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The authors show how Vγ1⁺ γδ T cells produce IL-4 to drive early CD8⁺ T cell and dendritic cell responses to malaria infection in mice.

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.

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.

After spinal cord injury, lesion-remote astrocytes acquire heterogeneous, spatially restricted reactivity states that shape neuroinflammation, neural repair and neurological recovery.

People living with HIV (PLHIV) on antiretroviral therapy (ART) remain highly susceptible to pneumococcal colonisation and disease. In an analysis of 132 adults in Malawi, the authors report that long-term ART does not restore nasal mucosal immunity.

Here, Yang-Jensen et al. demonstrate that a scalable microbial protein lysate from Methylococcus capsulatus Bath reshapes gut microbiota and T cells and, via fermentation-driven GLP-2 receptor mimicry, protects against gastrointestinal inflammation while providing sustainable protein nutrition

The authors show that the CD4 mimetic CJF-III-288 stabilizes HIV-1 Env in an asymmetric “open” State-3 conformation, guiding anti-CoRBS antibodies to boost ADCC against infected cells and delay viral rebound in vivo, underscoring therapeutic promise.

In JAK2V617F mutant myeloproliferative neoplasms (MPN), inflammation impacts clinical outcomes. This study uncovers that the NLRP3 inflammasome drives thrombocytosis, granulocytosis, HSPC expansion, splenomegaly, and bone marrow fibrosis in MPN

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

Off-target activation of nerve fibers is an ongoing problem in bioelectronic medicines such as vagus nerve stimulation. Here, the authors show that high-frequency stimulation can selectively block nerve fibers in the vagus nerve in swine models.

Transcription factor osr2 is identified as a specific marker and regulator of mural lymphatic endothelial cell (muLEC) differentiation and maintenance, and muLECs and border-associated macrophages share functional analogies but are not homologous, providing an example of convergent evolution.

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.

Pathogenic variants in KIF1A give rise to KIF1A-associated neurodegenerative disorder (KAND). Here, the authors use antisense oligonucleotides targeting common polymorphisms to knock down pathogenic KIF1A expression in patient-derived stem cells.

Tree buds integrate cold and warm cues to control dormancy release. Extended warm periods block plasmodesmata opening by repressing Flowering Locus T and GA pathways in buds. This mechanism ensures robust temporal regulation of dormancy release.

Imaging and optogenetics in mice provide insight into the interplay between the primary motor cortex and the motor thalamus during learning, showing that thalamic inputs have a key role in the execution of learned movements.

Using data from the CoVPN 3008 study, the authors show that the neutralizing antibody correlate of risk holds in people living with HIV. However, the nAb correlate was weaker and shorter-lived in a vaccine-immunity versus hybrid-immunity population.

The neurobiological mechanisms by which binge alcohol consumption disrupts social and emotional functioning are unknown. Here, the authors demonstrate that sex-specific social and arousal disturbances induced by binge alcohol consumption are driven by dysregulation of serotonergic signaling and activation of 5HT_2c receptor-containing neurons in the lateral habenula in mice.

Glioblastoma is characterised by high levels of intratumoural heterogeneity and plasticity, hindering treatment. Here, the authors develop an analytical framework, scFOCAL, to predict the sensitivity of glioblastoma cell subpopulations to therapies based on reversal of disease transcriptional signatures to identify synergistic therapeutic combinations.

Previous work has described a neuroprosthesis to directly decode full words in real time during attempts to speak. Here the authors demonstrate that a patient with anarthria can control this neuroprosthesis to spell out intended messages in real time using attempts to silently speak.

Here, as part of the Sherlock-Lung study, the authors profile the microbiomes of 940 lung cancers in never smokers finding no significant associations with demographic and clinical features, suggesting lung bacteria are unlikely to have a sizable role in lung cancer.

Pathology-oriented multiplexing (PathoPlex) represents a framework for widespread access to multiplexed imaging and computational image analysis of clinical specimens at a relatively high throughput and subcellular resolution.

Cui and colleagues identify the chromatin organizer protein SATB1 as a critical regulator of quiescence in stem-like progenitor CD8⁺ T cells that arise during chronic viral infection and cancer.

Here the authors show that tissue-resident memory and exhausted T cells in tumors are distinct populations that are shaped by relative presence or absence of TCR signals, suggesting that a tailored therapeutic strategy is needed to target each subset.

Using pancreatic organoids and genetic mouse models, Antonucci et al. show that cellular stress activates an NRF2–EZH2 epigenetic axis leading to metabolic reprogramming and subsequent malignant transformation of KRAS-mutant benign lesions.

Activity in anterior deep cerebellar nuclei reduces food consumption in mice without reducing metabolic rate, potentially identifying a therapeutic target for disorders involving excessive eating.

Chronic nicotine exposure impacts various components of decision-making processes, such as exploratory behaviors. Here, the authors identify the cellular mechanism and show that chronic nicotine exposure increases the tonic activity of VTA dopaminergic neurons and reduces exploration in mice.

Whether paternal pre-conceptual SARS-CoV-2 infection impacts sperm RNA content, or effects offspring phenotypes, has not been previously investigated. Here authors report changes in sperm noncoding RNAs in SARS-CoV-2 infected sires and increased anxiety-like behaviors in offspring.

