Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS.     

Coumarins from Seseli devenyense Simonk.: Isolation by Liquid–Liquid Chromatography and Potential Anxiolytic Activity Using an In Vivo Zebrafish Larvae Model

Different types of anxiety disorders have become the number one mental health issue in developed countries. The search for new, safer and effective drug-like molecules among naturally derived substances faces two difficulties: an efficient method of isolation compounds with a high-purity and high-throughput animal model for activity assay. Thus, the aim of the present study was to isolate by liquid–liquid chromatography high-purity rare coumarins from the fruits of Seseli devenyense Simonk. and evaluate their anxiolytic effect (defined as reversed thimotaxis) using a 5-days post-fertilization (dpf) Danio rerio larvae model. Liquid–liquid chromatography enabled the isolation of one simple hydroxycoumarin (devenyol) and four pyranocoumarins (cis-khellactone, d-laserpitin, isolaserpitin and octanoyllomatin). The anxiolytic effect was defined as a decrease in the time spent in the boundaries of the living space (also described as reversed thigmotaxis). Our results show that all isolated courmarins exerted a significant influence on the anxiety behavior (anxiolytic activity) in the zebrafish larvae model. According to our knowledge, this is the first report of anxiolytic activity of pyranocoumarins and devenyol.     

基于Matlab的量子激光雷达稳频通信模拟系统设计

传统通信模拟系统设计较为复杂,导致模拟过程消耗能量较大,不能准确模拟稳频通信质量。因此,提出基于Matlab的量子激光雷达稳频通信模拟系统。由于振荡器是雷达形成初始信号源的基础,通过分析振荡电路与相位噪声,获得相位噪声函数与通信频率存在的关系;为确保通信过程的稳定,将准确性与稳定性作为信号质量的评价指标,并采用锁频环稳频技术计算频率偏移程度,根据PID控制算法控制频率,量子激光雷达稳频通信;利用Matlab确定激光器、探测器等硬件组成结构,通过时序与数字阵列的设置完成模拟系统设计。仿真结果表明所提系统结构简便、性能稳定,能够真实模拟出稳频通信的信号质量。     

An Injectable Hydrogel for Simultaneous Photothermal Therapy and Photodynamic Therapy with Ultrahigh Efficiency Based on Carbon Dots and Modified Cellulose Nanocrystals

The convenience of injectable hydrogels that can provide high loading of diverse phototherapy agents and further long-time retention at the tumor site has attracted tremendous interest in simultaneous photothermal and photodynamic cancer therapies. However, to incorporate the phototherapy agents into hydrogels, complex modifications are generally unavoidable. Moreover, these phototherapy agents usually suffer from low efficiency and work at different irradiation wavelengths outside the near infrared windows. Hence, a method for the fabrication of an injectable hydrogel for simultaneous photothermal therapy and photodynamic therapy, through the Schiff-base reaction between amido modified carbon dots (NCDs) and aldehyde modified cellulose nanocrystals is proposed. The NCDs act as both phototherapy agents and crosslinkers to form hydrogels. Significantly, the NCDs demonstrate an extremely high photothermal conversion efficiency of 77.6% which is among the highest levels for photothermal agents and a high singlet quantum yield of 0.37 under a single 660 nm light-emitting diode irradiation. The hydrogels are examined through in vitro and in vivo animal experiments which show nontoxic and effectively tumor inhibition. Thus, the strategy of direct reaction of phototherapy agents and the matrix not only provides new strategies for injectable hydrogel fabrication but paves a new road for advanced tumor treatment.     

认知双向中继网络在κ-μ衰落信道下的中断性能分析

针对认知双向中继网络在进行数据传输时面临的复杂无线信道场景问题,采用广义κ-μ分布构建认知双向中继网络中的视距和非视距无线传输信道,推导次网络在κ-μ衰落信道下的统一中断概率,并分析次网络在多种单一和混合衰落信道情况下的中断性能。仿真结果表明,无线信道的衰落程度对次网络的中断概率影响显著,依据衰落信道类型合理设置网络参数将有助于提升次网络中断性能。     

Predicting the mechanical properties of Cu–Al2O3 nanocomposites using machine learning and finite element simulation of indentation experiments

