PTH 1-34 reduced apoptosis of MLO-Y4 osteocyte-like cells by activating autophagy and inhibiting ER stress under RPM conditions.

Osteocytes, as mechanosensitive cells residing within bone tissue, hold a pivotal role in averting the occurrence and progression of osteoporosis. The apoptosis of osteocytes induced by unloading is one of the contributing factors to osteoporosis, although the underlying molecular mechanisms have not been fully elucidated. PTH 1-34 is known to promote bone formation and inhibit bone loss by targeting osteoblasts and osteocytes. However, it is not known whether PTH 1-34 can inhibit osteocyte apoptosis under unloading conditions and the molecular mechanisms involved. In this study, we employed a Random Positioning Machine (RPM) to emulate unloading conditions and cultured MLO-Y4 osteocyte-like cells, in order to unravel the mechanisms through which PTH 1-34 constrains osteocyte apoptosis amidst unloading circumstances. Our findings revealed that PTH 1-34 activated autophagy while suppressing endoplasmic reticulum stress by curtailing the generation of reactive oxygen species (ROS) in MLO-Y4 osteocyte-like cells during unloading conditions. By shedding light on the osteoporosis triggered by skeletal unloading, this study contributes vital insights that may pave the way for the development of pharmacological interventions.

Moderate static magnetic field promotes fracture healing and regulates iron metabolism in mice.

BACKGROUND: Fractures are the most common orthopedic diseases. It is known that static magnetic fields (SMFs) can contribute to the maintenance of bone health. However, the effect and mechanism of SMFs on fracture is still unclear. This study is aim to investigate the effect of moderate static magnetic fields (MMFs) on bone structure and metabolism during fracture healing. METHODS: Eight-week-old male C57BL/6J mice were subjected to a unilateral open transverse tibial fracture, and following treatment under geomagnetic field (GMF) or MMF. The micro-computed tomography (Micro-CT) and three-point bending were employed to evaluate the microarchitecture and mechanical properties. Endochondral ossification and bone remodeling were evaluated by bone histomorphometric and serum biochemical assay. In addition, the atomic absorption spectroscopy and ELISA were utilized to examine the influence of MMF exposure on iron metabolism in mice. RESULTS: MMF exposure increased bone mineral density (BMD), bone volume per tissue volume (BV/TV), mechanical properties, and proportion of mineralized bone matrix of the callus during fracture healing. MMF exposure reduced the proportion of cartilage in the callus area during fracture healing. Meanwhile, MMF exposure increased the number of osteoblasts in callus on the 14th day, and reduced the number of osteoclasts on the 28th day of fracture healing. Furthermore, MMF exposure increased PINP and OCN levels, and reduced the TRAP-5b and ß-CTX levels in serum. It was also observed that MMF exposure reduced the iron content in the liver and callus, as well as serum ferritin levels while elevating the serum hepcidin concentration. CONCLUSIONS: MMF exposure could accelerate fracture healing via promote the endochondral ossification and bone formation while regulating systemic iron metabolism during fracture healing. This study suggests that MMF may have the potential to become a form of physical therapy for fractures.

An efficient performance evaluation method of the traveling wave rotary ultrasonic motor's flexible rotor.

For a traveling wave rotary ultrasonic motor, matching the stator with a proper flexible rotor can be challenging because of the actual contact mechanism's complexity. Due to the lack of effective evaluation and prediction means in the rotor design process, the prototype test is usually needed to truly measure how well it performs, leading to high cost and long design cycle. In order to solve this problem, an efficient performance evaluation method of the flexible rotor based on equivalent contact pressure is proposed. By the key parameters of the flexible rotor's contact surface (area and pressure), an equivalent pressure model of the contact surface is established, which reveals the influence law of the flexible rotor's structural parameters on the motor's output performance. It is doubly verified by dynamics simulation and experiments. The advantage of this method is that without dynamics computation and prototype test, only statics analysis can evaluate the matching score of flexible rotor and target stator quickly and accurately. This study is expected to provide support for the structure design and performance prediction of the traveling wave rotary ultrasonic motor's rotor, in which significant time and cost savings can be achieved.

MRPL51 is a downstream target of FOXM1 in promoting the malignant behaviors of lung adenocarcinoma.

