Di-caffeoylquinic acid: a potential inhibitor for amyloid-beta aggregation.

Alzheimer's disease (AD) remains a challenging neurodegenerative disorder with limited therapeutic success. Traditional Chinese Medicine (TCM), as a promising new source for AD, still requires further exploration to understand its complex components and mechanisms. Here, focused on addressing Aß (1-40) aggregation, a hallmark of AD pathology, we employed a Thioflavin T fluorescence labeling method for screening the active molecular library of TCM which we established. Among the eight identified, 1,3-di-caffeoylquinic acid emerged as the most promising, exhibiting a robust binding affinity with a KD value of 26.7 nM. This study delves into the molecular intricacies by utilizing advanced techniques, including two-dimensional (2D) 15N-1H heteronuclear single quantum coherence nuclear magnetic resonance (NMR) and molecular docking simulations. These analyses revealed that 1,3-di-caffeoylquinic acid disrupts Aß (1-40) self-aggregation by interacting with specific phenolic hydroxyl and amino acid residues, particularly at Met-35 in Aß (1-40). Furthermore, at the cellular level, the identified compounds, especially 1,3-di-caffeoylquinic acid, demonstrated low toxicity and exhibited therapeutic potential by regulating mitochondrial membrane potential, reducing cell apoptosis, and mitigating Aß (1-40)-induced cellular damage. This study presents a targeted exploration of catechol compounds with implications for effective interventions in AD and sheds light on the intricate molecular mechanisms underlying Aß (1-40) aggregation disruption.

A multifunctional ionic liquid coating on 3D-Printed prostheses: Combating infection, promoting osseointegration.

Periprosthetic infection and mechanical loosening are two leading causes of implant failure in orthopedic surgery that have devastating consequences for patients both physically and financially. Hence, advanced prostheses to simultaneously prevent periprosthetic infection and promote osseointegration are highly desired to achieve long-term success in orthopedics. In this study, we proposed a multifunctional three-dimensional printed porous titanium alloy prosthesis coated with imidazolium ionic liquid. The imidazolium ionic liquid coating exhibited excellent bacterial recruitment property and near-infrared (NIR) triggered photothermal bactericidal activity, enabling the prosthesis to effectively trap bacteria in its vicinity and kill them remotely via tissue-penetrating NIR irradiation. In vivo anti-infection and osseointegration investigations in infected animal models confirmed that our antibacterial prosthesis could provide long-term and sustainable prevention against periprosthetic infection, while promoting osseointegration simultaneously. It is expected to accelerate the development of next-generation prostheses and improve patient outcomes after prosthesis implantation.

Water-stable boroxine structure with dynamic covalent bonds.

Boroxines are significant structures in the production of covalent organic frameworks, anion receptors, self-healing materials, and others. However, their utilization in aqueous media is a formidable task due to hydrolytic instability. Here we report a water-stable boroxine structure discovered from 2-hydroxyphenylboronic acid. We find that, under ambient environments, 2-hydroxyphenylboronic acid undergoes spontaneous dehydration to form a dimer with dynamic covalent bonds and aggregation-induced enhanced emission activity. Intriguingly, upon exposure to water, the dimer rapidly transforms into a boroxine structure with excellent pH stability and water-compatible dynamic covalent bonds. Building upon these discoveries, we report the strong binding capacity of boroxines toward fluoride ions in aqueous media, and develop a boroxine-based hydrogel with high acid-base stability and reversible gel-sol transition. This discovery of the water-stable boroxine structure breaks the constraint of boroxines not being applicable in aqueous environments, opening a new era of researches in boroxine chemistry.

Correction: Intelligent antibacterial surface based on ionic liquid molecular brushes for bacterial killing and release.

Correction for 'Intelligent antibacterial surface based on ionic liquid molecular brushes for bacterial killing and release' by Lunqiang Jin et al., J. Mater. Chem. B, 2019, 7, 5520-5527, https://doi.org/10.1039/C9TB01199D.

Lysozyme-Immobilized Polyethersulfone Membranes with Satisfactory Hemocompatibility and High Enzyme Activity for Endotoxin Removal.

