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Modulating mitochondrial NAD⁺ levels by changing the expression of the mitochondrial NAD⁺ transporter, SLC25A51, Mukherjee et al. demonstrate that mitochondrial, rather than cytosolic or nuclear, NAD⁺ levels are a key determinant of the rate of liver regeneration.

White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

This work presents a 7 × 7 crossbar array based on analog perovskite synapses and suggests that ion transport and interfacial barrier changes are more important than filaments with localized ions when constructing neuromorphic AI accelerators.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Despite the progression of Actinium-225 (225Ac) radiopharmaceuticals, there is still a limited understanding of Ac coordination chemistry due to its radioactivity, poor availability, and lack of stable isotopes. Here, the authors demonstrate a platform to characterize the solution and solid-state behavior of the longest-lived Ac isotope, 227Ac.

Personalized prediction of tumor radiosensitivity would facilitate development of precision medicine workflows for cancer treatment. Here, the authors integrate machine learning and genome-scale metabolic modeling approaches to identify multi-omics biomarkers predictive of radiation response.

The cell adhesion molecule E-selectin regulates haematopoietic stem cell self-renewal in the bone marrow vascular niche. Here, the authors show E-selectin adhesion directly induces survival signaling in acute myeloid leukaemia and therapeutic inhibition improves chemotherapy outcomes in mice.

Sulfur fluoride exchange (SuFEx) is a click reaction used to rapidly synthesize and discover functional molecules. In this Primer, Homer et al. discuss the essential elements of SuFEx operation, catalysis and SuFExable connective hubs and explore applications of SuFEx in drug development, polymer science and biochemistry.

Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

Phase-resolved mid-infrared observations from JWST of the hot gas giant WASP-43b detect a day–night difference of 659 ± 19 K. Comparison with climate models shows that the observations are compatible with cloudy skies, at least on the nightside, and the lack of methane detection suggests the presence of disequilibrium chemistry.

During development of myointimal hyperplasia in human arteries, smooth muscle cells have hyperpolarized mitochondrial membrane potential (ΔΨm), high proliferation and apoptosis resistance; PDK2 is a key regulatory protein whose activation is necessary for myointima formation, and its blockade with dichloroacetate prevents Δψm hyperpolarization, facilitates apoptosis and reduces myointima formation in injured arteries, without preventing vessel re-endothelialization, possibly representing a novel strategy to prevent proliferative vascular diseases.

The response to infectious and inflammatory challenges differs among people but the reasons for this are poorly understood. Here the authors explore the impact of variables such as age, sex, and the capacity for controlling inflammation and maintaining immunocompetence, linking this capacity to favourable health outcomes and lifespan.

Foreign body response can result in failure of biomaterials in vivo. Solvent-free crystals containing anti-fibrotic drugs now show the potential for long-term inhibition of fibrosis on a number of implantable devices in rodents and non-human primates.

T cell antigen receptor stimulation by the ligand antigen triggers multiple downstream pathways that affect CD4 + T cell function. Here authors show that activation of the downstream WNK1 kinase causes water entry into the cells, which is essential for CD4⁺ T cell proliferation.

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined and the pathophysiology unknown. Here, the authors conduct deep phenotyping of a cohort of PI-ME/CFS patients.

White and colleagues identify a role for host autophagy in restraining T-cell-dependent immune responses, specifically against tumors with high mutational burden.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

This study provides a nucleotide-level survey of genome variation in 63 Saccharomyces cerevisiae strains sampled from different ecological niches and geographical locations. The analysis of genome-wide patterns of the nucleotide polymorphism and deletion variants discovered lays the foundation for genome-wide association studies in yeast.

The Suzuki-Miyaura coupling (SMC) is widely used in C-C bond forming reactions but the dominant mode of transmetalation remains controversial. Here the authors report a mechanistic study of a Pd catalyzed SMC under biphasic conditions where using phase transfer catalysts shifts the dominant mode of transmetalation resulting in rate enhancement.

Multi-ancestry genome-wide association meta-analysis identifies new risk loci for CAC. Functional evidence implicates candidate causal genes as regulators of smooth muscle cell-mediated calcification.

The role of pathogenic mitochondrial DNA (mtDNA) mutation in cancer remains to be studied. Here the authors show that high mtDNA mutation burden in lung cancer models leads to increased glycolysis but limited de novo serine synthesis, rendering sensitivity to dietary serine and glycine deprivation.

Here, the authors perform a meta-analysis in 26,699 people with seizures and 492,324 controls to identify 25 genome-wide significant copy-number variants. The discovered loci point to known disease genes and associations with clinical annotations.

