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Little work has been done to describe and address the variability inherent in the agroinfiltration and genetic engineering of Nicotiana benthamiana. Here, the authors identify and quantify the sources of virtually all variation and develop recommendations for minimizing variation.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Greenwald, Nederlof and colleagues developed a computational pipeline analyzing multiplex imaging data and established spatial patterns within breast cancer microenvironment that are predictive of immune checkpoint blockade response across treatment time course.

Primary cutaneous B-cell lymphoma encompass clinically heterogeneous entities, including indolent and aggressive subtypes. Here, the authors show that the two indolent subtypes exhibit a persistent germinal centre reaction and thus may be driven by (a yet unknown) antigen.

Chromosome folding in early zebrafish development starts with formation of fountains. These patterns, also prominent in other systems, form at active enhancers, depend on transcription factors, and reflect preferential loading of loop extruding cohesin at enhancers.

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.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

In a phase 1b/2 trial, an off-the-shelf vaccine using gorilla adenoviral and modified vaccinia Ankara vectors with over 200 mutated peptides known to be present in persons with mismatch-repair-deficient tumors is safe and elicits neoantigen-specific T cells in individuals with Lynch syndrome.

It is unclear whether the harsh abiotic conditions of drylands hinder biological invasions. This global analysis shows that drylands are vulnerable to non-native plants and are likely to become more so as native plant diversity declines and grazing pressure intensifies.

The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

HOM formation from a same VOC can vary by over a factor of three depending on chemical conditions. A RO₂ oxidation fraction concept explains this variability and cautions against directly applying lab yields to the atmosphere.

Melting ice and associated sea-level change will expose new land in Antarctica. Here the authors quantify this change and combine it with our understanding of known Antarctic mineral occurrences, showing that substantial mineral deposits may become accessible over the next few centuries in Antarctica.

The substantia nigra and all Parkinson’s disease deep-brain stimulation targets are selectively connected to the somato-cognitive action network rather than to effector-specific motor regions.

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.

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.

There is a lack of effective therapies for patients with non-V600E BRAF mutant cancer. Here, the authors report limited response in a phase II trial investigating the combination of binimetinib (MEK inhibitor) and encorafenib (BRAF inhibitor) for the treatment of non-V600E BRAF mutant cancer and subsequently investigate resistance mechanisms and combination therapeutic strategies in patient-derived models.

Here they establish an NTR-based genetic ablation tool in axolotls to investigate the function of specific cells. They use this system to demonstrate the capacity of ependymoglial cells for central nervous system regeneration.

This study introduces a sediment-based method to reconstruct Antarctic fast-ice change during the late Holocene, revealing cyclic patterns linked to solar variability and offering insight into long-term cryosphere climate dynamics.

This study examines long-term changes in species richness across tropical forests in the Andes and Amazon. Hotter, drier and more seasonal forests in the eastern and southern Amazon are losing species, while Northern Andean forests are accumulating species, acting as a refuge for climate-displaced species.

An algorithm that combines deep learning, Bayesian optimization and computer vision techniques can be used to autonomously tune a semiconductor spin qubit from a grounded device to Rabi oscillations.

In this work, the authors propose and experimentally test a framework to analyse the fundamental limits of quantum detector tomography, i.e., the limits to extractable information from probing unknown quantum measurements. They introduce the detector quantum Fisher information, which physically connects measurement structure to quantum advantage, complementing previously known state and channel metrics.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Bauer et al. analyze blood-based immune and transcriptomic markers in tuberculosis patients to identify treatment failure and recurrence. They find that specific markers reliably detect microbiological non-conversion during treatment and recurrence after therapy, providing a sputum-independent tool for patient monitoring.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

The perceived toxicity of organometallic reagents has limited their use in living systems. Now it has been shown that balancing flexible chelation with biocompatible ligands without precluding chemical reactivity enables organonickel-mediated S-arylation inside cells. This reaction enables deep chemical surveys of reactive proteins and covalent tracking of intracellular viral and bacterial pathogens.

