Identification of Flavonoids from Scutellaria barbata D. Don as Inhibitors of HIV-1 and Cathepsin L Proteases and Their Structure-Activity Relationships.

Scutellaria barbata D. Don (SB, Chinese: Ban Zhi Lian), a well-known medicinal plant used in traditional Chinese medicine, is rich in flavonoids. It possesses antitumor, anti-inflammatory, and antiviral activities. In this study, we evaluated the inhibitory activities of SB extracts and its active components against HIV-1 protease (HIV-1 PR) and SARS-CoV2 viral cathepsin L protease (Cat L PR). UPLC/HRMS was used to identify and quantify the major active flavonoids in different SB extracts, and fluorescence resonance energy transfer (FRET) assays were used to determine HIV-1 PR and Cat L PR inhibitions and identify structure-activity relationships. Molecular docking was also performed, to explore the diversification in bonding patterns of the active flavonoids upon binding to the two PRs. Three SB extracts (SBW, SB30, and SB60) and nine flavonoids inhibited HIV-1 PR with an IC50 range from 0.006 to 0.83 mg/mL. Six of the flavonoids showed 10~37.6% inhibition of Cat L PR at a concentration of 0.1 mg/mL. The results showed that the introduction of the 4'-hydroxyl and 6-hydroxyl/methoxy groups was essential in the 5,6,7-trihydroxyl and 5,7,4'-trihydroxyl flavones, respectively, to enhance their dual anti-PR activities. Hence, the 5,6,7,4'-tetrahydroxyl flavone scutellarein (HIV-1 PR, IC50 = 0.068 mg/mL; Cat L PR, IC50 = 0.43 mg/mL) may serve as a lead compound to develop more effective dual protease inhibitors. The 5,7,3',4'-tetrahydroxyl flavone luteolin also showed a potent and selective inhibition of HIV-1 PR (IC50 = 0.039 mg/mL).

Model Integration in Computational Biology: The Role of Reproducibility, Credibility and Utility

During the COVID-19 pandemic, mathematical modeling of disease transmission has become a cornerstone of key state decisions. To advance the state-of-the-art host viral modeling to handle future pandemics, many scientists working on related issues assembled to discuss the topics. These discussions exposed the reproducibility crisis that leads to inability to reuse and integrate models. This document summarizes these discussions, presents difficulties, and mentions existing efforts towards future solutions that will allow future model utility and integration. We argue that without addressing these challenges, scientists will have diminished ability to build, disseminate, and implement high-impact multi-scale modeling that is needed to understand the health crises we face.

Marine Natural Products in Clinical Use.

Marine natural products are potent and promising sources of drugs among other natural products of plant, animal, and microbial origin. To date, 20 drugs from marine sources are in clinical use. Most approved marine compounds are antineoplastic, but some are also used for chronic neuropathic pain, for heparin overdosage, as haptens and vaccine carriers, and for omega-3 fatty-acid supplementation in the diet. Marine drugs have diverse structural characteristics and mechanisms of action. A considerable increase in the number of marine drugs approved for clinical use has occurred in the past few decades, which may be attributed to increasing research on marine compounds in laboratories across the world. In the present manuscript, we comprehensively studied all marine drugs that have been successfully used in the clinic. Researchers and clinicians are hopeful to discover many more drugs, as a large number of marine natural compounds are being investigated in preclinical and clinical studies.

Effectiveness of adenovirus type 5 vectored and inactivated COVID-19 vaccines against symptomatic COVID-19, COVID-19 pneumonia, and severe COVID-19 caused by the B.1.617.2 (Delta) variant: Evidence from an outbreak in Yunnan, China, 2021.

BACKGROUND: In partial response to the coronavirus disease 2019 (COVID-19) pandemic, countries around the world are conducting large-scale vaccination campaigns. Real-world estimates of vaccine effectiveness (VE) against the B.1.617.2 (Delta) variant are still limited. An outbreak in Ruili city of Chinaprovided an opportunity to evaluate VE against the Delta variant of two types of COVID-19 vaccines in use in China and globally - inactivated (CoronaVac and BBIBP-CorV) and adenovirus type 5 vectored (Convidecia) vaccines. METHODS: We estimated VE using a retrospective cohort study two months after the Ruili vaccination campaign (median: 63 days). Close contacts of infected people (Chinese nationality, 18 years and above) were included to assess VE against symptomatic Covid-19, COVID-19 pneumonia, and severe COVID-19. We calculated the relative risks (RR) of the outcomes for unvaccinated compared with fully vaccinated individuals. We used logistic regression analyses to estimate adjusted VEs, controlling for gender and age group (18-59 years and 60 years and over).We compared unvaccinated and fully vaccinated individuals on duration of RT-PCR positivity and Ct value. FINDINGS: There were 686 close contacts eligible for VE estimates. Adjusted VE ofad5-vectored vaccine was 61.5% (95% CI, 9.5-83.6) against symptomatic COVID-19, 67.9% (95%CI: 1.7-89.9) against pneumonia, and 100% (95%CI: 36.6-100) against severe/critical illness. For the two inactivated vaccines, combined VE was 74.6% (95% CI, 36.0-90.0) against symptomatic COVID-19, 76.7% (95% CI: 19.3-93.3) against pneumonia, and 100% (95% CI: 47.6-100) against severe/critical COVID-19. There were no statistically significant differences in VE between twoinactivated vaccines for symptomatic COVID-19 and for pneumonia, nor were there statistically significant differences between inactivated and ad5-vectored VE in any of the three outcomes. The median durations of RT-PCR positivity were 17 days for fifteen people vaccinated with an inactivated vaccine, 18 days for forty-four people vaccinated with the Ad5 vectored vaccine, and 26 days for eleven unvaccinated individuals. INTERPRETATION: These results provide reassuring evidence that the three vaccines are effective at preventing Delta-variant COVID-19 in short term following vaccination campaign, and are most effective at preventing more serious illness. The findings of reduced duration of RT-PCR positivity and length of hospital stay associated with full vaccination suggests potential saving of health-care system resources.

