Secular trends in chronic respiratory diseases mortality in Brazil, Russia, China, and South Africa: a comparative study across main BRICS countries from 1990 to 2019.

BACKGROUND: As the emerging economies, the BRICS (Brazil, Russia, India, China, and South Africa) shared 61.58% of the global chronic respiratory diseases (CRD) deaths in 2017. This study aimed to assess the secular trends in CRD mortality and explore the effects of age, period, and cohort across main BRICS countries. METHODS: Data were obtained from the Global Burden of Disease Study (GBD) 2019 and analyzed using the age-period-cohort (APC) model to estimate period and cohort effects between 1990 and 2019. The net drifts, local drifts, longitudinal age curves, period/cohort rate ratios (RRs) were obtained through the APC model. RESULTS: In 2019, the CRD deaths across the BRICS were 2.39 (95%UI 1.95 to 2.84) million, accounting for 60.07% of global CRD deaths. Chronic obstructive pulmonary disease (COPD) and asthma remained the leading causes of CRD deaths. The age-standardized mortality rates (ASMR) have declined across the BRICS since 1990, with the most apparent decline in China. Meanwhile, the downward trends in CRD death counts were observed in China and Russia. The overall net drifts per year were obvious in China (-5.89%; -6.06% to -5.71%), and the local drift values were all below zero in all age groups for both sexes. The age effect of CRD presented increase with age, and the period and cohort RRs were following downward trends over time across countries. Similar trends were observed in COPD and asthma. The improvement of CRD mortality was the most obvious in China, especially in period and cohort effects. While South Africa showed the most rapid increase with age across all CRD categories, and the period and cohort effects were flat. CONCLUSIONS: BRICS accounted for a large proportion of CRD deaths, with China and India alone contributing more than half of the global CRD deaths. However, the declines in ASMR and improvements of period and cohort effects have been observed in both sexes and all age groups across main BRICS countries. China stands out for its remarkable reduction in CRD mortality and its experience may help reduce the burden of CRD in developing countries.

Piperazine ring formation by a single-module NRPS and cleavage by an α-KG-dependent nonheme iron dioxygenase in brasiliamide biosynthesis.

Brasiliamides are a class of piperazine-containing alkaloids produced by Penicillium brasilianum with a range of pharmaceutical activities. The mechanism of brasiliamide biosynthesis, including piperazine ring formation and multiple tailoring modifications, still remains unclear. In this study, the biosynthetic gene cluster of brasiliamides, brs, was identified from the marine-derived fungal strain Penicillium brasilianum WZXY-M122-9. Deletion of a histone deacetylase-encoding gene using a CRISPR/Cas9 gene editing system led to the production of a new compound, namely brasiliamide I (1). The brs-encoded single-module nonribosomal peptide synthetase (NRPS) BrsA is involved in the formation of the piperazine skeleton of brasiliamides. Full-length BrsA protein (113.6 kDa) was purified, and reconstitution of enzymatic activity in vitro confirmed that BrsA stereoselectively accepts L-phenylalanine as the substrate. Multiple deletion of tailoring genes and analysis of purified proteins in vitro enabled us to propose a brasiliamide biosynthetic pathway. In the tailoring steps, an α-ketoglutarate (KG)-dependent nonheme iron dioxygenase, BrsJ, was identified to catalyze piperazine ring cleavage during biosynthesis of brasiliamide A (2). KEY POINTS: The gene cluster encoding brasiliamide biosynthesis, brs, is identified. Deletion of a histone deacetylase-encoding gene produces brasiliamide I. BrsA catalyzes brasiliamide piperazine skeleton formation. BrsJ catalyzes piperazine ring cleavage to produce brasiliamide A. Graphical abstract.