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A lipid nanoparticle that delivers mRNA encoding for regenerative factors to the endometrium with high specificity restores implantation rates in a murine model of endometrial injury with potentially improved safety.

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.

MK-7762 is a new oxazolidinone antitubercular agent that is structurally similar to linezolid, and demonstrated in vivo efficacy, lesion penetration and limited toxicity compared to linezolid, indicating it could be used in broad tuberculosis regimens.

The existing ENCODE registry of candidate human and mouse cis-regulatory elements is expanded with the addition of new ENCODE data, integrating new functional data as well as new cell and tissue types.

This study shows that many small RNAs in Capsella rubella pollen originate from maternal tissues. These mobile small RNAs support proper pollen development, revealing that non-cell-autonomous small RNAs are crucial for successful plant reproduction.

Centrosome dynamics play a central role in immune regulation. Here, the authors demonstrate that centrosome integrity as well as centriole numbers and spatial organisation emerge as critical determinants of effective T cell responses.

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.

MCM2-7 complexes drive genome duplication, but their assembly in human cells is not fully understood. Here, the authors identify the CRL4-DCAF12 ubiquitin ligase as crucial for MCM2-7 maturation, safeguarding accurate DNA replication, and genome stability.

Tau phosphorylation was found to hinder the formation and protective functionality of tau envelopes against microtubule-severing enzymes, providing a potential explanation for microtubule destabilization observed in neuropathology.

This study uses single-nucleus RNA sequencing to analyze lung tissue from 141 individuals with chronic obstructive pulmonary disease. Distinct patterns of spatially resolved changes in cell composition and cell states that correlate with clinical features are highlighted.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Sidewinder enables high-fidelity DNA assembly by separating the information that guides assembly from the final assembled sequence.

Chronic stress disrupts the brain vasculature and contributes to mood disorders, but mechanisms of resilience remain unclear. Here, the authors show that enriched environments increase astrocytic Fgf2 to prevent stress-induced vascular alterations and depressive behavior with relevance to human depression.

Mitochondria that are transported from satellite glial cells in dorsal root ganglia to peripheral sensory neurons through tunneling nanotube-like structures provide protection against peripheral neuropathy.

Metastatic triple negative breast cancer (mTNBC) has limited treatments options. Here, this group presents a combination of low-dose cyclophosphamide, anti-CSF1R, and anti-PD-1 therapies to boost immune cell infiltration and reduce recurrence in aggressive TNBC models.

Lung adenocarcinomas bearing the ID2 mutational signature display increased LINE-1 retrotransposon activity, which contributes to their fast evolutionary dynamics and aggressive phenotype.

In a phase 1b/2 trial, an off-the-shelf vaccine using gorilla adenoviral and modified vaccinia Ankara vectors with over 200 mutated peptides known to be present in persons with mismatch-repair-deficient tumors is safe and elicits neoantigen-specific T cells in individuals with Lynch syndrome.

Basal cells, rather than neuroendocrine cells, have been identified as the probable origin of small cell lung cancer and other neuroendocrine–tuft cancers, explaining neuroendocrine–tuft heterogeneity and offering new perspectives for targeting lineage plasticity.

The bacterial protein H-NS prevents costly expression of horizontally acquired genes such as those in Salmonella pathogenicity islands (SPIs), which are essential for infection. Here, Kortebi et al. show that the expression of SPI-1 is associated with Salmonella chromatin remodelling and with the repositioning of this region toward the nucleoid periphery.

Five-year survival data and biomarker analysis of the PRADO extension cohort of the phase 2 OpACIN-neo trial, in which patients with high-risk stage III melanoma received neoadjuvant ipilimumab and nivolumab and underwent pathologic response-directed surgery and adjuvant therapy, show 71% event-free survival and 88% overall survival, with tumor mutational burden, IFNγ signature and PD-L1 expression associated with favorable outcomes.

Inhibition of the histone methyltransferase NSD2 and the androgen receptor in preclinical models can reverse lineage plasticity to suppress tumour growth and promote cell death in multiple subtypes of castration-resistant prostate cancer.

Paul and colleagues report the development and characterization of an antibody–drug conjugate targeting TRBC2 for the treatment of T cell malignancies.

This study reveals how distal DNA ‘switches’ control gene activity in human astrocytes. Using CRISPRi screens and single-cell RNA-seq, we map enhancer–gene links, highlight Alzheimer’s disease-related targets and introduce a model that predicts additional regulatory interactions.

