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In an integrated analysis of transcriptomic data from the SUBSPACE consortium and public datasets of patients with sepsis, acute respiratory distress syndrome, trauma and burns, dysregulation within four consensus molecular clusters related to myeloid and lymphoid cells is associated with mortality and illness severity.

Hematoxylin and eosin (H&E) staining is a widely used method in histopathology, but it cannot directly inform about specific molecular markers. Here, the authors present ROSIE, a deep-learning framework that computationally imputes the expression and localisation of dozens of proteins from H&E images.

Proteomic analysis of paired cerebrospinal fluid and plasma samples from 2,171 individuals drawn from multiple cohorts, including the Global Neurodegeneration Proteomics Consortium, reveals age-related changes in the ratios of proteins in the cerebrospinal fluid and plasma that are associated with cognitive function, enhancing understanding of blood–brain barrier dynamics in aging.

Across species, how aging leads to progressive spatial memory decline is not fully understood. This study reports dysfunctional spatial coding by aged entorhinal grid cells and networks related to impaired spatial memory and identifies implicated neuronal gene expression changes.

Here the authors use a range of approaches to examine the interplay between genetic variants linked to risk for polygenic skin diseases and transcription factors (TFs) important for skin homeostasis. The findings implicate dysregulated binding of specific TF families in risk for diverse skin diseases.

Graphene systems have the potential to host Wigner crystal states at zero magnetic field. Here, the authors report transport signatures consistent with Wigner crystallization in AB-stacked bilayer graphene at both zero and finite magnetic fields.

While the connectivity of VTA dopamine neurons is well studied, less is known about the connectivity of VTA glutamate and GABA neurons. Here, authors show that these neurons form local circuits to modulate reward, aversion, feeding and locomotion.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer. Here, the authors develop a NLPHL specific model to identify 34 distinct cell states across 14 cell types that co-occur within 3 lymphocyte predominant ecotypes (LPEs) for 171 cases.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

RNA base editing represents an exciting modality in precision genetic medicine. Here the authors develop short, metabolically stable RNA oligonucleotides (RESTORE 2.0) that enable precise and efficient RNA base editing, demonstrating successful in-vivo correction of a disease-causing human mutation.

Polar skyrmions are nanoscale topological structures of electric polarizations. Their collective modes, dubbed as “skyrons”, are discovered by the terahertz-field-excitation, femtosecond x-ray diffraction measurements and advanced modeling.

The ratio between the levels of two synaptic proteins in cerebrospinal fluid predicts future cognitive resilience versus decline among presymptomatic individuals and individuals with early Alzheimer’s disease harboring amyloid and tau pathology.

Hypertrophic cardiomyopathy-causing mutations in cardiac myosin disrupt its auto-inhibited OFF state, leading to hypercontractility. Here, the authors show that disease-linked mutations remote from intramolecular OFF state interfaces can allosterically impair myosin autoinhibition

A modularized open-source pipeline for invasive brain signal decoding bridges the gap between closed-loop neuromodulation and clinical brain–computer interface approaches in a large patient cohort.

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.

Plasmacytoid dendritic cells are type 1 interferon (IFN-I)-producing antiviral specialists that have been shown to be able to differentiate into conventional dendritic cells. Here the authors show how this differentiation is controlled by tumor necrosis factor driving type 2 conventional dendritic cell-like reprogramming and IFN-I blocking it, a process that occurs during inflammation, injury and aging.

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

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

The roles of distinct dopaminergic neuron subpopulations and the circuit projections driving their activity during threat behaviors remain incompletely understood. Here, the authors demonstrate that substantia nigra pars lateralis dopamine neurons receive selective, robust excitation from auditory and temporal association cortices, which, combined with rapid action potential firing, contributes to auditory threat conditioning.

Clonalscope is a method for cancer subclone detection leveraging copy number profiles estimated using spatial and single-cell sequencing data.

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.

Acoustically activatable nanocarriers made by incorporating 5% sucrose into liposomes release drug with low-intensity ultrasound, providing a readily clinically translatable system for both central and peripheral noninvasive neuromodulation.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

A fresh approach to protein design that incorporates excited intermediate states enables precise control over the lifetime of protein interactions, with potential applications in cell-signalling modulation and in biosensors and synthetic circuits.

