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Natural variation in the promoter of OsTPS8 contributes to differences in grain chalkiness and seed vigor between indica and japonica rice subspecies by altering trehalose-6-phosphate biosynthesis and α-amylase levels.

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.

While EGFR mutations are drivers of cancer, the function of extracellular domain mutations remains poorly defined. Here, the authors show that the R252C extracellular mutation induces conformational change of EGFR to directly activate ERK and promote cancer growth, which can be targeted by afatinib.

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.

The molecular heterogeneity of brain metastases (BrMs) poses challenges for their treatment. Here, the authors generate a multi-omic, single cell, and spatially resolved atlas of 1,032 pan-cancer BrMs and identify four molecular subtypes with distinct biological and clinical features.

Chen et al. report a tailored self-assembled monolayer to create a localized 2D/3D perovskite heterojunction. This strategy reduces interfacial loss, achieving photovoltages >90% of thermodynamic limit for wide-bandgap cells, and enables perovskite-organic tandem solar cells with efficiency of 27.11%.

The efficacy of radiotherapy is sometimes hindered by the hypoxic and immunosuppressive tumor microenvironment. Chen et al. develop an injectable hydrogel encapsulating IL-12/aCTLA-4 co-engineered red blood cells, thereby alleviating hypoxia-induced radioresistance and sequentially releasing aCTLA-4/IL-12 to relieve tumor immunosuppression.

Alternative splicing greatly expands the transcriptomic and proteomic diversity in vertebrates. Here, the authors develop a machine-learning tool to identify functional splicing events during hematopoietic cell differentiation, revealing new regulators of hematopoiesis.

Co-fractionation mass spectrometry reveals protein interactions but is low throughput and data-limited. Here, the authors present ProteoAutoNet, a robotic platform integrated with machine learning that doubles sample processing throughput and predicts thousands of co-eluted protein interactions in thyroid cancer cells, revealing disease-relevant complexes like upregulated proteasome, prefoldin, and a predicted HK1-TGM2 interaction.

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.

Sclerostin impairs whole-body lipidandglucosemetabolism. Here, the authors further demonstrate that adipocytic sclerostin loop3-LRP4 interactionparticipatesin the impairment effect of sclerostin on whole-body lipid and glucose metabolism.

High sugar intake is a potential risk factor for heart failure, but there is insufficient evidence for the benefit of restricting sugar intake during pregnancy or early life. Using the end of UK sugar rationing as a natural experiment, this study shows that lower sugar intake early in life is linked to lower risk of heart failure and later disease onset.

Genome evolutionary history of wild Arachis species remains unclear. Here, the authors report the origin of small chromosome A08 and genome evolution of Arachis species via comparative oligopainting and genomic analysis of A. hoehnei.

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.

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.

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.

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.

Purinergic signalling dysregulation can drive inflammatory disorders, but effective targeted therapy is still lacking. Here, authors develop a smart DNA origami nanodevice that can precisely sense and metabolize high levels of extracellular ATP, thereby fine-tuning purinergic signalling and immune homeostasis.

Schizophrenia risk at 1p36.23 lacked functional insight. Here, the authors identify two enhancer variants that upregulate RERE, which disrupts neurogenesis and synaptic function by regulating Grin2a, linking genetic risk to neuronal development and excitatory signaling.

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.

Zhang et al. report a foundry-compatible γ-ray treatment to induce chemical bond changes of organic contaminants in carbon nanotube transistors, mitigating the imperfections at the carbon nanotube/dielectric interface, reducing the off-state current density to 112.2 pA μm-1, and achieving radiation tolerance up to 100 Mrad(Si).

The formation of catenanes through dynamic covalent reaction of self-assembling precursors in one pot offers a powerful route to complex interlocked architectures, yet the mechanistic insight remains underexplored. Here, the authors elucidate the nucleation–elongation mechanism in the one-pot synthesis of topologically distinct catenanes.

Here the authors systematically benchmark 13 polygenic score (PGS) methods in UK Biobank European and African populations, revealing factors that affect prediction accuracy. They also introduce an automated platform for standardized and reproducible PGS computation.

A percolating interaction between antipolar regions and engineered defect pairs facilitates antipolar rotations, enabling superior energy storage performance in AgNbO₃-based ceramics.

Biological system for stable object manipulation is facilitated by a unified tactile memory system. Here, GenForce enables transferable force sensing across diverse tactile sensors using a unified representation, enhancing robot manipulation through cross-sensor transfer and multi-sensor coordination.

All-in-one computing, which merges sensing, linear computing, and nonlinear activation, is a critical goal for next-generation AI hardware. Here, Zhang et al. introduce a high-speed, reconfigurable split-floating-gate memory, enabling multi-function integration within a unified platform and hardware native neuromorphic processing.

Papaya is a trioecious species with XX females, XY males, and XY^h hermaphrodites, and the combination of Y and Y^h chromosomes is lethal. Here, the authors identify the degeneration of the YY lethality gene on the Y chromosome as the causal balancing lethal factor that reenforces dioecy and stabilizes balanced sex ratios.

