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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.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Single atom catalysts, comprising minute amounts of transition metals dispersed on inert substrates, have emerged as prominent materials in heterogenous catalysis but their precise arrangement on surfaces is challenging. Here, the authors introduce the on-surface synthesis of a single atom platform wherein atoms are firmly anchored to specific coordination sites evenly distributed along carbon-based polymers.

Caspase 8 protein expression is largely absent in small cell lung cancer (SCLC) patients. Here, the authors generate a caspase 8 deletion SCLC mouse model and show that it promotes a neuronal progenitor-like cell state and pre-tumoral immunosuppression triggered by necroptosis that promotes metastasis.

Krisai et al. compare brain structure and cognitive function in elderly patients with and without atrial fibrillation using brain MRI and cognitive testing. They find that atrial fibrillation is associated with more brain lesions and lower cognitive function, but the cognitive impairment occurs primarily through direct effects of the arrhythmia rather than through brain damage.

To characterize molecular changes during cell type transitions, the authors develop a method to simultaneously measure protein expression and thermal stability changes. They apply this approach to study differences between human pluripotent stem cells, their progenies, parental and allogeneic cells.

Here the authors show that human pancreatic islets adapt during pregnancy with increased α-cell area and GLP-1 abundance, while key differences from islet adaptations in mouse pregnancy include unchanged β-cell PRLR abundance and absent β-cell 5-HT_2B receptor expression.

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.

It is important to know how the recent COVID-19 pandemic shaped the immune memory against the causal SARS-CoV-2 virus. Here authors show that long years following mild disease at primary infection, SARSCoV-2 spike-specific CD4 + T cells with distinct phenotypes and T cell receptor clonotypes, associated with viral suppression persist.

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

TUG protein localizes to the endoplasmic reticulum-Golgi intermediate compartment, forms biomolecular condensates, and organizes and stabilizes these membranes to support their function in diverse secretory and degradative trafficking pathways.

Over 20 species of geographically and phylogenetically diverse bird species produce convergent whining vocalizations towards their respective brood parasites. Model presentation and playback experiments across multiple continents suggest that these learned calls provoke an innate response even among allopatric species.

The Cia21 locus on chromosome 3 has been associated with rheumatoid arthritis severity in females. Here the authors show this locus houses a non-coding polymorphic estrogen receptor binding site and how it regulates neighbouring gene expression of CD2, implicating CD2 signalling in the sexual dimorphism of a variety of T cell-dependent autoimmune diseases.

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

A comparison of alpha diversity (number of plant species) and dark diversity (species that are currently absent from a site despite being ecologically suitable) demonstrates the negative effects of regional-scale anthropogenic activity on plant diversity.

Graphene nanoribbons show promise for high-performance field-effect transistors, however they often suffer from short lengths and wide band gaps. Here, the authors use a bottom-up synthesis approach to fabricate 9- and 13-atom wide ribbons, enabling short-channel transistors with 10⁵ on-off current ratio.

Identifying cellular identities is crucial in single-cell transcriptomics. Here, authors show that large-scale deep learning-based cell annotation models, trained on hundreds of cross-tissue scRNA-seq datasets, enhance prediction quality for fine-grained highly related cell types and states.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

An analysis involving the shotgun sequencing of more than 300 ancient genomes from Eurasia reveals a deep east–west genetic divide from the Black Sea to the Baltic, and provides insight into the distinct effects of the Neolithic transition on either side of this boundary.

Hybrid metal halide semiconductors typically rely on chiral A-site ammonium cations for chiral induction in the lattice. Now it has been shown that chirality in low-dimensional achiral metal halide semiconductors can be induced by non-ammonium, non-A-site chiral molecules through remote stereocontrol of the inorganic framework.

Ultrasensitive, spatially-resolved proteomics techniques allow mapping the organisation of healthy and diseased tissues. Here, the authors develop a workflow for spatially-resolved, quantitative tissue proteomics with spatially aware statistics and clustering, with which they characterise a human atypical teratoid-rhabdoid tumour at different spatial resolutions.

Small regulatory RNAs (sRNAs) in Vibrio cholerae have been shown to modulate several biological processess including virulence, biofilm formation, quorum sensing, colony morphology and stress resistance. Here, the authors show that VadR sRNA acts as a posttranscriptional inhibitor of the crvA mRNA and that mutation of vadR increases cell curvature, whereas overexpression has the inverse effect.

Large Clostridial toxins infiltrate host cells using a translocation domain (LCT-T). Here, using a genomics-driven approach and functional assays, the authors uncover the presence of distant LCT-T homologs in bacteria outside clostridia and provide evidence for a toxic effector function in the gammaproteobacterium Serratia marcescens.

Here, the authors employ Raman-Activated Cell Sorting (RACS) and metagenomics to identify organisms that can forage on O-glycan monosaccharides in the mouse gut, which they use to construct a bacterial consortium able to reduce Clostridioides difficile colonization based on competition for mucosal sugars.

Pitulescu et al. and Hasan et al. show that Dll4–Notch signalling in endothelial tip cells regulates angiogenesis through control of artery formation, linking sprouting angiogenesis and artery formation.

