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Sulfilimines are a class of chiral molecules that bear S(IV) stereocentres, which are of high value in drug discovery but difficult to synthesize. Now the authors report a chemo- and enantioselective Chan–Lam S-arylation of sulfenamides with arylboronic acids that delivers diaryl and alkyl aryl sulfilimines.

Sulfenamides are a class of divalent sulfur-derived scaffolds featuring an S-N bond with many industrial applications, however, they are also challenging substrates for synthetic transformations. Here, the authors present a highly chemoselective ligand-controlled Chan–Lam coupling of sulfenamides as a straightforward route to N-arylated sulfenamides.

Floquet engineering is often limited by weak light–matter coupling and heating. Now it is shown that exciton-driven fields in monolayer semiconductors produce stronger, longer-lived Floquet effects and reveal hybridization linked to excitonic phases.

How white matter develops along the length of major tracts in humans remains unknown. Here, the authors identify fundamental patterns of human white matter development along distinct axes that reflect brain organization.

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

O’Shea and colleagues establish that optimisation of charge and stability is sufficient to enable any single-chain variable fragment intrabody to function within the cell. The authors use AI-led inverse folding to optimise intrabody characteristics, and they present hundreds of intrabody sequences targeting sixty cytoplasmic proteins.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Rice paddies contribute to atmospheric methane (CH₄) levels. Here the authors show that increasing levels of the rice plant hormone PSY can reduce CH₄ emissions by over 50% via alteration of microbial H₂ cycling in the rhizosphere.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Muscularis macrophages, housekeepers of enteric nervous system integrity and intestinal homeostasis, modulate α-synuclein pathology and neurodegeneration in models of Parkinson’s disease, and understanding the accompanying mechanisms could pave the way for early-stage biomarkers.

Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

Integrated single-cell and spatial data analysis, combined with bidirectional CRISPR screens, identify the transcription factor GLIS3 as a key driver of chronic inflammation and fibrosis and a potential marker of disease severity in patients with ulcerative colitis.

Insulin signaling plays a crucial role in coordinating skeletal development with whole‑body energy metabolism. Here, the authors use phosphoproteomics to show insulin-signaling rewiring in aged, insulin-resistant bone and identify defective phosphorylation of AFF4 as a key mechanism for regulating gene-specific transcriptional activation.

MultiSuSiE is an extension of the Sum of Single Effects fine-mapping model that allows causal effect sizes to vary across ancestries. Applying MultiSuSiE to quantitative traits in All of Us identifies fine-mapped variants not implicated by other methods.

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.

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.

Vinyl acetate is an important polymer building block, but the mechanisms governing its catalytic production are not well understood. This study shows that dynamic palladium-acetate clusters determine catalyst efficiency and selectivity in vinyl acetate synthesis.

High-throughput chemical ligand discovery is challenged by false positives. Here, authors introduce a scalable enantioselective affinity-selection mass spectrometry approach for proteome-wide ligand discovery with high sensitivity and selectivity

In an arm of an ongoing multicenter phase 2 trial testing different therapies in patients with genetically profiled grade 2 or 3 meningiomas, treatment with an oral CDK4/6 inhibitor met the primary endpoint for progression-free survival at 6 months in patients with CDK or NF2 alterations.

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.

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.

Single-cell RNA sequencing and assay for transposase-accessible chromatin using sequencing profiling of human retinal samples from diverse ancestries create an epitranscriptomic atlas characterizing over 130 cell types. Integration with genome-wide association study and expression quantitative trait loci data provides further insights into gene regulation and disease etiology.

Somatic instability plays a role in Huntington’s disease. Here, the authors show that lowering HTT levels by transcriptional repression suppresses somatic instability. This can also be done without affecting HTT levels by direct CAG repeat binding.

RUVBL1 and RUVBL2 are AAA+ ATPases that are involved in transcriptional regulation. Here, the authors discover that RUVBL1/2 regulation of KLF5 modulates both classical and basal-like transcriptional lineage programs in pancreatic cancer.

