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High fat (HF) diet is a major factor in the development of metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatis (MASH), and mitochondria have been proposed to play a role in the pathogenesis of HF diet-induced MASH. Because Mitochondrial topoisomerase I (Top1MT) is exclusively present in mitochondria and Top1MT knock-out mice are viable, we were able to assess the role of Top1MT in the development of MASH. We show that after 16 weeks of HF diet, mice lacking Top1MT are prone to the development of severe MASH characterized by liver steatosis, lobular inflammation and hepatocyte damage. Mice lacking Top1MT also show prominent mitochondrial dysfunction, ROS production and mitochondrial DNA (mtDNA) release, accompanied by hepatic inflammation and fibrosis. In summary, our study demonstrates the importance of Top1MT in sustaining hepatocyte functions and suppressing MASH., Competing Interests: Conflict of interests The authors declare no competing interests.

Objective: The effectiveness of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is threatened by increasing SP-resistance in Africa. We assessed the level of SP-resistance markers, and the clinical and parasitological effectiveness of IPTp-SP in southern Mozambique., Methods: P. falciparum infection, antimalarial antibodies and dhfr/dhps SP-resistance mutants were detected by quantitative polymerase chain reaction (qPCR), suspension array technology and targeted deep sequencing, respectively, among 4016 HIV-negative women in Maputo province (2016-2019). Univariate and multivariate regression models were used to assess the association between taking the recommended three or more IPTp-SP doses (IPTp3+) and parasitological and clinical outcomes., Results: 84.3% (3385/4016) women received three or more IPTp-SP doses. The prevalence of quintuple mutants at first antenatal care (ANC) visit was 94.2%. IPTp3+ was associated with a higher clearance rate of qPCR-detected infections from first ANC visit to delivery (adjusted odds ratio [aOR]=5.9, 95% CI: 1.5-33.3; p = 0.012), lower seroprevalence at delivery of antibodies against the pregnancy-specific antigen VAR2CSA DBL34 (aOR=0.72, 95% CI: 0.54-0.95; p = 0.022), and lower prevalence of low birth weight deliveries (aOR: 0.61, 95% CI: 0.41-0.90; p = 0.013)., Conclusion: A sustained parasitological effect of IPTp-SP contributes to the clinical effectiveness of IPTp3+ in areas with high prevalence of SP-resistance markers., Competing Interests: Declaration of Competing Interest All authors reported no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Emerging spatially resolved transcriptomics technologies allow for the measurement of gene expression in situ at cellular resolution. We apply direct RNA hybridization-based in situ sequencing (dRNA HybISS, Cartana part of 10xGenomics) to compare male and female healthy mouse kidneys and the male kidney injury and repair timecourse. A pre-selected panel of 200 genes is used to identify cell state dynamics patterns during injury and repair. We develop a new computational pipeline, CellScopes, for the rapid analysis, multi-omic integration and visualization of spatially resolved transcriptomic datasets. The resulting dataset allows us to resolve 13 kidney cell types within distinct kidney niches, dynamic alterations in cell state over the course of injury and repair and cell-cell interactions between leukocytes and kidney parenchyma. At late timepoints after injury, C3+ leukocytes are enriched near pro-inflammatory, failed-repair proximal tubule cells. Integration of snRNA-seq dataset from the same injury and repair samples also allows us to impute the spatial localization of genes not directly measured by dRNA HybISS., (© 2024. The Author(s).)