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Self-amplifying RNA enables durable therapeutic expression, but its high immunogenicity and low-fidelity replication limit its use. Here, authors engineer a Norovirus-derived VPg-saRNA platform that achieves cap-independent, low-immunogenic and precise therapeutic protein expression in vivo.

Macrophages play an important role in repair and regeneration of damaged nerves in spinal cord injury (SCI). Here, Guo et al. investigate effects of endoplasmic reticulum-mitochondria crosstalk on macrophage phenotype and develop a targeted nanorobot inhibiting the Ero1α/MAMs/mtCa²⁺ axis, promoting M2 polarization and neural repair as a therapeutic strategy to treat SCI.

Bacteria can infect tumour cells which may affect the biological characteristics of the tumour or even the therapeutic outcome. Here authors show that Stenotrophomonas, upon entering tumour cells, trigger endoplasmic reticulum stress, leading to STING degradation and inhibition of MHC-II⁺ macrophages, which ultimately cause tumour progression and immunotherapy resistance.

Phagocytes must safely remove mitochondria released after tissue injury to prevent harmful immune activation. Here, the authors show that TMEM110 preserves lysosomal function to clear mitochondrial DNA, thereby limiting organ damage and mortality after traumatic brain injury.

The performance of π-conjugated polymers films is limited by the short exciton diffusion lengths due to local imperfections or variations in interchain packing. Here, the authors report on large-area submillimeter-scale spherulites achieved by treating a spin-coated polydiarylfluorene film under solvent vapor annealing.

Newly emerging SARS-CoV-2 variants underscore the need for broad-spectrum antiviral solutions. This study shows a macrocyclic peptide inhibitor that locks the SARS-CoV-2 spike trimer into a “closed” conformation by engaging a conserved region, and demonstrates that intranasal administration of the peptide inhibitor protects against Omicron variants.

Distributed multiparameter quantum metrology allows to probe multiple spatially distributed parameters across networked quantum systems. Here, the authors demonstrate distributed multiparameter quantum metrology in a modular superconducting quantum processor network.

Hole–electron resonance in WTe2 unlocks Coulomb-unconstrained spin transfer across WTe2/Fe3GaTe2, producing a giant 289% unusual anisotropic magnetoresistance and chiral transverse transport beyond conventional spin-transport models.

OTX2 acts as a barrier to the formation of human 8-cell-like and morula-like cells in vitro. Deleting OTX2 enhances their induction efficiency and developmental potential, uncovering key mechanisms of totipotency regulation and early human development.

How the vascular endothelial cells support the functional adaptation of pancreatic islets under obesity-associated metabolic stress is poorly understood. Here, the authors show that the ER stress sensor IRE1α employs its RNase activity to play an important regulatory role in this process.

This study shows that WDR5 remodels NANOG condensates to control transcriptional programs. Disrupting their interaction compromises stem cell identity and suppresses leukemia stem cell expansion.

Soil life relies on microbial nutrient exchange to maintain ecosystem balance. This study shows that cobamide-producing microbes act as essential connectors in soil food webs, supporting host health and highlighting cross-kingdom links central to One Health.

In the phase III NAPOLI-3 trial, first-line treatment with NALIRIFOX was associated with improved overall survival compared to gemcitabine plus nab-paclitaxel in patients with metastatic pancreatic adenocarcinoma. Here the authors report the results of a randomized phase II trial comparing the two regimens, NALIRIFOX versus Gemcitabine plus Nab-Paclitaxel, in Chinese patients.

The presence of EGFR mutations and de novo MET aberrations limited response to EGFR inhibitors in patients with advance non-small cell lung cancer (NSCLC). Here, the authors report a phase 2 randomised clinical trial investigating first-line osimertinib (EGFR inhibitor) plus savolitinib (c-MET inhibitor) in patients with MET-aberrant, EGFR-mutant advanced NSCLC.

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.

In osteoporotic fracture-related infection (FRI), coordinated bone healing is compromised by cortical bone lysis and persistent bacterial colonization. Here, Li et al. report a dual-action nanocomposite bisphosphonates hydrogel for treatment of osteoporotic FRI that preserves cortical bone integrity and restores fracture healing.

Optomechanical crystals are promising building blocks for quantum networks but suffer from thermal mechanical noise. Here the authors demonstrate on-demand conversion of single phonons into high-purity telecom photons with low thermal noise and MHz-scale narrow bandwidth using a quasi-2D optomechanical system.