Decreased functionality and expression of trypanosome haptoglobin-hemoglobin receptor (HpHbR) is one of the evolutionary modifications that have allowed Trypanosoma brucei gambiense to infect humans. Here, Horakova et al. show that hemoglobin uptake in African trypanosomes is mediated almost exclusively by HpHbR and relevant for slender-to-stumpy differentiation. T. b. gambiense is poorly competent to differentiate into stumpy forms compared to T. b. brucei, due to reduced functionality of HpHbR.

Pancreatic beta-cell glucose metabolism is coupled to insulin secretion. Here the authors set out to characterize changes in beta-cell metabolism in hyperglycemia which may contribute to insufficient insulin secretion in type 2 diabetes and, using a multi-omics approach, find that mitochondrial metabolism is perturbed.

An important contribution of cancer associated fibroblasts (CAFs) in regulating chemoresistance has been reported. Here the authors investigate the impact of chemotherapy on CAF subsets in patients with high-grade serous ovarian cancer, suggesting that residual ANTXR1+ myofibroblasts are associated with inhibition of anti-tumor immunity.

The microscopic structure of quantum defects in 2D materials is crucial to understand their optical properties and spin-photon interface. Here, the authors report the direct imaging of charge state-dependent symmetry breaking of sulfur vacancies and rhenium dopants in 2D MoS₂, showing evidence of a Jahn-Teller effect.

A fluorescence-based assay that leverages the enzyme Cas12a to transduce and amplify cumulative forces generated by cells allows for the quantification of platelet dysfunction, as shown with patients who had undergone cardiopulmonary bypass.

Structural, biochemical and cellular studies reveal JMJD7 to be a Jumonji-C oxygenase that catalyzes (3S)-lysyl hydroxylation of the translation factor family of GTPases, DRG1 and DRG2.

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

Altered expression and function of the extracellular matrix protein PRG4 have been associated with osteoarthritis. Here, the authors show that mast cell tryptase β cleaves PRG4, resulting in a reduction of lubrication and activation of inflammation in this context.

Although anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis and generally considered pathogenic, their functional relevance is incompletely understood. In this study, the authors describe an ACPA with a protective effect against antibody-induced arthritis in mice.

Planar cell polarity (PCP) is generated by the restricted localization of membrane-bound multiprotein complexes, but how they are trafficked to the correct location is unknown. Here, the authors show that the GTPase ARF1 and the AP-1 adaptor complex are major regulators of PCP protein trafficking in vivo.

Multiregion sequencing is needed to better capture the heterogeneity of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Here, the authors analyse HCC and iCCA tumours with multiregion single-cell RNA-seq, revealing cellular dynamics and communication networks with immune cells.

Here the authors identify novel PML-partners and demonstrate that PML NBs control their sumoylation and that PML-controlled sumoylation of transcriptional regulators maintains the embryonic stem cell transcriptome and transposable element silencing.

We uncover key processes of the genomic evolution of small cell lung cancer under therapy, identify the common ancestor as the source of clonal diversity at relapse and show central genomic patterns associated with drug response.

Aircraft measurements over the Amazon show that new particle formation in the upper troposphere emerges when isoprene, emitted by forests, undergoes oxidation in the presence of nitrogen oxides produced by lightning.

Using cryo-electron tomography (cryo-ET) and proteomics, this study identifies the tethering of pathological tau filaments within defined brain extracellular vesicles in Alzheimer’s disease, shining light on the link between these vesicles and tau pathology.

Magma transports metals to the Earth’s surface to form ore deposits, but only sulphide-undersaturated magmas were thought to be capable of generating large amounts of ore. Laboratory experiments indicate that large volumes of gold ore can also be generated by sulphide-saturated magma, if the redox conditions of the magma are suitable.

Multiple molecular profiling methods are required to study urothelial non-muscle-invasive bladder cancer (NMIBC) due to its heterogeneity. Here the authors integrate multi-omics data of 834 NMIBC patients, identifying a molecular subgroup associated with multiple alterations and worse outcomes.

The tumour microenvironment counteracts immune therapy in Glioblastomas. Authors show here, using spatially resolved and single cell transcriptomics, that dysfunctional T cells are induced by a myeloid cell subset via Interleukin-10 signalling, and inhibition of the downstream JAK/STAT pathway might restore glioblastoma immune therapy responsiveness.

Ancient diets have been reconstructed from archaeological pottery based on lipid remains, but these can lack specificity. Here, Hendy and colleagues analyze ancient proteins from ceramic vessels up to 8000 years old to produce a more nuanced understanding of ancient food processing and diet.

Although progress in the coverage of routine measles vaccination in children in low- and middle-income countries was made during 2000–2019, many countries remain far from the goal of 80% coverage in all districts by 2019.

Though ubiquitin is known to broadly influence endosomal trafficking, few ubiquitin-utilizing enzymes targeting endosomal regulators are known. Here, the authors find that the deubiquitylating enzyme (DUB) USP32 influences endosomal membrane dynamics by deubiquitinating Rab7.