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Lipoproteins are major cell-surface components in archaea, but their functions and the lipidation mechanisms are unclear. Here, Hong et al. identify two proteins required for attachment of proteins to unique archaeal membrane lipids via thioether bonds, and demonstrate their importance in archaeal physiology.

Huang et al. show that 3D hydrogel embedding supports more organotypic kidney development in culture. Matrix stiffness and adhesion properties were found to regulate nephron formation, highlighting the intervention potential of physical boundary conditions.

Electron hopping in geometrically frustrated lattices can result in a rich variety of unusual behaviours. Now, the orbital arrangement in a van der Waals metal with a non-frustrated, primitive lattice is found to show similar effects.

A genome-wide CRISPR screen helps to identify the Epstein–Barr virus receptor desmocollin 2 for primary epithelial cell infection. Additional infection assays revealed that desmocollin 3 also aids infection.

Given rising diabetes prevalence globally, access to diabetes treatments is gaining urgency. Here, the authors show patterns of glucose-lowering medication use for diabetes across 62 low- and middle-income countries.

Human airway contains physiologically relevant yet rare cells, but their scarcity prevents thorough profiling and differentiation studies. Here the authors use single cell RNA sequencing to identify rare ionocytes and tuft cells, as well as a potential progenitor population with cytokine-guided differentiation into either the ionocytes or tuft cell lineage.

Antibiotics and nutritional stresses can inactivate Pseudomonas aeruginosa efflux pump mexEFoprN. Here, the authors demonstrate that the inactivation of this efflux pump impacts quorum sensing mediated virulence in P. aeruginosa clinical isolates.

Tissue phenotypes arise from molecular states of individual cells and their spatial organisation, so spatial omics assays can help reveal how they emerge. Here, the authors apply graph neural networks to classify tissue phenotypes from spatial omics patterns, and use this approach to understand patterns in cancers and their microenvironments.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Multiple bonds involving heavier elements were considered impossible but have recently been shown to be stable and offer divergent reactivity. Here the isolation of an alumene (a compound containing an Al=C bond) via direct CO reduction is described. Analysis of the alumene and its ability to homologate CO is reported.

Peripheral artery disease is a vascular disorder characterized by narrowing of the peripheral arteries owing to atherosclerosis or thrombosis. In this Primer, Aboyans and colleagues review the epidemiology, pathophysiology, diagnosis and management of peripheral artery disease, and discuss areas for future research.

Type 2 inflammation drives the formation of pathologic mucus in patients with asthma. Here, authors reveal a role for intelectin-1 in IL-13-induced mucus properties, and that an ITLN1 eQTL is associated with protection from the formation of mucus plugs in T2-high asthma.

Conditional genetic ferret models enable ionocyte lineage tracing, ionocyte ablation and ionocyte-specific deletion of CFTR to elucidate the roles of pulmonary ionocyte biology and function during human health and disease.

Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

A human in vitro model of coeliac disease comprising duodenal organoids that maintain both epithelium and an immune microenvironment finds a previously unsuspected role for IL-7 in gluten-induced epithelial destruction.

Chronic lung diseases are characterized by molecular and cellular composition changes. Here the authors use single-cell RNA sequencing to map cell type-specific changes in human tracheal epithelium related to smoking, and to provide evidence for a tuft-like progenitor for pulmonary neuroendocrine cells and ionocytes.

Lipid nanoparticles (LNPs) are a promising platform for mRNA delivery, but their use in inflammatory pulmonary diseases is limited by reactogenicity and suboptimal delivery. Here, the authors report a VATPase activating non-inflammatory LNP (NIF-LNP) exhibiting a 40fold enhancement in lung protein expression without causing significant reactogenicity compared to commercial LNPs.

An inherently explainable AI trained on 1,015 expert-annotated prostate tissue images achieved strong Gleason pattern segmentation while providing interpretable outputs and addressing interobserver variability in pathology.

