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RNA interference (RNAi) is originally regarded as a mechanism of eukaryotic posttranscriptional gene regulation mediated by small interfering RNA (siRNA)-induced sequence-specific RNA degradation (1). It is also well known to exert as an important antiviral defense mechanism in a wide range of organisms, from plants to invertebrates (2). During the virus infection, the virus-derived long double-stranded RNA (dsRNA) is cleaved by RNAIII-like endonuclease (named Dicer) into approximately 21-to 23-nucleotide (nt) siRNA, which is incorporated into the RNA-induced silencing complex (RISC) and activates the antiviral RNAi for viral RNA degradation. In mammalian cells, although the activation of RNAi by synthetic siRNA or short hairpin RNA (shRNA) is widely used as a tool for gene knockdown and antiviral treatment, the RNAi-mediated antiviral mechanism has been debated for a long time (3), because the interferon (IFN) response of the innate immune system is well known as the dominant antiviral mechanism (4). However, more and more evidence has provided strong support for the existence of a natural RNAi-mediated antiviral response in mammals (5). Moreover, recent studies showed that in undifferentiated cells and immature mice, the RNAi-mediated antiviral response is essential (6-8).To overcome the RNAi-mediated antiviral defense, viruses have evolved to encode a viral suppressor of RNA silencing (VSR) (9, 10). For example, in plant viruses, rice hoja blancavirus NS3, tombusvirus P19, and tomato aspermy virus 2b bind to long dsRNA or siRNA to block RNAi (11-13). Turnip crinkle virus P38 and cauliflower mosaic virus P6 disrupt the components of RNAi machinery (14,15). In insect viruses, flock house virus (FHV) B2 blocks RNAi by dsRNA binding (16,17), and Wuhan nodavirus (WhNV) B2 was identified as a VSR by targeting both dsRNAs and 19). Although the majority of VSRs have been identified in plant and invertebrate viruses, several mammalian viruses were shown to encode VSRs. For instance, Ebola virus VP35, influenza A virus NS1, vaccinia virus E3L, and Nodamura virus (NoV) B2 act as VSRs by binding dsRNA (20-23). Hepatitis C virus core and HIV-1 Tat block RNAi by inhibiting the activity of

BackgroundThe Internet has become an established source of health information for people seeking health information. In recent years, research on the health information seeking behavior of Internet users has become an increasingly important scholarly focus. However, there have been no long-term bibliometric studies to date on Internet health information seeking behavior.ObjectiveThe purpose of this study was to map publication trends and explore research hot spots of Internet health information seeking behavior.MethodsA bibliometric analysis based on PubMed was conducted to investigate the publication trends of research on Internet health information seeking behavior. For the included publications, the annual publication number, the distribution of countries, authors, languages, journals, and annual distribution of highly frequent major MeSH (Medical Subject Headings) terms were determined. Furthermore, co-word biclustering analysis of highly frequent major MeSH terms was utilized to detect the hot spots in this field.ResultsA total of 533 publications were included. The research output was gradually increasing. There were five authors who published four or more articles individually. A total of 271 included publications (50.8%) were written by authors from the United States, and 516 of the 533 articles (96.8%) were published in English. The eight most active journals published 34.1% (182/533) of the publications on this topic. Ten research hot spots were found: (1) behavior of Internet health information seeking about HIV infection or sexually transmitted diseases, (2) Internet health information seeking behavior of students, (3) behavior of Internet health information seeking via mobile phone and its apps, (4) physicians’ utilization of Internet medical resources, (5) utilization of social media by parents, (6) Internet health information seeking behavior of patients with cancer (mainly breast cancer), (7) trust in or satisfaction with Web-based health information by consumers, (8) interaction between Internet utilization and physician-patient communication or relationship, (9) preference and computer literacy of people using search engines or other Web-based systems, and (10) attitude of people (especially adolescents) when seeking health information via the Internet.ConclusionsThe 10 major research hot spots could provide some hints for researchers when launching new projects. The output of research on Internet health information seeking behavior is gradually increasing. Compared to the United States, the relatively small number of publications indexed by PubMed from other developed and developing countries indicates to some extent that the field might be still underdeveloped in many countries. More studies on Internet health information seeking behavior could give some references for health information providers.

The H3 histone variant CENP-A is an epigenetic marker critical for the centromere identity and function. However, the precise regulation of the spatiotemporal deposition and propagation of CENP-A at centromeres during the cell cycle is still poorly understood. Here, we show that CENP-A is phosphorylated at Ser68 during early mitosis by Cdk1. Our results demonstrate that phosphorylation of Ser68 eliminates the binding of CENP-A to the assembly factor HJURP, thus preventing the premature loading of CENP-A to the centromere prior to mitotic exit. Because Cdk1 activity is at its minimum at the mitotic exit, the ratio of Cdk1/PP1α activity changes in favor of Ser68 dephosphorylation, thus making CENP-A available for centromeric deposition by HJURP. Thus, we reveal that dynamic phosphorylation of CENP-A Ser68 orchestrates the spatiotemporal assembly of newly synthesized CENP-A at active centromeres during the cell cycle.

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Intracellular delivery of messenger RNA (mRNA)-based cancer vaccine has shown great potential to elicit antitumor immunity. To achieve robust antitumor efficacy, mRNA encoding tumor antigens needs to be efficiently delivered and translated in dendritic cells with concurrent innate immune stimulation to promote antigen presentation. Here, by screening a group of cationic lipid-like materials, we developed a minimalist nanovaccine with C1 lipid nanoparticle (LNP) that could efficiently deliver mRNA in antigen presenting cells with simultaneous Toll-like receptor 4 (TLR4) activation and induced robust T cell activation. The C1 nanovaccine entered cells via phagocytosis and showed efficient mRNA-encoded antigen expression and presentation. Furthermore, the C1 lipid nanoparticle itself induced the expression of inflammatory cytokines such as IL-12 via stimulating TLR4 signal pathway in dendritic cells. Importantly, the C1 mRNA nanovaccine exhibited significant antitumor efficacy in both tumor prevention and therapeutic vaccine settings. Overall, our work presents a C1 LNP-based mRNA cancer nanovaccine with efficient antigen expression as well as self-adjuvant property, which may provide a platform for developing cancer immunotherapy for a wide range of tumor types.

We report the visible‐light‐induced trifluoromethylation of arenes and heteroarenes using sodium trifluoromethanesulfinate catalyzed by anthraquinone‐2‐carboxylic acid. This reaction is a metal‐free trifluoromethylation of arenes and heteroarenes catalyzed by a photoredox organocatalyst. Perfluoroalkylated arenes were also produced using sodium perfluoroalkylsulfinates.magnified image

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