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A loss-of-function mutation in the gene encoding scavenger receptor class B member 1 (SRB1) has been identified. This mutation increases the risk of coronary heart disease (CHD) despite being associated with increased concentration of HDL cholesterol. Upregulation of SRB1 expression might be a novel therapeutic approach for reducing CHD risk.

Together with a companion paper, molecular details of immune responses in a pig-to-human xenotransplantation are identified through dense longitudinal multi-omics profiling of the xenograft and the host recipient, across the 61-day procedure.

Non-canonical inflammasome activation is mediated by caspase-11 in mice and caspase-4 in humans. Here the authors show that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (oxPAPC) competes with LPS for binding to these caspases and in so doing is a negative regulator of non-canonical inflammasome activation in macrophages, but not in dendritic cells.

Converting low-cost inorganic chemicals into value-added organic chemicals is a longstanding goal in chemistry. Here the authors describe a silver-catalysed chemoselective carbene N−H insertion reaction, providing access to primary amines from aqueous ammonia and diazo compounds.

The Qinghai-Tibet Plateau is as cold as the Arctic, but presents unique hypoxia and high ultraviolet conditions. Here the authors find that gene flow from Arctic gyrfalcons aids plateau saker falcons’ cold adaptation, and independent non-coding genomic changes underlie hypoxic and ultraviolet responses.

Genome-wide association analyses identify 30 risk loci for IgA nephropathy. Functional annotations of putative causal genes converge on inflammatory signaling pathways and cytokine ligand–receptor pairs, prioritizing potential new drug targets.

The oxytocin/oxytocin receptor (OT/OTR) signalling system is a promising therapeutic target for socioemotional disorders, yet its clinical potential is limited by a lack of in vivo molecular tools. Here, the authors develop and validate [¹⁸F]dOTK⁸[SFB] as a PET radiotracer, demonstrating its specificity and potential for in vivo mapping OT/OTR biodistribution.

Prioritized Single-Cell ProtEomics (pSCoPE) introduces the concept of using priority levels that define the temporal order of peptide analysis for single-cell proteomic analysis. Prioritized data acquisition aims to simultaneously optimize the consistency, sensitivity, depth and accuracy of protein quantification.

The selective functionalization of trifluoromethyl groups is challenging due to the inertness of the C–F bonds. Here the authors report a method for the carbodefluorination of C–F bonds of fluoroalkyl ketones via a carbene-initiated rearrangement strategy.

Here, the authors have performed a multi-population GWAS meta-analysis of pediatric steroid sensitive nephrotic syndrome cases to discover 12 loci (4 novel), fine-map HLA, implicate kidney and immune factors, and associate the polygenic risk score with earlier disease onset.

Immunoglobulin A protects against infectious disease and contributes to autoimmune and inflammatory disorders. Here, the authors perform a genome-wide association study for serum IgA levels, identifying 20 genome-wide significant loci, providing new insights into the genetic regulation of IgA levels.

A fluorescently labelled inhibitor of the DNA repair enzyme poly(ADP–ribose) polymerase 1 is used to detect epithelial cancers of the upper intestinal tract in animals, in biopsied human tissue and in a human patient.

Since fluoro-compounds are popular in industrial settings, efficient methods for incorporation of fluoride into organic molecules are desirable. Here, the authors developed trifluoroacetaldehyde N-tfsylhydrazone (TFHZ-Tfs) as a CF₃CHN₂ surrogate that generates CF₃CHN₂ in situ under basic conditions.

Sulfinyl radicals are an underexplored synthon in organic chemistry due to the fact that they reversibly add to pi systems and undergo homodimerization. Here the authors synthesize sulfonyl sulfones, previously thought to be unstable, and demonstrate their broad use as sulfinyl radical precursors in disulfurizations of alkenes and alkynes.

Membranous nephropathy (MN) is a rare autoimmune disease of podocyte-directed antibodies, such as anti-phospholipase A2 receptor. Here, the authors report a genome-wide association study for MN and identify two previously unreported loci encompassing the NFKB1 and IRF4 genes and additional ancestry-specific effects.

Still’s disease is an inflammatory syndrome linked to the development of further immune dysregulation and hypercytokinaemia termed macrophage activation syndrome. Here the authors implicate the mechanistic target of rapamycin complex 1 in murine models of Still’s disease and macrophage activation syndrome, and provide associations with clinical cases in patients

Age-specific differences upon SARS-CoV-2 infection are marked by emergence of goblet 2 inflammatory cells expressing antiviral interferon stimulating genes in paediatric nasal cultures, and basaloid-like cells with increased viral spread in cultures from older adults.

Single-cell and spatial gene expression analyses of pancreatic ductal adenocarcinoma uncover a population of interleukin-1β-expressing macrophages that drive inflammatory reprogramming of neighboring tumour cells leading to disease progression and poor prognosis for patients.

Kellner et al. develop respiratory and intestinal organoids from Rousettus aegyptiacus to show elevated basal expression of interferon-ε (IFNε) and IFN-stimulated genes, along with robust, self-amplifying type III IFN responses that drive antiviral defense against zoonotic RNA viruses.

A knowledgebase developed for increased the transparency of reporting in spheroid research.

Recent technological advances permit the profiling of metabolic changes in single cells, which sheds light on how metabolism regulates immune responses. We advocate for accessible and standardized tools to reduce the barrier of entry to immunometabolism studies and facilitate the translation of fundamental findings towards clinical applications.

Nanomaterials may present interesting catalytic properties, but well-defined model systems are rare. Here, a Au–Pd core–shell catalyst is investigated for selective hydrogenation of butadiene, with shell-thickness-dependent catalytic activity, high selectivity and activity 50 times greater than that of alloyed counterparts.

On the basis of new mechanistic studies of a mutant form of the apolipoprotein apoC-III that protects against coronary heart disease, Khetarpal et al. have developed therapeutic apoC-III-targeting monoclonal antibodies that lower circulating apoC-III protein and triglyceride levels in mice.

Here, CD14 is shown to regulate mouse dendritic cell apoptosis after lipopolysaccharide stimulation via a pathway involving activation of the transcription factor NFAT; an event that is essential for maintaining self-tolerance and preventing autoimmunity. Given the involvement of CD14 in diseases such as sepsis and heart failure, the discovery of signal transduction pathways activated exclusively by CD14 is an important step towards the development of potential new treatments.

Across 34 countries, fear of disease and empathic concern encouraged adherence to COVID19 preventive measures. When trust in government is high, the link is weaker between preventive behaviour and fear but stronger between preventive behavior and empathic concern.