Tb y Dy 1-x-y )(HL)(H 2 O)(DEF) (DEF, N,N-diethylformamide), were designed and obtained, which displayed highly temperature-tuned emission in the visible region, including white light emission. Additionally, tunable luminescence can also be achieved by changing the excitation wavelength.
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