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A CRISPR knock-in strategy that uses endogenous gene regulatory mechanisms can engineer ‘armoured’ CAR T cells that secrete proinflammatory cytokines directly within a tumour without causing toxicity, leading to prolonged survival in mice.

The efficacy of CAR-T cells against solid tumors is still limited by immunosuppressive factors. Here, the authors show that engineering of CAR T cells with A1R enhances their efficacy against solid tumors in vitro and in vivo.

Single cell analysis of histologic variant bladder tumors detects a shared CA125+ tumor cell state associated with aggressive clinical features and reveals enriched expression of TM4SF1, a membrane protein that can be targeted with CAR T cells.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Megakaryocytes are responsible for releasing platelets into the blood to maintain homeostasis. Here, Gao et al. find that Mll3 and Mll4 help direct the expression of genes that regulate megakaryocyte function and platelet production.

Generalizable prediction of RNA secondary structure remains a challenge on unseen families. Here, the authors propose BPfold, which integrates a base pair motif library with thermodynamic energy into a deep learning framework, gaining superior accuracy and robustness over state-of-the-art methods.

Here the authors report asperigimycins, fungal ribosomally synthesized and post-translationally modified peptides with a heptacyclic scaffold. After chemically modifying them for nanomolar anticancer activity, CRISPR screening identifies SLC46A3 as a key transporter for their uptake in cells.

Here, the authors systematically interrogate the impact of acute stress on the sexually-dimorphic ventral subiculum circuitry and identify sex-specific synaptic and behavioral adaptations. Critically, these sex-specific adaptations are driven by distinct signaling pathways.

This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

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.

PAPD5 is responsible for adenylation of microRNAs. Here, the authors show that elevated level of PAPD5 enhances the adenylation and reduced expression of miR-7-5p. As a result, expression of TAB2, a target of miR-7-5p, is induced triggering neuronal apoptosis in Huntington’s disease.

Chen at al. show that CHD1 loss in SPOP-mutated prostate tumors confers castration resistance by increasing SREBP2-mediated cholesterol synthesis and subsequent androgen supply, an effect counteracted by combined androgen and cholesterol inhibition.

Citizen science taps the efforts of non-experts. Here, authors describe Drugit, an extension of the crowdsourcing game Foldit, and its use in designing a non-peptide binder of Von Hippel Lindau E3 ligase for use with proteolysis targeting chimeras.

Gain-of-function mutations in CTNNB1 (encoding for b-catenin) leading to deregulated Wnt/β-catenin signaling are frequently observed in patients with hepatocellular carcinoma (HCC). Here the authors show that inhibiting b-catenin with lipid nanoparticles encapsulating siRNA targeting CTNNB1 impairs tumor growth and promotes anti-tumor immunity in preclinical HCC models.

Small cell lung cancer presents high and multi-site metastatic potential. Here, the authors discover that FOXA2, regulated by ASCL1, promotes multi-site metastasis in small cell lung cancer by inducing a fetal neuroendocrine gene expression program.

A dynamic Cu–Pt dual-atom catalyst supported on 1Tʹ-MoS₂ can be electrically switched between single- and dual-atom configurations, enabling on-demand control for alkyne semi-hydrogenation.

The histone methyltransferase ASH1L has been linked to tumorigenesis, mainly in leukemia. Here, authors report that ASH1L cooperates with HIF-1α to induce a pro-metastatic transcriptome in prostate cancer cells, and promotes conversion of monocytes to lipid-associated tumor-associated macrophages in the bone metastatic niche.

Immunotherapy has yet to demonstrate efficacy for patients with glioblastoma. Here, the authors employ human single-cell RNA-seq, spatial transcriptomics, and a preclinical mouse model to show that glioblastoma cell-derived synaptogenic factor Thrombospondin-1 promotes neuronal circuit remodeling and regional immunosuppression, highlighting a potential therapeutic target.

Smale and colleagues explore evolutionary divergence in the NF-κB family. They show that intrinsic DNA-binding affinity rather than specificity led to neofunctionalization in mammals within this transcription factor family, supporting immunoregulatory rewiring in mammalian species.

Toxic chemicals can transform in the environment, often forming more harmful products. This study provides evidence for the aqueous formation of organophosphate esters (OPEs) in aerosols, highlighting their fate and implications for risk assessment.

Long-circulating, transfection-competent LNP-mRNA systems are key for effective extrahepatic delivery. Here, authors show that LNPs with high bilayer lipid ratios yield high mRNA encapsulation, prolonged circulation, and enhanced transfection in extrahepatic tissues.

Wastewater treatment plants are important reservoirs of antibiotic resistance genes (ARGs). Here, the authors analyze ARGs in a global collection of samples from wastewater treatment plants across six continents, providing insights into biotic and abiotic mechanisms that appear to control ARG diversity and distribution.

This study showed that vagal sensory neurons in the nodose ganglia selectively encode specific cytokines, enabling real-time body-brain communication of immune signals. This neural encoding of cytokines is disrupted during inflammation associated with a colitis model.

Here, the authors perform large trans-ancestry fine-mapping analyses identifying large numbers of association signals and putative target genes for colorectal cancer risk, advancing our understanding of the genetic and biological basis of this cancer.

The authors present a multiomics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits in Hispanic/Latino populations. They demonstrate how integrating GWAS with omics characterization can advance precision medicine.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

This study, together with a companion manuscript, shows that in mice, weight loss as a result of GIP receptor antagonism requires and potentiates functional GLP-1 receptor signalling in the brain, explaining how both GIP receptor agonists and antagonists trigger weight loss through different mechanisms.

This Review discusses recent advances in vascular biology, biomaterials chemistry and 3D printing techniques for vascular patterning in engineered tissues.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Growth of high-quality III–V semiconductors for electronics and optoelectronics usually requires an atomic-lattice matched substrate. Here, the authors use templated liquid-phase crystal growth to create single-crystalline III–V material up to ten micrometres across on an amorphous substrate.

Some cancer patients first present with metastases where the ___location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

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.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Faust, Chen, and colleagues present PHARAOH, a collaborative computational pathology platform that allows histologists to quickly develop custom labelled image datasets to train and catalogue a variety of machine learning models for histopathological analysis.

Cosmic rays flying through superconducting quantum devices create bursts of excitations that destroy qubit coherence. Rapid, spatially resolved measurements of qubit error rates make it possible to observe the evolution of the bursts across a chip.

Protease containing ABC Transporters (PCAT) play a critical role in the translocation of polypeptides across membranes. Here, authors reveal the structural and energetic of the ATP-powered conformational cycle that enable this process.

Profiling crRNAs revealed optimal length for Cas12-based molecular testing and SNP detection. Investigation into multivalent architectures elucidated valency and distance dependence for synergistic Cas12 activity.

Activated carbon has been widely used for PFAS adsorption, but this method generates secondary solid wastes. The flash Joule heating approach realizes mineralization of PFAS and generation of useful flash graphene in waste granular activated carbon.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Bacteria can use different mechanisms to become resistant to the same antibiotic class. Here, the authors study bacterial strains that express genes conferring tetracycline resistance via different mechanisms, and find that each mechanism is preferentially selected for by specific tetracycline generations.