Semaglutide outperforms insulin in restoring neutrophil function against implant-related infection in diabetic and obese mice: experimental research.

BACKGROUND: Bone and joint infections (BJI) are a significant complication after arthroplasty and fracture fixation, particularly challenging in patients with type 2 diabetes mellitus (T2DM) and obesity. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), have shown efficacy in managing T2DM and obesity. However, its impact on BJI risk and neutrophil function remains unclear. To investigate whether preoperative semaglutide treatment (1) reduces the risk of BJI in diabetic and obese mice undergoing intra-articular implants, and (2) outperforms insulin in restoring neutrophil function to mitigate implant-related infection. METHODS: A C57BL/6 mouse model of T2DM/obesity was induced using a high-fat diet (HFD) for 12 weeks. Mice received preoperative insulin or semaglutide therapy for 1-28 days. BJI risk was assessed using an intraarticular-implant model challenged with S. aureus or E. coli. Neutrophil function was evaluated through bactericidal activity, superoxide production, and migration ability. RESULTS: Semaglutide treatment led to a significant and sustained reduction in body weight and improved glucose tolerance in HFD mice. Both insulin and semaglutide therapies significantly reduced BJI risk, with semaglutide showing a more pronounced effect over time. Semaglutide therapy also enhanced neutrophil bactericidal activity, superoxide production, and migration ability compared to insulin therapy. CONCLUSIONS: Preoperative semaglutide treatment effectively reduces BJI risk and improves neutrophil function in diabetic and obese mouse models. These findings suggest that semaglutide may be a promising pharmacological intervention to mitigate infection risk in orthopedic patients with T2DM or obesity.

AAV-mediated VEGFA overexpression promotes angiogenesis and recovery of locomotor function following spinal cord injury via PI3K/Akt signaling.

Spinal cord injury (SCI) is a disorder of the central nervous system resulting from various factors such as trauma, inflammation, tumors, and other etiologies. This condition leads to impairment in motor, sensory, and autonomic functions below the level of injury. Limitations of current therapeutic approaches prompt an investigation into therapeutic angiogenesis through persistent local expression of proangiogenic factors. Here, we investigated whether overexpression of adeno-associated virus (AAV)-mediated vascular endothelial growth factor A (VEGFA) in mouse SCI promoted locomotor function recovery, and whether the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway was mechanistically involved. Three weeks before SCI, AAV-VEGFA was injected at the T10 level to induce VEGFA overexpression. Neurofunctional, histological, and biochemical assessments were done to determine tissue damage and/or recovery of neuromuscular and behavioral impairments. Daily injections of the PI3K/Akt pathway inhibitor LY294002 were made to assess a possible mechanism. AAV-VEGFA overexpression dramatically improved locomotor function and ameliorated pathological injury caused by SCI. Improved motor-evoked potentials in hindlimbs and more spinal CD31-positive microvessels were observed in AAV-VEGFA-overexpressing mice. LY294002 reduced PI3K and Akt phosphorylation levels and attenuated AAV-VEGFA-related improvements. In conclusion, sustained local AAV-mediated VEGFA overexpression in spinal cord can significantly promote angiogenesis and ameliorate locomotor impairment after SCI in a contusion mouse model through activation of the PI3K/Akt signaling pathway.

Agile wide-field imaging with selective high resolution.

Wide-field and high-resolution (HR) imaging are essential for various applications such as aviation reconnaissance, topographic mapping, and safety monitoring. The existing techniques require a large-scale detector array to capture HR images of the whole field, resulting in high complexity and heavy cost. In this work, we report an agile wide-field imaging framework with selective high resolution that requires only two detectors. It builds on the statistical sparsity prior of natural scenes that the important targets locate only at small regions of interest (ROI), instead of the whole field. Under this assumption, we use a short-focal camera to image a wide field with a certain low resolution and use a long-focal camera to acquire the HR images of ROI. To automatically locate ROI in the wide field in real time, we propose an efficient deep-learning-based multiscale registration method that is robust and blind to the large setting differences (focal, white balance, etc) between the two cameras. Using the registered location, the long-focal camera mounted on a gimbal enables real-time tracking of the ROI for continuous HR imaging. We demonstrated the novel imaging framework by building a proof-of-concept setup with only 1181 gram weight, and assembled it on an unmanned aerial vehicle for air-to-ground monitoring. Experiments show that the setup maintains 120° wide field of view (FOV) with selective 0.45mrad instantaneous FOV.

Tunable Mechanical Properties of Ti-Zr-Ni-Cr-V Amorphous Ribbons via Different Melt Spinning Speeds during Rapid Solidification Process.

In this paper, the effects of different melt spinning speeds on the mechanical properties of (TiZr)0.5(Ni0.6Cr0.1V0.1)2.1 amorphous ribbons were studied. Tensile tests of the specimens were used to investigate mechanical behavior and mechanical properties of amorphous ribbons. The effects of cooling rate on the glass transition temperature of amorphous ribbons was discussed. The correlation between the microstructure of serrated flow behavior in stress-strain curves and melt spinning speeds of ribbons was also evaluated. In addition, when the spinning speed was 45 m/s, a large number of dense and uniform dimples appeared on the fractured surface of the specimens. Furthermore, characteristics of serrated flow behavior were obvious, which meant that Ti-Zr-Ni-Cr-V amorphous ribbons showed minor plastic behavior. It is assumed that the influence of free volume led to a serrated flow behavior of the amorphous materials, and made the amorphous material exhibit partially plastic properties. Increasing the strain rate sensitivity meant the free volume increased with the increasing spinning speed. Tensile strength (σb) and elongation (δ) of samples exhibited a dramatic increasing trend with an increase in the spinning speed. In particular, Ti-Zr-Ni-Cr-V amorphous ribbons showed better mechanical properties, namely the tensile strength of the amorphous ribbon samples significantly increased from 321 MPa at a spinning speed of 30 m/s to 675 MPa at a speed of 45 m/s. The elongation increased from 0.53% at a speed of 30 m/s to 1.29% at a speed of 45 m/s.