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In targeted protein degradation, a degrader molecule brings a neosubstrate protein proximal to a hijacked E3 ligase for its ubiquitination. Here, pseudo-natural products derived from (−)-myrtanol—iDegs—are identified to inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs prime apo-IDO1 ubiquitination and subsequent degradation using its native proteolytic pathway.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

The authors report long-lived pump-induced conductivity suppression in metallic Ti₃C₂ MXenes using ultrafast terahertz and reflectance spectroscopy. The effect is attributed to strong photothermal heating and slow heat dissipation.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Multi-trait genome-wide analyses identify variants associated with comorbid lung diseases. Polygenic scores leveraging shared components of heritable risk improve prediction of asthma, chronic obstructive pulmonary disease and lung cancer in a multi-ancestry cohort.

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.

Taveneau et al. leverage artificial-intelligence-driven protein design to create inhibitors that control RNA-targeting enzymes in cells, revealing a strategy to rapidly design off-switches for RNA-editing systems.

A wearable paper-based microfluidic device tracks cortisol in sweat via gold nanoflower colorimetric assays and captures circadian rhythms, stress responses and jet lag disruptions.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

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.

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here the authors report the results of a phase II clinical trial of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in RMC, associating the activation of a myeloid mimicry program in tumor cells to the rapid disease progression and hyper-progression observed in treated patients.

How cells respond to replication-derived DNA damage that is carried over into mitosis is not well understood. Here, the authors show that CIP2A with TOPBP1 mediates the mitotic recruitment of the SLX4/MUS81/XPF nuclease complex to replication stress-induced DNA lesions to maintain genome integrity.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

This study reports the mouse islet atlas, a curated resource integrating scRNA-seq data of over 300,000 cells from nine datasets, covering pancreas development, homeostasis and disease states.

Central charge, a key quantity in conformal field theories, is crucial in the study of critical phenomena, yet its measurement has remained elusive. Here, the authors extract the central charge of several quantum critical models by accurately preparing their ground states on a superconducting quantum processor.

A groundbreaking study reveals how physical confinement triggers ferroptosis. It finds the nucleus acts as a mechanosensor, orchestrating Drp1 and cPLA2 that leads to mitochondrial dysfunction and ultimately, cell death.

Feng et al. report a dynamic template-assisted strategy for depositing perovskite nanowire arrays across areas 12 times larger than the template itself, on diverse substrates. Large-area pixelated photodetectors with a responsivity of 1660A W⁻¹, detectivity of 3.9E14 Jones, and linear dynamic range of 160.3 dB are achieved.

Allosteric transcription factors (aTFs) are promising tools for environmental and human health monitoring. Here the authors develop a multi-objective, machine learning-guided method to engineer an aTF-based portable diagnostic for environment sensing of lead in drinking water at the legal limit.

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.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

This study shows that optimally sized nanocarriers reach Duchenne muscular dystrophy muscle primarily through transcytosis, where they can deliver tamoxifen to improve muscle health and strength in mice.

Ubiquitination is a versatile modification system in eukaryotic cells. Here, the authors unveil that the ubiquitin ligase HUWE1 can modify drug-like small-molecule substrates, beyond proteins. This discovery may be harnessed to develop specific tool substrates or inhibitors of HECT-type ligases.

Single-layer graphene, owing to its impermeability, is a promising candidate to prevent transmembrane ion transport. Here, the authors report a covalent functionalization method that enables centimeter-sized graphene to function as a proton exchange membrane in a direct methanol fuel cell.

Genome-wide CRISPRi screens for modulators of androgen receptor (AR) protein levels using live-cell quantitative endogenous AR fluorescence reporters identify PTGES3 as a new regulator of AR stability and function in prostate cancer.

Using lipid nanoparticle delivery of mRNAs to the liver in aged mice, T cell function and declining immune cues can be restored.

BARCODE is an open-access software that automates high throughput screening of microscopy video data to produce a unique fingerprint or ‘barcode’ of performance metrics that enables optimization and accelerates discovery of soft, active materials.

Water and sediments in artificial reservoirs face increasing pollution from polycyclic aromatic hydrocarbons, and effective management depends on considering distinct chemical and regional patterns, according to analysis of a global dataset.

