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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.

Here, the authors develop a cell-permeable chemical catalyst that acetylates histone H2BK120 in leukemia cells, attenuates NELFE chromatin binding, reprograms transcription, and reduces the tumorigenic potential of leukemia cells in mice.

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.

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.

Poor access to suitable light-sheet microscopes remains a big obstacle for many end-users in biomedical research. Here, the authors present descSPIM, a low-cost, low-expertise light-sheet microscope for routine 3D imaging of cleared samples.

In view of previous work suggesting that low-voltage areas may promote atrial fibrillation, a multicenter, randomized controlled trial tested the hypothesis that ablation of low-voltage areas in addition to pulmonary vein isolation might reduce the recurrence of atrial arrhythmic events, but found no significant benefit to the combined procedure.

The key to enhance the output of a thermoelectric device is to be able to regulate the thermoelectric voltage generation. Topological magnet Co₃Sn₂S₂-based devices show the way to achieve that goal.

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.

The source and network mechanisms underlying visual object memory are not fully understood. By combining chemogenetics with neuroimaging and electrophysiology in behaving macaques, here authors provided multi-scale causal evidence on the top-down regulation in the ventral fronto-temporal network for short-term visual object memory.

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.

The OFC is at the core of value-based adaptive decision-making. Here, the authors demonstrate dissociable contributions of primate OFC-subcortical pathways to different behavioral strategies by combining chemogenetics with a model-fitting approach.

Nakao et al. conduct and validate a phenome-wide association study on foveal thickness and find DPF3 (rs4903064) correlates with a reduced risk of arrhythmia, specifically premature cardiac complex, suggesting a link between foveal thickness and cardiovascular health.

Using more than 100 independent iPSC lines derived from patients with Alzheimer’s disease, the authors discovered loci associated with the neuronal production of amyloid β and confirmed their influence using RNA interference.

Effective antivirals are critical for combatting SARS-CoV-2 infections. Here, the authors develop two orally available small molecules, which specifically inhibit the activity of the SARS-CoV-2 main protease and potently block the infectivity and replication of various SARS-CoV-2 strains in cells and mice.

The dopamine D₂ receptor (D₂R) is a GPCR and an important drug target for schizophrenia treatment. Here, the authors present the crystal structure of human D₂R in complex with the antipsychotic drug spiperone, which is of interest for designing antipsychotics with improved receptor selectivity.

Proliferative and effector functions of T cells are determined by T cell receptor signalling and modulated by activator and inhibitory co-receptors. Authors report here that the G-protein-coupled receptor GPR171 functions as a co-inhibitor of T cell signalling and might serve as a target for cancer immunotherapy.

The Philippine Sea/Pacific boundary megathrust is another possible source of seismic hazard in the Tokyo Region and tsunamis in the Pacific, according to an assessment of 1,000 years of tsunami deposits along the Japanese coastline.

Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) suffer from limited maturation. Here the authors identify ERRγ agonist as a factor that enhances cardiac morphological, metabolic, contractile and electrical maturation of hiPSC-derived CMs with T-tubule formation.

Immunologically cold tumours don’t respond to immune checkpoint blockade inhibition due to poor recruitment of anti-tumour T cells. Authors show here that melanoma-associated lymphatic endothelial cells express G Protein-Coupled Receptor 182 that scavenges CXCL9 and other chemokines necessary for T cell recruitment.

Mental conflict has been regarded as subjective instead of quantitative. This study developed a data-driven method to decode temporal dynamics of conflict between reward and curiosity, which can elucidate mechanisms of irrational decision-making.

Environmental cues instruct cell fate during hematopoiesis. Igarashi and colleagues show that the transcription factors Bach1 and Bach2 promote erythropoiesis and suppress myelopoiesis. Infection and inflammatory signals suppress Bach expression, which results in anemia.

Here, using in vitro assays and structural analysis, the authors characterize the anti-SARS-CoV-2 properties of two small molcules, showing these to bind and target the virus main protease (M^pro), and to exhibit a synergistic antiviral effect when combined with remdesivir in vitro.

This study developed a novel method for the control of the cellulose crystal of cellulose I and II. The crystal transition from cellulose I to II was tracked when cellulose I, which is soaked in a low-concentration NaOH aqueous solution, was quenched using liquid nitrogen. The crystal transition progressed from the surface to the center of the sample. This quench treatment has the potential to fabricate new cellulose materials with a cellulose I core and a cellulose II surface.

The treatment of ROS1-rearranged non-small cell lung cancer with the TKI crizotinib is limited due to the emergence of resistance. Here, the authors develop a new ROS1/NTRK inhibitor, DS-6051b, which overcomes crizotinib resistance in preclinical models.

The intercalation of metal ions in layered structures has a wide variety of applications, from energy storage to environmental remediation. Here the authors report that layered telluride structures can selectively bind transition metals and this intercalation can occur in solid state at mild conditions.

Hyperuricemia, or gout, is thought to arise either from urate overproduction or from decreased renal excretion of urate. Ichidaet al. show that the extra-renal excretion of urate also has a role in the pathogenesis of hyperuricemia, and propose a new classification for patients with this disease.