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.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

A phase 1/2 trial of dual-vector rAAVrh8 gene therapy for GM2 gangliosidosis, administered by bilateral intrathalamic, cisterna magna and intrathecal delivery found a dose-dependent biochemical correction of the disease.

The Taiwan Precision Medicine Initiative recruited and genotyped more than half a million Taiwanese participants, almost all of Han Chinese ancestry, and performed comprehensive genomic analyses and developed polygenic risk score prediction models for numerous health conditions.

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.

The Taiwan Precision Medicine Initiative (TPMI) has built a cohort of more than half a million individuals with Han Chinese ancestry, providing a rich resource of genetic and medical data for this group.

Neri et al. develop elegant tools to understand how the sympathetic nervous system regulates intrascapular brown adipose tissue (iBAT) function. Using these tools, they find that sympathetic nerves targeting the iBAT parenchyma control local blood flow and heat production, while those innervating the iBAT vasculature regulate systemic glucose metabolism.

With rich, multi-layered baseline data and long-term follow-up through linkage, the HELIOS Study provides a resource to investigate the behavioural, environmental, genomic, and molecular factors impacting health in Asian populations.

Lo and colleagues report that double-positive thymocytes from neonates express less Zap70 and show reduced Ca^2⁺/NFAT signaling compared to double-positive thymocytes from older thymi. This diminished Ca^2⁺ signaling alters negative selection for self-reactive TCRs, resulting in a cell-intrinsic temporal window for regulatory T versus conventional T cell development in the thymus.

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.

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.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Cornell et al. show that target cells with low cortical tension induce macrophages to preferentially trogocytose, or engulf in small fragments, whereas target cells with high cortical tension tend towards phagocytosis.

Korobkina et al. show that ACLY in brown fat prevents metabolic overload in the tricarboxylic acid cycle, thus ensuring adequate thermogenesis by avoiding cellular stress.

In this study, the authors show that integrating a host gene biomarker with a large language model (LLM) improved lower respiratory tract infections diagnosis in a cohort of critically ill patients. The LLM plus biomarker outperformed the diagnosis made by the initial medical team and each component alone.

Here the authors reveal a study of 486,956 Han Chinese individuals showing that most people with genetic variants affecting drug response do not have the predicted adverse events, highlighting the challenges of implementing pharmacogenetics in clinical practice.

Ewing sarcoma (ES) is driven by the oncogenic fusion-protein EWSR1::FLI1. Here the authors identify that a galactosyltransferase C1GALT1 stabilizes Smoothened protein to activate Hedgehog signaling and promote EWSR1::FLI1 transcription in ES cells, which could be therapeutically targeted by an anti-fungal drug itraconazole that inhibits C1GALT1.

Therapeutic modulation of Janus kinase family enzymes is an established approach for inflammatory and autoimmune skin diseases. Here the authors rationally design small interfering RNAs to enable single Janus kinase targeting and test this new therapeutic approach in a skin disease model for maintaining efficacy and improving selectivity.

Metabolic liver disease is highly prevalent in subjects with obesity and involves inflammation, insulin resistance, and fibrosis, leading to cirrhosis. Here, the authors show the IFNγ-IL12 axis in regulating intercellular crosstalk in the liver and playing a major role in the pathogenesis of metabolic liver disease.

Single-molecule chromatin fiber sequencing exposes single-cell-level heterogeneity in the chromatin architecture of individual regulatory elements.

Small RNAs such as snaR-A (small NF90-associated RNA isoform A) may contribute to cancer-related phenotypes. Here the authors find that snaR-A interacts with mRNA splicing factors in subnuclear foci and causes splicing defects in mRNA subpopulations, which is associated with increased cell proliferation, and poor outcomes in cancer patients.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

DNA methylation and copy number variant analyses across a large number of genetic mouse models of pediatric brain tumors reveal subtype-specific molecular alterations shared with the corresponding human diseases.

Many premalignant colorectal polyps in familial adenomatous polyposis arise polyclonally rather than from a single mutated cell, showing diverse early evolutionary trajectories that frequently occur without clonal APC or KRAS driver events.