Pathogen inhibition and indication by gelatin nonwoven mats with incorporation of polyphenol derivatives.

There is a need for non-pharmaceutical intervention methods that can prevent and indicate the risk of airborne disease spread. In this study, we developed a nonwoven mat based on the polyphenol gallic acid, which can inhibit pathogens growth and also indicate pathogen levels in the surrounding environment. Using nuclear magnetic resonance, Fourier-transform infrared spectroscopy, and high-performance liquid chromatography, we characterized this novel gelatin-based nonwoven mat and investigated the mechanism governing its ability to indicate pathogen levels. We demonstrated that the incorporation of gallic acid serves a vital role in indicating the presence of bacteria, causing the nonwoven mat to change in color from white to brown. We have proposed a plausible mechanism for this color change behavior based on a reaction of gallic acid with components excreted by bacteria, including glutamate, valine, and leucine. The concentrations of these components reflect the bacterial counts, enabling a real-time indication of pathogen levels in the surrounding air. In summary, the nonwoven mat presented herein can serve as an excellent antibacterial agent and as an indicator of nearby bacteria for fabricating personal protection equipment like filtration mask.

Discovery of novel glucosinolates inhibiting advanced glycation end products: Virtual screening and molecular dynamic simulation.

Protein glycation can result in the formation of advanced glycation end products (AGEs), which pose a potential health risk due to their association with diabetic complications. Natural products are a source of drugs discovery and the search for potential natural inhibitors of AGEs is of great significance. Glucosinolates (GSLs) mainly from cruciferous plants have potential antioxidant, anti-inflammatory, and anti-glycation activities. In this study, the inhibitory activity of GSLs on bovine serum albumin (BSA) along with its mechanism was investigated by virtual screening and various computational simulation techniques. Virtual screening revealed that 174 GSLs were screened using Maestro based on the glide score and 89% of the compounds were found to have potential anti-glycation ability with the docking scores less than -5 kcal/mol. Molecular docking showed that the top 10 GSLs were bound to the IIA structural domain of BSA. Among them, glucohesperin (1) and 2-hydroxyethyl glucosinolate (2) had the lowest docking scores of -9.428 and -9.333 kcal/mol, respectively, reflecting their good binding affinity. Molecular dynamics simulations of 1 (ΔG = -43.46 kcal/mol) and 2 (ΔG = -43.71 kcal/mol) revealed that the complexes of these two compounds with proteins had good stability. Further binding site analysis suggested that the mechanism of inhibition of protein glycation by these two active ingredients might be through competitive hydrogen bonding to maintain the structural integrity of the protein, thus inhibiting glycation reaction. Moreover, the ADMET values and CYP450 metabolism prediction data were within the recommended values. Therefore, it can be concluded that 1 and 2 may act as potential anti-glycation agents.

Alginate-Capped Silver Nanoparticles as a Potent Anti-mycobacterial Agent Against Mycobacterium tuberculosis.

Tuberculosis (TB) is a leading cause of death from a single infectious agent, Mycobacterium tuberculosis (Mtb). Although progress has been made in TB control, still about 10 million people worldwide develop TB annually and 1.5 million die of the disease. The rapid emergence of aggressive, drug-resistant strains and latent infections have caused TB to remain a global health challenge. TB treatments are lengthy and their side effects lead to poor patient compliance, which in turn has contributed to the drug resistance and exacerbated the TB epidemic. The relatively low output of newly approved antibiotics has spurred research interest toward alternative antibacterial molecules such as silver nanoparticles (AgNPs). In the present study, we use the natural biopolymer alginate to serve as a stabilizer and/or reductant to green synthesize AgNPs, which improves their biocompatibility and avoids the use of toxic chemicals. The average size of the alginate-capped AgNPs (ALG-AgNPs) was characterized as nanoscale, and the particles were round in shape. Drug susceptibility tests showed that these ALG-AgNPs are effective against both drug-resistant Mtb strains and dormant Mtb. A bacterial cell-wall permeability assay showed that the anti-mycobacterial action of ALG-AgNPs is mediated through an increase in cell-wall permeability. Notably, the anti-mycobacterial potential of ALG-AgNPs was effective in both zebrafish and mouse TB animal models in vivo. These results suggest that ALG-AgNPs could provide a new therapeutic option to overcome the difficulties of current TB treatments.

Nanoparticular CpG-adjuvanted SARS-CoV-2 S1 protein elicits broadly neutralizing and Th1-biased immunoreactivity in mice.