The molecular mechanism underlying DNA entrapment during loop extrusion by condensin remains poorly understood. Here, the authors use multiscale molecular simulations to show that DNA itself steers a flexible “safety belt” in condensin.

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

Grain chalkiness is an undesirable trait that severely compromises rice quality. Here, the authors report the cloning of an E3 ubiquitin ligase encoding gene Chalk9 and reveal its crucial role in regulating grain chalkiness through mediating the ubiquitination-dependent degradation of OsEBP89.

Strong paramagnetism is generated in hydrogels rich in carbon–oxygen double bonds simply by coupling with diamagnetic Ca cations. These paramagnetic hydrogels are applied as magnetic resonance imaging contrast agents and magnetic drug carriers.

Xu et al. report that inhibition of the F-box protein FBXL2 enhances HER2 expression, rendering HER2-negative breast cancer sensitive to the anti-HER2–drug conjugate trastuzumab deruxtecan.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Grain number per panicle (GNP) is a critical yield component trait of rice. Here, the authors clone a MAPKKK encoding gene GNP3 positively regulating grain yield and show its role in rice panicle development by interacting and destabilizing ethylene biosynthesis related enzyme SADENOSYLMETHIONINE SYNTHETASE 1.

Controllable and scalable phase transition of transition metal chalcogenides is challenging. Using in situ microscopic analysis, a non-stoichiometric phase transition from PdTe₂ to PdTe is observed on the atomic scale, providing mechanistic insights into the scalable phase engineering of transition metal chalcogenide films and heterostructures.

Liu et al. report Chinese normative lifespan brain charts showing later neurodevelopmental milestones than those detected in Western cohorts. Individual deviations from these norms are valuable in assessing clinical risk and outcomes.

NatD is an acetyltransferase responsible for N-α-terminal acetylation of the histone H4 and H2A and has been linked to cell growth. Here the authors show that NatD-mediated acetylation of histone H4 serine 1 competes with the phosphorylation by CK2α at the same residue thus leading to the upregulation of Slug and tumor progression.

A biohybrid chiral hydrogel combining cell-membrane-coated nanoparticles with a D-chiral matrix reduces tumour stemness via biochemical and biophysical regulation, boosting radioimmunotherapy and preventing postoperative glioblastoma recurrence.

Positive glacial regulatory processes could mitigate approximately 236–255 gigatonnes of glacier water loss across High Mountain Asia in the 21st century, representing about 9%–13% of total mass loss, according to glacier water balance modelling.

Programable coatings are promising for information encryption, though it is challenging to design stimuli-responsive materials. Here the authors integrate a photochromic switch into a polymer system for programmable encryption.

Chen et al. identify a brain-to-bone communication axis whereby extracellular vesicles from aged brain neurons transport WDFY1 protein to distal bone, driving bone-fat imbalance and promoting osteoporosis.

CAR-T cell efficacy is often limited by the inability to maintain a memory T cell program. Here, the authors show that intrinsic CXCR4 expression enhances CAR-T cell persistence and memory differentiation in acute myeloid leukemia.

The authors conducted a genome-wide association study of bipolar disorder (BD) in Han Chinese and integrated PGC4 East Asian and European datasets, discovering 23 novel loci, prioritizing 39 credible risk genes and implicating BD-related cell types and druggable targets.

The dynamics of antimicrobial-resistance plasmid transmission in hypervirulent Klebsiella pneumoniae are poorly understood. Here, Yong et al. show that anaerobic conditions favour the transfer of a distinct plasmid lineage, and the bacterial capsule poses only a modest barrier for plasmid transfer in the mouse gut.

A label-free imaging approach detects differences in NIR-II autofluorescence intensity between human liver malignancy and the adjacent tissue.

A wearable paper-based microfluidic device tracks cortisol in sweat via gold nanoflower colorimetric assays and captures circadian rhythms, stress responses and jet lag disruptions.

This study reveals that the TRPC3 channel is essential for HPV-driven cervical cancer. TRPC3 promotes malignant transformation by regulating the RASA4/MAPK pathway and EMT. Targeting TRPC3 could be a new therapeutic strategy.

Aqueous zinc-ion batteries are promising for sustainable energy storage but challenged in low temperatures. Here, authors develop a gradient chaotropic ionic liquid-based aqueous electrolyte design that enables dendrite-free operation and robust low-temperature performance (to −40 °C).

Synovitis is a key early driver of osteoarthritis (OA), and RANKL contributes to cartilage degradation in OA. Here the authors show that denosumab, an anti-RNKL antibody, reduces synovitis and delays OA progression in animal models and patients.