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Clinical manifestations in patients with systemic sclerosis (SSc) are highly heterogeneous, and identifying the root causes of clinical symptoms is challenging. Here, by performing single-cell profiling of peripheral blood from SSc patients, the authors identify distinct immune abnormalities associated with acute organ complications, including interstitial lung disease and scleroderma renal crisis.

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.

Space division multiplexing offers increased capacity over current fiber networks. Here, the authors demonstrate petabit/s transmission in a standard-sized 19-core multi-core fiber, while minimizing the required digital signal processing complexity.

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.

Paracrystalline state is still challenging to reach in alloy systems in a controlled manner. Here, the authors present an atomic-level tailoring route to create paracrystalline Zr-Nb-Hf-Ta-Mo high-entropy alloy through local amorphization induced by atomic-level Pt with negative mixing enthalpy.

Here, using cryo-electron microscopy and solution NMR, the authors reveal the structural and dynamic mechanisms underlying the signaling versatility of a muscarinic receptor regulated by orthosteric and allosteric ligands.

Spatially resolved images of M87 obtained at a wavelength of 3.5 mm in 2018 show a ring-like accretion structure, the inner (outer) edge of which connects the black hole (jet).

The glutamate transporter GLAST in astrocyte regulates synapse function by glutamate clearance. Here, the authors show that Down syndrome cell adhesion molecule (DSCAM) in Purkinje cells controls synaptogenesis through the intercellular association with GLAST in the developing cerebellum.

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.

GPR88 is an orphan GPCR and regulates diverse brain functions. Here, the authors report two structures of the human GPR88-Gi complex, showing an allosteric ligand directly involved in the interaction interface between the receptor and G-protein, and a density which may represent an endogenous ligand of GPR88.

In cancer it is assumed that microRNAs recognise and regulate their targets uniformly. Here, the authors show that in gastrointestinal cancers methylation of microRNAs may impact their stability, and that levels of microRNA methylation are distinct in pancreatic cancer patients compared to healthy controls with potential diagnostic implications.

The authors report a Hall effect that originates from a fictitious magnetic field associated with antiferromagnetic order that breaks time-reversal symmetry, followed by translation symmetry.

Somatic mutations in ASXL1 lead to clonal hematopoiesis, and Sato et al. elucidate the molecular mechanisms by which mutated ASXL1 in hematopoietic cells drives atherosclerosis in mice.

Voltage-gated Na+ channel β-subunits are concentrated in the nodes of Ranvier and axon initial segments of myelinated axons and have a variety of functions. Here the authors show, using genetically modified mice, that this subunit is present in unmyelinated fibres in the striatum and is required for generation of resurgent Na+ current in striatal neurons.

A tetravalent peptide can finely modulate the multivalent interaction between RANK and TRAF6 to inhibit osteoclastogenesis by specifically inhibiting the recruitment of MAPK kinase 3 to TRAF6 without affecting other signal transducers.

The Southern Annular Mode is a dominant climate variability mode in the Southern Ocean. Using observational data, the authors show a strong climatic modulation of ocean acidification via Southern Annular Mode -related winds.

The FANTOM4 study identified transcriptional start sites active during proliferation arrest and differentiation of the human monocytic cell line THP-1. Systematic knockdown of 52 transcription factors provide support for their model in which a complex transcriptional network regulates the differentiation process.

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.

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.

Targeted protein degradation is a powerful tool, but difficult to achieve in vivo with high specificity and control. Here, the authors develop two in vivo targeted protein degradation systems in mice, which enable the selective degradation of target proteins in a cell type-specific manner and can be applied in both fetuses and neonates.

Adenosine A₃ receptor (A₃AR) holds promise for treating inflammatory and cancer conditions. Here, Cai et al. present cryo-EM structures of  A₃AR bound to agonists CF101 and CF102, offering insights into its activation and ligand interaction, crucial for developing targeted therapies.

Yasuda et al. evaluated serum from people with chronic kidney disease following dialysis initiation. High levels of IgM free apoptosis inhibitor of macrophage (AIM) is associated with increased mortality and cardiovascular risk and a cutoff value is established that predicts patient outcomes.

Cytotoxic T lymphocytes play important roles in the anti-viral immune response in COVID-19, and it is important to know how they contribute to disease outcome. Authors here identify a dominant SARS-CoV-2 M protein epitope, M_198–206, and show that M_198–206-specific cytotoxic T cells from convalescent patients with severe disease harbour a gene expression pattern indicative of poor functionality.