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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.

A pathogenic subset of NK cells is identified that promotes type 1 diabetes and is generated via T cell-derived IL-21.

In a multicenter, randomized trial of patients with atrial fibrillation and a low risk of thromboembolic events, treatment with the anticoagulant rivaroxaban showed no benefit in reducing cognitive decline, stroke or transient ischemic attack when compared to placebo.

Measles virus and canine distemper virus (CDV) are still causing health impairments in humans and animals. Here, the authors develop a synthetic antibody protecting ferrets from lethal CDV infections, providing a roadmap for antiviral drug design.

A global synthesis of >600 studies finds that across agro-ecosystems, grasslands and forests in temperate and tropical zones, increasing plant diversity has a consistently positive effect on plant performance and the suppression of antagonists.

Without key cell cycle control genes, SAR11 cells experience aneuploidy and growth inhibition when exposed to changes in nutrients, carbon sources or temperature stress, a vulnerability that may represent an evolutionary trade-off for adaptation to oligotrophic environments.

The authors conduct a national inventory on individual tree carbon stocks in Rwanda using aerial imagery and deep learning. Most mapped trees are located in farmlands; new methods allow partitioning to any landscape categories, effective planning and optimization of carbon sequestration and the economic benefits of trees.

Men and women differ in their lipid biology. Here, the authors identify NCOA1 as a female-specific regulator that promotes the conversion of white fat into energy-burning fat, protecting women from obesity and metabolic disease by enhancing thermogenic activity in subcutaneous fat.

Respiration enhances cerebrospinal fluid flow through mechanical and autonomic pathways. Inhale length and diaphragm motion influence its displacement and net flow, identifying a modifiable, noninvasive mechanism relevant to brain homeostasis.

Decarbonizing road transport is critical, but the costs and emissions of low-carbon vehicles in Africa remain uncertain. The authors show that battery electric vehicles with solar off-grid systems can cost effectively reduce life-cycle emissions well before 2040.

The systemic discovery of metal–small-molecule complexes from biological samples is a difficult challenge. Now, a method based on liquid chromatography and native electrospray ionization mass spectrometry has been developed. The approach uses post-column pH adjustment and metal infusion combined with ion identity molecular networking, and a rule-based informatics workflow, to interrogate small-molecule–metal binding.

Recent work has revealed that dendritic cells (DCs) are more heterogeneous than previously thought, yet the functional roles of these newly described DC subsets remain unclear. Here, Li et al. find that in mice, TSLP from keratinocytes activates transitional DC-derived DC2 to promote GATA3⁺ regulatory T cells and mediate immunosuppression during inflammation and cancer.

Centrosome dynamics play a central role in immune regulation. Here, the authors demonstrate that centrosome integrity as well as centriole numbers and spatial organisation emerge as critical determinants of effective T cell responses.

Bruijns et al. present a modeling tool that enables the tracking of learning dynamics across subjects to reveal how behaviors emerge and adapt. Applying the tool to a decision-making task in mice uncovers similarities and differences across individuals.

The authors propose a Generalized Latent Equilibrium framework for fully local credit assignment in physical, dynamical neuronal networks such as the brain. By exploiting dendritic structure and prospective coding in cortical neurons, it enables an online approximation of backpropagation through space and time.

Decentralized natural resource governance is thought to aid conservation and reduce poverty, but its heterogeneous local effects are under-explored. A study in Nepal shows that forest governance decentralization reduces poverty but the benefits are greater for dominant ethnic and caste groups compared with minority ones.

Using whole-brain MRSI, this study builds a metabolic connectome derived from five metabolite signals. It reveals a network topology balancing local similarity and global diversity, mirroring structural, cytoarchitectonic and genetic organization.

Results from the phase ELAD 2 trial reveal that liraglutide is safe and well tolerated in people with mild to moderate Alzheimer’s disease but does not significantly slow brain metabolism decline.

In this phase 1 trial, treatment of patients with fibrolamellar hepatocellular carcinoma with a therapeutic peptide vaccine targeting the fusion kinase DNAJB1–PRKACA, which is the driver of the disease, together with nivolumab and ipilimumab, was safe and led to encouraging preliminary clinical responses, and translational analysis showed activation of immune responses.

Here the authors report a randomized controlled trial showing that a previously developed artificial intelligence model estimates patient mortality risk as accurately as doctors and standard risk scores, but did not change clinical care decisions in the emergency department. This suggests that prediction accuracy alone does not necessarily translate into real-world clinical impact.

Blocking peptidoglycan synthesis kills bacteria. The authors show that the E. faecium PBP5 peptidoglycan binding site is distal to the active site, which could be the focus of antibiotic strategies that hinder substrate recruitment.

This study discusses polygenic, omnigenic and stratagenic models developed to explain multigenic disease risk. It proposes means to test their validity, which has implications for research, drug development and precision medicine.

The Taiwan Precision Medicine Initiative (TPMI) has built a cohort of more than half a million individuals with Han Chinese ancestry, providing a rich resource of genetic and medical data for this group.

An implantable vagus nerve-targeted device safely reduces disease activity and joint damage in rheumatoid arthritis, offering a new nondrug treatment for patients who do not respond to or cannot tolerate medication.

