Influenza is one of the most common human respiratory diseases, and represents a serious public health concern. However, the high mutability of influenza viruses has hampered vaccine development, and ...resistant strains to existing anti-viral drugs have also emerged. Novel anti-influenza therapies are urgently needed, and in this study, we describe the anti-viral properties of a Spirulina (Arthrospira platensis) cold water extract. Anti-viral effects have previously been reported for extracts and specific substances derived from Spirulina, and here we show that this Spirulina cold water extract has low cellular toxicity, and is well-tolerated in animal models at one dose as high as 5,000 mg/kg, or 3,000 mg/kg/day for 14 successive days. Anti-flu efficacy studies revealed that the Spirulina extract inhibited viral plaque formation in a broad range of influenza viruses, including oseltamivir-resistant strains. Spirulina extract was found to act at an early stage of infection to reduce virus yields in cells and improve survival in influenza-infected mice, with inhibition of influenza hemagglutination identified as one of the mechanisms involved. Together, these results suggest that the cold water extract of Spirulina might serve as a safe and effective therapeutic agent to manage influenza outbreaks, and further clinical investigation may be warranted.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
With the rapid development of machine learning technology, as a regression problem that helps people to find the law from the massive data to achieve the prediction effect, more and more people pay ...attention. Data prediction has become an important part of people’s daily life. Currently, the technology is widely used in many fields such as weather forecasting, medical diagnosis and financial forecasting. Therefore, the research of machine learning algorithms in regression problems is a research hotspot in the field of machine learning in recent years. However, real-world regression problems often have very complex internal and external factors, and various machine learning algorithms have different effects on scalability and predictive performance. In order to better study the application effect of machine learning algorithm in regression problem, this paper mainly adopts three common machine learning algorithms: BP neural network, extreme learning machine and support vector machine. Then, by comparing the effects of the single model and integrated model of these machine learning algorithms in the application of regression problems, the advantages and disadvantages of each machine learning algorithm are studied. Finally, the performance of each machine learning algorithm in regression prediction is verified by simulation experiments on four different data sets. The results show that the research on several machine learning algorithms and their integration models has certain feasibility and rationality.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, ODKLJ, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
SARS-CoV-2, the causative agent of COVID-19
, features a receptor-binding domain (RBD) for binding to the host cell ACE2 protein
. Neutralizing antibodies that block RBD-ACE2 interaction are ...candidates for the development of targeted therapeutics
. Llama-derived single-domain antibodies (nanobodies, ~15 kDa) offer advantages in bioavailability, amenability, and production and storage owing to their small sizes and high stability. Here, we report the rapid selection of 99 synthetic nanobodies (sybodies) against RBD by in vitro selection using three libraries. The best sybody, MR3 binds to RBD with high affinity (K
= 1.0 nM) and displays high neutralization activity against SARS-CoV-2 pseudoviruses (IC
= 0.42 μg mL
). Structural, biochemical, and biological characterization suggests a common neutralizing mechanism, in which the RBD-ACE2 interaction is competitively inhibited by sybodies. Various forms of sybodies with improved potency have been generated by structure-based design, biparatopic construction, and divalent engineering. Two divalent forms of MR3 protect hamsters from clinical signs after live virus challenge and a single dose of the Fc-fusion construct of MR3 reduces viral RNA load by 6 Log
. Our results pave the way for the development of therapeutic nanobodies against COVID-19 and present a strategy for rapid development of targeted medical interventions during an outbreak.
