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Ranek et al. developed a computational method that analyzes proteomic imaging and detects differentially enriched cellular niches, including low-prevalence niches. They applied this tool to inform therapy response in triple-negative breast cancer.

A multiancestry phenome-wide analysis of copy number variants in the UK Biobank genomes increases power to detect genetic associations with complex traits across human populations.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

Greenwald, Nederlof and colleagues developed a computational pipeline analyzing multiplex imaging data and established spatial patterns within breast cancer microenvironment that are predictive of immune checkpoint blockade response across treatment time course.

Self-DNA has been implicated in the activation of cGAS/STING/IFN-I responses in autoimmunity and inflammatory diseases. Here the authors show that macrophage uses a process termed ‘nucleocytosis’ to extract nuclear DNA from lysosome-impaired, dying target cells, thereby activating downstream cGAS-STING signaling and IFN-I production.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

A spatial and single-cell transcriptomics study across multiple mammalian species identifies epidermal BMP signalling as a functional requirement for rete ridge formation, providing insight into mechanisms underlying hair density loss and wound healing.

The systemic discovery of metal–small-molecule complexes from biological samples is a difficult challenge. Now, a method based on liquid chromatography and native electrospray ionization mass spectrometry has been developed. The approach uses post-column pH adjustment and metal infusion combined with ion identity molecular networking, and a rule-based informatics workflow, to interrogate small-molecule–metal binding.

A genome assembly method called hifiasm (ONT) allows the assembly of chromosomes from telomere to telomere without the need for ultra-long reads, and outperforms conventional methods on most evaluation metrics.

Changing fire regimes, leading to higher likelihood of high severity fire, are having unknown impacts on biodiversity. This study identifies regions of high avian biodiversity and individual bird species predicted to be highly exposed to future high severity.

To achieve simultaneous transparency and vivid multicolor switching in electrochromics is desirable owing to their potential as next-generation transparent displays. Here, the authors show a single-molecule design strategy that integrates a rhodamine moiety with a propylenedioxythiophene unit and incorporates molecular doping to achieve high optical transmittance with three distinct optical states.

Hi-C methods for studying 3D genome structure typically require millions of cells and struggle with repetitive regions. Here, authors develop CiFi, combining 3C with PacBio HiFi sequencing, enabling chromatin analysis from as few as 60,000 cells and chromosome-scale assembly from small samples.

Polymer thin films that emit and absorb circularly polarised light are promising in achieving important technological advances, but the origin of the large chiroptical effects in such films has remained elusive. Here the authors demonstrate that in non-aligned polymer thin films, large chiroptical effects are caused by magneto-electric coupling, not structural chirality as previously assumed.

Incorporating membrane-destabilizing zwitterionic lipids into commercially available LNPs boosts mRNA expression in antigen-presenting cells within lymph nodes, enhancing cytotoxic T cell activation, and dampens reactogenicity in mice.

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.

This study finds that native tree extinctions and alien naturalizations are pushing forests towards fast-growing, resource-demanding species. This global shift could affect carbon storage and ecosystem stability, highlighting the need to protect slow-growing trees.

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.

Medication non-adherence represents a healthcare challenge, generating over $100 billion in additional costs annually in the USA. Here, the authors developed a resorbable and ingestible system designed for assessing medication adherence.

Figure 1. Schematic illustration of capsule based, biodegradable medication adherence tracking system with envisioned scenario for clinical use. A, Bio-RFID capsule administration. B, Shielding coating dissolution and payload release C, Monitoring of the Tag ID and frequency range, recording of the payload for tracking adherence. D, Dissolution and biosorption of the coating, tag and the capsule.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Rjoob et al. develop CardioKG, a knowledge graph built on cardiac imaging traits to identify genetic associations and potential therapeutic strategies and drug repurposing opportunities for cardiovascular diseases.

This work highlights how changes to beaches are related to sand movement and human impacts to the coast and illuminates opportunities for sand management to resolve shoreline erosion and enhance beach sustainability.

Nitazenes are potent synthetic opioids that are difficult to detect. Here, authors computationally redesign a plant receptor to create sensitive sensors capable of detecting diverse nitazenes and their metabolites in biological samples.

An exploratory analysis of the phase 3 ECOSPOR III trial shows that a higher dosage of the oral microbiome therapeutic VOWST led to enhanced pharmacokinetics, increased species engraftment and altered microbiome and metabolite profiles, providing mechanistic insights into how it may prevent Clostridioides difficile infection recurrence.

