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A single-cell multiomic immune cell atlas from 235 Japanese, including patients with COVID-19 and healthy individuals, linked with host genetics including germline and somatic mutation, plasma proteomics and metagenomics data reveals that immune cells are dynamically regulated in a cell state-dependent manner.

A genome-wide association study highlights a variant in DOCK2, which is common in East Asian populations but rare in Europeans, as a host genetic risk factor for severe COVID-19.

Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

Water at interfaces plays crucial roles in various natural phenomena and in material sciences. Here, the authors report the formation of a supramolecular crystal forming a porous framework with anisotropic, information-rich surfaces, accommodating water molecules to form multi-layered water channels.

The XRISM Resolve spectrum of the galactic neutron star X-ray binary, GX 13+1, reveals one of the densest winds ever seen in absorption lines.

A newly identified bacterial strain (YB328) isolated from the faeces of patients who responded to immune checkpoint blockade therapies can promote antitumour immunity through the activation of tumour-specific CD8⁺ T cells.

Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity.

Resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) is prevalent. Here the authors establish a biobank of patient-derived EGFR-mutant lung cancer organoids and identify a subgroup of EGFR-TKI-resistant lung adenocarcinoma organoids, which exhibit a basal-shift phenotype and vulnerability to CDK4/6 inhibitors.

Nicotinamide riboside (NR) is a NAD + precursor exhibiting beneficial effects against aging. Here the authors demonstrate that orally administered NR increases NAD + levels in a diphasic manner and that bone marrow stromal cell antigen 1 plays a crucial role for NAD + synthesis from NR.

Ueda et al. develop a sensor targeted to tumour cells that tracks extracellular H₂O₂. Tumour cells in H₂O₂ hotspots undergo partial epithelial–mesenchymal transition and migrate away from H₂O₂ hotspots. This is not seen in NRF2-hyperactivated tumours.

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.

Four transcription factors Oct4, Sox2, c-Myc and Klf4 are known to convert fibroblasts to pluripotent stem cells, if Fbx15 expression is also selected. But the induced stem cells were shown to be distinct from normal embryonic stem cells. However, if cells expressing Nanog and Oct4 are selected, then the reprogrammed fibroblasts are similar to embryonic stem cells in both biological potency and epigenetic state.

Human induced pluripotent stem cells are generated with episomal plasmid vectors at increased efficiency using non-transforming L-Myc and knockdown of p53. Also in this issue, Chen et al. report defined conditions for human cell reprogramming and culture.

The safety of induced pluripotent stem cells seems to depend on how they were generated. Miura et al. examine the effects of the c-myc transgene, tissue of origin and selection method on the tumor-forming propensity of iPS-cell derivatives.

Sato and colleagues present a biobank of patient-derived SCLC organoids, conducting a comprehensive genome and transcriptome profiling that reveals the existence of NE and non-NE subtypes with distinct molecular dependencies.

Autoimmune pulmonary alveolar proteinosis (aPAP) is a complex lung disease caused by abnormal surfactant homeostasis. Here, the authors carry out a genome-wide association study of aPAP in a Japanese cohort, finding variants in the MHC and suggesting predisposition to abnormal antibody production.

Pexophagy plays a pivotal role in the selective removal of ROS-generating peroxisomes, which protects plants from oxidative damage during photosynthesis under high-intensity light.

The requirement of a high applied voltage remains a critical issue for blue organic-light emitting diodes. Here, the authors determine the appropriate donor-acceptor combination for triplet-triplet annihilation upconversion emission, achieving a low turn-on voltage of 1.47 V in blue devices.

The saccus vasculosus is a circumventricular organ of the hypothalamus of many jawed fish whose function has remained a mystery for more than 300 years. Here the authors provide evidence that the saccus vasculosus functions as a sensor of seasonal changes in day length.

Observations of a luminous quasar from the high-resolution spectrometer Resolve aboard XRISM revealed highly inhomogeneous wind structure outflowing from a supermassive black hole, which probably consists of up to a million clumps.

Yanagawa et al. show that the autophagy-related protein Rubicon recruits WIPI2d to endosomes to promote exosome biogenesis. Rubicon promotes both an increase in exosome release during ageing and the pro-senescent effects of these exosomes.

In this study, the authors isolated SARS-CoV-2 receptor binding site monoclonal antibodies resistant to Omicron mutations. An amino acid in the receptor binding domain, tyrosine-489, is a virus-vulnerable site and a common footprint of broadly neutralizing antibodies.

Antibody cross-reactivity can help to prevent escape mutations from enabling viral escape, but underlying mechanisms are unclear. Here the authors identify influenza hemagglutinin epitopes that are exposed during viral replication and which result in the generation of a class of protective cross-reactive antibodies.

The rice Lsi1 aquaporin mediates uptake of silicic acid via the roots. Here the authors show the crystal structure of rice Lsi1 and characterize a unique five residue hydrophilic selectivity filter providing a structural basis for the highly selective activity of Lsi1 in Si uptake.

Michiaki Kubo and colleagues report a genome-wide association study for age-related macular degeneration in individuals of Japanese ancestry. They identify two genetic loci newly associated with this disease.

Induced pluripotent stem (iPS) cells are generated from mouse and human somatic cells by the introduction of four genes, but with low efficiency. Here it is reported that 10% of transduced mouse embryonic fibroblasts lacking p53 became iPS cells, even without the Myc retrovirus, and iPS cells were also generated from terminally differentiated T lymphocytes in the p53-null background.

The reasons why influenza infection promotes a broader antibody response compared with vaccines are not fully understood. Here the authors show that unmasking of haemagglutinin epitopes and IL-4 signals in the germinal centre contribute to broader antibody responses after infection.

Chalcone synthase is the first committed enzyme in the plant flavonoid biosynthesis pathway, yet shows low product specificity in vitro. Here Waki et al. show that chalcone isomerase-like proteins bind to and reduce the catalytic promiscuity of chalcone synthase, ensuring efficient flavonoid production in planta.

A culture system allows the long-term expansion of human haematopoietic stem cells (HSCs) in vivo without the use of recombinant cytokines or albumin, with potential applications for clinical therapies involving HSCs.

X-ray spectroscopic observations of the Centaurus galaxy cluster with the X-Ray Imaging and Spectroscopy Mission satellite show that the hot gas flows along the line of sight relative to the central galaxy.