Prognostic Value of Coronary CT Angiography-Derived Fractional Flow Reserve in Non-obstructive Coronary Artery Disease: A Prospective Multicenter Observational Study

Coronary artery disease (CAD) is a major contributor to morbidity and mortality worldwide. Myocardial ischemia may occur in patients with normal or non-obstructive CAD on invasive coronary angiography (ICA). The comprehensive evaluation of coronary CT angiography (CCTA) integrated with fractional flow reserve derived from CCTA (CT-FFR) to CAD may be essential to improve the outcomes of patients with non-obstructive CAD. China CT-FFR Study-2 (ChiCTR2000031410) is a large-scale prospective, observational study in 29 medical centers in China. The primary purpose is to uncover the relationship between the CCTA findings (including CT-FFR) and the outcome of patients with non-obstructive CAD. At least 10,000 patients with non-obstructive CAD but without previous revascularization will be enrolled. A 5-year follow-up will be performed. The primary endpoint is the occurrence of major adverse cardiovascular events (MACE), including all-cause mortality, non-fatal myocardial infarct, unplanned revascularization, and hospitalization for unstable angina. Clinical characteristics, laboratory and imaging examination results will be collected to analyze their prognostic value.

Multipurpose Mobile Apps for Mental Health in Chinese App Stores: Content Analysis and Quality Evaluation.

BACKGROUND: Mental disorders impose varying degrees of burden on patients and their surroundings. However, people are reluctant to take the initiative to seek mental health services because of the uneven distribution of resources and stigmatization. Thus, mobile apps are considered an effective way to eliminate these obstacles and improve mental health awareness. OBJECTIVE: This study aims to evaluate the quality, function, privacy measures, and evidence-based and professional background of multipurpose mental health apps in Chinese commercial app stores. METHODS: A systematic search was conducted on iOS and Android platforms in China to identify multipurpose mental health apps. Two independent reviewers evaluated the identified mobile apps using the Mobile App Rating Scale (MARS). Each app was downloaded, and the general characteristics, privacy and security measures, development background, and functional characteristics of each app were evaluated. RESULTS: A total of 40 apps were analyzed, of which 35 (87.5%) were developed by companies and 33 (82.5%) provided links to access the privacy policy; 21 (52.5%) apps did not mention the involvement of relevant professionals or the guidance of a scientific basis in the app development process. The main built-in functions of these apps include psychological education (38/40, 95%), self-assessment (34/40, 85%), and counseling (33/40, 82.5%). The overall quality average MARS score of the 40 apps was 3.54 (SD 0.39), and the total score was between 2.96 and 4.30. The total MARS score was significantly positively correlated with the scores of each subscale (r=0.62-0.88, P<.001). However, the user score of the app market was not significantly correlated with the total MARS score (r=0.17, P=.33). CONCLUSIONS: The quality of multipurpose mental health apps in China's main app market is generally good. However, health professionals are less involved in the development of these apps, and the privacy protection policy of the apps also needs to be described in more detail. This study provides a reference for the development of multipurpose mental health apps.

Willingness to Adopt Health Information Among Social Question-and-Answer Community Users in China: Cross-sectional Survey Study.

BACKGROUND: COVID-19 has spread around the world and has increased the public's need for health information in the process. Meanwhile, in the context of lockdowns and other measures for preventing SARS-CoV-2 spread, the internet has surged as a web-based resource for health information. Under these conditions, social question-and-answer communities (SQACs) are playing an increasingly important role in improving public health literacy. There is great theoretical and practical significance in exploring the influencing factors of SQAC users' willingness to adopt health information. OBJECTIVE: The aim of this study was to establish an extended unified theory of acceptance and use of technology model that could analyze the influence factors of SQAC users' willingness to adopt health information. Particularly, we tried to test the moderating effects that different demographic characteristics had on the variables' influences. METHODS: This study was conducted by administering a web-based questionnaire survey and analyzing the responses from a final total of 598 valid questionnaires after invalid data were cleaned. By using structural equation modelling, the influencing factors of SQAC users' willingness to adopt health information were analyzed. The moderating effects of variables were verified via hierarchical regression. RESULTS: Performance expectation (ß=.282; P<.001), social influence (ß=.238; P=.02), and facilitating conditions (ß=.279; P=.002) positively affected users' willingness to adopt health information, whereas effort expectancy (P=.79) and perceived risk (P=.41) had no significant effects. Gender had a significant moderating effect in the structural equation model (P<.001). CONCLUSIONS: SQAC users' willingness to adopt health information was evidently affected by multiple factors, such as performance expectation, social influence, and facilitating conditions. The structural equation model proposed in this study has a good fitting degree and good explanatory power for users' willingness to adopt health information. Suggestions were provided for SQAC operators and health management agencies based on our research results.