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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.

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.

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.

LINE-1 retrotransposons are implicated in aging, but their role in cardiac aging specifically is not well understood. Here the authors show that LINE-1 expression rises in mouse hearts with age. Genetic LINE-1 derepression is accompanied by cGAS–STING activation and cardiac dysfunction, while pharmacological inhibition of LINE-1 or STING improves cardiac function in aged mice.

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

The existence of a long-lived, prethermal regime in many-body systems with tunable heating rates, driven by structured random protocols, is observed using a 78-qubit superconducting quantum processor.

Calcium entry into mitochondria couples neuronal activity to energy supply, but whether boosting this drive can enhance brain function has remained unclear. Vishwanath et al. now demonstrate that tuning mitochondrial calcium extrusion enhances ATP production and improves cognitive performance in flies and mice, paving the way for a new paradigm of systems neurometabolism.

Paired electrolysis converts industrial SO₂ directly into valuable cyclic sulfite esters, turning a common pollutant into useful chemicals. Mechanistic studies reveal key intermediates, offering a sustainable and versatile platform for green organosulfur synthesis and pollutant valorization.

YTHDC2 is a promising therapeutic target, but lacks potent inhibitors. Yang et al. develop a deep learning-based molecule generator EPMolGen. Using this model, they discover a potent, selective, and cell-active small molecule inhibitor of YTHDC2.

Plasmonic nanocavities enable universal detection of layer-breathing modes in two-dimensional materials via plasmon-enhanced Raman spectroscopy, overcoming the limit of weak electron-phonon coupling or Raman inactivity, and delivering a quantitative framework for interlayer coupling analysis.

Charge recombination of perovskite nanocrystals is crucial for their optoelectronic performance. Here the authors develop a continuous-wave-photoexcitation platform to study their time-resolved photoluminescence under operational conditions.

The oxygen evolution reaction enables many clean energy technologies, but most acid-unstable catalysts still block deployment. Here the authors report a temperature dependent mechanistic evolution in RhRu3Ox that links reaction pathways to stability, enabling durable acidic water electrolysis.

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.

By resonant excitation of an InAs quantum dot embedded in a microcavity, a deterministic single-photon source is demonstrated. Single-photon purity of 0.9795(6), photon indistinguishability of 0.9856(13), and an overall end-to-end efficiency of 0.712(18) are simultaneously obtained.

Allogenic mesenchymal stem cells are engineered with three mRNAs to bind to multiple myeloma B cells while activating T cells for cancer therapy.

The photochemical transformations of aryl thiols to other functional groups have been scarcely explored. Here the authors present a carboxylation of aryl thiols using 1 atmosphere of CO₂ under photoirradiative conditions, a methodology which can be extended to the degradation of polyphenylene sulfide.

A study of millions of couples shows spouses often share psychiatric disorders. This pattern is consistent across cultures (Taiwan and Nordic countries) and has persisted for generations, impacting how these disorders are inherited.

Huang and colleagues report that TIM4–AMPK signaling induces downregulation of the mitochondrial HSP90 chaperone TRAP1 in tumor-associated macrophages, thereby enhancing their immunoinhibitory function and promoting immune evasion and tumorigenesis.

The insertion of thin layers of cobalt can stabilize β-tungsten under back-end-of-line thermal constraints, allowing a 64-kb spin–orbit torque magnetic random-access memory to be fabricated that offers a spin–orbit torque switching of 1 ns, data retention of more than 10 years and a tunnelling magnetoresistance of 146%.

Molecular ferroelectric crystals hold promise in data storage applications, yet their preparations by maximizing molecular polarization are challenging. Here, Youet al. report quinuclidinium periodate with six rotation axes and grow them in macroscopic ferroelectric thin films via a solution process.

Molecular recognition is an important biological process where guest and host molecules interact through non-covalent bonding. Yeet al. show that this can be sensed by the dielectric and ferroelectric signals of the final complexes in a series of metal-coordination compounds with different diol molecules.

