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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.

Watt, Dauber, Szkop and colleagues find that H3K4me3 remodels 5′UTR selection in hypoxia and that this process is independent of HIF-1 transcriptional mechanisms.

A technique called condense-seq has been developed to measure nucleosome condensability and used to show that mononucleosomes contain sufficient information to condense into large-scale compartments without requiring any external factors.

Activity in a set of parabranchial neurons in the mouse brain is increased during chronic pain, predicts coping behaviour, and can be modulated by circuits activated by survival threats.

Acetyl-CoA synthetases have been proposed as targets for development of new antimicrobial drugs. Here, Jezewski et al. identify isoxazole-based compounds with activity against the pathogenic fungus Cryptococcus neoformans, and describe their mechanism of action as inhibitors of fungal acetyl-CoA synthetases.

Chronic Kidney Disease affects 1 in 10 people worldwide with prevalence continuing to rise, thus there is a need to identify novel biomarkers that can add value to existing clinical and biochemical risk predictors. Here the authors identify miR190a-5p as potential indicator of kidney health and disease progression in patients with chronic kidney disease.

Apoptotic cells often release extracellular vesicles that aid in their clearance and provide molecular information to cellular neighbours. Here, the authors show that some adherent apoptotic cells also create vesicles that remain attached at the site of death.

2D semiconductors hold promise for solution-processed circuits requiring low-cost components and manufacturing scalability. Here, the authors investigate the criteria for the electrochemical exfoliation of high aspect-ratio nanosheets from 28 different layered materials, identifying the most promising candidates and key bottlenecks for solution-processed complementary electronics and functional circuits.

Despite improving therapeutic options, the prognosis for patients with metastatic castration-resistance prostate cancer (mCRPC) remains poor. Here, the authors identify MCL1 copy number alterations as a prognostic and predictive biomarker, demonstrating its therapeutic potential as a drug target, either alone or in combination, in patients with mCRPC.

Whether paternal pre-conceptual SARS-CoV-2 infection impacts sperm RNA content, or effects offspring phenotypes, has not been previously investigated. Here authors report changes in sperm noncoding RNAs in SARS-CoV-2 infected sires and increased anxiety-like behaviors in offspring.

Organ banking via vitrification could transform transplantation but has never been achieved at human organ scales. Here, the authors demonstrated successful vitrification in ≤ 3L CPA volumes and ~<1L porcine liver with successfully rewarming ≤ 2L CPA volumes using nanowarming.

Human host-associated cellular products may act as induction agents for bacteriophages.

The authors conducted prospective multimodal monitoring of simultaneous brain and heart function to define physiological changes during the human dying process leading to circulatory arrest.

Tan et al. identify PRDM16 as a key repressor of fibrotic switching in smooth muscle cells and show that its downregulation in atherosclerosis drives smooth muscle cells toward a synthetic fate, promoting fibrous plaques.

Pucella, Maqueda-Alfaro and colleagues distinguish three developmentally related subsets of mouse plasmacytoid dendritic cells that differ in their ability to produce type I interferon and their susceptibility to virus.

A capillary flow printing technique can be used to fabricate printed carbon nanotube thin-film transistors with submicrometre channel lengths on rigid or flexible substrates.

Limited diagnostic capacity for asymptomatic individuals hinders malaria elimination efforts in Africa. Here, the authors present a near point-of-care method based on colorimetric LAMP detection that outperforms expert microscopy and commercial rapid diagnostic tests for Plasmodium detection in asymptomatic and submicroscopic individuals.

Klein and colleagues characterize 04_A06, a new V_H1-2-encoded broadly neutralizing antibody that has marked breadth and potency against extended multiclade HIV-1 pseudovirus panels and can maintain full viral suppression in HIV-1-infected humanized mice.

The authors identify AgcT as the glycosyltransferase required for synthesis of Bacteroides fragilis-derived α-galactosylceramides (BfaGCs), metabolites known to regulate natural killer T cells, and its structural homologue BgsB that synthesizes α-glycosyl diacylglycerols (aGDGs). They establish a functional link between the production of BfaGCs or aGDGs and the activity and development of natural killer T cells.

Adoptive regulatory T cell (Treg) therapy holds promise for the treatment of a range of immunopathological conditions. Here the authors explore the HLA engineering of allogenic Treg products that avoid T cell and NK cell attack and maintain immunomodulatory function in a human skin-xenograft model.

Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

Bacterial antigens, such as lipopolysaccharides, are complex structures which remain difficult to synthesise or purify for antibody generation. Here, authors present a platform technology using Citrobacter rodentium - an enteric mouse pathogen - to both produce and present complex antigens for antibody generation.

DIAL designs synthetic promoters for generation of heritable setpoints of gene expression across a range of cell types.

The molecular and cellular evolution of the superior colliculus, a key visual center, is unclear. Liu et al. revealed conserved and species-specific cell types, genes, and circuits across mice, tree shrews, and humans by single-cell transcriptomics.

This study introduces a system called TArgeted Cohesin Loader (TACL) that recruits cohesin complexes at defined genomic regions and induces loop extrusion events in living cells, exploring its impact on chromatin organization and gene expression.

Non-steroidal anti-inflammatory drugs (NSAIDs) are known to alleviate pain by reducing inflammation. To the contrary, here, the authors show that selective inhibition of the prostaglandin E2 receptor (EP2) in Schwann cells eliminates pain without disrupting the protective and healing functions of inflammation.

