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Difelikefalin is an FDA-approved KOR-targeted drug for chronic pruritus yet exhibits side effects. Here, researchers solve cryo-EM structure of difelikefalin KOR-Gi, identifying Y320^7.43 as a key bias residue. Substituting D-Phe1 with β-phenylalanine develops beta01 which retains analgesic/antipruritic efficacy via a unique receptor conformation that reduces adverse effects.

Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

LHAASO has detected γ-ray emission with a spectrum extending to 2 PeV from the pulsar wind nebula (PWN) powered by PSR J1849-0001, indicating an extreme particle acceleration efficiency and challenging the current particle acceleration theories.

A genome-to-genome association study identifies host and viral risk factors that interact to drive nasopharyngeal carcinoma endemicity in southern China.

The CMS experiment at CERN reports one of the highest-precision measurements of the W boson mass, finding it in line with standard model predictions and at odds with recent anomalous measurements.

Direct and selective functionalization of pyridine scaffold is of importance across numerous fields, yet remains challenging due to the inherent inertness of pyridines and the presence of competing reactive sites. Here, the authors report a room-temperature electrochemical strategy that enables the direct hydroxyalkylation of diverse pyridines with carbonyl compounds.

Cardiovascular surgery and haemodialysis urgently need durable vascular grafts. Here, authors develop a decellularized polymer skeleton-reinforced biotube as a readily-available vascular graft and demonstrate utility in vivo across multiple large animal preclinical models.

Reducing dissipation when generating spin currents remains a central challenge in spintronics. Now, an artificial ferrimagnet is shown to produce spin current output and simultaneously lower magnetic damping.

High-latitude soils are future soil organic carbon loss hotspots, with losses dominated by particulate organic carbon (POC). The fraction of POC in total SOC (f_POC) is a key indicator, emphasizing the climate importance of preserving POC.

Chern ferromagnetism is established in twisted bilayer MoTe₂ devices at large twist angles. Here, the authors observe evidence of antiferromagnetic ground states with zero Hall resistance at an intermediate twist angle around three degrees, demonstrating the sensitivity of the magnetic ground state.

Antibody mediated prevention (AMP) trials with the broadly neutralizing antibody VRC01 showed protection against VRC01-sensitive viruses. Here, by deep sequencing plasma samples from 172 participants of the AMP trials, the authors show a high frequency of multilineage HIV infections (38%), including coinfection with both sensitive and resistant viruses, and demonstrate that VRC01 doesn’t alter the transmission bottleneck.

Pulmonary microbiotacomponents in bronchiectasis patients receive repeated antibiotic exposures, whereas previous studies on the effects ofantibiotic treatment focused on typical pathogens rather than commensals. By integrating experimental evolution withsingle-cell resolution, the authors reveal a multifaceted strategy by which Neisseria subflava, a common airwaycommensal associated with bronchiectasis, exploits antibiotic selection to transition towards pathogenicity.

The role of long non-coding RNAs (lncRNAs) in regulating cancer progression remains to be explored. Here, the authors identify an antisense lncRNA in the IGF1R locus (IGF1RAS1) which strongly interacts with super enhancers and modulates MYC expression in metastatic prostate cancer.

The authors deplete the cohesin activator NIPBL during the mitosis-to-G1-phase transition. They observe that structural loop formation is impaired proportionally to loop length, while gene activation and enhancer–promoter interactions are only mildly impaired.

Authors demonstrate layer-selective conductor–insulator transitions in twisted bilayer graphene driven by hydrogenation, realising an electrochemical interface with two decoupled 2D electron gases that enables configurable logic gates.

Extracellular vesicles from lung epithelial cells deliver ACE2 and TMPRSS2 to recipient cells, enabling SARS-CoV-2 infection beyond receptor-expressing cells and expanding viral tropism.

Glaucoma is a common cause of vision loss. Here the authors show that elevated intraocular pressure disrupts the blood retinal barrier (BRB) and contributes to retinal ganglion cell death in mouse glaucoma models, and detect similar BRB disruption in human glaucoma donor eyes.

A tissue-clearing protocol integrated with mRNA and protein detection is applied to human bone to reveal quantitative differences in osteo-sinusoidal niches of human young and aged mesenchymal stromal cells.

Atmospheric river (AR) characteristics, particularly AR shape associated with large-scale circulation, as well as interactions with other weather systems, significantly influence surface warming over Antarctic ice shelves and their future stability.

Orbital hybridization and quantum confinement are used to realize Ising-like superconductivity in trilayers of gallium, which alone is probably not strongly enough spin–orbit coupled to host such superconductivity under high in-plane magnetic fields.

A deep learning framework integrates protein language models, protein interactions and domains, medical knowledge graphs and electronic health records to map variants to phenotypes.

Coronary artery disease has several genetic risk factors. Here, the authors develop a model that combines germline and somatic genetic drivers to predict coronary artery disease risk, identifying high-risk individuals not detected by polygenic risk scores alone.

Methane is a potent greenhouse gas, but can also be used as a source for advanced carbon materials. This work shows a sustainable approach to produce high-value carbon fibres through methane pyrolysis.

