NOD2 attenuates osteoarthritis via reprogramming the activation of synovial macrophages.

OBJECTIVE: Synovial inflammation, which precedes other pathological changes in osteoarthritis (OA), is primarily initiated by activation and M1 polarization of macrophages. While macrophages play a pivotal role in the inflammatory process of OA, the mechanisms underlying their activation and polarization remain incompletely elucidated. This study aims to investigate the role of NOD2 as a reciprocal modulator of HMGB1/TLR4 signaling in macrophage activation and polarization during OA pathogenesis. DESIGN: We examined NOD2 expression in the synovium and determined the impact of NOD2 on macrophage activation and polarization by knockdown and overexpression models in vitro. Paracrine effect of macrophages on fibroblast-like synoviocytes (FLS) and chondrocytes was evaluated under conditions of NOD2 overexpression. Additionally, the in vivo effect of NOD2 was assessed using collagenase VII induced OA model in mice. RESULTS: Expression of NOD2 was elevated in osteoarthritic synovium. In vitro experiments demonstrated that NOD2 serves as a negative regulator of HMGB1/TLR4 signaling pathway. Furthermore, NOD2 overexpression hampered the inflammatory paracrine effect of macrophages on FLS and chondrocytes. In vivo experiments revealed that NOD2 overexpression mitigated OA in mice. CONCLUSIONS: Supported by convincing evidence on the inhibitory role of NOD2 in modulating the activation and M1 polarization of synovial macrophages, this study provided novel insights into the involvement of innate immunity in OA pathogenesis and highlighted NOD2 as a potential target for the prevention and treatment of OA.

STING/TBK1 Regulates Inflammation in Macrophages and Titanium Particles-Induced Osteolysis.

Inflammatory response in macrophages on account of prostheses-derived wear particles is the leading cause of artificial joint failure. However, the mechanism by which wear particles initiate macrophage inflammation has not been fully elucidated. Previous research studies have identified TANK-binding kinase 1 (TBK1) and stimulator of interferon genes (STING) as potential factors in inflammation and autoimmune diseases. Here, we found that both TBK1 and STING were increased in synovium from aseptic loosening (AL) patients and were activated in titanium particles (TiPs)-stimulated macrophages. Lentivirus-mediated knockdown of TBK or STING significantly inhibited the inflammatory effects of macrophages, while overexpression of TBK or STING exerted opposite results. In concrete, STING/TBK1 promoted the activation of NF-κB and IRF3 pathways and macrophage M1 polarization. For further validation, a mice cranial osteolysis model was constructed for in vivo assays, and we found that STING-overexpressed lentivirus injection exacerbated osteolysis and inflammation, which was counteracted by TBK1-knockdown injection. In conclusion, STING/TBK1 enhanced TiP-induced macrophage inflammation and osteolysis via orchestrating the activation of NF-κB and IRF3 pathways and M1 polarization, which suggested STING/TBK1 as potential therapeutic targets for preventing AL of prostheses.

Experimental modeling and application of push-pull electrostatic speakers.

This study modeled the circular diaphragm of push-pull electrostatic speakers using electro-mechano-acoustical equivalent circuits to determine the frequency responses related to the average displacement and sound pressure of the diaphragm with respect to acoustic impedance effects. A laser vibrometer system was used to measure the displacement in the center of the circular diaphragms (60 mm and 65 mm in diameter) in optically transparent indium tin oxide (ITO) electrostatic speakers. The sound pressure levels (SPLs) were predicted using the average displacement of the diaphragm without resorting to sound field measurements or finite element analysis. The predicted SPL results were then compared to acoustic measurements. The results demonstrate that ITO plates are a practical tool for the measurement of displacement and the prediction of SPLs. When the proposed electrostatic speaker (65-mm-diameter diaphragm) design was applied to the over-ear electrostatic headphone, the SPL curve obtained from artificial ear measurements was similar to the preferred target curve of Harman International (Stamford, CT). This resulted in outstanding sound quality comparable to that of high-end commercial dynamic headphones.

Vibration and sound radiation of an electrostatic speaker based on circular diaphragm.

