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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.

K11/K48 branched ubiquitin chains regulate protein degradation and cell cycle progression. Here, the authors report the structural basis of how such a branched ubiquitin chain is recognized by the human 26S proteasome, revealing a multivalent binding mode that underlies selective recognition.

This study identifies BAG3 as a conserved immune regulator in plants and demonstrates that its cleavage by metacaspase 4 triggers cell death and antiviral defense, offering a potential strategy for engineering virus-resistant crops.

Existing Moiré materials are mostly van der Waals heterostructures. Here the authors show that hydrogen-bond adaptability allows spontaneous formation of twisted bilayer ice at magic angles in 2D confinement, establishing a new class of Moiré materials.

The authors develop a low carbon cement-based material which exhibits hierarchical structure with low density (0.75 g cm⁻³), high specific compressive strength (344 (kN m⁻²)/(kg m⁻³)) and fracture toughness (4865 kJ m⁻³).

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

The synthesis of heavily substituted chiral cyclopropanes presents a significant challenge in organic chemistry due to the inherent strain and steric congestion of these three-membered rings. Here, the authors report a highly enantioselective intramolecular cyclopropanation of trisubstituted alkenes via a sulfoxonium-Rh-carbene intermediate, resulting in the formation of highly congested penta-substituted chiral cyclopropanes.

The genetic basis underlying resistance to Sclerotinia stem rot (SSR) in oilseed rape remains elusive. Here, the authors identify BnaA07.MKK9 as a pivotal regulator of SSR resistance in oilseed rape by GWAS, providing new insights into plant defense mechanisms against necrotrophic pathogens.

R-loops are DNA-RNA hybrids that can cause genome instability if not properly controlled. Here, the authors show that the RNA helicase Brr2 prevents harmful circRNA-associated R-loops, thereby safeguarding transcription and cell division.

Antiferromagnets have negligible stray magnetic fields and are robust against magnetic perturbations, making them ideal for high-density magnetic memory. However, these features make electrically switching the Néel vector challenging. Here, Guo, Lin and coauthors demonstrate layer-dependent electrical switching of a van der Waals antiferromagnet.

Bicyclo[n.1.1]alkyl skeletons are of significant interest as bioisosteres of phenyl groups for lead drug modification. Common strategies for their synthesis utilize bicyclo[1.1.0]butanes, wherein the electron-withdrawing groups serve solely as activating groups to facilitate the cleavage of the bridged σ bond, leading to ring expansion by an insertion manner. Here, the authors utilize ketones in bicyclo[1.1.0]butane as both activating and reacting groups, promoting a tandem nucleophilic addition/intramolecular Horner-Wadsworth-Emmons olefination process by an exo-cyclic annulation manner.

Spatiotemporal hierarchical modelling of geological sea-level proxies and tide gauge data suggest that the modern global mean sea-level rise rate since 1900 has exceeded any century over at least the past four millennia, breaking the long-term stability observed in southeastern China.

Liquid metal inks are promising for flexible electronics, but it is challenging to produce liquid metal inks due to surface tension and density. Here, the authors design a liquid metal-cryogel system to increase liquid metal concentration.

Lipid nanoparticles are the gold standard for mRNA delivery but suffer from low loading capacity. Here, the authors report on the use of manganese ions to form mRNA rich cores within lipid nanoparticles which increased mRNA loading, reducing the lipid needed and increasing transfection and immune response in vivo.

In multiple sclerosis, smoldering inflammation contributes to clinical progression. Using multi-omics data, here the authors link chronic inflammation to senescence-like processes and cellular network changes, suggesting a potential therapeutic target.

Yang et al. apply high-throughput structure probing approaches to characterize the secondary structure throughout the SARS-CoV-2 WT and VOC genomes, uncovering an ultra-long-range RNA-RNA interaction that directly binds ADAR1 to promote viral fitness.

An analogue matrix solver that combines low-precision matrix inversion and high-precision matrix–vector multiplication can be used to solve inversion problems involving 16 × 16 real-valued matrices with precision comparable to 32-bit floating point.

Anode catalysts in proton-exchange-membrane water electrolyzers usually trade activity for stability. Here, the authors report an electronic-structure-tuning strategy that modulates the metal–oxygen redox behavior of RuO₂, yielding a catalyst that is both highly active and durable.

Distinguishing glioblastoma and primary central nervous system lymphoma (PCNSL) remains challenging due to their overlapping pathology features. Here, the authors develop a computational tool, PICTURE, for differentiating similar pathological features enabling improved diagnosis of CNS tumours.

Static cloaking and camouflage remain a central challenge in mechanics. Yang et al. introduce an irregular growth strategy with limited building blocks of varying stiffness, enabling complex void structures for effective cloaking and mutual camouflage under diverse loading.

Stereoselective access to either E- or Z-cyclic alkenes remains a formidable challenge. Now it has been shown that Pd-catalysed formal cycloaddition can lead to the construction of 11-membered heterocyclic alkenes. Ligand-induced divergent catalysis gives controlled access to either E- or Z-trisubstituted cycloalkenes starting from common terminal alkene substrates.

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.

High-resolution satellite data enables a unique verification of national methane emissions worldwide. Global estimates are 63 Tg a⁻¹ for oil-gas, 30% higher than the UNFCCC reports due to under-reporting by four largest emitters, and 33 Tg a⁻¹ for coal, consistent with previous estimates.

Strain engineering is effective in modulating catalyst activity. Here, authors report a high-dimensional biaxial strained dichalcogenide catalyst to unlock inner metal sites, which accelerates sulfur redox kinetics and enables lithium–sulfur pouch cells with increased capacity and cycling stability.

