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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.

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.

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.

Solid-phase crystallized Ce and H codoped In₂O₃ (ICO:H) transparent conducting films achieve very high electron mobility values of over 100 cm²/Vs and suitable low-carrier concentration, leading to high electrical conductivity and broadband optical transparency. However, a high-temperature annealing process for solid-phase crystallization is necessary to obtain high mobility. Therefore, such a high processing temperature limits the formation and adoption of these films on heat-sensitive flexible substrates. Herein, we used excimer laser irradiation to achieve an ICO:H film on flexible polyethylene terephthalate that had ultrahigh mobility of 133 cm²/Vs, which is the highest among those reported for flexible transparent electrodes.

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.

Low-frequency earthquakes (LFEs) in megathrusts are due to weak shear strength and high fluid pressure, but controls on LFE location remain unclear. Nakajima and Hasegawa show that LFE occurrence is limited to beneath unmetamorphosed undrained portions of the overlying plate.

Targeting gluten antigens presents a plausible therapy option for celiac disease. Here the authors generate and characterize a broadly neutralizing antibody recognizing more than 25 gluten peptide:HLA-DQ2.5 complexes, with structural analyses implicating its mode of interaction, and with mouse in vivo studies supporting its therapeutic feasibility.

RaPID (Random non-standard Peptides Integrated Discovery) enables discovery of small macrocyclic peptides binding desired targets. Here, the authors propose lasso-grafting: the RaPID-derived peptides are implanted onto diverse proteins and maintain both the binding properties of the cyclic peptide and the host protein function.

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 change from low-spin hexacoordinated to high-spin pentacoordinated domed form in heam upon ligand detachment and the reverse process underlie the respiratory function. The authors, using femtosecond time-resolved X-ray emission spectroscopy, capture the transient states connecting the two forms in myoglobin-NO upon NO photoinduced detachment.

During development, astrocytes are generated from radial glia, and migrate to the cortical plate, but the process of astrocyte migration during development is not fully understood. Here the authors labelled cells derived from the cortical ventricular zone in the late stages of cortical plate development in mice, and identified a migration mode in which cells move rapidly and almost at random within the intermediate zone and the cortical plate.

Semaphorin 4A is implicated in photoreceptor survival. Nojima and colleagues generate transgenic mice with different mutations in the Sema4A gene and find that point mutation of F350 causes severe degeneration in photoreceptor cells, which can be rescued by virus-mediated gene therapy.

Therapeutic options for pancreatic ductal adenocarcinoma (PDAC) are limited. Here the authors report the characterization of a CEACAM6-targeting antibody drug conjugate loaded with a BET protein degrader, showing antitumour activity in PDAC preclinical models.

Immunomodulatory drugs are used for the treatment of multiple myeloma. ARID2, a component of the PBAF chromatin-remodeling complex, is a new pomalidomide-induced neosubstrate of CRL4^CRBN, which accounts for its superior efficacy over lenalidomide.

A potent inhibitor for hepatocyte growth factor was identified that utilizes an allosteric mode of inhibition revealed by atomic force microscopy imaging. The inhibitor could be used for positron emission tomography imaging of mouse tumors.

Zebrafish p63 isoforms were identified as thalidomide-dependent neosubstrates of the cereblon-containing E3 ligase complex. ∆Np63α and TAp63α are responsible for thalidomide-induced malformations of pectoral fins and otic vesicles, respectively.

The topological character of solids is usually revealed by considering the Berry curvature of electronic bands in a periodic crystal. Here, authors demonstrate the influence of the Berry curvature on the electronic properties of an amorphous thin film.

Ionizing radiation damages small intestinal crypt cells, including epithelial stem cells and their progeny. Here the authors show that radiation-induced crypt cell death is amplified by the release of cellular RNA from apoptotic epithelial cells, which then triggers pro-apoptotic TLR3 signalling on neighbouring cells.

Communication between osteoblasts and osteoclasts is essential for bone homeostasis, but the mode of interaction is unclear. The authors use intravital two-photon microscopy in mice to show that these cells directly interact, regulating activity of osteoclasts, and that the interaction is modulated by parathyroid hormone administration.

The activity of glycosyltransferase GnT-V correlates with cancer malignancy and poor prognosis but its mechanism of action is poorly understood. Here, the authors solve crystal structures of free and substrate analog-bound GnT-V, providing insights into its catalytic mechanism and a basis for GnT-V inhibition.

An iron-based superconductor Fe(Se,Te) is a candidate material for exploring nonreciprocal superconducting transport owing to its large critical parameters and spin-orbit interaction. Here, the authors find a scaling relation of the superconducting diode efficiency in Fe(Se,Te)/FeTe heterostructure, revealing the role of asymmetric vortex pinning effect coupled to the spin-orbit interaction.

A total of 1074 patients with a history of ischemic stroke enrolled in The Recurrent Stroke Prevention Clinical Outcome (RESPECT) Study were assigned to intensive blood pressure (BP) control group (blood pressure < 120/80 mmHg) or standard blood pressure control group (blood pressure < 140/90 mmHg) and were followed up for a mean of 3.9 years. Seventy-eight first recurrent strokes occurred, including 70 ischemic stroke and 8 intracerebral hemorrhage. Intensive treatment did not change annual risk of ischemic stroke (1.74% vs. 1.75%, P = 0.999), but markedly reduced risk of hemorrhagic stroke (0.00% vs. 0.39%, P = 0.005). Beneficial effect of intensive BP control were observed for risk of hemorrhagic stroke in the patients with a history of ischemic stroke.

The Tohoku Medical Megabank Organization establishes a biobank with detailed patient health care and genome information. Here the authors analyse whole-genome sequences of 1,070 Japanese individuals, allowing them to catalogue 21 million single-nucleotide variants including 12 million novel ones.

Magnetic Weyl semimetals, such as Co₃Sn₂S₂, are ideal to realise anomalous transport properties based on the Berry curvature in the specific electronic bands and are expected to be useful for topological spintronics. Here, the authors investigate the bulk and surface conduction channels of Co₃Sn₂S₂ determining the relationship between the film thickness and surface conductance.

Electric-field-induced superconductivity in samples of ultrathin FeSe grown on SrTiO₃ and MgO substrates shows that the superconductivity is not an interfacial effect but is rather related to a charge imbalance of electrons and holes.

A novel tumor suppressing role for RUNX3 is shown where a direct interaction with MYC leads to disruption of MYC-MAX heterodimers and consequent degradation of the MYC oncoprotein.