Morrisdillard2843

Glycosaminoglycans (GAGs) are conserved polysaccharides composed of linear repeating disaccharides and play crucial roles in multiple biological processes in animal kingdom. However, saccharide-branched GAGs are rarely found, except the fucose-branched one from sea cucumbers. There was conjecture about the presence of disaccharide-branched GAG since 30 years ago, though not yet confirmed. Here, we report a GAG containing galactose-fucose branches from Thelenota ananas. This unique branch was confirmed as d-Gal4S(6S)-α1,2-l-Fuc3S by structural elucidation of oligosaccharides prepared from T. ananas GAG. Bioassays indicated that oligomers with a larger degree of polymerization exhibited a potent anticoagulation by targeting the intrinsic tenase. Heptasaccharide was proven as the minimum fragment retaining the anticoagulant potential and showed 92.6% inhibition of venous thrombosis in vivo at sc. of 8 mg/kg with no obvious bleeding risks. These results not only solve a long-standing question about the presence of disaccharide-branched GAG in Holothuroidea, but open up new opportunities to develop safer anticoagulants.Reactions of the pentaruthenium cluster complexes Ru5(μ5-C)(CO)15 (5), Ru5(μ5-C)(CO)14[μ-η2-O═C(NMe2)](μ-H) (6), and Ru5(μ5-C)(CO)15Cl(μ-H) (7) with ethyne (C2H2) in the presence of Me3NO yielded the zwitterionic complexes Ru5(μ5-C)(CO)13[μ-η2-CHCH(NMe3)] (8), Ru5(μ5-C)(CO)13[μ-η2-O═C(NMe2)](η1-E-CH═CH(NMe3)(μ-H) (9), and Ru5(μ5-C)(CO)13Cl[η1-E-CH═CH(NMe3)](μ-H) (11). Each product contains a positively charged trimethylammonioethenyl ligand, CH═CH(+NMe3), that is derived from a 2-trimethylammonioethenide, -CH═CH(+NMe3), zwitterion that formally has a positive charge on the nitrogen atom and a negative charge on the terminal enyl carbon atom. The trimethylammonioethenyl ligand, CH═CH(+NMe3) in 8 is a η2-ligand that bridges a Ru-Ru bond on a basal edge of the square-pyramidal Ru5 cluster by a combination of σ + π cooordination of the ethenyl group. Compounds 9 and 11 each contain a η1-terminally coordinated [η1-E-CH═CH(+NMe3)] ligand with an E stereochemistry at the C═C double bond in open Ru5 cluster complexes2C)HC═CH] (15) which contains a bridging methoxycarbonyl-substituted alkenyl ligand and the known compound Ru5(μ5-C)(CO)13[μ-η2-O═C(NMe2)](HNMe2)(μ-H) (16).The weak adhesion between two hydrogel layers may lead to the delamination of bilayer hydrogels or low force transfer efficiency during deformation. Here, tough interfacial adhesive bilayer hydrogels with rapid shape deformation and recovery were prepared by simple attachment-heating of two gel layers. The bilayer hydrogels, composed of a shape memory gel (S-gel) and an elastic gel (E-gel), exhibited extremely tough interfacial adhesion between two layers (Γ ∼ 2200 J/m2). The shape deformation and shape recovery of the bilayer hydrogels, tuned by "heating-stretching" mode and "stretching-heating-stretching" mode, were rapid ( less then 5 s) and no delamination between two gel layers was detected during shape deformation. Based on the fast shape deformation and recovery, the bilayer hydrogels could mimic the flower and hand, and a gel gripper could be fabricated to catch the object in the hot water. This work provides a simple method to prepare tough adhesive bilayer hydrogels with controlled shape deformation.Electrode-electrolyte interfaces (EEIs) affect the rate capability, cycling stability, and thermal safety of lithium-ion batteries (LIBs). Designing stable EEIs with fast Li+ transport is crucial for developing advanced LIBs. Here, we study Li+ kinetics at EEIs tailored by three nanoscale polymer thin films via chemical vapor deposition (CVD) polymerization. Small binding energy with Li+ and the presence of sufficient binding sites for Li+ allow poly(3,4-ethylenedioxythiophene) (PEDOT) based artificial coatings to enable fast charging of LiCoO2. Operando synchrotron X-ray diffraction experiments suggest that the superior Li+ transport property in PEDOT further improves current homogeneity in the LiCoO2 electrode during cycling. PEDOT also forms chemical bonds with LiCoO2, which reduces Co dissolution and inhibits electrolyte decomposition. As a result, the LiCoO2 4.5 V cycle life tested at C/2 increases over 1700% after PEDOT coating. In comparison, the other two polymer coatings show undesirable effects on LiCoO2 performance. These insights provide us with rules for selecting/designing polymers to engineer EEIs in advanced LIBs.One potential approach to address the rising threat of antibiotic resistance is through novel formulations of established drugs. We designed antibiotic cross-linked micelles (ABC-micelles) by cross-linking the Pluronic F127 block copolymers with an antibiotic itself, via a novel one-pot synthesis in aqueous solution. ABC-micelles enhanced antibiotic encapsulation while also reducing systemic toxicity in mice. Using colistin, a hydrophilic, potent ″last-resort" antibiotic, ABC-micelle encapsulation yield was 80%, with good storage stability. ABC-micelles exhibited an improved safety profile, with a maximum tolerated dose of over 100 mg/kg colistin in mice, at least 16 times higher than the free drug. Colistin-induced nephrotoxicity and neurotoxicity were reduced in ABC-micelles by 10-50-fold. Despite reduced toxicity, ABC-micelles preserved bactericidal activity, and the clinically relevant combination of colistin and rifampicin (co-loaded in the micelles) showed a synergistic antimicrobial effect against antibiotic-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. find protocol In a mouse model of sepsis, colistin ABC-micelles showed equivalent efficacy as free colistin but with a substantially higher therapeutic index. Microscopic single-cell imaging of bacteria revealed that ABC-micelles could kill bacteria in a more rapid manner with distinct cell membrane disruption, possibly reflecting a different antimicrobial mechanism from free colistin. This work shows the potential of drug cross-linked micelles as a new class of biomaterials formed from existing antibiotics and represents a new and generalized approach for formulating amine-containing drugs.