Severe acute respiratory syndrome coronavirus (SARS-CoV) caused a global panic due to its high morbidity and mortality during 2002 and 2003. Soon after the deadly disease outbreak, the ...angiotensin-converting enzyme 2 (ACE2) was identified as a functional cellular receptor in vitro and in vivo for SARS-CoV spike protein. However, ACE2 solely is not sufficient to allow host cells to become susceptible to SARS-CoV infection, and other host factors may be involved in SARS-CoV spike protein-ACE2 complex.
A host intracellular filamentous cytoskeletal protein vimentin was identified by immunoprecipitation and LC-MS/MS analysis following chemical cross-linking on Vero E6 cells that were pre-incubated with the SARS-CoV spike protein. Moreover, flow cytometry data demonstrated an increase of the cell surface vimentin level by 16.5 % after SARS-CoV permissive Vero E6 cells were treated with SARS-CoV virus-like particles (VLPs). A direct interaction between SARS-CoV spike protein and host surface vimentin was further confirmed by far-Western blotting. In addition, antibody neutralization assay and shRNA knockdown experiments indicated a vital role of vimentin in cell binding and uptake of SARS-CoV VLPs and the viral spike protein.
A direct interaction between vimentin and SARS-CoV spike protein during viral entry was observed. Vimentin is a putative anti-viral drug target for preventing/reducing the susceptibility to SARS-CoV infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Recent research on fabricating scaffold‐type perovskite solar cells on plastic substrates has reported noteworthy progress in replacing the high‐temperature processing of TiO2 scaffolds and compact ...layers with various low‐temperature processes. Herein, recent progress in the laboratory is reported regarding the development of electrodeposited TiOx compact layers and brookite TiO2 scaffolds, both of which can be processed under 150 °C without greatly sacrificing their photovoltaic performance. Through systematic characterization of device properties and careful optimization of the fabrication conditions, a record‐high 15.76% power conversion efficiency of a plastic TiO2 scaffold‐type perovskite solar cell is demonstrated. In addition, bending durability and preliminary stability tests on this plastic perovskite solar cell show promising results and indicate clear directions for future improvement.
An efficient plastic perovskite solar cell with a mesoporous scaffold structure is fabricated by using a low‐temperature processable electrodeposited TiOx compact layer and spin‐coated brookite TiO2 scaffold. The electrodeposition TiOx compact layer exhibits suitable morphology, favorable band position, and an extraordinary hole‐blocking effect, while brookite TiO2 offers the capability to form a tightly packed scaffold without the need of sintering. Bending and dry‐storage stability assessments are taken and showed promising results and clear direction of future improvements.
Ischemia/reperfusion is a key feature of acute ischemic stroke, which causes neuron dysfunction and death. Exosomes, small extracellular vesicles produced by most cell types, are implicated in the ...mediation of cellular interactions with their environment. Here, we investigated the contents and functions of exosomes from neurons under ischemic reperfusion injury. First, rat cortical primary neuronal cell cultures were placed in an oxygen- and glucose-deprived (OGD) medium, followed by reperfusion in a normoxic conditioned medium (OGD/R) to mimic ischemia/reperfusion in vitro. The neuron-derived exosomes were harvested from the conditioned medium under normoxia and OGD/R. Through next-generation sequencing, exosomal miRNA expression levels in normoxic and OGD/R condition were compared. Their functional activity in terms of neuron viability and quantitative analysis of neurite outgrowth were examined. The expression levels of 45 exosomal miRNAs were significantly different between normoxic and OGD/R conditions. Bioinformatics analysis of dysregulated exosomal miRNAs identified multiple pathways involved in cell survival and death processes and neuronal signaling. Moreover, treatment with exosomes from OGD/R to cultured cortical neurons significantly impaired neuronal cell viability and reduced neurite outgrowth in terms of the number of primary or total neurites as well as length of primary neurites, compared with exosomes from normoxic conditions. miRNA-packed exosomes released by neurons under OGD/R challenge may contribute to post ischemic neuronal injury and provide further understanding of the effect of stressed neurons on neighboring neuronal functions.
•This paper used a numerical model to study two trains intersecting in a tunnel.•The wall pressure, drag and side force coefficient on the train are calculated.•The pressure caused by two trains ...intersecting is larger than that of a single train.•The influences of train speed, blockage ratio, length ratio and location are studied.
This study uses a three-dimensional, compressible, turbulence model to investigate the pressure waves generated by two trains passing each other in a tunnel. The turbulent flow around the train bodies is computed by the RNG k–ɛ turbulence model; a sliding mesh method is utilized to treat the moving boundary problem. The numerical results are verified through the results of laboratory experiment and field observation. Then, a series of numerical simulations are carried out to examine the influences of the tunnel length, the blockage ratio, the train speed and the intersecting location on the interactions of aerodynamic waves generated by the trains. The simulation results reveal that the pressure and drag coefficients of the trains reach a maximum when the two trains intersect at the mid-point of the tunnel and the values of pressure and drag coefficients increase as the train speed and the blockage ratio increase due to the train/tunnel interaction. However, the side force coefficient is dominated by the train/train interaction and its maximum value occurs when the two trains are aligned side by side.
Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that has been shown to affect cancer cell metastasis and migration. In the present study, we investigated the mechanisms of ...BDNF-induced cell migration in colon cancer cells. The migratory activities of two colon cancer cell lines, HCT116 and SW480, were found to be increased in the presence of human BDNF. Heme oxygenase-1 (HO)-1 is known to be involved in the development and progression of tumors. However, the molecular mechanisms that underlie HO-1 in the regulation of colon cancer cell migration remain unclear. Expression of HO-1 protein and mRNA increased in response to BDNF stimulation. The BDNF-induced increase in cell migration was antagonized by a HO-1 inhibitor and HO-1 siRNA. Furthermore, the expression of vascular endothelial growth factor (VEGF) also increased in response to BDNF stimulation, as did VEGF mRNA expression and transcriptional activity. The increase in BDNF-induced cancer cell migration was antagonized by a VEGF-neutralizing antibody. Moreover, transfection with HO-1 siRNA effectively reduced the increased VEGF expression induced by BDNF. The BDNF-induced cell migration was regulated by the ERK, p38, and Akt signaling pathways. Furthermore, BDNF-increased HO-1 and VEGF promoter transcriptional activity were inhibited by ERK, p38, and AKT pharmacological inhibitors and dominant-negative mutants in colon cancer cells. These results indicate that BDNF increases the migration of colon cancer cells by regulating VEGF/HO-1 activation through the ERK, p38, and PI3K/Akt signaling pathways. The results of this study may provide a relevant contribution to our understanding of the molecular mechanisms by which BDNF promotes colon cancer cell motility.
The clinical management and treatment of cervical cancer, one of the most commonly diagnosed cancers and a leading cause of cancer-related female death, remains a huge challenge for researchers and ...health professionals. Cervical cancer can be categorized into two major subtypes: common squamous cell carcinoma (SCC) and adenocarcinoma (AC). Although it is a relatively rare histological subtype of cervical cancer, there has been a steady increase in the incidences of AC. Therefore, new strategies to treat cervical cancer are urgently needed. In this study, the potential uses of IFNγ-based therapy for cervical cancer were evaluated using bioinformatics approaches. Gene expression profiling identified that cell cycle dysregulation was a major hallmark of cervical cancer including SCC and AC subtypes, and was associated with poor clinical outcomes for cervical cancer patients. In silico and in vitro experimental analyses demonstrated that IFNγ treatment could reverse the cervical cancer hallmark and induce cell cycle arrest and apoptosis. Furthermore, we demonstrated that apigenin could enhance the anticancer activity of IFNγ in a HeLa cervical AC cell line by targeting cyclin-dependent kinase 1. Taken together, the present study suggests the selective therapeutic potential of IFNγ alone or in combination with apigenin for managing cervical SCC and AC.
Cardiac rehabilitation is a comprehensive intervention recommended in international and Taiwanese guidelines for patients with acute myocardial infarction. Evidence supports that cardiac ...rehabilitation improves the health-related quality of life, enhances exercise capacity, reduces readmission rates, and promotes survival in patients with cardiovascular disease. The cardiac rehabilitation team is comprehensive and multidisciplinary. The inpatient, outpatient, and maintenance phases are included in cardiac rehabilitation. All patients admitted with acute myocardial infarction should be referred to the rehabilitation department as soon as clinically feasible. Pre-exercise evaluation, including exercise testing, helps physicians identify the risks of cardiac rehabilitation and organize appropriate exercise prescriptions. Therefore, the Taiwan Myocardial Infarction Society (TAMIS), Taiwan Society of Cardiology (TSOC), and Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation (TACVPR) address this consensus statement to assist healthcare practitioners in performing cardiac rehabilitation in patients with acute myocardial infarction.
Mutations in the skeletal muscle-specific CLC-1 chloride channel are associated with the human hereditary disease myotonia congenita. The molecular pathophysiology underlying some of the ...disease-causing mutations can be ascribed to defective human CLC-1 protein biosynthesis. CLC-1 protein folding is assisted by several molecular chaperones and co-chaperones, including FK506-binding protein 8 (FKBP8). FKBP8 is generally considered an endoplasmic reticulum- and mitochondrion-resident membrane protein, but is not thought to contribute to protein quality control at the cell surface. Herein, we aim to test the hypothesis that FKBP8 may regulate CLC-1 protein at the plasma membrane. Surface biotinylation and subcellular fractionation analyses reveal that a portion of FKBP8 is present at the plasma membrane, and that co-expression with CLC-1 enhances surface localization of FKBP8. Immunoblotting analyses of plasma membrane proteins purified from skeletal muscle further confirm surface localization of FKBP8. Importantly, FKBP8 promotes CLC-1 protein stability at the plasma membrane. Together, our data underscore the importance of FKBP8 in the peripheral quality control of CLC-1 channel.
•This study develops a two-way coupled numerical model for fluid/structure interaction.•The fluid flow and hydrodynamic pressure are computed by Large Eddy Simulation model.•The free surface is ...tracked by the Volume-of-Fluid method.•The simulation results were validated by laboratory experiments.•This model can be applied to simulate the moving solids in free-surface flow.
This study developed a novel two-way dynamic coupled numerical model to simulate moving solids in free surface flows. The fluid flows and hydrodynamic pressures are simulated by a Large Eddy Simulation model, and the free surface is tracked by the Volume-of-Fluid (VOF) method. The fluid response from the solid motion is modeled through specifying the cell-face velocity with partial-cell treatment (PCT). The displacement and rotation of the solids are calculated by the Discrete Element Method (DEM). In order to verify the present model, two laboratory experiments of rectangular blocks floating and sinking in a water tank are conducted. The numerical simulations compare favorably with the experimental results on the trajectory of the moving blocks. The numerical scheme presented in this paper can be used as a design tool for practical problems involved moving objects in free-surface flows.
PDF
