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Understanding the mechanisms of chemoresistance in multiple myeloma (MM) remains elusive. Here, the authors identify a long non-coding RNA termed as PLUM that is overexpressed in NF-ĸB mutant high-risk MM and interacts with EZH2 to mediate PRC2 complex formation promoting chemoresistance via the activation of the UPR pathway.

Myelination is a key regulator of brain function. Here the authors use MR-based myelin measures to examine if cortico-cortical interactions, as assessed by paired pulse transcranial magnetic stimulation, are affected by variations in myelin in the human brain.

Demystifying the spawning strategies of fish can help us understand their evolutionary drivers and better inform fisheries management. This study reveals the spawning strategies of pelagic fish, showing that the benefits of co-located spawning across time and space outweigh the potential drawbacks.

At equilibrium, the ferroelectric polarization is proportional to the strain. At ultrafast timescales, an above-bandgap laser excitation decouples strain and polarization, which, out of equilibrium, is mainly determined by the photoexcited electrons.

New data show that the HMCES protein suppresses DNA double-strand break formation by cross-linking to and thereby stabilizing an abasic site generated during replication-coupled repair of a DNA interstrand cross-link, thus demonstrating a physiological role of HMCES in DNA repair.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Loss-of-function variants of ABCA7, associated with Alzheimer’s disease, result in disrupted lipid metabolism, mitochondrial function, DNA repair and synaptic signalling pathways in the human brain.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

As part of the SWEETSTONE trial, the authors report the ability of the sodium-glucose cotransporter 2 inhibitor empagliflozin to reduce the likelihood of kidney stone formation in individuals without diabetes.

Chen et al. show that PEX39 cooperates with PEX7 in the peroxisomal import of proteins containing a PTS2 site and uncover an (R/K)PWE motif in PEX39 and PEX13 that binds to PEX7 and facilitates the import of PTS2-containing proteins.

This study conducted a 20-year analysis in Stockholm showing that RSV epidemic patterns shifted due to viral interference from influenza, particularly, pandemic H1N1, highlighting the complex interactions between co-circulating respiratory viruses.

The combination of isotopic tracers with root phenotyping reveals specific patterns in photosynthate allocation. These patterns are reflected in rhizodeposition and result in spatially distinct microbiomes within the plant root system.

The peptide hormone GLP-1 has both antidiabetic and antihypertensive effects. Daniel Drucker and his colleagues now show that GLP-1 lowers blood pressure through indirect mechanisms involving the heart: GLP-1 acts on its receptor in atrial cardiomyocytes to stimulate secretion of the peptide hormone ANP, which in turn lowers blood pressure through direct effects on the vasculature and kidney.

In this study, the authors assess the global response to the toxic aldehyde glyoxal (GO) in Pseudomonas aeruginosa, suggesting that GO controls quorum sensing during infection through a mechanism involving a novel protein, ArqI.

Genomes of nine brown algal species with different sex determination systems show that U/V sex chromosomes evolved 450–224 Ma and show remarkable conservation of genes within the sex-determining region despite independent expansions of the sex locus in each lineage.

Using estimation data on neuron numbers in 111 bird species across 24 families, the authors show that number of neurons is positively associated with innovation propensity and encephalization.

Multi-omics analyses of faecal samples from patients with ulcerative colitis reveal a link between Bacteroides vulgatus protease activity and severity of disease symptoms.

Preventing endosomal damage sensing or using lipids that create reparable endosomal holes reduces inflammation caused by RNA-lipid nanoparticles while enabling high RNA expression.

Bacteria are increasingly known to employ internal organization strategies. Here, authors demonstrate that bacterial encapsulation peptides cause self-condensation of associated protein domains. These peptides may allow for programmable spatial control of metabolism.

Using data from 69 countries, Hässler et al. show that intergroup contact and support for social change towards greater equality are positively associated among members of advantaged groups, but negatively associated among disadvantaged groups.

Wildfire risk in California’s WUI is rising. Analysis of past events shows home hardening and defensible space can reduce structure loss by up to 52%, but coordinated, community-scale action is essential to maximize impact.

Tree shrews show a primate-like hierarchical organization in their visual pathway and object decoding accuracy, along with strongly face-selective cells, demonstrating how core computational principles of visual form processing found in primates are conserved yet compressed.

Our understanding of how post-translational modification—protein phosphorylation—impacts the complexity of eukaryotic signalling pathways is continuously expanding. Now, protein oligophosphorylation has been characterized as an additional phosphorylation mode. Structural and mass spectrometry methods revealed that NME1 catalysed its own oligophosphorylation, leading to altered protein–protein interactions.

Sequencing analysis of tamoxifen-associated uterine cancers and further in vivo analyses suggest that the drug tamoxifen can activate the PI3K pathway in the absence of oncogenic mutations.

Plant functional diversity is highly dynamic over time, driven by seasonal cycles and wet–dry periods and varying across biomes, based on an analysis of over 4,000 hyperspectral satellite scenes at the global scale.

