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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.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

G protein-coupled receptors (GPCRs) are important targets for drug discovery. Here, the authors develop a Virion Display array of 315 functional non-odorant GPCRs, providing a platform for high-throughput, unbiased screening for small molecule drugs, affinity reagents, and microbial interactions.

A pangenome analysis of 76 wild and domesticated barley accessions in combination with short-read sequence data of 1,315 barley genotypes indicates that allelic diversity at structurally complex loci may have helped crop plants to adapt to agricultural ecosystems.

Different molecular subtypes defined by specific gene rearrangements have been described for acute lymphoblastic leukaemia (ALL). Here, the authors show that ZNF384 fusion activates FLT3 expression conferring a therapeutic vulnerability for ZNF384- rearranged ALL subtype.

Aqueous organic redox flow batteries are promising for grid-scale energy storage, although their practical application is still limited. Here, the authors report highly ion-conductive and selective polymer membranes, which boost the battery’s efficiency and stability, offering cost-effective electricity storage.

Demographic analysis of life expectancy and maximum reported age at death provides evidence that human lifespan has reached its natural limit.

African Americans have an elevated risk of developing chronic kidney disease, yet only a fraction of those with high-risk genotypes develop the disease. Here, the authors show that a missense variant in APOL1 has a strong protective effect when co-inherited with the high-risk G2 allele of APOL1, with important implications for clinical practice and translational research.

Smart monitoring devices with integrated mechanical protection and piezoelectric induction are limited. Here, the authors report a strategy to grow piezoelectric Rochelle salt crystals in 3D-printed cuttlebone-inspired structures to produce smart monitoring devices with integrated mechanical protection and electrical sensing capability.

Using resonance Raman spectroscopy and serial femtosecond X-ray crystallography, the authors show the heme a₃ iron and Cu_B in the resting oxidized form of Cytochrome c Oxidase are coordinated by a hydroxide ion and a water molecule, respectively.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

A study presents a cross-species proteomic map of synapse development in neocortex and reveals that the human postsynaptic density assembly develops two to three times slower than that in macaques and mice.

Lysosomal storage diseases like mucopolysaccharidosis type I (MPS I) cause pathology before birth and result in early morbidity and mortality. Here, the authors show that in utero base editing mediates multi-organ phenotypic and survival benefits in a mouse model recapitulating a common human MPSI mutation.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

Analysis of genomic data from 25 distantly related plant species shows signatures of selection on the same gene families and functions that repeatedly contributed to local adaptation to climate.

The 3CL protease of SARS-CoV-2 is inhibited by PF-00835231 in vitro. Here, the authors show that the prodrug PF-07304814 has broad spectrum activity, inhibiting SARS-CoV and SARS-CoV-2 in mice and its ADME and safety profile support clinical development.

Particle nanofeatures activate the inflammasome and influence immunity.

Chemical upcycling of polyolefin plastic waste over metal-based catalysts is crucial for the circular economy, but currently available methods are incompatible with chlorine-contaminated feedstocks. Here the authors propose a two-stage dechlorination–hydrogenolysis (or hydrocracking) upcycling strategy to tackle this problem.

Widespread shallow-water hydrothermal venting in the North Atlantic, probably a source of methane, coincided with the onset of the Palaeocene–Eocene Thermal Maximum, according to borehole proxy records and seismic imaging.

A polymer patch that rapidly and robustly adheres to diabetic wounds and contracts in a pre-programmed manner promotes wound closure and re-epithelialization, as shown in mouse and human skin, in mini-pigs and in humanized mice.

Cryo-EM structures of simian immunodeficiency virus (SIV) envelope trimers with neutralizing antibodies reveal mechanisms—conserved throughout SIV evolution—of immune evasion through extended variable loops and glycan shielding, involving both N- and O-linked glycans.

Preparing two-dimensional heterolayers by vertically stacking chemically different layers with multiple anions remains challenging. Now, a general approach for the synthesis of heterolayered oxychalcogenides using molten hydroxides as unconventional solutions for the rapid stacking of oxide and chalcogenide layers with precise composition control is demonstrated.

The organization of chromatin into self-interacting domains is universal among eukaryotic genomes. Here, the authors report a reference-grade pepper genome assembly and use this reference to help describe the relationship among 3D chromatin conformation, chromatin function, and gene expression.

