Cell Reports

Convergent functional evolution of mRNA-binding proteins fuels allotetraploid adaptation in cyprinids Liu et al. report a phased genome assembly for Spinibarbus caldwelli, which is revealed to be of recent allotetraploid origin. The study identifies extensive segmental homoeologous exchanges and ongoing genic diploidization. Genome-scale convergent evolutionary analysis further implicates adaptive changes in RNA-binding proteins (e.g., Tia1) in polyploid adaptation within cyprinids.

Convergent functional evolution of mRNA-binding proteins fuels allotetraploid adaptation in cyprinids

Noradrenergic tuning of arousal is coupled to movement transitions Li et al. characterize the locus coeruleus (LC)-norepinephrine system in movement-arousal coupling during anesthetic emergence and awake-movement transitions. They find that LC activity correlates with, but is not causal to, movement transitions and that the LC more robustly activates sympathetic than behavioral arousal, suggesting that noradrenergic coupling to movement is indirect.

Noradrenergic tuning of arousal is coupled to movement transitions

Membrane dome-based regulation mechanism of the mechanosensitive PIEZO channel Liu et al. combined electrophysiological measurements, cryo-EM structural analysis, and in vivo investigations of C. elegans PEZO-1 isoforms to propose a distinct PIEZO-regulatory mechanism that modulates mechanosensitivity by adjusting the dome area via alternative splicing.

Membrane dome-based regulation mechanism of the mechanosensitive PIEZO channel

Actin cage for the synaptic vesicle liquid phase Brodin and Shupliakov demonstrate that synaptic activity triggers the formation of an actin cage that encapsulates the synaptic vesicle cluster. Disruption of this cage leads to the detachment of the cluster from the release site. These findings explain how the synaptic vesicle liquid phase can remain in place during activity.

Actin cage for the synaptic vesicle liquid phase

Antibody evasion and receptor binding of SARS-CoV-2 LP.8.1.1, NB.1.8.1, XFG, and related subvariants (Cell Reports 44, 116440; October 28, 2025)

Antibody evasion and receptor binding of SARS-CoV-2 LP.8.1.1, NB.1.8.1, XFG, and related subvariants

Dual inhibition of FACT and RRM2 suppresses the progression of pancreatic ductal adenocarcinoma driven by the oncohistone H2BG53D Qin et al. investigated the roles, mechanisms, and therapeutics of oncohistone mutation H2BG53D in PDAC. They found that H2BG53D promotes PDAC development in vivo, alters transcriptional profiles governed by the FACT complex, and proposed a potential therapeutic strategy for H2BG53D-mutant PDAC.

Dual inhibition of FACT and RRM2 suppresses the progression of pancreatic ductal adenocarcinoma driven by the oncohistone H2BG53D

Activation of the Yersinia type III secretion system induces large-scale spatial reorganization of chromosomal and virulence plasmid DNA Activation of the Yersinia type III secretion system triggers rapid, large-scale relocalization of both chromosomal and plasmid DNA. This spatial reorganization links secretion activity to growth inhibition, revealing a new connection between virulence and bacterial cell biology.

Activation of the Yersinia type III secretion system induces large-scale spatial reorganization of chromosomal and virulence plasmid DNA

Mechanisms governing poly(A)-tail-length specificity of the human PAN2-PAN3 deadenylase complex PAN2-PAN3 deadenylases are conserved but act on mRNA poly(A) tails of different lengths in yeast and human. Albrecht et al. show how metazoan-specific loops in PAN3 create distinct binding sites for poly(A)-PABPC1 ribonucleoproteins, favoring longer poly(A) tails than in yeast and rationalizing these substrate preferences.

Mechanisms governing poly(A)-tail-length specificity of the human PAN2-PAN3 deadenylase complex

Airway immunometabolic responses during pulmonary bacterial and viral infections Wadhwa et al. examine how respiratory bacterial and viral pathogens exploit host metabolism to evade immune responses and influence disease outcomes. They underscore the need for deeper insight into immunometabolic interactions, as host-derived metabolites can shape pathogen fitness/evolution—highlighting both the therapeutic promise and complexity of targeting metabolism in infection.

Airway immunometabolic responses during pulmonary bacterial and viral infections

Glycolysis inhibition functionally reprograms T follicular helper cells and reverses lupus Choi et al. show that pharmacologically restricting glycolysis improves the cellular, transcriptional, and metabolic machinery in murine lupus TFH cells. Transcript overlaps between TFH cells from lupus patients and experimental mice indicate glycolysis-sensitive mechanisms, thus demonstrating that uncontrolled glycolysis exacerbated TFH cell functions and autoantibody production in lupus.

