Hua Zhang

Drug-resistant bacterial infections in diabetic wound severely impair healing and may lead to life-threatening complications. Herein, a simple glucose oxidase (GOX) biomineralization nanozyme of GOX@CeO₂ was prepared which was further encapsulated with polydopamine (PDA) nanolayer (GOX@CeO₂@PDA termed as GCP_NPs) for diabetic wounds treatment. Due to the GOX and peroxidase (POD)-like activities of GCP_NPs, the excessive glucose at wound site could be consumed to conduct starvation therapy, which also activated cascade reaction to generate reactive oxygen species (ROS) to achieve chemodynamic therapy (CDT). The synergistic effect of cryogenic photothermal therapy (C-PTT) from PDA nanolayer could boost the wound healing. To further improve the therapy efficiency, biodegradable microneedles (MNs) were prepared to encapsulate the GCP_NPs, facilitating intimate contact between the nanodrugs and the deeper layers of the wound. In vitro and in vivo experimental results demonstrate the remarkable antibacterial property of the GCP_NPs against drug-resistant bacteria via the synergistic function of starvation therapy, CDT and C-PTT, which could promote epidermal tissue formation and collagen deposition to accelerate wound healing with negligible damage to healthy tissues. The consumption of glucose also contributes to the recovery of diabetic mice. These results highlight the potential of GCP_NPs in the treatment of bacterial infected diabetic wounds. Graphical abstract The alternative text for this image may have been generated using AI.

Janus Fe/FeO _x particles encapsulated within a nitrogen-doped carbon shell are developed for bifunctional oxygen electrocatalysis.

Lateral flow immunochromatography (LFIA) with gold nanoparticles (AuNPs) is widely used in the biomedical field as a rapid and simple in vitro detection technique. However, the conventional AuNP-LFIA has limitations in sensitivity and detection range. In this study, nonprecious metal iron-based bimetallic FeWO₄ nanomaterials with convenient and excellent enzyme-mimetic catalytic activities were synthesized by a one-pot hydrothermal method. Here, FeWO₄ nanomaterials were combined with C-reactive protein (CRP) detection antibodies to form a novel signal-enhancing probe for the analysis of CRP. The probe further achieves significant signal amplification by catalyzing the oxidation reaction of 3-amino-9-ethylcarbazole in the LFIA assay, thereby improving the sensitivity and accuracy of the assay. The application of FeWO₄-based LFIA improved the limit of detection of CRP to 19.38 ng/mL after catalytic amplification, which is approximately 30-fold lower than that of the conventional AuNP-LFIA method. In addition, the method demonstrated good stability and reproducibility, providing a promising and prospective strategy for the early diagnosis of inflammatory diseases.

Coronavirus epidemics have posed a serious threat to both human and animal health. To combat emerging infectious diseases caused by coronaviruses, various animal infection models have been developed and applied in research, including non-human primate models, ferret models, hamster models, mouse models, and others. Moreover, new approaches have been utilized to develop animal models that are more susceptible to infection. These approaches include using viral delivery methods to induce the expression of viral receptors in mouse tissues and employing gene-editing techniques to create genetically modified mice. This has led to the successful establishment of infection models for multiple coronaviruses, significantly advancing related research. In contrast, livestock and pets that can be infected by animal coronaviruses provide valuable insights when used as infection models, enabling the collection of accurate clinical data through the analysis of post-infection pathological features. However, despite the potential insights, there is a paucity of research data pertaining to these infection models. In this review, we provide a detailed overview of recent progress in the development of animal models for coronaviruses that cause diseases in both humans and animals and suggest ways in which animal models can be adapted to further enhance their value in research.

The interaction between electrocatalytic active centers and their support is essential to the electrocatalytic performance, which could regulate the electronic structure of the metal centers but requires precise design. Herein, we report on covalent grafting of graphene quantum dots (GQDs) on stepped TiO₂ as a support to anchoring cobalt phosphide nanoparticles (CoP/GQD/S-TiO₂) for electrocatalytic hydrogen evolution reaction (HER). The covalent ester bonds between GQDs and TiO₂ endow enlarged anchoring sites to achieve highly dispersed electroactive CoP nanoparticles but, more importantly, provide an efficient electron-transfer pathway from TiO₂ to GQDs which could regulate the electronic structure of CoP. Therefore, such CoP/GQD/S-TiO₂ exhibits a superior electrocatalytic HER performance compared with CoP/S-TiO₂, exhibiting a mass activity which is 6.3 times that of the CoP/S-TiO₂ counterpart and long-term stability over 100 h electrolysis. Mechanistic studies reveal that sufficient electron transfer occurs from TiO₂ to the π-conjunction in GQDs via the Ti-C-P pathway and further injects into grafted Co centers, inducing the formation of electron-rich Co centers to enrich and stabilize the hydrated alkaline cations (AC⁺) for facilitated alkaline HER kinetics. Our study provides a new idea for electronic structure engineering of catalysts via covalent bonding toward boosted electrocatalysis.