Mechanically locked molecules provide interesting topological structures and can present challenging synthetic targets. Here the authors report the synthesis of mechanically self-locked molecules, including chiral endo-spirobicyclics containing multiply interlocked rings within a single molecule.

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.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Oxidative carbonylation using CO/O₂ is an attractive strategy to construct carbonyl compounds, but the explosive limit of the gas mixture hampers its application. Now, this safety issue is overcome in the aminocarbonylation of alkynes by replacing the external oxidant O₂ by electrochemistry facilitating a mild and safe reaction.

Alcohol oxidation to carbonyl compounds is a very useful functional group transformation in organic synthesis. Here, the authors perform the direct electrochemical oxidation of various alcohols to the corresponding ketones in a continuous-flow reactor without external oxidants, base or mediators.

Layers of transition metal dichalcogenides (TMDs) are generally formed by covalently bonded atoms, enabling mechanical exfoliation only in the out-of-plane direction. Here, the authors show the fabrication of fractional 2/3-layers of WTe₂ and other TMDs by applying local scanning tunneling microscopy tip pulses and controllably removing the topmost chalcogen atoms.

Electronic wound bandages have to balance conformability and wound healing properties. Here, the authors develop a smart patch (iSAFE) using biomaterials with bioelectronics to facilitate permeability with waterproofing. This achieves intelligent wound management with real-time wound monitoring and active therapy.

Tergaonkar and colleagues identify a noncanonical interaction between the NF-κB transcription factor family member p52 and the ETS family member ETS1. They find that the p52–ETS1 complex is required for splenic germinal center B cell formation and T cell-dependent antibody responses.

Quantum information cannot be copied, posing challenges for long-distance communication due to signal losses. Here the quantum relay architecture using a single-photon source enhances the signal-to-noise ratio of quantum information transmission.

Limited whole genome sequencing (WGS) of Asian populations results in a lack of representative reference panels, hindering imputation of Asian ancestry-specific genetic variants. Here the authors use WGS data from 11,067 individuals across 17 Asian countries to create a new reference panel which shows improved imputation accuracy for South Asian populations.

Isotopic analysis of basalt clasts returned from the Moon by the Chang’e-5 mission indicates that the rocks were derived from a mantle source that lacked potassium, rare-earth elements and phosphorus.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Akincilar, Fidan et al. report a conserved role for telomerase reverse transcriptase in regulating inflammation via the cGAS–STING nucleic acid-sensing pathway in myeloid cells, independent of its telomerase activity.

Chemodynamic therapy (CDT) uses Fenton chemistry to covert hydrogen peroxide in cancer cells to toxic hydroxyl radicals, but endogenous hydrogen peroxide is insufficient to drive sustainable CDT. Here, the authors report a water oxidation CoFe Prussian blue nanoframe to provide sustained, external energy free self-supply of hydroxyl radicals for CDT.

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 O-alkylation of tertiary alcohols with racemic tertiary electrophiles to access chiral hindered dialkyl ethers has remained elusive. Now this synthetic challenge has been accomplished by copper-catalysed C–O cross-coupling between tertiary haloamides and alcohols using designed ligands.

Biofilm formation enhances bacterial survival and antibiotic tolerance. Here, the authors show that metabolic exchanges between the inner and outer regions of biofilms contribute to antibiotic tolerance and to survival of nutrient-starved cells in the biofilm interior.

Polyploidy and subsequent post-polyploid diploidization (PPD) contribute to evolutionary success of plant species. Here, using 11 genomes from all nine subfamilies of Malvaceae as an example, the authors provide evidence to support the “polyploidy for survival and PPD for success” hypothesis.

De la Rosa et al. developed an in vivo CRISPR screening system to dissect macrophage regulation in multiple sclerosis models, revealing key cytokine signaling pathways that control myeloid cell behavior in neuroinflammation.

Amino acids availability is normally a limitation for protein synthesis and can determine cancer progression and therapy response. Here, the authors show that MYC-associated cancer has a dependency on tryptophan not because of translation regulation, but Indole 3-Pyruvate synthesis.