The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and rapidly spread worldwide. To prevent SARS-CoV-2 ...dissemination, understanding the in vivo characteristics of SARS-CoV-2 is a high priority. We report a ferret model of SARS-CoV-2 infection and transmission that recapitulates aspects of human disease. SARS-CoV-2-infected ferrets exhibit elevated body temperatures and virus replication. Although fatalities were not observed, SARS-CoV-2-infected ferrets shed virus in nasal washes, saliva, urine, and feces up to 8 days post-infection. At 2 days post-contact, SARS-CoV-2 was detected in all naive direct contact ferrets. Furthermore, a few naive indirect contact ferrets were positive for viral RNA, suggesting airborne transmission. Viral antigens were detected in nasal turbinate, trachea, lungs, and intestine with acute bronchiolitis present in infected lungs. Thus, ferrets represent an infection and transmission animal model of COVID-19 that may facilitate development of SARS-CoV-2 therapeutics and vaccines.
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•SARS-CoV-2-infected ferrets exhibit elevated body temperature and virus replication•SARS-CoV-2 is shed in nasal washes, saliva, urine and feces•SARS-CoV-2 is effectively transmitted to naive ferrets by direct contact•SARS-CoV-2 infection leads acute bronchiolitis in infected ferrets
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spreads, leading to a pandemic infection. Kim et al. show that ferrets are highly susceptible to SARS-CoV-2 infection and effectively transmit the virus by direct or indirect contact, recapitulating human infection and transmission.
The synthesis of atomically thin transition-metal disulfides (MS2) with layer controllability and large-area uniformity is an essential requirement for their application in electronic and optical ...devices. In this work, we describe a process for the synthesis of WS2 nanosheets through the sulfurization of an atomic layer deposition (ALD) WO3 film with systematic layer controllability and wafer-level uniformity. The X-ray photoemission spectroscopy, Raman, and photoluminescence measurements exhibit that the ALD-based WS2 nanosheets have good stoichiometry, clear Raman shift, and bandgap dependence as a function of the number of layers. The electron mobility of the monolayer WS2 measured using a field-effect transistor (FET) with a high-k dielectric gate insulator is shown to be better than that of CVD-grown WS2, and the subthreshold swing is comparable to that of an exfoliated MoS2 FET device. Moreover, by utilizing the high conformality of the ALD process, we have developed a process for the fabrication of WS2 nanotubes.
Leg capacitor energy balancing control is one of the crucial issues for stable operation of a cascaded H-bridge (CHB) converter. Because this topology inherently consists of numerous submodule cells ...with DC capacitors, the cell voltages and leg capacitor energy instantaneously fluctuate depending on operation sequence of the CHB converter. In general, a wye-connected CHB-converter-based static synchronous compensator (STATCOM) utilizes a zero-sequence voltage component for leg capacitor energy balancing. In this paper, to improve the dynamics of leg energy balancing control, a feedforward calculation method of the zero-sequence voltage injection is proposed. The feedforward term can be instantaneously calculated by using the information from the measured leg voltages and leg currents, and the method ensures successful regulation of the leg energy balance even under unbalanced grid and load conditions. Moreover, the verification of the proposed method is supported by the mathematical vector theorems. A 50MVA full-scale wye-connected CHB–STATCOM system simulation was performed to verify the proposed feedforward calculation method considering unbalanced grid as well as unbalanced load conditions.