Glycolysis inhibition functionally reprograms T follicular helper cells and reverses lupus

Inhibition of respiration prompts commitment to unisexual reproduction in Cryptococcus deneoformans Yao et al. discovered that inhibition of respiration directs the fungal pathogen Cryptococcus species to undergo unisexual development. This metabolic cue activates the Znf2-Cln1 regulatory circuit that induces G2/M cell-cycle arrest, promoting unisexual self-filamentation while inhibiting α × a heterothallic cell fusion.

Inhibition of respiration prompts commitment to unisexual reproduction in Cryptococcus deneoformans

TREX1 enables viral entry in intestinal epithelia via immunity-independent control of endocytosis TREX1 is known for degrading cytosolic DNA to prevent unwanted immune activation. However, its role in all human cell types is not fully clear. Here, Liu et al. reveal an unexpected function of TREX1 in intestinal epithelial cells, showing that it regulates endocytosis to aid viral entry without affecting immune status.

TREX1 enables viral entry in intestinal epithelia via immunity-independent control of endocytosis

MYC inhibition by Omomyc causes DNA damage and overcomes PARPi resistance in breast cancer Giuntini et al. demonstrate that Omomyc, the only direct MYC inhibitor currently in phase 2 clinical trials, causes DNA damage and synergizes with PARPis in triple-negative breast cancer. Their findings provide compelling evidence for clinical exploration of this combination to overcome PARPi resistance.

MYC inhibition by Omomyc causes DNA damage and overcomes PARPi resistance in breast cancer

Maturation of human intestinal epithelial cell layers fortifies the apical surface against Salmonella attack van Rijn and Lopes et al. present a resource for live-cell imaging of bacterial infection dynamics atop human enteroid- and colonoid-derived intestinal epithelia, exhibiting varying maturation levels and in the presence or absence of soluble mucus production. Application of this resource reveals how absorptive epithelium maturation fortifies the surface against enterobacterial attack.

Maturation of human intestinal epithelial cell layers fortifies the apical surface against Salmonella attack

MITF, TFEB, and TFE3 drive distinct adaptive gene expression programs and immune infiltration in melanoma Dias et al. reveal that in melanoma, the transcription factors MITF, TFE3, and TFEB share common binding sites but impose distinct transcriptional programs. Stresses promoting an MITF-to-TFEB-to-TFE3 switch will lead cells to suppress proliferation, reprogram metabolism, and impact tumor immune cell infiltration quantitatively and qualitatively.

MITF, TFEB, and TFE3 drive distinct adaptive gene expression programs and immune infiltration in melanoma

Genetic determinants of gene expression noise and its role in complex trait variation Long et al. mapped expression noise QTLs (enQTLs) across immune cell types in an atlas of 1.23 million cells. These enQTLs are largely independent of eQTLs, exhibit cell-type-specific regulatory mechanisms, and colocalize with GWAS loci for hematopoietic traits and diseases, implicating noise as an underappreciated molecular mediator of complex traits.

Genetic determinants of gene expression noise and its role in complex trait variation

Sensory-neuron-derived CGRPα controls white adipocyte differentiation and tissue plasticity Sensory-neuron-derived CGRPα inhibits subcutaneous white adipocyte differentiation and alters adipogenic gene programs. Ectopic CGRPα expression in iWAT increases adipocyte size, and anti-CGRPα migraine therapy is linked to positive metabolic changes, revealing a neuron-adipose pathway that regulates fat homeostasis and systemic metabolism.

Sensory-neuron-derived CGRPα controls white adipocyte differentiation and tissue plasticity

Infection-induced elevation of gut glycosaminoglycans fosters microbiota expansion in Drosophila melanogaster Arias-Rojas et al. performed a genome-wide association study in Drosophila melanogaster and identified host genetic variants, particularly in heparan sulfate synthesis genes, associated with increased commensal Lactiplantibacillus plantarum abundance. Heparan sulfate enhances bacterial adhesion, biofilm formation, and modulates intestinal homeostasis, microbiota composition, and immune response, thus preventing dysplasia.

Infection-induced elevation of gut glycosaminoglycans fosters microbiota expansion in Drosophila melanogaster

Pathological tau alters head direction signaling and induces spatial disorientation Jiang and Hijazi et al. show that an early cognitive biomarker of dementia, spatial disorientation, can be induced in mice by expressing pathological tau in the anterodorsal nucleus of the thalamus. This alters the activity of head direction cells in this nucleus, affecting the animal’s sense of direction during spatial learning.

Pathological tau alters head direction signaling and induces spatial disorientation

Bacterial modification of the root cell wall facilitates rice aluminum resistance in acidic soils Root cell walls integrate microbial cues to shape crop stress resilience. Zhang et al. show that a synthetic microbial community (SynCom) mitigates aluminum toxicity in rice by reducing aluminum binding and promoting brassinosteroid biosynthesis. These coordinated actions reestablish hormonal homeostasis and direct cell-wall remodeling, enhancing root tolerance in acidic soils.

