Chen et al. established a cell-based model to investigate mitochondrial recovery after transient damage. They identified the E3 ligase MGRN1 as a mitochondrial repair regulator that is recruited via MFN1 and limits excessive mitophagy, thereby promoting preservation of mitochondria and facilitating recovery through DELE1-eIF2α-ATF4- and Nrf2-mediated antioxidant responses.

Xu et al. show that humans infer hidden rule changes by integrating outcome history with perceptual difficulty during hierarchical reasoning. A confidence-based Bayesian model and RNN capture this process, while human dACC represents errors and difficulty in a near-orthogonal geometry that supports switch-confidence readout and predicts individual performance.

Wang et al. identify a gut-brain pathway in which loss of the commensal bacterium Alistipes shahii reduces indole production, prevents hippocampal indole-AhR signaling, and drives anxiety and depression behaviors in patients and mouse models of irritable bowel syndrome.

Wang et al. report that Menin is essential for corticogenesis. The study reveals that Menin recruits the COMPASS family proteins and deposits H3K4me3 at loci governing neuronal development. This Menin-mediated epigenetic activation of EphA4 promotes neuronal polarization.

Song et al. identify that OTUD1 functions as an RNA-binding protein that stabilizes osteogenic transcripts in mesenchymal stem cells. OTUD1 deficiency drives age- and hormone-induced bone loss. These findings reveal a non-enzymatic function of OTUD1 in bone homeostasis and provide a potential therapeutic target for osteoporosis.

Perez, Schoenfeldt et al. present an integrated platform and methodology combining automation and machine learning to evaluate thousands of conditions across >400 compounds in yeasts, nematodes, flies, killifish, and mice, identifying conserved longevity-associated pathways and prioritizing interventions with strong translational potential.

Using paired genomic and direct in vivo transcriptomic sequencing of human oropharyngeal swabs, Faiola et al. demonstrate that GAS carriage is defined by unique phase-specific gene expression patterns. The results highlight a complex, mechanism of bacterial persistence, and transmission rather than conserved carriage genotypes.

Khan et al. show that long-term nicotinamide riboside produces divergent tissue responses in mitochondrial progeria mice: it restores cardiac NAD+ metabolism and function, but in bone marrow causes redox-metabolic remodeling, transcriptomic stress signatures and disrupted heme/iron pathways and impaired erythroid maturation, highlighting tissue-specific metabolic vulnerabilities when evaluating NAD+ boosting therapies.

(Cell Reports 44, 116363; October 28, 2025)

Epstein-Barr virus (EBV) establishes lifelong latency in human B cells by balancing latent and lytic programs. Dan and Jady et al. show that the viral snoRNA v-snoRNA1 directs 2′-O-methylation at two ribosomal A-site positions, inducing a ribosomopathy-like state that globally rewires gene expression and controls viral production.

This study proposes inferential planning as a framework for understanding frontal neural activity during sequential behaviour. Using active inference models, Donnarumma et al. reproduce key findings from monkey electrophysiology, including the simultaneous representation of multiple plan elements in separable neural subspaces, suggesting that these subspaces may support inferential message passing.

(Cell Reports 44, 115339; March 25, 2025)

Naz et al. benchmark reproducible microglial states across adulthood, aging, and parabiosis to define a conserved activation program and both shared and region-specific transcriptomic remodeling. They further reveal regional differences in microglial sensitivity to parabiosis-mediated accelerated aging and rejuvenation, with the cerebellum the most sensitive and the striatum the least.

Using a broad panel of ciliopathy iPSC-retinal pigment epithelium (RPE) new approach models, Reichert et al. identified shared cellular endophenotypes across patients, including mesenchymal drift and loss of polarization. Mechanistic studies implicated mitochondrial dysfunction and aberrant TGF-β signaling in RPE pathology. Drug screening identified pioglitazone and galunisertib as candidate therapeutics.

Using in vitro reconstitution assays and live-cell imaging, Adriaans et al. show how Bud3 and Bud4 drive septin double-ring assembly at the budding yeast division site during cytokinesis. Their findings also reveal how these proteins establish a septin-dependent memory of cytokinesis, providing insight into the mechanisms underlying division-site organization and inheritance.

Zhong et al. show that cPGES drives MASLD progression through cell type- and stage-specific, prostaglandin E2-independent control of glucocorticoid receptor signaling. Targeting cPGES restores hepatocyte cholesterol homeostasis and macrophage anti-inflammatory polarization, alleviating steatosis, inflammation, and fibrosis in preclinical models.

Wagner-Carena et al. pair calcium imaging of neural activity with nanoscale electron microscopy in a cubic millimeter of mouse visual cortex. They observed that neurons form cross-inhibiting assemblies that reliably encode natural visual stimuli. Over a quarter of the neurons join no assembly and are less integrated in the network.