Simultaneous profiling of spatial transcriptomics (ST) and metabolomics (SM) offers a novel way to decode tissue microenvironment heterogeneity. Here, the authors present SpatialMETA, a conditional variational autoencoder-based framework designed for the integration of ST and SM data.

Lo and colleagues report that double-positive thymocytes from neonates express less Zap70 and show reduced Ca^2⁺/NFAT signaling compared to double-positive thymocytes from older thymi. This diminished Ca^2⁺ signaling alters negative selection for self-reactive TCRs, resulting in a cell-intrinsic temporal window for regulatory T versus conventional T cell development in the thymus.

Here, the authors demonstrate that the Hand2 transcription factor partitions into the cell nucleolus to activate pacemaker-specific gene programs by accessing specific binding sites residing within repressive nucleolar heterochromatin.

Diabetes can contribute to pancreatic cancer development as well as be a consequence of it. Here, the authors report that diabetes-induced senescence of endothelial cells promotes pancreatic cancer progression.

Anti-TSLP biologics have shown promise for the clinical treatment of type 2 respiratory disease. Here the authors present a clinical trial of CM326, a monoclonal antibody against TSLP, and show the clinical effects in patients with eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP), who present with type 2-dominant inflammation.

Xu et al. report a Pockels photonic memory by integrating ferroelectric field-effect transistor with lithium niobate on insulator micro ring resonator. Through the manipulation of ferroelectric domains and the Pockels effect, the device achieves energy consumption at fJ/state level.

This study introduces a kinetic decoupling–recoupling strategy to overcome kinetic limitations in plastic recycling. A tandem catalytic reactor, utilizing zeolite catalysts, converts polyethylene into ethylene and propylene with yields of up to 79%, offering a promising pathway toward efficient closed-loop recycling of polyolefins.

Yin, Lin, Cai, Nie and colleagues report phase separation of ERCC6L2 as a mechanism that regulates RNF138-mediated ubiquitination and degradation of CtIP, thereby modulating DNA end resection and treatment response to ATM inhibitors in cancer.

Thermal lepton pairs are ideal probes for the temperature of quark-gluon plasma. Here, the STAR Collaboration uses thermal electron-positron pair production to measure quark-gluon plasma average temperature at different stages of the evolution.

Parasitoid wasps are reared and released as biocontrol agents to manage aphids and protect crops. Here, the authors use genomes from 542 wasps to show that, in spite of wide scale release of low-diversity captive individuals, diversity in wild populations is maintained.

Proteins in the fungal plasma membrane are key antifungal targets but their native structure and spatial distribution are poorly understood. Here, Jiang et al. use proteomics and cryo-electron tomography to investigate the organisation of membrane proteins in the fungal plasma membrane and how this is affected by antifungal drugs.

Rapeseed production is often threatened by drought stress. Here, the authors report transcription factor BnaA9.NFYA7 negatively regulates rapeseed drought tolerance through ABA signal transduction pathway via feedback inhibition of the expression of BnaABF3/4s-related genes.

The authors report spectral hole burning with a record hole lifetime in a Er³⁺ doped scheelite crystal CaWO₄ at mK temperatures. This can benefit applications in classical and quantum information processing.

Here, Ni-anchored Ru/RuO₂ heterostructure nanosheets serve as CO-tolerant hydrogen oxidation catalyst delivering a peak power density of 1.76 W cm^-2, along with long-term stability in an alkaline exchange membrane fuel cell operating under H₂/Air conditions.

A significant challenge in modern drug development is the comprehensive profiling of covalent inhibitors. Here, the authors develop COOKIE-Pro, an unbiased method for quantifying the binding kinetics of irreversible covalent inhibitors on a proteome-wide scale.

The Macaque Biobank initiated by Zhang et al. provides a comprehensive genetic and phenotypic characterization of Chinese rhesus macaques (CRMs). This resource enhances our understanding of the genetic diversity of CRMs and holds potential for biomedical research.

Li et al. report a high-order spatiotemporal processing vision sensor based on vdW phototransistors, leveraging Triplet-spike-timing dependent plasticity to extract the high-order correlation information, rendering spiking neural network for confusing object classifying and dynamic tracking.

A scalable strategy to assemble anisotropic GO and MXene membranes with pH-tuned edge functionalization enables programmable bending via thermo-responsive water release, with applications in soft robotics and adaptive bionic architecture

Small proteins (<50 kDa) are difficult to resolve by cryo-EM due to low signal-to-noise ratios and alignment challenges. Here, authors engineered conformationally rigid antibody fragments (Rigid Fabs) enabling high-resolution cryo-EM structures of small (~20 kDa) proteins like KRAS.

Immune checkpoint blockade is an effective therapy in melanoma, but response is highly variable between patients. Here, the authors show that Inducing co-stimulatory immune checkpoint CD137L expression in melanoma cells enhances T cell-mediated anti-tumor immunity.

Broad-spectrum vaccines have been proposed as a tool for rapid response to emerging infectious disease threats and are in pre-clinical development. Here, the authors use mathematical modelling to assess the potential impacts of broadly protective sarbecovirus vaccines for a hypothetical “SARS-X” outbreak.

Protein secondary structures are visualized in situ by hyperspectral stimulated Raman scattering microscopy, revealing disordered to ordered changes in protein phase separation and structural heterogeneity of subcellular aggregates in live cells.

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.

How replication stress affects nuclear integrity is not fully understood. Here, the authors report that replication stress induces DNA damage and nuclear envelope reassembly defect during mitosis, which is suppressed by DNA polymerase theta mediated end joining.