The widespread human parasite Schistosoma haematobium has a distinct, immunogenic glycan profile compared to S. mansoni, highlighting the role of glycans in species-specific parasite-host interactions and as diagnostic targets.

The authors from the ALICE collaboration identify multiple species of mesons and baryons and measure the anisotropic flow with non-flow removal techniques in pp and p-Pb collisions at the LHC, identifying the hallmark of quark flow associated with an expanding quark-gluon plasma.

Here, the authors show that the PLA2G6 protein is a component of the IP3R1–GRP75–VDAC1 complex at the mitochondria-associated endoplasmic reticulum (ER) membrane, maintaining the integrity and function of ER–mitochondria contacts.

Decreased brain volumes and increased NfL levels can be observed earlier than disease diagnosis in short-tandem-repeat-associated neurological diseases.

Adsorption of trace transition-metal cations endows common Ca/Mg-carbonates and phyllosilicates with catalytic activity for electrochemical CO2 reduction under planetary conditions, potentially promoting prebiotic chemistry and the origin of life.

The study reveals a ‘chemocentric’ strategy for identifying charged molecular glue degraders, through discovering a bromodomain-binding molecular glue degrader prodrug that is metabolically activated in cells to recruit the YPEL5-CTLH E3 ligase.

Conventional rechargeable zinc-air batteries face slow kinetics and thermodynamic incompatibility. Here, the authors propose a dual-cathode zinc-ethylene glycol/air battery, enabling concurrent efficient electricity generation and electro-reforming of plastic wastes into high-value C2 chemicals.

A large-scale study on the replicability of claims from social and behavioural science journals reports that about half of the results replicate in the same patterns as the original study.

Across 17 forest plots (2.7 million trees, 5,400 species), competition dominated overall, but facilitation was relatively stronger near the equator and declined towards higher latitudes, partly linked to temperature, legumes, mycorrhizal associations and canopy nursing effect.

Au nanowires with an unconventional hexagonal close-packed (4H) phase stabilize the 4H-phase high-entropy alloys grown epitaxially on their surface through a facile chemical synthesis. The resulting core–shell nanostructures demonstrate promising overall water electrolysis performance.

The authors present a multi-core neuromorphic architecture that enables energy‑efficient training of deep spiking neural networks via backpropagation. The design features a multi-engine core, multi-level parallelism, sparsity optimization, and FPGA validation.

Androgen activity in the male embryonic hindbrain prolongs hindbrain differentiation in male individuals and drives sex differences in the incidence and prognosis of posterior fossa type A (PFA) ependymoma, an aggressive childhood brain tumour.

RNA editing influences gene regulation in cancer. Here, the authors show that EZH2 regulates RNA editing by ADAR1 through remodeling its interactome and nuclear transport, thereby promoting MDM2 expression and prostate cancer progression.

The magnetospheric cusp is a key solar wind– magnetic field interface. Here, the authors show that Saturn’s cusp has a pronounced dawn–dusk asymmetry, with signatures reaching the postdusk region, unlike Earth’s near-noon cusp.

Drivers of fungal metabolic diversity are incompletely understood. Here, the authors conduct a global genomics study of over 1,000 pathogenic fungi to show that geography shapes the metabolic diversity in Aspergillus flavus revealing how climate drives fungal chemical adaptive evolution.

Argon-42 is a background in experiments that search for dark matter or neutrinoless double-beta decay. Now, the isotope’s abundance is measured by combining a laser-based atom trapping technique with isotope pre-enrichment.

Colonic stem cells retain a memory of inflammation following disease resolution and there is a mechanistic link between chronic inflammation and malignancy, suggesting potential strategies to mitigate cancer risk in patients with chronic inflammatory conditions.

In this phase 2 trial, combination treatment with elraglusib, a cell-permeable ATP-competitive inhibitor of glycogen synthase kinase-3β, and gemcitabine plus nab-paclitaxel (GnP), in patients with previously untreated metastatic pancreatic ductal adenocarcinoma led to prolonged overall survival compared with GnP only.

A study of reproducibility in a stratified random sample of 600 papers published from 2009 to 2018 in 62 journals spanning the social and behavioural sciences finds higher reproducibility among more recent papers and papers from journals that require data sharing.

Analysis of 15,836 ancient West Eurasian genomes reveals hundreds of instances of directional selection, showing that sustained changes in allele frequency were widespread, rather than being rare over this period as previously assumed.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

As Nature Climate Change celebrates its 15 year anniversary, we look back at some of the journal’s published works. In this Viewpoint, seven early-career researchers discuss how these papers influenced their research and careers.

Ji, He, Cai, and colleagues report an engineered senescence therapy that exploits lipid metabolic features of senescent cells, repurposing excess lipids as functional resources to improve joint function, and thus alleviating osteoarthritis without eliminating the cells.

Atopic dermatitis is an immune disease driven by cytokines including IL-4/IL-13. This study shows that a topical ITK/TRK inhibitor blocks an array of T cell cytokines, inhibits NGF-induced basophil activation, and reduces inflammation in human skin explants and dermatitis models, indicating therapeutic potential.