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In a study of four brain-dead human decedents, extracorporeal liver cross-circulation using genetically modified pig livers provides essential hepatic functions, supporting the feasibility of this approach for temporary liver support as a bridge to organ transplantation.

Authors study links between amyloid secondary nucleation and growth defects, demonstrating these sites on Aβ40/Aβ42 fibrils are rare compared to the number of protein molecules. Re-analysis of published data suggests that defects may also drive secondary nucleation generally.

Neuroimmune interactions are important in amyotrophic lateral sclerosis (ALS). Here the authors characterize the role of NK cells in mouse models of ALS, and in patient tissue.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Bång-Rudenstam et al. report that the acidic tumour microenvironment facilitates the assembly of chondroitin sulfate-enriched glycocalyx to disrupt lipid scavenging and prevent ferroptosis, thereby providing an adaptive mechanism upon tumour acidosis.

Patin and colleagues present a mineable Resource database for identifying demographic and genetic factors that impact antiviral antibody repertoires in humans.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

Zeng et al. analyzed cfDNA methylation and fragmentomic data from 1,294 patient plasma samples across 14 major cancer types to present a comprehensive landscape of pancancer and cancer-specific cell-free DNA methylation and fragmentomic features.

The authors survey community palaeontological databases, documenting their contributions to science as well as their vulnerabilities, and provide recommendations for the future of open science databases.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

The authors describe the isolation and characterization of broadly cross-neutralizing monoclonal antibodies (mAbs) against diverse H5Nx viruses from individuals who received a monovalent H5N1 vaccine 15 years ago. They identify five mAbs that potently neutralized the majority of H5 clades and protected against lethal 2.3.4.4b H5N1 infection in mice.

The relative contribution of lipid catabolism on fasting-induced longevity was unknown. Authors showed lifespan extension from fasting depend on silencing lipid catabolism upon nutrient replenishment through phosphorylation of NHR-49 by KIN-19.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

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.

Proxy records from Lake Baikal show that rapid cooling coincided with Northern Hemisphere ice sheet expansion 2.7 million years ago, a change accompanied by a transition to open steppe ecosystems.

Molecular mimicry between a gut commensal and a tumour antigen forms part of an important mechanistic framework that can boost the efficacy of immune checkpoint blockade therapy and restrain tumour growth.

Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

The high-plasticity cell state (HPCS) is a critical hub that enables reciprocal transitions between cancer cell states, and targeting the HPCS may suppress cancer progression and eradicate treatment resistance.

A high-resolution transcriptomic and epigenomic cell-type atlas of the developing mouse visual cortex from embryonic to postnatal development is presented, providing a real-time dynamic molecular map associated with individual cell types and specific developmental events.

Lipid nanoparticle based mRNA vaccines are known to induce robust CD4 + T cell responses. Here the authors establish a role of endogenously derived antigen processing in the optimal priming of CD4 + T cell responses to mRNA lipid nanoparticle vaccines.

Prenatal Zika virus (ZIKV) exposure can lead to a spectrum of developmental issues, but the mechanisms remain unclear. Here the authors show that prenatal ZIKV exposure in macaques disrupts neurodevelopment, causing prolonged maternal attachment and visual deficits at 3 months that normalize by 12 months, independent of sensory function.

Here they demonstrate a therapeutic intervention elevating levels of CYP450-derived lipids to control the expansion of intermediate monocytes in tissue and peripheral blood, presenting a first in class therapeutic approach for treating chronic inflammatory disease.

Juvenile idiopathic arthritis (JIA) associated uveitis can cause vision loss in children, but mechanisms remain unclear. The authors here identify elevated CD19⁺IgD^-CD27^- double negative type 1 B cells in JIA-uveitis and show that targeting B-T cell interactions suppresses disease in mouse models of uveitis.

BCNE, an unsupervised deep-learning method, reveals clear trajectories of brain activity and effectively distinguishes cognitive events, learning stages and active versus passive movement, outperforming traditional data visualization methods.

Scaling Si spin qubits relies on the uniform control of qubit-host interactions. This work finds correlations in qubit energy levels across a manufactured device arising from placement of Ge in the quantum well, consistent with atomistic modeling.

