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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.

Authors measure plasma proteins in a cohort of hospitalised patients presenting to the emergency department with suspected infection, revealing six discrete host response clusters that were driven by pathogen exposure and organ dysfunction, and had distinct clinical characteristics, hospital courses, and responses to treatment.

The molecular etiology of hypertensive disorders of pregnancy is largely unknown. Here the authors show from a prospective study of diverse pregnancies that the disease can be split into molecular subtypes based on RNA data and validated a classifier for individuals with no preexisting high risk factors.

Inflammasome activation requires a complex and incompletely understood network of signalling events. Here the authors characterize step-by-step contributions of TLR3, caspase-8, RIPK3 and MLKL to the activation of NLRP3 inflammasome in response to double-stranded RNA.

Prostate cancer progression may be enhanced by a high-fat diet. Here the authors show that a diet high in saturated fats enhance the MYC-driven transcriptional program, a feature that independently predicts prostate cancer progression and death.

In an updated report on 70 laboratory-confirmed highly pathogenic avian influenza A H5N1 cases in the USA between March 2024 and May 2025, the absence of human-to-human transmission to date was confirmed, with no known mutations of resistance to neuroaminidase inhibitors.

Polθ helicase is crucial for DNA repair and a target for precision medicine for cancer therapy. Here, the authors reveal the mechanism of action of the small-molecule inhibitor AB25583, and show its high specificity and selective killing of BRCA1/2^– cancer cells and synergy with olaparib.

Copper (Cu) dysregulation contributes to aging and oxidative stress. Here the authors develop imaging probes to detect labile hepatic Cu, revealing age-related increases that deplete ALDH1A1 activity, and show that chelation therapy restores Cu homeostasis, offering a potential strategy to mitigate liver aging.

The evolution of myeloid malignancies is investigated using combined single-cell sequencing and immunophenotypic analysis.

This multisite study detects a link between brain dynamic functional network connectivity and current and future post-traumatic stress symptom severity with a stronger effect in the female group.

‘Protein arginine methyltransferase 5 (PRMT5) is known to regulate the expression of genes involved in metastasis. Here, the authors show that PRMT5 methylates Akt and methylation is required for phosphorylation and activation of Akt; ultimately leading to the increase in expression of pro-metastatic transcription factors.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Imaging-based companion diagnostics can provide real-time information to match therapies to patients; however, glutathione is abundant in most cells, making it an unlikely candidate for companion diagnosis. Now, a chemical probe has been developed that can detect elevated glutathione concentrations via photoacoustic imaging. Using this probe enables normal and pathological states in a lung cancer model to be distinguished.

Wang et al. show how glucose sensing via O-GlcNAcylation drives the assembly of a glycolytic metabolon on the mitochondrial surface to couple metabolic efficiency with neuronal activity.

A new NMR method—requiring only milligram quantities of substrates—uses isotopically labeled neighbor atoms to directly and continuously report on KIEs at the reaction center. Application of the methodology defines a reaction coordinate for sialidase hydrolysis.

A high-resolution kidney cellular atlas of 51 main cell types, including rare and previously undescribed cell populations, represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

Pseudouridine (psi) is an RNA modification that can affect its physiology, including increased half-life. Here the authors identify sites of psi modification in the human transcriptome using direct RNA sequencing and provide a “ground truth” list of psi sites, sites of high psi occupancy, and transcripts that may be modified at multiple sites.

Back pain and sciatica are often caused by intervertebral disc degeneration. Sakai and colleagues identify a subset of nucleus pulposus progenitor cells from the intervertebral disc and show that loss of these progenitor cells correlates with ageing and intervertebral disc degeneration.

Copper contributes to regulating zebrafish rest–activity cycles through the locus coeruleus system by modulating the biosynthesis of norepinephrine; brain copper deficiency leads to lower levels of both synaptic norepinephrine and daytime activity.

EF-G drives ribosomal translocation along mRNA. Time-resolved cryo-EM captured translocation with EF-G•GTP—without inhibitors—revealing how EF-G uses ribosome fluctuations to drive translocation and GTP hydrolysis to leave at the right moment.

Intralesional injection of an oncolytic virus prior to surgery shows favorable clinical activity over surgery alone in patients with locally advanced, resectable melanoma, supporting further evaluation in the neoadjuvant setting for this population.

Hypoxia is a hallmark of many diseases including cancer and ischemia, and detection can be invasive and of low resolution and specificity. Here the authors show a hypoxia probe that converts non-ionizing light to ultrasound, which enables the acquisition of high-resolution 3D images in deep tissue.

Tumour cells utilize a pool of the molecular chaperone heat shock protein 90 to ensure correct protein folding in mitochondria. Here, the authors demonstrate that mitochondrial heat shock protein 90 regulates the folding of a subunit of the electron transport chain and that this can contribute to tumorigenesis.

A nanoparticle that senses reactive oxygen and nitrogen species in the liver should improve in vivo detection of cellular stress.

A collection of chemical tools and spectroscopic techniques demonstrate that Zn availability influences Cu⁺ storage and localization in the green alga Chlamydomonas, with Zn limitation causing the accumulation of Cu⁺ in lysosome-related organelles.

Biochemical analysis, and imaging using a copper-sensitive fluorescent sensor, demonstrate that copper regulates cAMP-mediated lipolysis by inhibiting the activity of the cAMP-degrading phosphodiesterase PDE3B.

Drugs and antibiotics induce oxidation and mobilization of membrane-bound copper(I) ions to copper(II) species within the E. coli cytosol, causing oxidation of a single cysteine residue of the multiple antibiotic-resistance regulator MarR, that leads to formation of disulfide-bonded MarR tetramers and release of dimers from sites of transcriptional activity.

A genome-wide association study for attention deficit/hyperactivity disorder (ADHD) identifies 12 loci and implicates neurodevelopmental pathways and conserved regions of the genome as being involved in underlying ADHD biology.

Han-Xiang Deng and colleagues identify TMEM230 mutations in Lewy body–confirmed Parkinson's disease. They also show evidence that disease-associated TMEM230 mutants impair synaptic vesicle trafficking in neurons.

Double deficiency of FADD and RIPK1 is shown to rescue the defects in mouse embryonic development and lymphocyte proliferation that are characteristic for mice with single gene deficiencies. This work suggests that the activity of FADD (presumably in conjunction with caspase-8 and c-FLIP) is to keep necrosis in check by causing the cleavage of RIPK1.