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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.

Spatial CRISPR screens probe the functional impact of mutations within intact tissues. Here, authors present Spatial Perturb-Seq, a technology that localizes CRISPR perturbations and cell identities in situ, uncovers communication between cells, and shows how genes act beyond their cellular borders.

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.

This paper identifies CD117 as a marker of a rare adult mouse prostate stem cell population, and uses this marker in combination with others to isolate single cells that can generate a prostate upon transplantation in vivo. These prostate stem cells also exhibit long-term self-renewal.

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.

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.

Transcriptional dysregulation contributes to tumor progression. Here the authors show that transcriptional complex NELF interacts with SLUG, and co-opts KAT2B, to promote the expression of epithelial-mesenchymal transition (EMT) and stemness-associated genes in breast cancer.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

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.

Intelligent artificial tactile system for neurorobotics remains challenging. Here, Chen et al. developed an artificial organic afferent nerve to implement slip recognition and prevention actions by learning the real-time spatial information of directional touch.

Perez, Kimoto, Rajakumar and colleagues present a fast and accurate DNA sequencing method that reads canonical and non-canonical bases using AI and nanopore technology. The approach enables an expanded genetic alphabet for data storage, nucleic acid therapeutics and synthetic biology.

Hypoxia and epithelial-to-mesenchymal transition promotes cancer metastasis. Here the authors show that Daxx inhibits hypoxia-induced lung cancer metastasis by attenuating Slug-mediated transcriptional repression of epithelial-like markers that in turn cause cells to exhibit low invasiveness.

Clinically significant genetic variation in Asian populations is under-characterized. Here, the authors show the diversity in prevalence and spectrum of human disease and pharmacogenetic variants in a multi-ethnic Asian population.

This study identifies four distinct polycystic ovary syndrome (PCOS) subtypes using unsupervised clustering analysis on data from 11,908 women and validated across five diverse cohorts. The subtypes show unique clinical features and suggest that subtype-specific management could enhance treatment precision for PCOS.

Structural variations (SV) contribute to inter-individual variability. Here, the authors describe a first-generation multi-ancestry Asian SV catalogue containing 73,035 SVs from 8392 Singaporeans to provide insights into Asian SV diversity.

The authors showcase a photonic tensor core in TFLN platform that achieves a computational speed of 120 GOPS for neural networks, with capabilities of in-situ training that support exciting prospects of negative number multiplication. The tensor core can efficiently process 112  × 112-pixel images, potentially scaling up AI tasks and offering nanosecond latency without needing a digital processor.

Here, the authors show a causal role for gut bacteria-derived metabolites tryptamine and phenethylamine in contributing to insulin resistance and the development of metabolic syndrome in patients with irritable bowel syndrome and type 2 diabetes.

In this study, the authors report that anionic nanoplastics can harness the paracellular space of endothelial cells and puncture blood vasculature ex vivo and in vivo, thereby entailing new environmental and health implications.

In order to design cancer immune therapies, it is important to understand how tumours evade the immune response that is mounted against them. Authors here analyse the distribution and properties of immune cells in hepatocellular carcinoma and describe a progressive tumour-immune co-evolution programme from early to late stage cancer.

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.

Electrochemical conversion of nitrate into ammonia offers a method for mitigating nitrate pollution in water. Here the authors report the electrochemical nitrate-to-ammonia conversion using high-entropy oxide Mg_0.2Co_0.2Ni_0.2Cu_0.2Zn_0.2O and find that the Co spin states are crucial for synergistic ammonia generation.

Aberrant hypertranscription in cells can affect development and disease. Here, the authors show that DNA topoisomerase I prevents hypertranscription; not through its catalytic function, but through a DNA binding mechanism.

Stable anti-ambipolar organic materials are limited, thus preventing the design of integrated, tunable, and multifunctional neuromorphic systems. Here, the authors report a small form factor neuromorphic circuit based on organic anti-ambipolar materials, mimicking the pre-processing functions of the retina.

Qing Lan and colleagues report the results of a genome-wide association study of lung cancer in never-smoking women from Asia. They identify three new susceptibility loci and confirm three other previously reported associations.

