Biochemical Approach to Poly(Lactide)-Copper Composite-Impact on Blood Coagulation Processes.

The paper presents the investigation of the biological properties of Poly(Lactide)-Copper composite material obtained by sputter deposition of copper onto Poly(lactide) melt-blown nonwoven fabrics. The functionalized composite material was subjected to microbial activity tests against colonies of Gram-positive (Staphylococcus aureus), Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria, Chaetomium globosum and Candida albicans fungal mold species and biochemical-hematological tests including the evaluation of the Activated Partial Thromboplastin Time, Prothrombin Time, Thrombin Time and electron microscopy fibrin network imaging. The substantial antimicrobial and antifungal activities of the Poly(Lactide)-Copper composite suggests potential applications as an antibacterial/antifungal material. The unmodified Poly(Lactide) fabric showed accelerated human blood plasma clotting in the intrinsic pathway, while copper plating abolished this effect. Unmodified PLA itself could be used for the preparation of wound dressing materials, accelerating coagulation in the case of hemorrhages, and its modifications with the use of various metals might be applied as new customized materials where blood coagulation process could be well controlled, yielding additional anti-pathogen effects.

Antibacterial and Antifungal Properties of Polyester, Polylactide, and Cotton Nonwovens and Fabrics, by Means of Stable Aqueous Dispersions Containing Copper Silicate and Some Metal Oxides.

Literature reviews have described the applications of silver, copper, and zinc ions and metallic particles of Cu, Ti, and Zn oxides, which have been found to be useful antimicrobial reagents for the biofunctionalization of various materials and their surfaces. For this purpose, compositions of water dispersions containing emulsions of synthetic copolymers based on acrylic and vinyl monomers, polysaccharides (hydroxyethyl cellulose and starch), and various additives with wetting and stabilizing properties were used. Many stable water dispersions of different chemical compositions containing bioactive chemical compounds (copper silicate hydrate, titanium dioxide, and zinc oxide (and other auxiliary substances)) were developed. They were used for the preparation of thin hybrid coatings having good antimicrobial properties against Gram-negative bacteria (Escherichia coli), Gram-positive bacteria (Staphylococcus aureus), and yeast fungus (Candida albicans). Polyester (PES) and polylactide (PLA) nonwovens were modified using the dip-coating method, while PES and cotton fabrics were biofunctionalized by means of dip-coating and coating methods. The antimicrobial (antibacterial and antifungal) properties of the textile materials (nonwovens and fabrics) biofunctionalized with the above-mentioned bioactive agents exhibiting antimicrobial properties (CuSiO3, TiO2, ZnO, or ZnO∙SiO2) were strongly dependent on the agents' content in the water dispersions. The PES and PLA nonwovens, modified on the surface with water compositions containing copper silicate hydrate, showed good antibacterial properties against the Gram-negative bacteria Escherichia coli, even at a content of 1 wt.% CuSiO3∙xH2O, and against the Gram-positive bacteria Staphylococcus aureus, at the content of at least 5 wt.% CuSiO3∙xH2O. The bacterial growth reduction factor (R) was greater than 99% for most of the samples tested. Good antifungal properties against the fungus Candida albicans were found for the PES and PLA nonwoven fabrics modified with dispersions containing 5-7 wt.% CuSiO3∙xH2O and 4.2-5.0 wt.% TiO2. The addition of TiO2 led to a significant improvement in the antifungal properties of the PES and PLA nonwovens modified in this way. For the samples of PES WIFP-270 and FS F-5 nonwovens, modified with water dispersions containing 5.0 wt.% CuSiO3∙xH2O and 4.2-5.0 wt.% TiO2, the growth reduction factor for the fungus Candida albicans (R) reached values in the range of 80.9-98.0%. These new biofunctionalized polymeric nonwoven textile materials can find practical applications in the manufacture of filters for hospital air-conditioning systems and for the automotive industry, as well as in air purification devices. Moreover, similar antimicrobial modification of fabrics with the dip-coating or coating methods can be applied, for example, in the fabrication of fungi- and mold-resistant garden furniture.

BERTrand-peptide:TCR binding prediction using Bidirectional Encoder Representations from Transformers augmented with random TCR pairing.

