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Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

STING–type-I interferon pathway regulates the immunogenicity of several cancer types, including head and neck squamous cell carcinoma. Here the authors describe that glutamine metabolism in the tumour microenvironment dampens the STING–type-I interferon pathway by epigenetically silencing the expression of BATF2, which functions as a tumour suppressor.

Rosiglitazone, identified through integrative network-based drug repurposing and Mendelian randomization, alleviates age-related sarcopenia in mice. It enhances muscle strength and mass, possibly through gut microbiota remodeling, activation of Igf1 signaling, and inhibition of muscle atrophy–related ubiquitin ligases.

Researchers studied the blood-based metabolome of over 23,000 people from ten ethnically diverse cohorts. They identified 235 metabolites associated with future risk of type 2 diabetes (T2D). By integrating genetic and modifiable lifestyle factors, their findings provide insights into T2D mechanisms and could improve risk prediction and inform precision prevention.

Extracellular vesicles (EVs) have shown potential as a therapeutic delivery system for cancer treatment. In here the authors have established HEK293T cells engineered with α-HLA-G VHH antibody-chimeric CD63 protein to promote the production of EVs that can augment the targeting of HLA-G-positive tumor cells

T cells have been shown to have a function in chronic lung inflammation in COPD. Here the authors characterise the single cell transcriptional profile of T cells after smoke inhalation in mouse models showing changes in TCR repertoire and Il17a expression in γδ T cells, suggesting smoke-associated γδ T cells are involved in COPD inflammation and implicating γδT17 cells as a possible target for early prevention and treatment of COPD.

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

Developing efficient non-precious catalysts is key to advancing water electrolysis. Here, the authors report a microbial vulcanization strategy that co-dopes cobalt hydroxide with sulfur and organic molecules to optimize O–O coupling and accelerate the electrocatalytic oxygen evolution reaction.

Colonic smooth muscle cell (CSMC) hypertrophy and hyperplasia have been described in human ulcerative colitis (UC) and animal models. Here the authors show that mice lacking smooth muscle (SM) 22a develop spontaneous colitis which has RSAD2-driven mitochondrial dysfunction and inflammation in CSMC and show dependence on RSAD2 for colitis alleviation.

The relative benefits of finerenone vs spironolactone in CKD with T2D are unclear. Here the authors show that in >2,200 matched patients, finerenone lowers risks of cardiovascular and kidney events, death, and hyperkalemia compared with spironolactone.

COPD patients are more likely to also have diabetes. Here the authors show that the use of SGLT2 inhibitors was associated with reduced all-cause mortality, hospitalization, acute exacerbations, and pneumonia in patients with COPD and diabetes.

Here the authors report a retrospective analysis showing lower risk of composite outcomes of all-cause hospitalization, all-cause mortality, major adverse cardiovascular events, major adverse kidney events and major adverse liver outcomes for patients with MASLD treated with combination therapy with GLP-1 receptor agonists and SGLT2 inhibitors versus SGLT2 inhibitor monotherapy. However, a sensitivity analyses suggests that these effects may be driven by the GLP-1 receptor agonist treatment.

Metamaterials can be used to alter the transmission of light or sound, with their tailored structures permitting control over their optical or acoustic properties. Meiet al. present a thin-film acoustic metamaterial that provides efficient absorption of sound over a broad range of wavelengths.

A trispecific T cell engager has been developed to redirect bystander T cells, overcoming immunosuppression and enhancing antitumour immunity across multiple solid tumour types, alongside a machine learning-based tool to predict its efficacy.

Here the authors show that radiation triggers oral mucositis via ferroptosis in basal epithelial cells, while fibroblasts provide early protection by supplying polyamines that inhibit this cell death pathway.

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.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

mlHsu et al. examine the effectiveness of Angiotensin Receptor-Neprilysin Inhibitors (ARNI) in individuals with Chronic Obstructive Pulmonary Disease (COPD) and heart failure. Findings reveal that ARNI treatment in people with both COPD and HF may lower the risk of COPD exacerbations, respiratory failure, and respiratory tract infections.

