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Virtual nature exposure reduces self-reported pain and is associated with decreased brain responses linked to somatosensory and nociceptive processing, providing new insights into the underlying mechanisms of nature-induced analgesia.

Patients with myelodysplastic syndromes (MDS) have limited therapeutic options. Here the authors show that functionally impaired NK cells contribute to immune escape of pre-malignant clones in early stage MDS and that NK adoptive cell therapy can be considered to prevent or delay the development of MDS.

Men and women differ in their risk of developing coronary artery disease, in part due to differences in their levels of sex hormones. Here, AlSiraj et al. show that the XX sex genotype regulates lipid metabolism and promotes atherosclerosis independently of sex hormones in mice.

Using the AstroLight system, the authors reveal that astrocytic ensembles in the nucleus accumbens regulate cue-motivated reward behavior, demonstrating that selective manipulation of tagged astrocytes can influence specific behavioral choices.

In mice, prolonged consumption of a high-fat diet decreases interest in calorie-rich foods as a result of reduced neurotensin expression and signalling, which uncouples hedonic feeding behaviour linked to neurons projecting from lateral nucleus accumbens to ventral tegmental area.

Cancer evolutionary dynamics are quantitatively inferred using a method, EVOFLUx, applied to fluctuating DNA methylation.

What drives the development of lateralized sound processing in the brain remains unclear. Here, the authors find that sex and hemispheric identity underlie asynchronous development between the auditory cortices, leading to distinct functional representations in adulthood.

Distal gene regulation is increasingly recognised as a major contributor to complex trait variability. Here, the authors show that a heritable, biologically interpretable transcriptome signature driven by distal regulation predicts metabolic traits across mice and humans.

Cocaine chemogenetics in rats is a selective approach for countering drug reinforcement by clamping dopamine release in the presence of cocaine.

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.

A combined sequencing technique assesses 18 patients with high-grade serous ovarian cancer over a multi-year period from diagnosis to recurrence and shows drug resistance typically arises from selective expansion of one or a few clones present at diagnosis.

Aarrestad et al. show that, in contrast to psychedelics, the nonhallucinogenic psychoplastogen tabernanthalog promotes neuroplasticity through 5-HT_2AR activation without immediately increasing extracellular glutamate levels or immediate early gene expression.

Extracellular anisotropic stresses trigger fibroblast transition into myofibroblasts by the mechanical self-reinforcement of cell–extracellular matrix interactions.

Viral vector integration can affect the safety of gene and cell therapies. Here, authors introduce MELISSA, a regression-based statistical tool that quantifies integration site risks and clone growth effects, aiding the safety evaluation of therapies in both research and clinical settings.

STING is a promising drug target, but selective activation is necessary for safety and efficacy. Researchers have developed a two-component prodrug system for potent pharmacological activation of STING that offers excellent tumour targeting.

Hydrogel materials have emerged as versatile platforms for biomedical applications. Here this group reports an mRNA lipid nanoparticle-incorporated microgel matrix for immune cell recruitment/antigen expression and presentation/cellular interaction thereby eliciting antitumor efficacy with a single dose.

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.

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.

B7-H3 is expressed at high levels in several cancer types and can suppress antitumor immune responses. Here the authors show that B7-H3 expression is dependent on mTORC1 activity and that inhibition of B7-H3 promotes antitumor immunity mediated by cytolytic CD4 + T cells in tumor models with mTORC1 hyperactivity.

Metabolomics analysis of the mouse embryo shows a metabolic shift towards the tricarboxylic acid cycle between gestational days 10.5 and 11.5, leading to the subsequent development of organ-specific metabolic programmes.

Genome-wide and targeted perturbation of DNA methylation at centromeres affects CENP-A positioning and centromere structure, resulting in aneuploidy and reduced cell viability.

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.

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.

Sarcomas are a group of mesenchymal malignancies which are molecularly heterogeneous. Here, the authors develop an in vivo muscle electroporation system for gene delivery to generate distinct subtypes of orthotopic genetically engineered mouse models of sarcoma, as well as syngeneic allograft models with scalability for preclinical assessment of therapeutics.

In this work, authors show that the nucleoside prodrug obeldesivir has potent antiviral activity across respiratory syncytial virus (RSV) clinical isolates with a high resistance barrier. Once-daily obeldesivir treatment was efficacious against RSV in a non-human primate model.

Döring, van der Vorst, Yan, Neideck et al. present a non-canonical chemokine pathway involving CCL17 signaling through CCR8, which induces CCL3 expression independent of CCR4 and suppresses the functions of atheroprotective T_reg cells.

Triple-negative breast cancers are aggressive tumours, but their prognosis is critically determined by the immune cell activity within the microenvironment, with the more inflamed, hot milieu predicting better prognosis. Here authors show that the tumour draining lymph nodes, even if not invaded by the tumours, reflect the difference between the cold and hot tumours via differential Th2 polarization.

Diabetes complications are attributed to reactive by-products of glycolysis, but cells consuming lactate and pyruvate are not spared. Here, the authors show that the reactive dicarbonyl dimethylglyoxal is formed from pyruvate, rises in diabetes, and potentially causes neurological complications of diabetes.

