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Progression-free survival with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors remains suboptimal in EGFR L858R-mutated advanced non-small-cell lung cancer (NSCLC), highlighting the need for strategies to delay resistance. Here this group reports a single-arm, phase II study evaluating first-line double-dose firmonertinib in 33 patients with L858R-mutated locally advanced or metastatic NSCLC.

Recovering nitrate from surface water can help address interconnected environmental, resource, and energy challenges. A bioinspired photothermal evaporation platform enabling the co-recovery of low-concentration nitrate and freshwater is proposed.

Heart failure affects millions worldwide with limited treatment options. Here, the authors develop a biodegradable, self-powered vagus nerve stimulator that attenuates cardiac damage at different disease stages without requiring battery replacement or surgical removal.

Here they show that G9a-mediated H3K9me2 regulates intestinal homeostasis and injury repair through repression of cell cycle arrest genes in both mouse and human.

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.

This study shows that excessive atmospheric nitrogen deposition can enhance methane production and emissions by impacting microbial phosphorus acquisition due to the change of N/P ratios in oxygenated surface oceans.

The controllable regio-divergent and enantioselective C–H bond transformation of secondary amines at different N-alkyl groups has remained underdeveloped. Herein, the authors report a Cu-catalyzed α’/β-regiodivergent and β-enantioselective cyanation of secondary amine-derived ureas through ligand-controlled adjustable 1,4’/1,5-hydrogen atom transfer.

The function of intermediate epithelial states in pulmonary fibrosis unknown. This study used RNA sensing technology to show selectively removal of alveolar epithelial stem cells trapping in an intermediate state reduced lung fibrosis.

The authors study a topological insulator (TI) sandwiched between two magnetic TIs. By keeping one of the magnetic TIs insulating, while tuning the other one into a metallic regime, they find half quantized anomalous Hall conductance, a boundary signature consistent with a quantized axion field.

The study shows forests near edges store less carbon due to higher environmental stress. Spatial optimization of new forest plantations could boost carbon storage by 986 Tg by 2060, with 53% of the gain from reducing edge effects.

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.

The complex interactions between the uterus microenvironment and the embryo during development are not fully understood. Here, authors engineer a 3D hydrogel culture system to investigate how the physical and biochemical properties of the uterine microenvironment impact embryo development in vitro.

Optical heterostructures have potential in integrated photonics and optoelectronics but are challenging to prepare in single-component systems. Here, the authors report an intrinsic optical heterostructure in an organic nanosheet, with enhanced fluorescence in an inner zone.

Highly-charged intrinsically disordered proteins (IDPs) underpin biomolecular condensate formation, however, the influence of charge sequences on the dynamics within the condensate phase remains underexplored. Here, the authors use molecular dynamics simulations with explicit hydrodynamics and electrostatics to study the dynamics in IDP condensates across different length and time scales by varying the charge sequences of the constituent IDPs, showing that hydrodynamic and electrostatic effects are strongly coupled to the IDP charge sequence, in contrast with the expectation of long-range interactions being heavily screened.

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.

Emu3 enables large-scale text, image and video learning based solely on next-token prediction, matching the generation and perception performance of task-specific methods, with implications for the development of scalable and unified multimodal intelligence systems.

Catalytic enantioselective hydroarylation of alkynes is a concise protocol towards axial, helical, and planar chirality, but most reactions involve noble-metal catalysts. Here, the authors report a copper-catalyzed intramolecular atroposelective hydroarylation of 1-alkynylindoles with (hetero)arenes, affording C─N axially chiral carbazolyl and phenanthryl indoles.

The pathophysiologic functions of small nucleolar RNAs (snoRNAs) remain to be studied. Here the authors report that snoRNA SNORA49 suppresses liver cancer stem cell renewal through transcriptional inhibition of the stemness factor SOX9.

Organoid modeling and single-cell profiling reveal TUBA4A and TUBB4B tubilin proteins-driven vascular smooth muscle cell migration and contractile-to-synthetic phenotypic switching via GJA1/PI3K/AKT/KLF4 pathway in Moyamoya disease.

The authors found esterified pectin localized at the stiff poles of maize stomata, modulating stomatal opening. These results reveal novel targets for stomatal engineering and breeding crops with higher water use efficiency.

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

IBI318 is a recombinant bispecific IgG1 antibody that targets PD-1 and PD-L1. Here the authors report the results of a phase II trial of IBI318 combined with the receptor tyrosine kinase inhibitor lenvatinib in patients with advanced non-small cell lung cancer with acquired resistance to first-line immune checkpoint inhibitors.

