Purpose
Decreased trabecular meshwork (TM) cellularity has been implicated as a major reason for TM dysfunction and aqueous humor (AH) outflow abnormalities in primary open angle glaucoma. We previously found that transplantation of induced pluripotent stem cell (iPSC)-derived TM cells can restore TM function and stimulate endogenous TM cell division. The goal of the present study is to investigate whether signaling via gap junctions is involved in this process.
Methods
Differentiated iPSCs were characterized morphologically, transcriptionally, and immunohistochemically. After purification, iPSC-TM were co-cultured with mouse TM (MTM) cells to mimic the transplantation procedure. Through the pharmacological antagonists and short hairpin RNA (shRNA) technique, the gap junction function in iPSC-based therapy was determined.
Results
In the co-culture system, iPSC-TM increase MTM cell division as well as transfer of Ca
2+
to MTM. This effect was blocked by treatment with the gap junction inhibitors carbenoxolone (CBX) or flufenamic acid (FFA). The shRNA mediated knock down of connexin 43 (Cx43) expression in iPSC-TM also results in decreased Ca
2+
transfer and lower MTM proliferation rates. In vivo, Cx43 downregulation in transplanted iPSC-TM weakened their regenerative role in an Ad5.myocilin
Y437H
mouse model of glaucoma. Mice receiving these cells exhibited lower TM cellularity and higher intraocular pressure (IOP) than those receiving unmodified iPSC-TM.
Conclusions
Our findings reveal a crucial role of gap junction, especially Cx43, in iPSC-based TM regeneration, and provides insights to enhance the regenerative effect of iPSCs in glaucoma therapy.
The hydraulic drive unit (HDU) applied in a hydraulic drive legged robot joints adopts an outer loop impedance control method based on the hydraulic control's inner loop during motion so that the entire system obtains certain compliance characteristics. There are two types of inner loops, namely, the position closed loop control and the force closed loop control; this paper studies a system in which the inner loop is a force closed loop control system and improves its accuracy in order to provide references for the outer loop impedance control. Therefore, designing a compensation method that improves the inner loop force control's accuracy has important research significance. In view of the above research significance, this paper first deduces a mathematical model for the force closed loop control and simplifies the sixth-order mathematical model to find the transfer function of each part. Second, combined with influence factors, such as pressure-flow nonlinearity, friction nonlinearity, and complex and variable loads on the system, the feedforward compensation controller of the force control input is derived. Considering the practical application in engineering, the controller order is reduced, and a partial compensation is achieved. Finally, on the HDU performance test platform, the force control performance is quantitatively analyzed by inputting typical signals and random signals. The experimental results show that the feedforward compensation controller can greatly improve the system force control performance with different input signals. The above research results can be combined with a corresponding disturbance rejection strategy for the force control system to provide an important reference and experimental basis for the hydraulic inner loop control strategy of force-based impedance.INDEX TERMS Legged robots, hydraulic drive unit (HDU), force control system, nonlinear feedforward compensation.
Caffeine (CA) is a common xanthine alkaloid found in tea leaves, coffee beans, and other natural plants, and is the most widely used psychotropic substance in the world. Accumulating evidence suggests that low plasma levels of CA and its metabolites may serve as reliable diagnostic markers for early Parkinson's disease (PD) patients. In this study, we demonstrated a new MEKC method for determining CA and its three main downstream metabolites, paraxanthine (PX), theobromine (TB), and theophylline (TP), in human plasma. Plasma samples were collected, and analyzed using MEKC, after SPE. The running buffer was composed of 35 mM phosphate, pH of 10.5, and 25 mM SDS. The separation voltage was 15 kV and the detection wavelength was at 210 nm. Under the optimum conditions, four distinct analytes were completely separated and detected in less than 12 min. Method limits of detection were as low as 7.5 ng/mL for CA, 5.0 ng/mL for TB, and 4.0 ng/mL for both PX and TP. The recoveries were between 88.0% and 105.9%. This method was successfully applied to 27 human plasma samples. The results indicate that the plasma concentrations of the four analytes are significantly lower in patients with early PD than in control subjects (p < 0.05). The area under curve was improved to 0.839 when CA and its three main metabolites were included, suggesting that MEKC testing of CA, TP, TB, and PX may serve as a potential method for early diagnosis of PD.
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