Mitochondrial ribosome protein L51 (MRPL51) is a 39S subunit protein of the mitochondrial ribosome. Its dysregulation may be involved in non-small cell lung cancer. The present study aimed to explore MRPL51 expression in lung adenocarcinoma (LUAD) and normal lung tissues, as well as its regulatory effects on malignant LUAD behaviors. In addition, the role of forkhead box protein M1 (FOXM1) in MRPL51 transcription was studied. Bioinformatics analysis and subsequent in vitro experiments, including western blotting, immunofluorescent staining, Transwell invasion assay, dual-luciferase assay and chromatin immunoprecipitation quantitative PCR were conducted. The results demonstrated that MRPL51 expression was upregulated at both the mRNA and protein levels in LUAD tissues compared with normal lung tissues. Gene Set Enrichment Analysis demonstrated that LUAD tissues with higher MRPL51 expression also had higher expression levels of genes enriched in multiple gene sets, including 'DNA_REPAIR', 'UNFOLDED_PROTEIN_RESPONSE', 'MYC_TARGETS_V1', 'OXIDATIVE_ PHOSPHORYLATION', 'MTORC1_SIGNALING', 'REACTIVE_OXYGEN_SPECIES_PATHWAY', 'MYC_ TARGETS_V2', 'E2F_TARGETS' and 'G2M_ CHECKPOINT'. MRPL51 expression was positively correlated with 'cell cycle', 'DNA damage', 'DNA repair', epithelial-mesenchymal transition ('EMT'), 'invasion' and 'proliferation' of LUAD cells at the single-cell level. Compared to the negative control, MRPL51 knockdown decreased N-cadherin and vimentin expression but increased E-cadherin expression in A549 and Calu-3 cells. MRPL51 knockdown suppressed cell proliferation, induced G1 phase arrest and decreased cell invasion. Patients with LUAD and higher MRPL51 expression had a significantly shorter overall survival (OS). FOXM1 could bind to the MRPL51 gene promoter and activate its transcription. In conclusion, MRPL51 was transcriptionally activated by FOXM1 in LUAD and contributed to the malignant behaviors of tumor cells, including EMT, cell cycle progression and invasion. High MRPL51 expression may be a prognostic biomarker indicating poor OS.

Research on Fast and Precise Positioning Strategy of an Ultrasonic Motor Based on the Ultrasonic Friction Reduction Theory.

To address the problems of the large positioning error and long positioning time of the traditional positioning strategy, namely, the two-phase simultaneous power-off method (TPSPM), a new positioning strategy, called the first single-phase then two-phase power-off method (FSPTTPPM), based on the ultrasonic friction reduction theory, has been proposed in this work. This method realizes zero sliding displacement between the friction material and the stator during the torsional oscillation of the shaft by controlling the driving circle frequency and the duration of the single-phase power-off period, which reduces the deviation of the displacement reservation value. In order to verify the correctness of the driving mechanism, a test platform has been built, and two positioning strategies have been used for experimental verification. The following experimental results have been obtained: compared to TPSPM, FSPTTPPM has the advantages of higher positioning accuracy and short positioning time. In terms of the positioning accuracy, the relative errors of the displacement reservation values of FSPTTPPM and TPSPM vary with the initial angular velocity (0.24 to 1.18 rad/s) in the range of -0.4 to 0.1 and -0.8 to 0.8, respectively. In addition, the relative error of the displacement reservation value is closer to zero than that of TPSPM at the same initial angular velocity. In terms of the positioning time, when the initial angular velocity is greater than 0.7 rad/s, the positioning time of the FSPTTPPM is approximately 10 ms smaller than that of the TPSPM.

Position control method for ultrasonic motors based on beat traveling wave theory.

Focusing on the application demand of ultrasonic motors in the field of space laser communication, a position control method is proposed in this study. Unlike other existing localization methods, this method is based on beat traveling wave theory, which possesses a particular performance in ultrasonic motors. In order to make the speed predictably drop to zero, the frequency difference of the two-phase drive signals is changed during normal operation. This motor deceleration stage is used to establish the positioning scheme. According to this scheme, the finite element analysis with commercial software ADINA is utilized to study the positioning characteristics and support the feasibility, adding details to the scheme. An experimental setup that depends on a DDS signal generator is built to validate this method. The data proves that it can achieve effective average results of about 15 arc-sec under open-loop control at low speed and fluctuate within 0.5 mrad, which can meet the requirement for engineering. Compared to conventional position control methods, it has attractive features of short positioning time, noiseless operation and simple control. This method provides selectivity for engineering applications of ultrasonic motors.

Design and Dynamic Simulation of a Novel Traveling Wave Linear Ultrasonic Motor.

