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Using inbred medaka strains, the authors mapped 59 genetic loci linked to heart rate. Gene editing validated conserved genes affecting heart rate and morphology, highlighting the power of isogenic strains in uncovering mechanisms of cardiac traits and disease.

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.

Given rising diabetes prevalence globally, access to diabetes treatments is gaining urgency. Here, the authors show patterns of glucose-lowering medication use for diabetes across 62 low- and middle-income countries.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

The protein, reverse transcriptase, has become an essential tool for making DNA copies of RNA.

The Ocean Equity Index provides a systematic, twelve-criteria framework to assess and improve equity in ocean initiatives, projects and policies, producing structured data that guide evidence-based decisions and support more equitable outcomes for coastal communities and ecosystems.

This study uses single-cell DNA sequencing to analyze genomic evolution in pancreatic cancer using a cohort of multiregionally and longitudinally sampled patients’ tissues across various clinical contexts.

Projected impacts of climate change on malaria burden in Africa by 2050 highlight the urgent need for climate-resilient malaria control strategies and robust emergency response systems to safeguard progress towards malaria eradication.

MK-7762 is a new oxazolidinone antitubercular agent that is structurally similar to linezolid, and demonstrated in vivo efficacy, lesion penetration and limited toxicity compared to linezolid, indicating it could be used in broad tuberculosis regimens.

Luppi et al. identify transcriptomic and connectomic controllers of information integration and its breakdown induced by anaesthesia in humans, macaques, marmosets and mice.

Applications of optical laser-based techniques are limited by the long wavelengths of the lasers. Now, observations of phonons and thermal transport at nanometre length scales are reported with an all-hard X-ray transient-grating spectroscopy technique.

Ribas and colleagues report the results of a phase 2 clinical trial of neoadjuvant PD-1 blockade in patients with surgically resectable desmoplastic melanoma.

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.

A nine-year transit-timing campaign has measured the extremely low masses and densities of four large planets orbiting the young star V1298 Tau, which are now predicted to contract and form a typical compact super-Earth and sub-Neptune system.

A large sulfur-bearing carbon ring molecule has been detected in space, 2,5-cyclohexadien-1-thione, using laboratory spectroscopy and a radio telescope. Found near the Galactic Centre, it opens the door to a new family of interstellar molecules.

dSHERLOCK is a nucleic acid platform for the quantification of double-stranded DNA targets using CRISPR/Cas and isothermal amplification and is applied to quantify pathogen C. auris in clinical surveillance swab samples.

A cavity-array microscope is realized using intra-cavity lenses to create a two-dimensional array of over 40 modes, each coupled to a single atom in free-space.

This study detects Chlamydia pneumoniae in human retina and brain, increasing with AD severity. Retinal pathogen load with Aβ₄₂ may predict AD stage. In models, infection drives Aβ deposition and NLRP3 activation, worsening pathology and cognition.

A rationally designed assay detects granzyme A activity by integrating peptide-based GzmA-targeted inhibitors and probes with chemiluminescent reporters to monitor inflammatory bowel disease.

Genomic and transcriptomic analysis of samples from patients with multiple myeloma, followed by in vitro validation, indicate mechanisms of antigen escape in response to GPRC5D T cell-engager talquetamab, including biallelic deletions, small nucleotide variants, insertion-deletions and chromatin silencing.

The distinct architecture of the Escherichia coli membrane transporter LetA mediates lipid trafficking across the bacterial envelope in partnership with the tunnel-like complex LetB.

During the Last Glacial Maximum, the deep Northwest Atlantic was only about 2 °C colder than today, suggesting sustained production of relatively warm North Atlantic Deep Water during the Last Glacial Maximum.

An implantable vagus nerve-targeted device safely reduces disease activity and joint damage in rheumatoid arthritis, offering a new nondrug treatment for patients who do not respond to or cannot tolerate medication.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

A van der Waals heterostructure made from atomic layers of ferroelectric CuCrP₂S₆ and ferromagnetic Fe₃GeTe₂ can offer reversible, non-volatile ferroelectric control of two-dimensional magnetism.

This study finds that crowd-sensed plants as living sensors uncover climate and soil patterns in 326 European cities; extend the urban heat island effect to moisture, pH, salinity and disturbance; and show built-up areas homogenize whereas urban forests preserve environmental diversity.

The structural anisotropy necessary for the powered directional rotation of chemically fuelled molecular motors had previously been provided by chiral fuels or enzymes. Now it has been shown that asymmetry in the organocatalyst itself is sufficient for directional fuelled rotation. This informs how chemical energy is transduced through catalysis, the fundamental process that powers biology.