Jiang et al. identify PTGS2-high macrophages enriched in aged joints and show that their THBS1-SDC4 signaling contributes to chondrocyte senescence. Local CXB-lipo delivery reduces PTGS2+ macrophages and attenuates OA progression in a surgically induced model.

Li et al. show that SADS-CoV triggers cGA-STING signaling via nuclear envelope rupture but evades immunity via its nucleocapsid (N) protein. The N protein displaces the ER-resident cofactor DAD1 from STING to block activation and reveals a viral antagonism mechanism and therapeutic targets.

Type 2 cytokines suppress antitumor immunity through coordinated effects on T cells and dendritic cells. Fabre et al. show that combined blockade of IL-4, IL-13, and TSLP enhances PD-1 checkpoint inhibition, promotes immune remodeling in tumors, and is supported by human data linking type 2 signaling to poor cancer outcomes.

Kishikawa et al. demonstrate that periodontitis induces anxiety-like behavior and cognitive dysfunction through IL-17A-producing γδ T cells that migrate from the cervical lymph nodes to the brain via the CCL20/CCR6 axis. They also show that neutralizing IL-17A prevents these behavioral deficits, identifying a neuroimmune mechanism linking periodontitis to brain dysfunction.

Miklas et al. characterize age-related C. elegans intestinal secretory-pathway proteins using proximity labeling tools and in vivo proteomics. They identify a conserved secreted phosphatase, ACP7, that extends lifespan in a secretion- and phosphatase-dependent manner. This resource highlights the role of extracellular enzymes in regulating lifespan.

Gu et al. use 1,150 complete genomes to construct gut microbial metabolic models that recover transport functions overlooked in draft assemblies. Interaction asymmetry defines four ecological groups with distinct IBD dysbiosis patterns, while keystones of the metabolic interaction network improve cross-validated disease classification.

Bourhy et al. show that sepsis strongly activates vagus nerve sensory neurons and downstream brain circuits in mice, driving behavioral changes including persistent anxiety. Manipulating vagal signaling altered sepsis-induced brain activation and anxiety-like behavior, highlighting potential therapeutic targets for sepsis-associated brain dysfunction.

How the cortex maintains stable memories despite highly volatile individual cell activity remains a fundamental puzzle. Using long-term imaging in mice, Descamps et al. reveal that the anterior cingulate cortex overcomes single-cell instability through collective network-level organization, creating stable and efficient population codes for spatial objects.

Ruan et al. show that loss of pericytic laminin-γ1 induces vascular dysfunction and matrix defects at middle age, followed by CSF influx/brain clearance defects, synaptic loss, and cognitive decline at old age. These findings establish an important role of laminin dysregulation in the pathogenesis of cerebral small vessel disease.

Mitochondrial Mg2+ transport is essential for cellular metabolism but remains poorly understood. Maity, Venkatesan et al. identify PHB1 as a positive regulator of the MRS2 Mg2+ channel and define the MRS2 complex architecture. Quantitative mitochondrial Mg2+ biosensors reveal high-capacity Mg2+ uptake, linking mitochondrial Mg2+ homeostasis to bioenergetic control.

Mooney et al. carried out surfaceome and global proteome profiling to identify new therapeutic targets in osteosarcoma. Their approach highlights known, as well as lesser known, targets on the surface of osteosarcoma cells, and presents their data as resource to be explored by the broader scientific community.

Dao and Carter find protein kinase C delta as a selective marker of the paratenial thalamus in the anterior midline thalamus and show that the paratenial thalamus engages multiple circuits within the limbic system, including reciprocal loops with the infralimbic cortex and subcortical projections to the nucleus accumbens and basolateral amygdala.

Sheng et al. show R-loops safeguard the chromatin and transcriptional landscape of mouse SN oocytes by stabilizing SPT6 at specific genomic loci, thereby promoting SETD2-dependent H3K36me3 deposition. RNASEH1-mediated R-loop loss disrupts the balance between gene-body H3K36me3 and broad H3K4me3, causing widespread transcriptional dysregulation, defective meiotic progression, and compromised oocyte maturation.

Kobayashi shows that Six2+ cells at the onset of mouse kidney development are not restricted to nephron fates but can also generate a subset of renal interstitial cells. These findings reveal transient lineage plasticity between nephron and interstitial progenitors before a stable nephron-interstitium lineage boundary is established.

Nuciforo et al. establish a biopsy-derived organoid biobank spanning the clinical diversity of liver cancer and use large-scale phenotypic screening to build rational drug combinations. Because the combined agents act through complementary mechanisms, triplet therapies remain effective across heterogeneous tumors, with in vivo efficacy and favorable tolerability supporting translational potential.

How the intracellular environment affects RNA-protein assemblies is still murky. Macedo de Vasconcelos et al. show that zinc and similar trace metals can directly modify a cell’s ability to form stress granules. This implicates zinc in the direct modulation of RNA dynamics.