Bacterial modification of the root cell wall facilitates rice aluminum resistance in acidic soils

Liquid-liquid phase separation of ATXN2L enhances mRNA translation in hepatocellular carcinoma Wang et al. find that ATXN2L is a novel RBP highly expressed in HCC. LLPS of ATXN2L promotes mRNA translation by recruiting eIFs and their target mRNAs, thereby facilitating HCC progression, and this process is modulated through interactions with SGs.

Liquid-liquid phase separation of ATXN2L enhances mRNA translation in hepatocellular carcinoma

Organoid-based precision cancer modeling: New frontier in lung cancer research This review outlines how patient-derived lung cancer organoids model tumor heterogeneity and integrate multi-omics, gene editing, immune co-culture, and drug screening. These systems offer robust platforms for dissecting tumor biology and advancing precision oncology, supporting the development of individualized therapeutic strategies.

Organoid-based precision cancer modeling: New frontier in lung cancer research

BDNF exerts an NRF2-dependent cytoprotective function via a receptor-independent pathway Fath et al. reveal that BDNF crosses cell membranes via a conserved C-terminal CPP sequence, independently of receptors or energy. Inside cells, BDNF binds KEAP1, promotes NRF2 nuclear translocation, and triggers a cytoprotective response. This evolutionarily conserved receptor-independent pathway enables extracellular BDNF to control cellular defenses beyond a classic neurotrophic role.

BDNF exerts an NRF2-dependent cytoprotective function via a receptor-independent pathway

MICU2 controls mitochondrial calcium signaling and migration in neurons during development Berezhnaya et al. showed that MICU2 is present in the brain during development but is replaced during maturation by MICU3. MICU2 loss during development results in neuronal overmigration in the cortex and anxiety-like behavior in mice that may contribute to the neurodevelopmental disorder observed in patients with the MICU2 null mutationreported previously.

MICU2 controls mitochondrial calcium signaling and migration in neurons during development

COPS2 coordinates biphasic autophagy hijacking for non-lytic propagation of enveloped RNA viruses This study using CSFV reveals how enveloped RNA viruses fully exploit autophagy for replication. The virus coopts the COPS2 protein to first enter autophagosomes and then accelerate their fusion with lysosomes, enabling non-lytic viral release through autolysosomal exocytosis and revealing a potential antiviral target.

COPS2 coordinates biphasic autophagy hijacking for non-lytic propagation of enveloped RNA viruses

Structural determination of the human taurine transporter TauT reveals the mechanism of substrate and inhibitor recognition Lu et al. determine structures of the human taurine transporter (TauT) in apo, substrate-bound, and inhibitor-bound states. Structural comparisons between inward-open and occluded conformations elucidate the transporter’s dynamic transitions. Furthermore, they reveal binding modes for inhibitors and demonstrate the role of the sodium ion in stabilizing the occluded conformation.

Structural determination of the human taurine transporter TauT reveals the mechanism of substrate and inhibitor recognition

Chromatin remodeler Chd7 regulates reactive astrogliosis after ischemic stroke Nagao et al. show that Chd7 orchestrates post-stroke reactive astrogliosis by partnering with Sox2 or Atf4 to regulate transcription of Trib3, C3ar1, and Malt1. Astrocyte-specific Chd7 deletion suppresses astrocyte proliferation and neuroinflammation, reduces lesion volume and astrocytic scarring, and improves motor recovery, indicating that Chd7-dependent transcriptional regulation underlies stroke-induced gliosis.

Chromatin remodeler Chd7 regulates reactive astrogliosis after ischemic stroke

The LACCASE3/5/12/13 clade mediates seed coat lignin deposition and regulates imbibition and germination Zhuang et al. show that the LACCASE3/5/12/13 clade in Arabidopsis is responsible for lignin deposition in the outer integument of the seed coat. Genetic deletion of this clade proves that seed coat lignin functions as a physical barrier to regulate water imbibition and germination.

The LACCASE3/5/12/13 clade mediates seed coat lignin deposition and regulates imbibition and germination

Modulation function of sphingomyelin molecular species in TLR4 signaling and cell death Huang et al. demonstrate that sphingomyelin species regulate macrophage pyroptosis and cytokine release via TLR4/MD-2 and caspase signaling, revealing lipid-mediated control of innate immunity.

Modulation function of sphingomyelin molecular species in TLR4 signaling and cell death

Blocking glycogen synthase 1 in white adipose tissue alleviates hypermetabolism following severe burn injury through inhibition of JAK2 by UDPG Zhuo et al. find that glycogen metabolism in white adipose tissue is involved in thermogenesis and hypermetabolism after burn injury. Suppression of glycogen synthesis elevates UDPG, which interacts with JAK2 and blocks interleukin-6 signaling. Inhibition of glycogen synthesis by a small chemical inhibitor alleviates hypermetabolism and improves survival after burn.

Blocking glycogen synthase 1 in white adipose tissue alleviates hypermetabolism following severe burn injury through inhibition of JAK2 by UDPG