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Cerebellar Purkinje cells feature intrinsic activity early in postnatal development. Here, the authors show that disrupting this early activity impairs gene expression, morphological development, and motor function, linking deficits to cerebellar disorders.

The growth of the smallest aerosol particles is critical to their impacts on climate and air quality. Here, the concentration gradient of nanoparticles is shown to be an important microphysical mechanism for their rapid initial growth.

Exposome analyses across 34 countries showed that social exposures were associated with faster functional brain aging and physical exposures with faster structural brain aging.

An analysis of rare disease cohorts from the UK, the USA, Italy and the Netherlands identifies a neurodevelopmental disorder caused by biallelic variants in RNU2-2. Individuals with this disorder have substantially reduced levels of U2-2 small nuclear RNA in blood.

Here, the authors show that bile salt hydrolase activity is common among human gut bacterial isolates spanning seven major phyla and identify strains capable of directly dehydrogenating conjugated bile acids via hydroxysteroid dehydrogenases to produce conjugated secondary bile acids, challenging the notion that deconjugation is a prerequisite for further bile acid modifications.

Post-transcriptional regulation of mRNA translation was explored using Ribo-STAMP and single-cell RNA sequencing to reveal cell-type-specific and isoform-specific translation patterns across hippocampal neuronal and non-neuronal cell types, highlighting functional differences between CA1 and CA3.

Using two newly developed immunoassays tested in three clinical cohorts, this study highlights CSF DOPA decarboxylase as a promising biomarker for differentiating dementia with Lewy bodies and Parkinson’s disease from Alzheimer’s disease and controls.

The phase 3 STEER trial showed that a single intrathecal dose of onasemnogene abeparvovec significantly improved motor function in children and adolescents with spinal muscular atrophy versus sham, with a similar and acceptable safety profile.

An algorithm that combines deep learning, Bayesian optimization and computer vision techniques can be used to autonomously tune a semiconductor spin qubit from a grounded device to Rabi oscillations.

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.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

Neurotrophic factor Nerve Growth Factor (NGF) is involved in bladder physiopathology. Here the authors report that mast-cell derived NGF sustains the pro-tumoral functions of ILC2s in bladder cancer (BC), showing that selective targeting of the NGF receptor TrkA improves survival and response to immune checkpoint blockade in BC models.

Lo Vecchio, Discepolo et al., characterize the serum metabolomic profiles of children with acute SARS-CoV-2 infection and multisystem inflammatory syndrome (MIS-C). Distinct metabolic signatures involving inflammation, oxidative stress, and lipid metabolism correlate with age and disease severity, associate with MIS-C as a unique metabolic phenotype and reverse upon recovery.

One of three back-to-back papers to show that dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance CAR T cell therapies for cancer.

Sheep producers face growing expectations to produce more food, conserve biodiversity, stay profitable and cut emissions. The authors find that interventions work best when addressing underperforming environmental, economic, or psychological areas.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Analysis of 37 genomes together with more than 140 phenotypic traits links genomic features to ecological fitness and lifestyle diversity in Trichoderma fungi.

Standard first line therapy in patients with non-small cell lung cancer is immunotherapy but responses vary and consistent predictive biomarkers are lacking. Here, using RNA-sequencing data from a large clinical trial in NSCLC patients, the authors define four molecular subsets with distinct tumour-intrinsic and -extrinsic features with differing outcomes to immunotherapy combinations.

The MOUNTAINEER phase 2 trial demonstrated the efficacy and safety of tucatinib (HER2-targeted TKI) and trastuzumab (anti-HER2 antibody) in patients with HER2 + , RAS wildtype unresectable or metastatic colorectal cancer that had progressed on chemotherapy, resulting in the approval of the regimen. Here, the authors report the updated analysis of the MOUNTAINEER trial.

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.

Nanomechanical measurements of molecular thin films are non-trivial due to ease of perturbation of the molecular surface. The authors present a direct, experimental demonstration of the tunability in the nanomechanical properties for a family of molecular semiconductors with systematic alkyl sidechain substitution.

Post-acute infection syndromes often have heterogeneous symptoms that are difficult to interpret. Here, the authors develop a latent trajectory analysis framework designed to categorise complex relationships in longitudinal data into distinct disease phenotypes and analyse transitions between them.

Quintana and colleagues describe the engineering of oncolytic viruses armed with multiple immunomodulators and with targeted tropism for tumor cells for glioblastoma immunotherapy.

Schiattarella and colleagues propose a framework linking heart failure with preserved ejection fraction and metabolic dysfunction-associated steatotic liver disease as interconnected syndromes rather than coincidental comorbidities. The authors delineate shared metabolic, inflammatory and endocrine drivers and propose a shift towards coordinated strategies and integrated clinical algorithms to improve prevention, risk stratification, early detection and co-management of these disorders.

Regrowth of lost enamel in tooth decay and sensitivity is a major obstacle to overcome. Here, the authors report on a protein-based material that mimics features of natural enamel formation, allowing for epitaxial growth of apatite nanocrystals to restore enamel structure and function.

iGluSnFR4f and iGluSnFR4s are the latest generation of genetically encoded glutamate sensors. They are advantageous for detecting rapid dynamics and large population activity, respectively, as demonstrated in a variety of applications in the mouse brain.

Natural products have historically made a major contribution to pharmacotherapy, but also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization. This Review discusses recent technological developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — that are enabling a revitalization of natural product-based drug discovery.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Multisystem inflammatory syndrome following SARS-CoV-2 infection results from increased serum levels of TGFβ, which impairs the reactivation of virus-specific T cells.

This study shows that Alteromonas is a key driver of phosphorus recycling in the ocean and that its alkaline phosphatases are multifunctional—with different families coexisting in one genome by adopting distinct functions and secretion strategies.

A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

Small-scale vorticity dynamics are central to turbulence, but their transient and chaotic nature makes direct measurement and control extremely challenging. By using magnetically driven particles, authors uncover stochastic resonance and a symmetry-breaking mechanism that may enable both control of particle dynamics and a magnetic resonance- based method for probing turbulence at its smallest scales.

The authors report on the implementation of a data-efficient machine learning approach to predict plasma dynamics. This enables offline design of robust trajectories to terminate the plasma without disruptive instabilities. Experimental results at the TCV tokamak show statistically significant improvements in key figures of merit and the ability to a priori predict the dynamics of key plasma properties.

Here, the authors experimentally demonstrate a platform for tunable polariton refractive and meta-optics based on hexagonal boron nitride and phase change Ge₃Sb₂Te₆. This combination has the advantage of the long-lived phonon-polariton with switchable refractive index of the phase change material.

Being able to predict the final size of an earthquake while rupture is ongoing is a largely debated scientific problem. Here, the authors suggest that the evolution of P-wave peak displacement holds information regarding the early stage of the rupture process and may be a proxy for the final size of the event.

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.

Here authors show loss of AKAP11, a strong genetic risk factor for bipolar disorder and schizophrenia, disrupts PKA proteostasis and signaling, leading to widespread transcriptomic alterations across the brain, particularly in striatal neurons, as well as altered behavior.

Consensus exists on the urgent need for food systems to be more sustainable, but defining their environmentally safe operating space is challenging. This study proposes food system boundaries as a share of planetary boundaries, defining budgets across nine boundaries and revealing where boundary transgression is most critical.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

Here, the authors compared measurements between 34 laboratories from 19 countries, to quantify by mass spectrometry four ceramides of clinical relevance in human blood plasma Standard Reference Materials. The main goals were to evaluate concordance obtained in a large inter-laboratory trial and to report absolute concentrations of four circulating lipids in a publicly available standard.