Endotoxin adsorption has received extensive attention in the field of blood purification. However, developing highly efficient endotoxin adsorbents with excellent hemocompatibility remains challenging. In this study, we propose a new approach for developing the functional polyethersulfone (PES) membrane to remove endotoxins. First, the PES polymer is grafted with polyethylene glycol methyl acrylate (PEG-MA) in a homogeneous phase system via γ irradiation, and PES-g-PEG can be directly used to prepare the membrane by the phase inversion method. Then, polydopamine (PDA) is coated as an adhesive layer onto a PES-g-PEG membrane in an alkaline aqueous solution, and lysozyme (Lyz) is covalently immobilized with PDA through the Schiff base reaction. Lysozyme acts as an affinity adsorption ligand of endotoxin through charge and hydrophobic action. Our study reveals that the PEG branched chain and the PDA coating on the PES membrane can maintain the secondary structure of lysozyme, and thus, the immobilized Lyz can maintain high activity. The adsorption capacity of endotoxins for the PES-g-PEG/PDA/Lyz membrane is 1.28 EU/mg, with an equilibrium adsorption time of 6 h. Therefore, the PES-g-PEG/PDA/Lyz membrane shows great potential application in the treatment of endotoxemia.

Disregarded Free Chains Affect Bacterial Adhesion on Cross-Linked Polydimethylsiloxane Surfaces.

The surface properties exhibited by chemically cross-linked polydimethylsiloxanes (CPDMS) such as morphology, stiffness, and wettability have garnered great interest in the study of bacteria-material interactions. Nevertheless, the hidden factor of uncross-linked free PDMS chains that dissociate in CPDMS has often been overlooked when studying the biofilm formation on these polymeric elastomer surfaces. Here, we undertake a comparative characterization of the effects of free chains in CPDMS on bacterial adhesion to both flat and textured Sharklet CPDMS surfaces. Surprisingly, compared to unextracted surfaces, removing free chains from flat and textured CPDMS through solvent extraction results in a tremendous increase in bacterial colony-forming units for both Gram-negative and Gram-positive bacteria up to 2-3 orders in the initial adhesion stage of 2 h. These findings demonstrate that the solvent extraction of free chains from CPDMS is essential in studying the interactions between bacteria and silicone elastomer materials when focusing on a single variable.

Order-order assembly transition-driven polyamines detection based on iron-sulfur complexes.

Innovative modes of response can greatly push forward chemical sensing processes and subsequently improve sensing performance. Classical chemical sensing modes seldom involve the transition of a delicate molecular assembly during the response. Here, we display a sensing mode for polyamine detection based on an order-order transition of iron-sulfur complexes upon their assembly. Strong validation proves that the unique order-order transition of the assemblies is the driving force of the response, in which the polyamine captures the metal ion of the iron-sulfur complex, leading it to decompose into a metal-polyamine product, accompanied by an order-order transition of the assemblies. This mechanism makes the detection process more intuitive and selective, and remarkably improves the detection efficiency, achieving excellent polyamines specificity, second-level response, convenient visual detection, and good recyclability of the sensing system. Furthermore, this paper also provides opportunities for the further application of the iron-sulfur platform in environment-related fields.

Broad-Spectrum Clearance of Lipopolysaccharides from Blood Based on a Hemocompatible Dihistidine Polymer.

Blood infection can release toxic bacterial lipopolysaccharides (LPSs) into bloodstream, trigger a series of inflammatory reactions, and eventually lead to multiple organ dysfunction, irreversible shock, and even death, which seriously threatens human life and health. Herein, a functional block copolymer with excellent hemocompatibility is proposed to enable broad-spectrum clearance of LPSs from whole blood blindly before pathogen identification, facilitating timely rescue from sepsis. A dipeptide ligand of histidine-histidine (HH) was designed as the LPS binding unit, and poly[(trimethylamine N-oxide)-co-(histidine-histidine)], a functional block copolymer combining the LPS ligand of HH and a zwitterionic antifouling unit of trimethylamine N-oxide (TMAO), was then designed by reversible addition-fragmentation chain transfer (RAFT) polymerization. The functional polymer achieved effective clearance of LPSs from solutions and whole blood in a broad-spectrum manner and had good antifouling and anti-interference properties and hemocompatibility. The proposed functional dihistidine polymer provides a novel strategy for achieving broad-spectrum clearance of LPSs, with potential applications in clinical blood purification.

Specific Clearance of Lipopolysaccharide from Blood Based on Peptide Bottlebrush Polymer for Sepsis Therapy.

