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Through integrated multi-omics and experimental validation, this study reveals that altered gut microbiota and bile acid metabolism activate TLR3 to induce urothelial injury in interstitial cystitis, identifying a pathway with therapeutic potential.

Untargeted metabolomics faces challenges in metabolite origin inference and metabolite annotation. Here, the authors present TidyMass2, a user-friendly computational framework with metabolite origin inference and feature-based functional module analysis to enhance biological interpretation.

In patients with hypopharyngeal squamous cell carcinoma (HPSCC), resistance to the standard-of-care induction chemotherapy often occurs. Here, using longitudinal single-cell transcriptomic profiling of HPSCC samples from patients receiving induction chemotherapy, the authors identify a ZNF683-high natural killer (NK) cell population as a predictor of chemotherapy response.

High-resolution satellite data enables a unique verification of national methane emissions worldwide. Global estimates are 63 Tg a⁻¹ for oil-gas, 30% higher than the UNFCCC reports due to under-reporting by four largest emitters, and 33 Tg a⁻¹ for coal, consistent with previous estimates.

This study identifies regions and features of three stages of plateau evolution in the present-day Tibetan Plateau, based on structural features of intra-crustal low-velocity zones, depth of the crust-mantle boundary and surface topography.

CRISPR-Cas12a diagnostics are limited by strict PAM requirements. Here, authors show that higher temperatures activate numerous noncanonical PAMs, enabling a versatile one-pot platform that improves sensitivity, specificity, and rapid on-site pathogen detection.

Multi-modal integration of spatial transcriptomes and metabolomes via haCCA reveals metabolic heterogeneity and NETs-mediated Scd1 upregulation driving fatty acid metabolism in intrahepatic cholangiocarcinoma.

NIID is a neurodegenerative disease caused by GGC repeat expansions within NOTCH2NLC gene. Here, authors develop a precise gene-editing therapy that effectively treats the disease in multiple models.

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.

Fibre integrated circuits created by first preparing circuitry on extremely thin and flexible substrates and then mechanically rolling them up demonstrate microdevice density reaching 100,000 transistors per centimetre and excellent stability under harsh service conditions.

A computational workflow, LyMOI, uses LLM, knowledge graphs and other tools to facilitate ’omic analysis and hypothesis generation related to autophagy.

A virus-mimicking micelle selectively delivers drugs to diseased chondrocytes in osteoarthritis, significantly alleviating disease progression in mouse and sheep models.

Medullary thyroid carcinoma (MTC) is a rare and aggressive neuroendocrine tumor with limited risk stratification. Here, the authors perform multi-omic analysis of MTC samples from 452 patients across 10 Chinese clinical centers, identify molecular subtypes and develop a prediction model.

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.

Nuclear Factor IA is important for development and metabolism. Here, the authors present high-resolution molecular structures of Nuclear Factor IA, and detail how it recognizes the TGGCA DNA motif.

Energy consumption is a challenge in AI hardware. The authors introduce a volitional neuromorphic device that mimics human visual attention, achieving high energy efficiency and precise object tracking with minimal data redundancy.

The mechanisms underlying oligodendrocyte precursor cells (OPCs) and neuron interactions remain unclear. Here, the authors show that chromatin remodeler BAF155 regulates OPC differentiation and myelination by coordinating synaptic genes for OPC neuron communication, contributing to autism-like behavioral deficits in mice

This study demonstrates a low-energy photon device based on the kagome metal RbV₃Sb₅. It demonstrates that Fermi surface reconstruction, driven by a phase transition, leads to the emergence of van Hove singularities near the Fermi level.

LINE-1 retrotransposons are implicated in aging, but their role in cardiac aging specifically is not well understood. Here the authors show that LINE-1 expression rises in mouse hearts with age. Genetic LINE-1 derepression is accompanied by cGAS–STING activation and cardiac dysfunction, while pharmacological inhibition of LINE-1 or STING improves cardiac function in aged mice.

Previous clinical studies suggested that Insulin-like growth factor binding-protein 7 (IGFBP7) is elevated in early stages of diabetes. Here authors showed tubule and glomerular-specific IGFBP7 promotes diabetic kidney disease.

The mechanisms underlying the improved survival in HPV-positive penile squamous cell carcinoma (PSCC) compared to HPV-negative counterparts remain to be explored. Here, single-cell sequencing highlights the role of the B cell-IgA-PIGR axis in enhancing antitumor immunity and improving clinical outcomes in HPV-positive PSCC.

Chen et al. show that redox signals activate ADAR1 to fix faulty RNA pieces during DNA copying, ensuring smooth replication and protecting genome stability.