How reduced blood flow plays a role in progressive white matter loss during aging and associated cognitive decline is unclear. Here the authors show that selective constriction and rarefaction of capillary–venous networks contribute to age-related hypoperfusion and white matter damage in mice.

Pre-satellite era observations of Antarctic glaciers are rare. A unique record of aerial expedition images of East Antarctic outlet glaciers since the 1930s reveal long-term stability and moderate thickening.

Hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and T cell priming in distinct lung dendritic cell subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality.

Base editor off-target effects are profiled with high precision in a tailored approach.

Human challenge studies with SARS-CoV-2 have shown changes in the innate and adaptive immune response. Here the authors are examining potential correlates of infection in virus challenged recipients by assessing baseline immune parameters and how this predicts virus control.

FACED 2.0 builds on and expands the capabilities of the free-space angular-chirp-enhanced delay microscopy approach. Its high speed, large field of view and volumetric coverage enable two-photon voltage imaging of hundreds of neurons or calcium imaging of thousands of neurons in the mouse or zebrafish brain.

In this study, the authors generated iPSC lines from more than 100 sporadic ALS cases, which recapitulated key disease phenotypes and enabled large-scale drug screening, identifying a promising combination therapy of baricitinib, memantine and riluzole.

TDP-43 dysfunction in ALS/FTD causes faulty splicing of the KCNQ2 ion channel, leading to toxic protein buildup, neuron hyperactivity and a potential new biomarker and treatment target using RNA-based therapies.

Jacks and colleagues demonstrate the effects of neoantigen expression level on T-cell priming and immune surveillance during tumor development and progression and explore implications for immunotherapies, using in vivo models of colorectal cancer.

Here, the authors provide evidence that the renal microbiome can be disrupted by antibiotics, leading to differential effects on anti-lithogenic taxa like Lactobacillus and pro-lithogenic bacteria such as Enterobacteriaceae.

A study using high-density surface recordings of the speech cortex in a person with limb and vocal paralysis demonstrates real-time decoding of brain activity into text, speech sounds and orofacial movements.

This study identifies transcription factor 7-like 2 (TCF7L2) as a key regulator of hepatic metabolic zonation, and demonstrates that disruption to the transcriptional activity of TCF7L2 exacerbates the development of dietary-induced hepatic fibrosis.

Bed nucleus of the stria terminalis (BNST) neurons that synthesize and release the stress neuropeptide corticotropin-releasing factor drive binge alcohol drinking and anxiety. The authors describe a complex feedforward inhibitory PVT^VGLUT2-BNST^CRF circuit in mice that plays sex-dependent roles in alcohol drinking and avoidance behavior.

The acidic tumour microenvironment in melanoma drives immune evasion by cAMP in tumor-infiltrating monocytes. Here, the authors show that the release of an adenylate cyclase inhibitor from micelles restores antitumor immunity and, when combined with regulatory T cell depletion, leads to remission of established B16-F10-OVA tumors.

Stowell, Sipe et al. describe how norepinephrine signaling to microglia during wakefulness influences the dynamic movement of microglial processes, affecting both microglial interactions with neurons and experience-dependent plasticity.

Naturalistic communication is an aim for neuroprostheses. Here the authors present a neuroprosthesis that restores the voice of a paralyzed person simultaneously with their speaking attempts, enabling naturalistic communication.

TCF1⁺ progenitor-exhausted CD8⁺ T cell populations mediate durable antitumor immunity. Upon antigenic stimulation, effector T cells upregulate aerobic glycolysis to support their cytotoxic phenotype. Here, Mittal and colleagues find that loss of metabolic regulator PKM2 enriches for TCF1⁺ progenitor-exhausted-like cells and improves responsiveness to PD-1 blockade.

Microglia play key roles during early neurodevelopment. Here the authors show that microglia are important mediators of ocular dominance plasticity (ODP). Microglia respond to monocular deprivation during the visual critical period, and disrupting microglial P2Y12 purinergic receptor abrogates ODP.

Understanding the mechanisms underlying the survival of drug tolerant persister cells following chemotherapy remains elusive. Here, multi-omics analysis and experimental approaches show that the germ-cell-specific H3K4 methyltransferase PRDM9 promotes metabolic rewiring in glioblastoma stem cells.

De Jesus et al. describe the redox-mediated regulation of m⁶A writer methyltransferase 3, which blunts innate immune responses by modification of RNA sensor and editor component mRNAs during the onset of type 1 diabetes in β-cells.

The precise mechanism by which seizures disrupt neural coding remains unclear. Here, the authors show that discharges arising from the seizure source travel macroscopic distances, where they go on to influence spiking sequences at the microscopic scale.

Cells can sense mitochondrial damage through signalling via an unimported mitochondrial targeting sequence.

Ionizing radiation and chemotherapy deplete haematopoietic stem cells and damage the vascular niche. Here the authors show that irradiation induces SEMA3A secretion from bone marrow endothelial cells (ECs), inducing EC apoptosis via NRP1 and that NRP1 inhibition promotes vascular regeneration and R spondin 2 dependent hematopoietic regeneration.