Dysregulation in proteolysis contributes to brain tumorigenesis. Here the authors report that USP10 deubiquitinase is enriched in glioma stem cells (GSCs), which antagonizes DTX3L-mediated ubiquitination of SATB2, a major driver of GSC proliferation and self-renewal.

Targeted degradation of proteins has therapeutic potential for a range of diseases. Here the authors report on an endosome-phagosome linking assembly for autophagic degradation of membrane and extracellular proteins, demonstrating degradation of a range of proteins of therapeutic interest.

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.

A new artificial intelligence model, DeepSeek-R1, is introduced, demonstrating that the reasoning abilities of large language models can be incentivized through pure reinforcement learning, removing the need for human-annotated demonstrations.

Iron–sulfur minerals play critical roles in regulating nitrogen cycling under anoxic conditions. This study shows that pyrrhotite with abundant iron vacancies promotes electron transfer and microbial nitrate reduction to dinitrogen.

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.

The genetic mechanisms of why polyploid plants exhibit adaptive advantages over diploids are unclear. Here, the authors assemble the autotetraploid alfalfa genome, incorporate it into a pangenome analysis, and reveal the trade-off between adaptive advantages and evolutionary constraints mediated by tetra-copy core genes.

Reducing the embodied carbon emissions of building material stock is essential for mitigation. Using a high-resolution multiyear dataset in China, researchers show the historically massive contributions of these emissions during past decades of rapid urbanization and the potential risks for future climate goals.

Lactate fuels cancer growth by activating ERK signaling through GCN5-mediated lactylation of ERK, which disrupts ERK–MEK interactions. Development of a cell-penetrating peptide blocking lactylation slows KRAS-mutant tumor development.

In an effort to deorphanize G-protein-coupled receptors, a photo-cross-linking platform was established to capture ligands from complex samples. Little-LEN was identified as a ligand for GPR50, which coordinately regulates body metabolism.

The authors find that O-GalNAc transferase 2 (GALNT2) restricts viral infection, probably through the regulation of the proteolytic processing of viral glycoproteins via its O-linked glycosylation activity, impairing virus–cell fusion.

Dendrobium is a genus of mostly epiphytic and lithophytic orchids. Here, the authors conduct comparative genome analysis for 24 chromosome-level genome assemblies and genome skimming sequencing data for 204 species in this genus, and reveal genomic variation, biosynthesis and evolutionary adaptation in Dendrobium orchids.

Selective lithium extraction from low-grade brines remains a substantial challenge due to intense competition from coexisting ions such as magnesium and sodium. In pilot-scale electrochemical systems, [100]-oriented LiFePO₄ nanosheets have shown enhanced lithium selectivity, effectively isolating lithium even from brines with extremely high Na/Li and Mg/Li ratios.

Here they show that gasdermin-E (GSDME) acts as a key driver of abdominal aortic aneurysm (AAA) by triggering senescence in vascular smooth muscle cells, a process reversible with senolytic drugs, highlighting a promising therapeutic target of AAA.

Finding efficient ways to release hydrogen from liquid carriers is key to advancing clean energy systems. This study introduces a resilient catalyst that drives highly selective hydrogen production from formic acid using low-grade heat.

Noise-induced hearing loss is commonly attributed to direct damage to sensory hair cells. Here, the authors reveal that non-sensory supporting cells play a critical role in the damage through Gasdermin D-mediated exacerbation of hair cell oxidative stress.

The NSUN family, comprising seven members, is the primary RNA m5C methyltransferase in higher eukaryotes. Here, the authors demonstrate that NSUN7 is a catalytically inactive RNA m5C protein due to sequence variations in its motif IV. Instead, the authors reveal a noncatalytic, regulatory role of NSUN7 in sperm flagellum assembly.

This work proposed a fully heterogeneous quantum network that connects diverse user systems and enables multiple quantum tasks. A software-defined quantum network structure is also proposed for coordinating network nodes and optimizing network performance. It paves the way for an open and versatile quantum internet.

Tracking the success rate of clinical drug development is key for pharmaceutical and economic decision making. Here, the authors establish a strategy enabling dynamic measurement of the success rate using public data and generate an online platform.

A modular nanobody-based approach assembles combination vaccines by stably attaching diverse antigens to hepatitis E virus-like particles, preserving native immunogenicity and inducing broad protection against respiratory pathogens.

Observations of γ-rays with energies up to 1.4 PeV find that 12 sources in the Galaxy are PeVatrons, one of which is the Crab Nebula.