ABSTRACT
Cutting fluid is indispensable in the machining industry as a fluid for lubrication and cooling in the metalworking process due to their ability to significantly improve various properties of cutting fluid. Castor oil, as a common base oil and additive in cutting fluid, can be grafted onto the surface of cellulose nanocrystals (CNC) to further enhance the lubricating properties of cutting fluid. It has been shown that cellulose nanocrystals and castor oil modified cellulose nanocrystals (CO-CNC) as additives in cutting fluid have good dispersion stability and can effectively improve the lubricating properties. When the amount of CNC or CO-CNC was added in the working fluid at about 0.5 wt%, the friction coefficient was significantly reduced. According to the results from this study, cellulose nanocrystal is a promising candidate as the nontoxic and renewable additive for the improvement of diverse performances for the water-based cutting fluid.
Subject(s)
Cellulose , Nanoparticles , Castor Oil , Cellulose/chemistry , Lubrication , Nanoparticles/chemistry , WaterABSTRACT
Coronavirus disease 2019 (COVID-19) is a newly emerged infectious disease caused by a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid global emergence of SARS-CoV-2 highlights the importance and urgency for potential drugs to control the pandemic. The functional importance of RNA-dependent RNA polymerase (RdRp) in the viral life cycle, combined with structural conservation and absence of closely related homologs in humans, makes it an attractive target for designing antiviral drugs. Nucleos(t)ide analogs (NAs) are still the most promising broad-spectrum class of viral RdRp inhibitors. In this study, using our previously developed cell-based SARS-CoV-2 RdRp report system, we screened 134 compounds in the Selleckchemicals NAs library. Four candidate compounds, Fludarabine Phosphate, Fludarabine, 6-Thio-20-Deoxyguanosine (6-Thio-dG), and 5-Iodotubercidin, exhibit remarkable potency in inhibiting SARS-CoV-2 RdRp. Among these four compounds, 5-Iodotubercidin exhibited the strongest inhibition upon SARS-CoV-2 RdRp, and was resistant to viral exoribonuclease activity, thus presenting the best antiviral activity against coronavirus from a different genus. Further study showed that the RdRp inhibitory activity of 5-Iodotubercidin is closely related to its capacity to inhibit adenosine kinase (ADK).
Subject(s)
Antiviral Agents/pharmacology , COVID-19 Drug Treatment , Nucleic Acid Synthesis Inhibitors/pharmacology , SARS-CoV-2/drug effects , Tubercidin/analogs & derivatives , Cell Line , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/pharmacology , Drug Evaluation, Preclinical/methods , HEK293 Cells , Humans , Microbial Sensitivity Tests , RNA, Viral/biosynthesis , RNA-Dependent RNA Polymerase/antagonists & inhibitors , SARS-CoV-2/genetics , Thionucleosides/pharmacology , Tubercidin/pharmacology , Vidarabine/analogs & derivatives , Vidarabine/pharmacology , Vidarabine Phosphate/analogs & derivatives , Vidarabine Phosphate/pharmacologyABSTRACT
Bactericidal/permeability increasing (BPI) is an antibiotic protein which kills Gram-negative bacteria and neutralizes endotoxin. We have previously developed a recombinant adeno-associated virus which contains human BPI amino acid residues 1-199 and Fc fragment of human IgG1 gene (AAV-hBPI-Fc) and shown that the recombinant virus can protect mice from lethal endotoxemia. However, whether AAV-hBPI-Fc can be used in vivo for the long term remains unclear. To address this, we established an adeno-associated virus-containing mouse BPI and Fc fragment genes (muBPI-Fc) and compared antigenicity of these recombinant proteins in murine models. Immunohistochemistry showed the expression of both fusion proteins at injected sites. ELISA and Western blotting showed that the muBPI-Fc protein was detected in serum up to 8 weeks after injection, without generation of autoantibodies against muBPI-Fc. In contrast, expressed hBPI-Fc protein was only detected on the 2nd week, whereas the autoantibody against hBPI-Fc protein occurred in serum from the 4th week to the end of study. muBPI-Fc also reduced production of proinflammatory cytokines and protected mice from endotoxemia and bacteremia. Our data showed that AAV-muBPI-Fc has potential long-term efficacy as an anti-endotoxin and has anti-bacterial activity in mice, suggesting the potential clinical application of AAV-hBPI-Fc, such as in endotoxin shock.
Subject(s)
Biological Therapy/methods , Endotoxemia/prevention & control , Endotoxemia/therapy , Escherichia coli Infections/prevention & control , Escherichia coli Infections/therapy , Adenoviridae/genetics , Animals , Anti-Bacterial Agents/metabolism , Antimicrobial Cationic Peptides/genetics , Antimicrobial Cationic Peptides/metabolism , Blood Proteins/genetics , Blood Proteins/metabolism , Blotting, Western , Disease Models, Animal , Drug Carriers , Enzyme-Linked Immunosorbent Assay , Female , Immunoglobulin Fc Fragments/genetics , Immunoglobulin Fc Fragments/metabolism , Immunoglobulin G/genetics , Immunoglobulin G/metabolism , Mice, Inbred BALB C , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Serum/chemistry , Time Factors , Treatment OutcomeABSTRACT
Influenza virus RNA-dependent RNA polymerase (RdRP) is essential for replication and expression of influenza virus genome. Viral genomic sequences encoding RdRP are highly conservative, thus making it a potential anti-influenza drug target. A cell-based influenza RdRP inhibitor screening assay was established by a luciferase reporter system to analyze the activity of RdRP. Specificity study and statistic analysis showed that the screening assay is sensitive and reproducible.