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In three-dimensional extracellular matrix, mesenchymal cells including hepatic stellate cells (HSCs) gain the ability to express matrix metalloproteinases (MMPs) on injury signals. In contrast, in myofibroblastic HSCs in fibrotic liver, many MMP genes are silenced into an epigenetically nonpermissive state. The mechanism by which the three-dimensional extracellular matrix confers the MMP genes into an epigenetically permissive state has not been well characterized. In continuation of previous work, we show here that the up-regulation of MMP genes is mediated through degradation of class IIa histone deacetylases (HDACs) by certain cysteine cathepsins (Cts). In three-dimensional extracellular matrix culture, CtsH, among other cysteine cathepsins, was up-regulated and localized as puncta in the nuclear and cytoplasmic compartments in a complex with HDAC4 for its degradation. Conversely, along with HSC trans-differentiation, CtsH and CtsL were progressively down-regulated, whereas HDAC4 was concurrently stabilized. The inhibition of cysteine cathepsins by specific proteinase inhibitors or chloroquine, which raises cellular pH, restored HDAC4. Recombinant CtsH could break down HDAC4 in the transfected cells and in vitro at acidic pH. In human cirrhotic liver, activated HSCs express high levels of class IIa HDACs but little CtsH. We propose that cysteine cathepsin-mediated degradation of class IIa HDACs plays a key role in the modulation of MMP expression/suppression and HSC functions in tissue injury and fibrosis.

AbstractThe study of dynamic performance and adaptive control of variable stiffness actuators with time-varying parameters is significant for the realization of stable and efficient human-computer interaction. In this paper, for the previously proposed variable stiffness actuator, the dynamics model of the variable stiffness actuator system is established according to the two-inertia-system theory, and the effects of time-varying parameters on the dynamic performance of the variable stiffness actuator system are analyzed. Then the adaptive control strategy of the variable stiffness actuator system with time-varying parameters is studied, and the correctness and effectiveness of the control strategy are verified experimentally. The results show that the time-varying parameters have a more obvious effect on the dynamic performance of the variable stiffness actuator system, and the difficulty in designing the system control strategy, which is caused by the complex dynamics modeling of variable stiffness actuator systems with time-varying parameters, can be effectively solved by using the proposed adaptive control strategy. Moreover, the control strategy has good stability and generalization ability. [ABSTRACT FROM AUTHOR]

With the increase of safety requirements for human-robot interaction, variable stiffness actuators are increasingly used in joints of medical rehabilitation robots, legged mobile robots and exoskeleton-assisted robots, so the research of the variable stiffness actuator becomes more and more important. In this paper, firstly, according to the human knee joint, a low-energy nonlinear variable stiffness actuator for knee joint is proposed, it conforms to characteristics of biological joints: the actuator can be flexible when it is subjected to the small load, and the actuator can be stabilized when it is subjected to the heavy load. The realization principle of this actuator, which is combining the eccentric cam with the leaf spring, is introduced in detail, and its relatively large range of variable stiffness is accurately deduced and analyzed. Secondly, the energy cost of this actuator is reduced as much as possible by some structural designs. Finally, by experiments, the correctness and accuracy of the resistance moment and expected stiffness of the proposed nonlinear variable stiffness actuator are verified, the high bandwidth and good stability of this actuator are also verified, which meets the design principles and requirements of the actuator, and it is verified that actuator's low energy cost. [ABSTRACT FROM AUTHOR]

The numerical solution model of the labyrinth seal considering the multiple frequencies elliptical whirling of the rotor and swirl brake was established by the computational fluid dynamics (CFD) technique. Then, the dynamic characteristics and response force characteristics of the labyrinth seal under the condition of a preswirl inlet were studied on the basis of experimental verification of the accuracy of the numerical solution method. The influence of the circumferential solidity of the swirl brake and the preswirl ratio on the flow field between the swirl brakes and the average circumferential velocity of seal cavities were analyzed. These results show that with the increasing rotor speed, the airflow circumferential velocity in the labyrinth seal chamber is increased, and the logarithmic decrement rate of the seal-rotor system is decreased, resulting in the rotor stability being decreased. With the increasing inlet/outlet pressure ratio, the airflow circumferential velocity of the labyrinth seal cavities is decreased, the logarithmic decrement rate of the seal-rotor system is increased, causing the rotor stability is increased. With the increasing circumferential solidity of the swirl brake, cross-coupled stiffness decreases, the direct damping and effective damping increase. It contributes to rotor whirling be inhibited, and rotor stability is increased. The rotor stability can be further improved with the increasing radial length of the swirl brake. The effective damping of the labyrinth seal with 40-extended swirl brakes increases by 33.7% compared to the labyrinth seal with no swirl brakes. With the increasing the preswirl ratio, the cross-coupled stiffness increases, the direct damping and effective damping decreases, and the phase angle of the response force is decreased. It arouses that the stability of the rotor is decreased. With the increasing of whirling frequency, the cross-coupling stiffness and direct damping increase, while the effective damping decreases first and then increases, resulting in the rotor stability being decreased first and then increased. The previous research provides a theoretical basis for the structure design of the swirl brake. [ABSTRACT FROM AUTHOR]