This work introduces synthetic gain to electron-beam spectroscopy, greatly enhancing spectral resolution and revealing hidden features, enabling advances in nanoscale analysis and free electron-based quantum optics under challenging signal conditions.

O-GlcNAc chromatin modifications dynamically reshape the transcriptional program of oncogene-induced senescence, forming complexes that activate SASP genes and repress cell-cycle genes; JUN and GATAD2A are identified as key regulators.

SARS-CoV-2 variants often exhibit immune evasion, necessitating antiviral strategies beyond vaccination. This study presents a papain-like protease (PLpro) inhibitor called YL1004, which exhibits potent, broad-spectrum antiviral activity against wild-type, Delta, and Omicron variants in vitro and in vivo.

Recent studies have shown the potential of higher-order exceptional points originating from the Liouvillian dynamics as opposed to their Hamiltonian counterparts. Here, the authors explore different classes of third-order Liouvillian exceptional points in a two-level system realised in a single trapped ion.

Intermittent fasting (IF) has been recognized as a potential cancer therapeutic approach but its effect on tumor growth is limited. This study demonstrates that response to IF varies between glioblastoma subtypes, with IF specifically inhibiting Tp53-driven glioblastoma due to a reshaping of the gut microbiota and subsequent altered methionine metabolism suppressing TGF- β signaling.

The mechanisms and kinetics behind the anti-sintering behavior of supported metal nanoparticles under ultrafast heating remain unclear. Here, in situ scanning transmission electron microscopy and theoretical analysis reveal an ultrafast-heating–induced metastable state that suppresses thermal sintering while enhancing crystallinity of the metal nanoparticles and their interfaces.

A genome-wide association study in rice identifies variation in SBRR1 associated with sheath blight resistance. Introducing the SBRR1-R allele into a commercial rice variety reduces yield loss under severe exposure to sheath blight disease.

The efficient mass transport is the key factor to advancing the flow-electrocatalytic chemosynthesis. Here, the authors design a flow-through architecture in flow electrolyzer, reinforcing mass transport in the electrolyte to achieve the high efficiency of continuous oxime electrosynthesis.

Enhancing the selectivity of molecular recognition within (photo)-electrochemical systems has consistently presented a challenge. Here, the authors report a dark-enhanced photoelectrochemical mechanism for the highly selective quantitative analysis of glutathione on a BiOBr photocathode.

Most studies assessing food self-sufficiency look at calories and neglect nutrient gaps. Comparing food demand and potential food production under land and water constraints, this study quantifies 9 key nutrient gaps for each of African’s 54 countries.

Tumor endothelial cells are essential stromal components in the tumor microenvironment. Here the authors find that endothelial-specific deletion of PDLIM5, an actin-binding protein, could inhibit tumor angiogenesis and tumor growth as well as enhance therapeutic responses in mouse tumor models.

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.

Authors overcome the “oxo-wall” effect of Co(IV) = O complexes, offering the lamellar Ce-Co tetra-(4-carboxyphenyl) porphyrin framework membrane for sustainable Co(IV) = O-mediated advanced oxidation processes in water treatment.

Scalable fabrication of perovskite films for large-area solar cells remains a critical challenge. Jin et al. identify the solvent-precursor interaction time as a crucial, yet overlooked, kinetic parameter controlling crystallization and propose a protocol for manufacturing high-quality perovskite films.

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.

In this work, Wu et al. develop and present PolyCLOVER, a framework that integrates multi-stage learning, active learning, and high-throughput experimentation to iteratively discover potent, low-toxicity polymeric antibiotics without relying on external labelled data.

To overcome inefficient recycling of carbon fibre waste, the authors develop a rapid, commercially attractive solid-flames upcycling technique that converts waste fibres into graphene-grafted carbon fibres and graphene powders.

Acute-on-chronic liver failure is a complex condition with varied definitions. Using unbiased clustering, the study identifies two distinct subtypes with markedly different 30-day mortality risks and highlights key determinants.

Dissipative many body systems provide quantum-enhanced sensitivity to external near gap-closing points. Here, the authors demonstrate record sensitivity in a Rydberg-atomic platform in correspondence of folded hysteresis trajectories under external microwave driving

Circulating N-glycomics studies have shown alterations in multiple cancer types. Here, the authors show that blood-based glycome patterns on proteins can be used to predict liver damage and liver cancer development.

The potential of detecting acidic tumor microenvironment (TME) is explored for early cancer diagnosis and treatment. Here, this group reports a pH-responsive ratiometric photoacoustic sensor that dynamically monitors TME acidity throughout HCC initiation, progression, and metastasis.

Protein kinases contribute to hepatocellular carcinoma progression and immune evasion. This study identifies SPAK as a key driver of oncogenesis and immune exhaustion, showing that SPAK inhibition synergizes with anti-PD-1 therapy to enhance antitumor efficacy.

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.