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.

A mass spectrometry-based approach globally identifies protein regulators of metabolism and reveals the role of LRRC58 in controlling cysteine catabolism.

Dioxythiophene-based polymers effectively convert electric potential into optical readouts. Here, the authors used such polymers to optically record bioelectric signals with microvolt sensitivity and sub-millisecond temporal resolution, highlighting their potential in optical bioelectronics.

In a prospective study enrolling 1,222 patients from 22 emergency departments, a device using a machine-learning-based signature of blood mRNAs demonstrated clinically acceptable performance to diagnose bacterial and viral infections and to predict the all-cause need for critical care interventions within 7 days, with benchmark to established biomarkers and risk scores.

Small proteins (<50 kDa) are difficult to resolve by cryo-EM due to low signal-to-noise ratios and alignment challenges. Here, authors engineered conformationally rigid antibody fragments (Rigid Fabs) enabling high-resolution cryo-EM structures of small (~20 kDa) proteins like KRAS.

UCHL5 is a deubiquitinating enzyme that cleaves Lys-48-linked polyubiquitin chains. Here, the authors discover through in-vivo CRISPR-Cas9 screens that Uchl5 is involved in immune evasion and modulation of extracellular matrix deposition in head and neck squamous cell carcinoma.

N-type sulfides are attractive solar-to-hydrogen photocatalysts but have faced challenges with overall water splitting. Here, the authors report that tailored surfaces and cocatalysts enable sulfides to achieve efficient, stable, and safe production of separate streams of stoichiometric hydrogen and oxygen.

Glutamatergic and GABAergic (γ-aminobutyric acid-producing) cortical neuronal activity drives proliferation of small lung cell cancer via paracrine interactions and through synapses formed with tumour cells.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

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.

Using data from the CoVPN 3008 study, the authors show that the neutralizing antibody correlate of risk holds in people living with HIV. However, the nAb correlate was weaker and shorter-lived in a vaccine-immunity versus hybrid-immunity population.

The Zika viral protease NS2B-NS3 is a crucial target for antiviral drug development due to its role in processing viral polyproteins. Here, the authors utilize crystallographic fragment screening and deep mutational scanning to identify binding sites for resistance-resilient inhibitors.

Antibiotics and nutritional stresses can inactivate Pseudomonas aeruginosa efflux pump mexEFoprN. Here, the authors demonstrate that the inactivation of this efflux pump impacts quorum sensing mediated virulence in P. aeruginosa clinical isolates.

Large-scale longitudinal health records reveal consistent association of varicella-zoster virus reactivation with dementia.

Analysis of human Robertsonian chromosomes originating from 13, 14 and 21 reveal that they result from breaks at the SST1 macrosatellite DNA array and recombination between homologous sequences surrounding SST1.

An artificial intelligence model defines a data-driven set of total parenteral nutrition compositions to assist clinicians in personalized treatment of neonates in intensive care and is able to adapt recommendations to patient status, with validation from large external cohorts and a blinded reader study.

Using cryo-electron microscopy, the interactions of Sestrin2 and CASTOR1 with GATOR2 were resolved, revealing how mTORC1 activation is regulated and how nutrient availability triggers signalling for cellular growth.

Charge transport and extraction in polycrystalline perovskite films are often hindered by inefficient carrier transfer across grain domain boundaries (GDBs). Here, authors employ supramolecular assisted Rb+ delivery for in-situ GDB bridging, achieving efficiency of 26.02% for perovskite solar cells.

Heo, Xu et al. used comprehensive plasma proteomics to identify 416 plasma proteins (294 new) associated with Alzheimer’s disease and applied machine learning to select 7 proteins that were highly predictive of Alzheimer’s disease across multiple cohorts.

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.

An optical slab waveguide with highly programmable nonlinear functionality is described, enabling the demonstration of versatile control over broadband second-harmonic generation across the spectral, spatial and spatio-spectral domains.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.