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.

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.

Population-level 3D genome atlas of 34 semi-wild and 267 cultivated allotetraploid cottons reveals domestication-selected chromatin conformations that enhance cotton fiber quality and unlock cryptic breeding targets.

Viruses such as SARS-CoV-2 can use programmed ribosomal frameshifting to turn off host translation and promote viral replication, expanding the known uses of programmed ribosomal frameshifting by viruses.

Glioma-derived guanidinoacetate depolarizes neighboring neurons through γ-aminobutyric acid (GABA) A receptors, and depleting this metabolite reduces both neuronal activity and glioma growth.

GORG-Dark presents genomes of 9,698 individual bacterial and archaeal cells from the ocean’s sunless interior. The atlas resolves depth stratification to abyssal waters, uncovers particle-attached Pelagibacterales, maps chemolithoautotrophy and biosynthetic gene clusters, and identifies a rhodopsin clade specific to the dark ocean.

By tethering a protein of interest to anti-CRISPR, protein degradation is transformed into amplified and programmable transcriptional outputs via Cas-based transcription factors, with sensitivity to p...

Spatiotemporal transcriptomics across conifer reproductive and vegetative shoots reveals candidate developmental regulators and evolutionarily conserved tissue patterning genes in seed plants.

Copper binding drives MYH9 polymerization, triggering cytoskeletal collapse and cuproptosis. HThPA releases intracellular copper through glutathione depletion, exposing a therapeutic vulnerability in drug-resistant tumors.

Metax is a cross-domain metagenomic profiler that uses genome-wide coverage evidence to improve species-level microbial profiling and distinguish supported taxa from artifacts. Across diverse datasets, Metax enables robust taxonomic profiling, pathogen detection, contamination assessment, and discovery of disease-associated bacterial and viral signatures.

Cell-mediated immunity requires cytotoxic CD8+ T cells that adopt and maintain an effector phenotype. Here, D-α-hydroxybutyrate (DAHB) is shown to act as a metabolic adjuvant, driving the conversion of proliferating CD8+ T cells into cytotoxic effector cells by linking mitochondrial ATP production to chromatin remodeling and gene expression.

Mesenchymal stem/stromal cell (MSC)-based therapy holds promise for reversal of bone loss in osteoporosis. This phase 1 study establishes the safety and feasibility of intravenous administration of glycocalyx-engineered human MSCs and provides evidence that MSCs derived from the bone marrow of older individuals with osteoporosis retain clinically meaningful osteoregenerative capacity.

Agarwal et al. introduce MitoSpace, a self-supervised model trained on 4D lattice light-sheet microscopy data. The model resolves drug-induced mitochondrial phenotypes without labels, predicts membrane potential from morphology and dynamics, generalizes to unseen perturbations and lung organoids, and shows that representation quality improves progressively from 2D to 4D.

Serotonin neurons innervate nearly the entire mammalian brain, yet how their projections are organized has remained unclear. Systematic whole-brain serotonergic axon collateralization mapping reveals five projectomic groups that preferentially target functionally related regions, with each projectomic group connecting to specific spatial transcriptomic and behavioral profiles.

Mutations accumulate in cells with age, while caloric restriction extends lifespan across diverse animals. Grońska-Pęski et al. study the effect of caloric restriction on mutations genome-wide in mice, finding reduced mutation burdens across several tissues and cell types, thereby establishing that diet can alter mutation accumulation genome-wide during aging.

Cryo-EM and genetic analyses reveal that the SWI/SNF chromatin remodeler is an integral component of the transcription pre-initiation complex. The structures demonstrate how SWI/SNF facilitates transcription initiation through stabilization of PIC organization and concerted remodeling of the +1 nucleosome.

The tendon/ligament stem cell is identified, and dysregulation of differentiation in this cell is shown as a mechanism contributing to lumbar spinal stenosis.

An expanded atlas of human cells maps the expression of nearly all human transcription factors across 701 cell-type/tissue combinations and uncovers the heterogeneous nature of senescence across tissues and cell types.

How do maternal gut bacteria seed the rapidly developing neonatal gut? Heo et al. show that Bacteroides fragilis produces a distinct membrane lipid that enables this strict anaerobe to tolerate a microaerobic environment. This finding highlights divergent evolutionary strategies among related species, most of which rely on lipids conferring broader fitness.

By tethering a protein of interest to anti-CRISPR, protein degradation is transformed into amplified and programmable transcriptional outputs via Cas-based transcription factors, with sensitivity to protein loss tuned by the anti-CRISPR-Cas ratio. These synthetic circuits can be multiplexed to enable high-throughput discovery of protein-degrading and -destabilizing molecules.

We developed an AI-based and principled computational strategy for de novo design of Rhobins, compact pan-rhodamine binders with high brightness, reversible binding, and extreme stability. It enables superior live-/fixed-cell, super-resolution, and single-molecule imaging with properties surpassing existing tags. It also supports extremophile imaging at 75°C, inaccessible with current tools.

Single-nucleus RNA sequencing and spatial validation across human and mouse striatum define principles of neuronal specialization across cell types, subregions, and species. These findings lay the foundation for understanding cell- and subregion-resolved contributions to brain function and disease, including addiction risk, antipsychotic responses, Huntington’s disease vulnerabilities, and pharmacologically relevant species differences.