MOTIVATION: The advent of T-cell receptor (TCR) sequencing experiments allowed for a significant increase in the amount of peptide:TCR binding data available and a number of machine-learning models appeared in recent years. High-quality prediction models for a fixed epitope sequence are feasible, provided enough known binding TCR sequences are available. However, their performance drops significantly for previously unseen peptides. RESULTS: We prepare the dataset of known peptide:TCR binders and augment it with negative decoys created using healthy donors' T-cell repertoires. We employ deep learning methods commonly applied in Natural Language Processing to train part a peptide:TCR binding model with a degree of cross-peptide generalization (0.69 AUROC). We demonstrate that BERTrand outperforms the published methods when evaluated on peptide sequences not used during model training. AVAILABILITY AND IMPLEMENTATION: The datasets and the code for model training are available at https://github.com/SFGLab/bertrand.

Evaluation of Polysaccharide-Peptide Conjugates Containing the RGD Motif for Potential Use in Muscle Tissue Regeneration.

New scaffold materials composed of biodegradable components are of great interest in regenerative medicine. These materials should be: stable, nontoxic, and biodegrade slowly and steadily, allowing the stable release of biodegradable and biologically active substances. We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. Scanning electron microscopy imaging and light microscopy studies with hematoxylin-eosin staining showed that C2C12 cells were able to interact with the tested peptide-polysaccharide conjugates. The release factor (Q) varied depending on both the peptide and the structure of the polysaccharide matrix. LDH, Alamarblue®, Ki-67, and cell cycle assays indicated that peptides 1 and 2 were characterized by the best biological properties. Conjugates containing chitosan and the ternary polysaccharide nonwoven with peptide 1 exhibited very high antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae. Overall, the results of the study suggested that polysaccharide conjugates with peptides 1 and 2 can be potentially used in regenerative medicine.

Preparation of Cotton-Zinc Composites by Magnetron Sputtering Metallization and Evaluation of their Antimicrobial Properties and Cytotoxicity.

The aim of this investigation was to evaluate the biological properties of cotton-zinc composites. A coating of zinc (Zn) on a cotton fabric was successfully obtained by a DC magnetron sputtering system using a metallic Zn target (99.9%). The new composite was characterized using scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS), UV/Vis transmittance, and atomic absorption spectrometry with flame excitation (FAAS). The composite was tested for microbial activity against colonies of Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria and antifungal activity against Aspergillus niger and Chaetomium globosum fungal mold species as model microorganisms. Cytotoxicity screening of the tested modified material was carried out on BALB/3T3 clone mouse fibroblasts. The SEM/EDS and FAAS tests showed good uniformity of zinc content on a large surface of the composite. The conducted research showed the possibility of using the magnetron sputtering technique as a zero-waste method for producing antimicrobial textile composites.

AI Aided Design of Epitope-Based Vaccine for the Induction of Cellular Immune Responses Against SARS-CoV-2.

The heavy burden imposed by the COVID-19 pandemic on our society triggered the race toward the development of therapies or preventive strategies. Among these, antibodies and vaccines are particularly attractive because of their high specificity, low probability of drug-drug interaction, and potentially long-standing protective effects. While the threat at hand justifies the pace of research, the implementation of therapeutic strategies cannot be exempted from safety considerations. There are several potential adverse events reported after the vaccination or antibody therapy, but two are of utmost importance: antibody-dependent enhancement (ADE) and cytokine storm syndrome (CSS). On the other hand, the depletion or exhaustion of T-cells has been reported to be associated with worse prognosis in COVID-19 patients. This observation suggests a potential role of vaccines eliciting cellular immunity, which might simultaneously limit the risk of ADE and CSS. Such risk was proposed to be associated with FcR-induced activation of proinflammatory macrophages (M1) by Fu et al. (2020) and Iwasaki and Yang (2020). All aspects of the newly developed vaccine (including the route of administration, delivery system, and adjuvant selection) may affect its effectiveness and safety. In this work we use a novel in silico approach (based on AI and bioinformatics methods) developed to support the design of epitope-based vaccines. We evaluated the capabilities of our method for predicting the immunogenicity of epitopes. Next, the results of our approach were compared with other vaccine-design strategies reported in the literature. The risk of immuno-toxicity was also assessed. The analysis of epitope conservation among other Coronaviridae was carried out in order to facilitate the selection of peptides shared across different SARS-CoV-2 strains and which might be conserved in emerging zootic coronavirus strains. Finally, the potential applicability of the selected epitopes for the development of a vaccine eliciting cellular immunity for COVID-19 was discussed, highlighting the benefits and challenges of such an approach.