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Large biospecimen banks are limited by a lack of fast, flexible, database-like retrieval. Here, authors encode metadata as DNA barcodes on silica-encapsulated samples and demonstrate numerical range, categorical, and Boolean queries, enabling rapid, precise recall from pooled DNA/RNA archives.

There are currently no licensed vaccines to prevent Group A Streptococcus (GAS) infections. In this study, the authors evaluate the immune response and preclinical efficacy of a multicomponent mRNA lipid-nanoparticle vaccine against GAS.

Differentiating DCs express ALDH1A2, which produces retinoic acid and suppresses DC activity. Blocking this pathway with a new inhibitor, KyA33, enhances immune responses and boosts the effectiveness of DC cancer vaccines in mouse models.

Therapy to allergy often targets a specific allergen without addressing cross-reactivity. Here the authors develop a consensus, cross-reactive allergen, use mRNA-lipid nanoparticle immunization to induce specific, neutralizing IgG responses, but find no therapeutic effects in mouse allergy models, hinting the need for further optimization prior to translation.

Here the authors show that persistent antigen stimulation drives the generation of CD8⁺ tissue-resident exhausted T cells with distinct developmental origins, function and therapeutic responsiveness when compared to CD8⁺ tissue-resident memory T cells.

Brown et al. show that mouse islet progenitors with different transcriptomes produce distinct β-cell subtypes and maternal diet alter the subtype proportions. Similar β-cell subsets exist in humans, with a subset enriched in genes related to β cell function reduced in diabetes.

Here, the authors develop Q4ddPCR, a high-throughput assay to quantify genetically intact HIV reservoirs by targeting four regions, and demonstrate that it reduces assay dropout to 5%, tracks reservoir decay, and closely correlates with viral outgrowth.

Here the authors show that endogenous or therapeutically delivered GDF-15 activates brainstem neurons that trigger splenic β-adrenergic signaling. This, in turn, suppresses autoreactive T cells and reduces neuroinflammation, identifying a possible target for multiple sclerosis treatment.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Two new phosphorylation sites, p-tau₂₆₂ and p-tau₃₅₆, detect the formation of prefibrillar tau aggregates and may serve as early-stage biofluid-based biomarkers of tau neurofibrillary tangle pathology in Alzheimer’s disease.

In mice, a circuit between the spinal cord and various regions of the brain, centring on spinal-cord-projecting neurons in the rostral ventromedial medulla, has a key role in driving chronic pain.

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.

A new strategy that uses prime editing to convert an endogenous tRNA into a suppressor tRNA shows therapeutic potential for multiple genetic diseases that are caused by premature stop codons.

A genetic method to block immune rejection of allogeneic cells is validated in monkeys.

DNA methylation heterogeneity and dynamics hinder distinguishing early pathological changes from normal variation. Here, the authors identify stable sites whose disruption is linked to blood cancers, aging, and cardiovascular risk.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

Decreased brain volumes and increased NfL levels can be observed earlier than disease diagnosis in short-tandem-repeat-associated neurological diseases.

González-Gualda, Reinius et al. demonstrate that platinum-based chemotherapy-induced senescence promotes malignancy in ovarian and lung cancer via TGFβ ligands, with evidence in mouse models validated in clinical samples. Concomitantly blocking TGFβ signaling with chemotherapy reduces tumor burden and increases survival in mice.

Antibody conjugation has many uses in clinical and research settings. Here, the authors present a supramolecular synthetic strategy for site-specific antibody conjugation which enables the synthesis of stable conjugates using coil-coil supramolecular assembly and demonstrate a range of applications.

Pocock et al. reveal that transient activation of 5′ AMP-activated protein kinase and estrogen-related receptor drives robust maturation of multicellular human cardiac organoids, enabling modeling of desmoplakin cardiomyopathy dysfunction, which could be rescued using the bromodomain and extra-terminal inhibitor INCB054329.

Hepatic glycogenolysis is essential for protein glycosylation and rhythmic secretion by the liver. Disruptions to hepatic glycogenolysis, caused by congenital diseases or physiological factors such as obesity, caloric restriction and changes to meal timing, alter hepatic protein secretion.

Recently published results from a Phase I trial showed the blood brain barrier could be transiently opened in glioblastoma patients using low-intensity ultrasound and microbubbles. Here, the authors develop a microfluidic chip to capture tumour-derived extracellular vesicles and particles in response to paclitaxel treatment.

This pilot trial showed that perioperative treatment with the isocitrate dehydrogenase (IDH) inhibitor safusidenib of patients with low-grade IDH-mutant glioma, with craniotomy and lumbar puncture before and after treatment, is feasible and safe and enabled in-depth translational investigation of safusidenib treatment-induced changes in the tumor, including electrophysiological effects.

