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Native top-down proteomics reveals epidermal growth factor receptor–estrogen receptor-alpha (EGFR–ER) signaling crosstalk in breast cancer cells and dissociation of nuclear transport factor 2 (NUTF2) dimers to modulate ER signaling and cell growth.

Virtual nature exposure reduces self-reported pain and is associated with decreased brain responses linked to somatosensory and nociceptive processing, providing new insights into the underlying mechanisms of nature-induced analgesia.

In this study, the authors present optimization and efficacy testing of apolipoprotein-based lipid nanoparticles for delivering various nucleic acid therapeutics in vivo to immune cells and their progenitors in the bone marrow.

Rickettsia species are bacterial pathogens that obligately reside in the host cell cytosol. Here, Sun et al. report that Rickettsia use host glutathione as a nutrient source that enables bacterial cell division and innate immune evasion.

Sydnor et al. developed a new tractography atlas of thalamocortical structural connections and applied it to three youth samples. They uncovered coordinated development between thalamic connectivity and hierarchical cortical plasticity in humans.

N-acetyltransferase 10 (NAT10) is an N⁴‐acetylcytidine (ac⁴C) writer, which catalyzes RNA acetylation at cytidine N⁴ position on RNAs. Here, the authors show that NAT10 catalyzes ac⁴C addition to a long non-coding RNA encoded by the oncogenic DNA virus Kaposi’s sarcoma-associated herpesvirus (KSHV), triggering viral lytic reactivation from latency, which promotes NAT10 recruitment of IFI16 mRNA, resulting in inflammasome activation.

In this work, authors report a mechanism for how phage can promote the spread of costly antibiotic resistance. They show that faster-growing sensitive cells dominate the biomass periphery where they encounter more phage, allowing for slower growing resistant cells to persist.

Hydrogel materials have emerged as versatile platforms for biomedical applications. Here this group reports an mRNA lipid nanoparticle-incorporated microgel matrix for immune cell recruitment/antigen expression and presentation/cellular interaction thereby eliciting antitumor efficacy with a single dose.

Tumor-associated macrophages are pivotal in control over solid tumors. Here the authors show that these macrophages express chemosensors that detect lipid variants in the tumor microenvironment that can regulate the function of these cells.

Spatially segregated rRNA processing dictates nucleolar morphology and drives outward progression of pre-ribosomal RNA through nucleolar phases.

ACTA2 p.R179 variants cause pediatric strokes due to moyamoya disease (MMD)-like occlusions. Here, the authors show that Acta2^R179C/+ smooth muscle cells are immature, causing MMD-like lesions that are reversed by altering cellular metabolism.

The authors identify a single main-chain hydrogen bond required to keep GABA_A receptors closed in the absence of neurotransmitter. Electrophysiology and molecular dynamics simulations suggest disruption of this bond is a key component of channel opening during inhibitory synaptic signaling in the brain.

Pocock et al. reveal that transient activation of 5′ AMP-activated protein kinase and estrogen-related receptor drives robust maturation of multicellular human cardiac organoids, enabling modeling of desmoplakin cardiomyopathy dysfunction, which could be rescued using the bromodomain and extra-terminal inhibitor INCB054329.

Mammalian recombination activating genes RAG1 and RAG2 are essential for the production and diversification of antibodies and T-cell receptors via V(D)J recombination in lymphocytes but are absent in simpler eukaryotes such as the yeast Saccharomyces cerevisiae. Here the authors integrate mouse RAG1/2 in S. cerevisiae and demonstrate the ability to create combinatorial diversity starting from a single genetic locus in vivo.

Acyl-CoA synthetase long-chain family 4 (ACSL4)-driven changes in lipid metabolism are shown to modulate the sensitivity of intestinal epithelial cells to ferroptosis, thereby exacerbating inflammatory bowel disease.

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.

Colobomatous microphthalmia often lacks a genetic diagnosis despite its developmental complexity. Here, the authors show that rare variants in NR6A1 cause a syndromic form with eye, kidney, and vertebral defects, supported by zebrafish functional validation.

This work develops dye-lanthanide tandem-sensitized perovskite nanocrystals that can harvest a broad range of infrared light, upconvert it to sensitize excitons, and generate multicolor band-edge exciton luminescence

Iron has been shown to be necessary for the activation and differentiation of CD8⁺ T cells. Here the authors investigate changes in CD8⁺ T cell metabolism in iron limiting conditions and find that aspartate is increased yet downstream nucleotide synthesis is suppressed and addition of exogenous aspartate partially rescues T cell function.

Proteins are often modified by complex carbohydrates (N-glycans). Here, authors identified gene regulators of this process and uncovered links between plasma protein Nglycosylation, metabolic and liver diseases, and anti-inflammatory proteins.

In Myeloiddysplastic syndromes, CEBPA mutations are linked to disease progression and AML. Here, the authors use somatic reprogramming and genome editing to generate isogenic cell lines from an MDS patient, identifying CEBPA bZIP ___domain disruption as causative for disease progression.

The pathogen Orientia tsutsugamushi is an obligate intracellular bacterium that depends on host cell machinery for intracellular movement. Here, Manigrasso et al. provide insights into the molecular mechanisms by which the bacteria hijack the host’s microtubule networks to navigate within cells.

This study demonstrates that high alcohol concentrations during binge drinking activate a small GABAergic neuronal ensemble in the medial orbitofrontal cortex, which subsequently reduces further alcohol consumption. This effect is mediated by the ensemble’s projections to the mediodorsal thalamus.

Vertical transmission is thought to favour beneficial host–microbe interactions, but these may also be context dependent. Here Bruijning et al. show with a model that variable environments can select for bet-hedging by hosts via imperfect vertical transmission of microbes.

