Pan-histone deacetylase inhibitor vorinostat suppresses osteoclastic bone resorption through modulation of RANKL-evoked signaling and ameliorates ovariectomy-induced bone loss.

BACKGROUND: Estrogen deficiency-mediated hyperactive osteoclast represents the leading role during the onset of postmenopausal osteoporosis. The activation of a series of signaling cascades triggered by RANKL-RANK interaction is crucial mechanism underlying osteoclastogenesis. Vorinostat (SAHA) is a broad-spectrum pan-histone deacetylase inhibitor (HDACi) and its effect on osteoporosis remains elusive. METHODS: The effects of SAHA on osteoclast maturation and bone resorptive activity were evaluated using in vitro osteoclastogenesis assay. To investigate the effect of SAHA on the osteoclast gene networks during osteoclast differentiation, we performed high-throughput transcriptome sequencing. Molecular docking and the assessment of RANKL-induced signaling cascades were conducted to confirm the underlying regulatory mechanism of SAHA on the action of RANKL-activated osteoclasts. Finally, we took advantage of a mouse model of estrogen-deficient osteoporosis to explore the clinical potential of SAHA. RESULTS: We showed here that SAHA suppressed RANKL-induced osteoclast differentiation concentration-dependently and disrupted osteoclastic bone resorption in vitro. Mechanistically, SAHA specifically bound to the predicted binding site of RANKL and blunt the interaction between RANKL and RANK. Then, by interfering with downstream NF-κB and MAPK signaling pathway activation, SAHA negatively regulated the activity of NFATc1, thus resulting in a significant reduction of osteoclast-specific gene transcripts and functional osteoclast-related protein expression. Moreover, we found a significant anti-osteoporotic role of SAHA in ovariectomized mice, which was probably realized through the inhibition of osteoclast formation and hyperactivation. CONCLUSION: These data reveal a high affinity between SAHA and RANKL, which results in blockade of RANKL-RANK interaction and thereby interferes with RANKL-induced signaling cascades and osteoclastic bone resorption, supporting a novel strategy for SAHA application as a promising therapeutic agent for osteoporosis.

Loss-Optimized Design of Magnetic Devices.

Maximizing efficiency, power density, and reliability stands as paramount objectives in the advancement of power electronic systems. Notably, the dimensions and losses of magnetic components emerge as primary constraints hindering the miniaturization of such systems. Researchers have increasingly focused on the design of loss minimization and size optimization of magnetic devices. In this paper, with the objective of minimizing the loss of magnetic devices, an optimal design method for the winding structure of devices is proposed based on the coupling relationship between the loss prediction model and the design variables. The method examines the decoupling conditions between the design variables and the loss model, deriving optimized design closure equations for the design variables. This approach furnishes a technical foundation for the miniaturized design of miniature apparatuses incorporating magnetic components, offering a straightforward and adaptable design methodology. The finite element method simulation results and experimental measurement data verify the accuracy of the prediction of the proposed method and the validity of the optimal design theory of device loss.

GRU-ESO Strategy for a Distributed Coil Magnetically Levitated Planar Micromotor.

Traditional magnetic levitation planar micromotors suffer from poor controllability, short travel range, low interference resistance, and low precision. To address these issues, a distributed coil magnetically levitated planar micromotor with a gated recurrent unit (GRU)-extended state observer (ESO) control strategy is proposed in this paper. First, the structural design of the distributed coil magnetically levitated planar micromotor employs a separation of levitation and displacement, reducing system coupling and increasing controllability and displacement range. Then, theoretical analysis and model establishment of the system are conducted based on the designed distributed coil magnetically levitated planar micromotor and its working principles, followed by simulation verification. Finally, based on the established system model, a GRU-ESO controller is designed. An ESO feedback control term is introduced to enhance the system's anti-interference capability, and the GRU feedforward compensation control term is used to improve the system's tracking control accuracy. The experimental results demonstrate the reliability of the designed distributed coil magnetic levitation planar micromotor and the effectiveness of the controller.

Crosstalk Between the Neuroendocrine System and Bone Homeostasis.

The homeostasis of bone microenvironment is the foundation of bone health and comprises 2 concerted events: bone formation by osteoblasts and bone resorption by osteoclasts. In the early 21st century, leptin, an adipocytes-derived hormone, was found to affect bone homeostasis through hypothalamic relay and the sympathetic nervous system, involving neurotransmitters like serotonin and norepinephrine. This discovery has provided a new perspective regarding the synergistic effects of endocrine and nervous systems on skeletal homeostasis. Since then, more studies have been conducted, gradually uncovering the complex neuroendocrine regulation underlying bone homeostasis. Intriguingly, bone is also considered as an endocrine organ that can produce regulatory factors that in turn exert effects on neuroendocrine activities. After decades of exploration into bone regulation mechanisms, separate bioactive factors have been extensively investigated, whereas few studies have systematically shown a global view of bone homeostasis regulation. Therefore, we summarized the previously studied regulatory patterns from the nervous system and endocrine system to bone. This review will provide readers with a panoramic view of the intimate relationship between the neuroendocrine system and bone, compensating for the current understanding of the regulation patterns of bone homeostasis, and probably developing new therapeutic strategies for its related disorders.

Effect of mixed magnetic field on physical properties of atmospheric suspended fine particles.

In recent years, the fine particles suspended in the atmosphere, especially the particle size less than 10 µ m , have caused very adverse effects on the climate environment and human health. However, the current research on the causes of air pollution mainly focuses on human activities and weather conditions. Considering the weak magnetism and chargeability of atmospheric fine particles, this study proposed a new view that space electromagnetic radiation may affect the physical properties of fine particles. We first analyzed the dynamic characteristics of magnetic micro-particle in the electromagnetic environment, and built a simulation model in the COMSOL simulation software. Finally, based on the theoretical analysis and simulation results, we built an experimental verification system to evaluate the effects of electromagnetic radiation on the physical properties of micro-particle, and carried out a 30-day control experiment. The experimental results showed that the physical properties such as particle size distribution, mass concentration, and morphology of suspended fine particles in the atmosphere under electromagnetic radiation are significantly different from those under non-electromagnetic radiation environment. It can be inferred that the aggregation, fusion, and deposition of suspended particles in the atmosphere are closely related to the complex electromagnetic environment in space.