A multi-modal analysis of pre-metastatic liver biopsies from patients with localized pancreatic cancer with a minimum of 3 years of follow-up shows that immunological, proliferative and metabolomic features distinguish patients who develop metastases from disease-free survivors and can be used to predict outcomes.

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.

Munger et al. show that infection with human cytomegalovirus upregulates fatty acid biosynthesis and that pharmacological inhibition of this pathway inhibits replication of both this virus and influenza A. This approach, the first to reliably map major carbon fluxes in mammalian cells, extends the promise of metabolomics from diagnostic applications to identification of new therapeutic concepts.

CRISPR/Cas9-based homing gene drives have emerged as a potential new approach to mosquito control. Here the authors use transgenic lines with germline-specific regulatory elements to express Cas9 and achieve up to 94% inheritance bias, closing the gap between A. aegyptidrives and the highly efficient drives observed in Anopheles species.

Direct observation of G-quadruplexes (G4s) in live cells is challenging. Here the authors report a method to identify G4s within the nuclei of live and fixed cells using a fluorescent probe combined with fluorescence lifetime imaging microscopy.

O’Donnell and colleagues report that activation of the integrated stress response in non-small cell lung cancer cells by impairing heme production leads to enhanced PD-L1 translation in an eIF5B-dependent manner.

SLEAP is a versatile deep learning-based multi-animal pose-tracking tool designed to work on videos of diverse animals, including during social behavior.

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.

Type IV pili (T4P) are retractile appendages used by bacteria for DNA uptake and other purposes. T4P extension is thought to occur through the action of a single motor protein, PilB. Here, Ellison et al. show that T4P synthesis in Acinetobacter baylyi depends not only on PilB but also on an additional, distinct motor, TfpB.

The specifics of the pediatric immune response that gives rise to antibodies capable of neutralising diverse HIV-1 strains is not fully understood. Here the authors characterise the immune environment of Simian-HIV infected paediatric macaques and link to antibody neutralisation induction.

The decision to form a fruiting body have been studied extensively, however, the mechanical events that trigger the creation of multiple cell layers is poorly understood. Here the authors find M. xanthus cells adjust their reversal frequency to control mechanical stresses that triggers layer formation in the colonies.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

An inadequate supply of cofactors often limits the production of target molecules in metabolic engineering. Here, the authors report cofactor engineering through decompartmentalization of the yeast mitochondrial metabolism to improve succinic acid production in Issatchenkia orientalis.

The barnase-barstar pair is effective in Aedes aegypti as a basis for toxin-antidote gene drive systems, barnase is able to kill mosquitoes and cells and barstar rescues the effect in a ubiquitous or tissue-specific manner.

Identification of an improved glucose-6-phosphate dehydrogenase (G6PD) inhibitor G6PDi-1 blocks G6PD activity more robustly than the widely cited antagonist DHEA. G6PDi-1 treatment blocks T cell cytokine production and neutrophil oxidative burst.

The US COVID-19 Scenario Modeling Hub produced medium to long term projections based on different epidemic scenarios. In this study, the authors evaluate 14 rounds of projections by comparing them to the epidemic trajectories that occurred, and discuss lessons learned for future similar projects.

Kinase inhibitors are widely used to treat cancer, however patients frequently develop resistance. Here, the authors investigate adaption mechanisms during drug persistence and show that stimulation of the innate immunity sensor RIG-I enhances cancer cell death when combined with kinase inhibition.

Insufficient AHR activation has been suggested in SLE, and augmenting AHR activation therapeutically may prevent CXCL13⁺ T_PH/T_FH differentiation and the subsequent recruitment of B cells and formation of lymphoid aggregates in inflamed tissues.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Doan et al. show that loss of cardiac NAD⁺ is sufficient to drive metabolic derangements, hypertrophic remodeling and lethal arrhythmias in adult mouse hearts, despite maintenance of ejection fraction and bioenergetics.

Arany and colleagues integrate metabolomics data, tissue RNA-sequencing data and proteomics data from explanted hearts of patients with end-stage heart failure to provide a comprehensive ‘multi-omic’ evaluation of the metabolic pathways affected by heart failure.

The dayside thermal emission spectrum and brightness temperature map of the ultra-hot Jupiter WASP-18b obtained from the NIRISS instrument on the JWST showed water emission features, an atmosphere consistent with solar metallicity, as well as a steep and symmetrical decrease in temperature towards the nightside.

The civil war in Mozambique led to the collapse of large-mammal populations and the spread of the invasive plant Mimosa pigra. Experimental exclosures and DNA metabarcoding are used to show how trophic rewilding since the end of the war has reduced the invasive population.