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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.

Healing of infected tendons is hindered by mechanical dysfunction, tissue adhesion, and immune imbalance. Here, Li et al. develop a multifunctional Janus hydrogel with asymmetric adhesion, antibacterial properties, and pH-responsive release of tendon stem cell-derived exosomes for infected tendon repair.

The longevity of leaves determines the overall duration of photosynthesis for plants. This study suggests that climate change drives leaf longevity convergence toward intermediate ranges, which, by altering leaf traits and enhancing photosynthetic capacity, strengthens ecosystem stability and is closely linked to vegetation diversity.

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.

Induction of CD11b-positive regulatory B cells and low expression of CD40 in melanoma cells have been associated with resistance to agonist CD40 (aCD40) and immune checkpoint blockade (ICB). Here the authors show that the addition of RAS/MEK/PI3K inhibitors to aCD40 abrogates these effects and reverses ICB resistance in preclinical melanoma models.

The spatial organisation of the tumour microenvironment (TME) can affect immune responses that control tumour growth. Here, the authors use single-cell transcriptomics and spatial transcriptomics to identify a lymphocyte aggregated region (LAR) in gastric cancer and compare its cellular and molecular composition with the neighbouring TME.

Intrauterine adhesions (IUA) are a leading cause of female infertility. Here, authors engineer a Tβ4-releasing ECM hydrogel that mimics decidualization to promote endometrial regeneration as a therapeutic strategy for treatment of IUA.

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.

The role of RNA-binding protein (RBP) phase separation in transcriptional regulation and its contribution to tumorigenesis remains to be characterised. Here, the authors show that RBP AKAP95 physically co-condenses with the mixed lineage leukemia 1 (MLL1) translocated fragment commonly found in MLL rearranged (MLLr) leukemia to promote leukemogenesis.

Fracto-mechanoluminescence is the emission of light from fracturing solids. Here, the authors show that this emission in Mn halides arises from elastic stiffness, electromechanical coupling, and trap states that activate Mn²⁺ d−d transitions.

Solving ordinary differential equations (ODE) on the von Neumann architecture normally demands a large amount of computational resources. Yu et al. build ODE solver hardware using a computing-in-memory-based implementation, showing orders of magnitude improvement in energy consumption and speedup.

Yang et al. introduce a unified framework for liquid electrolyte design, integrating a forward predictive model with an inverse generative approach, where three generated high-conductivity candidates were identified and experimentally validated.

Materials with room temperature phosphorescence have a range of potential applications, but when crystalline can be brittle and optically non-transparent. Here, the authors report the development of supramolecular glasses by evaporation-induced assembly, with high-temperature afterglow properties.

Most kiwifruit species are vulnerable to high levels of heat stress. Here, the authors report natural variation at the GATA transcription factor binding site of EGY3 gene mediates chloroplastic ROS homeostasis to confer kiwifruit thermotolerance.

Escalating phosphorus pollution and depleting reserves necessitate sustainable control and recovery strategies. Here the authors develop a microbially enhanced La–Zr-loaded basalt system that achieves over 90% phosphorus removal and recovery, promoting a circular economy and reducing ecological impacts, offering an economically superior alternative to traditional chemical methods.

Light launched into a disordered photonic chip first drifts, then unexpectedly reverses and returns to its point of origin. This work presents the first real-space observation of this quantum boomerang effect and demonstrates how engineered loss and time-varying couplings can accelerate the return dynamics.

On-chip circularly polarized light (CPL) detectors are relevant for various applications, but current approaches have shown a trade-off between wide spectral detection range, high discrimination ratio and high polarization sensitivity. Here, the authors report broadband high-performance CPL detectors based on twisted black phosphorus structures.

Off-the-shelf, on-demand allogeneic CAR-T cells could represent a therapeutic alternative to autologous products for cancer therapy. Here the authors report the preclinical characterization of off-the-shelf CRISPR-Cas9– edited IL-13Rα2-specific allogeneic universal CAR-T cells and the results of a first-in-human phase I trial in patients with high-grade glioma.

Precise activation of endogenous genes is a powerful strategy for research and therapy, but existing tools are too large for efficient delivery. Here, authors create a compact and programmable CRISPRa platform that can be remotely controlled and shows therapeutic benefits in mouse disease models.