This study investigated the lumped parameter method (LPM) and distributed parameter method (DPM) in the measurement of vibration and prediction of sound pressure levels (SPLs) produced by an electrostatic speaker with circular diaphragm. An electrostatic speaker with push-pull configuration was achieved by suspending the circular diaphragm (60 mm diameter) between two transparent conductive plates. The transparent plates included a two-dimensional array of holes to enable the visualization of vibrations and avoid acoustic distortion. LPM was used to measure the displacement amplitude at the center of the diaphragm using a scanning vibrometer with the aim of predicting symmetric modes using Helmholtz equations and SPLs using Rayleigh integral equations. DPM was used to measure the amplitude of displacement across the entire surface of the speaker and predict SPL curves. LPM results show that the prediction of SPL associated with the first three symmetric resonant modes is in good agreement with the results of DPM and acoustic measurement. Below the breakup frequency of 375 Hz, the SPL predicted by LPM and DPM are identical with the results of acoustic measurement. This study provides a rapid, accurate method with which to measure the SPL associated with the first three symmetric modes using semi-analytic LPM.

High-frequency resonant characteristics of triple-layered piezoceramic bimorphs determined using experimental measurements and theoretical analysis.

This is an experimental, theoretical, and numerical investigation of vibration characteristics in high-frequency resonance, which are studied for parallel- and series-type piezoelectric bimorphs. In the experimental measurements, the full-field optical technique known as electronic speckle pattern interferometry (ESPI) is used to measure the transverse (out-of-plane) and planar (in-plane) resonant frequencies and corresponding mode shapes for piezoelectric bimorphs. In addition, in-plane resonant frequencies are obtained from impedance analysis and the response curves of the frequency spectra show different vibration characteristics of the piezoelectric bimorphs with different electrical connections. Piezoelectric bimorphs with normal connections have three-dimensional coupled vibration characteristics and the out-of-plane vibration dominates the motion. However, only in-plane vibration motions can be excited in the high-frequency range for abnormal connections, and the resonant characteristics are similar to the single-layered piezoelectric plate. The triple-layered piezoelectric bimorphs with abnormal connection are also analyzed using theoretical analysis. The resonant frequencies, mode shapes, and normalized displacements are calculated based on the analytical solution. The experimental results and the theoretical analysis are in good agreement with the numerical calculations using the finite element method. From the discussion of the results for the parallel- and series-type piezoelectric bimorphs with normal and abnormal connections, the vibration characteristics at high frequencies are completely analyzed in this study.

Experimental measurements and finite element analysis of the coupled vibrational characteristics of piezoelectric shells.

Piezoelectric plates can provide low-frequency transverse vibrational displacements and high-frequency planar vibrational displacements, which are usually uncoupled. However, piezoelectric shells can induce three-dimensional coupled vibrational displacements over a large frequency range. In this study, three-dimensional coupled vibrational characteristics of piezoelectric shells with free boundary conditions are investigated using three different experimental methods and finite element numerical modeling. For the experimental measurements, amplitude-fluctuation electronic speckle pattern interferometry (AF-ESPI) is used to obtain resonant frequencies and radial, lateral, and angular mode shapes. This optical technique utilizes a real-time, full-field, non-contact optical system that measures both the natural frequency and corresponding vibration mode shape simultaneously. The second experimental technique used, laser Doppler vibrometry (LDV), is a pointwise displacement measurement method that determines the resonant frequencies of the piezoelectric shell. An impedance analyzer is also used to determine the resonant frequencies of the piezoelectric shell. The experimental results of the resonant frequencies and mode shapes for the piezoelectric shell are verified with a numerical finite element model. Excellent agreement between the experimental and numerical results is found for the three-dimensional coupled vibrational characteristics of the piezoelectric shell. It is noted in this study that there is no coupled phenomenon at low frequencies over which radial modes dominate. However, three-dimensional coupled vibrational modes do occur at high resonant frequencies over which lateral or angular modes dominate.

Investigation of the transient behavior of a cantilever beam using PVDF sensors.

In this paper, a PVDF film sensor was used to measure the transient responses of a cantilever beam subjected to an impact loading. The measurement capability of a PVDF sensor is affected by the area of the PVDF film sensor and the signal conditioner (charge amplifier). The influences of these effects on the experimental measurements were investigated. The transient responses for the dynamic strain of the beam were measured simultaneously by the PVDF sensor and a conventional strain gauge. The resonant frequencies of the beam were determined by applying the Fast Fourier Transform on transient results in the time domain of the PVDF sensor and the strain gauge. The experimentally measured resonant frequencies from the PVDF sensor and the strain gauge were compared with those predicted from theoretical and FEM numerical calculations. Based on the comparison of the results measured for these two sensors, the PVDF film sensor proved capable of measuring transient responses for dynamic strain, and its sensitivity is better than that of the strain gauge. Furthermore, almost all the resonant frequencies can be obtained from the results of transient responses for PVDF film.

