Viral and Host Transcriptomes in SARS-CoV-2-Infected Human Lung Cells.

Coronaviruses are commonly characterized by a unique discontinuous RNA transcriptional synthesis strategy guided by transcription-regulating sequences (TRSs). However, the details of RNA synthesis in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been fully elucidated. Here, we present a time-scaled, gene-comparable transcriptome of SARS-CoV-2, demonstrating that ACGAAC functions as a core TRS guiding the discontinuous RNA synthesis of SARS-CoV-2 from a holistic perspective. During infection, viral transcription, rather than genome replication, dominates all viral RNA synthesis activities. The most highly expressed viral gene is the nucleocapsid gene, followed by ORF7 and ORF3 genes, while the envelope gene shows the lowest expression. Host transcription dysregulation keeps exacerbating after viral RNA synthesis reaches a maximum. The most enriched host pathways are metabolism related. Two of them (cholesterol and valine metabolism) affect viral replication in reverse. Furthermore, the activation of numerous cytokines emerges before large-scale viral RNA synthesis. IMPORTANCE SARS-CoV-2 is responsible for the current severe global health emergency that began at the end of 2019. Although the universal transcriptional strategies of coronaviruses are preliminarily understood, the details of RNA synthesis, especially the time-matched transcription level of each SARS-CoV-2 gene and the principles of subgenomic mRNA synthesis, are not clear. The coterminal subgenomic mRNAs of SARS-CoV-2 present obstacles in identifying the expression of most genes by PCR-based methods, which are exacerbated by the lack of related antibodies. Moreover, SARS-CoV-2-related metabolic imbalance and cytokine storm are receiving increasing attention from both clinical and mechanistic perspectives. Our transcriptomic research provides information on both viral RNA synthesis and host responses, in which the transcription-regulating sequences and transcription levels of viral genes are demonstrated, and the metabolic dysregulation and cytokine levels identified at the host cellular level support the development of novel medical treatment strategies.

Binary information propagation in circular magnetic nanodot arrays using strain induced magnetic anisotropy.

Nanomagnetic logic has emerged as a potential replacement for traditional Complementary Metal Oxide Semiconductor (CMOS) based logic because of superior energy-efficiency (Salahuddin and Datta 2007 Appl. Phys. Lett. 90 093503, Cowburn and Welland 2000 Science 287 1466-68). One implementation of nanomagnetic logic employs shape-anisotropic (e.g. elliptical) ferromagnets (with two stable magnetization orientations) as binary switches that rely on dipole-dipole interaction to communicate binary information (Cowburn and Welland 2000 Science 287 1466-8, Csaba et al 2002 IEEE Trans. Nanotechnol. 1 209-13, Carlton et al 2008 Nano Lett. 8 4173-8, Atulasimha and Bandyopadhyay 2010 Appl. Phys. Lett. 97 173105, Roy et al 2011 Appl. Phys. Lett. 99 063108, Fashami et al 2011 Nanotechnology 22 155201, Tiercelin et al 2011 Appl. Phys. Lett. 99 , Alam et al 2010 IEEE Trans. Nanotechnol. 9 348-51 and Bhowmik et al 2013 Nat. Nanotechnol. 9 59-63). Normally, circular nanomagnets are incompatible with this approach since they lack distinct stable in-plane magnetization orientations to encode bits. However, circular magnetoelastic nanomagnets can be made bi-stable with a voltage induced anisotropic strain, which provides two significant advantages for nanomagnetic logic applications. First, the shape-anisotropy energy barrier is eliminated which reduces the amount of energy required to reorient the magnetization. Second, the in-plane size can be reduced (∼20 nm) which was previously not possible due to thermal stability issues. In circular magnetoelastic nanomagnets, a voltage induced strain stabilizes the magnetization even at this size overcoming the thermal stability issue. In this paper, we analytically demonstrate the feasibility of a binary 'logic wire' implemented with an array of circular nanomagnets that are clocked with voltage-induced strain applied by an underlying piezoelectric substrate. This leads to an energy-efficient logic paradigm orders of magnitude superior to existing CMOS-based logic that is scalable to dimensions substantially smaller than those for existing nanomagnetic logic approaches. The analytical approach is validated with experimental measurements conducted on dipole coupled Nickel (Ni) nanodots fabricated on a PMN-PT (Lead Magnesium Niobate-Lead Titanate) sample.

Furanocoumarins are a novel class of modulators for the transient receptor potential vanilloid type 1 (TRPV1) channel.

Furanocoumarin imperatorin is the major active component of Angelica dahurica root extracts, widely used in traditional medicine to treat headache, toothache, and orbital eye pain. In this study, we investigated the mechanisms that may underlie the pain-relieving effects of the compound. We found that imperatorin significantly inhibited formalin- and capsaicin-induced nocifensive responses but did not alter baseline thermal withdrawal thresholds in the rat. We established that imperatorin is a weak agonist of TRPV1, a channel implicated in detecting several noxious stimuli, exhibiting a 50% effective concentration (EC50) of 12.6 ± 3.2 µM. A specific TRPV1 antagonist, JNJ-17203212 (0.5 µM), potently inhibited imperatorin-induced TRPV1 activation. Site-directed mutagenesis studies revealed that imperatorin most likely acted via a site adjacent to or overlapping with the TRPV1 capsaicin-binding site. TRPV1 recovery from desensitization was delayed in the presence of imperatorin. Conversely, imperatorin sensitized TRPV1 to acid activation but did not affect the current amplitude and/or the activation-inactivation properties of Na(v)1.7, a channel important for transmission of nociceptive information. Thus, our data indicate that furanocoumarins represent a novel group of TRPV1 modulators that may become important lead compounds in the drug discovery process aimed at developing new treatments for pain management.