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How dsRNAs translocate to the cytosol during soaking RNAi remains unclear. Here, the authors show that the Cl⁻/H⁺ antiporter supports dsRNA-induced LMP and the cytosolic release of dsRNAs.

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Wnt5a is a member of the Wnt family of proteins that mainly activates the noncanonical Wnt signaling pathway. Here, the authors discover that inflammatory fibroblasts expressing Wnt5a, which are induced by hypoxia, contribute to colon cancer progression.

Shinoda and Kitakaze et al. prepared recombinant hIDUA from transgenic silkworm cocoons and transglycosylated to mannose-6-phosphate- or α2,6-sialyl glycan-type using ENGases. These enzymes were administrated to a mucopolysaccharidosis type I macaque and succeeded in improving the clinical signs and reducing the urinary glycosaminoglycan levels.

Reversible internal RNA phosphrylation contributes to thermal stability and nuclease resistance of tRNA, and cellular thermotolerance of hyperthermophiles. 

Rare subtypes of renal cancers can be difficult to diagnose. Here, the authors use transcriptional analysis to show utility in aiding histological classification.

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.

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.

The stability of the benzene molecule reduces its tendency to react in ways that perturb the aromaticity—for example, in Diels–Alder reactions. Here the authors report a diene capable of not only inducing benzene to react under mild conditions but also of breaking apart the ring system itself.

The engineered Streptococcus pyogenes Cas9 variant SpCas9-NGv1, known to recognize relaxed NG protospacer adjacent motifs (PAMs) in human cells, can also mediate targeted mutagenesis with NG PAMs in rice and Arabidopsis. When fused with cytidine deaminase, it mediates C-to-T substitutions.

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.

Bach2 limits T cell effector functions. Here the authors show that Bach2–Batf complex antagonizes the recruitment of the Batf–Irf4 complex to AP-1 motifs and suppresses Th2 cytokine production, and describe mechanisms of negative feedback by which Bach2 restricts Baft-mediated Th2 response.

This paper reports the synthesis of simple polyprenoids through a halocyclization reaction that used a nucleophilic promoter. This enabled halogenated cyclic products in high yields and enantiomeric purity to be obtained.

Two new types of imaging technology—laser-scanning confocal endoscopy series and contact endoscopy series—could reduce the number of biopsies that need to be taken by enabling anin vivo'virtual' histological diagnosis. Although it is currently not clear which technology should be adopted, microscopic evaluation of living tissue is now a reality.

Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.

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.

Wnt11 is more strongly expressed in small cell lung cancer (SCLC) than in non-SCLC. Ascl1 promotes Wnt11 expression by altering H3K27Ac levels at the enhancer region of the WNT11 gene. Ascl1-induces Wnt11 regulates neuroendocrine differentiation, cell proliferation, and E-cadherin expression in SCLC. The Ascl1-Wnt11 axis has potential as a therapeutic target and supports the clinical utility of Wnt11 as a biological marker in SCLC.

The skin has emerged as a regulator of blood pressure, but the mechanisms remain unclear. Here, the authors show that skin RAS activity, controlled by ATRAP in keratinocytes, modulates hypertension through effects on vasoconstriction and water loss.

Idiopathic pulmonary fibrosis is associated with increased abundance of Staphylococcus and Streptococcus in the lungs. Here, the authors identify a Staphylococcus nepalensis-derived peptide, named corisin, to induce apoptosis of lung epithelial cells and exacerbation of pulmonary fibrosis in mice.

Here, the authors identify six risk SNPs for systemic sclerosis by performing GWAS on Japanese patients and meta-analyzing Japanese and European GWAS datasets. Downstream analyses indicate that B cells contribute to pathogenesis.

Two optogenetic methods for vagus-nerve stimulation, via the selective expression of opsins in either subdiaphragmatic or pancreas-innervating nerve fibres, led to enhanced glucose-stimulated insulin secretion and β cell proliferation in mice.

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.

Cell-ID facilitates the analysis of cell-type heterogeneity and cell identity across multiple samples at the single-cell level.

Senescent and injured cells affect tissue functions and can drive tumorigenesis. Thus, efficient elimination of these cells is pivotal for tissue integrity. Here Miyamuraet al. show that YAP acts as a cellular stress sensor and promotes the elimination of damaged cells to maintain tissue homeostasis.

Optical Einstein–Podolsky–Rosen correlation is observed on a picosecond timescale in a continuous-wave system. By introducing waveguide optical parametric amplifiers and balanced detectors, the quantum correlation 4.5 dB below the shot-noise level is observed.

The use of optical phase sensitive amplifiers (PSA) has been shown to allow fast quantum tomography of Gaussian states, but non-Gaussian states are a key component for quantum computation using optical continuous-variable systems. Here, the authors extend PSA-enhanced high-bandwidth homodyne detection to non-Gaussian states.

This study shows that the preferential use of gluconeogenic pathways in the liver depends on exercise load.

Currently, tracking cell proliferation in vivo is hard. Here the authors report a method where the time series of proliferation of targeted cell types can be monitored in vivo in the same individuals, with no need for animal sacrifice: they use this to assess β-cell and hepatocyte proliferation in mice.