Mode excitation efficiency for contour vibrations of piezoelectric resonators.

This paper addresses a theoretical procedure for control of the contour mode excitation efficiency in thin piezoelectric arbitrarily-shaped resonators by adjusting the surface electrode configuration to the mechanical stress distribution. The procedure allows accurate determination of at least five efficiently excited modes for various electrode configurations. This is validated by experimentally measured data for rectangular resonators. For the first time, electrode configurations are suggested that provide high values of the dynamic electromechanical coupling factor for the longitudinal edge mode in a rectangular resonator, while the excitation of spurious modes is suppressed.

Experimental and numerical investigations of vibration characteristics for parallel-type and series-type triple-layered piezoceramic bimorphs.

The dynamic characteristics of parallel-type and series-type piezoelectric bimorphs are analyzed in this study. The transverse (out-of-plane) and planar (in-plane) vibrations for piezoceramic bimorphs in normal and abnormal connections are investigated experimentally by 2 noncontact optical techniques and impedance analyzer. Electronic speckle pattern interferometry (ESPI) is the major experimental technique for measuring the resonant frequency and corresponding vibration mode shape. Out-of-plane and in-plane vibrations of piezoelectric bimorphs at resonance are obtained by a self-arranged ESPI optical setup. The laser Doppler vibrometer (LDV) is a point-wise measurement technique for out-of-plane displacement and is used to determine the out-of-plane resonant frequencies. The impedance analyzer is used to measure the resonant frequencies for in-plane motions. It is noted from the experimental results that the out-of-plane modes are the dominant motion for the normal connection and only symmetric vibration mode shapes can be excited. The in-plane motions are large enough to be measured using the ESPI method for normal connections. The in-plane resonant modes are observed for parallel-type piezoelectric bimorph in parallel connections; however, the in-plane mode shapes are similar to the out-of-plane mode shapes for the series-type piezoelectric bimorph in series connection. Hence, the particle motions of the piezoelectric bimorph at resonance are essentially 3-D for the normal connection. It is interesting to note that both symmetric and asymmetric out-of-plane vibration mode shapes can be excited with large applied voltage but no in-plane motion is observed for the abnormal connection. In addition to experimental methods, numerical computations based on the finite element method are used to verify the experimental results. Good agreements of the resonant frequencies and mode shapes are obtained for experimental and numerical results.

Experimental measurement and numerical analysis on resonant characteristics of cantilever plates for piezoceramic bimorphs.

Three experimental techniques are used in this study to access the resonant characteristics of piezoceramic bimorphs in parallel and series connections. These experimental methods, including the amplitude-fluctuation electronic speckle pattern interferometry (AF-ESPI), laser Doppler vibrometer-dynamic signal analyzer (LDV-DSA), and impedance analysis, are based on the measurement of full-field displacement, point-wise displacement, and electric impedance, respectively. Because the clear fringe patterns will be shown only at resonant frequencies, both the resonant frequencies and the corresponding vibration mode shapes are successfully obtained at the same time by the AF-ESPI method. LDV-DSA is used to determine the resonant frequencies of the vibration mode for out-of-plane motion. The impedance analysis is used to measure the resonant and antiresonant frequencies for in-plane motion. Although the out-of-plane mode is the dominant motion of piezoceramic bimorphs, it is found in this study that the amount of displacement for the in-plane motion in parallel connection is large enough to be measured by AF-ESPI and impedance. It is interesting to note that resonant frequencies of the specimen in parallel connection for the out-of-plane motion determined by LDV-DSA are the same as that for the in-plane motion obtained by impedance. Furthermore, both in-plane and out-of-plane mode shapes for the specimen in parallel connection are obtained in the same resonant frequency from the AF-ESPI method. It is concluded in this study that the particle motions of piezoceramic bimorphs for parallel connection in resonance are essentially three-dimensional. However, it is found that only out-of-plane vibration modes can be excited for the specimen in series connection. Numerical computations based on the finite-element method are presented, and the theoretical predicted results are compared with the experimental measurements. Good agreements between the experimental measured data and numerical calculated results are found for resonant frequencies and mode shapes of the piezoceramic bimorph.