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Excess nitrogen fertilization in maize production harms the environment and society, yet farmers face yield risks when reducing inputs. Using field trials across the US Corn Belt, this study suggests that nitrogen rates can be reduced by 12–16% with minimal yield risk, reducing emissions and leaching.

At single-cell resolution, Tarkhov et al. delineate stochastic and co-regulated components of epigenetic aging, revealing a simultaneous loss of regulation at the epigenetic and transcriptional levels in aging.

The authors in this work present a study with multiplexed gene editing that is used to assess all possible mutations at a native drug binding site. The approach yields data that predicts spontaneous resistance, that aligns with in silico predictions, and that promises to facilitate drug discovery.

Vocal fold cancer tumours lose some of their malignant traits when mechanically stimulated by physiological stretch or vibrations, mimicking the opening and closing of vocal folds and phonation.

Operating a photonic chip that integrates quantum dots with lithium niobate resonators at an exceptional point allows for spontaneous single-photon emission with an exceptional-point-induced transparency window, a squared-Lorentzian line shape or a Fano-asymmetric line shape.

METALoci, a new three-dimensional genome computational tool, reveals a major rewiring of regulatory interactions during sex determination. By combining this method with transgenic models, the authors identify a noncoding regulatory region at the Fgf9 locus and reveal that Meis genes are key regulators of sexual differentiation.

Wang et al. introduce Mac-Diff, a conditional diffusion model with locality-aware attention across modalities, to generate diverse conformational ensembles for unseen proteins, capturing both dynamic flexibility and structural heterogeneity.

GDF15 has been associated with cancer-associated cachexia. Here, the authors show that STK11/LKB1 loss-of-function mutations in non-small cell lung cancer result in an exaggerated integrated stress response culminating in the tumor cell secretion of the cytokine GDF15 promoting cachexia.

The burden of dengue disease in infants has increased in Brazil over the last 25 years. Here, the authors analyse spatiotemporal heterogeneity in disease incidence to characterise the contribution of changing maternal immunity to infant dengue risk.

The lowest-frequency gravitational wave background may be shaped by supermassive black hole binaries that scatter nearby stars or dark matter. In this case, the NANOGrav 15-year dataset favours dense galactic centres with 10⁶ solar masses per cubic parsec.

Quantum fluctuations have been detected in a macroscopic, millimole-scale solid-state spin ensemble without the use of external excitations, enabling non-invasive quantum sensing techniques.

Here the authors compare genetic testing strategies in rare movement disorders, improve diagnostic yield with genome analysis, and establish CD99L2 as an X-linked spastic ataxia gene, showing that CD99L2–CAPN1 signaling disruption likely drives neurodegeneration.

Execution of mRNA cleavage in nonsense-mediated decay remained elusive. The authors show that SMG5 complements SMG6 to form a highly active, composite endonuclease with expanded catalytic center that enables regulated substrate cleavage.

The relocalization of the vacuolar calcium pump Cdt1 to the plasma membrane contributes to fluconazole adaptation in Candida auris.

By using analogue in-memory computing technology to integrate edge computing and wireless communication into a learnable system, communication-aware in-memory wireless neural networks can be created that can adapt to different wireless conditions.

Millions of urban commuters experience daily exposure to subway air. This study characterizes the microscopic properties and formation mechanisms of airborne iron-oxide nanoparticles in subway air, detects their presence in human lungs and confirms their role in mouse pulmonary injury.

Negative regulator of thermotolerance 1 (NAT1) is identified as a negative regulator of thermotolerance in rice through the NAT1–bHLH110–CER1/CER1L module. Modifying NAT1 by targeted gene editing increases wax deposition and enhances thermotolerance in rice.

The SONAR trial showed that the endothelin receptor antagonist atrasentan improves kidney outcomes in patients with type 2 diabetes and chronic kidney disease, though individual responses varied. Here the authors report exploratory analyses of the SONAR trial that identify urinary clusterin as a potential predictor of kidney disease progression and response atrasentan in type 2 diabetes.

Kayama et al. present a blueprint for a national genomic surveillance study that conducts genome sequencing of thousands of strains, integrates standardized quantitative antimicrobial susceptibility testing, and characterizes antimicrobial resistance determinants.

A human spinal cord organoid model can replicate two different types of spinal cord injury and can be used as an in vitro system to evaluate therapeutics and inflammatory reactions to treatments.

The transcription factor ATF4 and its effector lipocalin 2 (LCN2) have a key role in immune evasion and tumour progression, and targeting the ATF4–LCN2 axis might provide a way to treat several types of solid tumour by increasing anti-cancer immunity.

Seed size plays an important role in determining soybean yield. Here, the authors report GmSW17, encoding a homolog of Arabidopsis UBP22 that plays a role in deubiquitination, as a positive regulator of soybean seed width and seed weight through inhibition of the G1-to-S transition by interacting with GmSGF11 and GmENY2.

In a case series of five patients with treatment-refractory antisynthetase syndrome and five patients with treatment-refractory systemic sclerosis, bispecific T cell engagers blinatumomab and teclistamab improved disease activity and were well tolerated.

[n.1.1]Propellanes are versatile precursors to bicyclo[n.1.1]alkane benzene bioisosteres, but heterocyclic variants have eluded synthesis. Now, a unified synthetic strategy has been developed to access hetero[3.1.1]propellanes on multigram scale. Their ring-opening under radical conditions affords a variety of heterobicyclo[3.1.1]heptanes, which are important motifs in drug design.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

The usage of pretrained protein language models (pLMs) is rapidly growing. However, Szymborski and Emad find that pretrained pLMs can be a source of data leakage in the task of protein–protein interaction inference, showing inflated performance scores.