Sepsis remains a major clinical challenge due to dysregulated inflammation. Here, the authors develop a chemogenetic RNA-editing system using bioengineered lentiviruses to target and downregulate NLRP3 mRNA in inflammatory macrophages, offering a controllable and effective strategy for sepsis treatment.

Multislice electron ptychography reveals that gradient-distributed ions induce progressive lattice distortions from bulk to surface, driving monoclinic γ-WO3 electrochromic materials to transform into tetragonal and cubic phases and forming the gradient-distributed colour centers.

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.

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.

Cardiometabolic disease and depression often co-occur, but their multi-organ basis was unclear. Here, the authors analyse UK Biobank imaging and genetics, identifying abdomen-heart-brain networks and 43 shared loci, improving multimorbidity prediction

The authors report superconducting topological surface states (TSS) on MBE-grown Fe(Te,Se) films by high-resolution laser-ARPES. Near the FeTe limit, the surface state disappears due to an electron-correlation-driven topological transition associated with decoherence of the d_xy-orbital-derived bands.

A flexible digital artificial intelligence chip with a compute-in-memory architecture is fabricated using a commercial low-temperature polycrystalline silicon thin-film transistor process and shows high accuracy in human daily activity monitoring using multimodal physiological signals.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

The role of protein UFMylation in cancer remains to be understood. Here, the authors show that UFM1-specific ligase 1 and AKT positively regulate each other through UFMylation and phosphorylation, facilitating lipid synthesis and breast tumor growth.

NIID is a neurodegenerative disease caused by GGC repeat expansions within NOTCH2NLC gene. Here, authors develop a precise gene-editing therapy that effectively treats the disease in multiple models.

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.

Using pear as a study system, the biosynthetic pathway of acetophenones has been elucidated: naturally impaired side-chain shortening of aromatic 3-ketoacyl-CoAs leads them to undergo hydrolysis, followed by decarboxylation, to yield acetophenones.

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.

Elevated adipocyte-derived AFABP in obesity disrupts iron homeostasis in intestinal stem cells (ISCs), which impairs PPARα signalling and blocks ISC differentiation after injury.

2D diamond is expected to show superior properties compared to bulk diamond, but its synthesis remains challenging. Here, the authors report a high-temperature high-pressure method to fabricate thermally stable 2D diamond via laser-heating of few-layer graphene in a diamond anvil cell, providing relevant insights into the 2D graphene-diamond transformation mechanisms.

Staphylococcus aureus can aggregate within human synovial fluid and lead to joint infections. Here, the authors reveal that the fatty acid kinase system and its downstream saeRS regulator control S. aureus aggregation within synovial fluid.

A microwave-assisted process is developed for the rapid and scalable manufacture of pure-phase metallic MoS₂ nanosheets, enabling practical electrochemical devices for energy applications.

Accurately assessing the sustainability of grassland ecosystems affected by grazing is challenging at the continental scale. Using the developed alert index, this study suggests that 51.02% of grasslands exceed their carrying capacity, while 26.53% remain underutilized.

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.

Optical switching of a moiré Chern ferromagnet is demonstrated in twisted molybdenum ditelluride bilayers using continuous-wave circularly polarized light, paving the way for dissipationless spintronics and quantized Chern junction devices.

Here the authors present NCATS-SM0225, a small molecule that inhibits ERAD and selectively kills cancer cells by binding VDACs, disrupting calcium homeostasis, and triggering the PERK-STIM1 pathway to degrade ERAD regulators.

The mechanisms underlying oligodendrocyte precursor cells (OPCs) and neuron interactions remain unclear. Here, the authors show that chromatin remodeler BAF155 regulates OPC differentiation and myelination by coordinating synaptic genes for OPC neuron communication, contributing to autism-like behavioral deficits in mice

Psychedelics and their non-hallucinogenic analogues were compared, revealing that serotonin 2A receptor (5-HT_2AR)-mediated G_i signalling is essential for hallucinogenic effect, with the functional mechanisms underlying this providing insights for designing therapeutic drugs without hallucinogenic effects.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

LncRNA P4HA2-AS1 drives renal fibrosis by stabilizing TRIM32 to promote K63-linked ubiquitination of ULK1.