Search

Mass spectrometry is a cornerstone of untargeted metabolomics, but comparisons across ionization modes have remained a substantial challenge due to the distinct fragmentation patterns produced by each polarity. Here, the authors present MS2DeepScore 2.0, a machine learning-based model to predict chemical similarity between mass fragmentation spectra, which works both between different and the same ionization modes.

ATPγS, a slowly-hydrolysed ATP analogue, causes kinesin to take extra backsteps under load. Here, the authors examine single-molecule mechanics and propose a state in which forward steps and coupled ATP hydrolysis are turned off, but unsteered steps are allowed.

Controlling reaction selectivity in complex multistep electrochemical transformations remains a major challenge. Here, the authors report that molecular interface engineering on silver electrodes enables precise regulation of key reaction intermediates for efficient ammonia electrosynthesis.

Neural mechanisms underlying active avoidance are not fully understood. Here authors show that avoidance actions are positively reinforced by learned safety signals. With training, control shifts from goal-directed to habitual behavior via distinct dorsal striatal circuits, like reward-based learning.

Houx and colleagues introduce a single-particle fluorescence spectroscopy method that detects and quantifies nanoscale condensates, revealing their rapid formation, dynamic behaviour, coalescence and selective maturation into amyloid-like aggregates.

In this article, the authors characterise genetic variation in CARTaGENE, a population-based cohort from Quebec, Canada. This genomic resource enables population and disease genetic studies in a founder population and other under-represented groups.

KRAS is an oncogene that switches between a GDP-bound inactive state and a GTP-bound active state. Recently developed KRAS G12C inhibitors are specific to the GDP-bound inactive state. Here, the authors develop a class of covalent KRAS G12C inhibitors capable of targeting both states for the treatment of KRAS-driven cancer.

Nudt21-mediated 3′UTR regulation orchestrates tissue regeneration through dose-dependent control of stem cell differentiation and multiprotein complex assembly, revealing alternative polyadenylation as essential for organismal survival.

Thermal imaging lenses are typically made from expensive materials such as germanium and silicon. Here, the authors synthesise a sulfur-based polymer with high mid-wave infrared and long-wave infrared transparencies, presenting a high-performing, low-cost alternative to traditional thermal imaging lens materials.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

A wearable that continuously measures the concentration of a drug is demonstrated in humans.

Using human iPSC-derived motor and cortical neurons as well as Drosophila models, the authors have identified a dysregulated Ku80–p53–SIRT1 axis downstream of DNA damage repair as a common pathogenic mechanism in both sporadic ALS and familial FTD.

Using 63 globally distributed grassland and shrubland sites from the International Drought Experiment, this study identified plant traits linked to drought resistance after 1 year of extreme drought across growth forms, lifespans and climate.

The authors present a genetically encoded tool based on a bifunctional enzyme that can regenerate NAD⁺ while executing an engineered glycerol shunt. The tool successfully restored redox imbalance and modulated lipid metabolism in vitro and in a mouse hepatic steatosis model.

Antibodies against SARS-CoV-2 continue to evolve 6 to 12 months after infection in patients who have recovered from COVID-19, increasing in potency and breadth with time.

Pangenomic and epidemiological analyses reveal a genetic shift in U.S. Salmonella Hadar populations during 2019–20, driven by expansion of a lineage carrying a prophage-like element that likely arose in commercial poultry and spread to backyard flocks.

PhenoMol integrates graph theory and biological knowledge to reduce multi-omic dimensionality, predict phenotypes, and reveal causal patterns. It outperforms conventional models that lack biological constraints and is openly available for health, performance, and disease research.

A comprehensive atlas platform integrating transcriptional and epigenetic data enables more precise engineering of T cell states, accelerating the rational design of more effective cellular immunotherapies.

A lipid nanoparticle that delivers mRNA encoding for regenerative factors to the endometrium with high specificity restores implantation rates in a murine model of endometrial injury with potentially improved safety.

Natural Killer cells are key mediators of anti-tumour immunosurveillance and anti-viral immunity. Here, the authors map regulatory genetic variation in primary Natural Killer cells, providing new insights into their role in human health and disease.

New York City’s walkability and climate goals require better city-scale pedestrian data, yet such data are mostly absent. This study develops a foot-traffic model for New York City, revealing undercounted pedestrian corridors, with major implications for planning and safety interventions.

The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

Disease course and pathology an infection may cause can change owing to the structural and functional physiological changes that accumulate with age, but therapy can be tailored accordingly; disease tolerance genes show antagonistic pleiotropy.

N¹-Methylpseudouridine enhances the translation of synthetic mRNAs, independently of innate immunity.

The West Antarctic Ice Sheet responded to different natural forcing mechanisms than the East Antarctic Ice Sheet through the mid-Pliocene due to a greater sensitivity to oceanic feedbacks, according to iceberg-rafted debris records and ice-sheet modelling experiments.

