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N-Arylation of NH-diaryl sulfoximines faces synthetic challenges among reported methods. Here, the authors present a mild copper-catalyzed photoredox dehydrogenative Chan-Lam coupling of free diaryl sulfoximines and arylboronic acids via an auto-catalytic process.

Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

In vivo adenine base editing corrects a common Pex1 pathogenic allele in mouse models of Zellweger spectrum disorder, rescuing liver pathology, fatty acid levels, body weight and peroxisome function.

Given rising diabetes prevalence globally, access to diabetes treatments is gaining urgency. Here, the authors show patterns of glucose-lowering medication use for diabetes across 62 low- and middle-income countries.

Pathological neovascularization is a leading cause of vision loss. In this study, the authors identify FRZB and its NTR domain as suppressors of ocular angiogenesis. FRZB prevents CAV1 phosphorylation at Tyr42 which enhances downstream TGFβ signaling via ALK5 retention.

A series of in vitro and in vivo CRISPR activation screens combined with in situ Perturb-seq identify regulators of T cell-dependent cytotoxicity in melanoma.

Kancharla, Kelly et al. identify an acridone antimalarial potent across all major parasite life stages. Lead candidate T111 shows oral efficacy, low toxicity, and synergy with tafenoquine, providing a unique mechanism to overcome resistance.

Placenta plays a central role in prenatal development, yet it has been notably underrepresented in large-scale tissue-specific genomic and transcriptomic initiatives. Here, the authors generate a comprehensive placental transcriptome reference using long-read sequencing, revealing unexpected transcriptional complexity. Applied to gestational diabetes data, the reference identified pregnancy hormone isoforms mediating effects on newborn birth weight.

Here, the authors show that continuous glucose metrics capture some components of glycaemic physiology in euglycaemic individuals. An evaluation of health outcomes longer-term would be required to assess whether continuous glucose monitoring has utility for health management in this population.

Authors present a framework that harmonizes electronic health record data across hospitals by integrating medical knowledge, large language models, and graph learning. It enables cross-institutional analysis without sharing patient-level data.

Here the authors report real-world evidence through a retrospective analysis of a multinational cohort of 1.8 M older adults showing that GLP1RAs and SGLT2 inhibitors carry lower risk for hyperkalemia than sulfonylureas. However, SGLT2 inhibitors increased risk of ketoacidosis. Findings support safety-conscious prescribing for older adults, who are often underrepresented in clinical trials.

This 5-year follow-up of the double-blinded, placebo-controlled phase 3 DEN-03-IB trial evaluating the efficacy and safety of the Butantan dengue vaccine in participants aged 2–59 years in Brazil found that a single dose of the vaccine was effective against DENV-1 and DENV-2, regardless of serostatus at baseline, and was safe.

tRNA deacylases have evolved as resistance genes towards natural products that contain non-canonical amino acids by preventing their mistranslation. Now a strategy has been developed that leverages tRNA deacylases as class-agnostic genomic markers for amino acid-based biosynthetic gene clusters, identifying thousands of cryptic clusters and enabling the discovery of amino acid-based natural products.

Using efficacy estimates from a previous cluster randomized trial in Senegal and accounting for differences in weather, vegetation and population density between trial and non-trial areas, a machine learning-enabled method estimates intervention efficacy for mass drug administration against malaria at a granular scale and beyond the trial period.

A study examines the effects of mutations that occur naturally in T cell cancers, reporting that such mutations can potentially be exploited to increase the potency of T cell therapies.

A multiplexed RNA detection method exploits crRNA-dependent variability in Cas13a activity on RNA targets for kinetic barcoding and can be used to distinguish among SARS-CoV-2 variants in clinical samples.

Here the authors use CRISPR activation screens to identify metabolite-sensing receptors that affect lymphocyte targeting and infiltration of tumors and engineer CAR T and CAR NK cells with these receptors to enhance solid tumor killing in mice.

Esophageal motility is difficult to model accurately, hindering studies of dysphagia and achalasia. The authors present a soft‑robotic esophagus that independently replicates muscle actions to simulate both healthy and diseased swallowing.

When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

The cellular origin and developmental trajectory of DICER1 syndrome-associated tumors are currently unknown. Here, the authors employ a lineage-traceable genetically modified mouse model for DICER1 syndrome to identify universal fibroblasts as the likely cellular origin of mouse Dicer1 sarcoma and map their developmental trajectory, findings that are validated in human DICER1 mesenchymal tumors.

