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An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Reduced fitness of the tumor microenvironment is mediated by a long non-coding RNA expressed in tumors.

This study shows that liquid-liquid phase separation enhances the catalytic efficiency of peptides by up to 15,000-fold through the formation of peptide coacervates. These microreactors can also selectively recruit phosphorylated proteins, providing insights into the evolution of enzymatic activity.

Despite advances in GPCR structures and peptide design, creating high-affinity ligands remains a challenge. Here the authors develop a computational method, successfully identifying peptide-based molecules for KOR: their platform shows promise for streamlined GPCR ligand discovery.

Cardiac developmental genes have been associated with regenerative potential. Here the authors identify a Nkx2.5-dependent gene regulatory network operating through ect2, psmb3, and psmd7 to orchestrate cell cycle re-entry, proteolysis, and mitochondrial metabolism during myocardial repair.

Cancer associated fibroblasts (CAFs) are known to promote pro-tumorigenic inflammation. Here, the authors show that CAFs sense tissue damage and activate NLRP3 inflammasome and pro-inflammatory IL-1β secretion, and CAF-derived inflammasome signalling promotes breast tumour growth and metastasis.

Latin Americans trace their ancestry to the admixture of Native Americans, Europeans and Sub-Saharan Africans. Here, the authors develop a novel haplotype-based approach and analyse over 6,500 Latin Americans to infer the geographically-detailed genetic structure of this population.

Markov, Ren, Senkow and colleagues report that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterized patients who recovered, whereas responses against nonstructural proteins and activation of NF-κB were associated with poor outcomes.

Whole genome sequencing data are increasingly becoming routinely available but generating actionable insights is challenging. Here, the authors describe Pathogenwatch, a web tool for genomic surveillance of S. Typhi, and demonstrate its use for antimicrobial resistance assignment and strain risk assessment.

Mucins play critical roles in maintaining the human microbiome, with their O-glycosylated tandem repeats (TRs) providing important cues for microbiota. Here, the authors develop a cellular platform for producing TRs with defined O-glycan structures to dissect the functions of TR O-glycosylation.

Genetic and Structural analysis of COVID patients cohort reveals a correlation between mitochondrial haplogroup and SARS-CoV-2 severity.

Determination of interactions between native proteins in cells is important for understanding function. Here the authors report MolBoolean as a method to detect interactions between endogenous proteins in subcellular compartments, using antibody-DNA conjugates for identification and signal amplification.

Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson’s disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.

Vancomycin-resistant Enterococcus (VRE) represents a major threat for patients’ health. Here, using a mouse model, the authors show that specific commensals restrict VRE gut colonization through depletion of fructose, a nutrient source that boosts VRE growth in vivo.

Regulatory factor X (RFX) is a transcription factor family comprising seven known members, yet the functional roles of RFX7 remain unknown. Guarda and colleagues show that RFX7 regulates natural killer (NK) cell survival and activity by limiting their cellular metabolism.

In this Consensus Statement, an international group of experts and patient representatives validates and endorses the transition from the term ‘Sjögren syndrome’ to ‘Sjögren disease’, and issue several additional recommendations regarding the nomenclature of this disorder.

Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality.

Children often show milder COVID-19 symptoms, but the underlying mechanistic insights are still lacking. Here the authors profile both pediatric and adult cohorts of COVID-19 patients in Brazil to find that children exhibit higher viral load but stronger and biased cellular immunity, thereby serving clues for the differential responses in children.

A high-quality sequence assembly of the zebrafish genome reveals the largest gene set of any vertebrate and provides information on key genomic features, and comparison to the human reference genome shows that approximately 70% of human protein-coding genes have at least one clear zebrafish orthologue.

The harvest of large quantities of lysine by yeast and other microbes triggers a reprogramming of redox metabolism, in which NADPH is channelled into glutathione metabolism to reduce levels of reactive oxygen species and increase tolerance to oxidative stress.

The battle between humans and plant pests is as old as agriculture, but the movement of pests as a consequence of human activities has been exacerbated only recently. International research collaboration is increasingly important to tackle pests causing serious damage to economies.

DNA capture and sequencing from patients with syphilis highlights the origins of a Treponema pallidum pandemic.

Chan Wah Hak et al. show how plasma membrane patches are primed for fast endophilin-mediated endocytosis and disassembly, in the absence of receptor stimulation, through FBP17 and CIP4 binding to SHIP2 and lamellipodin.

Miguel et al. identify a new enzyme belonging to the GDSL lipase-like family that is involved in the final stage of transformation of 5-CQA into 3,5-diCQA. This enzyme is able to realize an efficient transformation by over 60%, making the transformation process a valuable technological tool that can be easily transferred on an industrial scale.

‘Squeezed light’ enables quantum noise in one aspect of light to be reduced by increasing the noise, or more accurately the quantum uncertainty, of a complementary aspect. This has now been used to push the detectors at the heart of the GEO600 gravitational wave observatory to unprecedented levels of sensitivity.