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Carnot efficiency is the highest theoretically possible efficiency that a heat engine can have. Verley et al.use the fluctuation theorem to show that the Carnot value is the least likely efficiency in the long time limit.

Ocean acidification can affect growth and calcification rates of calcifying phytoplankton. Mesocosm experiments reveal that acidification can also cause declines in population size and inhibit bloom formation.

Multiregion sequencing is needed to better capture the heterogeneity of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Here, the authors analyse HCC and iCCA tumours with multiregion single-cell RNA-seq, revealing cellular dynamics and communication networks with immune cells.

Epidemiological estimates from wastewater are not biased by testing rates but may be subject to other biases. Here, the authors investigate the impact of variable virus shedding profiles for different SARS-CoV-2 variants on estimates of their selection advantage.

This systematic review and meta-analysis provides an updated assessment of the efficacy and safety of intravenous iron therapy in patients with heart failure and iron deficiency, incorporating the results of the newly conducted FAIF-HF2 trial.

Mechanosensitive ion channels protect bacteria from a hypoosmotic shock. Here, Flegler et al. use electron microscopy to describe the gating transition of the MscS-like channel YnaI and a chimera generated from MscS and YnaI.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

An open-source platform for data-independent acquisition proteomics adapts predicted libraries to experimental settings.

HistoPlexer, a deep learning model, generates multiplexed protein expression maps from H&E images, capturing tumour–immune cell interactions. It outperforms baselines, enhances immune subtyping and survival prediction and offers a cost-effective tool for precision oncology.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

The authors find subtype-specific influenza cross-reactivity patterns, including rapid declines for A(H3N2) within 6 years, sustained responses for A(H1N1)pdm09 and increased cross-reactive responses in humans after repeated A(H3N2) exposure.

Stress on land is dynamic, entailing swift and drastic changes. Integrated time-course stress and co-expression analysis predict a gene regulatory network that retraces a web of ancient signal convergences shared by land plants and their algal sisters.

Kidney organoids derived from human pluripotent stem cells are infused in a normothermic machine perfusion system to condition explanted porcine kidneys, and the feasibility and viability of their in vivo engraftment are demonstrated.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

While most quantum optical techniques reveal either the wave or particle nature of light, weak-field homodyne detection combines wave- and particle-like descriptions. Here, Donati et al.employ this hybrid detection scheme to study the coherence between photon number states across two-mode entangled states.

Förster resonance energy transfer, where energy is transferred between luminescent states, is a mechanism used for applications in photovoltaics or bio-imaging. Here, the authors show that these energy transfer rates are independent of the photonic environment, providing valuable feedback for applications.

Mass spectrometry (MS) is a powerful tool for the structural characterization of protein complexes. Here the authors offer a path for direct integration of MS and electron microscopy with a MS approach that enables grid deposition and structural preservation of gaseous protein complex ions.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Substrate-specific proteases have an enormous potential in the life sciences, but tailoring their specificity remains challenging. Here, the authors describe a data-driven approach combining DNA recording and epistasis-aware deep learning to augment protease specificity engineering at large scale.

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

Interpretation of lipid-like densities in cryo-EM structures of membrane proteins is challenging. Here authors present LipIDens, enabling molecular dynamics analysis of protein-lipid interactions.

NV center-based quantum sensors integrated into diamond anvil cells have enabled magnetic imaging under high pressure but are less suited for studying magnetic van der Waals materials. Here, the authors demonstrate magnetic imaging of micrometer-sized flakes of 1T-CrTe2 under high pressure using spin-centers in a thin hBN layer.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

An inherently explainable AI trained on 1,015 expert-annotated prostate tissue images achieved strong Gleason pattern segmentation while providing interpretable outputs and addressing interobserver variability in pathology.

Hypothalamic melanocortin neurons control energy homoeostasis by modulating appetite. Here, the authors reveal a role for the transcription factor Tbx3 as a regulator of the peptidergic identity and function of immature and mature mouse melanocortin neurons.

Surface wrinkling reduces the performance of mixed-halide perovskite solar cells. Here, the authors identify that sequential nucleation of bromide-rich and iodide-rich domains results in compositional heterogeneity and subsequent wrinkling.

A longitudinal multiomics analysis of a patient with multiple myeloma who developed peripheral T cell lymphoma after treatment with anti-BCMA CAR T cells and a GPRC5D-directed bispecific antibody reveals that two mutated CAR⁺CD8⁺ T cell clones were probably drivers of the neoplasm.

In mature continental rifts, magma intrusion appears to accommodate significant crustal extension. Here, radiometric ages for lavas suggest that this style of focused magmatic accretion and rifting remained stable in the Ethiopian crust for at least ~200 kyr, prior to the onset of true oceanic spreading.

Our understanding of the evolutionary sequence of tetrapod characters is hindered by a limited fossil record of primitive finned tetrapods. This study reports a new stem-tetrapod from ~409 million years ago, which displays morphological features shared by tetrapods and lungfishes, and extends the earliest record of tetrapods by ~10 million years.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

The first experimental demonstration of saturable absorption in core-electron transitions in aluminium paves the way for investigating warm dense matter, which potentially has an important role in planetary science and the realization of inertial confinement fusion.

Secondary acute myeloid leukemias (sAMLs) evolving from myeloproliferative neoplasms (MPNs) associate with poor prognosis. Here authors identify RSK1 as a vulnerability for MPN and sAML and show the efficacy of a first-in-class RSK inhibitor, PMD-026, against these types of myeloid malignancies.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Amide synthases catalyse the formation of macrolactam rings from aniline-containing polyketide-derived seco-acids. In this study, the authors solved the crystal structure of the geldanamycin amide synthase GdmF and demonstrated that it catalyses amide formation using synthetically derived substrates.

By analysing the smartphone data of 2,112,288 participants, in particular observing and comparing the activity of the same individual in two different environments, we find that increases in the walkability of environments result in increases in daily physical activity, providing evidence of the importance of the built environment on physical health.

In this Consensus Statement, an international panel of experts present an overview of the latest developments in the field of cholangiocarcinoma. A set of consensus recommendations and research priorities is provided.

The transcription factor ATF6 causes an enrichment in long-chain fatty acids in the colonic epithelium, which leads to changes in the gut microbiota and contributes to the development of colorectal cancer in humans and mice, thereby linking endoplasmic reticulum stress responses to lipid metabolism and tumorigenesis.

Immune genetic and disease surveillance of a wild meerkat population over 20 years shows that tuberculosis imposes strong pathogen-mediated balancing selection on the meerkats’ major histocompatibility complex via rare-allele advantage or fluctuating selection.

COVID-19 has exposed the fragility of supply chains, particularly for goods that are essential or may suddenly become essential, such as repurposed pharmaceuticals. Here the authors develop a methodology to provide routes to pharmaceutical targets that allow low-supply starting materials or intermediates to be avoided, with representative pathways validated experimentally.