C o r r e s p o n d e n c e Detection of Covid-19 in Children in Early January 2020 in Wuhan, China To the Editor: A small number of cases of coronavirus disease 2019 (Covid-19) have been described in children, 1,2 and our understanding of the spectrum of illness is limited. 3 We conducted a retrospective analysis involving hospitalized children in Wuhan, China. From January 7 to January 15, 2020, a total of 366 hospitalized children (≤16 years of age) were enrolled in a retrospective study of respiratory infections at three branches of Tongji Hospital, which are located 14 km to 34 km from one another in central Wuhan (Fig. S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). The study was approved by the ethics committee of Tongji Hospital. Among the 366 children, the most frequently detected pathogens were influenza A virus (in 23 patients [6.3%]) and influenza B virus (in 20 [5.5%]). SARS-CoV-2, the virus that causes Covid-19, was detected in 6 patients (1.6%). In

Herein, we report a DNA nanomachine, built from a DNA-functionalized gold nanoparticle (DNA-AuNP), which moves a DNA walker along a three-dimensional (3-D) DNA-AuNP track and executes the task of releasing payloads. The movement of the DNA walker is powered by a nicking endonuclease that cleaves specific DNA substrates on the track. During the movement, each DNA walker cleaves multiple substrates, resulting in the rapid release of payloads (predesigned DNA sequences and their conjugates). The 3-D DNA nanomachine is highly efficient due to the high local effective concentrations of all DNA components that have been co-conjugated on the same AuNP. Moreover, the activity of the 3-D DNA nanomachine can be controlled by introducing a protecting DNA probe that can hybridize to or dehybridize from the DNA walker in a target-specific manner. This property allows us to tailor the DNA nanomachine into a DNA nanosensor that is able to achieve rapid, isothermal, and homogeneous signal amplification for specific nucleic acids in both buffer and a complicated biomatrix.

Upon recognition of viral components by pattern recognition receptors, such as the toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like helicases, cells are activated to produce type I interferon (IFN) and proinflammatory cytokines. These pathways are tightly regulated by the host to prevent an inappropriate cellular response, but viruses can modulate these pathways to proliferate and spread. In this study, we revealed a novel mechanism in which hepatitis C virus (HCV) evades the immune surveillance system to proliferate by activating microRNA-21 (miR-21). We demonstrated that HCV infection upregulates miR-21, which in turn suppresses HCV-triggered type I IFN production, thus promoting HCV replication. Furthermore, we demonstrated that miR-21 targets two important factors in the TLR signaling pathway, myeloid differentiation factor 88 (MyD88) and interleukin-1 receptor-associated kinase 1 (IRAK1), which are involved in HCV-induced type I IFN production. HCV-mediated activation of miR-21 expression requires viral proteins and several signaling components. Moreover, we identified a transcription factor, activating protein-1 (AP-1), which is partly responsible for miR-21 induction in response to HCV infection through PKCε/JNK/c-Jun and PKCα/ERK/c-Fos cascades. Taken together, our results indicate that miR-21 is upregulated during HCV infection and negatively regulates IFN-α signaling through MyD88 and IRAK1 and may be a potential therapeutic target for antiviral intervention.

Background Failure of the glomerular filtration barrier, primarily by loss of slit diaphragm architecture, underlies nephrotic syndrome in minimal change disease. The etiology remains unknown. The efficacy of B cell-targeted therapies in some patients, together with the known proteinuric effect of antinephrin antibodies in rodent models, prompted us to hypothesize that nephrin autoantibodies may be present in patients with minimal change disease. Methods We evaluated sera from patients with minimal change disease enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) cohort and from our own institutions for circulating nephrin autoantibodies by indirect ELISA and by immunoprecipitation of full-length nephrin from human glomerular extract or a recombinant purified extracellular domain of human nephrin. We also evaluated renal biopsies from our institutions for podocyte-associated punctate IgG colocalizing with nephrin by immunofluorescence Results In two independent patient cohorts, we identified in a subset of patients with minimal change disease circulating nephrin autoantibodies during active disease that were significantly reduced or absent during treatment response. We correlated the presence of these autoantibodies with podocyte-associated punctate IgG in renal biopsies from our institutions. We also identified a patient with steroid-dependent childhood minimal change disease that progressed to end-stage kidney disease; she developed a massive posttransplant recurrence of proteinuria that was associated with high pretransplant circulating nephrin autoantibodies. Conclusions Our discovery of nephrin autoantibodies in a subset of adults and children with minimal change disease aligns with published animal studies and provides further support for an autoimmune etiology. We propose a new molecular classification of nephrin autoantibody minimal change disease to serve as framework for instigation of precision therapeutics for these patients.