Reactive Oxygen-Correlated Photothermal Imaging of Smart COF Nanoreactors for Monitoring Chemodynamic Sterilization and Promoting Wound Healing.

Chemodynamic therapy (CDT) has emerged as a promising approach for treating infected diabetic wounds, while reliable imaging technology for simultaneous monitoring of ROS and therapeutic processes is still a formidable challenge. Herein, smart covalent organic framework (COF) nanoreactors (COF NRs) are constructed by hyaluronic acid (HA) packaged glucose oxidase (GOx) covalently linked Fe-COF for diabetic wound healing. Upon the breakdown of the HA protective layer, GOx consumes glucose to produce gluconic acid and hydrogen peroxide (H2O2), resulting in decreased local pH and H2O2 supplementation. Density functional theory (DFT) calculations show that Fe-COF has high catalytic activity towards H2O2, leading to in situ generation of hydroxyl radicals (·OH) for sterilization, and the localized downregulation of glucose effectively improved the microenvironment of diabetic wounds. Meanwhile, based on the near-infrared photothermal imaging of oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB), the authors showed that TMB can be applied for the point-of-care testing of ·OH and glucose, and assessing the sterilization progress in vivo. More significantly, the facile photothermal signaling strategy can be extended to monitor various ROS-mediated therapeutic systems, enabling accurate prediction of treatment outcomes.

Ambient Synthesis of Porphyrin-Based Fe-Covalent Organic Frameworks for Efficient Infected Skin Wound Healing.

Reactive oxygen species (ROS) have emerged as a promising treatment option for antibacterial and biofilm eradication. However, their therapeutic efficacy is significantly hampered by the unique microenvironments of diabetic wounds. In this study, we designed and synthesized porphyrin-based Fe covalent organic frameworks (Fe-COF) through a Schiff base condensation reaction. Subsequently, Fe-COF were encapsulated with hyaluronic acid (HA) through electrostatic adsorption, resulting in a novel formulation named HA-Fe-COF for diabetic wound healing. HA-Fe-COF were engineered to respond to hyaluronidase in the infected wound, leading to the controlled release of Fe-COF. Those released Fe-COF served a dual role as photosensitizers, generating singlet oxygen and localized heating when exposed to dual light sources. Additionally, they acted as peroxidase-like nanozymes, facilitating the production of ROS through enzymatic reactions. This innovative approach enabled a synergistic therapeutic effect combining photodynamic, photothermal, and chemodynamic modalities. Furthermore, the sustained release of HA from HA-Fe-COF promoted angiogenesis, collagen deposition, and re-epithelialization during the diabetic wound healing process. This "all-in-one" strategy offers a novel approach for the development of antimicrobial and biofilm eradication strategies that minimize damage to healthy tissues in vivo.

Fluorometric determination of copper(II) by using 3-aminophenylboronic acid-functionalized CdTe quantum dot probes.

Water-soluble cadmium telluride quantum dots capped with 3-mercaptopropionic acid were synthesized and further modified with 3-aminophenylboronic acid to form boronic acid-functionalized quantum dots (QDs). Under excitation at 350 nm, the modified QDs display yellow fluorescence with a peak at 566 nm. On exposure to copper(II), the fluorescence of the QDs is quenched. Under optimal conditions, fluorescence drops linearly in the 0.01 to 20 µM Cu(II) concentration range, and the detection limit is 7.6 nM. This fluorescent probe was applied to the determination of Cu(II) in spiked human serum and water samples and gave satisfactory results. Graphical abstract Schematic presentation of the principle for fluorometrice detection of copper(II) based on the use of boronic acid-functionalized cadmium telluride quantum dots (CdTe QDs).

Visual discrimination of phenolic group ß2-agonists and the ultrasensitive identification of their oxidation products by use of a tyrosinase-based catalytic reaction.

