Spatial biology reveals altered macrophage states in immunosuppressed non-melanoma skin cancer

Spatial multi-omics reveals macrophage states that constrain adaptive immunity in immunosuppressed non-melanoma skin cancer.

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Targeting peripheral 5-HT2AR enhances antitumor immunity in colorectal cancer

By selectively targeting peripheral 5-HT2AR without inducing psychedelic effects, a non-brain-penetrant agonist boosts antitumor CD8+ T cell immunity and improves immunotherapy responses in preclinical models of colorectal cancer.

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Metabolic atlas of early human cortex reveals glycolytic remodeling and pentose phosphate pathway control of cell fate transitions

The developing human cortex is composed of diverse cell types, but how nutrient metabolism shapes their fate has remained unclear. This study maps the metabolic landscape of the developing human cortex and identifies glycolysis and pentose phosphate pathway activity as key regulators of radial glia fate, controlling the generation of outer radial glia and inhibitory neurons.

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Distinct cellular phenotypes of language and executive decline in amyotrophic lateral sclerosis

Beyond its motor dimension, ALS can also involve cognitive impairment, with affected domains varying across individuals. Rather than a single common disease process, this heterogeneity reflects regionally and cellularly distinct alterations in the prefrontal cortex that are only partially predicted by TDP-43 neuropathology.

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Ultrarapid deep 3D histology enables intraoperative mapping of glioma infiltration

ULTRA compresses 3D histology from days or hours to within 30 minutes by leveraging the chemical specificity of stimulated Raman scattering (SRS) microscopy through the synergistic development of rapid tissue clearing and unsupervised AI. The platform enables intraoperative visualization of glioma architecture and depth-dependent tumor infiltration margins.

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Milk osteopontin alters the infant microbiome to drive DC hematopoiesis and disease tolerance

Milk-derived osteopontin confers protection from viral or bacterial severe lower respiratory illness by altering the neonatal gut microbiome.

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Co-option of retrotransposons promotes antibody diversification

A longstanding mystery in antibody diversification is how AID specifically targets immunoglobulin V genes. Ancient LINE-1 retrotransposons embedded within the immunoglobulin locus provide a recruitment platform for the HUSH complex and AID to drive somatic hypermutation.

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Spatial atlas of the human brain vasculature reveals specialized cell ensembles

An integrative cell and spatial atlas defines the organizing logic of the adult human cerebrovasculature, providing a framework for studying how vascular cell states support brain function and shape neurological disease vulnerability.

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Dietary arginine drives codon-dependent MHC class I translation and improves immunity in colon tumorigenesis and respiratory viral infection

Arginine availability regulates arginyl tRNA levels and codon-dependent translation of MHC class I, tuning antigen presentation and shaping anti-viral and anti-tumor immunity.

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Basement membrane turnover controls cell shape

Basement membranes are scaffolds of proteins, like collagen, that give organs shape. During development, basement membranes must adapt to the growing organ. We infer how fast the basement membrane adapts by measuring collagen turnover. We find that perlecan, another basement membrane protein, regulates collagen turnover to control organ shape.

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CRISPR screens identify targets to rescue age-related T cell dysfunction in cancer

Dusp5 and Zfp219 serve as critical regulators of age-related T cell dysfunction, with the loss of either driving T cells into an effector-like state that improves tumor control through distinct mechanisms within the aged tumor microenvironment.

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Gasdermin E couples viral pyroptosis to lethal hepatic lipid accumulation

Wetland virus activates dual apoptotic cascades to trigger GSDME-dependent hepatocyte pyroptosis, which rewires cellular lipid metabolism and ultimately causes severe hepatic steatosis. Therapeutic targeting of this pyroptosis-metabolism axis alleviates lethal wetland virus infection in mice.

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Coordinated RNA- and protein-templated synthesis of double-stranded DNA by a dual reverse transcriptase immune system

Bacterial reverse transcriptases defend against viruses, yet how their DNA products stop infection remains unknown. Bacteriophage inhibition of a host recombination enzyme activates the DRT3 defense system, which employs RNA- and protein-templated reverse transcriptases to synthesize antiviral double-stranded DNA.

