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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.

In nasopharyngeal carcinoma (NPC), cisplatin is known to be associated with poor treatment compliance and notable side effects therefore more effective platinum drugs are expected. Here this group updates the 10-year survival analysis results of a multicenter, randomized, phase 3 trial evaluating the efficacy of lobaplatin and fluorouracil induction chemotherapy plus concurrent chemoradiotherapy on 502 NPC patients.

Obesity impairs metabolic flexibility-the capacity to adapt to fluctuating energy demands. Here, authors show that PRMT3 mediates the post-translational adaptation of visceral fat to fasting regulates metabolic flexibility and could be a therapeutic target for obesity.

Yin et al. report linear conjugated polymer donors with chlorinated backbone for modulating polymer aggregation and surface tension, and optimised compatibility with norfullerene acceptors. By using binary blends, a 20.42% efficiency is achieved for organic solar cells.

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.

Low outcrossing rate of sterile lines limits hybrid rice seed production. Here, the authors report that mutation of a SET domain-containing protein HER1 leads to enlarged stigma, enhanced stigma exsertion, and hybrid seed production in rice.

This study presents the inhibitory primary auditory cortex – anterior cingulate cortex pathway underlying the auditory-pain crosstalk in mice, thus serving as a neural substrate for music therapy in visceral pain management.

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.

Designing superelastic materials remains challenging. Here, the authors reveal that hidden atomic-scale strain order in a high-entropy alloy enables reversible switching between linear and nonlinear superelasticity through subtle composition tuning.

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.

Apomixis allows plants to reproduce clonally, yet it is unclear how rare sexual events shape their genomes. This study shows that residual sex in apomictic hickories causes recombination-driven loss of heterozygosity that exposes harmful mutations to selection and helps maintain clonality.

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.

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.

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.

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.

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.

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.

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.

A platinum(II) azido complex (complex 1) that releases platinonitrene upon X-ray exposure induces DNA damage and enhances immune checkpoint blockade outcomes via the abscopal effect.

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.

Mouse models show that lymphoedema caused by impaired lymphatic drainage is ameliorated by removal of cholesterol deposits, which promotes the regeneration of lymphatic vessels.

A graph-based pangenome constructed from 39 reference-quality genomes of wild and cultivated cucumber accessions, including 27 newly assembled, highlights the dynamics of structural variants during cucumber domestication and range expansion.

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.

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.

Tellurium vacancies can drive atomic reconstruction in PdTe₂ thin films, converting them into non-layered PdTe. Such a non-stoichiometric phase transition yields large-scale thin-film superconductors and can also create an intermediate heterostructure that enables helicity-sensitive terahertz emission.

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

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.

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.

The enantioselective construction of α-diheteroatomic carboxylic acids has long been a synthetic hurdle. Now, a thia-Rh-carbene platform enables O–H or N–H insertions, delivering this rare chiral motif for applications in peptide chemistry and drug development.

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.

This study uncovers genetic links between plant roots and their microbiome in Brassica napus, identifying microbe-associated loci and a beneficial bacterium, Sphingopyxis, that promotes nitrogen uptake.

He and colleagues develop a METTL3-based RNA base-editing screening strategy to identify functional N⁶-methyladenosine (m⁶A) sites that are important for prostate cancer cells and validate the role of a top m⁶A target, CHD9, in this context.

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.

Surface decoration of E. coli Nissle 1917 with modified lignin creates a robust living therapeutic that survives the GI tract to effectively treat ulcerative colitis by reshaping the gut microbiota.

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.

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.

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.

CO₂-driven warming reduces phosphorus availability in rice paddies by promoting its binding with iron and organic carbon in the soil, according to a ten-year experiment using a free-air CO₂ enrichment system to simulate in situ climate warming.

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.