Porous Mg-Zn-Ca scaffolds for bone repair: a study on microstructure, mechanical properties and in vitro degradation behavior.

Biodegradable porous Mg scaffolds are a promising approach to bone repair. In this work, 3D-spherical porous Mg-1.5Zn-0.2Ca (wt.%) scaffolds were prepared by vacuum infiltration casting technology, and MgF2 and fluorapatite coatings were designed to control the degradation behavior of Mg-based scaffolds. The results showed that the pores in Mg-based scaffolds were composed of the main spherical pores (450-600 µm) and interconnected pores (150-200 µm), and the porosity was up to 74.97%. Mg-based porous scaffolds exhibited sufficient mechanical properties with a compressive yield strength of about 4.04 MPa and elastic modulus of appropriately 0.23 GPa. Besides, both MgF2 coating and fluorapatite coating could effectively improve the corrosion resistance of porous Mg-based scaffolds. In conclusion, this research would provide data support and theoretical guidance for the application of biodegradable porous Mg-based scaffolds in bone tissue engineering.

Adaptive Optics Tip-Tilt Correction Based on Smith Predictor and Filter-Optimized Linear Active Disturbance Rejection Control Method.

A tip-tilt mirror (TTM) control method is designed to enhance the control bandwidth and ensure the rejection performance of the adaptive optics (AO) tip-tilt correction system. Optimized with the Smith predictor and filter, linear active disturbance rejection (LADRC) is adopted to achieve the tip-tilt correction. An AO tip-tilt correction experimental platform was built to validate the method. Experimental results show that the proposed method improves the control bandwidth of the system by at least 3.6 times compared with proportional-integral (PI) control. In addition, under the same control bandwidth condition, compared with the Smith predictor and proportional-integral (PI-Smith) control method, the system is more capable of rejecting internal and external disturbances, and its dynamic response performance is improved by more than 29%.

Coupled dynamic reaction force study of a large-aperture piezoelectric fast steering mirror.

The reaction force of a large-aperture piezoelectric fast steering mirror (PFSM) has adverse coupling interference for the stability and pointing accuracy of laser beams, and the dynamic characteristics of the reaction force are coupled with the inner components of the PFSM. In order to compensate for and eliminate the reaction force, it is essential to accurately analyze the dynamic characteristics. In this paper, a simplified piezoelectric-coupling model of PFSM is established. The coupling mathematical equations for investigating the characteristics of the reaction force are deducted based on the piezoelectric constitutive equation and Hamiltonian's principle. Then the coupling characteristics of the reaction force are probed by a finite element (FE) piezoelectric-coupling method. The simulations for three large apertures' (250, 320, and 400 mm) FE models show that the reaction force has a linear positive correlation with the actuating voltage, and coupled with the materials of the central flexure hinge, the relationship between the reaction force and driving frequency is not completely quadratic. Experiments with the 320 mm aperture are completed, and the testing results are consistent with the mathematical model and the FE piezoelectric-coupling simulation. The dynamic characteristics of the reaction force demonstrated in this paper are significance for the accurate estimation of the reaction force, the design of compensation structure, and the optimization of algorithm for beam jitter controlling.

Design and analysis of a reactionless large-aperture fast steering mirror with piezoelectric actuators.

The reaction force of a fast steering mirror (FSM) directly transmits to the FSM's base, leading to dynamic coupling interference to the optical platform and degradation of laser beam quality in an adaptive optics system. In this paper a $\Phi {320}\;{\rm mm}$Φ320mm aperture symmetrically arranged reactionless FSM actuated by piezoelectric actuators was proposed. The corresponding dynamic equation about reaction force was established by rotational equation of Newton's second law, and the equilibrium condition of reaction force compensation was deduced. Then, the finite element (FE) piezoelectric-coupling method was used to simulate dynamic characteristics, which shows that the elimination ratios of the reaction force are 99% at low frequency (at 50 Hz) and 94.1% at high frequency (at 120 Hz). The experimental results show that the first resonance frequency of the FSM is 159.82 Hz, the tilting angle is $\pm {1.3}^\prime$±1.3', the reaction force at high frequency (at 120 Hz) is 112.95 N, and the elimination ratio of reaction force is 90.14%. The simulation and corresponding test results indicate that the developed reactionless FSM significantly eliminates reaction force and therefore improve the FSM's stability and pointing accuracy.

Testing for a slope-based decoupling algorithm in a woofer-tweeter adaptive optics system.

It is well known that using two or more deformable mirrors (DMs) can improve the compensation ability of an adaptive optics (AO) system. However, to keep the stability of an AO system, the correlation between the multiple DMs must be suppressed during the correction. In this paper, we proposed a slope-based decoupling algorithm to simultaneous control the multiple DMs. In order to examine the validity and practicality of this algorithm, a typical woofer-tweeter (W-T) AO system was set up. For the W-T system, a theory model was simulated and the results indicated in theory that the algorithm we presented can selectively make woofer and tweeter correct different spatial frequency aberration and suppress the cross coupling between the dual DMs. At the same time, the experimental results for the W-T AO system were consistent with the results of the simulation, which demonstrated in practice that this algorithm is practical for the AO system with dual DMs.

Vibration identification based on Levenberg-Marquardt optimization for mitigation in adaptive optics systems.

