• Hviid Brogaard posted an update 5 hours, 3 minutes ago

    Our findings provide an experimental evidence that exposure to PM may adversely affect the manifestation and progression of COVID-19, mediated by the impact of SARS-CoV-2 on the site of entry. The study results suggest that examining these effects might help to advance our understanding of COVID-19 and aid the development of appropriate social interventions.Most studies on the diversity of magnetotactic bacteria (MTB) have been conducted on samples obtained from the Northern or the Southern hemispheres. The diversity of MTB in tropical Asia near the geo-equator, with a close-to-zero geomagnetic inclination, weak magnetic field and constantly high seawater temperature has never been explored. This study aims to decipher the diversity of MTB in the marine environment of Singapore through shotgun metagenomics. Although MTB has been acknowledged to be ubiquitous in aquatic environments, we did not observe magnetotactic behaviour in the samples. THAL-SNS-032 concentration However, we detected the presence and determined the diversity of MTB through bioinformatic analyses. Metagenomic analysis suggested majority of the MTB in the seafloor sediments represents novel MTB taxa that cannot be classified at the species level. The relative abundance of MTB (~0.2-1.69%) in the samples collected from the marine environment of Singapore was found to be substantially lower than studies for other regions. In contrast to other studies, the genera Magnetovibrio and Desulfamplus, but not Magnetococcus, were the dominant MTB. Additionally, we recovered 3 MTB genomic bins that are unclassified at the species level, with Magnetovibrio blakemorei being the closest-associated genome. All the recovered genomic bins contain homologs of at least 5 of the 7 mam genes but lack homologs for mamI, a membrane protein suggested to take part in the magenetosome invagination. This study fills in the knowledge gap of MTB biodiversity in the tropical marine environment near the geo-equator. Our findings will facilitate future research efforts aiming to unravel the ecological roles of MTB in the tropical marine environments as well as to bioprospecting novel MTB that have been adapted to tropical marine environments for biotechnological applications.One of the most prevalent cancers in men is prostate cancer and could be managed with immunotoxins or antibody treatment. Because of the substantial rise of the Prostate-Specific Antigen and the Prostate-Specific Membrane Antigen (PSMA), cancer vaccination should be rendered with these antigens. Through pharmacodynamic experiments in a library of natural compounds from ZINC database, the current research sought to identify compounds that could suppress PSMA protein. To test the most productive compounds for further research, the Library has been scanned with Pharmacophore and ADMET analysis followed by molecular docking methods in the first phase. After selecting 15 ligands with the best pose related to docking results, to evaluate the stability of the ligand-protein bounds of the compounds, a molecular dynamics simulation considering the effect of the presence of zinc ions on the protein structure was performed. The measurement of ligand binding modes and free energy has shown that four compounds, including Z10, Z06, Z01, and Z03, have formed critical interactions with the active site’s residues. Besides, multiple approaches were employed to determine their inhibition rating and describe the variables that facilitate the attachment of ligands to the protein active site. The results are obtained from the MMPBSA/GBSA analysis of four selected small molecules (Z10, Z06, Z01, and Z03), which are very close to the IC50 value of reference ligand (DCIBzl); they are -13.85 kcal/mol, -12.58 kcal/mol, -10.71 kcal/mol and -9.39 kcal/mol respectively. Finally, we evaluate the results obtained from selected ligands using hydrogen bond and decomposition analyzes. We have examined the effective interactions between ligands and S1/S1’pockets in protein. Our computational results illustrate the design of more efficient inhibitors of PSMA.Protein encapsulation into nanocarriers has been extensively studied to improve the efficacy and stability of therapeutic proteins. However, the chemical modification of proteins or new synthetic carrier materials are essential to achieve a high encapsulation efficiency and structural stability of proteins, which hinders their clinical applications. New strategies to physically incorporate proteins into nanocarriers feasible for clinical uses are required to overcome the current limitation. Here we report the spontaneous protein-induced reorganization of ‘pre-formed’ unilamellar lipid vesicles to efficiently incorporate proteins within multilamellar protein-lipid hybrid vesicles without chemical modification. Epidermal growth factor (EGF) binds to the surface of cationic unilamellar lipid vesicles and induces layer-by-layer self-assembly of the vesicles. The protein is spontaneously entrapped in the interstitial layers of a multilamellar structure with extremely high loading efficiency, ~99%, through polyionic interactions as predicted by molecular dynamics simulation. The loaded protein exhibits much higher structural, chemical, and biological stability compared to free protein. The method is also successfully applied to several other proteins. This work provides a promising method for the highly efficient encapsulation of therapeutic proteins into multilamellar lipid vesicles without the use of specialized instruments, high energy, coupling agents, or organic solvents.This study reports on the development of a novel lipid combination that permits the efficient and highly selective delivery of plasmid DNA (pDNA) to immune cells in the spleen. Using DODAP, an ionizable lipid that was previously thought to be inefficient for gene delivery, we show for the first time, that this ignored lipid can be successfully used for efficient and targeted gene delivery in vivo, but only when combined with DOPE, a specific helper lipid. Using certain DODAP and DOPE ratios resulted in the formation of lipid nanoparticles (LNPs) with a ~ 1000-fold higher gene expression, and this expression was specific for the spleen, making it the most spleen-selective system for transfection using pDNA. The developed DODAP/DOPE-LNPs target immune cells in the spleen via receptors for complement C3 and this pathway is critical for efficient gene expression. We hypothesize that the high spleen transfection activity of DODAP/DOPE-LNPs is caused by the promotion of gene expression associated with B cell activation via complement receptors.