Notes

Microtubule nucleation without having a ring?
In an in vivo liver defect model, PL-CNC cryogels showed similar hemostatic performance in comparison with gelatin sponges and normal material-induced tissue response upon subcutaneous implantation. Overall, owing to their structure and bioactive composition, the proposed PL-CNC cryogels provide an alternative off-the-shelf hemostatic and antibacterial biomaterial with the potential to deliver therapeutically relevant proteins in situ.Organophosphorus nerve agents (OPNAs), used in chemical warfare, irreversibly inhibit essential cholinesterases (ChEs) in the cholinergic neurotransmission system. Several potent nucleophilic oximes have been approved for the treatment of acute poisoning by OPNAs, but they are rapidly cleared from blood circulation. Butyrylcholinesterase (BChE) stoichiometrically binds nerve agents, but because the molecular weight of a nerve agent is about 500-fold less than the enzyme, the bioscavenger has had limited utility. We synthesized BChE-polymer-oxime conjugates using atom transfer radical polymerization (ATRP) and azide-alkyne "click" chemistry. The activity of the BChE-polymer-oxime conjugates was dependent on the degree of oxime loading within the copolymer side chains. The covalent modification of oxime-containing copolymers prolonged the activity of BChE in the presence of the VX- and cyclosarin-fluorogenic analogues EMP-MeCyC and CMP-MeCyC, respectively. After complete inactivation by VX and cyclosarin fluorogenic analogues, the conjugates demonstrated efficient self-reactivation of up to 80% within 3-6 h. Repeated inhibition and high-level self-reactivation assays revealed that the BChE-polymer-oxime conjugates were excellent reactivators of OPNA-inhibited BChE. Recurring self-reactivation of BChE-polymer-oxime conjugates following repeated BChE inhibition by fluorogenic OPNAs (Flu-OPNAs) opens the door to developing the next generation of nerve agent "catalytic" bioscavengers.Synthetic gene delivery systems employ multiple functions to enable safe and effective transport of DNA to target cells. Here, we describe metabolite-based poly(l-lysine) (PLL) modifiers that improve transfection by imparting both pH buffering and nanoparticle stabilization functions within a single molecular unit. PLL modifiers were based on morpholine (M), morpholine and niacin (MN), or thiomorpholine (TM). PLL modification with (MN) or (TM) imparted buffering function over the pH range of 5-7 both in solution and live cells and enhanced the stability of PLL DNA nanoparticles, which exhibited higher resistance to polyanion exchange and prolonged blood circulation. These properties translated into increased transfection efficiency in vitro coupled with reduced toxicity compared to unmodified PLL and PLL(M). Furthermore, PEG-PLL(MN) DNA nanoparticles transfected muscle tissue in vivo for >45 days following intramuscular injection. These polymer modifiers demonstrate the successful design of multifunctional units that improve transfection of synthetic gene delivery systems while maintaining biocompatibility.Oral bacterial infection represents the leading cause of the gradual destruction of tooth and periodontal structures anchoring the teeth. click here Lately, injectable hydrogels have gained increased attention as a promising minimally invasive platform for localized delivery of personalized therapeutics. Here, an injectable and photocrosslinkable gelatin methacryloyl (GelMA) hydrogel is successfully engineered with ciprofloxacin (CIP)-eluting short nanofibers for oral infection ablation. For this purpose, CIP or its β-cyclodextrin (β-CD)-inclusion complex (CIP/β-CD-IC) has been incorporated into polymeric electrospun fibers, which were subsequently cut into short nanofibers, and then embedded in GelMA to obtain an injectable hybrid antimicrobial hydrogel. Thanks to the solubility enhancement of CIP by β-CD-IC and the tunable degradation profile of GelMA, the hydrogels promote localized, sustained, and yet effective cell-friendly antibiotic doses, as measured by a series of bacterial assays that demonstrated efficacy in attenuating the growth of Gram-positive Enterococcus faecalis. Altogether, we foresee significant potential in translating this innovative hybrid hydrogel as an injectable platform technology that may have broad applications in oral infection ablation, such as periodontal disease and pulpal pathology.Saccharide stereochemistry plays an important role in carbohydrate functions such as biological recognition processes and protein binding. Synthetic glycopolymers with pendant saccharides of controlled stereochemistry provide an attractive approach for the design of polysaccharide-inspired biomaterials. Acrylamide-based polymers containing either β,d-glucose or β,d-galactose pendant groups, designed to mimic GM1 ganglioside saccharides, and their small-molecule analogues were used to evaluate the effect of stereochemistry on glycopolymer solution aggregation processes alone and in the presence of Aβ42 peptide using dynamic light scattering, gel permeation chromatography-multiangle laser light scattering, and fluorescence assays. Fourier transform infrared and nuclear magnetic resonance (NMR) were employed to determine hydrogen bonding patterns of the systems. The galactose-containing polymer displayed significant intramolecular hydrogen bonding and self-aggregation and minimal association with Aβ42, while the glucose-containing glycopolymers showed intermolecular interactions with the surrounding environment and association with Aβ42. Saturation transfer difference NMR spectroscopy demonstrated different binding affinities for the two glycopolymers to Aβ42 peptide.Mussel wet adhesion is known for its outstanding strength on a variety of surfaces. On the basis of the hypothesis that 3,4-dihydroxyphenylalanine, a catecholic amino acid, governs mussel adhesion, chemists have put much effort into the design of adhesive synthetic polymers containing catechols. However, the exceptional properties exhibited by the native proteins were hardly captured. The attempts to make those polymers stick to wet inorganic surfaces resulted in low adhesive forces. Here we synthesized poly(dopamine acrylamide) and measured the interaction forces with various inorganic surfaces using atomic force microscopy-based single-molecule force spectroscopy. We show that hydroxylation of the surface plays a pivotal role on the formation of strong bonds. We demonstrate that depending on the conditions, the whole range of interactions, from weak interactions to covalent bonds, can come into play.
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