This study shows that contrail avoidance can recover 9% of the global temperature budget by 2050. For every year of delay, the recoverable warming will diminish by 0.6%. This makes inaction (not fuel penalties) the most significant climate risk associated with avoidance.

Werner et al. present the results of the 201 Trial, a 12-week randomized, double-blind placebo-controlled phase 2a study of risvodetinib, in patients with early untreated Parkinson’s disease. Risvodetinib was found to be safe and well tolerated.

The role of the innate immune system in pancreatic cancer is largely unexplored. Here, the authors reveal a targetable cancer cell-intrinsic axis in pancreatic cancer comprising ASC inflammasome complexes that link innate immunity with mitochondrial function and metabolism.

Here the authors identify the fungal effector Hap1 as a key driver of maize leaf tumor growth. Hap1 rewires plant metabolism and the cell cycle via SnRK1 signaling, promoting starch accumulation and cell enlargement.

Therapies combining chemotherapy and immune checkpoint inhibitors have shown limited efficacy in patients with advanced pancreatic ductal adenocarcinoma (PDAC). Here the authors report the results of a pilot phase 1 trial of neoadjuvant modified Folfirinox plus nivolumab in borderline-resectable PDAC, including safety, efficacy and immunological correlates.

Polyamides (PAs) or nylons are types of plastics with wide applications, but due to their accumulation in the environment, strategies for their deconstruction are of interest. Here, the authors screen 40 potential nylon-hydrolyzing enzymes (nylonases) using a mass spectrometry-based approach and identify a thermostabilized N-terminal nucleophile hydrolase as the most promising for further development, as well as crucial targets for progressing PA6 enzymatic depolymerization.

Icosahedral viruses package their genomes into a proteinaceous capsid to near crystalline density. Here, the authors report cryo-EM-based insights into the post-packaging genome positioning, virion assembly and maturation mechanisms in the tailed bacteriophage T4.

Rare coding variants that reduce the activity of a protein can have a beneficial impact on health. Here, researchers identify rare genetic variants in the CHRNB3 gene that associate with reduced cigarette smoking across diverse populations.

In vivo base editing of a causative mutation that leads to the neurodevelopmental disorder Snijders Blok–Campeau syndrome restores protein dosage and ameliorates molecular and behavioural deficits in a humanized mouse model of the condition.

This multidisciplinary response to investigate the large outbreak of unknown febrile illness in the Panzi Health Zone in the Democratic Republic of the Congo in late 2024 suggests that the outbreak was largely associated with malarial cases and concurrent viral respiratory infections.

Conventional type 1 dendritic cells (cDC1) can boost the precursor exhausted T cell population thought to be essential for efficacy of immune checkpoint therapy. Here the authors enhance this cellular network using Flt3L to expand cDC1s and then map the movement of T cells and DCs between tumors and lymph nodes.

In this analysis of biomolecular and archaeological data from a ninth-century BCE mass grave in the Carpathian Basin, Fibiger et al. find evidence for the targeted killing of mostly unrelated women and children, challenging views of prehistoric violence.

Bees are crucial for the maintenance of healthy ecosystems, yet rigorous estimates of their species’ richness are lacking. This study estimates taxonomic gaps for bees around the world and provides a standardised method for occurrence data.

The depiction of crop exposure to heat stress is fundamental for reliably quantifying extreme-heat-induced yield loss and crop failure. Using more than 130,000 subnational yield records, this study estimated spatially explicit extreme degree day thresholds for maize and soybean across major Northern Hemisphere breadbaskets, revealing strong geographic heterogeneity.

Farside ground truth information gathered by Chang’e-6, integrated with orbital and nearside sample data, refines global lunar chemical maps and provides a framework to guide future exploration.

Cobalt-based catalysts are regarded as a potentially cheaper alternative to platinum and chromium systems for the non-oxidative dehydrogenation of propane, although they often feature lower performance. Now mixed-valence Co^0/IIO_x clusters supported on silicalite-1 are identified as a competitive system for this reaction.

Bioactivity benchmarks are key to evaluating and improving methods to predict chemicals’ specific biological activity. Here, the authors find existing benchmarks poorly suit this goal; their assays are often well-predicted simply by counting cells. They propose new guidelines and curated benchmarks.

Trimodal single-cell analysis reveals gene-regulatory architecture in complex tissues.

The factors contributing to the onset of Barrett’s esophagus, a precancerous stage of the highly lethal esophageal cancer, remain elusive. Here, the authors identify inherited mutations in the VSIG10L gene as a key etiologic determinant affecting esophageal biology and facilitating the development of Barrett’s esophagus.

Influenza can cause Acute Necrotizing Encephalopathy (ANE), a rare brain inflammatory disease. This study shows that loss or mislocalisation of RANBP2, as seen with ANE-linked mutations, boosts viral replication and triggers excessive inflammation.

Non-additive effect and trait-trait interactions are often overlooked in current genomic prediction approaches. Here, the authors extend quadratic phenotypic selection index to the genomic domain to enable phenotype-free, rapid-cycle multi-trait selection while capturing genome-wide nonlinear relationships.

Plasma p-tau217 tests used to develop clocks that predict when cognitively unimpaired individuals would develop symptoms of Alzheimerʼs disease.

Drug-controlled DROP-CARs enable reversible extracellular control of CAR T cell function via human-derived protein switches that modulate cell–cell interactions and support dual-antigen targeting as well as logic-gated signaling.

An ion mobility-resolved mass cytometry method for single-cell metabolomics enables multidimensional metabolomic profiling. The approach was used to curate a metabolic single-cell atlas containing 45,603 primary liver cells from aging mice.