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Barnett et al. disentangle the differential contribution of mitochondrial complex I- and complex III-derived ROS to astrocytic function, with CIII-derived ROS being a major driver of neuroinflammatory responses.

Semaglutide, a GLP-1 receptor agonist, may offer neuroprotective benefits after stroke, but its effects in large vessel occlusion (LVO) are unknown. Here the authors show, in a phase 2 randomized trial, that semaglutide is safe after endovascular therapy and may improve recovery in patients not receiving intravenous thrombolysis.

FIKK effector kinases underwent rapid evolutionary expansion and are a druggable target in Plasmodium falciparum.

Tetrandrine is one of the most potent inhibitors of Ebola Virus infection. Here the authors identify LIMP-2 as a direct cellular target of Tetrandrine and establish a functional connection between lysosomal sphingosine homeostasis and calcium regulation.

While catalytic reduction of quinolines has gained interest as a way to provide direct and efficient access to tetrahydroquinolines or 1,2-dihydroquinolines, the catalytic synthesis of 1,2-dihydroquinolines remains underdeveloped. Here, the authors demonstrate a catalytic 1,2-reduction of quinolines using a dinuclear aluminum complex.

Artemisinin-resistant Plasmodium falciparum can use tRNA modification reprogramming and codon bias translation as an epitranscriptomic response to survive artemisinin-induced stress.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

An analysis of sera samples collected between January and July of 2022 in Hong Kong shows that the effectiveness of both the BNT162b2 and CoronaVac COVID-19 vaccines against SARS-CoV-2 Omicron BA.2 variant infection waned rapidly after the third and fourth doses.

An individual's risk of developing cardiovascular disease is somewhat dependent on their ethnic origin, and is increased by the presence of inflammatory rheumatic disease. However, little is known about the relative contributions of ethnicity and rheumatic disease activity to a patient's overall risk of cardiovascular morbidity and mortality. This Review explores known risk factors for, surrogate markers of, and the epidemiology of heart disease in Asian and non-Asian patients with rheumatic diseases.

‘Molecular anvil’ molecules consisting of a compressible mechanophore and incompressible ligands react under hydrostatic pressure to produce elemental metal via an unexplored mechanism.

Several studies show that APOE-ε4 coding variants are associated with Alzheimer’s disease (AD) risk. Here, Zhou et al. perform fine-mapping of the APOE region and find AD risk haplotypes with non-coding variants in the PVRL2 and APOC1 regions that are associated with relevant endophenotypes.

Spatial maps in the medial temporal lobe (MTL) have been proposed to map abstract conceptual knowledge. Rather than grounding abstract knowledge in a spatial map, the authors propose a general-purpose clustering algorithm that explains how both spatial (including place and grid cells) and higher-dimensional conceptual representations arise during learning.

This manuscript evaluates forecasts of laboratory-confirmed influenza hospital admissions, a new target for influenza forecasting in the United States. Across two influenza seasons, the FluSight ensemble is robust compared to submitted models.

Mechanisms underlying increasing artemisinin resistance of Plasmodium in Southeast Asia remain unclear. Here, Zhu et al. integrate TWAS, GWAS and eQTL analyses for 773 P. falciparum isolates and identify genetic and transcriptomic backgrounds to artemisinin resistance.

Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

Virus triggered lipophagy is important for flaviviral assembly and coordinated by Aup1 and the ubiquitin conjugating enzyme E2. Here, Lan et al further characterise the interplay between these proteins and how they function to modulate selective autophagy and viral replication.

The emergence and spread of artemisinin resistance has compromised antimalarial efficacy. Here, Mok et al. apply quantitative transcriptomics, proteomics, and metabolomics to provide evidence that K13 mutations alter multiple aspects of the parasite’s intra-erythrocytic development to enhance survival following artemisinin treatment.

Despite the efficacy of artemisinin against Plasmodium falciparum, young intraerythrocytic ring stage parasites may survive and persist in a dormant state. In this study, Yu et al elucidate the epigenetic regulatory mechanism of artemisinin resistance in P. falciparum ring-stage survival.

Comprehensive glycome profiling of immunoglobulin G (IgG) in 95 strains of mice from the Collaborative Cross genetics resource reveals the extent and variability of IgG glycosylation in vivo.

Africa-specific genetic variation on chromosome 1 near CHD1L is associated with HIV replication in vivo.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The antibody response of children to SARS-CoV-2 is less well studied than in adults. Here Hachim et al. show that children have reduced antibody levels to structural proteins and suggest that the predominance of antibody responses to non-structural proteins can be used to discriminate infection and vaccination.

John Chambers, Jaspal Kooner, Pim van der Harst, Shyong Tai, Paul Elliott, Jiang He, Norihiro Kato and colleagues performed a genome-wide association study of blood pressure phenotypes in individuals of European, East Asian and South Asian ancestry. They find trait-associated SNPs at 12 loci, some of which are associated with methylation at nearby CpG sites.

The authors present the largest genome-wide association study to date for a rare Parkinsonian disorder, progressive supranuclear palsy (PSP). They include follow-up investigations of the identified susceptibility loci, functional consequences, and cell-specific pathologies, providing insights into genetic and molecular mechanisms underlying PSP.

Very early observations of a type Ia supernova—from within one hour of explosion—show a red colour that develops and rapidly disappears. These data provide information on the initial explosion mechanism: surface nuclear burning on the white dwarf or extreme mixing of the nuclear burning process.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Certain specific antigens have been shown to activate T cells in an MHC independent manner. Here the authors show a phycoerythrin reactive mouse TCR which recognises native protein and characterise the molecular nature of this interaction and that this specific TCR can be selected in the thymus.