APOA1 may protect against atherosclerotic plaque rupture by removing cholesterol from plaques and proteases such as MMP2 promote rupture. Here, the authors show that APOA1 interacts with MMP2 in a way which may affect rupture independently of cholesterol.

Glucagon is hormone that signals via a dedicated g-protein coupled receptor, but downstream signaling is poorly understood. Here, Wu et al. uncover liver glucagon signaling using phosphoproteomics and define a role for the vesicle trafficking protein SEC22B in distinct metabolic actions.

LXRα is highly expressed in hepatocytes, where it regulates cholesterol abundance and stimulates lipogenesis. The authors provide evidence in humans and mice that impaired LXRα signalling is hepatotoxic, despite its potent lipogenic actions.

In mouse brain, neurotensin released into the basolateral amygdala by neurons in the paraventricular nucleus of the thalamus assigns positive or negative valence during associative learning.

Vascular cells express various G-protein-coupled receptors (GPCRs) with yet unknown function, among them orphan receptor GPR153. GPR153 is upregulated in injured vessels, where it promotes smooth muscle proliferation and endothelial inflammation, and its inactivation protects mice in models of vascular diseases.

Understanding how adenoviruses transduce cells is important for their use and development as vaccine vectors. Adenovirus type 5 (Ad5) is known to bind coagulation factor X (FX), and FX is thought to act as a bridge between the virus and its receptor on hepatocytes. Andrew Byrnes and his colleagues now report that the major role of FX binding to Ad5 is actually to protect Ad5 from neutralization by complement and natural antibodies, and in the absence of B cells, Ad5 does not require FX binding for effective liver transduction.

The brain selects stimuli for preferential processing on the basis of both their physical salience and their relevance to behavior. Recording from the midbrain of the barn owl, the authors show that a single inhibitory circuit is critical for both physical salience-driven (exogenous) and internally driven (endogenous) control of stimulus selection.

It is unknown whether unrepaired DNA damage in lung endothelial cells causes persistent pulmonary arterial hypertension. Here, the authors combine oxidative stress with impaired BMPR2 signaling to link a reduction in FOXF1 to unrepaired DNA damage and impaired regeneration of normal endothelium.

Delineating the specific role of Polycomb Repressive Complex 2 (PRC2) in various cancer systems is desirable as inhibitors for EZH2 inhibitors are approved for some cancers. Here the authors show haplo- and full-insufficiency of EZH2 drive divergent phenotypes in lung cancer. 3D tumoroids recapitulate transcriptional profiles, including FOXP2 derepression, and drug responses of in vivo tumors.

Deep phenotyping of responses to carbohydrate meals and mitigators revealed interindividual differences in postprandial glycemic responses that reflect underlying metabolic physiology, such as insulin resistance and beta cell dysfunction.

Understanding functional role of different neuronal cell types is challenging. Here the authors associate multi-modal in vitro cell properties with in vivo physiology of mouse visual cortex.

Tumor-associated macrophages are mostly pro-tumorigenic, due to their re-programming by the tumor microenvironment. Here authors show that nanoliposomes, incorporating phospholipids with a flipping-tail chain, are engulfed specifically by intratumoral, alternatively activated macrophages, while delivering a cargo that converts these cells into anti-tumor macrophages.

Epigenetic perturbations may be an important factor in diseases where both genes and environment play a role. Here, Ventham and colleagues show that DNA methylation changes in inflammatory bowel disease are related to the underlying genotype, and are associated with cell-specific changes to gene expression.

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.

Antigen-activated B cells are short lived in the absence of a second signal provided by CD4⁺ T cells or cytokines. Zikherman and colleagues report that the NR4A family of nuclear receptors (NUR77 and NOR-1) are responsible for enforcing this ‘tolerance’ to self-antigen (signal 1 only) and explain, in part, why B cells are dependent upon a second signal.

Goal-directed behaviors require the brain to integrate information across many task-related dimensions. Here, the authors use a virtual context discrimination paradigm in mice to demonstrate the capacity for neurons in the retrosplenial cortex to exhibit multidimensional encoding across learning.

Multilingual articulatory representations in the speech-motor cortex of a participant with vocal-tract and limb paralysis enabled the development of a bilingual speech neuroprosthesis.

Vaccination in glioblastomas does lead to the emergence of tumour-antigen-specific T cells but T cell dysfunction, poor tumour infiltration and persistence hinder efficient tumour killing. Here authors identify a T cell receptor in a vaccinated glioblastoma patient that specifically recognizes the glioblastoma stem cell antigen PTPRZ1 and utilise it in T cell receptor-engineered T (TCR-T) cell therapy, resulting in efficient tumour cell killing in vitro and in a mouse model.

Current treatment options for Mycobacterium marinum infections are extensive and challenging. In this work, authors explore the potential of functionalized mesoporous silica nanoparticles as a carrier for delivery of drugs against M. marinum.

Infected wounds pose a major mortality risk in animals and are common in predatory ants. Here, the authors show that M. analis ants apply antimicrobial compounds produced in the metapleural glands to treat infected wounds and reduce nestmate mortality.