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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.

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.

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.

Cystine levels in pancreatic ductal adenocarcinoma (PDAC) tumour microenvironment are deficient, despite its crucial role for cancer cell maintenance. Here, the authors show that adaptation to cystine limitation stress promotes PDAC growth through induces metabolic reprogramming to promote PDAC tumor growth, while conferring a vulnerability in lipid metabolism targetable by lomitapide.

High-order modes of hyperbolic polaritons – hybrid light-matter interactions – in anisotropic van der Waals materials hold potential for nanophotonics applications. Here, the authors report the observation of polariton mode conversion in step-shaped terraces of hexagonal boron nitride and α-MoO3.

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.

China’s crowded coasts must balance seafood demand with conserving migratory shorebirds that rely on tidal flats along the East Asian–Australasian Flyway. This study suggests that well-managed mariculture feeds shorebirds and limits overharvest, benefiting seafood production and biodiversity.

Differentiating the structural order of the commensurate modulated antiferroelectric can double the energy storage density of ceramics to over 23 J/cm³ while maintaining their efficiency.

Natural disasters induce power outages with unequal impacts on poverty and non-poverty counties in China. Climate change will further exacerbate this disparity.

It is unclear how early-life urbanicity influences adult neurobehavioral traits. This study reveals that earlier menarche mediates the relationship between early-life urbanicity and adult neurobehavioral traits associated with mental disorders.

A cross-ancestry GWAS meta-analyses of brainstem structures identify 713 associations. It reveals shared/distinct genetic architectures across ancestries/substructures and overlaps with neuropsychiatric disorders and physiological functions.

On-chip phased interdigital metamaterials have electrodes encoded with deep-subwavelength-resolution phase profiles, enabling versatile transformation of surface acoustic waves, diode-like acoustic routing, and manipulation of fluids and particles.

By unifying ultra-high optical gain and broadband electro-optic dynamics in an Er-doped lithium niobate thin-film platform, the authors demonstrate an exciting monolithic integration of amplification and modulation on a compact photonic chip. This exciting work showcases record performance for on-chip amplifiers while enabling self-amplified 50 Gbps digital encoding and pre-amplified RF front-end signal recovery.

Metallic glasses can break ductility bottlenecks: 10% tensile plasticity with strain-hardening emerges from a synergy between relaxation-assisted and transformation-mediated deformation mechanisms, overcoming a long-standing challenge in metallic glasses.

Anti-TSLP biologics have shown promise for the clinical treatment of type 2 respiratory disease. Here the authors present a clinical trial of CM326, a monoclonal antibody against TSLP, and show the clinical effects in patients with eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP), who present with type 2-dominant inflammation.

Nociceptive sensory nerves infiltrate the peripheral trauma area, mediating the biased repair response due to the formation of fibrotic mesenchymal stromal cells (MSCs) neurogenic niche. Nociceptive sensory neuron-derived nerve growth factor activates the TrkA receptors in MSCs and triggers the Hif1α-Twist1 pathway, driving the differentiation of MSCs into myofibroblasts to mediate fibrosis. TPX-0005 exerts therapeutic effects by inhibiting TrkA to reverse fibrosis.

Researchers discovered that electronic pressure relaxation drives ultrafast heterogeneous melting in metals at speeds up to 2500 m/s, ten times faster than thermal mechanisms.

Interfacial segregation of boron generates gradient-ordering and achieves improved mechanical performance across ambient temperature to 2073 K, providing a new pathway to overcome the strength-plasticity trade-off under extreme thermal conditions.

Immune checkpoint inhibitors have shown promise in tumour immunotherapy but resistance has been seen. Here using pre-treatment hepatocellular carcinoma patient biopsies from patients scheduled for immunotherapy, the authors implicate BCL9 and show that a BCL9-targeting peptide promotes anti-tumour immunity in mouse models through targeting macrophages and promoting anti-tumour T cell responses.

Here, the authors present Ediacaran fossils from the Tongshan Lagerstätte (South China), including Burgess Shale-type rangeomorphs preserved both with fronds and holdfasts. They use sedimentary and chemical evidence to suggest that fast burial and early diagenetic mineralization produced excellent preservation.

Spin photocurrents can be efficiently generated by the resonant excitation associated with defect states in unintentionally doped GaN. Here, the authors show that shallow Si-donor states can be utilised to enhance the magnitude of the spin photocurrent, and that defect induced deep level states provide a feasible method to modulate the direction of the spin photocurrent.

Drug-tolerant persister (DTP) cells are a rare subpopulation of cancer cells that can survive chemotherapy through reversible non-genetic mechanisms. Here, the authors provide their perspective on the existing gaps and outline the research paths still required to bridge basic DTP research with effective clinical strategies.

