Sex differences in antibody-based cancer therapy remain poorly understood. This study identifies estrogen-driven STING reprogramming and neutrophil extracellular trap formation as a mechanism of functional antigen shielding that limits ADC efficacy.

Glutathione (GSH) robustly defends against ferroptosis independently of GPX4. FSP1 utilizes GSH to reduce ubiquinone and subsequently inhibits ferroptosis, which is distinct from the NAD(P)H-FAD axis. Targeting the FSP1-GSH axis efficiently alleviated ferroptosis-induced tissue injury.

A 3D spatiotemporal cell atlas of rice spanning the entire seed-to-seed lifecycle. Developmental trajectories are captured, and the spatially distinct roles of OsARF1 in rice development and dorsoventral endosperm asymmetry related to starch and protein accumulation are revealed.

Current genetic screens face a trade-off between scaling to large mutant libraries and measuring information-rich phenotypes. SPARCS automates laser microdissection to enable pooled forward genetic screens for complex image-based phenotypes at scale. By physically recovering individual mutants, SPARCS supports multimodal profiling of hits beyond genotyping, including via mass spectrometry-based proteomics.

A CRISPR screen of solute carriers reveals that T cells depend on SLC52A3 for VB2 uptake, whereas tumors preferentially exploit SLC52A2 to outcompete them, thereby driving T cell ferroptosis. Enforced SLC52A3 overexpression in T cells reverses this metabolic competition and enhances their antitumor activity.

Cryo-electron tomography (cryo-ET) resolves and quantifies an almost complete view of bacterial translation, revealing how gene expression machineries coordinate across the processes of transcription,...

Acanthamoeba castellanii, a pathogenic amoeba, belongs to an evolutionary branch distinctly removed from humans and fungi. Cryo-EM of the organism’s ATP synthase enzyme using raw mitochondrial lysates...

(Cell 189, 5214–5231.e1–e12; August 20, 2026)

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 rapi...

The amoeba Incendiamoeba cascadensis demonstrates that eukaryotic life can withstand temperatures beyond what was thought possible and sheds light on molecular strategies for survival in extreme heat.

Our textbook view of mitochondria, which has been shaped by studies in animals and yeast, fails to do justice to the organelle’s broader eukaryotic diversity. While most mitochondria retain a tiny gen...

The immune signal SA triggers metabolic changes to activate SnRK1 while inhibiting TOR. These central metabolic kinases antagonistically phosphorylate the key immune regulator NPR1, thereby coupling cellular metabolic state to systemic acquired resistance.

(Cell 187, 2875–2892.e1–e10; May 23, 2024)

In a large, real-world mixed-cancer cohort, analyses accounting for comorbidities and additional confounders indicate that most microbiome alterations are shared across cancers rather than specific to individual cancers. Distinct associations are limited to a subset of cancers and, in separate analyses, to age of onset and specific treatment-related adverse events.

Indole-producing Escherichia coli worsens ischemic stroke through the activation of aryl hydrocarbon receptor signaling in dendritic cells. Limiting AHR signaling in DCs promotes gut-derived DC migration to the meninges, expands meningeal regulatory T cells, and reduces neuroinflammation. This microbiota-AHR axis offers a promising therapeutic target.

Pancreatic cancer cachexia is accompanied by progressive assembly of a spatially organized tumor-macrophage-fibroblast niche. Reciprocal signaling among the cellular populations in the niche is associated with muscle wasting and cachexia progression.

Cargo has traditionally been viewed as a passive substrate of coat-mediated transport. Cryo-EM reveals that cargo containing tandem sorting motifs directly promotes higher-order adaptor assembly by bridging AP-1 complexes, enabling efficient trafficking and neuronal development in zebrafish.

Remote activation of a single-AAV-deliverable photoswitchable Cas12f system enables precise spatial and temporal control of genome editing in deep tissues without surgery or implanted devices.

Gut microbial taxonomy alone is a poor predictor of CAR-T cell therapy outcome. Instead, specific gut immunomodulatory metabolites exert opposing effects on CAR-T cell function and tumor control, identifying microbial metabolism as a potential target to predict and improve CAR-T cell outcomes.

In-cell cryo-electron tomography (cryo-ET) combined with proteomics, integrative structural modeling, and bioinformatics enables discovery and functional annotation of uncharacterized proteins. In the minimal bacterium Mycoplasma pneumoniae, this reveals a complex that links Sec-based protein translocation and extracellular folding, capable of supporting both co- and post-translational pathways.

Cryo-electron tomography (cryo-ET) resolves and quantifies an almost complete view of bacterial translation, revealing how gene expression machineries coordinate across the processes of transcription, translation, and membrane engagement directly within a minimal bacterium.

Resident tissue macrophages establish a selenium-rich niche at the pancreatic tumor border and protect invading tumor cells from ferroptosis by transferring Selenop protein to EMThi cancer cells.