Nebulized mRNA delivery has broad therapeutic potential but has proven challenging. Here, the authors report on a modified lipid nanoparticle with improved conditions to allow nebulization and demonstrate its application for delivering mRNA to the lungs.

Lung damage increases abdominal aortic aneurysm (AAA) incidence, but the mechanism was unclear. Here, the authors show that injured lungs leak HMGB1, increasing RIPK3 expression in arterial macrophages that subsequently alters mitochondrial function, leading to MMP12 expression and AAA development.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

The Panoptes antiphage system defends bacteria by detecting phage-encoded counter-defences that sequester cyclic nucleotide signals, triggering membrane disruption and highlighting a broader strategy of sensing immune evasion through second-messenger surveillance.

Electrochemical CO_x reduction to multi-carbon products is hindered by low energy efficiency, in part due to sluggish ion transport across charge-selective membranes used in electrolysers. Here the authors use a porous, non-charge-selective separator that enhances ion transport and improves performance for CO electrolysis.

The pandemic of COVID-19, caused by SARS-CoV-2 infection, warrants immediate investigation for therapy options. Here the authors show, using epithelial and air-liquid interface cultures, that SARS-CoV-2 hijacks host cell metabolism to facilitate viral replication, and that inhibition of mTORC1, a master metabolic regulator, suppresses viral replication.

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

A combined sequencing technique assesses 18 patients with high-grade serous ovarian cancer over a multi-year period from diagnosis to recurrence and shows drug resistance typically arises from selective expansion of one or a few clones present at diagnosis.

Epithelia are barriers against environmental insults and express the transcription factor aryl hydrocarbon receptor (AhR). Here the authors show that AhR regulates multiciliogenesis via cyclin O and Multicilin in a Notch-dependent manner and that this is blocked by toxic ligands.

Hundreds of mutations in the gene CFTR lead to cystic fibrosis and represent a challenge to developing therapeutics. Here, authors demonstrate the ability of airway cells derived from human iPSCs to model genotype-specific CFTR function as well as pharmacologic rescue of disease causing mutations.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

ACE2 and TMPRSS2 have received recent attention as entry factors for SARS-CoV-2. Here the authors analyze nasal airway transcriptome data from 695 children determining ACE2 and TMPRSS2 expression is induced by viral and type2 inflammation, respectively, and both exhibit eQTLs that vary across world populations.

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

Retinoids can act as transcriptional regulators to regulate cell proliferation, differentiation, and other processes. Here, the authors show that uncompromised vitamin A (retinoid) metabolism and signaling in alveolar lipofibroblasts, endothelial and epithelial cells are required to lessen the severity of an acute inflammatory challenge in adult mouse lungs.

Here the authors identify upstream open reading frames (uORFs), uORF1 and uORF2 in the Asian/American lineage and African uORF in the African lineage of Zika viruses, and show that uORF1 affects vimentin filaments and that the identified uORFs affect virus replication in neural cells.

Systematic analysis from the Global Burden of Disease study reported that, despite global improvements from 1990 to 2021, dietary iron deficiency-associated disease burden remains high in women, children and residents in low socio-demographic index countries.

In the lungs, recently identified epithelial structures known as hillocks can act as injury-resistant reservoirs of stem cells.

Multiciliogenesis requires activation of transcriptional and protein assembly programs; however, the mechanisms that initiate the formation of these multiprotein complexes are unclear. Here the authors show that after inducing centriole biogenesis genes, the transcription factor E2f4 is required in the cytoplasm for assembly and nucleation of deuterosomes.

Tracheobronchopathia osteoplastica (TO), is an underreported affliction characterized by squamous metaplasia and heterotopic bone formation in trachea and bronchi. Here the authors apply functional, as well as genome-wide transcriptional and epigenetic profiling to identify airway basal cells dysfunction underlying TO.

Novel technology to rapidly clone patient-specific, ‘ground state’ stem cells of columnar epithelia reveals their proliferative potential, remarkably precise and origin-dependent lineage commitment as well as genomic stability, despite extensive culturing, thereby skirting limitations associated with pluripotent stem cells.