Accumulation of senescent cells in the elderly impairs bone homeostasis. It is important to alleviate cell senescence and scavenge excessive oxidative stress for enhanced bone fracture healing in elderly patients. In this study, resveratrol (RSV), an antioxidant drug, was encapsulated in a biocompatible zeolitic imidazolate framework-8 (ZIF-8) nanoparticle to protect it from oxidation and improve its bioavailability. Cells responsible for bone healing, including osteoblasts, bone marrow-derived mesenchymal stem cells (BMSCs), macrophages, and endothelial cells, were used to evaluate the regulatory role of the nanoformulation in the alleviation of cellular senescence and promotion of cell functions. It was proved that the nanoformulation sustainably released RSV with well-preserved bioactivity and improved bioavailability. Cell experiments confirmed that ZIF-8/RSV was capable of alleviating the senescence of cells [human osteoblasts (HOBs), BMSCs, H2O2-induced senescent vascular endothelial cells (HUVECs)] and scavenging excessive intracellular reactive oxygen species (ROS). Excitingly, the ZIF-8/RSV improved the osteogenic ability of senescent osteoblasts and promoted macrophage M2 polarization. In addition, the ZIF-8/RSV also enhanced the angiogenic function of senescent HUVECs. More importantly, the ZIF-8/RSV nanoformulation outperformed the REV alone, indicating the critical role of encapsulation using ZIF-8. These findings suggest that the ZIF-8/RSV nanoformulation exhibits potential for bone fracture treatment in elderly patients.
Chang’E-7 will be launched around 2026 to explore resources at the lunar south pole. Glaciers are suitable scenes on the earth for lunar penetrating radar verification. In the verification experiment, ice-penetrating signals are inevitably polluted by noise, affecting the accuracy and reliability of glacier detection. This paper proposes a denoising method for ice-penetrating signals based on the combination of whale optimization algorithm (WOA), variational mode decomposition (VMD), and the improved Bhattacharyya distance (BD). Firstly, a fitness function for WOA is established based on permutation entropy (PE), and the number of decomposition modes K and the quadratic penalty factor α in the VMD are optimized using WOA. Then, VMD is performed on the signal to obtain multiple intrinsic mode functions (IMFs). Finally, according to the BD, the relevant IMFs are selected for signal reconstruction and denoising. The simulation results indicate the strengths of this method in enhancing the signal-to-noise ratio (SNR), and its performance is better than empirical mode decomposition (EMD). Experiments on the detected signals of the Mengke Glacier No. 29 indicate that the WOA-VMD-BD method can efficiently eliminate noise from the data and procure well-defined layered profiles of the glacier. The research in this paper helps observe the layered details of the lunar regolith profile and interpret the data in subsequent space exploration missions.
Bispecific T-cell engager (BiTE) immunotherapy is a promising therapy for cancer treatment. However, the high cost and short life-time in vivo of the BiTE limit its wide clinical application. Here, we built for the first time a gene delivery system based on MIL-88A metal organic framework nanoparticles and minicricle DNA (MOF/MC) to realize high-efficient in vivo expression of anti-CD3/anti-EpCAM BiTE. X-ray photoelectron spectroscopy (XPS) and dynamic light scattering (DLS) analysis verified that MC molecules were loaded onto MOF nanoparticles through metal-phosphate bonds and electrostatic interactions. It is found that intraperitoneal injection (i.p.) of MOF/MC suspensions showed good transfection performance in mice abdominal cavity with low toxicity. In an intraperitoneal xenograft mice model established using SKOV3 ovarian cells, i.p. injection of MOF/MC.BiTE significantly inhibited tumor growth and prolonged the average survival time of the mice. Overall, our study demonstrates a simple and highly efficient MOFbased gene delivery system holding promise for effective ovarian cancer immunotherapy. (c) 2020 Elsevier Ltd. All rights reserved.