It remains unknown why only some sickle cell disease (SCD) patients develop lung thrombosis. Here, the authors show that an extracellular vesicle-dependent mechanism prevents lung thrombosis in SCD and how a CD39 polymorphism impairs this protection to promote lung thrombosis in subset of patients.

Approved antibody–drug conjugates (ADCs) remain constrained by a limited repertoire of payloads with restricted modes of action. Here, the authors present phosphoramidate-based self-immolative linker units that facilitate stable attachment in serum and traceless drug release in the target cell from aliphatic and aromatic alcohols with various modes of action.

Li and colleagues describe a monocyte-specific transcriptional state along with a persistent elevation of inflammatory markers specifically found in individuals with long COVID who had mild-to-moderate disease during acute SARS-CoV-2 infection.

pH is a critical regulator of (bio)chemical processes and therefore tightly regulated in nature. Now, proteins have been shown to possess the functionality to drive pH gradients without requiring energy input or membrane enclosure but through condensation. Protein condensates can drive unique pH gradients that modulate biochemical activity in both living and artificial systems.

How inflammation spreads from the skin to the joints in psoriatic disease is unclear. Here, the authors show that joint-resident fibroblasts can control differentiation of infiltrating skin-derived myeloid precursors that can become inflammatory macrophages.

Gravitational lens modelling of a million-solar-mass dark object reveals that it cannot be a free-floating black hole or dark-matter halo as predicted by cold dark matter, instead indicating a peculiar and highly concentrated mass distribution.

In a randomized phase 2 trial in patients with acute coronary syndrome and high levels of the inflammation biomarker C-reactive protein, treatment with low-dose interleukin-2 increased the numbers of regulatory T cells and reduced arterial inflammation, compared to placebo.

Based on two waves of data collection from 748 households in Hong Kong, this analysis sheds light on the number of transmission events that occurred before manifestation of symptoms in influenza A and B cases.

The engagement of immunological memory is a key component to the protective anti-SARS-CoV-2 B and T cell responses. Here the authors assess the B and T cells of a cohort of UK healthcare workers in response to infection and longitudinally track the compartment showing distinct trajectories following early priming.

Scourzic et al. show that germinal centre B cells display an enhanced ability to reprogram to induced pluripotent stem cells compared to mature B cells. This ability indicates their higher plasticity level and is T follicular helper cell-dependent.

How landscapes are arranged affects soil pathogenic fungi worldwide. The authors reveal the global pattern and pronounced scale-dependency of landscape complexity and land-cover quantity on soil pathogenic fungal diversity.

Uropathogenic Escherichia coli infection of a murine prostate organoid model reveals a bacterial FimH–host prostatic acid phosphatase adhesin-receptor interaction enabling invasion and replication within the host tissue.

Non-Annex I countries—mostly developing countries under the UN climate framework—excluding China accounted for approximately 61% of hydrofluorocarbon emission growth during 2011–2020, while China’s emissions have been overestimated since 2017, according to atmospheric observational data and inverse modelling.

Activity-based protein profiling identifies covalent small molecules that potentiate the activity of the METTL5:TRMT112 complex through binding to a complexoform-restricted allosteric pocket absent in other TRMT112:methyltransferase complexes

Baked sediment, heat-shattered artefacts and introduced pyrite in a 400,000-year-old Palaeolithic occupation site in Suffolk, UK provide evidence of intentional fire-making, marking a pivotal moment in human development.

In colorectal cancer, therapeutic resistance is driven by MAPK-dependent epithelial cell plasticity.

Glioblastoma is characterised by high levels of intratumoural heterogeneity and plasticity, hindering treatment. Here, the authors develop an analytical framework, scFOCAL, to predict the sensitivity of glioblastoma cell subpopulations to therapies based on reversal of disease transcriptional signatures to identify synergistic therapeutic combinations.

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.

Here the authors show that tissue-resident memory and exhausted T cells in tumors are distinct populations that are shaped by relative presence or absence of TCR signals, suggesting that a tailored therapeutic strategy is needed to target each subset.