Hydronium ions bordering cancer cells are highly concentrated into a small extracellular region, and in tumour tissue such severely polarized acidity correlates with the expression of monocarboxylate transporters and with the exclusion of cytotoxic T cells.

In the CELLTOP Phase I trial, stem cells were harvested from patients with spinal cord injury and injected into their central nervous system after processing. The procedure was safe, with no reported serious adverse events during the 2-year follow-up period.

A description is given of the ENCODE effort to provide a complete catalogue of primary and processed RNAs found either in specific subcellular compartments or throughout the cell, revealing that three-quarters of the human genome can be transcribed, and providing a wealth of information on the range and levels of expression, localization, processing fates and modifications of known and previously unannotated RNAs.

T cell-specific antigens are discovered at high throughput without killing target cells.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

Ultrasound neuromodulation overcomes limitations of electrode-based stimulation through improved

targeting and long-term stability for treating neurological disorders. Here, authors present a hair-thin, implantable piezoelectric stimulator that selectively modulates neurons in the deep brain.

A newly discovered negative allosteric modulator of the µ-opioid receptor works together with naloxone to potently block opioid agonist signalling with reduced adverse effects.

Rapamycin and FK506 are macrocycles that contain an FKBP-binding domain and an effector domain responsible for interacting with their respective targets, mTOR and calcineurin. Now, a 45,000-compound macrocycle library has been synthesized by fusing oligopeptides with synthetic FKBP-binding domains. Screening and subsequent optimization yielded a highly potent FKBP-dependent inhibitor of hENT1.

Jayavelu, Samaha et al., apply machine learning models on hospital admission data, including antibody titers and viral load, to identify patients at high risk for Long COVID. Low antibody levels, high viral loads, chronic diseases, and female sex are key predictors, supporting early, targeted interventions.

Transposon-associated inverted repeats play a role in drought resistance and yield-related traits in maize.

This study uses gene expression predictors for the dorsolateral prefrontal cortex and other brain regions to perform a transcriptomic imputation analysis of schizophrenia, identifying 413 genic associations across 13 brain regions and 36 significantly enriched pathways.

Traditional 2D cell culture platforms do not accurately reflect the physiology of human tumors. Here, authors combine bioprinting and high-speed live cell interferometry with machine learning to measure drug sensitivity at single-organoid resolution in a label-free manner.

Roland et al. report the results of a randomized, non-comparative phase 2 trial of neoadjuvant nivolumab or a combination of nivolumab and ipilimumab in patients with resectable retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.

The NetID algorithm annotates untargeted LC-MS metabolomics data by combining known biochemical and metabolomic principles with a global network optimization strategy.

High-resolution subnational mapping of child growth failure indicators for 105 low- and middle-income countries between 2000 and 2017 shows that, despite considerable progress, substantial geographical inequalities still exist in some countries.

Whole-exome sequencing of 250 parent–offspring trios identifies an enrichment of rare damaging de novo mutations in individuals with cerebral palsy and implicates genetically mediated dysregulation of early neuronal connectivity in the etiology of this disorder.

Analysis of chromatin state and accessibility in mouse tissues from twelve sites and eight developmental stages provides a comprehensive view of chromatin dynamics.

Mechanisms occurring during seawater corrosion of as-built laser powder bed fusion 316L stainless steels are largely unknown. Here, the authors show that Mn, Si-rich slags found in between laser tracks are responsible for corrosion.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Activation of the non-canonical NF-κB signalling pathway by AZD5582 results in the induction of HIV and SIV RNA expression in the blood and tissues of antiretroviral-therapy-treated humanized mice and rhesus macaques.

The miniaturization of antennas beyond a wavelength is limited by designs which rely on electromagnetic resonances. Here, Nan et al. have developed acoustically actuated antennas that couple the acoustic resonance of the antenna with the electromagnetic wave, reducing the antenna footprint by up to 100.

Cryo-EM is used to visualize the SARS-CoV-2 RTC bound to each of the natural NTPs as well as remdesivir triphosphate (RDV-TP) in states poised for incorporation, explaining the interactions required for NTP recognition and RDV-TP selectivity.

Insights on the mechanistic differences between artificial metalloenzymes (ArMs) with non-native metal centres and the free cofactor or natural enzymes are scarce. Now, a detailed mechanistic analysis of a cyclopropanation reaction catalysed by such an ArM is provided, revealing intriguing differences to the natural system.