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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.

Here the authors report that some aspects of clinical heterogeneity in type 2 diabetes vary across populations. Using a deep-learning–based tree model built from over 32,000 patients, they document disease patterns and risks specific for the Chinese population, potentially enabling more precise prediction and personalized care.

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.

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.

In this double-blind, randomised, crossover trial, a diet rich in fermentable foods was shown to improve the glucose-lowering efficacy of metformin due, at least in part, to changes in gut microbiota composition.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

In an updated report on 70 laboratory-confirmed highly pathogenic avian influenza A H5N1 cases in the USA between March 2024 and May 2025, the absence of human-to-human transmission to date was confirmed, with no known mutations of resistance to neuroaminidase inhibitors.

A 50 microRNA-based dynamic risk score for stratifying individuals with and without type 1 diabetes was developed using samples obtained from multicenter and multiethnic cohorts.

Rodrigues and Queiroz et al. report the discovery of Naiavirus, the largest enveloped virus, isolated from a Brazil biome. With an oval capsid and flexible tail, its giant genome holds many novel genes, underscoring the value of viral isolation studies.

A study reveals that the skin acts as an autonomous lymphoid organ, producing antibodies to control the local biomass of the microbiota and protect against systemic infection, maintaining homeostasis between the host and its microbiota.

In this Perspective, the authors explore the concept of multifactorial chronic kidney disease and examine the different factors that might compromise kidney functional capacity or increase kidney workload throughout the life-course, and how their cumulative effects can lead to chronic kidney disease.

Tailored to provide diabetes management recommendations from large training and validation datasets, an artificial intelligence system integrating language and computer vision capabilities is shown to improve self-management of patients in a prospective implementation study.

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.

Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants.

Exome-sequencing analyses of a large cohort of patients with type 2 diabetes and control individuals without diabetes from five ancestries are used to identify gene-level associations of rare variants that are associated with type 2 diabetes.

The MYST acetyltransferase HBO1 is a critical regulator in maintaining leukaemia stem cells, and a small-molecule inhibitor of HBO1 is developed that shows efficacy against a range of acute myeloid leukaemia cells.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

In this Review, the authors summarize epidemiological trends of type 2 diabetes in China, discuss unique risk factors contributing to diabetes risk in the Chinese population and highlight how recent advances from multi-omics studies can affect treatment of diabetes in China.

With whole-genome screens using a bivalent MHC class I gene expression readout, Sparbier et al. identify opposing roles for Menin and KMT2A/B in modulating activating H3K4me3 versus repressive H3K27me3 at bivalent promoters to regulate gene activation.

A meta-analysis of genome-wide association study data from 77,418 individuals of East Asian ancestry with type 2 diabetes identifies novel variants associated with increased risk of type 2 diabetes.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Epigenetic markers are potential biomarkers for diabetes and related complications. Here, the authors identify CpG sites associated with kidney function and its subsequent decline using both single-site and multisite analyses, which are shown to have functional significance in the kidney.

Platelet factors transfer the benefits of young blood to the ageing brain in mice through CXCR3, which mediates the cellular, molecular and cognitive benefits of systemic PF4 on the aged brain.

Treatment of patients with metastatic salivary gland cancer with anti-PD-1 and anti-CTLA-4 led to encouraging clinical benefit in certain histologic subtypes, with translational analyses showing pre-existing T cell clonal expansion in responding tumors.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

In a prospective international cohort of 1,127 patients with non-small-cell lung cancer and ctDNA-guided therapy, ctDNA detection was associated with shorter survival, independently of clinicopathologic features and metabolic tumor volume.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Daniel Gudbjartsson and colleagues report a genome-wide association study for atrial fibrillation, a condition associated with increased risk of stroke. They report a variant in ZFHX3 associated with atrial fibrillation as well as ischemic stroke.

The genetic variation of LukAB toxin among S. aureus clonal complexes determines its binding to different host receptors and influences staphylococcal pathogenicity.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cancer. In this Perspectives article, Xilin Yang and colleagues discuss risk factors (subphenotypes) for cancer in Chinese patients with T2DM, which can lead to drug-subphenotype interactions. The authors also propose plausible biological links between T2DM and cancer and underlying the drug-subphenotype interactions.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

Improving recombinant protein expression and stabilization remains a significant challenge. Here, the authors engineer Archaeoglobus fulgidus ferritin as a thermostable exoshell to provide steric accommodation and charge complementation for recombinant proteins, which can improve yields by 100 fold.

Bhattacharjee and Schaeffer et al. map exclusive breastfeeding (EBF) in 94 low- and middle-income countries (LMICs), finding increased EBF practice and reduced subnational variation across the majority of LMICs from 2000 to 2018. However, only six LMICs will meet WHO’s target of ≥70% EBF by 2030 nationally, and only three will achieve this in all districts.

High aspect ratio nanomaterials enable efficient delivery of DNA into mature plant cells in a species-independent and non-integrating manner for plant genetic engineering applications.

Following a wide-ranging review of studies, reports and policies about nature’s multiple values, combinations of values-centred approaches are proposed to improve valuation of nature, address barriers to uptake in decision-making, and make transformative changes towards more just and sustainable futures.

The mechanisms underlying neuron specification and maturation are unclear. Here the authors provide an integrated epigenomic and transcriptomic analysis of mouse and marmoset neocortical neuronal classes. Pan-neuronal programs active during early development are more evolutionary conserved but not neuron-specific, whereas pan-neuronal programs active during later stages of maturation are more neuron- and species-specific.

Here, Imamuraet al. conduct meta-analysis of genome-wide association studies to identify novel susceptibility loci for type 2 diabetes (T2D) in the Japanese population. By doing so, this study shows that both ethnicity-specific and ethnically-shared genetic loci can contribute to T2D risk.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

As the most common cardiac arrythmia, atrial fibrillation is of interest to physicians, and has recently been shown to have genetic components. Gudjbartsson et al. have conducted a genome-wide association scan in populations from around the globe, and find a strong link to a gene involved in early heart development. This gene, PITX2, could be a candidate for therapeutic intervention.

A large empirical assessment of sequence-resolved structural variants from 14,891 genomes across diverse global populations in the Genome Aggregation Database (gnomAD) provides a reference map for disease-association studies, population genetics, and diagnostic screening.

Multi-nucleotide variants (MNV) are genetic variants in close proximity of each other on the same haplotype whose functional impact is difficult to predict if they reside in the same codon. Here, Wang et al. use the gnomAD dataset to assemble a catalogue of MNVs and estimate their global mutation rate.

A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.

Yoon Shin Cho, Mark Seielstad and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes in individuals of east Asian ancestry. They identify eight new loci associated with type 2 diabetes.