Here, authors present three-dimensional rolled-up, magnetically integrated microinductors, demonstrating a superlinear scaling law of inductance density. This design makes the device suitable for a compact radiofrequency on-chip system for the Internet of Things and 6G applications.

The authors show that Galectin-3 is up–regulated in brain tissues from patients and a mouse model of Huntington’s disease (HD) and correlates with disease severity. Galectin-3 accumulates at damaged lysosomes in HD microglia, prevents the clearance of damaged lysosomes, and promotes inflammation.

Scalable routes towards porous graphene are useful for developing materials for mass transfer applications. Here, the authors report the fabrication of porous graphene with controllable pore size and nitrogen content via the carbothermal reaction of graphene and (poly)oxometallates.

A gene-edited pig liver transplanted into a human recipient remains functional after 10 days and indicates that porcine organs could help meet the growing demand for liver transplants.

Low-frequency quasiperiodic oscillations in X-ray data are thought to trace the accretion flow in X-ray binaries. Here, the detection of 200 keV oscillations probes the innermost regions of MAXI J1820+070, revealing the precession of a small-scale jet.

This study identifies TriDTCs as a family of terpene cyclases responsible for harzianol I and wickerol A biosynthesis in Trichoderma fungi and are found to regulate Trichoderma’s chlamydospore and Aspergillus oryzae’s sclerotia formation through producing harzianol I.

Cancer cells adapt to the changing microenvironment by activating different pathways through multiple mechanisms. Here the authors identify long noncoding RNAMIR31HGas a HIF-1α co-activator required for the induction of the hypoxic response and show its oncogenic role in oral carcinogenesis.

Cerebrospinal fluid circulating tumor DNA profiling had prognostic value in a cohort of 584 patients with lung cancer and central nervous system metastases, and could be used to inform personalized therapies.

Maintaining proper reactive oxygen species (ROS) balance is critical for cellular and individual health, yet its dynamic nature encumbers monitoring and assessment. Here the authors propose a platform using mass cytometry-based detection, termed SN-ROP, to identify distinct ROS profiles associated with specific immune cell functions and disease states.

Frequencies for motor kinematics are encoded by the cerebellum through population tuning of firing probabilities, which leads to cerebellar oscillations and corresponding motions.

Catalytic reductive coupling of two electrophiles and one C = C bond is usually performed by two electron transfer metal catalysis. Herein, the authors show a visible light photoredox-catalyzed successive single electron transfer leading to dearomative arylcarboxylation of indoles with CO₂ and generating indoline-3-carboxylic acids.

Tumor-derived extracellular vesicles (EVs) critically regulate tumor development and progression. Here the authors show that, in a mouse model of breast cancer, miR-9-5p-loaded EVs promote cholesterol biosynthesis and conversion into the oncometabolite 25-hydroxycholesterol, favoring immune evasion and promoting liver metastasis.

As immune checkpoint therapy is more frequently used for cancer, side effects such as Stevens-Johson syndrome / toxic epidermal necrolysis (SJS/TEN) are becoming more common. Here the authors use single cell transcriptomics to implicate TNF and CXCL10 in recruitment of CXCR3⁺ cytotoxic T cell in SJS/TEN skin lesions.

Two mGlu3–βarr1 cryo-EM structures with 2:1 and 2:2 stoichiometries are reported, revealing that the inactive state involves mGlu3 engagement of βarr1 through phosphorylated C-terminal tail and intracellular loops.

Severe acne is a common skin disease characterized by chronic inflammation and potential scarring. Here, the authors have identified genetic variants at two loci associated with severe acne and provide insight into the genetic architecture and biological pathways underlying the disease.

Developing multi-cancer early detection (MCED) tests based on cfDNA or protein markers holds great promise for effective cancer screening. Here, the authors show a sensitive, non-invasive pan-cancer detection method that concurrently detects the oncofetal chondroitin sulfate (ofCS) glycans and its protein backbone in plasma.