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Biomarkers that predict mortality are of interest for clinical as well as research applications. Here, the authors analyze metabolomics data from 44,168 individuals and identify key metabolites independently associated with all-cause mortality risk.

An approximately 2-million-year-old male Paranthropus robustus cranium from Drimolen Main Quarry in South Africa refutes influential ideas of sexual dimorphism in this taxon and instead suggests local microevolution within robust australopiths.

The Great Oxidation Event represents a tipping point in Earth’s O₂ mass balance—when more O₂ was being produced than destroyed—that forever changed the habitability of worldwide oceans.

Examination of archaeological pottery residues and modern genes suggest that environmental conditions, subsistence economics and pathogen exposure may explain selection for lactase persistence better than prehistoric consumption of milk.

To promote the recovery of the currently declining global trends in terrestrial biodiversity, increases in both the extent of land under conservation management and the sustainability of the global food system from farm to fork are required.

Vast networks of capillaries feed the brain. Hartmann et al. show that pericyte contractility is critical for maintenance of enduring capillary tone, which sets an optimized rate and distribution of blood flow through brain capillary networks.

Anaerobic microorganisms can oxidize short-chain gaseous alkanes such as ethane, propane and butane using sulfate as electron acceptor. Here, the authors show that a bioreactor enrichment of a wastewater microbial community can perform anaerobic propane oxidation coupled to nitrate reduction.

Shi et al. present a hybrid dependency map based on machine-learning analysis of gene essentiality data from the DEPMAP database, translated to data from TCGA. This application can be used to visualize other gene essentiality data.

Netie, a hierarchical Bayesian model to infer the neoantigen evolution and immune selection pressure during tumor progression.

Pericytes play an essential role in blood brain barrier (BBB) integrity. Here, the authors generate pericyte-like cells (PCs) from human pluripotent stem cells (hPSCs) which display functional properties and also promote BBB recovery in a mouse model of cerebral artery occlusion.

TMEM16A, a calcium-activated chloride channel involved in multiple cellular processes, is implicated in various diseases, but its pharmacology remains poorly understood. Here, the authors combine cryo-EM and electrophysiology to elucidate the mechanism of TMEM16A inhibition by the pore blocker 1PBC.

Opioids modulate pain, anxiety and stress by activating four subtypes of opioid receptors. The authors show that atypical chemokine receptor 3 (ACKR3) is a scavenger for various endogenous opioid peptides regulating their availability without activating downstream signaling.

Single-cell RNA sequencing (scRNA-seq) is widely used to characterize cell types based on their average gene expression profiles, however most studies do not consider cell type-specific variation across individuals. Here the authors introduce a model to study cell type-specificity of inter-individual variation in scRNA-seq data and show that it can identify biologically meaningful signals missed by conventional differential expression tests.

Type 1 regulatory T cells (Tr1) represent a major obstacle that compromises naturally occurring and therapeutically induced tumour-specific immunity.

A closed-loop and wireless 128-channel neuromodulation device enables electrical stimulation as well as artefact-free long-term recording of local field potentials in the brain of an untethered non-human primate.

Microfluidic chain reactions encode programs structurally in situ, and can form a frugal, versatile, bona fide lab-on-a-chip with wide-ranging applications in liquid handling and point-of-care diagnostics

The mechanisms that control the presynaptic abundance of GABAB receptors (GBRs) remains unclear. This study shows that sequence-related epitopes in APP, AJAP-1 and PIANP bind with nanomolar affinities to the N-terminal sushi-domain of presynaptic GBRs, and that selective loss of APP impaired GBR-mediated presynaptic inhibition and axonal GBR expression

How We Feel is a web and mobile-phone application for collecting de-identified self-reported COVID-19-related data. These data are used to map a diverse set of symptomatic, demographic, exposure and behavioural factors relevant to the ongoing pandemic.

Conserving biodiversity for its own sake and conserving it to safeguard ecosystem services are distinct goals that cannot both be achieved through a single target analogous to climate’s 1.5 °C, argues Andy Purvis.

JWST/NIRSpec observations of Abell2744-QSO1 show a high black-hole-to-host mass ratio in the early Universe, which indicates that we are seeing the black hole in a phase of rapid growth, accreting at 30% of the Eddington limit.

A microglial state, featuring lipid droplets and secretion of neurotoxic factors, is shown to be most prominent in people with Alzheimer’s disease who have the APOE4 genotype.

A single-cell transcriptomic analysis of 63 patients with colorectal cancer classifies tumor cells into two epithelial subtypes. An improved tumor classification based on epithelial subtype, microsatellite stability and fibrosis reveals differences in pathway activation and metastasis.