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Why machines don’t speak biology: Toward native biological language models

Advances in AI have shown promise in protein structural information, but in this perspective, the authors argue that biology’s true complexity—emergent, evolved, and irreducibly messy—demands more than bigger models or more data and that unlocking a genuine “biological” AI requires anchoring machine learning in canonical, process-based “world models,” rather than chasing a universal theory built from parts alone.

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Advancing cancer detection and treatment using longitudinal routine clinical data

Liu et al. develop Oncoformer, a multimodal transformer that reads routine laboratory tests and chest X-rays already collected in everyday care. Across more than 3.6 million individuals, it detects cancer, infers tumor stage, and stratifies treatment response and recurrence risk, pointing toward risk-adapted cancer care built on data already in hand.

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UniPert-G2CP bridges genetic and chemical screens from molecular representation to phenotype modeling

UniPert-G2CP is an AI framework for jointly modeling molecular-level perturbation causes with phenotypic-level cellular effects across genetic and chemical domains. These complementary views enable more accurate perturbation prediction, mechanistic discovery, and efficient in silico drug screening.

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Dynamic dimer-of-dimers architecture defines Mg2+ transport in human CNNM4

Cryoelectron microscopy structures of human CNNM4 in distinct conformational states reveal how an unexpected dimer-of-asymmetric-dimers architecture mediates Mg2+/Na+ exchange and identify an intracellular acidic patch that may function in cellular magnesium sensing.

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An Oryza orphan gene confers trans-species drought tolerance

ROAD1 is an Oryza-specific orphan gene that co-opts conserved ABA signaling to enhance drought tolerance without obvious growth defects or yield penalty under normal conditions. Elite rice lines carrying its functional allele exhibited higher grain yield than controls under drought, and its heterologous expression enhanced drought tolerance across diverse angiosperms.

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Trichoderma swollenin activates AtABCB5-dependent auxin efflux to promote plant development

The beneficial fungus Trichoderma acts through the secreted swollenin ThSWO, which crosses the plant cell wall and engages AtABCB5, an auxin efflux carrier, at the host cell surface. This effector-transporter module tunes auxin-associated cellular responses, revealing how beneficial fungi co-opt host hormone transport to promote root development.

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Condensates of the chromatin regulator ANKRD11 restrict hypertranscribed genes to safeguard development

ANKRD11 restricts hypertranscribed genes by forming biomolecular condensates that spatially sequester elongation factors, with disruption of this condensate-mediated control leading to aberrant organo...

cell.com

Condensates of the chromatin regulator ANKRD11 restrict hypertranscribed genes to safeguard development

ANKRD11 restricts hypertranscribed genes by forming biomolecular condensates that spatially sequester elongation factors, with disruption of this condensate-mediated control leading to aberrant organogenesis and underlying the pathogenesis of developmental disorders like KBG syndrome.

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The intrinsic cardiac nervous system is essential for cardiac function and survival

Two genetically distinct neuronal subtypes in the intrinsic cardiac nervous system are differentially required for baseline cardiac function and stress resilience to maintain cardiac stability and survival.

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A domestication-selected enhancer coordinates source-sink balance to improve harvest index and yield in maize

A teosinte-derived enhancer boosts the harvest index and grain yield in maize by optimizing source-to-sink carbon and nitrogen allocation, revealing a physiological pathway to yield during maize domestication.

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Expanding the scope of protein language modeling to protein-protein interactions with MSA Pairformer

Protein language models have excelled at modeling individual proteins, but extending these capabilities to protein complexes remains a major challenge. MSA Pairformer, a parameter-efficient protein la...

cell.com

Localized PD-1 CAR T therapy reprograms neuroinflammation

PD-1+ T follicular helper-like cells drive B cell-associated pathology in multiple sclerosis. Programmable PD-1-targeting CAR T cells selectively eliminate these pathogenic CD4 T cells while delivering IL-10 at sites of inflammation, thereby suppressing neuroinflammation across preclinical models.

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CSF clearance through arachnoid fenestrations to olfactory meningeal lymphatics

Cerebrospinal fluid (CSF) crosses arachnoid fenestrations near the olfactory bulbs to reach dural lymphatics that traverse the cribriform plate, connect to nasal lymphatics, and drain to cervical lymph nodes. Aging impairs this pathway, but intranasal VEGF-C restores the lymphatics and the CSF outflow.

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