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In the nucleus accumbens, acetylcholine boosts dopamine release to promote effortful behaviour.

How neuron-level interactions produce complex cognitive behavior remains unclear. Here, the authors develop a brain circuit mechanistic model based on physiological computation, that uncovers an unexpected neural code, subsequently validated by empirical data.

Saito et al. identify sphingosine kinase 1 as a critical regulator of physiological ductus arteriosus closure and pathological supravalvular aortic stenosis through its role in smooth muscle cell proliferation and propose potential therapeutics.

The activity of the membrane-bound enzyme pMMO depends on copper but the location of the copper centers is still under debate. Here, the authors reconstitute pMMO in nanodiscs and use native top-down MS to localize its copper centers, providing insights into which sites are essential for activity.

The meningeal compartment communicates with the brain to modulate homeostatic functions. Here, the authors demonstrate that natural killer (NK) cells and innate lymphoid cells (ILC) 1 shape synaptic neuronal transmission and affect mouse behavior.

Pseudaminic acids (Pse) are a family of carbohydrates found within bacterial lipopolysaccharides, capsular polysaccharides and glycoproteins. Now, monoclonal antibodies have been developed that recognize diverse Pse across several bacterial species, enabling mapping of the Pse glycoproteome and demonstrating therapeutic potential against multidrug-resistant Acinetobacter baumanii in in vitro and in vivo infection models.

Zhang et al. show that the activation of RIPK1 is suppressed by acetylhypusination in a spermidine-dependent manner. Disruption of this axis contributes to RIPK1-mediated vascular pathology to promote insulin resistance and diabetic kidney pathology.

Antigen presentation in skull bone marrow by hematopoietic stem and progenitor cells induces myelopoiesis and generates CD4⁺ regulatory T cells in a mouse model of ependymoma, promoting immune tolerance. Treatment with anti-GM-CSF antibody has antitumor effects that are augmented by immunotherapy.

The viscosity of tumour cells is shown to govern their ability to disseminate through the bloodstream and extravasate, establishing a key biomechanical factor of metastasis.

VTA dopamine activity control movement-related performance, not reward prediction errors. Here, authors show that behavioral changes during Pavlovian learning explain DA activity regardless of reward prediction or valence, supporting an adaptive gain model of DA function.

The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

An anti-HIV-1 antibody that targets an N332_gp120 glycan-independent V3 epitope, a site of Env vulnerability, can decline viremia in HIV-1-infected humanized mice while overcoming classical V3 escape mutations.

Nucleosides, nucleotides and nucleic acids with N6 modified adenosine are important for the areas of disease diagnosis and treatment, biological chemistry, and nanotechnology, but challenging to synthesize. Here, the authors develop a practical alkylation at the N6-position of adenines in adenosine and its analogues, as well as late-stage functionalization of nucleotides/oligonucleotides through photoredox and copper co-catalyzed decarboxylative C(sp³)-N cross-coupling reaction.

Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

Mutations in the PBAF chromatin-remodeling complex cause various neurodevelopmental disorders. This study shows that PBAF shapes distinct motor neuron identities, revealing how its disruption impairs movement and offering insight into neurodevelopmental disorders caused by PBAF mutations.

A flexible, floating microelectrode array that has a reconfigurable spiral thread design can be used to create large-scale, long-term brain–computer interfaces in the primate brain.

Zhu et al. find that aging causes region-specific myelin damage in the spinal cord, which is counteracted by enhanced TGFβ signaling in microglia, revealing a protective mechanism for healthy aging.

Functional studies of O-GlcNAcylation have often focused on individual modifications. Now, a systems-level approach has identified simultaneous O-GlcNAcylation events that coordinate cellular activities and tissue-specific functions.

Muscularis macrophages, housekeepers of enteric nervous system integrity and intestinal homeostasis, modulate α-synuclein pathology and neurodegeneration in models of Parkinson’s disease, and understanding the accompanying mechanisms could pave the way for early-stage biomarkers.

Thymine DNA glycosylase (TDG) was identified as a synthetic-lethal target in p53-deficient cancers through alterations in double-stranded RNA accumulation. A covalent small-molecule inhibitor of TDG exhibited potent efficacy against p53-deficient tumors.

Cryogenic transport measurements of CsV₃Sb₅ nanobeams show a zero-field Josephson diode effect and radio-frequency rectification with power-dependent quantized voltage output.

Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

How leptin signalling produces anti‑obesity effects is incompletely understood. Here, the authors demonstrate that FAK and PYK2 are required for STAT3 activation, normal leptin responses, and HDAC6 inhibitor‑mediated weight loss, with their loss causing hyperphagic obesity.

Intelectin-2 defends mucosal interfaces by crosslinking mucus and blocking microbial growth. This study reveals that mouse and human intelectin-2 recognizes galactose-rich glycans to bind and target diverse bacteria—uncovering a potent, dual-action lectin that shapes host–microbe balance.