APOE4 causes a pericyte-to-myofibroblast transition that promotes cerebrovascular fibrosis and perivascular amyloid accumulation. TGF-β inhibition reverses this pathological remodeling and thus presents a therapeutic strategy to restore cerebrovascular homeostasis in these high-risk individuals.

Mammalian embryos see a substantial increase in available oxygen once the placenta forms. This increase in oxygen exposure serves as a trigger for initiating the development of the hindlimb, thus controlling developmental timing and, more broadly, linking the maternal environment to evolutionary changes in body plan.

This study reveals an egg-associated bacterial signaling mechanism that couples reproductive synchronization with offspring defense in the locust L. migratoria, expanding the functional landscape of insect-microbe-predator interactions and demonstrating how microbial signals can shape complex ecological behaviors.

Retrotransposons can infect neighboring cells using a mechanism that relies on a small fusogen-like protein rather than on the envelope protein that is typically required for infection.

The mouse motor cortex divides into 16 spatially organized modules based on distinct subcortical projections. This specificity covaries with cortical connectivity patterns and cell-type composition along two spatial axes, thereby defining the rules by which motor cortex modules integrate with granularity into brainwide and precisely wired neuronal networks to influence movement.

An AI-designed IL-21 mimetic converts transient KRAS inhibitor responses into durable pancreatic cancer remissions through CD4 T cells, independent of CD8 T cells and tumor MHC class I expression.

Toll-like receptor signaling activates proinflammatory interferon-stimulated genes (ISGs) even in the absence of interferon by triggering a shift from IRF2 to IRF1 occupancy at ISG promoters and enhancers. Newly translated IRF1 promotes proteasomal degradation of the weaker transcriptional activator IRF2 by engaging the E3 ubiquitin ligase SPOP.

The amoeba Incendiamoeba cascadensis demonstrates that eukaryotic life can withstand temperatures beyond what was thought possible and sheds light on molecular strategies for survival in extreme heat.

Cold-stress signals are transmitted to chloroplasts and subsequently trigger cold responses through an RAF-like bi-kinase module where cytoplasmic RAF3 and plasma membrane RAF6 translocate to chloroplasts, where they inhibit photosynthetic activity but activate nuclear cold-responsive gene expression.

An mRNA-lipid nanoparticle-encoded CD19×CD3 T cell engager depletes B cells with attenuated cytokine release in preclinical models. In three patients with treatment-refractory immune thrombocytopenia, treatment with this T cell engager achieved sustained platelet recovery over 6 months, suggesting that mRNA-encoded T cell engagers represent a promising therapeutic approach for resetting autoreactive immunity in B cell-driven autoimmune disease.

Oligodendrocytes, predominantly known for their role in myelination, play a broader role in regulating the central nervous system, including feeding axons and reshaping neural circuits, with their malfunction in diseases ranging from multiple sclerosis to Alzheimer’s. This review covers oligodendrocyte biology and their therapeutic relevance.

Biomedical artificial intelligence is advancing from tools that answer human-posed questions to agents that ask their own. Guo et al. assess this transition, including scaling logic, autonomous-laboratory trajectory, and the risks of hallucination, bias, dual use, and cognitive deskilling. This perspective argues that progress depends on responsible human-AI collaboration.

Artificial intelligence (AI) is changing the way biomedical research is conducted by making it possible to integrate diverse types of biological data and tackle questions that were previously difficul...

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 tha...

Salaudeen et al. review common reliability failures in predictive and generative AI for healthcare, including erroneous model outputs, clinically unjustified performance differences, and deployment-ti...

Drawing inspiration from Hilbert’s list of 23 mathematical problems that have focused the mathematical community’s attention for more than a century, we propose fifteen grand AI challenges to focus th...

Biological processes continuously adapt in response to intervention. Unlike static predictive models, biomedical world models support action-conditioned simulations for counterfactual reasoning, inter...

The virtual cell is envisioned as a multi-modal, multi-scale, and stateful world model that can simulate, perturb, and ultimately program cellular systems. This perspective outlines how this paradigm could transform cell biology from experimental trial-and-error toward simulation-driven discovery, counterfactual exploration, and rational intervention design.

The Virtual Cell Challenge returns in 2026 with a more demanding test of biological generalization: zero-shot prediction across multiple independent cellular contexts. Participants will build models t...

I know what you think about papers in Cell. They are long. Mechanistic. “Complete.” They report deep biological insights. I know this because I hear it a lot from researchers. There is truth to it. Ce...

Phosphorothioates, stereospecific modifications of the RNA phosphate backbone in anaerobic archaea, expand the epitranscriptome beyond nucleobases and ribose sugars. Installed by Esti enzymes at conserved rRNA and tRNA hotspots, these environmentally responsive marks stabilize tRNAs and support growth at high temperatures.