Wang et al. construct a single-cell atlas of neonatal sepsis across the clinical course, identifying S100A8+ MDSC-like cells as major contributors to cytokine storm, potentially through an S100–TLR4–MYD88 circuit. They also reveal lymphoid apoptosis, exhaustion, mitochondrial dysfunction, and tolerogenic B-cell reprogramming, highlighting coexisting hyperinflammation and immunoparalysis.

Chowdhary et al. uncover a stepwise mechanism of transcriptional condensate assembly through the sequential recruitment of a transcriptional activator, a coactivator, and RNA Pol II. This ordered condensate assembly enables graded, rather than switch-like, gene control and adaptive three-dimensional genome reorganization to promote cellular fitness.

Chen et al. uncover that rather than fueling tumor growth, acetate triggers an ACSS2-H2A.Zac-ATM feedback loop to suppress proliferation in esophageal squamous cell carcinoma, pointing to a potential therapeutic strategy targeting the otherwise undruggable chromatin regulator H2A.Z.

Enervald et al. show that DIS3, one of the catalytic subunits of the human RNA exosome, facilitates the resolution of stalled RNAPII transcription complexes by engaging in the degradation of the 3′ end of backtracked RNA. This activity of DIS3 is necessary for efficient transcription elongation.

Park et al. show that a conserved 16S rRNA modification in bacteria enables transcript-specific translation by overcoming inhibitory mRNA secondary structures to fine-tune the production of key regulatory proteins. Their findings establish ribosome modification as a mechanism for controlling protein dosage during development.

Accurate sound encoding requires auditory brainstem synapses to sustain temporally precise action-potential (AP) firing over large and rapid fluctuations in activity. Whether presynaptic CaV2.1 Ca-dependent facilitation (CDF) enables high-fidelity auditory information transfer is unclear. Al-Yaari et al. show that CaV2.1 CDF is essential for faithful auditory information transfer.

Pathogenic bacteria release ATP that is sensed by airway tuft cells. In response, tuft cells produce leukotrienes that orchestrate early antibacterial immunity by promoting neutrophil recruitment and enhancing macrophage bactericidal activity, identifying a previously unrecognized epithelial sensing pathway in the airways.

Single-cell and spatial transcriptomics identify type I interferon-activated myeloid states associated with less fibrotic stages in idiopathic pulmonary fibrosis. These inflammatory myeloid niches are spatially segregated from advanced, SPP1+ macrophage-enriched fibrotic regions, suggesting distinct immune microenvironments across different stages of tissue remodeling.

Rice chilling tolerance varies between japonica and indica, with japonica generally exhibiting greater chilling tolerance. Zheng et al. identify a japonica-specific COG5 promoter variation that enables preferential activation of COG5jap by OsDREB6, thereby enhancing rice chilling tolerance.

Detecting a target odor against complex backgrounds requires separating signal from interference. McCalmon et al. show that discrimination performance depends on target odor concentration but not background complexity. This dependence arises because sparse glomerular input representations limit background interference and leave neural variability as the dominant constraint on odor discrimination.

Yi et al. uncover a TAF15-oxidative stress axis in neurodegeneration. They demonstrate that the neuronal TAF15 overexpression triggers oxidative stress and neurotoxicity, leading to gliosis and behavioral abnormalities. Notably, the antioxidant N-acetylcysteine amide (NACA) rescues these phenotypes, highlighting TAF15 as a potential therapeutic target.

Zhang et al. identify a missense mutation in BCHE that affects lipid metabolism in horses. Cellular and mouse models show that the C variant increases BChE activity and reduces lipid accumulation. Ancient DNA analyses reveal positive selection in Asian horses until the mid-13th century CE.

Zhang et al. show that voluntary running induces highly excitable newborn neurons to compete with helplessness-related neuronal ensembles in the dentate gyrus. This competition is associated with changes in spine density and Ca2+ activity in LH-TRAPed neurons, thereby attenuating helpless behaviors.

Wu et al. show that the Burkholderia pseudomallei effector Hcp1 redirects macrophage arginine metabolism to drive multinucleated giant cell formation through ARG1 activation and E-selectin induction. Targeting this host pathway reduces bacterial burden and improves survival in infected mice, revealing a potential therapeutic target for melioidosis.

Yu et al. show that DMV neuronal hypoexcitability drives gut motility dysfunction in Parkinson’s disease. They reveal that electroacupuncture at ST36 restores gut motility via the brain-gut axis, offering a promising therapeutic strategy.

Tang et al. demonstrate that SPINK1 is a key regulator of pancreatic cancer progression by regulating epigenomic remodeling. Through a COL18A1-endostatin signaling axis, SPINK1 drives histone H3 modifications that promote stemness and plasticity in PDAC cells, revealing a potential therapeutic vulnerability in this aggressive disease.