Li et al. demonstrate that SULTR-mediated sulfur input is a pivotal step in regulating nodule senescence, and provide insights for developing strategies to enhance symbiotic nitrogen fixation in legumes by delaying nodule senescence.

Zhang et al. report green-emitting colloidal quantum dots with a large CdZnSe core and a thin ZnS shell, enabling the weak hole confinement for efficient exciton formation. LEDs with efficiency of 30.7%, peak luminance of 1.9 million nits, and T95 of 21,900 h at 1,000 nits are achieved.

In a prespecified interim analysis of the randomized, double-blind phase 3 COMPASSION-15 trial, patients with advanced HER2-negative gastric/GEJ cancer treated with the anti-PD-L1/CTLA-4 bispecific Ab cadonilimab plus chemotherapy showed significantly improved overall survival compared with patients treated with placebo plus chemotherapy as first-line treatment.

Achieving complete coverage of 2-4 μm pyramids on industrial fully-textured silicon with solution processed perovskite film remains challenging. Here, authors spray-coat alumina particles on silicon for near-conformal deposition of perovskites, achieving efficiency of 32.74% for tandem solar cells.

Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.

Ovarian endometriomas, with distinct microenvironment and heightened hormonal sensitivity, are recognized as precursors of ovarian carcinomas. This study decodes ovarian endometriomas by integrating single-cell and spatial transcriptomics with spatial metabolomics to reveal key markers and altered pathways, offering new avenues for diagnosis and therapy.

The role of vascular plasticity in brain function remains poorly understood. Here, the authors demonstrate that a significant portion of blood vessels in the adult brain periodically occlude and regress, a process that is associated with a reduction in neuronal activity.

The backbones of all natural peptides and proteins are composed of amide bonds. In the laboratory, the construction of such bonds generally relies on dehydrative approaches, although there are alternatives. It is now shown that the activation of amines and nitroalkanes with an electrophilic iodine source can lead directly to amide products.

Ceramic preparation of spinels — materials useful for a wide range of applications — requires complicated procedures and heat treatment over long periods. Now, it is shown that rapid synthesis of nanocrystalline Co–Mn–O spinels can be achieved under ambient conditions, and the resulting nanoparticles exhibit considerable catalytic activity towards the electrochemical oxygen reduction/evolution reactions.

Blue QD-LEDs suffer from poor operational stability due to the carrier accumulation at transport layers. Here, the authors propose a strategy to mitigate the hole accumulation driven oxidation in hole transport layer, effectively elongating the operational lifetime of blue QD-LEDs.

Around 50% of patients with ulcerative colitis who undergo ileal pouch–anal anastomosis develop at least one episode of pouchitis. In this Review, Bo Shen describes the aetiology and pathogenesis of pouchitis, particularly the role of dysbiosis andClostridium difficileinfection. Risk factors, clinical features, disease courses and prognoses of pouchitis are discussed, as well as the diagnosis and management of patients with 'conventional' pouchitis and systemic immune-mediated disorders associated with pouchitis.

Optically reconfigurable elements are in demand for future applications. The authors report on the use of chirality-invertible cholesteric liquid crystals to actively manipulate geometric phase and create switchable planar optics elements that perform a variety of functions.

Freestanding membranes of hafnium zirconium oxide can be created using pulsed laser deposition method and used as the top-gate dielectric in molybdenum disulfide transistors.

The prevalence of mutations that can predispose to pancreatic adenocarcinoma (PDAC) remains unclear, especially in underrepresented populations. Here, the authors create a germline mutation map of 1,123 Chinese PDAC patients and compare them to cohorts from other populations, finding CFTR as a potential driver.

Fused N-heterocycles are structural motifs observed in natural products and bioactive compounds. Here, the authors developed divergent copper- and gold-catalyzed oxidative cyclizations of diynes to two types of tricyclic N-heterocycles and rationalized the product selectivity by theoretical calculations.

A molybdenum disulfide/tungsten diselenide van der Waals heterostructure can exhibit a room-temperature valley Hall effect with electrically tunable magnitude and polarity, which can be used to create a bipolar valleytronic transistor.

A simple and versatile strategy is established to facilitate molecular recognition by extending electron catalysis for use in supramolecular non-covalent chemistry.

The authors find that the dielectric performance of capacitors will be significantly overestimated due to the influences of fringing effect and parasitic capacitance. Methods to solve the problem are proposed to ensure measurement validity.

Of the 3 classes of dimeric lindenane sesquiterpenoids, only type I And II have been targeted in total synthesis. Here, the authors report a unified strategy to synthetically access the 3 classes of lindenane sesquiterpenoids dimers by developing a [4 + 2] cycloaddition between a common furyl diene and various dienophiles.