To overcome the problem of frequency consistency and simplify the design process of linear ultrasonic motor, a novel traveling wave linear ultrasonic motor with a ring-type stator is proposed in this paper. The combination of two orthogonal bending vibration modes with the same order is selected as the operating mode of the motor. A traveling wave along the side of the stator is utilized to drive the slider to move linearly. The stator adopts a ring symmetrical structure, which can effectively ensure that the resonance frequencies of the two vibration modes are consistent. Thus, we do not need to tune the frequencies of the two vibrations by constantly adjusting the shape of the stator or designing complex clamping parts to fix the stator without making any influence on the vibrations. Meanwhile, a three-dimensional finite element model of the motor is built. Using the model, we obtain the elliptical motion trajectories of the stator driving surface, the output performance of the motor, the sticking-slipping-separation contact characteristic between the stator and the slider and fabricate and measure a prototype of the proposed motor.

PTH 1-34 promoted bone formation by regulating iron metabolism in unloading-induced bone loss.

PTH 1-34 (teriparatide) is approved by FDA for the treatment of postmenopausal osteoporosis. Iron overload is a major contributing factor for bone loss induced by unloading. Whether iron metabolism is involved in the regulation of PTH 1-34 on unloading-induced osteoporosis has not yet been reported. Here, we found that PTH 1-34 attenuated bone loss in unloading mice. PTH 1-34 regulated the disturbance of iron metabolism in unloading mice by activating Nrf2 and further promoting hepcidin expression in the liver. In addition, the Nrf2 inhibitor selectively blocked hepcidin expression in the liver of unloading mice, which neutralized the inhibitory effect of PTH 1-34 on bone loss and the recovery of iron metabolism in unloading mice. Finally, we found that PTH 1-34 promoted the differentiation and inhibited apoptosis of osteoblasts by regulating iron metabolism and maintaining redox balance under unloading conditions. Our results suggested that PTH 1-34 promoted bone formation by regulating iron metabolism under unloading conditions.

Magnetic fields as a potential therapy for diabetic wounds based on animal experiments and clinical trials.

Diabetes mellitus (DM) is a chronic metabolic disorder with various complications that poses a huge worldwide healthcare burden. Wounds in diabetes, especially diabetic foot ulcers (DFUs), are difficult to manage, often leading to prolonged wound repair and even amputation. Wound management in people with diabetes is an extremely clinical and social concern. Nowadays, physical interventions gain much attention and have been widely developed in the fields of tissue regeneration and wound healing. Magnetic fields (MFs)-based devices are translated into clinical practice for the treatment of bone diseases and neurodegenerative disorder. This review attempts to give insight into the mechanisms and applications of MFs in wound care, especially in improving the healing outcomes of diabetic wounds. First, we discuss the pathological conditions associated with chronic diabetic wounds. Next, the mechanisms involved in MFs' effects on wounds are explored. At last, studies and reports regarding the effects of MFs on diabetic wounds from both animal experiments and clinical trials are reviewed. MFs exhibit great potential in promoting wound healing and have been practised in the management of diabetic wounds. Further studies on the exact mechanism of MFs on diabetic wounds and the development of suitable MF-based devices could lead to their increased applications into clinical practice.

Mechanical simulation and contact analysis of the hybrid longitudinal-torsional ultrasonic motor.

A slender type of ultrasonic motor using longitudinal-torsional hybrid vibration is proposed and investigated in this paper. To acquire the response and mechanical capacity of the assembled and complete hybrid longitudinal-torsional ultrasonic motor, a 3D finite element model has been established by the commercial FE software ADINA. The numerical results agree with the experimental results in terms of the trend and the order of magnitude, meaning that it is easy to evaluate the mechanical characteristics of the motor before prototype manufacture. Meanwhile, the radial, circumferential and axial displacements of the contact nodes can be obtained to simulate the actual elliptical motions of the stator teeth. In addition, the practical contact mechanism between the stator and rotor can be accurately reflected by the stress nephogram of the contact surfaces. This research provides a convenient method for the structure optimization and mechanical capacity prediction of the hybrid longitudinal-torsional ultrasonic motor.

Improving efficiency of traveling wave rotary ultrasonic motor by optimizing stator.

The application of ultrasonic motor (USM) has been seriously restricted by its relatively low efficiency. The energy loss caused by the radial sliding on the contact surface of the motor is considered as one of the major reasons for the low efficiency of USM. In this report, the solution is proposed to reduce the radial sliding by optimizing the stator comb-teeth of the traveling wave rotary ultrasonic motor (TWUSM). Theoretical analysis, simulation, and experiments were conducted in PMR60 type TWUSM (motor model) to verify the optimized method. The results indicate that the friction angle α, which represents the degree of radial sliding, can be efficiently reduced by chamfering the teeth on the stator of motor. The maximum efficiency of 44.3% is obtained in the modified motor of which the stator chamfer size is 1.0 mm × 45°, which is nearly two times higher than that of the nonmodified motor (25%). Therefore, it is a feasible and simple pathway to improve the efficiency of the USM.