An Immunomodulatory Biomimetic Single-Atomic Nanozyme for Biofilm Wound Healing Management.

Nanozyme-driven catalytic antibacterial therapy has become a promising modality for bacterial biofilm infections. However, current catalytic therapy of biofilm wounds is severely limited by insufficient catalytic efficiency, excessive inflammation, and deep tissue infection. Drawing from the homing mechanism of natural macrophages, herein, a hollow mesoporous biomimetic single-atomic nanozyme (SAN) is fabricated to actively target inflamed parts, suppress inflammatory factors, and eliminate deeply organized bacteria for enhance biofilm eradication. In the formulation, this biomimetic nanozyme (Co@SAHSs@IL-4@RCM) consists of IL-4-loaded cobalt SANs-embedded hollow sphere encapsulate by RAW 264.7 cell membrane (RCM). Upon accumulation at the infected sites through the specific receptors of RCM, Co@SAHS catalyze the conversion of hydrogen peroxide into hydroxyl radicals and are further amplify by NIR-II photothermal effect and glutathione depletion to permeate and destroy biofilm structure. This behavior subsequently causes the dissociation of RCM shell and the ensuing release of IL-4 that can reprogram macrophages, enabling suppression of oxidative injury and tissue inflammation. The work paves the way to engineer alternative "all-in-one" SANs with an immunomodulatory ability and offers novel insights into the design of bioinspired materials.

Modulating the local coordination environment of cobalt single-atomic nanozymes for enhanced catalytic therapy against bacteria.

Single-atomic nanozymes (SANZs) characterized by atomically dispersed single metal atoms have recently contributed to breakthroughs in biomedicine due to their satisfactory catalytic activity and superior selectivity compared to their nanoscale counterparts. The catalytic performance of SANZs can be improved by modulating their coordination structure. Therefore, adjusting the coordination number of the metal atoms in the active center is a potential method for enhancing the catalytic therapy effect. In this study, we synthesized various atomically dispersed Co nanozymes with different nitrogen coordination numbers for peroxidase (POD)-mimicking single-atomic catalytic antibacterial therapy. Among the polyvinylpyrrolidone modified single-atomic Co nanozymes with nitrogen coordination numbers of 3 (PSACNZs-N3-C) and 4 (PSACNZs-N4-C), single-atomic Co nanozymes with a coordination number of 2 (PSACNZs-N2-C) had the highest POD-like catalytic activity. Kinetic assays and Density functional theory (DFT) calculations indicated that reducing the coordination number can lower the reaction energy barrier of single-atomic Co nanozymes (PSACNZs-Nx-C), thereby increasing their catalytic performance. In vitro and in vivo antibacterial assays demonstrated that PSACNZs-N2-C had the best antibacterial effect. This study provides proof of concept for enhancing single-atomic catalytic therapy by regulating the coordination number for various biomedical applications, such as tumor therapy and wound disinfection. STATEMENT OF SIGNIFICANCE: The use of nanozymes that contain single-atomic catalytic sites has been shown to effectively promote the healing of bacteria-infected wounds by exhibiting peroxidase-like activity. The homogeneous coordination environment of the catalytic site has been associated with high antimicrobial activity, which provides insight into designing new active structures and understanding their mechanisms of action. In this study, we designed a series of cobalt single-atomic nanozymes (PSACNZs-Nx-C) with different coordination environments by shearing the Co-N bond and modifying polyvinylpyrrolidone (PVP). The synthesized PSACNZs-Nx-C demonstrated enhanced antibacterial activity against both Gram-positive and Gram-negative bacterial strains, and showed good biocompatibility in both in vivo and in vitro experiments.

Designing Single-Atom Active Sites on sp2 -Carbon Linked Covalent Organic Frameworks to Induce Bacterial Ferroptosis-Like for Robust Anti-Infection Therapy.

