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Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Li et al. uncover a lysosomal surveillance response whereby intestinal lumen deacidification induces a transcriptional programme that boosts lysosomal activity and improves protein aggregate clearance in multiple worm disease models, extending healthspan.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

A study reports on the antigenic characterization of SARS-CoV-2 BA.1, BA.1.1 and BA.2 and the neutralizing activity of different monoclonal antibodies and sera against them.

Yu and colleagues leverage population-level data to construct a large-scale, geographically defined, inter-household social network. Using a multilevel network model, they show that having social ties in close geographic proximity is associated with stable household asset conditions, while geographically distant ties correlate to changes in asset allocation. Notably, they find that localised network interactions are associated with an increase in wealth inequality at the regional level, demonstrating how macro-level inequality may arise from micro-level social processes.

Growth of high-quality III–V semiconductors for electronics and optoelectronics usually requires an atomic-lattice matched substrate. Here, the authors use templated liquid-phase crystal growth to create single-crystalline III–V material up to ten micrometres across on an amorphous substrate.

Optical frequency combs in the mid-infrared are required for molecular gas detection applications but their realization in compact microresonator-based platforms is challenging. Here, Griffith et al. demonstrate on-chip broadband comb generation on a silicon microresonator spanning from 2.1 to 3.5 μm.

Materials that can alter their structure in response to light have potential as functional materials such as motors and actuators. Here the authors describe a low-cost system capable of rapid, reversible and wavelength-selective responses to light.

The semileptonic decay channels of the Λc baryon can give important insights into weak interaction, but decay into a neutron, positron and electron neutrino has not been reported so far, due to difficulties in the final products’ identification. Here, the BESIII Collaboration reports its observation in e+e- collision data, exploiting machine-learning-based identification techniques.

Thermal lepton pairs are ideal probes for the temperature of quark-gluon plasma. Here, the STAR Collaboration uses thermal electron-positron pair production to measure quark-gluon plasma average temperature at different stages of the evolution.

Two out of 15 dogs from households with confirmed human cases of COVID-19 were asymptomatically infected with SARS-CoV-2 and showed antibody responses to the virus.

The mechanisms by which Johari-Goldstein relaxation is accommodated in metallic glasses are difficult to clarify. Here, the authors elucidate the mechanism in an ultra-quenched metallic glass with a cooling rate of ~1010 K s⁻¹, by extended X-ray absorption fine structure spectroscopy.

Unlike the other iron-based superconductors, the parent compounds of the alkaline iron selenide superconductors are insulators. Dai and colleagues examine the spin-wave excitations in these materials and uncover evidence for a common magnetic origin for all iron-based superconductors.

Magnetic interactions in solids are usually short-range or else they involve itinerant electrons. Here, the authors evidence a long-range magnetic coupling mediated by orbital moments in a polar spacer layer of nonmagnetic insulating oxide, with a sign which oscillates with spacer thickness.

The recently discovered kagome metal AV₃Sb₅ is a new playground to study the interplay between superconductivity and charge-density-wave (CDW) state. Here, the authors report pressure-dependent evolution of CDW and superconductivity in CsV₃Sb₅, suggesting an unusual competition between the two phases.

Single molecular machines are capable of a variety of functions, but methods to couple motion between them are still lacking. Here, Wasioet al. report the emergent behaviour of spontaneously formed two-dimensional crystals, which display correlated switching of their sub-molecular rotor units.

Complex oxide interfaces are important for electronic and spintronic applications. In this study, the authors show the emergence of spontaneous magnetism at one such interface between two phases of BiFeO₃due to strain effects and piezoelectric coupling.

The CMS Collaboration reports the study of three simultaneous hard interactions between quarks and gluons in proton–proton collisions. This manifests through the concurrent production of three J/ψ mesons, which consist of a charm-quark–antiquark pair.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

The authors report upconversion in few-layer transition metal dichalcogenides, and attribute it to a resonant exciton-exciton annihilation involving a pair of dark excitons with opposite momenta, followed by the spontaneous emission of upconverted bright excitons.

The approval of first line immune checkpoint blockade (ICB) has improved outcomes for patients with metastatic non-small cell lung cancer (mNSCLC), however, whether patients would benefit more from ICB alone or alongside chemotherapy is unclear. Here, the authors develop a machine-learning based approach to help guide individual treatment selection patients with mNSCLC.

A new study generated and optimized a polygenic score for chronic kidney disease with reproducible performance across 15 cohorts of different ancestries, and identified potentially clinically relevant thresholds with predicted effects comparable to having a family history of the disease.

Ferromagnetic systems produced by the transition metal doping of semiconductors may be used as components of spintronic devices. Here, a new ferromagnet, Li_1+y(Zn_1-xMn_x)As, is prepared in bulk quantities and shown to have a critical temperature approaching 50 K.

Hsu and co-workers integrate cryo-electron tomography, cryo-electron microscopy and mass spectrometry to reveal the structural polymorphism of a pig coronavirus spike protein within intact viral particles, and how glycosylation modulates the conformational changes pertinent to host recognition.

OmiCLIP is a visual–omics foundation model that integrates histology and spatial transcriptomics. The associated Loki platform offers accurate and robust tools for alignment, annotation, cell-type decomposition and spatial gene expression prediction.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

Early Pleistocene artefacts at Calio suggest that Sulawesi was populated by hominins at around the same time as Flores, if not earlier.

Collagen-binding peptides identified via phage display can be used to enhance the homing of mesenchymal stem cells to osteoarthritic tissue, its lubrication by hyaluronic acid and its visualization via magnetic resonance imaging.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

The most up-to-date combination of results on the properties of the Higgs boson is reported, which indicate that its properties are consistent with the standard model predictions, within the precision achieved to date.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

Transcription factors (TFs) represent an emerging class of therapeutic targets in oncology. Here, the authors develop Epiregulon, a computational method that constructs gene regulatory networks from ChIP-seq, ATAC-seq and RNA-seq data for accurate prediction of TF activity at the single-cell level, thereby facilitating the discovery of therapeutics targeting TFs.

Here, the authors perform large trans-ancestry fine-mapping analyses identifying large numbers of association signals and putative target genes for colorectal cancer risk, advancing our understanding of the genetic and biological basis of this cancer.

Hydrogel materials have emerged as versatile platforms for biomedical applications. Here this group reports an mRNA lipid nanoparticle-incorporated microgel matrix for immune cell recruitment/antigen expression and presentation/cellular interaction thereby eliciting antitumor efficacy with a single dose.

We can flexibly coordinate our movements with external stimuli, but no circuit-level model exists to explain this ability. Inspired by fundamental concepts in control theory, the authors construct a modular neural circuit that captures human behavior in a wide range of temporal coordination tasks.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

Investigating the inner structure of baryons is important to further our understanding of the strong interaction. Here, the BESIII Collaboration extracts the absolute value of the ratio of the electric to magnetic form factors and its relative phase for e + e − → J/ψ → ΛΣ decays, enhancing the signal thanks to the vacuum polarisation effect at the J/ψ peak.

While the STING-type-I interferon pathway plays a key role in anti-tumour immunity, current direct STING agonists have limited therapeutic benefit. Here, the authors identify ENPP1 as a safer and more effective STING-modulating target than direct STING agonism, and use an AI-based drug design platform to design the ENPP1-selective inhibitor ISM5939.