Here the authors show a feedback loop between active aldehydes and fatty acid oxidation that can reprogram T cell metabolism to promote exhaustion thereby limiting antitumor T cell immunity.

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.

Quantum interference of sodium nanoparticles, which can each contain more than 7,000 atoms at masses greater than 170,000 Da, is demonstrated.

This study examines long-term changes in species richness across tropical forests in the Andes and Amazon. Hotter, drier and more seasonal forests in the eastern and southern Amazon are losing species, while Northern Andean forests are accumulating species, acting as a refuge for climate-displaced species.

Induction of hypothermia during hibernation/torpor enables certain mammals to survive under extreme conditions. Here, the authors show that the natural product P57 induces hypothermia by targeting pyridoxal kinase and has a potential application in therapeutic hypothermia.

The enzyme PCMT1 was found to install a C-terminal cyclic imide modification on proteins that marks them for degradation by CRBN, uncovering a conserved protein turnover pathway with implications in metabolism and neurological function.

This study uses single-nucleus RNA sequencing to analyze lung tissue from 141 individuals with chronic obstructive pulmonary disease. Distinct patterns of spatially resolved changes in cell composition and cell states that correlate with clinical features are highlighted.

Polyamines prevent the action of kinases on acidic phosphorylatable motifs in spliceosomal proteins, thus providing a mechanism for metabolite-mediated regulation of alternative splicing in cells.

Inhibitor-induced kinase degradation is a common event that positions supercharging of endogenous degradation circuits as an alternative to classical proximity-inducing degraders.

Using low-intensity focused ultrasound, the authors show that targeted modulation of specific thalamic subregions alters human visual perception, revealing a causal role of the anterior thalamus in shaping conscious experience.

This work presents a unified MS/MS spectral library of drugs and metabolites integrated with standardized pharmacologic metadata, enabling scalable, individualized profiling of drug exposure and metabolism directly from untargeted metabolomics data.

Activity-based protein profiling identifies covalent small molecules that potentiate the activity of the METTL5:TRMT112 complex through binding to a complexoform-restricted allosteric pocket absent in other TRMT112:methyltransferase complexes

Cataloguing Nt-arginylated proteins is prone to false positives. Here, the authors use MS-based fine-tuned LLM models with molecular proxies-physically identical yet known false positives-to discriminate true sites. They further track the modifications over time using prediction-based targeted MS.

Selecting for varieties of commercial crops with enhanced nutritional quality is important in agriculture. Here, the authors identify alleles of a gene in tomatoes that give rise to increased levels of vitamin E and find that the promoter of the gene is differentially methylated.

The existence of a long-lived, prethermal regime in many-body systems with tunable heating rates, driven by structured random protocols, is observed using a 78-qubit superconducting quantum processor.

The hierarchy of DNA repair pathways at stalled replication forks is not fully understood. Here, the authors isolate two mutations in yeast RAD51 with defects in binding to duplex DNA and stalled replication forks, suggesting a role of Rad51 duplex DNA binding in fork stabilization and postreplication repair.

Moral-Sanz, Fernández-Carrasco and colleagues identify senolytic properties of sea anemone-derived pore-forming toxins, with selectivity mediated by senescence-associated lipid profiles. An optimized senotoxin improves the efficacy of chemotherapy in mouse models.

DNA damage can arise from natural cellular processes, but how cells prevent resulting mutations is unclear. Here, the authors show that the enzyme Polκ protects mouse tissues from mutations caused by endogenous guanine lesions, revealing how DNA repair and damage tolerance pathways cooperate to maintain genome integrity.

Floquet engineering is often limited by weak light–matter coupling and heating. Now it is shown that exciton-driven fields in monolayer semiconductors produce stronger, longer-lived Floquet effects and reveal hybridization linked to excitonic phases.

Chemical language models trained on known metabolites can identify previously unknown metabolites from mass spectrometry-based metabolomics data with high accuracy.

LipoID profiles lipid droplet interactions and identifies interorganelle regulators.

The efficiency of selenium photovoltaics is hindered by the poor crystallization of the Se film. Wen, Li, Lu and colleagues use light to initiate Se crystallization, suppressing dewetting and enabling the formation of a continuous film, which achieves a certified efficiency of 10.3%.

Reconfigurable cell-sized compartments can act as artificial cellular models that dynamically respond to environmental stimuli, mimicking the adaptive behaviours of living cells. Here, the authors present enzymatically active liquid crystalline (LC) coacervate microdroplets as a protocell model, which undergoes differentiation into helicoidal vesicles and eventually membranous protocells containing artificial organelles.

A soft, biodegradable, wireless sensing device can monitor pressure, temperature and strain over long distances (up to 16 cm), maintaining accuracy across varying positions and angles.