The dietary fibre inulin is shown to promote fructose catabolism by the small intestinal microbiome, thereby mitigating fructose-induced hepatic lipogenesis and steatosis.

Chronic inflammation affects the male reproductive system, contributing to infertility. Using a mouse model of epididymitis, here, the authors report on the formation of tertiary lymphoid structures (TLS) under conditions of chronic inflammation, and show that TLSs sustain immune activation, contributing to anti-sperm autoantibody production and epididymal injury.

Wu, Zhang and colleagues introduce ‘compare and contrast spatial transcriptomics’ (CoCo-ST), a graph contrastive learning-based method for spatial transcriptomics analysis that detects low-variance structures.

The authors assessed echocardiographic parameters in adults from rural areas endemic for loiasis in the Republic of Congo. They report significant differences in the Congolese adults from existing standard measurements, which highlights need for population-specific reference values and a standardized approach to their establishment to improve comparability across studies.

The pathogenic avian flu H5N1 virus remains stable in raw milk and throughout the cheese-making process, but contaminated cheese fed to ferrets did not lead to infection, whereas raw milk did.

Polyamides (PAs) or nylons are types of plastics with wide applications, but due to their accumulation in the environment, strategies for their deconstruction are of interest. Here, the authors screen 40 potential nylon-hydrolyzing enzymes (nylonases) using a mass spectrometry-based approach and identify a thermostabilized N-terminal nucleophile hydrolase as the most promising for further development, as well as crucial targets for progressing PA6 enzymatic depolymerization.

Viruses generally have compact genomes, resulting in many viral mRNAs with short 5’ untranslated regions. An antiviral complex exploits this feature of viral mRNAs to selectively inhibit viral protein synthesis and repress viral replication.

The authors describe the isolation and characterization of broadly cross-neutralizing monoclonal antibodies (mAbs) against diverse H5Nx viruses from individuals who received a monovalent H5N1 vaccine 15 years ago. They identify five mAbs that potently neutralized the majority of H5 clades and protected against lethal 2.3.4.4b H5N1 infection in mice.

Matrix viscoelasticity regulates cell behavior in a stiffness-dependent manner. Here, the authors reveal that the mechanosensitive channel Piezo1 transduces soft matrix viscoelastic cues, through a coordinated interaction with molecular clutch mechanisms.

Exercise promotes recovery after stroke, but the underlying mechanisms are unclear. Here, the authors show that regulatory T cells enable exercise-induced repair by reducing neuronal hyperexcitability via interleukin-10, linking immunity to functional regeneration.

GTPase-activating proteins (GAPs) often contain regulatory PH domains. In this work, Soubias et al, using an integrated structure-function approach, discovered a mechanism where a GAP PH domain binds directly to a GTPase to induce allosteric changes facilitating GTP hydrolysis.

Particles produced by intense biomass burning can be transported, potentially by deep convection, in large numbers to the lower stratosphere, changing the stratospheric aerosol layer’s chemical and radiative properties, according to in situ measurements during an active fire season.

Here, authors provide a molecular view of a clustered saccharide patch on mucins as recognized by a bacterial binding module. This work provides insights into how microbes can remain attached to mucins in the mucus while grazing on their glycans.

Hydrogen exchange–mass spectrometry (HX–MS) is used to qualitatively assess how perturbations such as mutations and ligand binding impact protein ensembles. However, in theory, HX–MS data contain the information necessary to derive residue-level energies of local unfolding (ΔG_op). Now, a method called PIGEON-FEATHER has been developed, which can unambiguously determine residue-level ΔG_op from conventional HX–MS datasets.

The Panoptes antiphage system defends bacteria by detecting phage-encoded counter-defences that sequester cyclic nucleotide signals, triggering membrane disruption and highlighting a broader strategy of sensing immune evasion through second-messenger surveillance.

Rizzollo et al. show that BDH2 participates in iron distribution between cellular compartments, which sets the threshold for the ferroptosis vulnerability of the melanoma cell phenotypes, ultimately affecting their metastatic capacity

Scoliosis is a common yet poorly understood pediatric disorder. Using zebrafish disease models, Pumputis et al. identify pervasive cell stress responses as causing spine deformity and present possibilities for new therapies and diagnostic tools.

A high-resolution antigenic map of influenza A(H5) haemagglutinin (HA) enables the design of immunogenic and antigenically central vaccine HA antigens that elicit antibody responses broadly covering the A(H5) antigenic space.

Studies in mice show that acute stress activates hyperglycaemia via activation of a medial amygdala–ventral hypothalamic circuit that controls glucose metabolic responses in the liver, independently of adrenal and pancreatic hormones.

Plasmodium vivax reticulocyte binding protein 2b (PvRBP2b) is important for invasion of reticulocytes and PvRBP2b antibodies correlate with protection. Here, Chan et al. isolate and characterize anti-PvRBP2b human monoclonal antibodies and describe mechanisms by which these antibodies inhibit invasion.

Plasma proteomics plays a key role in advancing clinical research and biomarker discovery. Here, the authors show in a large MSCoreSys multicenter benchmark study that DIA outperforms DDA, delivering robust, precise, and reproducible label-free protein quantification across sites.

MrVI, based on deep generative modelling, is a unified framework for integrative, exploratory and comparative analyses of large-scale (multi-sample) single-cell RNA-seq datasets.

Multi-template PCR enables parallel DNA amplification but suffers from sequence-specific biases. Here, the authors develop a 1D-CNN model predicting amplification efficiency directly from the DNA sequence and discover adapter-mediated self-priming as a key cause of uneven amplification during PCR.