The fast, visual discrimination of ß2-agonist drugs is needed for the on-site screening of various types of ß2-agonists in blood and urine samples. We developed a simple, rapid, one-step colorimetric method to detect phenolic ß2-agonists by use of a tyrosinase catalytic reaction, which involved the oxidation of the phenol group on the benzene rings of ß2-agonists. The enzymatic oxidation products of ß2-agonists with phenolic groups exhibited different color transitions based on the different substituent groups on the aromatic ring, whereas ß2-agonists with the aniline group or the resorcinol group remained colorless. This visual color discrepancy has been used to intuitively and conveniently differentiate the phenolic group ß2-agonists, such as ractopamine, isoxsuprine, ritodrine, and fenoterol. The oxidation products of these compounds have been identified using mass spectrometry, and the possible reaction mechanisms between ß2-agonists and tyrosinase have been deduced. The parameters that govern the analytical performance of the reaction product, including the pH of the buffer solution, the concentration of tyrosinase, and the incubation time, have been studied and optimized using ultraviolet-visible (UV-vis) spectroscopy and electrochemical methods. Under the optimal experimental conditions, the absorbance intensity and electrochemical signal were found to increase proportionally to the concentrations of the phenolic group ß2-agonists, which gave a quantitative description of the ß2-agonists in solution.

Regional coordinated development of low-carbon sports industry in China.

This study develops a systematic modeling framework, comprising a prediction model, a super-SBM model, and a spatial autocorrelation analysis model, to explore the spatial-temporal evolution tendencies of development efficiency within China's 30 regions in the low-carbon sports industry from 2006 to 2025. This framework aims to provide theoretical insights for the formulation of more targeted policies. Based on the empirical findings, the main conclusions of this study are as follows: (1) The optimal buffer operator grey prediction model demonstrates the highest accuracy among the prediction models examined. (2) The development efficiency curves of the 30 regions exhibit a significant increasing trend from 2006 to 2021, with values generally peaking between 0.4 and 0.6. (3) Notably, the disparity in development efficiency between developed and less developed regions is expected to progressively widen. (4) The development efficiency of the low-carbon sports industry across the 30 regions typically displays high-high clustering and low-low clustering during China's four five-year plan periods. This underscores the importance and urgency of promoting regional coordinated development within the low-carbon sports industry.

Nano-induced endothelial leakiness-reversing nanoparticles for targeting, penetration and restoration of endothelial cell barrier.

Nano-induced endothelial leakiness (NanoEL) can improve the ability of nanoparticles (NPs) to enter the tumor environment, nevertheless, it can inadvertently trigger adverse effects such as tumor metastasis. To overcome these concerns, it becomes important to develop a NPs design strategy that capitalizes on the NanoEL effect while averting unwanted side effects during the drug delivery process. Herein, we introduce the PLGA-ICG-PEI-Ang1@M NP which has a core comprising poly (lactic-co-glycolic acid) (PLGA) and the inner shell with a highly positively charged polyethyleneimine (PEI) and the anti-permeability growth factor Angiopoietin 1 (Ang1), while the outer shell is camouflaged with a Jurkat cell membrane. During the drug delivery process, our NPs exhibit their capability to selectively target and penetrate endothelial cell layers. Once the NPs penetrate the endothelial layer, the proton sponge effect triggered by PEI in the acidic environment surrounding the tumor site can rupture the cell membrane on the NPs' surface. This rupture, in turn, enables the positively charged Ang1 to be released due to the electrostatic repulsion from PEI and the disrupted endothelial layer can be restored. Consequently, the designed NPs can penetrate endothelial layers, promote the cell layer recovery, restrict the tumor metastasis, and facilitate efficient cancer therapy. STATEMENT OF SIGNIFICANCE.

Acid-degradable nanocomposite hydrogel and glucose oxidase combination for killing bacterial with photothermal augmented chemodynamic therapy.

Bacterial infection often delays diabetic wound healing, and even causes serious life-threatening complications. Herein, we successfully developed a Cu2O/Pt nanocubes-dopping alginate (ALG)- hyaluronic acid (HA) hydrogel (Cu2O/Pt hydrogel) by simple assembly of the Cu2O/Pt nanocubes and the ALG-HA mixture. The Cu2O/Pt hydrogel combined with the glucose oxidase (GOx) can be used for photothermal- and starving-enhanced chemodynamic therapy (CDT) against Gram-negative and Gram-positive bacteria. The GOx can catalyze the glucose to produce gluconic acid and H2O2 for starvation therapy, following which the released Cu2O/Pt nanocubes react with H2O2 in the acidic microenvironment to generate highly cytotoxic hydroxyl radicals (·OH) for CDT. Additionally, the Cu2O/Pt hydrogel can release copper ions gradually with the decrease of pH induced by gluconic acid, which can increase the protein expression and secretion of vascular endothelial growth factor (VEGF) and promote endothelial cell proliferation, migration and angiogenesis, subsequently promoting diabetic wound healing in rats. Our results suggested that the Cu2O/Pt hydrogel combined with GOx may be a potential therapeutic approach for treating the infected diabetic wound.