Lipopolysaccharide (LPS) is the primary bacterial toxin that is vital to the pathogenesis and progression of sepsis associated with extremely high morbidity and mortality worldwide. However, specific clearance of LPS from circulating blood is highly challenging because of the structural complexity and its variation between/within bacterial species. Herein, a robust strategy based on phage display screening and hemocompatible peptide bottlebrush polymer design for specific clearance of targeted LPS from circulating blood is proposed. Using LPS extracted from Escherichia coli as an example, a novel peptide (HWKAVNWLKPWT) with high affinity (KD < 1.0 nм), specificity, and neutralization activity (95.9 ± 0.1%) against the targeted LPS is discovered via iterative affinity selection coupled with endotoxin detoxification screening. A hemocompatible bottlebrush polymer bearing the short peptide [poly(PEGMEA-co-PEP-1)] exhibits high LPS selectivity to reduce circulating LPS level from 2.63 ± 0.01 to 0.78 ± 0.05 EU mL-1 in sepsis rabbits via extracorporeal hemoperfusion (LPS clearance ratio > 70%), reversing the LPS-induced leukocytopenia and multiple organ damages significantly. This work provides a universal paradigm for developing a highly selective hemoadsorbent library fully covering the LPS family, which is promising to create a new era of precision medicine in sepsis therapy.

Secreted endogenous macrosomes reduce Aß burden and ameliorate Alzheimer's disease.

Innovative therapeutic strategies are urgently needed for Alzheimer's disease (AD) due to the increasing size of the aging population and the lack of effective drug treatment. Here, we report the therapeutic effects of extracellular vesicles (EVs) secreted by microglia, including macrosomes and small EVs, on AD-associated pathology. Macrosomes strongly inhibited ß-amyloid (Aß) aggregation and rescued cells from Aß misfolding-induced cytotoxicity. Furthermore, macrosome administration reduced Aß plaques and ameliorated cognitive impairment in mice with AD. In contrast, small EVs slightly promoted Aß aggregation and did not improve AD pathology. Proteomic analysis of small EVs and macrosomes revealed that macrosomes harbor several important neuroprotective proteins that inhibit Aß misfolding. In particular, the small integral membrane protein 10-like protein 2B in macrosomes has been shown to inhibit Aß aggregation. Our observations provide an alternative therapeutic strategy for the treatment of AD over conventional ineffective drug treatments.

Recent Progress on Bioinspired Antibacterial Surfaces for Biomedical Application.

Surface bacterial fouling has become an urgent global challenge that calls for resilient solutions. Despite the effectiveness in combating bacterial invasion, antibiotics are susceptible to causing microbial antibiotic resistance that threatens human health and compromises the medication efficacy. In nature, many organisms have evolved a myriad of surfaces with specific physicochemical properties to combat bacteria in diverse environments, providing important inspirations for implementing bioinspired approaches. This review highlights representative natural antibacterial surfaces and discusses their corresponding mechanisms, including repelling adherent bacteria through tailoring surface wettability and mechanically killing bacteria via engineering surface textures. Following this, we present the recent progress in bioinspired active and passive antibacterial strategies. Finally, the biomedical applications and the prospects of these antibacterial surfaces are discussed.

Enrichment of IgG and HRP glycoprotein by dipeptide-based polymeric material.

Separation, purification, and identification of glycoproteins are essential for understanding their vital roles in biological and pathological processes. However, glycoproteins are difficult to be captured due to their low abundance, strong interference from non-glycosylated proteins. Here, we report a promising dipeptide-based saccharide recognition platform to selectively enrich two typical glycoproteins, named immunoglobin G (IgG) and horseradish peroxidase (HRP). Different from the conventional glycoprotein enrichment method based on boronic acid affinity or hydrophilic interaction with glycans, the present method was established based on affinity between Pro-Glu (PE) dipeptide and mannose, which is a key unit in the pentasaccharide core of the IgG and HRP glycans. The prepared PE homopolymer surface was proved to selectively bind IgG and HRP superior to that of bovine serum albumin (BSA). Benefiting from this feature, selective enrichment of IgG and HRP was achieved from a protein mixture containing 200-fold BSA interference by using polyPE@SiO2 under a dispersive solid-phase extraction (dSPE) mode. High adsorption capacity, controllable and selective adsorption behaviors, as well as satisfactory recovery demonstrated the high potential of the dipeptide-based polymeric material in IgG and HRP enrichment. This study might provide a new insight to solve the challenging problem of glycoprotein separation.

