ZnO nanoparticles are widely used in biological, chemical, and medical fields, but their toxicity impedes their wide application. In this study, pristine ZnO NPs (~ 7 nm; ~ 18 nm; ~ 49 nm) and lipid-coated ZnO NPs (~ 13 nm; ~ 22 nm; ~ 52 nm) with different morphologies were prepared by chemical method and characterized by TEM, XRD, HRTEM, FTIR, and DLS. Our results showed that the lipid-coated ZnO NPs (~ 13 nm; ~ 22 nm; ~ 52 nm) groups improved the colloidal stability, prevented the aggregation and dissolution of nanocrystal particles in the solution, inhibited the dissolution of ZnO NPs into Zn2+ cations, and reduced cytotoxicity more efficiently than the pristine ZnO NPs (~ 7 nm; ~ 18 nm; ~ 49 nm). Compared to the lipid-coated ZnO NPs, pristine ZnO NPs (~ 7 nm; ~ 18 nm; ~ 49 nm) could dose-dependently destroy the cells at low concentrations. At the same concentration, ZnO NPs (~ 7 nm) exhibited the highest cytotoxicity. These results could provide a basis for the toxicological study of the nanoparticles and direct future investigations for preventing strong aggregation, reducing the toxic effects of lipid-bilayer and promoting the uptake of nanoparticles by HeLa cells efficiently.
The C-terminal sequences of porcine thrombin encode a series of peptides with the characteristics of net positive charge and hydrophobicity, suggesting antimicrobial potential. In this study, we synthesized truncated C-terminal peptides to explore their antimicrobial potency and structure-activity relationship. The results showed that some peptides exerted antimicrobial activity against Gram-positive and Gram-negative bacteria, with selectivity for microbial membranes. The antimicrobial potency of the peptides increased with the extension of chain length. Considering toxicity to red blood cells, the 21-mer peptide T-6 displayed the highest therapeutic index of 43.4, suggesting its higher cell selectivity. Typical α-helical conformations were observed upon binding to a bacteria-mimicking environment. The derivatives tended to interact preferentially with negatively charged vesicles compared to zwitterionic vesicles. Flow cytometry and electron microscopy revealed that the peptides targeted bacterial cell membranes and disrupted cytoplasmic membrane integrity, thereby causing the release of cellular contents leading to cell death. Peptide-membrane interaction experiments provided evidence that the peptides killed bacteria via a membrane-mediating mechanism. In summary, the C-terminal sequence of porcine thrombin has antimicrobial functions.
Background: A previous publication demonstrated that the oral intake of losartan promoted microfracture-mediated hyaline-like cartilage repair in osteochondral defects of a rabbit knee model. However, an intra-articular (IA) injection of losartan may have direct beneficial effects on cartilage repair and has not been studied. Purpose: To determine the dosage and beneficial effects of an IA injection of losartan on microfracture-mediated cartilage repair and normal cartilage homeostasis. Study Design: Controlled laboratory study. Methods: Rabbits were divided into 5 groups (n = 6 each): a microfracture group (MFX group) and 4 different losartan treatment groups that received varying doses of IA losartan (0.1, 1, 10, and 100 mg per knee). An osteochondral defect (5 mm) was created in the trochlear groove cartilage of 1 limb in each rabbit, and 5 microfracture perforations were made in the osteochondral defect. Both the injured and the contralateral knee joints were injected with IA losartan immediately after microfracture and at 2 and 4 weeks after surgery. Rabbits were sacrificed at 6 weeks after surgery for analysis including gross observation, micro–computed tomography, histology, and reverse transcription quantitative polymerase chain reaction. Results: Micro–computed tomography and gross observation demonstrated comparable subchondral bone healing and hyaline-like cartilage morphology in the 0.1-, 1-, and 10-mg losartan groups relative to the MFX group. Conversely, the 100-mg losartan group showed neither bony defect healing nor cartilage repair. Histology revealed higher O’Driscoll scores and hyaline-like cartilage regeneration in the 1-mg losartan group compared with the MFX group. In contrast, the 100-mg losartan group showed the lowest histology score and no cartilage repair. An IA injection of losartan at the doses of 0.1, 1, and 10 mg did not cause adverse effects on uninjured cartilage, while the 100-mg dose induced cartilage damage. Quantitative polymerase chain reaction results showed downregulation of the transforming growth factor β (TGF-β) signaling pathway after IA losartan injection. Conclusion: An IA injection of losartan at the dose of 1 mg was most effective for the enhancement of microfracture-mediated cartilage repair without adversely affecting uninjured cartilage. Conversely, a high dose (100 mg) IA injection of losartan inhibited cartilage repair in the osteochondral defect and was chondrotoxic to normal articular cartilage. Clinical Relevance: An IA injection of losartan at an optimal dosage represents a novel microfracture enhancement therapy and warrants a clinical trial for future clinical applications.
