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This study shows how the bacterial retron Eco2 defends against viruses. Phage nucleases trigger activation of Eco2, which cuts RNAs, shuts down protein production and stops phage replication.

Native top-down proteomics reveals epidermal growth factor receptor–estrogen receptor-alpha (EGFR–ER) signaling crosstalk in breast cancer cells and dissociation of nuclear transport factor 2 (NUTF2) dimers to modulate ER signaling and cell growth.

Mucosal administration of a multivalent, adjuvanted vaccine against Clostridioides difficile promoted bacterial clearance and protected against morbidity, mortality, tissue damage and recurrence in mice.

Taniuchi and colleagues show that differential phosphorylation of the terminal Y residue in Runx proteins connect MHC restriction with the helper versus cytotoxic T cell lineage choice.

The transcription factor ATF4 and its effector lipocalin 2 (LCN2) have a key role in immune evasion and tumour progression, and targeting the ATF4–LCN2 axis might provide a way to treat several types of solid tumour by increasing anti-cancer immunity.

Alternative splicing generates diverse protein isoforms, yet the functions of most exons remain unknown. Here, the authors introduce scCHyMErA-Seq, a scalable single-cell CRISPR exon-deletion platform that maps exon-specific transcriptional functions shaping gene expression and cell-cycle states.

Heparan sulfate proteoglycans facilitate the assembly of clusters of glycoRNAs and cell surface RNA-binding proteins, which negatively modulate VEGF-A signalling and angiogenesis.

Wei et al. perform spatial transcriptomic profiling on synovial tissue biopsy samples from individuals with recent-onset rheumatoid arthritis, finding TGFβ signaling and fibrogenic fibroblast activation drive a treatment-refractory tissue phenotype.

During development of eutherian females, one of the X-chromosomes is silenced. Here, authors show that alleles on the inactive X-chromosome are dynamically expressed along neural differentiation enhancing resilience of female neural tissue.

Verhaege et al. identify a conserved fibroblast barrier population at the base of the choroid plexus that compartmentalizes brain–CSF interfaces and is disrupted by inflammation, revealing a new site of central nervous system immune entry and barrier regulation.

The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

Langstein-Skora, Schmid, Huth et al. propose that intrinsically disordered region functionality can be driven by the interplay between linear binding motifs and contextual chemical characteristics such as charge and hydrophobicity.

Tissue stiffness mediated by Piezo1 is shown to regulate the expression of diffusive guidance cues in the developing Xenopus laevis brain, revealing a crosstalk between mechanical signals and long-range chemical signalling.

In this work, the authors propose and experimentally test a framework to analyse the fundamental limits of quantum detector tomography, i.e., the limits to extractable information from probing unknown quantum measurements. They introduce the detector quantum Fisher information, which physically connects measurement structure to quantum advantage, complementing previously known state and channel metrics.

Insights into regulatory T cell biology are accelerating therapeutic innovation in cancer immunotherapy, autoimmune diseases and transplant rejection.

Cancer immunotherapy benefits from antibody-lectin chimeras that block glyco-immune checkpoints.

Large-scale computational and in vitro analyses identify commensal type III secretion systems and substrates in the human gut microbiome that can interact with human proteins to modulate immune pathways.

Using two newly developed immunoassays tested in three clinical cohorts, this study highlights CSF DOPA decarboxylase as a promising biomarker for differentiating dementia with Lewy bodies and Parkinson’s disease from Alzheimer’s disease and controls.

How leptin signalling produces anti‑obesity effects is incompletely understood. Here, the authors demonstrate that FAK and PYK2 are required for STAT3 activation, normal leptin responses, and HDAC6 inhibitor‑mediated weight loss, with their loss causing hyperphagic obesity.

Donahue et al. show that ageing is associated with changes in ER morphology. ER-phagy drives age-associated ER remodelling through tissue-specific factors.

Risk associated with genetically defined forms of autism spectrum disorder (ASD) can propagate by means of transcriptional regulation to affect convergently dysregulated pathways, providing insight into the convergent impact of ASD genetic risk on human neurodevelopment.

In this work, the authors reveal that three non-ribosomal peptides targeting a common protein quality system differentially alter the Mycobacterium tuberculosis proteome, providing new insight into the molecular mechanisms behind their antimycobacterial activity.

Taveneau et al. leverage artificial-intelligence-driven protein design to create inhibitors that control RNA-targeting enzymes in cells, revealing a strategy to rapidly design off-switches for RNA-editing systems.

