he prevalence of coronavirus disease 2019 has posed a great threat to people's health worldwide, bringing a great challenges to the public healthcare systems. A recent study has confirmed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses severe acute respiratory syndrome coronavirus (SARS-CoV) receptor angiotensin-converting enzyme 2 (ACE2) for host cell entry. 1 ACE2 expression was previously found to correlate with susceptibility to SARS-CoV infection in vitro. 2 As with SARS-CoV, higher ACE2 expression might also lead to higher risk of SARS-CoV-2 infection.

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Using the Millstone Hill incoherent scatter radar observations during 2015 St. Patrick's Day storm, subauroral polarization streams (SAPSs) have been specified in the nonhydrostatic Global Ionosphere‐Thermosphere Model simulations. The results reveal that the effect of SAPS on the coupled thermosphere‐ionosphere system includes the following: (1) Sudden frictional heating of SAPS results in acoustic‐gravity waves in the thermosphere. The vertical oscillation is localized, while the meridional disturbance propagates poleward and equatorward. (2) The SAPS‐associated horizontal wind field includes an enhanced westward wind within SAPS channel and a twin of vortex‐like winds north (clockwise) and south (anticlockwise) of subauroral latitudes. (3) Due to the neutral‐ion drag, ions in the vicinity of SAPS channel oscillate vertically with neutrals, resulting in a perturbation of ~0.3 TECu in ionospheric total electron content. The SAPS‐induced traveling atmospheric disturbances can elevate the plasma and increase the total electron content in midlatitude ionosphere. (4) It is confirmed that the Coriolis force can contribute to the poleward turning of the neutral wind during the post‐SAPS interval. In addition, the traveling atmospheric disturbance induced by the variation of auroral input and high‐latitude convection is possibly the primary cause of the poleward neutral wind surge during the magnetic storm on 17–18 March 2015. The combination of the two factors can make the northward meridional wind surge reach a magnitude of 100 m/s. This study improves our understanding of the SAPS's effect on neutral dynamics and ion‐neutral coupling processes during geomagnetically disturbed intervals.

Background. Inflammation and oxidative stress are involved in the initiation and progress of heart failure (HF). However, the role of the IL6/STAT3 pathway in the pressure overload-induced HF remains controversial. Methods and Results. Transverse aortic constriction (TAC) was used to induce pressure overload-HF in C57BL/6J mice. 18 mice were randomized into three groups (Sham, TAC, and TAC+raloxifene, n = 6 , respectively). Echocardiographic and histological results showed that cardiac hypertrophy, fibrosis, and left ventricular dysfunction were manifested in mice after TAC treatment of eight weeks, with aggravation of macrophage infiltration and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) expression in the myocardium. TAC (four and eight weeks) elevated the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) and prohibitin2 (PHB2) protein expression. Importantly, IL-6/gp130/STAT3 inhibition by raloxifene alleviated TAC-induced myocardial inflammation, cardiac remodeling, and dysfunction. In vitro, we demonstrated cellular hypertrophy with STAT3 activation and oxidative stress exacerbation could be elicited by IL-6 (25 ng/mL, 48 h) in H9c2 myoblasts. Sustained IL-6 stimulation increased intracellular reactive oxygen species, repressed mitochondrial membrane potential (MMP), decreased intracellular content of ATP, and led to decreased SOD activity, an increase in iNOS protein expression, and increased protein expression of Pink1, Parkin, and Bnip3 involving in mitophagy, all of which were reversed by raloxifene. Conclusion. Inflammation and IL-6/STAT3 signaling were activated in TAC-induced HF in mice, while sustained IL-6 incubation elicited oxidative stress and mitophagy-related protein increase in H9c2 myoblasts, all of which were inhibited by raloxifene. These indicated IL-6/STAT3 signaling might be involved in the pathogenesis of myocardial hypertrophy and HF.

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The interleukin (IL)‐6/glycoprotein (GP)130/signal transducer and activator of transcription (STAT)3 pathway is emerging as a target for the treatment of hepatocellular carcinoma. IL‐6 binds to IL‐6R, forming a binary complex, which further combines with GP130 to transduce extracellular signaling by activating STAT3. Therefore, blocking the interaction between IL‐6 and GP130 may inhibit the IL‐6/GP130/STAT3 signaling pathway and its biological effects. It has been reported that bazedoxifene acetate (BAZ), a selective estrogen receptor modulator approved by the US Food and Drug Administration, could inhibit IL‐6/GP130 protein‐protein interactions. Western blot, immunofluorescence staining, wound healing and colony formation assays were used to detect the effect of BAZ on liver cancer cells. Cell viability was evaluated by MTT assay. Apoptosis of cells was determined using the Annexin V‐FITC detection kit. Mouse xenograft tumor models were utilized to evaluate the effect of BAZ in vivo. Our data showed that BAZ inhibited STAT3 phosphorylation (P‐STAT3) and expression of STAT3 downstream genes, inducing apoptosis in liver cancer cells. BAZ inhibited P‐STAT3 induced by IL‐6, but not by leukemia inhibitory factor. BAZ inhibited P‐STAT1 and P‐STAT6 less significantly as elicited by interferon‐α, interferon‐γ and IL‐4. In addition, pretreatment of BAZ impeded the translocation of STAT3 to nuclei induced by IL‐6. BAZ inhibited cell viability, wound healing and colony formation in vitro. Furthermore, tumor growth in HEPG2 mouse xenografts were significantly inhibited by daily intragastric gavage of BAZ. Our results suggest that BAZ inhibited the growth of hepatocellular carcinoma in vitro and in vivo, indicating another potential strategy for HCC prevention and therapy.

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In this study, the ionospheric responses in the Asian-Australian, American, and African sectors during the August 2018 geomagnetic storm were investigated based on the Beidou geostationary orbit (GEO) satellite and Massachusetts Institute of Technology (MIT) Madrigal total electron contents (TECs), combined with measurements from ionosondes, magnetometers, and Global Ultraviolet Imager (GUVI). The middle-and low-latitude TECs were dominated by positive responses over the three longitudinal sectors during the storm on 26-29 August. It is unique that daytime TECs at the Asian-Australian, American, and African sectors displayed large enhancements larger than 10 TEC units (TECu) on 27-29 August, during the recovery phase, when the ionosphere is usually dominated by plasma depletions due to the ionospheric disturbance dynamo and/or disturbed thermospheric compositions. The combination and competition of the disturbed vertical plasma drifts through the solar wind-magnetosphere-ionosphere (SW-M-I) coupling and disturbed neutral compositions contribute significantly to the daytime TEC responses at different longitudinal sectors on 26 August during the main and early recovery phases. The eastward equatorial electrojet and O/N 2 during the recovery phase on 27-29 August are larger than the quiet reference, which suggest that the enhanced upward vertical plasma drifts combining with higher O/N 2 make an important contribution on the daytime positive ionospheric storm during the recovery phase. The enhanced vertical plasma drifts could not be driven by the SW-M-I coupling or ionospheric disturbance dynamo associated with the geomagnetic storm. Further studies should be untaken to explore the dominant sources for the enhanced upward vertical drifts during the recovery phase.