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.
Despite the excellent sorption ability of biochar for heavy metals, it is difficult to separate and reuse after adsorption when applied to wastewater treatment process. To overcome these drawbacks, ...we developed an engineered magnetic biochar by pyrolyzing waste marine macro-algae as a feedstock, and we doped iron oxide particles (e.g., magnetite, maghemite) to impart magnetism. The physicochemical characteristics and adsorption properties of the biochar were evaluated. When compared to conventional pinewood sawdust biochar, the waste marine algae-based magnetic biochar exhibited a greater potential to remove heavy metals despite having a lower surface area (0.97m2/g for kelp magnetic biochar and 63.33m2/g for hijikia magnetic biochar). Although magnetic biochar could be effectively separated from the solution, however, the magnetization of the biochar partially reduced its heavy metal adsorption efficiency due to the biochar's surface pores becoming plugged with iron oxide particles. Therefore, it is vital to determine the optimum amount of iron doping that maximizes the biochar's separation without sacrificing its heavy metal adsorption efficiency. The optimum concentration of the iron loading solution for the magnetic biochar was determined to be 0.025–0.05mol/L. The magnetic biochar's heavy metal adsorption capability is considerably higher than that of other types of biochar reported previously. Further, it demonstrated a high selectivity for copper, showing two-fold greater removal (69.37mg/g for kelp magnetic biochar and 63.52mg/g for hijikia magnetic biochar) than zinc and cadmium. This high heavy metal removal performance can likely be attributed to the abundant presence of various oxygen-containing functional groups (COOH and OH) on the magnetic biochar, which serve as potential adsorption sites for heavy metals. The unique features of its high heavy metal removal performance and easy separation suggest that the magnetic algae biochar can potentially be applied in diverse areas that require biosorbents for pollutant removal.
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•Magnetic biochar derived from marine macro-algae was made for heavy metal adsorption.•Physicochemical properties and isotherms were characterized using various techniques.•Iron-loaded condition was optimized for Cd, Cu, and Zn removal and magnetic separation simultaneously.•Magnetic macro-algae biochar had high selectivity for Cu with plentiful O-containing groups.•Adsorption and recovery ability showed an opposite tendency as iron doping increased.
Thin films of block copolymers are widely seen as enablers for nanoscale fabrication of semiconductor devices, membranes, and other structures, taking advantage of microphase separation to produce ...well‐organized nanostructures with periods of a few nm and above. However, the inherently three‐dimensional structure of block copolymer microdomains could enable them to make 3D devices and structures directly, which could lead to efficient fabrication of complex heterogeneous structures. This article reviews recent progress in developing 3D nanofabrication processes based on block copolymers.
This article reviews nanofabrication methods based on the inherently three‐dimensional structure of block copolymer microdomains, which could lead to efficient fabrication of complex heterogeneous nanostructures and devices. The image shows an example in which a bilayer of cylindrical microdomains is ordered using topographical posts to form a three‐dimensional crosspoint structure.
For the purpose of reusing wasted marine macro-algae generated during cultivation, harvesting, processing and selling processes, biochars derived from Saccharina japonica (known as kelp) and ...Sargassum fusiforme (known as hijikia) were characterized and their removal capacities for Cu, Cd, and Zn in aqueous solution were assessed. Feedstocks, S. japonica, S. fusiforme, and also pinewood sawdust as a control, were pyrolyzed at 250, 400, 500, 600 and 700 °C. In evaluating heavy metal removal capacities, SJB (S. japonica biochar) showed the best performance, with removal efficiencies of more than 98% for the three heavy metals when pyrolyzed at over 400 °C. SFB (S. fusiforme biochar) also showed good potential as an adsorbent, with removal efficiencies for the three heavy metals of more than 86% when pyrolyzed at over 500 °C. On the contrary, the maximum removal efficiencies of PSB (pinewood sawdust biochar) were 81%, 46%, and 47% for Cu, Cd, and Zn, respectively, even at 700 °C, the highest pyrolysis temperature. This demonstrates that marine macro-algae were advantageous in terms of production energy for removing heavy metals even at relatively low pyrolysis temperatures, compared with PSB. The excellent heavy metal adsorption capacities of marine macro-algae biochars were considered due to their higher pH and more oxygen-containing functional groups, although the specific surface areas of SJB and SFB were significantly lower than that of PSB. This research confirmed that the use of marine macro-algae as a heavy metal adsorbent was suitable not only in the removal of heavy metals, but also in terms of resource recycling and energy efficiency.
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•Marine macro-algae wastes were reused as biochar for the pollutant removal.•Marine macro-algae biochar (MMAB) showed an excellent heavy metal removal performance.•MMAB exhibits high pH and abundant oxygen-containing functional groups on the surface.•The yield and efficiency of MMAB were higher than those of conventional woody biochar.•MMAB can work efficiently even as pyrolyzed at relatively low temperatures (400–500 °C).
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.
We recently developed a method called expansion microscopy, in which preserved biological specimens are physically magnified by embedding them in a densely crosslinked polyelectrolyte gel, anchoring ...key labels or biomolecules to the gel, mechanically homogenizing the specimen, and then swelling the gel-specimen composite by ∼4.5× in linear dimension. Here we describe iterative expansion microscopy (iExM), in which a sample is expanded ∼20×. After preliminary expansion a second swellable polymer mesh is formed in the space newly opened up by the first expansion, and the sample is expanded again. iExM expands biological specimens ∼4.5 × 4.5, or ∼20×, and enables ∼25-nm-resolution imaging of cells and tissues on conventional microscopes. We used iExM to visualize synaptic proteins, as well as the detailed architecture of dendritic spines, in mouse brain circuitry.
