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3-Hydroxypropionic acid (3HP) is a top Department of Energy value-added chemical and precursor to bioplastics, yet cost-effective microbial bioproduction remains elusive. Here the authors establish efficient 3HP production in an acid tolerant yeast and validate its financially viability.

From 6,141 Qatari genomes the authors chart structural variants tied to large-scale protein data, biobank traits and everyday health measures. When combined with single nucleotide variants, they find that 1 in 30 participants have a medically actionable genomic finding. The work builds a detailed structural variation reference for Arab ancestries worldwide.

Microbial mutualists could affect plant population persistence under climate change. Here the authors show that fungal endophytes contribute to the population persistence of a grass species by ameliorating drought stress but are more likely to disappear locally under climate variability.

Rare loss-of-function mutations in SETD1A are associated with schizophrenia, but how SETD1A haploinsufficiency leads to disease phenotypes remains unknown. Here, authors show that SETD1A regulates genes at common schizophrenia risk loci regulating genomic stability and synaptic function.

The bacterial protein H-NS prevents costly expression of horizontally acquired genes such as those in Salmonella pathogenicity islands (SPIs), which are essential for infection. Here, Kortebi et al. show that the expression of SPI-1 is associated with Salmonella chromatin remodelling and with the repositioning of this region toward the nucleoid periphery.

Optomechanical crystals are promising building blocks for quantum networks but suffer from thermal mechanical noise. Here the authors demonstrate on-demand conversion of single phonons into high-purity telecom photons with low thermal noise and MHz-scale narrow bandwidth using a quasi-2D optomechanical system.

The study presents a recyclable polymer system that stores solar energy and releases it as hydrogen on demand, offering an efficient and sustainable route for renewable energy storage and fuel generation.

This study provides new insights into the role of endoglin (ENG) as a co-receptor in endothelial cells and addresses a gap-in-knowledge on how ENG could be involved in both TGF-β and BMP9 signalling. Such knowledge greatly facilitates therapeutic targeting of ENG-related pathways.

This study reveals how atmospheric warming drives glacier instabilities by analyzing multi-decadal in-situ measurements in the High Arctic. Using borehole seismology, it shows that surface melt promotes crevasse opening and sliding.

A strategy based on the design of a composite coating that enables slip-enhanced close-contact melting inside sealed phase-change thermal batteries to improve charging rates enables high-performance thermal energy storage over a wide range of temperatures.

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.

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.

Global post-fire soil erosion accounts for approximately 8.1 ± 0.72 Pg per year, or 19%, of total global soil erosion, and Africa is the most impacted continent given its larger burned area, according to a global assessment of soil erosion produced by wildfires over the last 18 years.

The West Antarctic Ice Sheet responded to different natural forcing mechanisms than the East Antarctic Ice Sheet through the mid-Pliocene due to a greater sensitivity to oceanic feedbacks, according to iceberg-rafted debris records and ice-sheet modelling experiments.

Vibrio cholerae O1 outbreak strains are classified as Ogawa or Inaba serotypes, but the impact of serotype on pathogenicity is understudied. Here, the authors show that O1 antigen methylation in Ogawa strains promotes colonization and infectivity.

In a prespecified secondary analysis of the SURMOUNT-OSA trial, tirzepatide improved cardiometabolic outcomes in patients with moderate-to-severe obstructive sleep apnea and obesity.

Cosgun et al. show that, in B cell leukemia, β-catenin expression is maintained at low levels through glycogen synthase kinase 3B (GSK3β)-mediated phosphorylation. Inhibition of GSK3β results in β-catenin–Ikaros–NuRD complex formation, leading to B-ALL cell death through MYC repression.

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.

A histone ubiquitin-dependent regulatory hub governs stimulus-dependent heterochromatin propagation, with important implications for understanding mechanisms governing rapid changes in the epigenetic landscape in physiology and disease.

Exercise has considerable health benefit, including modulation of the immune system. Here the authors compare the molecular make-up of peripheral blood immune cells at resting state and upon a single bout of two different aerobic exercise modes by proteomics and show that although both exercise modes trigger similar changes, the effect is more pronounced after high intensity interval training.

The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

The discovery of a vast reservoir of primordial neutral hydrogen gas surrounding a young galaxy cluster just one billion years after the Big Bang offers new insight into how the first large cosmic structures assembled.

Liu and colleagues demonstrate that biomimetic fractal patterns derived from glomerular histology can enhance the maturation of podocytes (highly differentiated glomerular cells) that are grown in culture. This work presents a bioengineered platform for improved cell culture fidelity.

The emergent electric field induced by pinned magnetic solitons remains poorly understood. Now the dissipative motion of magnetic domain walls under an alternating current in Weyl magnet NdAlSi devices is shown to induce a large emergent electric field.

Tracking the success rate of clinical drug development is key for pharmaceutical and economic decision making. Here, the authors establish a strategy enabling dynamic measurement of the success rate using public data and generate an online platform.

Baird et al. present the phase 2 PIONEER trial findings on the antitumor activity of combining aromatase inhibitor letrozole with megestrol in postmenopausal women with operable estrogen-receptor-positive human epidermal-growth-factor-receptor-2-negative breast cancer.

IBI318 is a recombinant bispecific IgG1 antibody that targets PD-1 and PD-L1. Here the authors report the results of a phase II trial of IBI318 combined with the receptor tyrosine kinase inhibitor lenvatinib in patients with advanced non-small cell lung cancer with acquired resistance to first-line immune checkpoint inhibitors.