SCEP3 is a new synaptonemal complex protein that prevents clustering of crossovers during meiosis in Arabidopsis, so that every pair of homologous chromosomes receives at least one ‘obligate’ crossover.

Quantum lock-in detection (QLID) is crucial for extracting oscillating signals from noise, while quantum entanglement is vital to surpass the standard of quantum limit in precision measurement. Here, the authors experimentally realise entanglement-enhanced QLID using two trapped ions, achieving frequency measurement precision at the Heisenberg limit and demonstrating an improved inverse-quadratic temporal scaling.

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.

Structure-specific endonucleases play an important role in several DNA repair pathways. Here the authors present structures of the endonuclease XPF-ERCC1 in complex with SLX4, SLX4IP, and DNA. Combined with functional analysis, these results provide insight into the mechanisms of XPF-ERCC1 recruitment and activation during DNA repair.

Microwave observations of Jupiter’s moon Europa reveal subsurface properties of the ice shell covering a purported global ocean. The shell is 29 ± 10 km thick, with fractures or pores a few centimetres across that extend hundreds of metres deep.

Electronic, health-care and energy applications largely rely on miniaturized structures, the fabrication of which, although technically beneficial, is energy intensive and requires the use of hazardous chemicals. Now, research shows an effective bioinspired strategy to reduce such environmental impacts while retaining the benefits of microfabrication.

After a long hiatus, a recent paper identifies the molecular basis of Mendel’s remaining three traits and demonstrates that the genes concerned are major contributors to phenotypic variation in pea.

High-throughput chemical ligand discovery is challenged by false positives. Here, authors introduce a scalable enantioselective affinity-selection mass spectrometry approach for proteome-wide ligand discovery with high sensitivity and selectivity

Employing intrusions with varying SiO₂ to represent the different layers of the continental crust (CC), a bulk CC δ^98/95Mo of −0.116 ± 0.011‰ is established, pointing to long-term mass balance between crustal growth and destruction.

Breast cancer cells interact with neighbouring adipocytes, but the mechanisms are not fully understood. Here, the authors show that triple-negative breast cancer (TNBC) cells transfer cAMP through gap junctions, activating lipolysis in tumour-associated adipocytes to promote TNBC growth.

DNA methylation is a critical component for repression of fetal haemoglobin in adult blood cells. Removing DNA methylation from the fetal haemoglobin promoter effectively upregulates the gene, opening avenues for the treatment of blood disorders.

Three BRAF inhibitors are used to treat melanoma and colorectal cancer. Here, the authors demonstrate that these drugs bind and activate the protein kinase GCN2, a previously unappreciated off-target effect that may modulate tumour cell responses.

Applying high pressures to a crystalline material usually dramatically alters its properties. Feng et al.now demonstrate, however, that antiferromagnetism in gadolinium-silicon is robust even under pressures that are large enough to compress the volume of the crystal by one seventh.

China’s crowded coasts must balance seafood demand with conserving migratory shorebirds that rely on tidal flats along the East Asian–Australasian Flyway. This study suggests that well-managed mariculture feeds shorebirds and limits overharvest, benefiting seafood production and biodiversity.

Dextran sulfate sodium is a colitis inducer that stimulates a ROS–Src–IP6K2 signaling axis to generate 5-IP₇, which sterically inhibits PI(4,5)P₂ phosphatases to promote PI(4,5)P₂-mediated E-cadherin endocytosis and epithelial junction breakdown.

Large-scale combinatorial perturbation screens are important to identify genetic interactions and synthetic lethal gene pairs. Here, Burgold et al. present a next-generation dual guide system that allows library-scale screening across hundreds of thousands of genetic interactions.

Pollen vegetative cells undergo epigenetic reprogramming, including DNA demethylation. In these cells, the authors show that the methyl readers MBD5 and MBD6 help prevent excessive demethylation by antagonizing MBD7-mediated active demethylation.

In this study, authors show that the El Niño–Southern Oscillation (ENSO) drives 63% of dengue case variation via rising local temperatures. They estimate future cases may increase by 39–82% due to increasing ENSO events under human-induced warming.