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Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

An attractive route for carbon-negative synthesis of biochemical products is the reverse β-oxidation pathway coupled to the Wood-Ljungdahl pathway. Here the authors use a high-throughput in vitro prototyping workflow to screen 762 unique pathway combinations using cell-free extracts tailored for r-BOX to identify enzyme sets for enhanced product selectivity.

Self-propelled colloidal particles can be potentially used to transport cargoes at the microscale, but it is challenging to prevent randomization of their motion by Brownian rotations. Here, Das et al.quench these rotations by solid walls, which guide in-plane swimming without the need for external fields.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

Single-cell analyses of immune cells from patients with pathogenic, single large-scale mitochondrial DNA (mtDNA) deletions including Pearson syndrome describe heteroplasmy dynamics consistent with purifying selection, as well as T-cell state-specific regulatory mechanisms and metabolic vulnerabilities.

In this Perspective article, Garg and colleagues discuss the evidence linking abnormal aortic flow patterns with adverse cardiovascular outcomes and describe how changes in aortic flow can be targeted by novel aortic valve interventions.

La proteins are conserved factors critical for the maturation of RNA polymerase III transcripts. In the ciliate T. thermophila and related alveolates, La proteins have a novel domain arrangement and are linked to a distinct pre-tRNA processing pathway.

Environmental influences during prenatal development may have implications for health and disease later in life. Here, Czamara et al. assess DNA methylation in cord blood from new-born under various models including environmental and genetic effects individually and their additive or interaction effects.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

The association between obesity and breast cancer biology remains understudied in humans. Here, using a large retrospective data collection, the authors identify obesity associated changes in the genomic, transcriptomic profile, and the tumor microenvironment of primary untreated breast tumors.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Metabolomics data from germ-free and specific-pathogen-free mice reveal effects of the microbiome on host chemistry, identifying conjugations of bile acids that are also enriched in patients with inflammatory bowel disease or cystic fibrosis.

Accurate, phased assemblies are a key tool in understanding the human genome, particularly in highly polymorphic regions like the medically important MHC. Here the authors provide an assembly-based benchmark for this difficult-to-characterize region.

Genome-wide association analysis of an improved telomere length score, calculated from quantitative PCR and whole-genome sequencing measurements in 462,666 individuals in the UK Biobank, identifies novel genes and variants underlying this trait.

The interplay between amyloid and tau pathology in Alzheimer’s disease is still not well understood. Here, the authors show that amyloid-related increased in soluble p-tau is related to subsequent accumulation of tau aggregates and cognitive decline in early stage of the disease.

Ten years after the discovery of the Higgs boson, the ATLAS  experiment at CERN probes its kinematic properties with a significantly larger dataset from 2015–2018 and provides further insights on its interaction with other known particles.

An antibiotic identified via molecular-docking simulations and screening, and loaded into a bone-cement matrix, performs better than currently used antibiotic-loaded bone cements in the treatment of staphylococcal bone infections in rats.

Rich evidence of the potential co-benefits and trade-offs of natural climate solutions is available but remains poorly understood. Assessing the literature with machine learning methods, this study maps and analyses the growing evidence of trade-offs in natural climate solutions globally.

Recall-by-Genotype (RbG) is an approach to recall participants from genetic studies based on their specific genotype for further, more extensive phenotyping. Here, the authors discuss examples of RbG as well as practical and ethical considerations and provide an online tool to aid in designing RbG studies.

A set of three papers in Nature reports a new proteomics resource from the UK Biobank and initial analysis of common and rare genetic variant associations with plasma protein levels.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

In Alzheimer’s disease (AD) tau and neurodegeneration have complex regional relationships. Here, the authors show neuronal hypometabolism discordant with tau burden defines functional resilience or susceptibility to Alzheimer’s pathology via limbic/cortical axes. Susceptible groups have faster cognitive decline and evidence of non-Alzheimer’s pathologies.

Combining analysis of host proteome and transcriptome perturbations induced by tumour virus proteins with ongoing genome-wide studies of cancer facilitates the prioritization of cancer genes.

Measurements of the inelastic cross section of anti-³He allow the estimation of the transparency of the Milky Way to the propagation of these light antinuclei produced in either cosmic-ray collisions or annihilation of dark-matter particles.

A study comparing the pattern of single-nucleotide variation between unique and duplicated regions of the human genome shows that mutation rate and interlocus gene conversion are elevated in duplicated regions.

In a double-blind, randomized phase 2 trial, treatment of patients with heart failure with preserved ejection fraction (HFpEF) with the oral antifibrotic agent pirfenidone reduced myocardial fibrosis.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.

The KL-VS haplotype of the Klotho gene has been associated with reduced risk of Alzheimer’s disease and dementia. Here the authors show an association between the KL-VS haplotype and amyloid-dependent tau accumulation using PET data.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

A proportion of neurodevelopmental disorder and congenital anomaly cases remain without a genetic diagnosis. Here, the authors study aberrations of DNA methylation in such cases and find that epivariations might provide an explanation for some of these undiagnosed patients.

Analysis of two homologous groups of fungal pericyclases demonstrates how they can catalyse either an Alder-ene reaction—which has not previously been found in nature—or a hetero-Diels–Alder reaction.

By using sub-cycle light transients to induce optical field emission of electron pulses from tungsten nanotips and a weak replica of the same transient, investigation of attosecond emission dynamics in real time is demonstrated.

Bioinspired vascular networks transport heat and mass in multifunctional materials but lengthy multistep fabrication processes hinder large-scale application of structural vascular materials. Here, the authors report rapid, scalable, and synchronized fabrication of vascular thermosets and fiberreinforced composites under ambient conditions.

The identification of prognostic biomarkers can help stratify cancer patients. Here, the authors apply deep RNA sequencing from primary melanomas coupled with long-term clinical outcome data from a prospective multicentre phase III trial, to develop and validate a 121 metastasis-associated gene signature identifying early-stage melanoma patients at higher risk of metastasis and worse survival.

The direct measurement of the QCD dead cone in charm quark fragmentation is reported, using iterative declustering of jets tagged with a fully reconstructed charmed hadron.

Transplantation of glia-enriched organoids into the mouse brain enables the study of astrocyte subtypes.

Whole-genome sequencing of 3,171 cultivated and 195 wild chickpea accessions is used to construct a chickpea pan-genome, providing insight into chickpea evolution and enabling breeding strategies that could improve crop productivity.

Tau accumulation is associated with disease progression in Alzheimer’s disease. Here the authors use resting state fMRI and tau-PET to demonstrate that baseline connectivity in Alzheimer's disease is associated with tau spreading.

Polycyclic aromatic hydrocarbons play an important role in interstellar chemistry, where interaction with high energy photons can induce ionization and fragmentation reactions. Here the authors, with XUV-IR pump-probe experiments, investigate the ultrafast photoinduced dynamics of fluorene, phenanthrene and pyrene, providing insight into their preferred reaction channels.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Transcriptomic and proteomic profiling of breast cancer biopsies identifies baseline features of the tumor immune microenvironment associated with T cell clonal expansion following neoadjuvant anti-PD-1 treatment.

The Vertebrate Genome Project has used an optimized pipeline to generate high-quality genome assemblies for sixteen species (representing all major vertebrate classes), which have led to new biological insights.