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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).

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

Bioprinting has potential in the biofabrication of three dimensional tissues, but is poorly suited to the manipulation of neural organoids. Here, the authors develop a bioprinting platform to allow the arrangement of organoids to form assembloids.

A survey of sharks and rays on coral reefs within 66 marine protected areas across 36 countries showcases that the conservation benefits of full MPA protection to sharks almost double when accompanied by effective fisheries management.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Fishing has had a profound impact on global reef shark populations, and the absence or presence of sharks is strongly correlated with national socio-economic conditions and reef governance.

The soft-grainy microstructure of cooked egg yolk is the result of a series of out of equilibrium processes of its protein-lipid contents. Here, the authors develop a time-temperature phase diagram that shows the coupling of the nanoscale processes that result in the grainy-gel microstructure of cooked egg yolk.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Transferrin receptor (TfR) and CD98hc are increasingly used to enable more effective drug delivery to the central nervous system. Here, the authors reveal comprehensive and distinct brain cellular and whole body biodistribution patterns of TfR- and CD98hc-binding molecules.

Transcriptomic analysis of BCR-ABL1 lymphoblastic leukemia identifies three subgroups, each associated with a maturation arrest at a specific stage of B-cell progenitor differentiation and distinct genetic and clinical features.

The authors identify the interaction between transcription factor YY1 and DNA G4 structures, which contributes to chromatin looping induced by YY1 dimerization as well as its transcriptional regulation.

Fibroblasts play critical roles in tissue homeostasis, but in pathologic states they can drive fibrosis, inflammation, and tissue destruction. Here, Faust et al. find that healthy human synovial fibroblasts under the influence of adjacent adipocytes have altered lipid metabolism driven by cortisol signaling. Both adipocytes and these characteristics are lost in inflammatory arthritis.

A substantial proportion of patients with cardiometabolic conditions appear to have normal BMI. Conversely, not all obese individuals exhibit these disorders. Here, we show that a metabolic BMI score derived from lipidomic models, allows quantify metabolic dysregulation in obesity independently of BMI.

Single-cell transcriptomic and proteomic data from synovial tissue from individuals with rheumatoid arthritis classify patients into groups based on abundance of cell states that can provide insights into pathology and predict individual treatment responses.

Using machine learning, Zhang et al. identify EEG signature to predict psychotherapy outcomes in PTSD, paving the way towards the development of scalable biomarkers.

Dysregulation of lipid metabolism is associated with coronary artery disease (CAD). Here, the authors perform GWAS of the serum lipidome to identify variants associated with lipid species that are putatively in the mechanistic pathway to CAD.

The dynamics of SARS-CoV-2 transmission in the Middle East have been relatively under-studied. Here, the authors integrate genomic and travel data and show that introductions to the region were initially driven by intercontinental air travel, after which regional land travel became a more important driver.

SCENT is a nonparametric method that models association between chromatin accessibility and gene expression in single-cell multimodal datasets, enabling construction of cell-type-specific enhancer–gene maps to aid mapping of candidate causal variants and genes for common diseases.

New delivery platforms are needed to allow broader application of biotherapeutics for CNS diseases. Here, the authors show enhanced CNS delivery with a transport vehicle engineered to bind CD98hc, a highly expressed target at the blood-brain barrier.

van Lengerich et al. developed a human TREM2 antibody with a transport vehicle (ATV) that improves brain exposure and biodistribution in mouse models. ATV:TREM2 promotes microglial energetic capacity and metabolism via mitochondrial pathways.

The epigenetic changes underlying the heterogeneity of RA disease presentation have been the subject of intense scrutiny. In this study, the authors use multiple single-cell sequencing datasets to define ‘chromatin superstates’ in patients with RA, which associate with distinct transcription factors and disease phenotypes.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Insufficient AHR activation has been suggested in SLE, and augmenting AHR activation therapeutically may prevent CXCL13⁺ T_PH/T_FH differentiation and the subsequent recruitment of B cells and formation of lymphoid aggregates in inflamed tissues.

As metabolic reactions are often in equilibrium, product sequestration is often used to drive engineered pathways forward. For n-butanol, however, this is not possible; instead, introducing kinetic barriers for backwards reactions significantly increases product yield.

BACH2 is required for lymphocyte differentiation. Afzali et al. describe mutations that cause BACH2 disruption, immunodeficiency and autoinflammatory disease via haploinsufficiency, a mechanism shared by other super-enhancer-regulated genes.

The detrimental effects of aged blood on cognition and nervous system function in mice can be combatted by targeting brain endothelial cell dysfunction via inhibition of aberrant VCAM1 signaling at the blood–brain barrier.

Fluorescence lifetime imaging microscopy can offer insights into biological processes such as metabolic imaging, protein–protein interactions and live-cell intracellular dynamics. In this Primer, Torrado et al. discuss methods for measuring fluorescence lifetimes, including time-tagging and phase-modulation shift methods, along with fluorescence lifetime imaging microscopy setup variations.

The long non-coding RNA Morrbid controls myeloid cell lifespan and regulates apoptosis by repressing the adjacent pro-apoptotic Bcl2l11 gene in cis.

The heterogeneity of androgen receptor (AR) gene alterations across metastases in prostate cancer remains unresolved. Here, the authors characterise AR genomic complexity across spatially separated lethal metastases from 10 prostate cancer patients and investigate how AR alterations evolve.

Changes in the seasonal cycle amplitude of atmospheric CO₂ (SCA) reflect large-scale changes in the global carbon cycle. This Review summarizes the positive SCA trend in the northern high latitudes, where the signal is strongest, and explores the underlying mechanisms driving the trend and their relative importance.