Here, the authors present archaeology of the Namorotukunan site in Kenya’s Turkana Basin that demonstrates adaptive shifts in hominin tool-making behaviour spanning 300,000 years and increasing environmental variability. They contextualize these findings with paleoenvironmental proxies, dating, and geological descriptions.

It is uncertain how much life expectancy of the Chinese population would improve under current and greater policy targets on lifestyle-based risk factors for chronic diseases and mortality behaviours. Here we report a simulation of how improvements in four risk factors, namely smoking, alcohol use, physical activity and diet, could affect mortality. We show that in the ideal scenario, that is, all people who currently smokers quit smoking, excessive alcohol userswas reduced to moderate intake, people under 65 increased moderate physical activity by one hour and those aged 65 and older increased by half an hour per day, and all participants ate 200 g more fresh fruits and 50 g more fish/seafood per day, life expectancy at age 30 would increase by 4.83 and 5.39 years for men and women, respectively. In a more moderate risk reduction scenario referred to as the practical scenario, where improvements in each lifestyle factor were approximately halved, the gains in life expectancy at age 30 could be half those of the ideal scenario. However, the validity of these estimates in practise may be influenced by population-wide adherence to lifestyle recommendations. Our findings suggest that the current policy targets set by the Healthy China Initiative could be adjusted dynamically, and a greater increase in life expectancy would be achieved.

Thirty years of forest demographic data, combined with recent ecophysiological measurements, reveal that intense Amazon droughts sharply increase tree mortality once soil moisture falls below a threshold, and that these hot droughts will become more frequent and intense as Earth warms towards hypertropical conditions.

Triacetic acid lactone (TAL) is a platform chemical with a wide range of applications. Here, the authors report the discovery of a polyketoacyl-CoA thiolase from Burkholderia sp. RF2-non_BP3, termed as BktBbr, which has unusually high in vivo and in vitro activity for production of TAL.

Despite observed routinely from spacecrafts landing on, e.g., lunar soil, the origin of radial streak patterns has been unclear up to now. Here, the authors report an experimental study of such instabilities in the coupled dynamics of rocket plumes and sand surfaces.

Neutrophils infiltrate glioblastomas with the capacity to engage pro/anti tumoural responses. Here the authors developed proteomic workflows to stratify neutrophil heterogeneity by function. This work provides a platform to study neutrophil proteomes with single cell resolution in glioblastoma.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Immune evasion mechanisms of initial HIV infection are incompletely understood. Here, the authors show that HIV rewires the glycosylation machinery of infected myeloid cells, forming a glycan shield that engages glyco-immune checkpoints and inhibits cell function, and thus targeted killing of infected cells.

This computational modelling study unveils the detailed DNA translocation mechanisms of two archetypal SF2 family helicases, XPD and DinG, and sheds light on the functional impact of XPD-associated mutations on genetic disease etiology.

A wide range of policies and actions can be used to address energy insecurity, and there are many actors and institutions to carry them out. This Perspective provides an overview of the many levers, or opportunities, that electricity sector actors have to reduce energy insecurity and affordability in the United States.

Here they show that PPARα-dependent mitochondrial programming promotes the differentiation of pluripotent stem cell-derived β cells. Targeting mitochondria has the potential to improve β cell replacement efforts for the treatment of type 1 diabetes.

Evaluating long-term immunogenicity and safety, this study shows that fractional and standard dose boosting with Pfizer and AstraZeneca vaccines following CoronaVac or AstraZeneca priming produces adequate immune responses, informing COVID-19 booster vaccination policy.

The impact of ACKR3 constitutive activity is unknown. Here, the authors suppress basal ACKR3 activity using inverse agonistic nanobodies to stabilize an inactive conformation and revealing a role for ACKR3 in basal cell motility.

The authors reveal that the C-terminal tail anchors of BCL-2 family proteins control BH3 binding and cell survival by allosteric regulation at the mitochondrial membrane, involving BAX recruitment and complex disruption upon BH3 mimetic antagonism.

The authors examine the impact of monthly unconditional cash transfers starting at childbirth on families with low incomes. Transfers had minimal effects on family processes and maternal wellbeing, but improved family incomes and time mothers spent doing enriching activities with their child.

Here the authors report an allotrope to the nanocarbon family, Graphene-P-phenyl-Graphene, for potassium-ion batteries.

Here authors demonstrate how opposing trajectories of dopamine transmission underlie changes in drug seeking and taking over chronic drug use. Increased dopamine to drug cues elevates craving, whereas decreased dopamine produces escalation of drug consumption.

Bergel et al. show that an infraslow rhythm connecting the brain and body during sleep is shared by lizards, mammals and birds, revealing an ancestral process and reshaping our understanding of the evolution of sleep states.

Myocardial infarction disrupts cardiac repair mechanisms, limiting regeneration. Here, the authors show that extracellular matrix therapies activate spatial and cell-specific pro reparative programs, revealed through spatial transcriptomics and snRNA-seq.

FUS drives the formation of biomolecular condensates in cells. Here, the authors reveal the dynamics and biophysical properties of FUS nanoclusters, an intermediate state in the phase separation pathway of FUS.

Here authors identify GluN2D-containing NMDA receptors on interneurons as a specific target for rapid antidepressant action. Blocking GluN2D restores stress-impaired plasticity and mimics the effects of ketamine with fewer side effects.