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The type VI secretion system (T6SS) and Eag chaperones deliver toxic membrane protein effectors into rival cells. However, it is unknown how Eags and their effectors dissociate. Here, the authors show Eag chaperones bind effectors tightly and may release them via a subtle conformational change.

dSHERLOCK is a nucleic acid platform for the quantification of double-stranded DNA targets using CRISPR/Cas and isothermal amplification and is applied to quantify pathogen C. auris in clinical surveillance swab samples.

Enterololin is a narrow-spectrum antibiotic that selectively kills Enterobacteriaceae in vitro and in a mouse model of adherent-invasive Escherichia coli gut infection. AI-guided mechanism-of-action studies identified LolCDE as its molecular target.

In a multicenter, randomized trial of patients with atrial fibrillation and a low risk of thromboembolic events, treatment with the anticoagulant rivaroxaban showed no benefit in reducing cognitive decline, stroke or transient ischemic attack when compared to placebo.

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.

As Nature Aging celebrates its fifth anniversary, the journal asks some of the researchers who contributed to the journal early on to reflect on the past and the future of aging and age-related disease research, the impact of the field on human health now and in the future, and what challenges need to be addressed to ensure sustained progress.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Artificial intelligence is increasingly used for data analysis, literature synthesis and experimental design, posing a challenge to open research. Here, David Moher of the Ottawa Hospital Research Institute discusses how researchers, institutes, funders and publishers all have a role in keeping research transparent.

Anxiety-like behaviour in mice, as a result of psychological stress, is shown to be mediated by GDF15 release in response to adipose tissue lipolysis.

In this work, authors utilise a prefractionation natural product extract screening platform, which uncovers coniotins, lipopeptaibiotics with broad antifungal activity and a mechanism of action that targets fungal cell wall β-glucan.

Krisai et al. compare brain structure and cognitive function in elderly patients with and without atrial fibrillation using brain MRI and cognitive testing. They find that atrial fibrillation is associated with more brain lesions and lower cognitive function, but the cognitive impairment occurs primarily through direct effects of the arrhythmia rather than through brain damage.

MYC amplification is an independent prognostic factor for the most aggressive subgroup (Group 3) of pediatric medulloblastoma (G3 MB). Here, the authors highlight the role of the RNA-binding protein, Musashi-1 (MSI1) in G3 MB and identify MSI1-bound targets sharing MYC associated pathways.

Laser ablation of imaged surface layers under adaptive control enables volumetric imaging of samples consisting of heterogeneous tissues, such as the skull and brain.

Functional CRISPR screens in patient-matched pre-treatment and post-treatment glioblastoma models identify the PTP4A–ROBO1 axis as a driver of tumorigenicity and enriched ROBO1 expression in recurrent glioblastoma that can be targeted with CAR T cell therapy.

Gastrointestinal motility disorders affect over 20% of the population, yet current therapies provide limited relief. Here, the authors show that in a swine model a closed-loop GI neuroprosthesis restores peristalsis and enhances metabolic responses via targeted electrical and chemical stimulation

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Head-fixation system is widely used in neuroscience research but has limitations in application due to restraint. Here the authors developed a magnetic voluntary head-fixation system that allows stable rat hippocampal imaging during complex behaviors.

Caffeine may reduce cardiovascular disease risk, but the underlying mechanisms for these effects are incompletely understood. Here the authors report that caffeine inhibits the activation of the transcription factor SREBP2 to promote LDLc clearance through the PCSK9-LDLR axis.

Expression of VIM-2 leads to physiological trade-offs for bacterial pathogens that can be exploited to treat infections caused by multidrug-resistant bacteria.

A remora-inspired mechanical underwater adhesive device adheres securely to a range of soft substrates and maintains performance under extreme pH and moisture conditions, with potential applications in biosensing and drug delivery.

Microfluidic-generated polymer microparticles have been shown to have superior pharmacological performance; yet, mass production remains a challenge to industrial application. Here, the authors present and test a device that incorporates arrays of microparticle generators for mass production.

The Wnt molecular subgroup of medulloblastoma is associated with better prognosis than the other molecular subgroups. Here, the authors show that activating Wnt signaling impairs tumor development and improves survival in Group 3 and Group 4 medulloblastoma preclinical models.

The roles played by thrombin in the human intestinal mucosa are unclear. Here, the authors show that the commensal microbiota modulates epithelial production of active thrombin, which controls biofilm growth and contributes to protection of the mucosa from bacterial invasion.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

SynGFN integrates synthesis constraints directly into the chemical design process. The result is a generative framework that produces diverse, high-quality molecules that can be readily synthesized in the laboratory.

Reactive capture bypasses CO₂ regeneration, enabling efficient CO production but with low Faradaic efficiency. The authors report a Ni–N₃ molecular catalyst that resists amino acid adsorption and promotes efficient CO production in amino-acid systems.

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).

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Expansion of the chemical diversity of glycopeptide antibiotics (GPAs) to deal with the emergence and spread of GPA resistance is challenging. Here, the authors report a GPA synthetic biology platform in Streptomyces coelicolor for Type IV–V glycopeptide antibiotic production and discovery.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Using a neural network trained on bacterial growth inhibition data, in silico prediction of molecules with activity against Acinetobacter baumannii led to the identification of the narrow-spectrum abaucin, which perturbs lipoprotein trafficking.

Microbial natural products represent a large reservoir of potential pharmaceutical agents. Here, Johnston et al. describe a computer-automated programme for connecting genome sequences with identified and isolated natural products.

Choby et al. show that dynamic increases in the copy number of preexisting β-lactamase genes in heteroresistance enables resistance of continua of cellular subpopulations, flexibly overcoming enhanced β-lactams without new evolution and threatening the β-lactam pipeline.

Candida albicans must adapt to hypoxia. Here, the authors discover the sterol C4-methyl oxidase (SMO) Erg251 is essential for extreme hypoxic growth, as well as virulence and colonization, and that SMO inhibitors have therapeutic potential.

In this study, the authors analyse 2,409 nasopharyngeal swabs from 300 infants in Botswana to investigate the impacts of respiratory virus infection on the colonisation dynamics of bacterial respiratory pathobionts.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

A new lasso peptide antibiotic exhibits broad-spectrum activity against Gram-negative and Gram-positive bacteria by interfering with bacterial protein synthesis, is unaffected by common resistance mechanisms and shows no toxicity towards human cells.