Understanding the mechanisms underlying the survival of drug tolerant persister cells following chemotherapy remains elusive. Here, multi-omics analysis and experimental approaches show that the germ-cell-specific H3K4 methyltransferase PRDM9 promotes metabolic rewiring in glioblastoma stem cells.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

Pertpy serves as a one-stop and performant framework for single-cell perturbation data analysis.

The immune response to tumour development is frequently targeted with therapeutics but remains largely unexplored in diagnostics. Here this groups designs an immunodiagnostic platform targeting amino acid residue biomarkers associated with tumour development and distinct from autoimmune and infectious diseases.

This study releases a very high-resolution migration dataset that reveals trends that shape daily life: rising moves into high-income neighborhoods, racial gaps in upward mobility, and wildfire-driven moves.

Achieving high resolution with optical neural interfaces is challenging. Here, the authors developed and chronically implanted 100-pixel microLED arrays on the surface of the mouse auditory cortex for optogenetic behavioural experiements.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Using terahertz spectroscopy and ultrafast electron diffraction, the paper shows how the DC conductivity of warm dense matter depends on material phase. This provides insight to how electron scattering processes impact conductivity in this regime.

This Primer provides an introduction to quantum imaging with correlated photon pairs, from core concepts to experimental realizations. It discusses potential advantages over classical imaging, practical design issues, and the emerging applications and challenges that will shape future progress of the field.

There is still a need for effective HIV vaccines. In this phase I clinical trial, the authors show that an HIV-1 vaccine candidate, ConM SOSIP.v7, is well-tolerated in HIV-negative adults and that it elicits a strain-specific neutralising antibody response that differed between female and male participants.

Even when neocortical neurons form in abnormal locations, they retain their identity and function, revealing that brain circuit formation can be guided by intrinsic developmental programs rather than physical position.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Cancer detection is challenging, especially in patients with diffuse symptoms that overlap with non-malignant conditions. Here, the authors develop a proteomics- and minimally invasive blood sampling-based classification model as a triage tool to identify and prioritize individuals at high cancer risk that would benefit the most from rapid and highly sensitive diagnostic modalities.

Ion-mobility mass spectrometry has been used to identify and characterize the oligomeric assemblies of amyloid-β proteins under physiologically relevant conditions. Hexamers and dodecamers are formed only from Aβ42 proteins and the dodecamer is identified as a candidate for the primary toxic agent in the development of Alzheimer's disease.

Multimodal biological data is challenging to analyze. Here, the authors develop UnitedNet, an explainable deep neural network for analyzing single-cell multimodal biological data and estimating relationships between gene expression and other modalities with cell-type specificity.

Hughes and colleagues present a developmentally inspired tissue engineering strategy to overcome barriers in kidney tissue generation, enhancing prospects for renal replacement therapies.

Human brain structure changes throughout the lifespan. Brouwer et al. identified genetic variants that affect rates of brain growth and atrophy. The genes are linked to early brain development and neurodegeneration and suggest involvement of metabolic processes.

Approaches combining genetic association and Perturb-seq data that link genetic variants to functional programs to traits are described.

SARS-CoV-2 infection is milder in children, but direct comparison with adults is rare. Here the authors show that immune responses are higher in children, retained for 12 months or longer and can neutralize Alpha, Beta and Delta variants.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

The authors identify pathogenic variants in the SMARCA1 gene as the cause of a variable neurodevelopmental disorder. Mouse studies suggest diverse genetic mechanisms related to NURF complex composition mediate the phenotype.

Jonaitis et al demonstrate that serotonin differentially modulates feedforward inhibitory neurons in the olfactory system of Drosophila which likely reflects odor categorization in higher order brain regions.

Using an exploratory phenome-wide association study of polygenic risk scores (PRS) in children aged 9–13 from the Adolescent Brain Cognitive Development Study cohort, the authors identify neurodevelopmental and internalizing PRS associations with multiple phenotypes similar to the constituent GWAS indicators (for example, neurodevelopmental and internalizing traits) as well as cross-trait phenotypes (for example, screen time, cortical volume).

A large-scale genome-wide meta-analysis conducted across different platforms identifies genetic loci regulating levels of circulating metabolites.