Universal adhesion of hydrogels to diverse materials is essential to their extensive applications. Unfortunately, tough adhesion of wet surfaces remains an urgent challenge so far, requiring robust cohesion strength for effective stress dissipation. In this work, a dual-network hydrogel polyethylenimine–poly(acrylic acid)/alginate (PEI–PAA/Alg) with excellent mechanical strength is realized via PEI–PAA complex and calcium alginate coordination for universal adhesion by the synergistic effort of topological entanglement and catechol chemistry. The dual networks of PEI–PAA/Alg provide mechanically reinforced cohesion strength, which is sufficient for energy dissipation during adhesion with universal materials. After the integration of mussel-inspired dopamine into PAA or Alg, the adhesive demonstrates further improved adhesion performance with a solid adherend and capability to bond cancellous bones. Notably, the dopamine-modified adhesive exhibits better instant adhesion and reversibility with wet surfaces compared with commercial fibrin. Adhesion interfaces are investigated by SEM and micro-FTIR to verify the effectiveness of strategies of topological entanglement. Furthermore, the adhesive also possesses great injectability, stability, tissue adhesion, and biocompatibility. In vivo wound healing and histological analysis indicate that the hydrogel can promote wound closure, epidermis regeneration, and tissue refunctionalization, implying its potential application for bioadhesive and wound dressing.
Summary Nanoparticles (NPs) were fabricated by xanthan gum (XG) and lysozyme (Ly), and the preparation was further analysed to explore the synthesis mechanism. Measurement of sizes and zeta (ζ) potential, transmission electron microscopy, and rheological and spectral demonstration were conducted to investigate molecular changes and interactions between XG and Ly under alkaline conditions and in the gelatinisation process. Results indicated that the ζ potential of the Ly/XG mixture was lower than the sum of Ly and XG at initial alkalisation. The interactions, hyperchromic effect and emission intensity of Ly were enhanced with increased XG concentration. Thus, XG and Ly lost their initial structures and formed metastable state complex. Heating at a high temperature promoted Ly/XG gelatinisation and fabricated stable Ly/XG nanogel for further molecular rearrangement. The worthwhile endeavour prepared Ly/XG NPs through alkali‐coupled thermal method and attempted to provide useful information regarding the synthesis mechanism from rheological and spectral perspectives by simulating preparation condition.
The alleviation of phosphorus (P) limitation by increasing carbon (C) input was an effective strategy in crop production. Yet, the effects of straw returning on soil microbial biomass P (MBP) turnover and P fractions in paddy-upland rotation remain poorly understood. Soil MBP turnover involves the mineralization and immobilization of organic P (Po), potentially altering P fractions and reducing the risk of P loss. The effects of straw returning on soil MBP turnover, P fractions and crop P utilization during the rice-oilseed rape rotation were evaluated in two field experiments with different soil Po levels. The treatments included no P fertilizer (-P), P fertilizer (+P) and P fertilizer plus straw returning (+P+S). The crop P uptake and cumulative P utilization efficiency were increased by straw returning. Straw addition promoted microbial biomass, decreased the MBC: MBP ratio in Po-high soil and increased the MBC: MBP ratio in Po-low soil, and increased MBP turnover rates and fluxes. According to structural equation modeling (SEM), soil MBC and MBP had significant effects on crop P uptake directly or via P fractions. In Po-high soil, straw addition increased inorganic P (Pi) (NaHCO3 and NaOH) and decreased Po content by increasing the MBP turnover, while the Po-low soil mainly increased Po content. Among multiple variables, MBP was the most important driving factor controlling P uptake in Po-high soil, while MBC and NaOH-Pi were the best driving factors in Po-low soil. Additionally, the soil MBC, MBP and MBC: MBP ratios were higher in the oilseed rape season than in the rice season. Consequently, straw returning improves soil P availability by increasing MBP turnover, which was beneficial for improving P utilization.
Polyimide/inorganics hybrid films fabricated by conventional approaches, including an in situ polymerization method, the sol–gel process, and a solution blending method, have a dramatic drop in malleability. In this work, a hydrogel strategy for preparing ductile polyimide/reduced graphene oxide (PI/rGO) nanohybrid films with internal porous structures has been proposed. The hydrogel strategy involved two steps. The polyamide acid carboxylate/GO (PAAC/GO) films were first prepared by tape casting, followed by a gelation process of the PAAC/GO aqueous solution; the PI/rGO films were then obtained after an imidization reaction of the PAAC/GO films. Interestingly, in this strategy, the PAA chains tended to self-assemble into microdomain crystalline structures assisted by their interactions with water, as revealed by XRD and Raman spectroscopy. The present PI/rGO films display more uniform microstructures, without aggregation of the rGO nanosheets. Furthermore, they exhibited an enhanced toughness property, with a high elongation at break of 37–55%. In addition, their dielectric property is more stable and less frequency-dependent due to the internal porous structure. This hydrogel strategy would appear to be a promising candidate for fabricating hybrid PI–inorganic composite materials, even other hybrid organic/inorganic composite materials with specific features.
A three-step synthesis from genistein of the water-soluble sodium salt of 7-O-carboxymethyl-genistein is described. Base-catalysed reaction of genistein with t-butyl bromoacetate gave 7-O-(carbo-t-butoxy)methyl-genistein, which was hydrolysed by aqueous acetic acid to 7-O-carboxymethyl-genistein and neutralised (NaHCO 3 ) to give the target compound. The carboxylate group enhanced the water-solubility of genistein more than a thousand-fold and the new derivate will be useful as a candidate compound in pharmacological and clinical chemistry studies of isoflavones.