When high performance is expected, vibrations are becoming a burning issue in adaptive optics systems. For mitigation of these vibrations, in this paper, we propose a method to identify the vibration model. The nonlinear least squares algorithm named the Levenberg-Marquardt method is adapted to acquire the model parameters. The experimental validation of the high performance of vibration mitigation associated with our identification method has been accomplished. Benefiting from this method, vibrations have been significantly suppressed using linear quadratic Gaussian control, where the root-mean-square of the residual vibrations has been reduced down to a portion of a microradian. Moreover, the experimental results show that with the model identified, vibrations ranging from wide low-frequency perturbation to high-frequency vibration peaks can be dramatically mitigated, which is superior to classical control strategies.

Adaptive compensation of intracavity tilts during lasing through detecting the direction of output beams.

We present adaptive compensation of intracavity tilts based on detecting the direction of the output beams. We use the initial direction of the output beam when the laser cavity is well collimated for reference. Then the difference between the actual direction of the output beam and the reference is used as feedback to control the intracavity tip/tilt mirror. The relation between the direction of the output beam and the intracavity tilt is investigated with both the Fox-Li method and measurements. A series of experiments demonstrate that intracavity tilts can be well compensated by the proposed method. We have also proved that it is possible to substitute the proposed method for conventional extracavity beam stabilization.

Automatic low-order aberration correction based on geometrical optics for slab lasers.

In this paper, we present a method based on geometry optics to simultaneously correct low-order aberrations and reshape the beams of slab lasers. A coaxial optical system with three lenses is adapted. The positions of the three lenses are directly calculated based on the beam parameters detected by wavefront sensors. The initial sizes of the input beams are 1.8 mm×11 mm, and peak-to-valley (PV) values of the wavefront range up to several tens of microns. After automatic correction, the dimensions may reach nearly 22 mm×22 mm as expected, and PV values of the wavefront are less than 2 µm. The effectiveness and precision of this method are verified with experiments.

Copper-catalyzed domino addition/double cyclization: an approach to polycyclic benzimidazole derivatives.

An efficient and versatile method for the assembly of novel polycyclic benzimidazole derivatives has been developed by Cu-catalyzed domino addition/double cyclization reactions. A wide variety of polycyclic benzimidazole derivatives, which might be used as synthetic medicines and functional materials, were successfully assembled from bis-(o-haloaryl)carbodiimides. Unexpected N-methylated benzo[4,5]imidazo[1,2-a]indoles can also be selectively assembled. Multibonds and polycyclic moieties were conveniently formed in one pot during these domino processes.

Concise synthesis and biological activity evaluation of novel pyrazinyl-aryl urea derivatives against several cancer cell lines, which can especially induce T24 apoptotic and necroptotic cell death.

Based on the structural modification of regorafenib, 28 pyrazinyl-aryl urea derivatives were synthesized and their in vitro antiproliferative activities were evaluated. Six compounds (5-16, 5-17, 5-18, 5-19, 5-22, and 5-23) exhibited favorable inhibitory activity against the human bladder cancer T24 cell line, and 5-23 demonstrated the strongest inhibitory activity (IC50 = 4.58 ± 0.24 µM) with high selectivity. Compound 5-23 induced apoptosis in the low concentration range (≤7.5 µM) combined with shorter incubation time (≤10 h) via the activation of caspases, while high concentrations and prolonged incubation times led to necroptotic cell death by activating the RIPK1/RIPK3/MLKL signaling pathway. Induced apoptosis and necroptosis were closely associated with intracellular reactive oxygen species generation and decreased mitochondrial membrane potential. Compared with regorafenib, 5-23 displayed improved pharmacokinetic profiles in an in vivo rat model. Molecular docking and structure-activity relationship analyses were in agreement with the biological data. Compound 5-23 may be a potent anti-bladder cancer agent and this small molecule can be considered as a promising structure for further optimization.

Correction: Concise synthesis and biological activity evaluation of novel pyrazinyl-aryl urea derivatives against several cancer cell lines, which can especially induce T24 apoptotic and necroptotic cell death.

[This corrects the article DOI: 10.1039/D1MD00306B.].

Arylurea Derivatives: A Class of Potential Cancer Targeting Agents.

Arylurea derivatives, an important class of small molecules, have received considerable attention in recent years due to their wide range of biological applications. Various molecular targeted agents with arylurea scaffold as potential enzyme/receptor inhibitors were constructed with the successful development of sorafenib and regorafenib. This review focuses on those arylureas possessing anti-cancer activities from 2010 to date. According to their different mechanisms of action, these arylureas are divided into the following six categories: (1) Ras/Raf/MEK/ERK signaling pathway inhibitors; (2) tumor angiogenesis inhibitors, their targets include Vascular Endothelial Growth Factor Receptors (VEGFRs), Fibroblast Growth Factor Receptors (FGFRs), Platelet-Derived Growth Factor Receptors (PDGFRs), Epidermal Growth Factor Receptors (EGFRs), Insulin-Like Growth Factor 1 Receptor (IGF-1R), Fmslike Tyrosine Kinase 3 (FLT3), c-Kit, MET, and Smoothened (Smo); (3) PI3K/AKT/mTOR signaling pathway inhibitors; (4) cell cycle inhibitors, their targets include Checkpoint Kinases (Chks), Cyclin- Dependent Kinases (CDKs), Aurora, SUMO activating enzyme 1 (SUMO E1), tubulin, and DNA; (5) tumor differentiation, migration, and invasion inhibitors, their targets include Matrix Metalloproteinases (MMPs), LIM kinase (Limk), Nicotinamide Phosphoribosyltransferase (Nampt), and Histone Deacetylase (HDAC); (6) arylureas from the rational modification of natural products. This review focuses on the Structure-Activity Relationships (SARs) of these arylureas. The structural evolution and current status of some typical anti-cancer agents used in clinic and/or in clinical trials are emphasized.