This article discusses the appropriate dispersant for titania (TiO2) nanopowder in organic‐based suspensions. Four types of oleyl‐based dispersants, namely, oleyl alcohol, oleic acid, oleylamine, and ...oleyl phosphate, which have the functional groups hydroxyl (–OH), carboxyl (–COOH), amino (–NH2), and phosphorous –P(=O)(OH)2, respectively, were compared for their ability to disperse TiO2. Experimental results for zeta potential, adsorption, FT‐IR spectroscopy, and rheology, as well as theoretical calculations, indicate that dispersants with –P(=O)(OH)2 and –NH2 were more efficient than those with –COOH or –OH. The primary reason for this difference is related to the different interactions of TiO2 with various dispersants and to different dispersion mechanisms. In addition to the major functional groups, –OH in the chemical structure of dispersants was important, as it might have other effects such as destabilization of the suspensions.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
An avian influenza A H7N9 virus emerged in March 2013 and caused a remarkable number of human fatalities. Genome variability in these viruses may provide insights into host adaptability. We scanned ...over 140 genomes of the H7N9 viruses isolated from humans and identified 104 positions that exhibited seven or more amino acid substitutions. Approximately half of these substitutions were identified in the influenza ribonucleoprotein (RNP) complex. Although PB2 627K of the avian virus promotes replication in humans, 45 of the 147 investigated PB2 sequences retained the E signature at this position, which is an avian characteristic. We discovered 10 PB2 substitutions that covaried with K627E. An RNP activity assay showed that Q591K, D701N, and M535L restored the polymerase activity in human cells when 627K transformed to an avian-like E. Genomic analysis of the human-isolated avian influenza virus is crucial in assessing genome variability, because relationships between position-specific variations can be observed and explored. In this study, we observed alternative positions that can potentially compensate for PB2 627K, a well-known marker for cross-species infection. An RNP assay suggested Q591K, D701N, and M535L as potential markers for an H7N9 virus capable of infecting humans.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Carbohydrate-based vaccines have shown therapeutic efficacy for infectious disease and cancer. The mushroom Ganoderma lucidum (Reishi) containing complex polysaccharides has been used as antitumor ...supplement, but the mechanism of immune response has rarely been studied. Here, we show that the mice immunized with a l -fucose (Fuc)-enriched Reishi polysaccharide fraction (designated as FMS) induce antibodies against murine Lewis lung carcinoma cells, with increased antibody-mediated cytotoxicity and reduced production of tumor-associated inflammatory mediators (in particular, monocyte chemoattractant protein-1). The mice showed a significant increase in the peritoneal B1 B-cell population, suggesting FMS-mediated anti-glycan IgM production. Furthermore, the glycan microarray analysis of FMS-induced antisera displayed a high specificity toward tumor-associated glycans, with the antigenic structure located in the nonreducing termini (i.e., Fucα1-2Galβ1-3GalNAc-R, where Gal, GalNAc, and R represent, respectively, D-galactose, D-N-acetyl galactosamine, and reducing end), typically found in Globo H and related tumor antigens. The composition of FMS contains mainly the backbone of 1,4-mannan and 1,6-α-galactan and through the Fucα1-2Gal, Fucα1-3/4Man, Fucα1-4Xyl, and Fucα1-2Fuc linkages (where Man and Xyl represent d -mannose and d -xylose, respectively), underlying the molecular basis of the FMS-induced IgM antibodies against tumor-specific glycans.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Avian influenza A viruses generally do not replicate efficiently in human cells, but substitution of glutamic acid (Glu, E) for lysine (Lys, K) at residue 627 of avian influenza virus polymerase ...basic protein 2 (PB2) can serve to overcome host restriction and facilitate human infectivity. Although PB2 residue 627 is regarded as a species-specific signature of influenza A viruses, host restriction factors associated with PB2
E have yet to be fully investigated. We conducted immunoprecipitation, followed by differential proteomic analysis, to identify proteins associating with PB2
K (human signature) and PB2
E (avian signature) of influenza A/WSN/1933(H1N1) virus, and the results indicated that Tu elongation factor, mitochondrial (TUFM), had a higher binding affinity for PB2
E than PB2
K in transfected human cells. Stronger binding of TUFM to avian-signature PB2
G/
Q and PB2
E in the 2009 swine-origin pandemic H1N1 and 2013 avian-origin H7N9 influenza A viruses was similarly observed. Viruses carrying avian-signature PB2
E demonstrated increased replication in TUFM-deficient cells, but viral replication decreased in cells overexpressing TUFM. Interestingly, the presence of TUFM specifically inhibited the replication of PB2
E viruses, but not PB2
K viruses. In addition, enhanced levels of interaction between TUFM and PB2
E were noted in the mitochondrial fraction of infected cells. Furthermore, TUFM-dependent autophagy was reduced in TUFM-deficient cells infected with PB2
E virus; however, autophagy remained consistent in PB2
K virus-infected cells. The results suggest that TUFM acts as a host restriction factor that impedes avian-signature influenza A virus replication in human cells in a manner that correlates with autophagy.