Treatment-seeking for fever is widely used to estimate treatment of childhood infections, but cross-country comparisons are problematic. Here, the authors estimate the probability of seeking treatment for fever at public facilities across 29 countries by quantifying person-level latent variables.

Vaginal birth, exclusive breastfeeding and early contact with siblings promote colonization of the infant gut with bifidobacteria capable of producing aromatic lactates, a microbial and metabolite signal that is inversely related to the risk of allergen-specific sensitization and dermatitis later in life.

In the adrenal cortex, cholesterol used for steroid production is stored in lipid droplets. The authors demonstrate here the importance of the transcription factor HHEX in maintaining glucocorticoid levels and protecting lipid droplets from androgen-induced lipid depletion.

Reported detections of gases in exoplanet atmospheres, including claims of biosignatures on K2-18 b, disappear when broader models are tested, revealing that such detections often reflect modelling limits rather than real signals.

How myelin plays a role in long-range processing of disparate inputs remains elusive. Here, the authors show that myelin loss within the neocortex reduces the reliability to propagate cortical bursts across axons, causing an impaired temporal sharpening to compute sensory and cortical signals within the thalamus.

Short-circuiting during fast charging through lithium dendrite intrusion into electrolytes is a major challenge in solid-state batteries. Here, using thermally annealed 3-nm-thick Ag coatings, lithium penetration into brittle electrolyte Li_6.6La₃Zr_1.6Ta_0.4O₁₂ is inhibited at local current densities of 250 mA cm⁻² due to an increase in surface fracture toughness.

Insecticide resistance can limit the effectiveness of insecticide-treated nets for malaria prevention, but other factors such as access and durability also contribute. Here, the authors quantify impacts of this ‘cascade’ of factors using a mathematical model.

T-cell–mediated rejection (TCMR) remains a major cause of kidney transplant failure with incompletely understood mechanisms. Here the authors use single-nucleus RNA sequencing, spatial transcriptomics and immunofluorescence to show that injured kidney epithelial cell states associate with poor transplant outcomes after T-cell–mediated rejection.

Wastewater treatment plants harbour extensive but poorly characterized microbial genetic diversity. Using 828 metagenomes from wastewater treatement plants globally, this study reconstructs >24,000 metagenome-assembled genomes, including >12,000 new species, providing a genome-resolved framework for understanding and engineering activated sludge functions.

Radiation-induced lung injury (RILI), a serious complication of radiation exposure, is associated with cGAS-STING pathway overactivation. Here, the authors developed a nanogel based on microalgal extracellular vesicles and a cGAS inhibitor to prevent and treat RILI and its progression to fibrosis.

Behçet’s syndrome is a chronic inflammatory disease with oral ulcers being the most common symptom. Here authors present results from a phase 2 randomized double-blind placebo-controlled clinical trial that shows that systemic low dose interleukin-2 could be safely administered to these patients, and the therapy may improve their quality of life.

The MOUNTAINEER phase 2 trial demonstrated the efficacy and safety of tucatinib (HER2-targeted TKI) and trastuzumab (anti-HER2 antibody) in patients with HER2 + , RAS wildtype unresectable or metastatic colorectal cancer that had progressed on chemotherapy, resulting in the approval of the regimen. Here, the authors report the updated analysis of the MOUNTAINEER trial.

Using chemical photoswitchable reagents to exert purely wavelength-dependent control over biological systems in deep tissue and in vivo requires a concentration-independent design paradigm. Here, such photoswitchable ligands are realized by ensuring that E/Z isomers have opposing efficacies yet similarly high affinity, allowing them to probe transient receptor potential C4 and C5 channel functions up to the tissue level.

Stable adipocytes resist lipolysis in healthy states but are highly susceptible to a catecholamine-independent, neurosystemic pathway-driven catabolic state.

GaitDynamics is a generative foundation model for accurately and efficiently estimating the motion and forces of human gaits from kinematic data, which will have impacts in injury prevention, therapies and performance coaching.

Hodgkin Reed Sternberg (HRS) cells and their surrounding microenvironment in Hodgkin lymphoma remain poorly characterized. Here, the authors perform genome-wide transcriptional profiling with spatial and single-cell resolution to explore the cellular and molecular composition of the Hodgkin lymphoma microenvironment and used machine learning to identify IL13 as a potential HRS cell survival factor.

Li, Cui, Yang, Lu, Jiang, Zhang and colleagues identify a lactate transport mechanism from tumour-associated macrophages that regulates DNA repair and immune cell infiltration, which could be targeted to enhance immunotherapy efficacy in glioblastoma models.

There are similarities in airway inflammatory endotype between eosinophilic granulomatosis with polyangiitis (EGPA) and type 2 eosinophilic asthma. Here, the authors perform single-cell transcriptomics to compare EGPA with severe eosinophilic asthma and find differences in the innate immune cell populations and use mouse models to characterise the function and phenotype of these cells.

This study uses single-nucleus RNA sequencing to analyze lung tissue from 141 individuals with chronic obstructive pulmonary disease. Distinct patterns of spatially resolved changes in cell composition and cell states that correlate with clinical features are highlighted.

Kalia et al. investigate metabolic changes in Alzheimer’s disease (AD) using blood metabolomics, and show that lysophosphatidylcholines are associated with early amyloidosis in AD as measured by P-tau181 and P-tau217.

Fusion genes involving KMT2A rearrangements are frequent oncogenic drivers of acute myeloid leukaemia (KMT2A-r AML) but the cell of origin remains unclear. Here, using preclinical models of EVI1 positive KMT2A-r AML the authors investigate the cell of origin and find that the presence of exogenous factors influences AML initiation and the resulting phenotype.