The heterogenous nature of rheumatoid arthritis renders the prediction of responsiveness to biological treatments difficult. Here the authors analyze bulk RNA-seq data from the STRAP trial (n = 208) to build a machine-learning model for predicting responses to etanercept, tocilizumab and rituximab with AUCs around 0.75 to potentially assist in therapy planning.

Analysis of whole-genome sequencing data from hematopoietic stem and progenitor cells taken from patients with myeloma shows how treatment shapes clonal architecture and sheds light on the evolution of treatment-related myeloid neoplasms.

Combining chemo- and biocatalytic sites within an integrated catalyst to perform complex, multi-step reactions is highly desirable but challenging. Here, the authors present an ionic organic cage platform for such a chemoenzymatic catalyst, achieved by electrostatic complexation of cationic molecular cage-encapsulated Pd clusters (Pd@C-Cage⁺) and anionic Candida antarctica lipase B.

Short-lived halogens have a substantial indirect cooling effect on climate and this cooling effect has increased since pre-industrial times owing to anthropogenic amplification of natural halogen emissions.

The mechanism of macrophage cytotoxicity against cancer cells requires further illustration. By employing CRISPR screening in CAR-macrophage and cancer cell co-culture system, the authors identify depletion of ATG9A on cancer cells sensitizes them to macrophage-mediated killing, which can be synergic with CSF1R inhibition in cancer treatment.

The role of bile acid receptor TGR5 in feeding regulation remains elusive. Here, authors show that physiological and pharmacological activation of TGR5 in the nucleus of the solitary tract lowers feeding and enhances leptin signaling in rats.

NIPBL perturbation activates long terminal repeat (LTR)-derived alternative promoters due to reorganization of chromatin’s hierarchical structure, leading to LTR co-option and oncogene activation in melanoma cell lines.

Tumour evolution and heterogeneity in high grade serous ovarian cancer (HGSOC) remains poorly characterised. Here, the authors investigate the genomic landscape of HGSOC and reveal two distinct evolutionary trajectories associated with clinical outcomes.

Furlan’s team engineered the printing of Gd₂Zr₂O₇ photonic coatings on curved metal surfaces, achieving high reflectivity values that outperform state-of-the-art thermal barrier coatings while having remarkably low density and minimal thickness

Enzymes with identical sequences of amino acids can display varying activities when encoded with mRNA with different properties, but why this is the case has been a mystery. Now, it has been shown that synonymous mutations in mRNA alter the partitioning of proteins into long-lived soluble misfolded states with varying activities.

Zhao et al. uncover the protein composition and atomic structure of ciliary radial spoke 3, revealing it as a metabolic hub that regulates ciliary motility, providing insights into ciliary diseases

The DEAD-box ATPase DDX39B (UAP56) plays a critical role in mRNP remodeling and nuclear export. Here, the authors identify TREX-2.1 complex that facilitates DDX39B release from mRNP and reveal the underlying mechanism via cryo-EM structures of TREX-2/DDX39B and TREX-2.1/DDX39B.

Miao et al. show that loss of neuronal Vps13d in mice leads to mitochondrial dysfunction, GSDME-mediated mitochondrial DNA release, cGAS–STING inflammatory signaling and activation of microglia, culminating in neuronal loss.

The activation and infiltration of immune cells to the vasculature is intimately linked to the immunopathology of hypertension. Here the authors implicate PI3Kγ signalling in the trafficking of CD8⁺ T cells between lymphoid and non-lymphoid organs, and the development of hypertension in a murine model.

Harty and colleagues report that physiological microbial exposures in mice can enhance memory T cell presence in the brain and influence neurological disease outcomes.

Catalytic asymmetric dearomatizations of electronically unbiased naphthalenes remains a long-standing challenge in organic chemistry. Here, the authors describe a silver-mediated enantioselective aza-electrophilic dearomatization approach that couples readily accessible vinylnaphthalenes in conjunction with azodicarboxylates to afford chiral polyheterocycles via formal [4 + 2] cycloaddition reactions.

Disordered rock-salt positive electrodes are promising for nickel- and cobalt-free lithium-ion batteries. Here, the authors demonstrate a synthesis method that yields highly crystalline, sub-200 nm dispersed single particles, enabling improved electrochemical cycling stability.

Here, the authors show that delafloxacin, a respiratory antibacterial fluoroquinolone, binds the Streptococcus pneumoniae topoisomerase IV-DNA cleavage complex in a distinct tilted-ring conformation involving multiple Mg^2 + , K⁺ and water links. Intrinsic target affinity likely contributes to activity against quinolone-resistant bacteria.

Porous graphene integrated into graphene oxide membranes yields smart molecular sieves that switch separation based on the solvent. This allows for graded separations of different-sized molecules.

Bacterial chromosomes segregate while undergoing replication. Here the authors show that such concurrent replication and segregation cannot be achieved by passive entropic forces alone, and that loop-extruders could be sufficient to explain segregation.

Projections of extinctions of bird species and losses of functional diversity over the next 100 years suggest that even immediate and widespread threat abatement would be insufficient to prevent losses, and targeted recovery programmes must also be implemented to conserve avian diversity.

Lymphostatin is a large protein required for Escherichia coli virulence. Here, Griessmann et al. use electron cryo-microscopy to describe the structure of lymphostatin determined at different pH values, showing three conformations, six distinct domains, and long inter-___domain linkers that occlude the catalytic sites of the N-terminal glycosyltransferase and protease domains.

Bacterial attachment on implanted medical devices depends on surface topography. Here, the authors screen combinatorially generated shapes embossed into polymers to investigate topographical control of bacterial responses to surfaces.