Incessant development and introduction of novel cultivars with improved floral attributes are vital in the dynamic ornamental industry. Chrysanthemum (
) is a highly favored ornamental plant, ranking ...second globally in the cut flower trade, after rose. Development of new chrysanthemum cultivars with improved and innovative modifications in ornamental attributes, including floral color, shape, plant architecture, flowering time, enhanced shelf life, and biotic and abiotic stress tolerance, is a major goal in chrysanthemum breeding. Despite being an economically important ornamental plant, the application of conventional and molecular breeding approaches to various key traits of chrysanthemum is hindered owing to its genomic complexity, heterozygosity, and limited gene pool availability. Although classical breeding of chrysanthemum has resulted in the development of several hundreds of cultivars with various morphological variations, the genetic and transcriptional control of various important ornamental traits remains unclear. The coveted blue colored flowers of chrysanthemums cannot be achieved through conventional breeding and mutation breeding due to technical limitations. However, blue-hued flower has been developed by genetic engineering, and transgenic molecular breeding has been successfully employed, leading to substantial progress in improving various traits. The recent availability of whole-genome sequences of chrysanthemum offers a platform to extensively employ MAS to identify a large number of markers for QTL mapping, and GWAS to dissect the genetic control of complex traits. The combination of NGS, multi-omic platforms, and genome editing technologies has provided a tremendous scope to decipher the molecular and regulatory mechanisms. However, the application and integration of these technologies remain inadequate for chrysanthemum. This review, therefore, details the significance of floral attributes, describes the efforts of recent advancements, and highlights the possibilities for future application towards the improvement of crucial ornamental traits in the globally popular chrysanthemum plant.
Under endoplasmic reticulum (ER)‐stress conditions, the unfolded protein response (UPR) generates a defense mechanism in mammalian cells. The regulation of UPR signaling is important in oocyte ...maturation, embryo development, and female reproduction of pigs. Recent studies have shown that melatonin plays an important role as an antioxidant to improve pig oocyte maturation. However, there is no report on the role of melatonin in the regulation of UPR signaling and ER‐stress during in vitro maturation (IVM) of porcine oocytes. Therefore, the objective of this study was to investigate the antioxidative effects of melatonin on porcine oocyte maturation through the regulation of ER‐stress and UPR signaling. We investigated the changes in the mRNA/protein expression levels of three UPR signal genes (Bip/Grp78, ATF4, P90/50ATF6, sXbp1, and CHOP) on oocytes, cumulus cells, and cumulus‐oocyte complexes (COCs) during IVM (metaphase I; 22 hours and metaphase II; 44 hours) by Western blot and reverse transcription‐polymerase chain reaction analysis. Treatment with the ER‐stress inducer, tunicamycin (Tm), significantly increased expression of UPR markers. Additionally, cumulus cell expansion and meiotic maturation of oocytes were reduced in COCs of Tm‐treated groups (1, 5, and 10 μg/mL). We confirmed the reducing effects of melatonin (0.1 μmol/L) on ER‐stress after pretreatment with Tm (5 μg/mL; 22 hours) in maturing COCs. Addition of melatonin (0.1 μmol/L) to Tm‐pretreated COCs recovered meiotic maturation rates and expression of most UPR markers. In conclusion, we confirmed a role for melatonin in the modulation of UPR signal pathways and reducing ER‐stress during IVM of porcine oocytes.
This study assessed the ecological risk posed by microplastics in surface and subsurface seawaters in coastal, continental shelf, and deep-sea areas of South Korea. The target microplastics for risk ...assessment were specified as only non-spherical type microplastics in the size range 20–300 μm, because this type was predominantly observed in our study areas, and adverse biological effects have previously been reported. Exposure data for non-spherical microplastics were obtained from a previous study or were measured for microplastics of sizes down to 20 μm. A predicted no-effect concentration (PNEC) of 12 particles/L was derived by employing a species sensitivity distribution approach. Then the results were compared to the in situ observed concentrations at each site. The detected microplastic concentrations did not exceed the derived PNEC, i.e., the current pollution levels of fragment and fiber microplastics in the size range 20–300 μm would not pose a significant threat to the marine ecosystem in South Korea. However, predictions are that microplastic pollution will increase to 50-fold by 2100 at the current rates, and in this scenario, the microplastic concentration is expected to far exceed the derived PNEC values for marine ecosystems. It is therefore urgent to take precautionary actions to prevent a further increase in microplastic concentrations in these environments.
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•Predicted no effect concentration (PNEC) for non-spherical microplastic was derived.•The microplastic concentrations in Korean marine water was lower than PNEC.•No ecological risk in Korean saltwater environments is suspected.•The microplastic concentration is predicted to well exceed PNEC value by 2100.•Actions to prevent a further increase in microplastic concentrations should be taken.
