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.     

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.     

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.     

Molecular Characteristics of Amyloid Precursor Protein (APP) and Its Effects in Cancer

Amyloid precursor protein (APP) is a type 1 transmembrane glycoprotein, and its homologs amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2) are highly conserved in mammals. APP and APLP are known to be intimately involved in the pathogenesis and progression of Alzheimer’s disease and to play important roles in neuronal homeostasis and development and neural transmission. APP and APLP are also expressed in non-neuronal tissues and are overexpressed in cancer cells. Furthermore, research indicates they are involved in several cancers. In this review, we examine the biological characteristics of APP-related family members and their roles in cancer.     

Adsorption of anionic dye on eco-friendly synthesised reduced graphene oxide anchored with lanthanum aluminate: Isotherms,kinetics and statistical error analysis

In the present study we made an effort to deploy eco-friendly synthesized reduced graphene oxide/Lanthanum Alluminate nanocomposites (RGO-LaAlO₃) and Lanthanum Alluminate (LaAlO₃) as adsorbents to remove dye from the synthetic media. XRD, SEM, BET surface area and EDX have been used to characterize the above-mentioned adsorbents. The impacts of different factors like adsorbent dosage, the concentration of adsorbate and PH on adsorption were studied. The best fit linear and nonlinear equations for the adsorption isotherms and kinetic models had been examined. The sum of the normalized errors and the coefficient of determination were used to determine the best fit model. The experimental data were more aptly fitted for nonlinear forms of isotherms and kinetic equations. Pseudo-second-order and Freundlich isotherm model fits the equilibrium data satisfactorily. Methyl orange (MO) has been used as model dye pollutant and maximum adsorption capacity was found to be 469.7 and 702.2 mg g^?1 for LaAlO₃ and RGO-LaAlO₃, respectively.     

Split Enzyme-Based Biosensors for Structural Characterization of Soluble and Insoluble β-Glucans

β-Glucan is widely distributed in various plants and microorganisms and is composed of β-1,3-linked d-glucose units. It may have a branched short or long side chain of glucose units with β-1,6- or β-1,4-linkage. Numerous studies have investigated different β-glucans and revealed their bioactivities. To understand the structure-function relationship of β-glucan, we constructed a split-luciferase complementation assay for the structural analysis of long-chain β-1,6-branched β-1,3-glucan. The N- and C-terminal fragments of luciferase from deep-sea shrimp were fused to insect-derived β-1,3-glucan recognition protein and fungal endo-β-1,6-glucanase (Neg1)-derived β-1,6-glucan recognition protein, respectively. In this approach, two β-glucan recognition proteins bound to β-glucan molecules come into close proximity, resulting in the assembly of the full-length reporter enzyme and induction of transient luciferase activity, indicative of the structure of β-glucan. To test the applicability of this assay, β-glucan and two β-glucan recognition proteins were mixed, resulting in an increase in the luminescence intensity in a β-1,3-glucan with a long polymer of β-1,6-glucan in a dose-dependent manner. This simple test also allows the monitoring of real-time changes in the side chain structure and serves as a convenient method to distinguish between β-1,3-glucan and long-chain β-1,6-branched β-1,3-glucan in various soluble and insoluble β-glucans.     

基于云网PoP的弹性边缘网络设计思路探讨

移动边缘云是公司“云+5G”双引擎战略的最佳契合点,边缘网络是发挥移动云“大云”产品和5G网络融合优势,实现云网统筹、构建运营商“连接+计算”核心能力的关键。运营商传统接入网存在云网割裂、分段入云和组网复杂等突出问题,难以适应边缘业务敏捷交付要求。本文通过深入分析边缘云业务特征和技术架构,对标业界主流云商建设实践,研究基于云网PoP网的边缘网络建设思路,创新性提出云网一体化规划设计和建设交付流程变革,基于云网POP统一网络和业务锚点,构建Overlay和Underlay融合双层加速网络架构,探索Spine-leaf化的新型城域接入网实现L3下沉和弹性扩容等方法,实现“云+网+应用”一体化敏捷交付的边缘网络能力。     

Various density light field image coding based on distortion minimization interpolation

In recent years, the light field (LF) as a new imaging modality has attracted wide interest. The large data volume of LF images poses great challenge to LF image coding, and the LF images captured by different devices show significant differences in angular domain. In this paper we propose a view prediction framework to handle LF image coding with various sampling density. All LF images are represented as view arrays. We first partition the views into reference view (RV) set and intermediate view (IV) set. The RVs are rearranged into a pseudo sequence and directly compressed by a video encoder. Other views are then predicted by the RVs. To exploit the four dimensional signal structure, we propose the linear approximation prior (LAP) to reveal the correlation among LF views and efficiently remove the LF data redundancy. Based on the LAP, a distortion minimization interpolation (DMI) method is used to predict IVs. To robustly handle the LF images with different sampling density, we propose an Iteratively Updating depth image based rendering (IU-DIBR) method to extend our DMI. Some auxiliary views are generated to cover the target region and then the DMI calculates reconstruction coefficients for the IVs. Different view partition patterns are also explored. Extensive experiments on different types LF images also valid the efficiency of the proposed method.