Soil fauna is an important but often neglected component of terrestrial food webs. Here the authors use a large dataset of stable isotope observations to analyse how soil animal trophic diversity varies across climates and land-use types and identify potential biotic mechanisms.

Thomas, Egan et al. report that hexokinase 2 localizes to the nucleus of leukaemic and normal haematopoietic cells to maintain stemness by interacting with nuclear proteins and modulating chromatin accessibility independently of its kinase activity.

The differentiation and function of regulatory T (Treg) cells are critically controlled by T cell receptor (TCR) signaling. Here the authors show that CARD11-BCL10-MALT1 (CBM) complexes are dispensable for effector Treg conversion under inflammatory conditions but are critical for mediating Treg suppressive activity in a MALT1 paracaspase-dependent manner.

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

Environmental influences during prenatal development may have implications for health and disease later in life. Here, Czamara et al. assess DNA methylation in cord blood from new-born under various models including environmental and genetic effects individually and their additive or interaction effects.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

This study provides new insights into the role of endoglin (ENG) as a co-receptor in endothelial cells and addresses a gap-in-knowledge on how ENG could be involved in both TGF-β and BMP9 signalling. Such knowledge greatly facilitates therapeutic targeting of ENG-related pathways.

The failure of metabolic tissues to respond to insulin is an early marker of type 2 diabetes. Here, the authors show, using global phosphoproteomics, that insulin resistance is caused by a marked rewiring of both canonical and non-canonical insulin signalling, and includes dysregulated GSK3 activity.

Motivated by the need for a non-living and versatile multiblock semi-crystalline polyolefin synthetic method, the authors report a method for producing previously inaccessible iPP-b-LLDPE linear multiblocks wherein the overall molecular weights, individual block lengths, and crystallinity can be controlled.

KRAS mutations are keenly associated with pancreatic ductal adenocarcinoma and represent a potential therapeutic target. Here the authors present the findings from a phase I clinical trial testing pooled KRAS mutant peptides in combination with immune checkpoint blockade in patients with resected pancreatic ductal adenocarcinoma.

The involvement of nuclear pore proteins in cellular mechanosensing and metastasis is unclear. Here the authors identify that nuclear pore protein NUP210 promotes metastasis through the interaction with mechanotransducer LINC complex protein and chromatin to regulate mechanosensitive genes.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

The evolution of insecticide resistance in the major malaria vector, Anopheles gambiae, remains an important issue in sustainable malaria control in Africa. Here, the authors present a framework for identifying resistance mechanisms before they arise in field mosquito populations. The findings have implications for public health surveillance and vector control.

Vaccination efficiency in HIV infection is hampered by the low immunogenicity of HIV-1 Env glycoprotein (Env). Here authors optimise the neutralising antibody response to Env by stabilizing the Env trimers in the context of expressing them in a Newcastle Disease Virus-like particle and providing conditions that mimics replicating virus infection.

Single-cell transcriptomic analysis of neurogenic niches in young and old mice reveals that T cells infiltrate the neurogenic niches of old mice and inhibit the proliferation of neural stem cells, in part through expression of interferon-γ.

Amit and colleagues report that the specific interaction of a CD4⁺PD-1⁺CXCL13⁺ T-cell subset with antigen-presenting cells reprograms the tumor microenvironment and response to immune checkpoint inhibitors in non-small cell lung cancer.

Meningiomas are common brain tumors with variable behavior. This study reveals high STING expression across multiple cell types in the meningioma microenvironment. STING agonism triggers tumor cell death via programmed necrosis and pyroptosis, enhancing survival in preclinical models.

Chronic alcohol use in humans and mice downregulates small intestinal mAChR4 and reduces goblet-cell-associated antigen passage formation, disrupting antimicrobial immunity.

Qiu et al. show that chronic interferon (IFN) stimulation establishes an epigenetic signature of inflammatory memory in tumor cells, resulting in elevated levels of IFN-stimulated genes that sustain immune cell dysfunction when IFN is low.

Cancer cells can squeeze through confined spaces and undergo nuclear deformation, leading to changes in chromatin organisation. Here, the authors show that mechanical constriction in microcapillaries reprograms melanoma cells to a tumorigenic stem cell-like state through the mechanosensor PIEZO1.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Components of the glycocalyx have been shown to impair immune cell functions, including of CAR-T cells. Here the authors show that CAR-T cell mediated cytotoxicity in pancreatic cancer models can be enhanced by incorporating non-signalling binding domains that target the glycocalyx.

Here the authors combine clinical and metabolomics data to identify distinct metabotypes of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD). The results provide information regarding heterogeneity of MASLD presentation, but require validation in independent cohorts.

The field of regenerative medicine would greatly benefit from the study of a non-human primate model. Here, the authors prospectively isolated two quiescent stem cell populations from the non-human primate mouse lemur.

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.