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Down syndrome (DS) increases gene dosage that disrupts neurodevelopment and cognition. Using human-derived isogenic neurons, this study reveals altered network activity, synaptic dysfunction, and ion channel defects underlying DS neural impairment.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

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.

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.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Differentiating DCs express ALDH1A2, which produces retinoic acid and suppresses DC activity. Blocking this pathway with a new inhibitor, KyA33, enhances immune responses and boosts the effectiveness of DC cancer vaccines in mouse models.

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.

Respiration enhances cerebrospinal fluid flow through mechanical and autonomic pathways. Inhale length and diaphragm motion influence its displacement and net flow, identifying a modifiable, noninvasive mechanism relevant to brain homeostasis.

HMGCR is upregulated by E2F1, driving ferroptosis resistance by reducing oxidative damage triggered by T cell-based therapy. Notably, targeting HMGCR restores ferroptosis sensitivity in immune-refractory tumors, enhancing response to PD-1 blockade as well as adoptive T cell transfer therapy.

The authors developed a highly sensitive skin-conformal NIR organic photodetector with fast photoresponse speed that achieves MHz-speed, angle-free, and long-range (100 m) wireless optical communication with stable performance under mechanical deformation.

A lead-free, flexible, and disposable ultrasound patch using silicon nanocolumns enables vascular imaging and real-time blood pressure monitoring, offering a low-cost and eco-friendly solution for wearable medical diagnostics.

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.

Autism spectrum disorder (ASD) is characterized by heterogeneous phenotypes. Disruption of the gut–brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, the authors propose a framework to leverage multi-omic datasets and investigate how the GBA influences ASD.

This study presents ECloudGen, which uses latent diffusion to generate electron clouds from protein pockets and decodes them into molecules. The adopted two-stage training expands the chemical space accessible to generative drug design.

Mutation detection in cfDNA is crucial for cancer diagnosis and monitoring. Here, the authors develop an Enzymatic Cleavage-directed Single Nucleotide Variant Sequencing by integrating Argonaute-mediated cleavage and stem-loop DNA-initiated PCR amplification for cfDNA mutation detection.

An effective CRISPR RNA occlusion strategy enhances mismatch detection when using Cas13.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

Colorectal cancer is often diagnosed at later stages, leading to poor prognosis. Here, the authors utilise analysis of rectal mucus specimens using host and microbial analysis to detect cancer lesions.

Transition metal dichalcogenides are emerging two-dimensional materials, yet monodisperse and stoichiometrically pristine sample production is challenging. Here, the authors employ a block copolymer to control buoyant density for isopycnic density gradient ultracentrifugation, allowing thickness sorting of the material.

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.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

Genetic background, plasma metabolome and dietary data from 4,215 women and 1,490 men reveal 57 metabolites whose associations with dementia risk vary by APOE4 genotype and other risk variants.

Thermal lepton pairs are ideal probes for the temperature of quark-gluon plasma. Here, the STAR Collaboration uses thermal electron-positron pair production to measure quark-gluon plasma average temperature at different stages of the evolution.

Metagenomic analysis of the gut microbiome of people with human immunodeficiency virus (HIV), from three distinct cohorts, revealed infection- and antiretroviral drug-linked alterations, which may contribute to HIV-associated non-infectious comorbidities.

Transcriptional and epigenetic mechanisms governing T cell exhaustion substantially impact immunotherapy effectiveness. In this Review, Kang et al. outline epigenetic regulatory programmes that influence T cell differentiation fates, proposing strategies to enhance clinical outcomes and immunotherapy durability in cancer through improved understanding of T cell biology.

Atomic structural changes in nanocrystals are still poorly understood. Here, the authors introduce time-resolved Brownian tomography to directly detect 3D atomic changes in Pt nanocrystals during oxidative etching and reveal disorder at sizes of ≈1 nm.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

The Mass Spectrometry Query Language (MassQL) is an open-source language that enables instrument-independent searching across mass spectrometry data for complex patterns of interest via concise and expressive queries without the need for programming skills.

Sorghum is a source of lignocellulosic biomass for the production of renewable fuels. Here the authors characterise the sorghum secondary cell wall using multi-dimensional magic angle spinning solid-state NMR and present a model dominated by interactions between three-fold screw xylan and amorphous cellulose.

The authors report resonant soft x-ray scattering and polarimetry measurements on epitaxial thin films of La3Ni2O7. They find a diagonal bicollinear double spin stripe order, with no evidence of charge modulation.

Polymersomes are used as a delivery vehicle for protein, nucleic acid adjuvant and siRNA payloads by enhancing the encapsulation efficiency through copolymer design.

The release of triplet or singlet oxygen is governed by individual Marcus normal and inverted region behaviour.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

In cuprates, superconductivity exists in a narrow window at high electron doping concentration with strong antiferromagnetic correlations. Here, the authors demonstrate superconductivity with no effect of antiferromagnetic order in a cuprate for a wide electron doping range following a protect anneal process.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

The management of ulcerative colitis (UC) remains challenging due to the complexity of its etiology. Here, the authors establish that argininosuccinate synthetase 1 (ASS1) and its metabolite arginine are pivotal inducers of UC, through the triggering of mTOR and iNOS activation, and the induction of gut microbiota dysbiosis by metabolomics and proteomics. Inhibition of ASS1 by C-01 provides a viable strategy for the treatment of UC.

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.

The placement of nanomaterials at predefined locations is a key requirement for their integration in nanoelectronic devices. Here, the authors devise a method allowing placement of solution-based nanomaterials by using structured graphene layers as deposition sites with the aid of an electric field.

Deltex E3s modify ADP-ribosylated targets with ubiquitin, creating a hybrid modification whose readers remains unknown. Here, the authors synthesise a non-hydrolysable probe that mimics the modification and identify RNF114 as an interactor. RNF114 binds tightly to this modification and further elongates it with a K11-linked ubiquitin chain.

How the dauer, an alternative developmental stage in nematodes, exhibits distinct behavioral traits remains unclear. Here, the authors reveal the neural circuitry underlying these distinctions by reconstructing the dauer connectome and comparing it with other stages.

A new artificial intelligence model, DeepSeek-R1, is introduced, demonstrating that the reasoning abilities of large language models can be incentivized through pure reinforcement learning, removing the need for human-annotated demonstrations.