With the threat posed by drug-resistant pathogenic bacteria, developing non-antibiotic strategies for eradicating clinically prevalent superbugs remains challenging. Ferroptosis is a newly discovered form of regulated cell death that can overcome drug resistance. Emerging evidence shows the potential of triggering ferroptosis-like for antibacterial therapy, but the direct delivery of iron species is inefficient and may cause detrimental effects. Herein, an effective strategy to induce bacterial nonferrous ferroptosis-like by coordinating single-atom metal sites (e.g., Ir and Ru) into the sp2 -carbon-linked covalent organic framework (sp2 c-COF-Ir-ppy2 and sp2 c-COF-Ru-bpy2 ) is reported. Upon activating by light irradiation or hydrogen peroxide, the as-constructed Ir and Ru single-atom catalysts (SACs) can significantly expedite intracellular reactive oxygen species burst, enhance glutathione depletion-related glutathione peroxidase 4 deactivation, and disturb the nitrogen and respiratory metabolisms, leading to lipid peroxidation-driven ferroptotic damage. Both SAC inducers show potent antibacterial activity against Gram-positive bacteria, Gram-negative bacteria, clinically isolated methicillin-resistant Staphylococcus aureus (MRSA), and biofilms, as well as excellent biocompatibility and strong therapeutic and preventive potential in MRSA-infected wounds and abscesses. This delicate nonferrous ferroptosis-like strategy may open up new insights into the therapy of drug-resistant pathogen infection.

Multifunctional Integrated Superhydrophobic Coatings with Unique Fluorescence and Micro/Micro/Nano-Hierarchical Structures Enabled by In Situ Self-Assembly.

Conferring versatility to superhydrophobic materials is extremely desirable to advance their utility. Herein, we have developed a superhydrophobic material with montmorillonite as microskeleton supports and in situ grown ZIF-8 nanoparticles and loaded them with newly developed fluorescent carbon dots. In situ growth of the ZIF-8 on OMMT constructs a dense nanoscale rough structure and meanwhile self-assembly generates abundant microporous, thus forming unique hierarchical microporous/microsheet/nanoparticle tri-tier micro and nano structures. Then the multifunctional superhydrophobic coating is fabricated by a facile spraying technique using polydimethylsiloxane (PDMS) as a multifunctional polymer binder. The PDMS/RB-CDs/ZIF-8@OMMT exhibits superhydrophobicity with a water contact angle of 164.7° and a water sliding angle of 1.4°, which also possesses good self-cleaning performance. Moreover, novel carbon dots are developed in this work which can confer unique fluorescent properties and photothermal properties to materials. Fluorescence characterization reveals the multiple emission peaks among 300-800 nm and excitation wavelength dependence and independence. Photothermal experiments unveil an efficient light-to-heat conversion caused by the light traps and absorption wavelengths associated with photothermal heating. Benefiting from the dense microporous/microsheet/nanoparticle structures, the superhydrophobicity is still maintained after 120 cycles of abrasion. Moreover, electrochemical impedance spectroscopy (EIS) reveals a significant increase in impedance, which is associated with excellent corrosion resistance. The superhydrophobic coating also exhibits superior UV resistance and good thermal stability. Multifunctional fluorescent superhydrophobic materials will enable the development of various and potential applications in different fields.

Physico-Chemical Properties of Sugar Beet Pectin-Sodium Caseinate Conjugates via Different Interaction Mechanisms.

Polysaccharides and proteins are frequently conjugated through electrostatic attraction, enzymatic cross-linking, and heat treatment (Maillard reaction) to obtain food structuring ingredients, mostly for their application as emulsifiers. The conjugate partners and their interaction type affect performance at acidic or neutral pH and during thermal processing, thus requiring careful selection. Here, the aggregate properties (particle size, conjugate charge, shear viscosity) of three types of sugar beet pectin (SBP)-sodium caseinate (SC) 1:1 conjugates, at acidic and neutral pH (4.5; 7), as well as their thermal processing stability (80 °C), were investigated. The enzymatically cross-linked SBP:SC was more acid tolerant than the electrostatically interacting conjugates. Maillard cross-linked conjugates aggregated at pH 4.5, suggesting poor emulsifier performance in acidic conditions. At pH 7, the three conjugate types showed similar aggregate properties. The results are discussed in terms of structural re-arrangement.

Policy and Practice Model of Public-Private Partnership in Public Hospitals during the New Medical Reform Period.

Purpose: Since the beginning of the new health care reform in 2009, the state has illustrated the top design and health care improvement strategy of "encouraging social capital to participate in the reform of public hospitals", in accordance with the program's general objective. All areas have been explored on this matter and the results obtained are very interesting, not to mention the acquisition of significant experience. At present, the existing business models in China are mainly the following: Rebuild-Operate-Transfer (ROT), franchise business model, Build-Own-Operate-Transfer (BOOT) model, mixed ownership model and business insurance model. This paper introduces a variety of alternative models, and provides a simple analysis of the advantages and disadvantages. Moreover, for the reform of public hospitals, the government shares should go into franchise mode or mixed ownership, and all property rights should be transferred to the government to ensure the conservation and proliferation of state-owned assets.