Ecological risk assessment was conducted by matching size range and morphology of microplastics in both toxicity data and field monitoring data.
In neutral point clamped (NPC) converters, the voltage ripples in each dc-link capacitor are mainly influenced by the third harmonic component in the neutral point of the three-level NPC converter. ...These low-order harmonic voltage ripples distort the output of the converter and compromise system stability. Moreover, as the converter's output increases, the capacitor's ripple component escalates correspondingly, necessitating capacitors with a higher capacitance to maintain the reliability of the NPC converter. In this article, a novel technique is introduced that is designed to mitigate voltage ripples in the dc-link capacitor of three-level NPC converters. By employing a zigzag transformer, the method effectively compensates for the third harmonic component of the voltage in the dc link, resulting in a significant reduction of ripple. The validity and effectiveness of the proposed method are corroborated through comprehensive simulations and experiments.
Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at ...clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2), suggesting that rapid preclinical animal studies are required to identify potential antiviral candidates for human trials. To this end, the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir for SARS-CoV-2 infection were assessed in the ferret infection model. While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Only the emtricitabine-tenofovir-treated group showed lower virus titers in nasal washes at 8 days postinfection (dpi) than the PBS-treated control group. To further explore the effect of immune suppression on viral infection and clinical outcome, ferrets were treated with azathioprine, an immunosuppressive drug. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. Taken together, all antiviral drugs tested marginally reduced the overall clinical scores of infected ferrets but did not significantly affect
virus titers. Despite the potential discrepancy of drug efficacies between animals and humans, these preclinical ferret data should be highly informative to future therapeutic treatment of COVID-19 patients.
The SARS-CoV-2 pandemic continues to spread worldwide, with rapidly increasing numbers of mortalities, placing increasing strain on health care systems. Despite serious public health concerns, no effective vaccines or therapeutics have been approved by regulatory agencies. In this study, we tested the FDA-approved drugs lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir against SARS-CoV-2 infection in a highly susceptible ferret infection model. While most of the drug treatments marginally reduced clinical symptoms, they did not reduce virus titers, with the exception of emtricitabine-tenofovir treatment, which led to diminished virus titers in nasal washes at 8 dpi. Further, the azathioprine-treated immunosuppressed ferrets showed delayed virus clearance and low SN titers, resulting in a prolonged infection. As several FDA-approved or repurposed drugs are being tested as antiviral candidates at clinics without sufficient information, rapid preclinical animal studies should proceed to identify therapeutic drug candidates with strong antiviral potential and high safety prior to a human efficacy trial.
During evolution, herpesviruses have developed numerous, and often very ingenious, strategies to counteract efficient host immunity. Specifically, Kaposi's sarcoma-associated herpesvirus (KSHV) ...eludes host immunity by undergoing a dormant stage, called latency wherein it expresses a minimal number of viral proteins to evade host immune activation. Here, we show that during latency, KSHV hijacks the complement pathway to promote cell survival. We detected strong deposition of complement membrane attack complex C5b-9 and the complement component C3 activated product C3b on Kaposi's sarcoma spindle tumor cells, and on human endothelial cells latently infected by KSHV, TIME-KSHV and TIVE-LTC, but not on their respective uninfected control cells, TIME and TIVE. We further showed that complement activation in latently KSHV-infected cells was mediated by the alternative complement pathway through down-regulation of cell surface complement regulatory proteins CD55 and CD59. Interestingly, complement activation caused minimal cell death but promoted the survival of latently KSHV-infected cells grown in medium depleted of growth factors. We found that complement activation increased STAT3 tyrosine phosphorylation (Y705) of KSHV-infected cells, which was required for the enhanced cell survival. Furthermore, overexpression of either CD55 or CD59 in latently KSHV-infected cells was sufficient to inhibit complement activation, prevent STAT3 Y705 phosphorylation and abolish the enhanced survival of cells cultured in growth factor-depleted condition. Together, these results demonstrate a novel mechanism by which an oncogenic virus subverts and exploits the host innate immune system to promote viral persistent infection.
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