Daratumumab, an anti-CD38 monoclonal antibody, was recently approved for patients with high-risk smoldering myeloma to prevent progression to overt myeloma. Here, the authors present results on a Phase II trial of daratumumab in patients of earlier stage to determine response and safety in that population.

Simultaneous profiling of adenylated and non-adenylated RNAs reveals regulatory programs across diverse cell types.

During olfactory navigation, Caenorhabditis elegans can execute error-correcting turns. Whole-brain imaging and perturbation experiments identify an ensemble of neurons that control reorientation and turning behaviors.

Appel et al. found that deceptive networks reached over 37 million Facebook and 3 million Instagram users during the 2020 US elections, with the majority of this exposure driven by 3 networks and amplified by ordinary users resharing the content.

Here, Wulczynski et al. find fewer small-intestinal fiber-degrading bacteria in CeD patients, independent of the gluten-free diet, while inulin-supplemented diet in gluten-sensitized mice facilitates microbial saccharolytic function and SCFAs, accelerating mucosal healing in the small intestine.

A strategy harnessing tissue-resident memory T cells to concentrate circulating immune cells enables non-invasive sampling of antigen-specific lymphocytes, providing a window into local and systemic immune responses in mice and humans.

NuMA activates dynein to organize the mitotic spindle by linking motor-driven transport with microtubule (MT) minus-end control. Mitotic phosphorylation relieves NuMA autoinhibition, enabling dynein motility and focusing MT minus-ends into asters.

Skin-targeted siRNA therapies require optimized delivery to achieve therapeutic efficacy. Here, authors show that increasing conjugate hydrophobicity enhances siRNA skin retention and gene silencing in porcine and human models while limiting systemic tissue exposure.

Analyses of snRNA genes in a French cohort of people with rare disorders, with validation through international collaboration, identify monoallelic and biallelic variants in RNU2-2 as frequent causes of neurodevelopmental disorders with epilepsy.

A tunable granular biomaterial matrix is developed to support long-term bioprinting. Stress relaxation at high strains and long timescales is shown to be important for tissue self-organization in intestinal organoids.

CREsted is an efficient and user-friendly toolbox for analysis, modeling and design of cell-type-specific enhancers across diverse species.

Biallelic variants in RNU4-2 cause a recessive neurodevelopmental disorder that is phenotypically and molecularly distinct from dominant ReNU syndrome and associated with reduced RNU4-2 transcript levels, consistent with a loss-of-function mechanism.

The Human Development Multiomic Atlas catalogues single-cell accessibility and gene expression data from human fetal cells across 12 organs, enabling the inference of syntactic rules for motifs that govern cell-type-specific transcription factor binding and chromatin accessibility during human development.

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

Glucocorticoid receptor activation is a key driver of resistance of triple-negative breast cancer to both CD8⁺ T cells and natural killer cells during initial metastatic seeding.

Conventional type 1 dendritic cells (cDC1) can boost the precursor exhausted T cell population thought to be essential for efficacy of immune checkpoint therapy. Here the authors enhance this cellular network using Flt3L to expand cDC1s and then map the movement of T cells and DCs between tumors and lymph nodes.

Phylogenomic analyses of newly sequenced and published decapodiform cephalopods separate open-ocean and coastal shallow-water clades, following rapid cladogenesis from the mid-Cretaceous.

The DNA origami vaccine platform DoriVac is shown to support multiplexed nanoparticles carrying diverse antigens against emerging infectious diseases and variants.

Chimaeric antigen receptor macrophages including the MyD88 activation domain target mesothelin for treatment of lung cancer brain metastases.

This Swedish population-based cohort study identified an association between exposure to assault/victimization and obsessive–compulsive disorder risk, particularly within the first year after exposure.

Genetic analyses in more than 15,000 individuals from across the Americas, including individuals with autism and family members, define the genetic landscape of autism in Latin American populations and identify significant overlap with other ancestries.

Long-term patterns of physical activity and the importance of consistent adherence to the recommended level remain poorly understood. Here, the authors show that maintaining physical activity over the long term offers added benefits beyond activity volume alone for chronic disease prevention.

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.

Single-variant and ultrarare variant burden analyses leveraging exome sequencing data from 22 cohorts identify new risk genes for amyotrophic lateral sclerosis and show cumulative effects of several rare variants on disease risk.

Low-valent sulfur-containing compounds are abundant among natural and synthetic products but remain underutilized as starting materials in desulfurative transformations. Here, the authors present thiols, disulfides, thioethers, and thioacetals as precursors in a direct desulfurative electrochemical process for the formation of alkylboronic esters.