Engineered inhalable exosomes deliver a bispecific T cell activator to pembrolizumab-resistant metastatic melanoma.

Overcoming the suppressive tumor microenvironment (TME) is crucial to improving the efficacy of cancer therapy. Here the authors show that, in mouse cancer models, administration of exogenous IL-16 establishes a Th1-dominant TME via regulation of glutamine catabolism and triggers a Th1 cell-macrophage crosstalk, enhancing anti-tumor immune responses and the efficacy of immunotherapy.

Stable adipocytes resist lipolysis in healthy states but are highly susceptible to a catecholamine-independent, neurosystemic pathway-driven catabolic state.

The exponential growth of data traffic demands efficient transmission systems. Here, authors exploit a self-injection-locked microcomb to achieve high-capacity optical transmission, demonstrating a compact, lightweight system with potential for data centers and edge computing applications.

The [2+2] cycloaddition of two alkenes is the most efficient route to four-membered carbocycles, but it is thermally forbidden. Now, installing fluorine atoms at the alkene terminus enables intramolecular thermally crossed [2+2] cycloaddition, providing a strategy for constructing gem-difluoro heterobicyclo[n.1.1]alkanes.

Bronchiectasis and asthma can co-exist in the same patient, and the characteristics may be different from bronchiectasis alone. Here the authors characterise the function of ILC3 cells and how IL-17C potentiates IL-17A expression promoting a neutrophil dominated asthma endotype in mouse bronchiectasis-asthma models.

Diabetes, a frequent co-morbidity to osteoarthritis, accelerates progression of joint inflammation. Here author show that hyperglycaemia enhances glycolysis in synovial macrophages, leading to increased lactylation of CD11b, which impairs the capacity of macrophages to phagocytose apoptotic cells, which eventually aggravates inflammation.

Acetyl-coenzyme A functions as a non-canonical signal to trigger mitophagy, and the acetyl-coenzyme A–NLRX1 axis underlies the KRAS-inhibitor-induced mitophagy response and promotes drug resistance, providing a metabolic mechanism of KRAS inhibitor resistance.

Here the authors report an analysis of two large nationwide cohort studies, the UK biobank and NHANES, suggesting that accelerated biological aging mediate a proportion of the association between social determinants of health and all-cause and cause-specific mortality.

Growth factor signalling has been shown to alleviate tissue fibrosis and promote repair. Here, the authors use fibroblast growth factor 7 (FGF7) knockout mice and an FGF7-loaded hydrogel to show that this factor can promote functional regeneration of tendon.

This study presents LoopID, which profiles proteins at targeted interacting enhancer–promoter (E-P) pairs, identifying the histone demethylase JMJD2 as a regulator of E-P interactions through biomolecular condensate formation independent of its catalytic activity.

The contribution of the extracellular matrix and its degradation to the aging process is not well understood. Here, the authors show that degraded elastin fragments, which increase in the circulation with age, promote aging, while counteracting elastin fragment signals alleviates inflammation, promotes healthy aging and extends lifespan.

Ternary nanoparticles have shown uses in areas such as thermoelectric devices. Here, the authors synthesise such nanoparticles and observe a crystalline ordering consisting of a global Bravais lattice, wherein the cation sublattice displays a range of interlaced chemical ordering.

Molar tooth structures are common in early- to mid-Proterozoic carbonates but extremely rare in rocks younger than 750 Ma. Here, the authors show molar tooth carbonate formation is related to benthic methane fluxes.

Inhibition of the histone methyltransferase NSD2 and the androgen receptor in preclinical models can reverse lineage plasticity to suppress tumour growth and promote cell death in multiple subtypes of castration-resistant prostate cancer.

Challenges remain in optimizing efficiency and stability of monolithic perovskite/Cu(In,Ga)Se₂ (CIGS) tandem solar cells. Here, authors develop a composite-structured intermediate recombination layer and achieve maximum efficiency of 28.04% and 30.71% for 0.51 cm² and 0.15 cm² cells, respectively.

Polymer dielectrics are key for capacitors in energy applications but are hard to improve for high temperatures. This work uses artificial intelligence to design fillers with a large bandgap and high affinity, enabling durable, high-energy polyimide composites for harsh environments.

The electrochemical semi-hydrogenation of C₂H₂ to C₂H₂ is a promising process, but the competing hydrogen evolution reaction remains a major obstacle. This work presents a novel catalytic strategy to steer active hydrogen species, thereby improving the Faradaic efficiency for ethylene.

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.

Cryo-electron microscopy structures of two PSII intermediates from psbV-deletion and wild-type strains of cyanobacteria show substantial structural changes. These provide a structural basis for understanding the assembly process of native PSII.