The spike (S) protein is a leading vaccine candidate against SARS-CoV-2 infection. The S1 domain of S protein, which contains a critical receptor-binding domain (RBD) antigen, potentially induces protective immunoreactivities against SARS-CoV-2. In this study, we presented preclinical evaluations of a novel insect cell-derived SARS-CoV-2 recombinant S1 (rS1) protein as a potent COVID-19 vaccine candidate. The native antigenicity of rS1 was characterized by enzyme-linked immunosorbent assay with a neutralizing monoclonal antibody targeting the RBD antigen. To improve its immunogenicity, rS1-adjuvanted with fucoidan/trimethylchitosan nanoparticles (FUC-TMC NPs) and cytosine-phosphate-guanosine-oligodeoxynucleotides (CpG-ODNs) were investigated using a mouse model. The S1-specific immunoglobulin G (IgG) titers, FluoroSpot assay, pseudovirus- and prototype SARS-CoV-2-based neutralization assays were assessed. The results showed that the rS1/CpG/ FUC-TMC NPs (rS1/CpG/NPs) formulation induced a broad-spectrum IgG response with potent, long-lasting, and cross-protective neutralizing activity against the emerging SARS-CoV-2 variant of concern, along with a Th1-biased cellular response. Thus, the rS1/CpG/NPs formulation presents a promising vaccination approach against COVID-19.

Nanoparticles assembled from fucoidan and trimethylchitosan as anthrax vaccine adjuvant: In vitro and in vivo efficacy in comparison to CpG.

Fucoidan/trimethylchitosan nanoparticles (FUC-TMC-NPs) have the potential to improve the immunostimulating efficiency of anthrax vaccine adsorbed (AVA). FUC-TMC-NPs with positive (+) or negative (-) surface charges were prepared via polyelectrolyte complexation, both charged NP types permitted high viability and presented no cytotoxicity on L929, A549 and JAWS II dendritic cells. Flow cytometry measurements indicated lower (+)-FUC-TMC-NPs internalization levels than (-)-FUC-TMC-NPs, yet produced high levels of pro-inflammatory cytokines IFN-γ, IL12p40, and IL-4. Moreover, fluorescence microscope images proved that both charged NP could deliver drugs into the nucleus. In vivo studies on A/J mice showed that (+)-FUC-TMC-NPs carrying AVA triggered an efficient response with a higher IgG anti-PA antibody titer than AVA with CpG oligodeoxynucleotides, and yielded 100 % protection when challenged with the anthracis spores. Furthermore, PA-specific IgG1 and IgG2a analysis confirmed that (+)-FUC-TMC-NPs strongly stimulated humoral immunity. In conclusion, (+)-FUC-TMC-NP is promising anthrax vaccine adjuvant as an alternative to CpG.

Fungicidal and anti-biofilm activities of trimethylchitosan-stabilized silver nanoparticles against Candida species in zebrafish embryos.

Herein, positively surface-charged silver nanoparticles (AgNPs) capped with trimethylchitosan nitrate (TMCN) were synthesized using an environmentally friendly method. Nano-sized TMCN-AgNPs (~80 nm) with high zeta potential (>30 mV) provide sufficient static repulsion to stabilize colloid AgNPs in aqueous solutions without aggregation for >3 months. In in vitro cell cycle assays, TMCN-AgNPs showed low cytotoxicity towards L929 cells. A microdilution inhibition assay demonstrated the antifungal potential of TMCN-AgNPs, with a minimum inhibitory concentration of 0.06 mM against Candida tropicalis ATCC 750, and 0.46 mM against both Candida albicans ATCC 76615 and Candida glabrata ATCC 15545. Moreover, the addition of TMCN-AgNPs at 0.23 mM significantly reduced biofilm formation in 96-well plates with C. albicans and C. tropicalis. Importantly, when zebrafish eggs were infected with Candida cells, 0.23 mM TMCN-AgNPs greatly diminished the amount of biofilm on eggs and rescued the survival of embryos by up to 70%.

A fucoidan-quaternary chitosan nanoparticle adjuvant for anthrax vaccine as an alternative to CpG oligodeoxynucleotides.

We examined the efficacy of fucoidan-N-(2-hydroxy-3-trimethylammonium)propylchitosan nanoparticles (FUC-HTCC NPs) as adjuvants for anthrax vaccine adsorbed (AVA). Positively and negatively surface-charged FUC-HTCC NPs were prepared via polyelectrolyte complexation by varying the mass ratio of FUC and HTCC. When cultured with L929 cells or JAWS II dendritic cells, both charged NPs showed high cell viability and low cytotoxicity, observed via MTT assay and lactate dehydrogenase release assay, respectively. In addition, we have monitored excellent NPs uptake efficacy by dendritic cells and observed that combining FUC-HTCC NPs with AVA significantly increases the magnitude of IgG-anti-protective antigen titers in A/J mice compared to that by CpG oligodeoxynucleotides plus AVA or AVA alone, and PA-specific IgG1 and IgG2a analysis confirmed that FUC-HTCC NPs strongly stimulated humoral immunity. Furthermore, FUC-HTCC NPs plus AVA provided a superior survival rate (100%) of A/J mice compared to CpG oligodeoxynucleotides plus AVA (75%) or AVA alone (50%) following anthrax lethal toxin challenge. The findings support FUC-HTCC NPs as a potential adjuvant of AVA for rapid induction of protective immunity.

Visibility Graph Feature Model of Vibration Signals: A Novel Bearing Fault Diagnosis Approach.