A cross-country survey among 82,324 sexual and gender diverse people finds that family rejection, homophobic reactions, and institutional stigma and discrimination are linked with individual well-being, especially for those facing poverty.

Virus-like particles are engineered to edit human hematopoietic cells in vivo.

Covalent KRAS inhibitors show initial responses but resistance limits durability. Here drug-induced hapten peptides are identified and characterized, enabling production of high affinity, cross-HLA T cell engagers that stabilize low density hapten peptide MHCs to drive tumor-specific killing.

The low-density lipoprotein receptor family members LRP1, LRP4 and VLDLR are entry receptors for yellow fever virus.

An enduring question in ecology is how new ecosystems form. Studying retreating glaciers, this study shows that life’s first foothold in these new environments is not established by photosynthetic organisms as long assumed, but rather by versatile microbes that harvest chemical energy from soil and thin air.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

A broad systems-level approach is necessary to understand the intricate etiology of clinical complications from atherosclerotic cardiovascular disease. Here, the authors reconstruct a causal network of circulating proteins and identify subnetworks linked to future risk of myocardial infarction and other cardiometabolic traits.

Hodgkin Reed Sternberg (HRS) cells and their surrounding microenvironment in Hodgkin lymphoma remain poorly characterized. Here, the authors perform genome-wide transcriptional profiling with spatial and single-cell resolution to explore the cellular and molecular composition of the Hodgkin lymphoma microenvironment and used machine learning to identify IL13 as a potential HRS cell survival factor.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

CD27 is a key T-cell costimulatory receptor, but efforts to target CD27 have been limited by the poor clinical efficacy of first-generation anti-CD27 antibodies. The authors here engineer higher-valency antibodies by more effectively engaging CD27 and selectively binding to FcγRIIB, which enhance anti-tumor activity.

Here authors show loss of AKAP11, a strong genetic risk factor for bipolar disorder and schizophrenia, disrupts PKA proteostasis and signaling, leading to widespread transcriptomic alterations across the brain, particularly in striatal neurons, as well as altered behavior.

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.

Genome-wide association studies (GWAS) of deep learning-derived measurements of aortic valve function, along with multitrait analyses incorporating disease-based GWAS, identify 166 genetic loci associated with aortic valve function or aortic stenosis.

Antigen escape relapse remains a major obstacle when treating B-cell malignancies with immunotherapies. Here, the authors show that IKAROS regulates the surface expression of CD19 and CD22, revealing a mechanism by which B-cell cancers evade targeted immunotherapies.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

u-Segment3D is a universal framework that translates and enhances 2D instance segmentations to a 3D consensus instance segmentation without training data. It performs well across diverse datasets, including cells with complex morphologies.

In vivo experiments and clinical cohort analyses show that hypoxia-inducible factor 2 (HIF2)-induced parathyroid hormone-related protein (PTHrP) expression contributes to cachexia in the context of renal cell carcinoma (RCC). The pathway can be targeted by HIF2 inhibitors, including belzutifan, which may reduce cachexia in patients with RCC.

Disassembly of three-dimensionally ordered materials generates nanoparticles with new structural and physicochemical properties. Here the authors show a fragmentation strategy applied to a perovskite material leading to nanostructures with improved catalytic activity in the methane combustion.

Human primary monocytes reversibly phase separate into regular, multicellular, multilayered domains on soft matrices with physiological stiffness due to local activation and global inhibition processes that occur during random cell migration.

The blood-brain barrier (BBB) regulates the extracellular composition of the central nervous system (CNS), but it is not known whether its properties differ across CNS regions. Here, the authors show in mice that the BBB exhibits regional specializations, and that such specializations can be important for the function of specific neural circuits.

African ancestry is a known risk factor for prostate cancer development, but the genetic determinants of this are incompletely understood. Here, the authors identify 172 potentially pathogenic variants which are enriched in an African population.

Rydberg atoms have the potential to serve as broadband receivers but require lasers with  > 100 GHz scan ranges to observe multiple states. We bridge this major gap with an optical frequency comb for rapid preparation of over 7 Rydberg states.

Signal peptide sequences appear in secreted proteins. Here, authors use these sequences in a proteomic search method called “signal strapping” to discover metalloproteins, which have an N-terminal histidine that chelates a transition metal ion.

Amouzgar and colleagues present a deep, single-cell mass cytometry approach to capture canonical and noncanonical cell cycle states using protein, phospho-protein, and DNA labelling measurements for high-throughput, multiplexed cell cycle quantification.