Prior hypoglycemia alters the paracrine interaction between islet α and δ cells, leading to impaired counter-regulatory glucagon secretion through somatostatin hypersecretion, increasing the risk of recurrent hypoglycemia.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

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.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

As Nature Aging celebrates its fifth anniversary, the journal asks some of the researchers who contributed to the journal early on to reflect on the past and the future of aging and age-related disease research, the impact of the field on human health now and in the future, and what challenges need to be addressed to ensure sustained progress.

In an arm of an ongoing multicenter phase 2 trial testing different therapies in patients with genetically profiled grade 2 or 3 meningiomas, treatment with an oral CDK4/6 inhibitor met the primary endpoint for progression-free survival at 6 months in patients with CDK or NF2 alterations.

Using single broadband X-ray pulses from a free-electron laser on a gaseous neon target, coherent, nonlinear four-photon interactions with core–shell electrons is demonstrated, representing a strategy for multidimensional correlation spectroscopy at the atomic scale.

Early results from the phase 2b VIBRANT-HD trial of the oral splicing modulator branaplam in Huntington’s disease suggested reduced cerebrospinal fluid huntingtin levels, but safety monitoring revealed signs of peripheral neurotoxicity, prompting early termination of the study.

Accurate projections of heating and cooling needs are vital for planning energy use and achieving the sustainable development goals. A global dataset now maps global heating and cooling degree days, finding future hotspots, rising cooling demand and early shifts in energy needs with major global impacts.

The authors report an enhancement of the superconducting onset temperature in nanometer-thin YBa₂Cu₃O₇-δ films grown on substrates with nanofaceted surfaces. They theoretically show that the enhancement is mainly driven by electronic nematicity and unidirectional charge density waves, and further suggest that the nanofacets themselves may promote these effects.

Medication non-adherence represents a healthcare challenge, generating over $100 billion in additional costs annually in the USA. Here, the authors developed a resorbable and ingestible system designed for assessing medication adherence.

Figure 1. Schematic illustration of capsule based, biodegradable medication adherence tracking system with envisioned scenario for clinical use. A, Bio-RFID capsule administration. B, Shielding coating dissolution and payload release C, Monitoring of the Tag ID and frequency range, recording of the payload for tracking adherence. D, Dissolution and biosorption of the coating, tag and the capsule.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

The study reports the discovery of a persistent bow shock around a diskless magnetic accreting white dwarf, revealing a powerful energy-loss mechanism that challenges current models of accretion and compact binary evolution.

Methods for the systematic synthesis and evaluation of large numbers of transition metal complexes at a time are still limited. Here, the authors report a high-throughput method to create and test hundreds of metal complexes, revealing potent new metalloantibiotics and a highly active iridium catalyst.

The discovery of new gold deposits has declined by 45% over the past 10 years. Lintern et al.present new evidence for the occurrence of particulate gold in trees growing above buried mineral deposits, and propose vegetation sampling as a mineral exploration method.

The [1,2]-Wittig rearrangement of allylic ethers is traditionally considered to proceed via formation and recombination of radical pairs. Now it has been shown that an alternative reaction cascade, involving initial enantioselective [2,3]-rearrangement followed by base-promoted anionic fragmentation–recombination that proceeds with high enantiospecificity, allows a catalytic enantioselective [1,2]-Wittig process.

This study applies a global food and land system modelling framework to quantify the impact of 23 food system measures on 15 outcome indicators related to public health, the environment, social inclusion and the economy—from today until 2050.

ADGRL4 is a cancer-implicated adhesion GPCR whose ability to couple to G proteins had been unclear. Here, authors show that ADGRL4 weakly engages Gq and determine its 3.1 Å active-state structure, revealing its mechanism of activation.

In this multicenter phase 1 trial of patients with advanced solid tumors resistant to anti-PD-1 therapy, treatment with the anti-latent TGFβ1 antibody linavonkibart with or without pembrolizumab was safe, and encouraging clinical response rates were associated with T cell infiltration and immune activation.

Pre-treatment dual immune checkpoint blockade in cervical cancer remains understudied. In this trial, the authors show that neoadjuvant immune checkpoint blockade enhances immune activation and correlates with improved response to subsequent chemoradiation in patients with cervical carcinoma.

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.

There is a trade-off between achieving fast qubit control and preserving long qubit lifetimes. In this work, the authors demonstrate single qubit gates by driving a transmon qubit parametrically at 1/3 of its frequency, creating fast, high-fidelity gates while protecting the qubit lifetime and mitigating heating.