Aviation is a major contributor to climate change. This study assesses the potential of bioenergy crops planted in the US Midwest to meet projected US jet-fuel demand in 2040, finding that planting roughly 23.2 million hectares of marginal land with miscanthus would meet this need.

From radio galaxies to robots, these trailblazers are at the forefront of AI advances.

Achieving extremely fast charging while maintaining high energy density remains a challenge in the battery field. Here the authors conceptualize a porous current collector that successfully reduces the effective Li⁺ transport distance by half, quadrupling the diffusion-limited C-rate capability without compromising battery energy density.

Staphylococcus aureuscan both cause disease in humans and be present with no discernible effect. Here, the authors look in detail at the memory immune response against a protein involved in iron acquisition.

The binding of cytoplasmic Ca²⁺ to the anion-selective channel TMEM16A triggers a conformational change around its binding site that is coupled to the release of a gate at the constricted neck. Here authors use cryo-EM and electrophysiology to identify three hydrophobic residues at the intracellular entrance of the neck as constituents of this gate.

Archaeogenetic study of ancient DNA from medieval northwestern Europeans reveals substantial increase of continental northern European ancestry in Britain, suggesting mass migration across the North Sea during the Early Middle Ages.

A computational system termed MetaWIBELE (workflow to identify novel bioactive elements in the microbiome) is used to identify microbial gene products that are potentially bioactive and have a functional role in the pathogenesis of inflammatory bowel disease.

In a prespecified interim analysis of a pivotal phase 2 trial, tisagenlecleucel, an autologous CD19-targeting CAR-T cell therapy, produced a high rate of complete responses with a manageable safety profile in adults with relapsed or refractory follicular lymphoma

A large resource of shared tumor neoepitopes aims to accelerate cancer immunotherapy.

Fiorina and colleagues document alterations in glucose metabolism in patients with COVID-19 and use continuous glucose monitoring to show that glycaemic abnormalities could still be detected 2 months after disease onset in patients who had recovered.

Pleuromutilin derivatives are potent antibacterial drugs obtained from Basidiomycete fungi. Here, the authors report the genetic characterisation of the steps involved in pleuromutilin biosynthesis through heterologous expression and generate a semi-synthetic pleuromutilin derivative with enhanced antibiotic activity.

Dissolved organic matter becomes highly labile in dark anoxic groundwater environments, suggesting that groundwater extraction and subterranean groundwater discharge could be significant sources of greenhouse gases to the atmosphere.

A noise-resilient protocol implemented in a cavity resonator coupled to a qubit demonstrates that large nonlinear couplings are not a necessary requirement for the fast universal control and state preparation of engineered quantum systems.

Overcrowded alkene-derived molecular motors convert light and heat into chirality-directed unidirectional rotary motion, but the efficiency of their photochemical isomerization remains limited. Now formylation of the motor core has been shown to boost all aspects of motor photochemistry by improving photochemical efficiency, diminishing competing processes and redshifting absorption.

By combining genome sequencing and antibody binding (to all common pneumococcal proteins) data, Croucher et al. present a high-resolution analysis of the emergence of immune responses in children that can protect against pneumonia.

Anaerobic methanotrophic archaea play crucial roles in the methane cycle. Here, Zhang et al. provide experimental evidence supporting that multi-heme cytochromes mediate extracellular electron transfer for the reduction of metals and electrodes in these microorganisms.

To succeed, the REDD initiative needs a dose of 'GREEN' to restore degraded forests and help boost economic development, argues Andy White.

While multiple resistance-to-Phytophthora sojae loci/alleles have been mapped in soybean, many of them have become ineffective to newly evolved isolates. Here, the authors show that a 27.7-kb nucleotide-binding site-leucine-rich repeat gene confers broad-spectrum resistance to P. sojae in soybean.

Influenza A infection results in γδ T cell influx and production of IL-17 in the lungs. Here, the authors show that this effect is primed by CD1-restricted ligands that are released by infected cells and presented by B1a cells in the lungs.

Bacteria represent an unexploited reservoir of biosensing proteins. Here the authors use genomic screens and functional assays to isolate a progesterone sensing allosteric transcription factor and use a FRET-based method to develop an optical progesterone sensor.

A hierarchical membrane design combines atomic-level catalytic precision and industrial-scale water treatment. This design achieves an unprecedented implementation of single-atom catalysts for real-world wastewater treatment at pilot scale.

A deep learning approach bypasses iterative trials associated with sensorless adaptive optics to compensate for wavefront deformations when imaging biological specimens, enabling improved deep tissue localization microscopy.

Researchers praise the time and funding they are given for deep exploration.