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G-protein-coupled receptors (GPCRs) function as monomers and in multiple oligomeric forms. Here, authors present a set of 12 assemblies of the apelin receptor (APLNR), providing a detailed view of the monomer-dimer transition.

The GABA_B receptor is a mandatory heterodimer. Here authors show the existence of GABA_B dimers of dimers in neurons, and their relevance in human health. By solving the structure of this tetramer, they show the structural basis for a negative cooperativity between the dimers within such a complex.

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.

A clinical trial testing whether monitoring ctDNA clearance during treatment for nasopharyngeal cancer could be used to inform decisions about an individual’s subsequent therapeutic programme shows promising results.

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.

Thymine DNA glycosylase (TDG) was identified as a synthetic-lethal target in p53-deficient cancers through alterations in double-stranded RNA accumulation. A covalent small-molecule inhibitor of TDG exhibited potent efficacy against p53-deficient tumors.

Small-cell lung cancer (SCLC) is a highly aggressive cancer type with immunosuppressed phenotype. Here, the authors find that depletion of nonhomologous end joining DNA repair regulator PRKDC is able to induce activation of the cGAS/STING pathway and potentiate the efficacy of immunotherapy in SCLC pre-clinical models.

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.

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.

In the dose-expansion cohort of this phase 1b trial, the EGFR×HER3 bispecific antibody–drug conjugate BL-B01D1 given to patients with metastatic esophageal squamous cell carcinoma led to encouraging clinical response rates, which need to be confirmed in larger efficacy trials.

A statistical method to quantify crystallographic textures in aluminum alloys under additive manufacturing conditions is introduced. Experiments and simulations reveal interfacial energy anisotropy dominates texture selection and grain competition.

B cell subsets expanding during tumor progression have been associated with impaired anti-tumor responses and resistance to immunotherapy. Here the authors report that STING agonism or anti-PD-1 induce intratumoral B cell infiltration, and that depleting B-cells improves response to immunotherapies in preclinical models of hepatocellular carcinoma.

Phylogenetic analysis of trait heritability (PATH) applies phylogenetic correlations to single-cell lineage tracing data, quantifying cell state plasticity and transition probabilities. PATH offers insights into cell state heritability and transition dynamics in cancers.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Flexible energy storage systems usually have limited energy densities. Here the authors report a flexible lithium–oxygen battery with the cathode consisting of titanium dioxide nanowire arrays grown on carbon textiles, which displays high mechanical strength as well as promising electrochemical performance.

Immune checkpoint inhibitors have shown some activity in patients with adrenocortical carcinoma (ACC), a rare aggressive malignancy with limited treatment options. Here the authors report the results of a phase 2 trial of camrelizumab (anti-PD1) plus apatinib (VEGFR inhibitor) for previously treated ACC.

This study introduces the concept of Ancestry Components and shows that they can offer improved population stratification correction for geographically correlated traits. By using ancestry-aware polygenic score construction in admixed individuals, the authors find that effect sizes are conserved across ancestry groups.

The CARseq method allows users to assess cell type-specific differential expression using RNA-seq data from bulk tissue samples, which opens up several opportunities for re-analyzing existing RNA-seq data and designing new studies.

The balance between radial progenitors and intermediate precursors to generate upper-layer neurons during the development and evolution of the cerebral cortex is mediated by members of the tuberous sclerosis complex.

In this multicenter phase 1 trial, patients with advanced gastric and gastroesophageal junction cancer were safely treated with the CLDN18.2-targeting antibody–drug conjugate SHR-A1904, leading to encouraging objective response rates.

Zinc affinity plays a key role in the zinc plating and stripping processes but its internal mechanism is still unclear. Here, the authors report a protective layer with controllable zinc affinity by adjusting the crystal orientation to suppress the dendrite growth on the zinc anode interface.

Haplotyping of human genomes is improved by augmenting experimental dilution-based haplotyping with statistical analyses, a strategy known until now only as 'Moleculo.'

DeepRETStroke is a deep learning system using retinal photographs to detect silent brain infarction and predict future stroke events.

Socioeconomic status is multidimensional and can change over time. Xu, Lui, Ji et al. found dimension-specific, late-stage-specific and change-specific socioeconomic effects on brain, cognition, personality and emotion.

A cross-ancestry GWAS meta-analyses of brainstem structures identify 713 associations. It reveals shared/distinct genetic architectures across ancestries/substructures and overlaps with neuropsychiatric disorders and physiological functions.

For specific computation problems where electronic digital processors have shortcomings in simulating, an analog optical system may be a solution, Here, the authors present an analog all-optical implementation of a coherent Ising machine based on a network of injection-locked multicore fiber lasers.

Liang, Yan, Long, Ji et al. find that the origin and dynamics of 5-hydroxymethylcytosine (5hmC) during early development are not conserved between humans and mice and that 5hmC contributes to the activation of human embryonic genes.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

It is unclear how early-life urbanicity influences adult neurobehavioral traits. This study reveals that earlier menarche mediates the relationship between early-life urbanicity and adult neurobehavioral traits associated with mental disorders.

A solid methodology that enables the facile manufacturing of large-scale metal–organic framework membranes sets the foundation for their potential commercialization and widespread industrial application.

The genetic basis of primary sclerosing cholangitis has only been partially uncovered. Here, the authors perform a multitrait genome-wide association study to provide insight into the genetic etiology of primary sclerosing cholangitis risk and possible therapeutic drug targets.

Optimal stochastic tracking control is a promising strategy for guiding therapeutic brain stimulation in neurological disorders.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

DNA methylation quantitative trait locus (mQTL) analyses on 32,851 participants identify genetic variants associated with DNA methylation at 420,509 sites in blood, resulting in a database of >270,000 independent mQTLs.

Growth hormone-releasing hormone (GHRH) controls metabolism and tissue growth through binding to the cognate receptor (GHRHR). Here authors report the structure of the human GHRHR bound to its endogenous ligand and the stimulatory G protein which reveals a characteristic hormone recognition pattern of GHRH by GHRHR.

A strategy with donor–acceptor covalent organic frameworks enhances photocatalysis by harnessing both singlet and triplet states, enabling metal-free, co-catalyst-free and sacrificial donor-free red-light-driven organic transformations with high efficiency.

Here, the authors report structures of corticotropin releasing factor receptor 2 (CRF2R) bound to agonist Urocortin 1 (UCN1) and coupled to G proteins G₁₁ and G_o, offering insight into the structural basis for the ability of CRF2R to couple with multiple G protein subtypes.