Tuberculosis remains a major public health problem in South Africa, with an estimated 300,000 cases and 55,000 deaths in 2021. New tuberculosis vaccines could play an important role in reducing this burden. Phase IIb trials have suggested efficacy of the M72/AS01 vaccine candidate and BCG-revaccination. The potential population impact of these vaccines is unknown.

Rapid spread of insecticide resistance among anopheline mosquitoes threatens malaria elimination efforts, necessitating development of alternative vector control technologies. Sterile insect technique (SIT) has been successfully implemented in multiple insect pests to suppress field populations by the release of large numbers of sterile males, yet it has proven difficult to adapt to Anopheles vectors. Here we outline adaptation of a CRISPR-based genetic sterilization system to selectively ablate male sperm cells in the malaria mosquito Anopheles gambiae. We achieve robust mosaic biallelic mutagenesis of zero population growth (zpg, a gene essential for differentiation of germ cells) in F1 individuals after intercrossing a germline-expressing Cas9 transgenic line to a line expressing zpg-targeting gRNAs. Approximately 95% of mutagenized males display complete genetic sterilization, and cause similarly high levels of infertility in their female mates. Using a fluorescence reporter that allows detection of the germline leads to a 100% accurate selection of spermless males, improving the system. These males cause a striking reduction in mosquito population size when released at field-like frequencies in competition cages against wild type males. These findings demonstrate that such a genetic system could be adopted for SIT against important malaria vectors.

Lead (Pb) and arsenic (As) are prevalent metal contaminants in the environment. Exposures to these metals are associated with impaired neuronal functions and adverse effects on neurodevelopment in children. However, the molecular mechanisms by which Pb and As impair neuronal functions remain poorly understood. Here, we identified F2RL2, TRIM16L, and PANX2 as novel targets of Nuclear factor erythroid 2-related factor 2 (NRF2)-the master transcriptional factor for the oxidative stress response-that are commonly upregulated with both Pb and As in human neural progenitor cells (NPCs). Using a ChIP (Chromatin immunoprecipitation)-qPCR assay, we showed that NRF2 directly binds to the promoter region of F2RL2, TRIM16L, and PANX2 to regulate expression of these genes. We demonstrated that F2RL2, PANX2, and TRIM16L have differential effects on cell death, proliferation, and differentiation of NPCs in both the presence and absence of metal exposures, highlighting their roles in regulating NPC function. Furthermore, the analyses of the transcriptomic data on NPCs derived from autism spectrum disorder (ASD) patients revealed that dysregulation of F2RL2, TRIM16L, and PANX2 was associated with ASD genetic backgrounds and ASD risk genes. Our findings revealed that Pb and As induce a shared NRF2-dependent transcriptional response in NPCs and identified novel genes regulating NPC function. While further in vivo studies are warranted, this study provides a novel mechanism linking metal exposures to NPC function and identifies potential genes of interest in the context of neurodevelopment.

Improving hypertension control in low- and middle-income countries has uncertain implications across socioeconomic groups. In this study, we simulated improvements in the hypertension care cascade and evaluated the distributional benefits across wealth quintiles in 44 low- and middle-income countries using individual-level data from nationally representative, cross-sectional surveys. We raised diagnosis (diagnosis scenario) and treatment (treatment scenario) levels for all wealth quintiles to match the best-performing country quintile and estimated the change in 10-year cardiovascular disease (CVD) risk of individuals initiated on treatment. We observed greater health benefits among bottom wealth quintiles in middle-income countries and in countries with larger baseline disparities in hypertension management. Lower-middle-income countries would see the greatest absolute benefits among the bottom quintiles under the treatment scenario (29.1 CVD cases averted per 1,000 people living with hypertension in the bottom quintile (Q1) versus 17.2 in the top quintile (Q5)), and the proportion of total CVD cases averted would be largest among the lowest quintiles in upper-middle-income countries under both diagnosis (32.0% of averted cases in Q1 versus 11.9% in Q5) and treatment (29.7% of averted cases in Q1 versus 14.0% in Q5) scenarios. Targeted improvements in hypertension diagnosis and treatment could substantially reduce socioeconomic-based inequalities in CVD burden in low- and middle-income countries.