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Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

Saturation genome editing of RNU4-2 identifies the functional and clinical impact of variants across the entire gene and delineates variants that cause a new recessive neurodevelopmental disorder distinct from ReNU syndrome.

The authors use a physiological approach, finding recent extreme heat events had deadly heat stress conditions, particularly for fully exposed older people. Conditions were well below wet-bulb temperatures of 35˚C, a common heat stress indicator.

Stable and cell-specific transgene expression can be achieved through in vivo site-specific integration of large DNA payloads using a two-vector system of enveloped delivery vehicles and adeno-associated viruses.

Cells use fluid flow to deliver proteins to their leading edge. An actin barrier creates a compartment where contraction drives flow, steering proteins toward growing regions. This mechanism coordinates protein distribution with cell shape changes.

In this work, authors provide evidence that bacteria in spatially structured populations protect each other from antibiotics through collective nutrient consumption, creating ‘death fronts’ that sweep through the colony– explaining why infections often survive treatments that work in lab tests.

Robin and colleagues describe a population of blood vessel-resident macrophages that function within the vasculature to maintain vascular and blood homeostasis in zebrafish and identify a conserved population of these cells in mice.

Results of the phase 2 POLAR trial show that biomarker-guided treatment in patients with metastatic pancreatic cancer based on homologous repair deficiency leads to encouraging clinical response rates in immune cell-infiltrated tumors.

The long-term natural history of long-COVID is not well understood. In this population-based cohort study from Scotland, the authors describe symptom prevalence and health-related quality of life up to 18 months after a positive SARS-CoV-2 test and compare with matched test-negative controls.

Regenerative agriculture promises lower emissions and healthier soils, but results vary by environment and practice. Across four diverse rainfall zones, this study finds that practices that yielded the largest soil carbon gains and greatest greenhouse gas mitigation were not always the most profitable, underscoring the need for context-specific evaluation using multiple sustainability metrics.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Expression of agouti signalling protein in neurons in the medial preoptic area is increased by group housing and negatively associated with care, and overexpression of Agouti reduces care and enhances infanticide in previously tolerant mice.

Here, the authors show that early-life high-fat/high-sugar diet induces sex-specific alterations in adult feeding behavior, hypothalamic transcriptome and blood metabolome, with Bifidobacterium longum and prebiotic FOS + GOS administration restoring these effects via distinct mechanisms, highlighting their therapeutic potential.

This study presents an organ-wide spatial transcriptomic analysis of human skin from different anatomical sites using a combination of MERFISH technology and existing datasets from healthy and diseased skin.

Subcellular compartmentalization of the glycolytic enzyme PFKM regulates cell fate and metabolic switch during skeletal muscle differentiation.

In this phase 2, randomized trial in early Alzheimer’s disease, the TREM2 agonistic antibody AL002 showed target engagement but did not meet the primary endpoint of change from baseline in Clinical Dementia Rating-Sum of Boxes score.

SARS-CoV-2 infection is associated with an increased risk of arterial and venous thrombotic events. Here, the authors investigate the degree to which this association is modified by virus variant and vaccination using electronic health record data for ~18 million adults in England.

While therapies targeting type I BRAF mutations have been developed, there are limited options for those with type II and III mutations. Here, the authors identify a subset of BRAF-mutant non-small cell lung cancer patients and characterise the pan-RAF inhibitor exarafenib, demonstrating efficacy in preclinical models and investigating subsequent resistance mechanisms.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

Da Pra, Boriati and colleagues show that physiological glucocorticoids suppress growth-factor-induced cardiomyocyte regeneration by inhibiting ERK signaling and propose glucocorticoid receptor antagonism as a strategy to enhance their protective and regenerative effects.

Endoplasmic reticulum (ER) and lysosomes mutually influence each other’s function. This study shows that ER-located ryanodine receptors physically connect with lysosomes, favoring lysosomal availability for autophagy over lysosomal secretion.

The authors present a genetically encoded tool based on a bifunctional enzyme that can regenerate NAD⁺ while executing an engineered glycerol shunt. The tool successfully restored redox imbalance and modulated lipid metabolism in vitro and in a mouse hepatic steatosis model.

Sangbum Park, Catherine Matte-Martone and colleagues track Langerhans cells, dendritic epidermal T cells and epithelial basal cells in living mice over time and show that immune cells coordinate with epidermal cells to maintain their positions.

Dual cyclin A/B RxL inhibitors selectively kill small cell lung cancer cells and other cancer cells with high E2F activity.

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Pulmonary type 2 inflammation is associated with type 2 innate lymphoid cells. Here the authors use the Collaborative Cross mouse panel to show that ILC2 abundance during type 2 lung inflammation is different across the panel and identify free-fatty acid receptor 3 (Ffar3) as a gene responsible and show cytokine and ILC2 functional changes.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Results of the phase 1/2 TACTOPS trial show that autologous T cell therapy targeting PRAME, SSX2, MAGEA4, Survivin and NY-ESO-1 in patients with pancreatic ductal adenocarcinoma is feasible and safe, and leads to encouraging clinical responses and evidence of antigen spreading in responders.

Multiple myeloma involves alterations to T cell function, but mechanisms underlying disease evolution remain unclear. Here the authors find that, unlike solid cancers, multiple myeloma lacks exhausted T cells and is instead characterized by antigen-driven terminal memory T cell differentiation, which may be driven by tumour-intrinsic features including tumour burden and antigen-presentation gene expression.

In this work, Wilson et al., examined sharing of Salmonella between humans, animals and the environment using household samples from Malawi. They revealed an interconnected web of Salmonella circulation, underscoring the importance of the One Health concept.

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

An outbreak of MPXV in sooty mangabeys in Côte d’Ivoire was linked to MPXV-infected fire-footed rope squirrels, providing direct evidence of interspecies transmission and indicating risk for zoonotic transmission of MPXV from both hosts.

The authors uncover a direct, BAI1-dependent, role for C1q in the control of neural stem cell proliferation and quiescence via MDM2–p53 and p32, a complement cascade-independent mechanism of C1q action that has implications for central nervous system health and disease.

In 2022, mpox predominantly spread through sexual contact, necessitating updated prevention strategies. Here, the authors show that rectal challenge in male cynomolgus macaques with a 2022 clade IIb MPXV isolate mimics sexual transmission, and that vaccination with modified-vaccinia Ankara protects pre- but not post-exposure.

Research on sustainable diets has primarily focused on human and planetary health, neglecting workers in food value chains. This study quantifies the risk of forced labour embedded in five different diets in the USA, underscoring the need to integrate such risk in sustainable diet transition efforts.

SARS-CoV-2 induces mild infection in ferret model. Here, Ryan et al. characterise optimal infection dosage inducing upper respiratory tract (UTR) viral shedding, progression time of viral shedding, and pathology in ferrets and finally provide evidence for protection after re-challenge.

Pluripotent stem cells are found throughout the planarian body but regenerate organs in distinct regions. This study shows that the receptor RoboA and the secreted protein Anosmin1a act as signals that restrict stem cell plasticity and differentiation.

Menstrual disturbance has been reported as a symptom of post-acute COVID-19 while other long COVID symptoms may vary across the menstrual cycle. Here, the authors investigate this possible bidirectional relationship in a series of observational studies of women in the UK.