Reliable fault diagnosis of rolling bearings is an important issue for the normal operation of many rotating machines. Information about the structure dynamics is always hidden in the vibration response of the bearings, and it is often very difficult to extract them correctly due to the nonlinear/chaotic nature of the vibration signal. This paper proposes a new feature extraction model of vibration signals for bearing fault diagnosis by employing a recently-developed concept in graph theory, the visibility graph (VG). The VG approach is used to convert the vibration signals into a binary matrix. We extract 15 VG features from the binary matrix by using the network analysis and image processing methods. The three global VG features are proposed based on the complex network theory to describe the global characteristics of the binary matrix. The 12 local VG features are proposed based on the texture analysis method of images, Gaussian Markov random fields, to describe the local characteristics of the binary matrix. The feature selection algorithm is applied to select the VG feature subsets with the best performance. Experimental results are shown for the Case Western Reserve University Bearing Data. The efficiency of the visibility graph feature model is verified by the higher diagnosis accuracy compared to the statistical and wavelet package feature model. The VG features can be used to recognize the fault of rolling bearings under variable working conditions.

Chondroitin sulfate-stabilized silver nanoparticles: Improved synthesis and their catalytic, antimicrobial, and biocompatible activities.

Herein, we describe an improved procedure for the green synthesis of chondroitin sulfate stabilized silver nanoparticles (ChS-AgNPs). Glucose was used as a reducing agent under alkaline conditions to obtain a small particle size (<10 nm), and the reduction was complete within one hour at room temperature. The concentration of NaOH affected the reaction rate, formation yield, and particle size of ChS-AgNPs. The formation of AgNPs was confirmed using UV-vis, TEM, XRD, and XPS. ChS-AgNPs showed excellent catalytic activities in the reduction of 4-nitrophenol by NaBH4, and the reaction rate increased linearly with increasing catalyst amounts. The antimicrobial activities of ChS-AgNPs against A. baumannii (including multidrug-resistant strains), E. coli, P. aeruginosa, and S. aureus were evaluated using the broth microdilution method. Finally, from the morphological observations and cell cycle analysis of L929 cells, we found that ChS-AgNPs exhibited antimicrobial and biocompatible activities.

Positively charged gold nanoparticles capped with folate quaternary chitosan: Synthesis, cytotoxicity, and uptake by cancer cells.

In this study, we synthesized various quaternary chitosan derivatives and used them to stabilize gold nanoparticles (AuNPs). These chitosan derivatives comprised N-(2-hydroxy)propyl-3-trimethylammonium chitosan chloride (HTCC), folate-HTCC, galactosyl-HTCC, and their fluorescein isothiocyanate-conjugated derivatives. Various positively surface-charged AuNPs were prepared under alkaline conditions using glucose as a reducing agent in the presence of the HTCC derivatives (HTCCs). The effects of the concentration of NaOH, glucose, and HTCCs on the particles size, zeta potential, and stability were studied in detail. Cell cycle assays verify that none of the HTCCs or HTCCs-AuNPs was cytotoxic to human umbilical vein endothelial cells. Flow cytometry analysis showed that the folate HTCC-AuNPs were internalized in Caco-2, HepG2, and HeLa cancer cells to a significantly greater extent than AuNPs without folate. But, galactosyl HTCC-AuNPs only showed high cell uptake by HepG2 cells.

Protective effect of mulberry fruit anthocyanin on human hepatocyte cells (LO2) and Caenorhabditis elegans under hyperglycemic conditions.

Type 2 diabetes is a chronic disease and hyperglycemia is important in the pathogenesis of diabetic complications. Exposure of LO2 cells to high glucose resulted in cellular glucose consumption and uptake decreases, reactive oxygen species (ROS) and superoxide anion (O2-) accumulation and mitochondrial dysfunction, which could be partly recovered by mulberry anthocyanin extract (MAE). And these protective effects were partly associated with regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream targets. As the insulin-signaling pathway is evolutionarily well conserved from Caenorhabditis elegans to mammals, C. elegans has been considered as a model system to study effects of glucose toxicity. Glucose shortened the lifespan of C. elegans, while MAE suppressed the damage, accompanied by malondialdehyde (MDA) and triglyceride accumulation reduction as well as total superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity recovery and PMK-1/p38 expression promotion. In contrast, MAE failed to recover shortened longevity, glucose and triglyceride accumulation in daf-2 (-) mutants fed a glucose-supplemented diet. Transcriptional profile revealed MAE intervention led to 92 genes alteration compared with the glucose-treatment. Interestingly, expressions of DAF-2/insulin receptor related genes were increased by glucose but impaired by MAE in nematodes. Our studies suggested that MAE might help to improve the antioxidant defense system, resulting in prevention of glucose-induced damage both in vitro and in vivo.

Photoelectric conversion switch based on quantum dots with i-motif DNA scaffolds.

Combining the best features of both inorganic quantum dots and i-motif DNA, a dynamic pH-driven modulation system of photoelectric conversion was realized by making use of their conjugates immobilized on a Au electrode.