Micromechanics model, finite element (FE) simulation of microindentation and machine learning were deployed to predict the mechanical properties of Cu–Al₂O₃ nanocomposites. The micromechanical model was developed based on the rule of mixture and grain and grain boundary sizes evolution to predict the elastic modulus of the produced nanocomposites. Then, a FE model was developed to simulate the microindentation test. The input for the FE model was the elastic modulus that was computed using the micromechanics model and wide range of yield and tangent stresses values. Finally, the output load-displacement response from the FE model, the elastic modulus, the yield and tangent strengths used for the FE simulations, and the residual indentation depth were used to train the machine learning model (Random vector functional link network) for the prediction of the yield and tangent stresses of the produced nanocomposites. Cu–Al₂O₃ nanocomposites with different Al₂O₃ concentration were manufactured using insitu chemical method to validate the proposed model. After training the model, the microindentation experimental load-displacement curve for Cu–Al₂O₃ nanocomposites was fed to the machine learning model and the mechanical properties were obtained. The obtained mechanical properties were in very good agreement with the experimental ones achieving 0.99 coefficient of determination R2 for the yield strength.     

Activation of the Complement System on Human Endothelial Cells by Urban Particulate Matter Triggers Inflammation-Related Protein Production

Exposure to particulate matter (PM) is becoming a major global health issue. The amount and time of exposure to PM are known to be closely associated with cardiovascular diseases. However, the mechanism through which PM affects the vascular system is still not clear. Endothelial cells line the interior surface of blood vessels and actively interact with plasma proteins, including the complement system. Unregulated complement activation caused by invaders, such as pollutants, may promote endothelial inflammation. In the present study, we sought to investigate whether urban PM (UPM) acts on the endothelial environment via the complement system. UPM-treated human endothelial cells with normal human serum showed the deposition of membrane attack complexes (MACs) on the cell surface via the alternative pathway of the complement system. Despite the formation of MACs, cell death was not observed, and cell proliferation was increased in UPM-mediated complement activation. Furthermore, complement activation on endothelial cells stimulated the production of inflammation-related proteins. Our results revealed that UPM could activate the complement system in human endothelial cells and that complement activation regulated inflammatory reaction in microenvironment. These findings provide clues with regard to the role of the complement system in pathophysiologic events of vascular disease elicited by air pollution.     

Weighted regularized extreme learning machine to model the discharge coefficient of side slots

In the current research, a modern learning machine algorithm named “Weighted Regularized Extreme Learning Machine (WRELM)" is implemented for the first time for the simulation of the coefficient of discharge of side slots. For this purpose, an effective variable on the coefficient of discharge of side slots is firstly introduced, then five distinctive WRELM models are produced by it for the estimation of the coefficient. In the next stage, a database is created for verification of WRELM results. it should be mentioned that 70% of the data are utilized for training the WRELM models, while the rest (i.e. 30%) for testing them. After that, the optimal number of hidden layer neurons as well as the best activation function of the WRELM algorithm are chosen. In addition, the best regularization parameter and also the weight function of the WRELM are achieved. By conducting a sensitivity analysis, the most effective variable for the simulation of the coefficient of discharge along with the WRELM superior model is introduced. The WRELM superior model estimates values of the coefficient of discharge with the maximum exactness and the highest correlation. For instance, the estimations of the correlation coefficient and scatter index for this model are computed to be 0.930 and 0.051, respectively. The sensitivity analysis shows that the ratio of the side slot crest height to its length and the Froude number should be considered as the most important input variables. A comparison between the WRELM with the ELM displays that the former works much better. Furthermore, an uncertainty analysis is executed for both models. Eventually, an equation is suggested for the estimation of the coefficient of discharge and a partial derivative sensitivity analysis is performed on it.     

Optimal Design of Novel Electromagnetic-Ring Active Balancing Actuator with Radial Excitation

Imbalance vibration is a typical failure mode of rotational machines and has significant negative effects on the effii-ciency,accuracy,and service life of equipment.To automatically reduce the imbalance vibration during the opera-tional process,different types of active balancing actuators have been designed and widely applied in actual produc-tion.However,the existing electromagnetic-ring active balancing actuator is designed based on an axial excitation structure which can cause structural instability and has low electromagnetic driving efficiency.In this paper,a novel radial excitation structure and the working principle of an electromagnetic-ring active balancing actuator with a combined driving strategy are presented in detail.Then,based on a finite element model,the performance param-eters of the actuator are analyzed,and reasonable design parameters are obtained.Self-locking torque measurements and comparative static and dynamic experiments are performed to validate the self-locking torque and driving effi-ciency of the actuator.The results indicate that this novel active balancing actuator has sufficient self-locking torque,achieves normal step rotation at 2000 r/min,and reduces the driving voltage by 12.5％.The proposed novel balancing actuator using radial excitation and a combination of permanent magnets and soft-iron blocks has improved electro-magnetic efficiency and a more stable and compact structure.