Data on the relationship between the triglyceride glucose (TyG) index and coronary artery calcification (CAC) progression is limited. This longitudinal study evaluated the association of TyG index ...with CAC progression in asymptomatic adults.
We enrolled 12,326 asymptomatic Korean adults who had at least two CAC evaluations. The TyG index was determined using ln (fasting triglycerides mg/dL × fasting glucose mg/dL/2). CAC progression was defined as a difference ≥ 2.5 between the square roots (√) of the baseline and follow-up coronary artery calcium score (CACS) (Δ√transformed CACS). Annualized Δ√transformed CACS was defined as Δ√transformed CACS divided by the inter-scan period.
During a mean 3.3 years, the overall incidence of CAC progression was 30.6%. The incidence of CAC progression (group I lowest: 22.7% versus vs. group II: 31.7% vs. group III highest: 37.5%, P < 0.001) and annualized Δ√transformed CACS (group I: 0.46 ± 1.44 vs. group II: 0.71 ± 2.02 vs. group III: 0.87 ± 1.75, P < 0.001) were markedly elevated with increasing TyG index tertiles. Multivariate linear regression analysis showed that TyG index was associated with annualized Δ√transformed CACS (β = 0.066, P = 0.036). In multivariate logistic regression analysis, the TyG index was significantly associated with CAC progression in baseline CACS ≤ 100.
The TyG index is an independent predictor of CAC progression, especially in adults without heavy baseline CAC.
We examined the connection between matrix metalloproteinase (MMP) expression/activity and pterygium fibroblast migration, and how these were affected by bevacizumab and/or cyclosporine A (CsA). ...Fibroblasts were obtained from 20 pterygia and 6 normal conjunctival specimens. Expression levels of MMP-3 and MMP-13 were examined after bevacizumab administration. Immunofluorescence staining was used to examine expression of both MMPs in fibroblasts migrating out from explanted pterygium tissues. Rates of cell migration from explant-cultured pterygia tissues and scratch-wounded confluent pterygium fibroblasts were examined in the presence of MMP-3 or MMP-13 inhibitors, as well as bevacizumab and/or CsA. A scratch wound healing migration assay was performed to determine the effects of bevacizumab and/or CsA. Protein expression of both MMPs in pterygium tissues and in cells migrating from organ-cultured pterygium tissues was greater than that observed in normal cells. Inhibition of the activities of both MMPs decreased their expression levels; these were also significantly reduced in bevacizumab-injected pterygium tissues. Bevacizumab significantly reduced the expression of both MMPs and cell migration. Pretreatment with CsA prior to bevacizumab exposure markedly inhibited cell migration and the expression of both MMPs. CsA enhanced the inhibitory effects of bevacizumab on pterygium fibroblast migration in vitro, possibly by inhibiting expression of both MMPs. These findings suggest that combined CsA and bevacizumab treatment may provide a potential therapeutic strategy for reducing the rate of pterygium recurrence.
Adipose tissue-derived stem cells (ADSCs), a type of mesenchymal stem cells (MSCs), have great potential as therapeutic agents in regenerative medicine. Numerous animal studies have documented the ...multipotency of ADSCs, showing their capabilities to differentiate into tissues such as muscle, bone, cartilage, and tendon. However, the safety of autologous ADSC injections into human joints is only beginning to be understood and the data are lacking.
Between 2009 and 2010, 91 patients were treated with autologous ADSCs with platelet-rich plasma (PRP) for various orthopedic conditions. Stem cells in the form of stromal vascular fraction (SVF) were injected with PRP into various joints (n = 100). All patients were followed for symptom improvement with visual analog score (VAS) at one month and three months. Approximately one third of the patients were followed up with third month magnetic resonance imaging (MRI) of the injected sites. All patients were followed up by telephone questionnaires every six months for up to 30 months.
The mean follow-up time for all patients was 26.62 ± 0.32 months. The follow-up time for patients who were treated in 2009 and early 2010 was close to three years. The relative mean VAS of patients at the end of one month follow-up was 6.55 ± 0.32, and at the end of three months follow-up was 4.43 ± 0.41. Post-procedure MRIs performed on one third of the patients at three months failed to demonstrate any tumor formation at the implant sites. Further, no tumor formation was reported in telephone long-term follow-ups. However, swelling of injected joints was common and was thought to be associated with death of stem cells. Also, tenosinovitis and tendonitis in elderly patients, all of which were either self-limited or were remedied with simple therapeutic measures, were common as well.
Using both MRI tracking and telephone follow ups in 100 joints in 91 patients treated, no neoplastic complications were detected at any ADSC implantation sites. Based on our longitudinal cohort, the autologous and uncultured ADSCs/PRP therapy in the form of SVF could be considered to be safe when used as percutaneous local injections.
Abstract Background Previous studies on patients diagnosed with social anxiety disorder (SAD) reported changed patterns of the resting-state functional connectivity network (rs-FCN) between the ...prefrontal cortices and other prefrontal, amygdalar or striatal regions. Using a graph theory approach, this study explored the modularity-based community profile and patterns of inter-/intra-modular communication for the rs-FCN in SAD. Methods In total, for 28 SAD patients and 27 healthy controls (HC), functional magnetic resonance imaging (fMRI) data were acquired in resting-state and subjected to a graph theory analysis. Results The within-module degree z-score for a hub region out of a total of 10 hub regions ranked using the participation coefficient named left middle temporal gyrus was impaired in SAD compared to HC, proportional to the severity of clinician-scored and patient-reported functional impairment in SAD. Limitations Most of participants included in this study were undergraduate students in their early-to-mid 20's. Conclusions This study showed the importance of functional communication from the left middle temporal gyrus with other opercular-insular-subcortical regions for better objective functioning and lesser subjective disability in SAD.
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