N¹-Methylpseudouridine enhances the translation of synthetic mRNAs, independently of innate immunity.

Analysis of the somatic and transcriptomic profile of 123 acral melanoma samples from Mexican patients helps understand tumour origins and prognosis, and highlights the importance of including samples from diverse ancestries in cancer genomics studies.

Systematic screening of transcription factors reveals conserved mechanisms governing cortical radial glia lineage progression across primates and provides a framework for functional dissection of gene regulatory networks in human cortical neurogenesis.

A 3D soft electronic mesh allows high-resolution electrical recording and stimulation across the full surface of neural organoids, enabling long-term studies, drug testing and optogenetic control without compromising their viability owing to its porous design.

Conventional type 1 dendritic cells (cDC1) can boost the precursor exhausted T cell population thought to be essential for efficacy of immune checkpoint therapy. Here the authors enhance this cellular network using Flt3L to expand cDC1s and then map the movement of T cells and DCs between tumors and lymph nodes.

A single-cell epigenomic atlas of human immune cells highlights cell-type-specific features associated with genetic or environmental exposures.

Population-scale WGS reveals genetic determinants of persistent EBV DNA, linking immune regulation—especially antigen processing and MHC class II variation—to EBV persistence and heterogeneous disease associations.

Dietary restriction promotes the expansion of effector T cells via ketone bodies, which enhances anti-tumour immunity and synergizes with immunotherapy in mice.

CFAP20 has a key role in rescuing RNA polymerase II complexes that have arrested during DNA transcription, limiting the accumulation of R-loops and preventing collisions between the transcription and replication machinery.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

Induction of hypothermia during hibernation/torpor enables certain mammals to survive under extreme conditions. Here, the authors show that the natural product P57 induces hypothermia by targeting pyridoxal kinase and has a potential application in therapeutic hypothermia.

This study detects Chlamydia pneumoniae in human retina and brain, increasing with AD severity. Retinal pathogen load with Aβ₄₂ may predict AD stage. In models, infection drives Aβ deposition and NLRP3 activation, worsening pathology and cognition.

This report describes a nanobody targeting glycine receptor mGlyR that inhibits its ability to regulate G protein signaling and produces anti-depressant effects in mice providing an immunotherapy approach to potentially treat depression.

CRISPR–Cas9 in Streptococcus pyogenes prevents self-cleavage through abasic CRISPR RNA oxidations that suppress off-target activity. Inspired by a natural mechanism, Gu and Kim et al. designed chemically modified abasic guide RNAs to enhance genome-editing specificity of SpCas9, suppressing off-target toxicity in in vivo applications.

Conventional slurry electrodes limit high-energy lithium batteries. This work shows that dry-processed electrodes with molecularly coupled carbon–binder networks enable high mass and active material loading, supporting stable high-voltage operation and enhancing battery energy density.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

A platform using matched patient-derived lung tumouroids and healthy lung organoids enables accurate examination of patient responses to CAR T therapy and offers a faithful framework for improved CAR T design.

Mouse models demonstrate that vagal sensory neurons transmit signals from lung adenocarcinoma to the brain, increasing sympathetic efferent activity in the tumour microenvironment and thereby creating a immunologically permissive environment for tumour growth.

Circadian clock in adipocytes maintains metabolic health by regulating mitochondrial complex I respiration.

Here the authors present NCATS-SM0225, a small molecule that inhibits ERAD and selectively kills cancer cells by binding VDACs, disrupting calcium homeostasis, and triggering the PERK-STIM1 pathway to degrade ERAD regulators.

ANKLE1 senses DNA tension and negative supercoiling, enhancing cleavage of stretched, supercoiled DNA to resolve chromatin bridges, highlighting its unique mechanosensitive role in maintaining genome stability during cell division.

How the complex interplay between multiple nutrients within the microenvironment dictates potential sites of metastatic cancer growth is explored.

Here authors show loss of AKAP11, a strong genetic risk factor for bipolar disorder and schizophrenia, disrupts PKA proteostasis and signaling, leading to widespread transcriptomic alterations across the brain, particularly in striatal neurons, as well as altered behavior.

In this study, Dahmane et al use a method called cryo-electron tomography to uncover new details of how tick-borne flaviviruses transform cells into virus factories.

Saito et al. identify sphingosine kinase 1 as a critical regulator of physiological ductus arteriosus closure and pathological supravalvular aortic stenosis through its role in smooth muscle cell proliferation and propose potential therapeutics.