Bleeding complications limits the use of effective antithrombotics therapeutics. Here, the authors developed next-generation direct thrombin inhibitors with low bleeding risks as safe peri-percutaneous coronary intervention anticoagulants when used in combination with antiplatelets.

Intratumoural heterogeneity is a feature of liver cancer. Here, the authors demonstrate that heterogeneity exists at the immune cell level in liver cancer and show that tumours with high intratumoural immune heterogeneity demonstrated an immune suppressive microenvironment, which was associated with tumour evolution and a poor prognosis.

Ito et al. present CoVFit, an AI model that predicts variant fitness (transmissibility) from spike protein sequences alone. They further demonstrate its utility in forecasting viral evolution via single amino acid mutations.

Mitochondrial dynamics change during ageing, with larger mitochondria and altered protein import in older animals. Here the authors show that Dosmit protein mediates mitochondrial morphology with Rab32 by inducing double-membraned vesicles that regulate protein trafficking into mitochondria.

Polymer-based bulk-heterojunction solar cells have shown some of the highest photoconversion efficiencies in organic photovoltaics, but polymer polydispersity impacts their performance. A small-molecule donor is now reported that enables the fabrication of bulk-heterojunction devices with low acceptor content and photoconversion efficiencies of up to 6.7%.

Biomarkers in biofluids are widely used for medical diagnosis, but their use is limited by accessibility. Here the authors present a stretchable wearable sensor allowing in situ detection of solid-state biomarkers on human skin, hence avoiding biofluid acquisition.

This analysis provides a collection of sequencing datasets generated from long-read and short-read RNA sequencing, serving as a valuable resource for transcriptome profiling.

Mito-SEPs are small peptides that can modulate oxidative metabolism in mitochondria. Here the authors show that C15ORF48 encodes a mito-SEP, MOCCI, capable of altering mitochondria respiration to suppress inflammation, while C15ORF48 3’ untranslated region also contains a miRNA, miR-147b, that synergizes with MOCCI to modulate host anti-viral responses.

Folate receptor-α (FRα) is overexpressed in many cancer cells and is therefore an important therapeutic target: here the X-ray crystal structure of folate-bound FRα is presented, revealing details of the ligand-binding pocket that may be useful in the development of small-molecule inhibitors for anticancer therapy.

This Perspective article discusses Singapore’s efforts to implement a National Precision Medicine Strategy through the integration of genomic, clinical and lifestyle data of up to one million Singaporean individuals.

Hu, Tan, Chia et al. identify negative elongation factor A as one of the earliest drivers of the mouse embryonic 2-cell-like state through interaction with Top2a, which mediates Dux expression.

Genomic and transcriptomic analysis of lung adenocarcinoma (LUAD) in Asia indicates that Asian LUADs have fewer mutations, lower driver prevalence and fewer copy number alterations than European LUADs.

Accomplishing complex cognitive tasks such as speech recognition calls for artificial intelligence hardware with high computing precision. John et al. propose deep recurrent neural networks based on optoelectronic transition metal dichalcogenide memristors with high weight precision for in-memory computing.

miRNAs can function either as proto-oncogenes or tumour suppressors in several cancers; however their function in tumour initiating cells is unclear. Here, Zhang et al. show that tumour initiating cell-specific miR-1246 and miR-1290 promote lung cancer initiation and metastasis and could serve as prognostic markers.

Cancers often harbor mutations in genes encoding important regulatory proteins, but therapeutic targeting of these molecules proves difficult due to their high structural similarity to their non-mutated counterpart. Here authors show the engineering of T cell engaging bispecific protein able to selectively target cancer cells with a high-frequency mutation in the KRAS oncogene.

Micropatterning of organic semiconductors by electron-beam exposure can be used to create vertical organic electrochemical transistor arrays and complementary logic circuits with densities of up to 7.2 million transistors per cm².

Mutations in the LaminA gene are the second most common inherited cause of Dilated Cardiomyopathy, a major form of heart failure. Here the authors show that disruption of the nuclear protein SUN1 in cardiomyocytes, by AAV mediated transduction of a SUN1 inhibitor, significantly suppress cardiomyopathy progression, providing a potential therapeutic route to treat this disease.