Multifunctional Injectable Microspheres Containing "Naturally-Derived" Photothermal Transducer for Synergistic Physical and Chemical Treating of Acute Osteomyelitis through Sequential Immunomodulation.

Osteomyelitis induced by Staphylococcus aureus (S. aureus) is a persistent and deep-seated infection that affects bone tissue. The main challenges in treating osteomyelitis include antibiotic resistance, systemic toxicity, and the need for multiple recurrent surgeries. An ideal therapeutic strategy involves the development of materials that combine physical, chemical, and immunomodulatory synergistic effects. In this work, we prepared injectable microspheres consisting of an interpenetrating network of ionic-cross-linked sodium alginate (SA) and genipin (Gp)-cross-linked gelatin (Gel) incorporated with tannic acid (TA) and copper ions (Cu2+). The Gp-cross-linked Gel acted as a "naturally-derived" photothermal therapy (PTT) agent. The results showed that the microspheres exhibited efficient and rapid bactericidal effects against both S. aureus and Escherichia coli (E. coli) under the irradiation of near-infrared light at 808 nm wavelength; moreover, the release of Cu2+ also induced sustained inhibitory effects against bacteria during the nonirradiation period. The in vitro cell culture results indicated that when combined with PTT, the microspheres could adaptively modulate macrophage M1 and M2 phenotypes in sequence. Additionally, these microspheres were found to enhance the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In vivo studies conducted in a rat femur osteomyelitis model with bone defects showed that under multiple laser irradiation the microspheres effectively controlled bacterial infection, improved the pathological immune microenvironment, and significantly enhanced the repair and regeneration of bone tissues in the affected area.

Reusable Solid-form Phase-Selective Organogelators for Rapid and Efficient Remediation of Crude Oil Spill.

Phase-selective organogelators (PSOGs) are considered as a prospective tool for their application in oil spill remediation. However, the number of reports on the PSOGs that can be used in powder form for prompt phase-selective gelation of crude oils is still limited. In this study, a series of compounds with l-mandelic acid as the scaffold bearing different amino acid fragments have been prepared. Also, the gelation behaviors and properties of these derivatives toward organic liquids, product oils, and a type of Chinese crude oil were investigated via heating-and-cooling process, stirring, or resting operation. Besides, the micromorphologies of the resulting gels and the driving forces for the gel formation have been studied by scanning electron microscopy, Fourier transform infrared, UV spectroscopy, concentration-dependent 1H NMR, and X-ray diffraction. Particularly, gelator C15-Phe-Mac-Nap was shown to have the capability of congealing the Chinese crude oil selectively from water in powder form with a relatively lower gelator dosage, as compared with the other gelators we reported in the current and previous works. Moreover, gelator C15-Phe-Mac-Nap displayed some advantageous behaviors such as the reusability of gelator, excellent mechanical and chemical stability of the crude oil gels, and nontoxicity of the gelator in the aquatic environment, indicating its great potential application value for marine oil spill remediation.

Diverse Antibacterial Treatments beyond Antibiotics for Diabetic Foot Ulcer Therapy.

Diabetic foot ulcer (DFU), a common complication of diabetes, has become a great burden to both patients and the society. The delayed wound closure of ulcer sites resulting from vascular damage and neutrophil dysfunction facilitates bacterial infection. Once drug resistance occurs or bacterial biofilm is formed, conventional therapy tends to fail and amputation is unavoidable. Therefore, effective antibacterial treatment beyond antibiotics is of utmost importance to accelerate the wound healing process and prevent amputation. Considering the complexity of multidrug resistance, biofilm formation, and special microenvironments (such as hyperglycemia, hypoxia, and abnormal pH value) at the infected site of DFU, several antibacterial agents and different mechanisms have been explored to achieve the desired outcome. The present review focuses on the recent progress of antibacterial treatments, including metal-based medications, natural and synthesized antimicrobial peptides, antibacterial polymers, and sensitizer-based therapy. This review provides a valuable reference for the innovation of antibacterial material design for DFU therapy.

Metabolic engineering of Saccharomyces cerevisiae for glycerol utilization.

Due to its wide availability, glycerol is considered as a promising alternative feedstock for microbial fermentation. As a model eukaryote, Saccharomyces cerevisiae is commonly adopted for bioproduction of various bulk and value-added chemicals, but it does not efficiently utilize glycerol. In this review, the metabolic pathway of glycerol and its regulation in S. cerevisiae are first introduced. Then, strategies, including metabolic engineering of the endogenous pathway, introduction of exogenous pathways, adaptive evolution, and reverse metabolic engineering, are summarized for improving the glycerol utilization in S. cerevisiae. Finally, methods for further improving glycerol utilization by S. cerevisiae are proposed. This review provides insights for designing engineered S. cerevisiae for efficient utilization of glycerol.

Development of an ELISA method for testing VWF ristocetin cofactor activity with improved sensitivity and reliability in the diagnosis of von Willebrand disease.

OBJECTIVES: Current methods in assessing von Willebrand factor (VWF) ristocetin cofactor activity for Von Willebrand's disease (VWD) diagnosis include platelet agglutination by aggregometer or macroscopic slide examination, which are both time-consuming with suboptimal interassay and intra-assay variation. The purpose of this study is to establish a sensitive assay to detect VWF:RCo activity and evaluate its performance in VWD diagnosis. METHODS: We have established a sensitive VWF:RCo-ELISA method using a monoclonal antibody, SZ-151, to immobilize the recombinant fragment of platelet glycoprotein Ib (rfGPIbα). VWF was captured by rfGPIbα in the presence of ristocetin, and then detected by HRP-conjugated rabbit anti-human VWF IgG. We tested the VWF:RCo level by this VWF:RCo-ELISA in 25 patients with different types of VWD and 36 healthy donors, and compared this method to a previously reported ELISA using 2D4 coating antibody. RESULTS: The sensitivity of VWF:RCo-ELISA was greatly improved with this assay (0.008 IU/dL compared to 0.031 IU/dL by 2D4 antibody). The interassay and intra-assay coefficient variation were 8% and 12%, respectively. The mean values (ranges) of VWF:RCo in patients with type 1, type 2A, type 2B, type 2M, and type 3 of VWD and control group are 31.8 (22.3-56.9), 4.8 (0.6-11.8), 8.6 (1.6-19.7), 3.9 (1.0-6.8), 1.0 (0.5-1.6), and 91.5 (47.3-169.2) IU/dL, respectively. The corresponding ratios (ranges) of VWF:RCo/VWF:Ag are 0.83 (0.70-1.16), 0.27 (0.08-0.58), 0.31 (0.15-0.40), 0.18 (0.14-0.21), 0.52 (0.13-1.19), and 0.92 (0.62-1.26). CONCLUSION: The VWF:RCo-ELISA using monoclonal anti-rfGPIbα antibody SZ-151 showed improved sensitivity and reliability in detecting VWF:RCo activity, and its clinical application would facilitate the diagnosis and classification of VWD.