Ambient air pollution exposure in early childhood has been linked to infection risk but the mechanism is unclear. Here, the authors investigate the association between air pollution-linked proteomic profiles in pregnancy and infection in early childhood using data from Denmark and Sweden.

Metabolic and alcohol-related liver disease presents challenges in clinical trials due to complex pathophysiology. This Review discusses noninvasive imaging, serum biomarkers and adaptive designs as modalities to enhance patient-centric end points, aiming to refine diagnostics and improve drug development.

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

The authors reveal that even within a few-nanometre thin films, ultrafast all-optical magnetisation switching is spatially inhomogeneous along the depth and driven by the picosecond propagation of a transient domain boundary.

Mutational signature analysis of blood cells isolated from 23 chemotherapy-exposed samples and 9 nonexposed controls characterizes the effects of various drugs on mutational burden, signature exposure and cell types.

High-resolution geospatial mapping found that the annual incidence of cholera shifted from western to central and eastern Africa between 2011 and 2020, with the latter regions more likely to report cholera in 2022–2023, reflecting instability in cholera burden patterns that can impact progress in disease control.

This study maps the connections of layer 5 pyramidal neurons in the mouse cortex, revealing distinct local and intercortical wiring patterns, and provides an open framework for exploring the connectivity of cell types.

To better understand the etiology of frailty, the authors perform a large genetic study. They identified 45 additional variants and implicated MET, CHST9, ILRUN, APOE, CGREF1 and PPP6C as potential causal genes, linking frailty to immune regulation, metabolism and cellular signaling.

The arts, according to a systematic synthesis of data from 95 studies (across 26 countries), may support non-communicable disease prevention by providing opportunities for increased physical activity, and helping to address social forces that contribute to health inequities.

Relapsed and/or refractory acute myeloid leukemia (AML) postallogeneic hematopoietic cell transplantation has limited treatment options. Here the authors report the clinical results and immune correlates of a phase I/II trial of adoptively transferred virus-specific donor CD8 + T cells engineered to express a WT1-specific T cell receptor in patients with acute myeloid leukemia and active disease post-allogeneic hematopoietic cell transplantation.

Observations of a fast X-ray transient reveal that it is a gamma-ray-burst explosion from a very distant galaxy that emits light with the wavelength necessary to drive cosmic reionization, the last major phase change in the history of the Universe.

The Connectome Annotation Versioning Engine (CAVE) is a platform for proofreading, annotating and analyzing datasets reaching the petascale. Currently, CAVE is used for electron microscopy datasets, but it can potentially be used for other large-scale datasets.

An analog optical computer that combines analog electronics, three-dimensional optics, and an iterative architecture accelerates artificial intelligence inference and combinatorial optimization in a single platform, paving a promising path for faster and sustainable computing.

Aarrestad et al. show that, in contrast to psychedelics, the nonhallucinogenic psychoplastogen tabernanthalog promotes neuroplasticity through 5-HT_2AR activation without immediately increasing extracellular glutamate levels or immediate early gene expression.

Nanoparticles (NPs) hold promise for therapeutic applications, but their interactions with biological environments remain poorly understood. Here, the authors reveal that the glycosylation of the biomolecular corona, particularly sialic acid content, significantly influences NP interactions with cellular uptake processes, offering new insights into predicting NPs’ biological fate.

Authors show that water trapped between 2D MXene sheets forms amorphous ice clusters at low temperatures, which cause a hysteresis of electrical conductivity. This structural rearrangement of water is affected by the presence of solvated cations, allowing reversible switching of the electronic properties of MXene films.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

The ocean carbon sink strengthened in previous warm El Niño years due to reduced CO₂ outgassing in the tropics. Here the authors show that the ocean carbon sink declined in 2023 despite record-high sea surface temperatures (SSTs), primarily due to SST-driven outgassing of CO₂ in the subtropics.

To improve annotation in non-targeted metabolomics studies, authors develop a Multiplexed Chemical Metabolomics (MCheM) platform, combining post-column derivatization with integrated data processing. MCheM enables feature-resolved chemical tagging across complex mixtures, which provides orthorgonal chemical information about unknown metabolites.

Hominin fossils from the Ledi-Geraru Research Project area, Ethiopia, suggest that early Homo and Australopithecus species co-existed in the region more than 2.5 million years ago.

Incomplete plumbing affects over a million people in the USA. Analysis of individual and household data for the 2015–2019 period from the US–Mexico border reveals the unequal nature of plumbing poverty in the borderlands and provides insight for future planning.

Current models suggest that DLK1 is an inhibitory ligand in the Notch pathway. Here, the authors show that DLK1 does not interact with Notch receptors, instead blocking Activin signaling via an interaction with Activin receptor type-2B.

Interact-omics, a high-throughput cytometry-based framework, resolves the cellular interaction landscape.