The impact of variants of uncertain significance (VUS) on protein function and cancer risk remain unclear. Here, the authors focus on the functional impact of VUS of the PALB2 gene and identify defects in DNA damage repair by homologous recombination associated with increased risk of breast cancer.

Biosynthesis of all androgens from cholesterol first requires cytochrome P450 (CYP) 11A1 for generation of pregnanes and then CYP17A1 for biosynthesis of androgens, but CYP17A1 inhibition cannot completely inhibit androgen biosynthesis in prostate cancer. Here, the authors identify a role for CYP51A1 in the biosynthesis of androgens that completely bypasses the requirement for CYP17A1 and demonstrate that CYP51A1 is essential for the biosynthesis of ¹³C-testosterone from ¹³C-cholesterol in prostate cancer cells.

Understanding of the immune microenvironment in pediatric acute T cell lymphoblastic leukemia is limited. By analyzing single-cell transcriptome, surface protein expression and immune repertoire data, the authors here identify non-malignant CD4^-CD8^- TCRαβ T cells that are present in a subset of patients with Rap1 signaling in leukemia cells and are associated with adverse clinical outcome in patients with low minimal residual disease.

In an integrated analysis of transcriptomic data from the SUBSPACE consortium and public datasets of patients with sepsis, acute respiratory distress syndrome, trauma and burns, dysregulation within four consensus molecular clusters related to myeloid and lymphoid cells is associated with mortality and illness severity.

Using cryo-electron microscopy technologies, Serianni and Škerlová et al. reveal how Np_nNs initiate bacterial transcription as noncanonical RNA caps by showing one nucleobase pairing with the template in canonical mode while the other pairs in reverse Watson–Crick mode.

The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

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.

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.

The vaccinia virus produces mRNA lacking the 5′ m⁷G cap structure. These uncapped mRNAs have long poly(A) leaders and dominate late in infection, suggesting a novel viral strategy for host takeover.

Brain-wide recordings in mice reveal that prior expectations are distributed through recurrent loops across all levels of cortical and subcortical processing.

Ginhoux, Dutertre and colleagues provide a comprehensive analysis of dendritic cell subsets and states across human tumoral and juxtatumoral tissues.

A resource of human RNA-protein associations is produced using a sequencing-based method.

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.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

Photosystem II drives photosynthesis, but how desert algae adapt to excess of light remains unclear. Here, authors present a cryo-EM structure of PSII from Chlorella ohadii, revealing structural features and antenna arrangements that may contribute to its stability.

Antibodies against SARS-CoV-2 continue to evolve 6 to 12 months after infection in patients who have recovered from COVID-19, increasing in potency and breadth with time.

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.

PU.1^low CD28-expressing microglia may act as suppressive cells in Alzheimer’s disease, mitigating its progression by reducing neuroinflammation and amyloid plaque load, indicating potential immunotherapeutic approaches for treatment.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

A two-component system, DbfRS, regulates biofilm formation in Vibrio cholerae. Here, Nguyen et al. identify a small periplasmic protein that controls the activity of the system’s receptor, and show that DbfRS responds to membrane stress and regulates additional processes such as metabolism and cell envelope biosynthesis.

This study investigates a calcium-permeable AMPAR–gated microcircuit in the nucleus accumbens during social bonding in prairie voles. By showing that disrupting calcium-permeable AMPAR signaling impairs ensemble-level encoding despite increasing single-neuron selectivity, the work reveals how coordinated ensemble dynamics transform social interaction into enduring attachment.

Reduced fitness of the tumor microenvironment is mediated by a long non-coding RNA expressed in tumors.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

An analysis of data from the Sherlock-Lung study provides insight into the mutational processes that contribute to lung cancer in never smokers, and looks at the possible role of factors such as air pollution and passive smoking.

In chemical-genetic and lipidomics analyses, the clinical candidate oncology drug tegavivint induced an unconventional form of nonapoptotic cell death that required the lipid metabolic enzyme trans-2,3-enoyl-CoA reductase.

Here the authors report single-cell and spatial transcriptomics of young and aged male fibrotic mouse lungs. Age-related alterations in capillary sub-populations are associated with a proangiogenic phenotype linked to regeneration of the alveolar niche.