Anticoagulant chitosan-kappa-carrageenan composite hydrogel sorbent for simultaneous endotoxin and bacteria cleansing in septic blood.

Here, we describe a green approach to fabricate genipin crosslinked chitosan-kappa-carrageenan composite hydrogels (C-K hydrogels) aiming at reducing endotoxin level and bacteria burden in septic blood synchronously. The chemical compositions and morphologies of the developed C-K hydrogels were characterized by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and scanning electron microscopy. The C-K hydrogels significantly inhibited adverse blood-material interactions such as hemolysis, complement activation, platelet activation and contact activation, and exhibited better anticoagulant properties than raw chitosan hydrogels. Most importantly, the optimized C2-K1 hydrogels were competent to eliminate 63.3 % of endotoxin in septic blood with a maximum adsorption capacity of 95.0 EU/g during a 3-h simulative hemoperfusion procedure. Bacteria cleansing experiments further demonstrated that the optimized C2-K1 hydrogels effectively decreased 46.0 % of E. coli and 68.7 % of S. aureus load, respectively. It is believed that the C-K hydrogels are promising hemoperfusion sorbents to treat severe septic patients.

Hemocompatible magnetic particles with broad-spectrum bacteria capture capability for blood purification.

Pathogen capture and removal from whole blood is a new strategy for extracorporeal blood purification, especially in initial treatment of sepsis before pathogen identification. Herein, hemocompatible magnetic particles with broad-spectrum bacteria capture capability were proposed for pathogen removal from whole blood, omitting the necessity of pathogen identification. Firstly, we designed and synthesized a new kind of imidazolium-based ionic liquid with good antibacterial activity, and polydopamine coating was utilized as a hemocompatible platform to immobilize ionic liquids on Fe3O4 nanoparticles, forming the hemocompatible magnetic particles (Fe3O4@PDA-IL). The magnetic particles exhibited good hemocompatibility and performed well in the removal of various species of clinically significant pathogens from human whole blood, including S. aureus, E. coli, and the hard-to-treat bacteria of P. aeruginosa and Methicillin-resistant S. aureus, which are the most common pathogens in bloodstream infections. Besides, the Fe3O4@PDA-IL particles were also capable to remove bacterial endotoxins from blood, inhibiting further aggravation of sepsis. Overall, we demonstrated the application of hemocompatible magnetic particles in the removal of pathogens and bacterial endotoxins from whole blood via electrostatic and hydrophobic interactions, without significant effects on blood cells or the activation of coagulation and complement, addressing the feasibility of using imidazolium-based ionic liquids for bacteria capture and removal from whole blood. It would contribute to the development of magnetic separation-based approaches to remove bacteria and bacterial endotoxin for extracorporeal blood purification, especially in initial sepsis therapy before pathogen identification.

Rationally designed magnetic poly(catechol-hexanediamine) particles for bacteria removal and on-demand biofilm eradication.

In this study, we proposed a green, facile and low-cost approach for the fabrication of multifunctional particles with robust bacteria removal capability and on-demand biofilm eradication activity. Based on mussel-inspired coating of catechol and hexanediamine on Fe3O4 in aqueous solution, magnetic poly(catechol-hexanediamine) particles (Fe3O4@HDA) were prepared successfully in 1 h, at room temperature. Microbiological experiments demonstrated the Fe3O4@HDA particles could capture bacteria in water efficiently. Meanwhile, with an integration of magnetic response property and near-infrared-triggered photothermal bactericidal activity, the Fe3O4@HDA particles showed a high potential for biofilm targeting and in-situ eradication. We believe that the rationally designed magnetic poly(catechol-hexanediamine) particles could extend the applications of smart antimicrobial agents to industrial fields such as water disinfection and biofouling clean-up.

Urease immobilized GO core@shell heparin-mimicking polymer beads with safe and effective urea removal for blood purification.

Adsorbents are usually used to remove uremic toxins for blood purification. However, the removal of urea is still an intractable problem, since no effective material has been found for urea removal by physical adsorption. Here, urease immobilized graphene oxide core@shell heparin-mimicking polymer (U-GO-HMP) beads were designed, which exhibited good urea removal ability with a removal amount of about 635 mg/g and a removal ratio of about 80% from urea solution. In addition, urea could be removed from collected dialysate and the removal ratio could reach 60% within 480 min. Beyond that, the U-GO-HMP beads also showed good reusability with sustainable relative activity after 5 cycles. Furthermore, the U-GO-HMP beads exhibited good blood compatibility with low hemolysis ratio, suppressed complement activation and contact activation, as well as increased clotting times. It is worthy believing that the U-GO-HMP beads may have great potential in the field of blood purification for urea removal.

