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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.

Here they demonstrate a therapeutic intervention elevating levels of CYP450-derived lipids to control the expansion of intermediate monocytes in tissue and peripheral blood, presenting a first in class therapeutic approach for treating chronic inflammatory disease.

A technique called condense-seq has been developed to measure nucleosome condensability and used to show that mononucleosomes contain sufficient information to condense into large-scale compartments without requiring any external factors.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

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.

McGrail and colleagues report that high intratumoral bacteria abundance is associated with an immunosuppressive microenvironment and resistance to immune checkpoint blockade in head and neck squamous cell carcinoma.

Uncertainty-aware machine learning models predict human toxicity for more than 100,000 chemicals, highlighting potency and uncertainty hotspots to guide safer use and to focus efforts to improve prediction confidence.

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.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

RNAi therapy has huge potential but effective delivery to target location is a major issue. Here, the authors report on the delivery of RNAi to tumors using self-agglomerating nanohydrogels that can overcome the different delivery barriers and supply multiple RNAi payloads.

The authors of this study map the human E3 ubiquitin ligome using a metric learning approach, revealing a unified classification framework that explains preserved patterns and functional segregation of E3 families, linking enzymes to substrates and drug interactions, and guiding strategies for targeted therapies.

Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

Several recent publications have attempted to detect novel unannotated microproteins using mass spectrometry proteomics. Here, the authors reassess these claimed microprotein detections, finding that many are poorly supported, while a subset represents likely genuine discoveries of novel proteins.

Although the number of participants is important for phenotypic prediction accuracy in brain-wide association studies using functional MRI, scanning for at least 30 min offers the greatest cost effectiveness.

Vaccine-derived poliovirus type 2 currently spreads similarly to historical poliovirus—unidirectionally across neighbouring countries at a median velocity of 2.3 km per day. International borders are associated with slower velocity when immunity is high.

The authors developed an LXR inverse agonist, TLC-2716, and show it is effective in reducing triglycerides and cholesterol in dysmetabolic preclinical models. Additionally, a phase 1 trial in healthy participants shows that TLC-2716 is well tolerated and reduces plasma triglycerides and postprandial remnant cholesterol, highlighting its potential for managing cardiovascular risk.

Pilcher et al. present a single-cell transcriptomics-based immune atlas of participants with newly diagnosed multiple myeloma, reporting on the association of cell types, gene expression and intercellular interactions with disease progression phenotypes.

Chromatin accessibility dynamics causally influence changes in gene expression levels, but these fluctuations may not be directly coupled over time. Here, authors develop computational causal framework HALO, examining epigenetic plasticity and gene regulation dynamics in single-cell multi-omic data.

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.

Genetic mapping in mice identified Homer1a as a key modifier of attention. Developmental downregulation in the prefrontal cortex enhances inhibitory tone, neural signal to noise and adult attentional performance, revealing a new control mechanism and target.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

The microbiota influences the cytotoxicity of chemotherapy in patients with colorectal cancer but the impact on metastatic relapse is less clear. Here, the authors report that chemotherapy-induced intestinal mucositis induces systemic immune changes via production the microbial metabolite, indole-3-propionic acid (IPA), preventing metastases.

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.

The efficacy of an antidepressant is predicted from an EEG signature.

This study reveals that anti-NS1 IgA antibodies in plasma, induced by prior Zika virus infection, activate neutrophils, underlying severe dengue disease upon a subsequent DENV2 infection, uncovering a pathogenic mechanism relevant for vaccines and therapeutics.

The authors present MorphoGenie, an unsupervised model that profiles cell shapes to predict cellular heterogeneity without manual labels. It provides a scalable, interpretable, and generalizable approach for data-driven exploration of cellular heterogeneity across diverse imaging modalities.

A benchmarking competition improves tools that predict how regulatory regions control gene expression.

In a randomized controlled trial that included 97 participants, 69% patients with Crohn’s disease (CD) allocated to a fasting-mimicking diet (FMD) achieved clinical response, and over 60% reached remission, outperforming the control group. The FMD also reduced markers of intestinal inflammation, suggesting this dietary intervention could serve as adjunctive treatment for CD.

Microflora Danica—an atlas of Danish environmental microbiomes—reveals that although human-disturbed habitats have high alpha diversity, species reoccur, revealing hidden homogeneity.

While the emergence of immune checkpoint inhibitors has improved outcomes in patients with small cell lung cancer (SCLC), tumour that develop means of immune evasion become resistant. Here, the authors report that ERBB2 signalling induces loss of MHC Class I expression and subsequently immune evasion in preclinical models of SCLC.

89ZED88082A is a zirconium-89-labeled one-armed anti-CD8α antibody for the non-invasive whole-body visualization of CD8 + T-cells by positron emission tomography (PET). Here the authors report the results of a phase 2 study of 89ZED88082A for whole-body CD8 + T-cell PET imaging in patients with large B-cell lymphoma before and during CD19-directed CAR T-cell therapy.

Murphy et al. reveal a unifying pathogenetic mechanism according to which diverse mutations in the muscle-specific ribosomal protein RPL3L cause severe neonatal dilated cardiomyopathy, establishing a framework for interpreting the growing spectrum of RPL3L variants.

Brain age gaps (BAGs) highlight deviations from healthy brain aging, yet their biophysical underpinnings in aging and dementia are not well understood. Here, the authors use EEG connectivity and generative modeling across diverse populations to reveal that BAGs are influenced by geography, income, sex and education, with implications for understanding accelerated aging and dementia.

Edge localised modes (ELMs) in highly confined plasmas are notoriously difficult to regulate. Here, the authors analyse multiscale modes and interactions by combining experimental measurements from DIII-D and modeling, showing promising results in ELM control.

Through an epigenome-wide blood analysis in children of mothers with or without type 1 diabetes, the authors identify epigenetic modifications of type 1 diabetes susceptibility loci through which maternal type 1 diabetes may protect from islet autoimmunity in offspring.

Around 20% of synonymous sites are conserved in placental mammal genomes, but the evolutionary forces determining this is unclear. This study show that a combination of GC-biased gene conversion, functional constraint, and mutation rate variation has likely shaped synonymous site evolution.

A wide survey of pesticide effects on soil biodiversity across 373 sites in Europe reveals that pesticide residues occur in 70% of sites and have major effects on soil biodiversity and functional ecology.

Bessler et al. developed a human organoid model for H3.3K27M-altered diffuse midline glioma that recapitulates key tumor features and demonstrated its utility for modeling CAR T cell and microglia functions.

A hidden Markov model that uses probabilistic retrospective inference allows for up to one month of unsupervised recalibration in an online cursor-based intracortical brain–machine interface.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

Creative experiences such as dance, music, drawing, and strategy video games might preserve brain health. The authors show that regular practice or short training in these activities is linked to brains that look younger and work more efficiently.

Genomic sequencing of the thermotolerant coral species Oculina patagonica, single-cell transcriptomic analyses of symbiotic and non-symbiotic specimens and comparisons with obligate symbiotic coral species reveal adaptations that provide resilience to coral bleaching.

Prime editing in mammalian cells benefits from a comprehensive list of genetic parts.

Lentivirus-based reporter assays for 680,000 regulatory sequences from three cell lines coupled to machine-learning models lead to insights into the grammar of cis-regulatory elements.

TIRTL-seq is a high-throughput method for paired T cell receptor sequencing at the cohort scale.

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.

The original Cancer Cell Line Encyclopedia (CCLE) is expanded with deeper characterization of over 1,000 cell lines, including genomic, transcriptomic, and proteomic data, and integration with drug-sensitivity and gene-dependency data.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.