Accurate detection of multiple cardiovascular biomarkers is crucial for the timely screening of acute coronary syndrome (ACS) and differential diagnosis from acute aortic syndrome (AAS). Herein, an antibody microarray-based metal-enhanced fluorescence assay (AMMEFA) has been developed to quantitatively detect 7 cardiovascular biomarkers through the formation of a sandwich immunoassay on the poly(glycidyl methacrylate-co-2-hydroxyethyl methacrylate)-decorated GNR-modified slide (GNR@P(GMA-HEMA) slide). The AMMEFA exhibits high specificity and sensitivity, the linear ranges span 5 orders of magnitude, and the limits of detection (LODs) of cardiac troponin I (cTnI), heart-type fatty acid binding protein (H-FABP), C-reactive protein (CRP), copeptin, myoglobin, D-Dimer, and N-terminal pro-brain natriuretic peptide (NT-proBNP) reach 0.07, 0.2, 65.7, 0.6, 0.2, 8.3, and 0.3 pg mL^-1, respectively. To demonstrate its practicability, the AMMEFA has been applied to quantitatively analyze 7 cardiovascular biomarkers in 140 clinical plasma samples. In addition, the expression levels of cardiovascular biomarkers were analyzed by the least absolute shrinkage and selector operator (LASSO) regression, and the area under receiver operator characteristic curves (AUCs) of healthy donors (HDs), ACS patients, and AAS patients are 0.99, 0.98, and 0.97, respectively.

A simple fluorescence resonance energy transfer (FRET) sensing platform (termed as USP), comprised of upconversion nanoparticles (UCNPs) as the energy donor and Cy5 as the energy acceptor, has been synthesized for cathepsin B (CTSB) activity detection in vitro and in vivo. When Cy5-modified peptide substrate (peptide-Cy5) of CTSB is covalently linked on the surface of UCNPs, the FRET between the UCNPs (excitation: 980 nm; emission: 541 nm/655 nm) and Cy5 (excitation: 645 nm) leads to a reduction in the red upconversion luminescence (UCL) signal intensity of UCNPs. Cy5 can be liberated from UCNPs in the presence of CTSB through the cleavage of peptide-Cy5 by CTSB, leading to the recovery of the red UCL signal of UCNPs. Because the green UCL signal of UCNPs remains constant during the CTSB digestion, it can be considered as an internal reference. The findings demonstrate the ability of USP to detect CTSB with the linear detection ranges of 1 to 100 ng·mL⁻¹ in buffer and 2 × 10³ to 1 × 10⁵ cells in 0.2 mL cell lysates. The limits of detection (LODs) are 0.30 ng·mL⁻¹ in buffer and 887 cells in 0.2 mL of cell lysates (S/N = 3). The viability of USP to detect CTSB activity in tumor-bearing mice is has further been investigated using in vivo fluorescent imaging. Graphical abstract

Because of the abnormal upregulation of matrix metalloproteinase (MMP) activities in tumors, MMP inhibitors (MMPIs) are validated anticancer drug candidates. We identified several MMPIs including mangiferin as an MMP-9 inhibitor with a half maximal inhibitory concentration (IC₅₀) value of 250 nM, isosilybin as an MMP-13 inhibitor with an IC₅₀ value of 250 nM, and isoliquiritigenin as a broad-spectrum MMPI (with IC₅₀ values of 16 nM for MMP-1, 10 nM for MMP-2, 81 nM for MMP-3, 8 nM for MMP-7, 10 nM for MMP-9, and 14 nM for MMP-13) through studying the interactions of 6 MMPs secreted by U-2OS cells with 51 phenolic natural products on the peptide microarray platform. In addition, the inhibitory mechanisms of as-discovered MMPIs were evaluated by a molecular docking simulation. The antitumor efficiencies of MMPIs were demonstrated by both a cell scratch test and growth suppression of mouse-born OS tumors. The results of the cell scratch test suggested that isoliquiritigenin significantly inhibited the migration of U-2OS cells. In addition, administration of isoliquiritigenin significantly reduced the tumor size (by about 80%) and prolonged the survival time (by more than 70 days). This study suggests that the discovery of MMPIs from phenolic natural products is a meaningful way to screen anticancer agents.