Intelligent antibacterial surface based on ionic liquid molecular brushes for bacterial killing and release.

The prevention of bacteria-induced infections has been increasing in importance in both clinical surgery and biomedical engineering. Although great attention has been paid to designing intelligent antibacterial surfaces, the fabrication processes are still not facile and universal enough, and the antibacterial efficiencies of these surfaces are also not ideal. Herein, ionic liquid (IL) molecules of 3-(12-mercaptododecyl)-1-methyl-1H-imidazol-3-ium bromide (IL(Br)) were synthesized with the minimum inhibitory concentrations as low as 4 and 8 µg mL-1 against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively. By simply immersing a polymeric substrate into the IL(Br) solution, an antibacterial surface with high killing efficiency of 99% against S. aureus (94% against E. coli) was achieved via a mussel-inspired approach. Subsequently, 97% S. aureus and 95% E. coli on the substrate could be released by simple ion-exchange of Br- with (CF3SO2)2N- due to the ion sensitivity of the IL molecular brushes. Thus, the proposed facile strategy towards a superior efficiency surface could be potentially used in intelligent antibacterial fields.

Engineering antimicrobial and biocompatible electrospun PLGA fibrous membranes by irradiation grafting polyvinylpyrrolidone and periodate.

Postoperative adhesion may form as the result of a complicated fibrosis and inflammatory response, thus leads to a series of complications or increases the risk of surgery failure. Herein, we prepared poly (lactic-co-glycolic acid)-graft-polyvinylpyrrolidone/polyiodide (PLGA-g-PVP/I) electrospun fibrous membranes to prevent postoperative adhesion and infection formation. Firstly, hydrophilic PVP molecules were grafted on the surface of PLGA powders by gamma ray, and then iodine ions were coordinated with the grafted PVP. Subsequently, PLGA-g-PVP/I fibrous membranes were prepared by electrospinning. The PLGA-g-PVP/I membranes were analyzed via UV-vis, FTIR, Raman, and XPS. The formed polyiodide endowed the membranes with sustained antibacterial activity. The antimicrobial property of PLGA-g-PVP/I membranes was ascribed to the synergistic effect of intracellular ROS production and glutathione oxidation. Furthermore, the prevention efficacy of postoperative abdominal adhesion from the PLGA-g-PVP/I composite membranes was characterized in a rat model of sidewall defect-cecum abrasion. The results demonstrated that the PLGA-g-PVP/I fibrous membranes could prevent the postoperative abdominal adhesion effectively. Therefore, to endow the PLGA-g-PVP/I electrospun fibrous membranes with durable antibacterial property may be a promising strategy towards an anti-bacterial and anti-adhesion system for commercial and clinical uses.

General Method for Synthesizing Transition-Metal Phosphide/N-Doped Carbon Nanomaterials for Hydrogen Evolution.

Applications of effective and steady metal catalysts for the hydrogen evolution reaction (HER) via electrolysis of water have a huge potential to relax energy crisis and reduce carbon dioxide emission. Herein, we design a simple, facile, and general approach for the synthesis of a series of transition-metal phosphide nanoparticles embedded in N-doped carbon (NC) nanomaterials using metal salts, abundantly available hexamethylene diamine tetra(methyl phosphonic acid), and urea as precursors. The resultant transition-metal phosphide nanoparticles can serve as high-efficiency and steady HER catalysts. Particularly, when the current density is 10 mA cm-2, the overpotentials of the obtained RhP2@NC are 30, 85, and 70 mV in acid (0.5 M H2SO4), neutral (1 M PBS), and alkaline (1 M KOH) solutions, respectively. Besides, the RhP2@NC exhibits good stability after 10 h in aforementioned solutions. More importantly, it is suited to fabricate other transition-metal phosphide nanoparticles/NC heterostructures by this synthetic strategy. The obtained CoP@NC, FeP@NC, Ni2P@NC, and Cu3P@NC also show relatively high efficiency for HER. Hence, the versatile synthesis strategy opens a new route for the research and fabrication of transition-metal phosphide-based catalysts for HER.