An understanding of the mechanisms that influenza A viruses utilize to shift host tropism and the identification of host restriction factors that can limit infection are both critical to the prevention and control of emerging viruses that cross species barriers to target new hosts. Using a proteomic approach, we revealed a novel role for TUFM as a host restriction factor that exerts an inhibitory effect on avian-signature PB2
E influenza virus propagation in human cells. We further found that increased TUFM-dependent autophagy correlates with the inhibitory effect on avian-signature influenza virus replication and may serve as a key intrinsic mechanism to restrict avian influenza virus infection in humans. These findings provide new insight regarding the TUFM mitochondrial protein and may have important implications for the development of novel antiviral strategies.
Background
Interferon in combination with ribavirin has been the standard of care for chronic hepatitis C virus infection (HCV) for the past few decades. However, its effect on the risk of autoimmune ...diseases (ADs) among patients with HCV infection remains unclear. We assessed the potential association between interferon-based therapy (IBT) and AD risk in patients with HCV infection.
Methods
This retrospective cohort study identified patients diagnosed with HCV infection between January 1, 2006, and December 31, 2015, from Taiwan’s National Health Insurance Research Database. In total, 16,029 patients with HCV infection who received IBT and 141,214 patients with HCV infection who did not receive IBT were included. Both cohorts were followed up to assess the development of ADs. Hazard ratios (HRs) were calculated using the Cox proportional hazards regression model, which was adjusted for potential confounders.
Results
The median follow-up period for IBT and non-IBT users was 4.53 and 3.34 years, respectively. No significant difference in the risk of overall ADs (adjusted HR aHR: 0.96, 95% confidence interval CI: 0.81–1.14) or systemic ADs (aHR: 0.88, 95% CI: 0.71–1.10) was noted during the study period. However, a slight increase in the risk of organ-specific ADs was noted among IBT users (incidence rate ratio: 1.33, 95% CI: 1.02–1.72). Furthermore, analysis of AD subgroups revealed a significant increase in the risks of Graves’ disease (aHR: 6.06, 95% CI: 1.27–28.8) and Hashimoto’s thyroiditis (aHR 1.49, 95% CI 1.01–2.21) among IBT users.
Conclusions
IBT use increases the risk of autoimmune thyroid diseases (Hashimoto’s thyroiditis and Graves’ disease) in patients with HCV infection to a greater extent than non-IBT use.
In recent years, social networking services (SNSs), for example, Facebook, have shown exponential growth in their number of users. Witnessing the popularity of these SNSs, educational researchers ...have also explored the potential educational value of using SNSs. Despite the few studies that have investigated learners’ attitudes toward and the effects of incorporating SNSs in class, limited attention has been paid to examining learners’ knowledge and cognitive processes involved in online discussions using SNSs. Although general public interest in life-long learning has been gradually increasing, relatively little attention has been devoted to exploring the application of SNSs in adult and continuing education programs.
To promote a better understanding of using SNSs in learning, this study seeks to explore learners’ online discussion behaviors in an art course that involved a project-based learning activity using a popular SNS, Facebook, to support students’ asynchronous online discussions. The participants in our study included 62 students enrolled in the school of continuing education at a university in northern Taiwan. Adapting the Revised Bloom’s Taxonomy as a coding scheme, this study employed a quantitative content analysis (QCA) and lag sequential analysis (LSA) to examine the content and behavioral patterns of students’ discussions. The results indicate that the most prominent knowledge dimension in students’ discussions is the meta-cognitive knowledge, while the cognitive process is primarily focused on understanding and comprehension. In addition, a moderate proportion of off-topic discussion was found in this study. Considering the different behaviors that may be exhibited by members of varied age and gender, a further analysis based on students’ individual differences was conducted. The results showed that, in the context of online discussions, female and older learners are more likely to engage in off-topic discussions. Based on these findings, this study suggests that when conducting online discussion activities using SNSs, instructors should consider the characteristics of adult learners and their individual differences and design their teaching activities accordingly. Implications and limitations of this study are discussed, and pedagogical suggestions for adapting SNSs to teaching activities for adult and continuing education are proposed.
► Adult learners’ cognitive process in Facebook project discussion is explored. ► Both quantitative content analysis and sequential analysis are used. ► The type of knowledge and cognitive process in discussion are lacked of diversity. ► Modest portion of off-topic discussions were found. ► Learners of older age or female are more likely to have off-topic discussions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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