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Anti-Infection Efficacy, Osteogenesis Potential, and Biocompatibility of 3D Printed PLGA/Nano-Hydroxyapatite Porous Scaffolds Grafted with Vancomycin/DOPA/rhBMP-2 in Infected Rabbit Bone Defects
Given the limitations of traditional therapies, the treatment of infected bone defects (IBD) remains a great challenge. It is urgent to find a novel method that can simultaneously eradicate infection and promote new bone formation. With the increasing application of personalized scaffolds in orthopedics, novel biomaterials with both antibacterial and osteoinductive properties have provided a viable option for IBD treatment. Through the three-dimensional (3D) printing technology, we fabricated a poly(lactic-co-glycolic acid)(PLGA)/nano-hydroxyapatite (n-HA) composite scaffold grafted with the antibiotic vancomycin and loaded with the osteoinductive agent recombinant human bone morphogenic protein-2 (rhBMP-2) via polydopamine (DOPA) chemistry, whose therapeutic effects on IBD were determined.
After examining the hydrophilicity, surface chemical composition, mechanical properties, and drug release of the PLGA/n-HA, PLGA/n-HA/VAN, and PLGA/n-HA/VAN+DOPA/rhBMP-2 composite scaffolds, pre-osteoblast MC3T3-E1 cells were seeded onto the scaffold surface to assess the biocompatibility and osteoconductive properties of the scaffolds in vitro. For in vivo experiments, the composite scaffolds contaminated with
were implanted into the defect sites of rabbit radius. After 12 weeks, micro-CT analysis, H&E and Masson staining, immunohistochemistry, and viable bacteria counting were conducted to compare the effects of three composite scaffolds on new bone formation and bone infection.
The surface modification with DOPA/rhBMP-2 increased the hydrophilicity of PLGA/n-HA scaffolds. Vancomycin and BMP-2 were continuously and regularly eluted from the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds. The PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds promoted MC3T3-E1 cell survival and proliferation and enhanced ALP activity and calcium deposition compared with the PLGA/n-HA and PLGA/n-HA/VAN scaffolds. Additionally, the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds significantly facilitated new bone formation and inhibited bone infection in IBD rabbit models. The rabbits implanted with the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds exhibited normal heart, lung, and kidney histologies and normal serum biochemical indices, suggesting the safety of the scaffolds.
The 3D-printed PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds exhibited both antibacterial and osteoinductive activities in IBD.
Journal Article
Modeling Road Accident Severity with Comparisons of Logistic Regression, Decision Tree and Random Forest
To reduce the damage caused by road accidents, researchers have applied different techniques to explore correlated factors and develop efficient prediction models. The main purpose of this study is to use one statistical and two nonparametric data mining techniques, namely, logistic regression (LR), classification and regression tree (CART), and random forest (RF), to compare their prediction capability, identify the significant variables (identified by LR) and important variables (identified by CART or RF) that are strongly correlated with road accident severity, and distinguish the variables that have significant positive influence on prediction performance. In this study, three prediction performance evaluation measures, accuracy, sensitivity and specificity, are used to find the best integrated method which consists of the most effective prediction model and the input variables that have higher positive influence on accuracy, sensitivity and specificity.
Journal Article
Luteolin Inhibits Tumorigenesis and Induces Apoptosis of Non-Small Cell Lung Cancer Cells via Regulation of MicroRNA-34a-5p
Luteolin (LTL) exerts remarkable tumor suppressive activity on various types of cancers, including non-small cell lung cancer (NSCLC). However, it is not completely understood whether the mechanism of its action against NSCLC is related to microRNAs (miRNAs). In the present study, we investigated the anti-tumor effects of LTL on NSCLC in vitro and in vivo. The results revealed that LTL could inhibit cell proliferation and induce apoptosis in both A549 and H460 cells. In a H460 xenograft tumor model of nude mice, LTL significantly suppressed tumor growth, inhibited cell proliferation, and induced apoptosis. miRNA microarray and quantitative PCR (qPCR) analysis indicated that miR-34a-5p was dramatically upregulated upon LTL treatment in tumor tissues. Furthermore, MDM4 was proved to be a direct target of miR-34a-5p by luciferase reporter gene assay. LTL treatment was associated with increased p53 and p21 protein expressions and decreased MDM4 protein expression in both NSCLC cells and tumor tissues. When miR-34a-5p was inhibited in vitro, the protein expressions of Bcl-2 and MDM4 were recovered, while that of p53, p21, and Bax were attenuated. Moreover, caspase-3 and caspase-9 activation induced by LHL treatment in vitro were also suppressed by miR-34a-5p inhibition. Overall, LTL could inhibit tumorigenesis and induce apoptosis of NSCLC cells by upregulation of miR-34a-5p via targeting MDM4. These findings provide novel insight into the molecular functions of LTL that suggest its potential as a therapeutic agent for human NSCLC.
Journal Article
Fe-S dually modulated adsorbate evolution and lattice oxygen compatible mechanism for water oxidation
Simultaneously activating metal and lattice oxygen sites to construct a compatible multi-mechanism catalysis is expected for the oxygen evolution reaction (OER) by providing highly available active sites and mediate catalytic activity/stability, but significant challenges remain. Herein, Fe and S dually modulated NiFe oxyhydroxide (R-NiFeOOH@SO
4
) is conceived by complete reconstruction of NiMoO
4
·xH
2
O@Fe,S during OER, and achieves compatible adsorbate evolution mechanism and lattice oxygen oxidation mechanism with simultaneously optimized metal/oxygen sites, as substantiated by in situ spectroscopy/mass spectrometry and chemical probe. Further theoretical analyses reveal that Fe promotes the OER kinetics under adsorbate evolution mechanism, while S excites the lattice oxygen activity under lattice oxygen oxidation mechanism, featuring upshifted O 2
p
band centers, enlarged d-d Coulomb interaction, weakened metal-oxygen bond and optimized intermediate adsorption free energy. Benefiting from the compatible multi-mechanism, R-NiFeOOH@SO
4
only requires overpotentials of 251 ± 5/291 ± 1 mV to drive current densities of 100/500 mA cm
−2
in alkaline media, with robust stability for over 300 h. This work provides insights in understanding the OER mechanism to better design high-performance OER catalysts.
The oxygen evolution reaction is crucial for energy conversion but faces challenges in catalyst optimization. Here, the authors present a dual-modulated NiFe oxyhydroxide (R-NiFeOOH@SO4) that enhances OER performance through optimized metal and lattice oxygen sites, achieving a compatible multi-mechanism.
Journal Article
Regional economic resilience and sustainable development: Does industrial diversity matter?
Regional sustainable development is a fundamental pathway toward achieving long-term economic stability, social equity, and ecological balance. Particularly in the face of unexpected shocks and systemic risks, economic resilience plays a critical role in ensuring the attainment of sustainability goals. Drawing on endogenous growth theory and dynamic capabilities theory, this study focuses on 31 provincial-level administrative divisions in mainland China as the target regions, utilizing panel data from 2004 to 2023 to empirically examine the relationships. The baseline regression results indicate a significant positive effect of economic resilience on sustainable development. Moderation analysis further reveals that industrial diversification, human capital, and environmental regulation significantly enhance the positive impact of resilience. Mediation tests show that economic resilience promotes sustainable development indirectly by improving the level of marketization. Heterogeneity analysis confirms that the impact of economic resilience on sustainable development varies significantly across regions. The findings of this study provide a scientific basis for governments to formulate more effective risk-mitigation policies and for firms to identify more stable regions for investment.
Journal Article