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TCR-engineered T cells have shown limited efficacy in part due to the absence of co-stimulation leading to limited accumulation in solid tumors. The authors here show engineering the CD8β coreceptor with an intracellular CD28 domain enhances cytokine production, persistence, and tumor control in vivo independent of tumor-associated co-stimulatory ligand encounter.

Tracheal defects lack effective long-segment repair solutions. Here, authors develop a bio-adaptive hydrogel strategy that guides cartilage, vascular, and epithelial regeneration to reconstruct a functional, long-segment trachea.

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.

This Commission aims to resolve the current dialysis policy challenges in Thailand and generate lessons for the global kidney community by drawing on empirical evidence, systems thinking and multidisciplinary expertise to generate policy goals and recommendations.

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.

Cell-cell adhesion plays critical roles in maintaining and regulating cellular functions. Here, authors present a diffusive N-cadherin functionalized hydrogel that provides cell-cell adhesion cues to modulate intercellular communication to promote neural regeneration for treatment of traumatic brain injury.

It was shown that early-day stem cell infusions reduced the severity of acute graft-versus-host disease (aGVHD). Our result suggested early morning cord blood transplantation reduces aGVHD severity and correlated with circadian sCD26 fluctuations.

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.

Authors propose a pathway to design GeTe based thermoelectric materials with high thermoelectric performance and mechanical properties by nanotwin architecture and inducing high valley degeneracy.

Functional evolution expands the catalytic repertoire of biosynthetic enzymes. Here, the authors reveal that a tripartite enzyme complex has evolved to catalyze Friedel–Crafts acylation through neofunctionalization of a conserved thiolase architecture.

Using single-nucleus and spatial transcriptomics, the authors reveal resilience signatures in neocortical layer 4 neurons. They show KCNIP4 protects these cells by reducing hyperexcitability, a driver of neurodegeneration.

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.

This study maps a spatiotemporal atlas of zebrafish cerebrovascular development, linking genes and cells to 3D vascular architecture. It reveals how vessel networks form and identifies key genes essential for blood-brain barrier integrity.

Multi-axis atropisomers are common, but techniques for structural elucidation are limited. Here, the authors report a correlation between molecular dynamics and electronic through-space conjugation (TSC), along with absolute separation of the syn and anti conformers.

This study shows that acidification increases substrate affinity in ammonia-oxidizing microbes, partly offsetting reduced ammonia availability. Stronger responses in archaea than bacteria explain contrasting ecosystem reactions.

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.

Phage therapy is an alternative treatment against biofilm-associated infections. In this case report, phage-antibiotic therapy was used to treat a vascular graft infection caused by a refractory fluoroquinolone non-susceptible Pseudomonas aeruginosa.

Plastic foams are widely used across industry, but petroleum-based materials are unfavorable. Here the authors report a cellulose-based molecular foam for thermal management as an environmentally friendly alternative.

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.

The role of lipid metabolism in Parkinson's disease is poorly understood. Here, Ren and co-authors identify a key enzyme in this process, mitochondrial glycerol 3-phosphate acyltransferase, as a critical driver of α-synuclein toxicity.

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.

This study applies generalized linear mixed models (GLMM) and advanced transcriptome wide association study (TWAS) methods to improve the discovery of colorectal cancer risk transcription factors and genes, including potential druggable targets.

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.

In osteoporotic fracture-related infection (FRI), coordinated bone healing is compromised by cortical bone lysis and persistent bacterial colonization. Here, Li et al. report a dual-action nanocomposite bisphosphonates hydrogel for treatment of osteoporotic FRI that preserves cortical bone integrity and restores fracture healing.

Non-traditional luminescent polymers are materials without extended π-conjugation. Here the authors develop highly luminescent supramolecular polymers using dynamic quadruple hydrogenbonded motifs with potential for sensing and fluorescent adhesives.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Thermoelectric materials have the potential to convert waste heat into electricity. Although some of the more viable thermoelectric materials are based on expensive rare earth elements, here the authors replace Yb with low-cost Ce by engineering Ce solubility, thereby making Ce-CoSb3 a competitive thermoelectric.

Altermagnets combine spin-split electronic bands with zero net magnetization, making them ideal for integration into spin-based information processing devices. Here Guo, Chen, Zeng, and coauthors demonstrate a magnetic memory making use of the altermagnetic spin splitting torque in a three terminal MRAM device.

Transcranial focused ultrasound can be used for neuromodulation, but its use in wearable systems remains challenging. The authors present a miniaturised wearable ultrasound device, integrated with a bioadhesive hydrogel for stable, long-term somatosensory cortical stimulation.

Microsatellite-instability-high gastric cancers typically respond to immune checkpoint inhibitors, but only a small proportion of patients in the microsatellite-stable group responds. Here authors stratify these patients via a semi-supervised learning approach using multi-omics input data and functionally validate T-bet+ CD8 + T cells as crucial factor in the immunotherapy response.

This study reveals stage-dependent cognitive network dedifferentiation in early psychosis, with increasing inter-domain correlations from healthy controls to clinical high risk to first-episode schizophrenia, linked to reduced general intelligence.

Understanding the dynamics of empirical food webs is of central importance for predicting the stability of ecological communities. Here Allesina et al.derive an approximation to accurately predict the stability of large food webs whose structure is built using the cascade model.

Tang, Chen, Qian et al. present a multimodal, interpretable dimension reduction framework called SpaHDmap, which leverages histology images and enhances the resolution of spatial transcriptomics, thus enabling the dissection of complex tissue structures.

A computational workflow, LyMOI, uses LLM, knowledge graphs and other tools to facilitate ’omic analysis and hypothesis generation related to autophagy.

BioPathNet predicts drug–disease indications, synthetic lethality and lncRNA–mRNA interactions using a deep learning framework.

A pathogenic subset of NK cells is identified that promotes type 1 diabetes and is generated via T cell-derived IL-21.

Efficient and durable energy storage is vital for renewable integration. Here, the authors design an aqueous iron-cerium redox flow battery using a universal complexing agent that enhances stability and efficiency, achieving long cycle life and high performance in neutral conditions.

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.