Effect of pinoresinol-lariciresinol reductases on biosynthesis of lignans with substrate selectivity in Schisandra chinensis.

Schisandra lignans are the main bioactive compounds found in Schisandra chinensis fruits, such as schisandrol lignans and schisandrin lignans, which play important roles in organ protection or other clinical roles. Pinoresinol-lariciresinol reductase (PLR) plays a pivotal role in plant lignan biosynthesis, however, limited research has been conducted on S. chinensis PLR to date. This study identified five genes as ScPLR, successfully cloned their coding sequences, and elucidated their catalytic capabilities. ScPLR3-5 could recognize both pinoresinol and lariciresinol as substrates, and convert them into lariciresinol and secoisolariciresinol, respectively, while ScPLR2 exclusively catalyzed the conversion of (+)-pinoresinol into (+)-lariciresinol. Transcript-metabolite correlation analysis indicated that ScPLR2 exhibited unique properties that differed from the other members. Molecular docking and site-directed mutagenesis revealed that Phe271 and Leu40 in the substrate binding motif were crucial for the catalytic activity of ScPLR2. This study serves as a foundation for understanding the essential enzymes involved in schisandra lignan biosynthesis.

Routine HIV Testing and Outcomes: A Population-Based Cohort Study in Taiwan.

INTRODUCTION: Routine HIV testing is expected to facilitate early diagnosis and treatment. Nevertheless, to date, limited data are available on the presumed benefit of early detection with improved outcomes through routine HIV testing. METHODS: This study was based on the Taiwan national HIV/AIDS registry, with follow-up data validated through December 31, 2014. Outcomes of people diagnosed with HIV infection through the routine (routinely offered in specific settings, opt-out) versus through nonroutine (individual risk-based) testing were compared. The main outcomes of the study were late diagnosis, HIV-related mortality, and all-cause mortality. Individuals were matched by year of HIV diagnosis and adjusted for age, sex, transmission routes, and SES. Analyses were conducted in 2019-2020. RESULTS: This study included all 28,674 people diagnosed with HIV infection during 1986-2014 (8,431 [29%] by routine testing, 18,305 [64%] by individual risk-based testing) with a mean follow-up time of 6.2 years. Routine testing was associated with an 80% lower likelihood of late HIV diagnosis (AOR=0.20, 95% CI=0.18, 0.23, p<0.001), a 37% lower HIV-related mortality (adjusted hazard ratio=0.63, 95% CI=0.53, 0.75, p<0.001), and a 27% lower all-cause mortality (adjusted hazard ratio=0.73, 95% CI=0.67, 0.79, p<0.001). CONCLUSIONS: Routine HIV testing was associated with highly favorable outcomes, including decreased late diagnosis, lower HIV-related mortality, and lower all-cause mortality, among people diagnosed with HIV infection. Under universal health coverage, expanding routine HIV testing in well-targeted settings may improve both HIV epidemic control for society and clinical outcomes for people living with HIV.