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.

The [1,2]-Wittig rearrangement of allylic ethers is traditionally considered to proceed via formation and recombination of radical pairs. Now it has been shown that an alternative reaction cascade, involving initial enantioselective [2,3]-rearrangement followed by base-promoted anionic fragmentation–recombination that proceeds with high enantiospecificity, allows a catalytic enantioselective [1,2]-Wittig process.

Detection of hot intracluster gas in SPT2349−56 with the Atacama Large Millimeter/submillimeter Array provides new insights into early cluster formation.

In this multicenter phase 1 trial of patients with advanced solid tumors resistant to anti-PD-1 therapy, treatment with the anti-latent TGFβ1 antibody linavonkibart with or without pembrolizumab was safe, and encouraging clinical response rates were associated with T cell infiltration and immune activation.

Here, in an open-label pilot trial, the authors show that multi-donor fecal microbiota transfer in young women with anorexia nervosa was well tolerated and led to lasting changes in gut bacteria, supporting further research on microbiome-based treatments.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

Mucosal influenza vaccines promise enhanced protection but lack defined immune correlates of protection. Here, the authors conduct a phase I trial of an intranasal recombinant influenza A/H5 vaccine with a nanoemulsion adjuvant, demonstrating successful mucosal priming and broad cross-clade immune responses, advancing the development of intranasal influenza vaccines.

FACED 2.0 builds on and expands the capabilities of the free-space angular-chirp-enhanced delay microscopy approach. Its high speed, large field of view and volumetric coverage enable two-photon voltage imaging of hundreds of neurons or calcium imaging of thousands of neurons in the mouse or zebrafish brain.

Host antibodies can alter the glycan binding of adhesin proteins from infectious bacteria, but the antibodies’ mechanisms of action remain unclear. Here, the authors define four mechanisms of modulation, including ligand mimicry and multiple modes of allosteric interference.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

Non-covalent lasso entanglements are pervasive structural features of increasing importance. Here, the authors show that these entanglements are associated with in vitro misfolding across the E. coli proteome and that chaperones preferentially rescue such misfolding in essential proteins.

The heteromeric insect TRPV channel, Nanchung-Inactive, is a previously structurally uncharacterized insecticide target. Here, Fedor et al. provide insights into how an insecticide and a natural agonist modulate channel behavior, paving the way for future insecticide development.

The origin of the nematic state in the kagome metal CsTi₃Bi₅ remains unclear. Here, using polarization-dependent angle-resolved photoelectron spectroscopy and ab initio based field theoretical methods, the authors propose a d-wave nematic order driven by electronic correlations via an orbital-selective mechanism.

Pulmonary type 2 inflammation is associated with type 2 innate lymphoid cells. Here the authors use the Collaborative Cross mouse panel to show that ILC2 abundance during type 2 lung inflammation is different across the panel and identify free-fatty acid receptor 3 (Ffar3) as a gene responsible and show cytokine and ILC2 functional changes.

This study demonstrates that the extracellular matrix (ECM) of the developing brain stabilizes recently born synapses. The authors identify a microglial metalloprotease that digests the ECM to increase the plasticity of these newborn synapses.

The disruption of the rhomboid protease gene glpG in E. coli leads to defects in bacterial colonization. Here, the authors show that GlpG is essential for the assembly of type 1 pili, a virulence factor required for colonization of bacteria in eukaryotic cells.

Animal models of drug use require specialized technical expertise and often differ from how humans consume drugs. Here, the authors establish a robust method which allows mice to self-administer intranasal cocaine, greatly improving face validity and ease of use.

Conventional PROTACs have limited capacity for misfolded proteins. Here, authors develop a BioPROTAC containing an scFv specifically targeting misfolded SOD1, fused to an E3 ligase, and demonstrate a strategy for reducing misfolded SOD1 accumulation.

Mass-wasting deposits that accumulated against mid-ocean ridge faults have high porosity in which calcium carbonate precipitated, storing seawater carbon dioxide, as revealed by cores of a 61-million-year-old seafloor talus deposit.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

In this 4-year unblinded follow-up study, the authors evaluate 63% of the participants of a double-blind randomised control trial that assessed the effects of faecal microbiota transplantation (FMT) on adolescents with obesity.

Vinyl acetate is an important polymer building block, but the mechanisms governing its catalytic production are not well understood. This study shows that dynamic palladium-acetate clusters determine catalyst efficiency and selectivity in vinyl acetate synthesis.

A high-resolution transcriptomic and epigenomic cell-type atlas of the developing mouse visual cortex from embryonic to postnatal development is presented, providing a real-time dynamic molecular map associated with individual cell types and specific developmental events.