Promotion of diabetic wound healing using novel Cu2O/Pt nanocubes through bacterial killing and enhanced angiogenesis in rats.

Chronic bacterial infection, local inflammation, and insufficient angiogenesis contribute to poor healing of diabetic wounds. Here, Cu2O/Pt nanocubes (CPN) are successfully developed with good biocompatibility for treatment of diabetic wounds in rats. The synthesized CPN are characterized using SEM, XPS, and XRD. CPN exhibit triple-enzyme mimetic activity: oxidase-like, peroxidase-like, and catalase-like activities. Moreover, CPN show significant antibacterial activity against Gram-negative and Gram-positive bacteria when combined with low concentration of H2O2, via generation of highly reactive ROS. CPN also exhibit significantly accelerated wound healing in a full-layer deprivation rat model infected by Staphylococcus aureus, which is ascribed to the constant release of copper ions, subsequently activating the VEGF/AKT/ERK1/2 signaling pathway and promoting angiogenesis. CPN are able to catalyze H2O2 to generate O2 for local hypoxia alleviation. Furthermore, in vivo results indicate that treatment with CPN promotes the expression of transforming growth factor and matrix metalloproteinases, causing enhanced cell proliferation and collagen deposition, as well as extracellular matrix remodeling. In contrast, CPN decrease the expression of proinflammatory cytokines, such as TNF-ɑ and IL-1ß, which are induced by bacterial infection and hyperglycemia. These results suggest a novel strategy for the treatment of diabetic wound healing.

An electrochemical sensor based on single-stranded DNA-poly(sulfosalicylic acid) composite film for simultaneous determination of adenine, guanine, and thymine.

Poly(sulfosalicylic acid) and single-stranded DNA composite (PSSA-ssDNA)-modified glassy carbon electrode (GCE) was prepared by electropolymerization and then successfully used to simultaneously determine adenine (A), guanine (G), and thymine (T). The characterization of electrochemically synthesized PSSA-ssDNA film was investigated by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). The modified electrode exhibited enhanced electrocatalytic behavior and good stability for the simultaneous determination of A, G, and T in 0.1M phosphate buffer solution (PBS, pH 7.0). Well-separated voltammetric peaks were obtained among A, G, and T presented in the analyte mixture. Under the optimal conditions, the peak currents for A, G, and T increased linearly with the increase of analyte mixture concentration in the ranges of 6.5×10(-8) to 1.1×10(-6), 6.5×10(-8) to 1.1×10(-6), and 4.1×10(-6) to 2.7×10(-5)M, respectively. The detection limits (signal/noise=3) for A, G, and T were 2.2×10(-8), 2.2×10(-8), and 1.4×10(-6)M, respectively.

Quantitative Analysis of Protein Corona on Precoated Protein Nanoparticles and Determined Nanoparticles with Ultralow Protein Corona and Efficient Targeting in Vivo.

The protein corona on nanoparticles (NPs) is a critical problem that often screens the targeting molecules and becomes one of the key reasons for the lack of practical application in nanotherapy. It is critical to fully understand the mechanism of the nanoparticle-biological interactions to design the nanoparticle-based therapeutic agents. Some types of proteins can be precoated on the nanoparticles to avoid unwanted protein attachment; however, the ultralow level of protein corona is hard to achieve, and the relationship of the antifouling property of the precoated protein nanoparticles with protein conformation and protein-nanoparticle interaction energy has never been investigated. In this work, we provided the quantitative protein corona composition analysis on different precoated protein nanoparticles, and on the basis of the molecular simulation process, we found their antifouling property strongly depended on the interaction energy of the precoated protein-serum protein pair and the number of hydrogen bonds formed between them. Furthermore, it also depended on the nanoparticle-serum protein pair interaction energy and the protein conformation on the nanoparticle. The casein coated nanoparticle with the antifouling property was determined, and after aptamer conjugation and drug loading, they exhibited superior targeting and internalization behavior for photodynamic and photothermal therapy in vitro and in vivo. Our work adds to the understanding of the protein corona behavior of precoated protein nanoparticles, and the determined antifouling NP can potentially be used as a highly efficient nanodrug carrier.