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Accuracy and robust trajectory tracking for electro-hydraulic servo systems in the presence of load disturbances and model uncertainties are of great importance in many fields. In this work, a new adaptive sliding mode control method based on the RBF neural networks (SMC–RBF) is proposed to improve the performances of a robotic excavator. Model uncertainties and load disturbances of the electro-hydraulic servo system are approximated and compensated using the RBF neural networks. Adaptive mechanisms are designed to adjust the connection weights of the RBF neural networks in real time to guarantee the stability. A nonlinear term is introduced into the sliding mode to design an adaptive terminal sliding mode control structure to improve dynamic performances and the convergence speed. Moreover, a sliding mode chattering reduction method is proposed to suppress the chattering phenomenon. Three types of step, ramp and sine signals are used as the simulation reference trajectories to compare different controllers on a co-simulation platform. Experiments with leveling and triangle conditions are presented on a robotic excavator. Results show that the proposed SMC–RBF controller is superior to existing proportional integral derivative (PID) and sliding mode controller (SMC) in terms of tracking accuracy and disturbance rejection. • A new adaptive sliding mode controller based on the RBF neural network is proposed for improving trajectory tracking performances. • System models and nonlinear factors of the electro-hydraulic servo system are described in detail. • A nonlinear term and a chattering reduction method are synthesized into the control law. • A co-simulation platform is built to compare different controllers. • Effectiveness of the proposed controller is validated by simulation and experiment. [ABSTRACT FROM AUTHOR]

[Display omitted] • PTEN regulated glucose metabolism through HK1-mediated glucose-6-phosphase production and PFK1-mediated fructose-1,6-biophosphase production. • The tumor suppressor role of PTEN was independent of its phosphatase activity. • The aberrant expression of PTEN was a marker of gastric cancer development, and was related with its hypermethlyation status in its promoter. • Procyanidin B2, an active compound from vegetables and fruits, reactivated PTEN's tumor-suppressor role in gastric cancer through combining and regulating DNMTs. Tumor suppressor PTEN was aberrant silenced in gastric cancer (GC) in our previous study. Activation of PTEN through DNA demethylation is a potential strategy for the treatment of GC. Procyanidin B2 (PB2), an effective DNMT inhibitor, exert positive effects on various diseases. In our work, PB2 suppressed cell proliferation and migration while inducing cell apoptosis in vitro , and inhibited tumorigenesis and development in vivo. PB2 hypomethylated and reactivated PTEN expression via targeting and combining with DNMTs. Targeted glucose metabolism and Seahorse analysis showed that PTEN inhibited cell proliferation via HK1-mediated G6P and PFK1-mediated F1,6-2P, and the tumor-suppressor role of PTEN was not dependent on its phosphatase activity. Furthermore, PTEN promoter methylation could be used as a potential marker to predict GC development. This work aimed to investigate whether PB2 inhibit GC by reactivating PTEN's tumor suppressor function, providing a powerful tool in the development of medical and editable natural compounds. [ABSTRACT FROM AUTHOR]

In order to improve the tracking accuracy of a hydraulic system, an improved ant colony optimization algorithm (IACO) is proposed to optimize the values of proportional–integral–derivative (PID) controller. In addition, this paper presents an experimental study on the parameters identification to deduce accurate numerical values of the hydraulic system, which also determines the relationship between control signal and output displacement. Firstly, the basic principle of the hydraulic system and the mathematical model of the electro-hydraulic proportional control system are analyzed. Based on the theoretical models, the transfer function of the control system is obtained by recursive least square identification method (RLS). Then, the key parameters of the control system model are obtained. Some improvements are proposed to avoid premature convergence and slow convergence rate of ACO: the transition probability is revised based adjacent search mechanism, dynamic pheromone evaporation coefficient adjustment strategy is adopted, pheromone update rule and parameters optimization range are also improved. Then the proposed IACO tuning based PID controller and the identification parameters are modeled and simulated using MATLAB/Simulink and AMESim co-simulation platform. Comparisons of IACO, standard ACO and Ziegler–Nichols (Z–N)PID controllers are carried out with different references as step signal and sinusoidal wave using the co-simulation platform. The simulation results of the bucket system using the proposed controller demonstrates improved settling time, rise time and the convergence speed with a new objective function J. Finally, experiments with leveling operations are performed on a 23 ton robotic excavator. The experimental results show that the proposed controller improves the trajectory accuracy of the leveling operation by 28% in comparison to the standard ACO-PID controller. • The mathematical models of electro-hydraulic proportional system are described. • The key control system parameters are identified and then validated against experiments. • An improved ant colony optimization algorithm is proposed for achieving excellent control performances. • Co-simulation platform is carried out to estimate the performance of controller. • Effectiveness of the improved ant colony optimization algorithm is validated by experiment. [ABSTRACT FROM AUTHOR]

Aberrant methylation of promoter CpG islands (CGIs) can inactivate the expression of many tumor suppressor genes and play an important role in the carcinogenesis of gastric cancer. The tumor suppressor gene RB1, which encodes a cell cycle regulator, is hypermethylated and downregulated in multiple kinds of cancer. Activation of RB1 expression through DNA demethylation is a potential strategy for the treatment of gastric cancer. Herein, we found that the methylation status of the RB1 promoter was negatively related to the development of gastric tumors, while its expression was positively correlated with TET2 and TET3 expression. Further reactivation of RB1 expression by curcumin could inhibit gastric cell viability and carcinogenesis both in vitro and in vivo. Molecular docking and other studies confirmed that curcumin could bind to and upregulate the expression of TET2 and TET3 with hydrogen bonds and arene-H bonds, suggesting that demethylation of RB1 was attributed to reactivation of the demethylation enzymes TET2 and TET3 after curcumin treatment. Thus, our findings reveal a promising therapeutic strategy for gastric cancer prevention and treatment through RB1 demethylation and reactivation. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that aberrant DNA methylation and gene silencing of tumor suppressors are pervasive in gastric malignancies, supporting reactivation of tumor suppressors through DNA demethylation as a potential therapeutic opportunity. Atp4a is an important tumor suppressor gene, encoding H+, K+-ATPase, and mediating gastric acid secretion in the stomach. Using transgenic gastric cancer model K19-Wnt1/C2mE (Gan) mice, by combining the transcriptome and MeDIP (methylated DNA immunoprecipitation) sequencing, together with qRT-PCR, we showed that Atp4a was expressed at low levels in tumor tissues and multiple GC cells, while both 5-aza-CdR and 18β-glycyrrhetinic acid (GRA) pharmacological treatment triggered Atp4a activation with downregulation of DNMT1. In addition, CpG island (CGI) search showed that the CpG rich region is absent in the promoter region but present in exons 9–14 of Atp4a. Methylation specific PCR (MSP) indicated that Atp4a was fully or partly methylated in multiple GC cells. Further MassArray suggested that the demethylation in the CpG site 75, 183, 196, 262–268 might be responsible for the reactivation of Atp4a. Our research identified that GRA, a bioactive component found in abundance in Radix Glycyrrhiza , reactivated Atp4a expression and inhibited gastric tumorigenesis as a potential demethylation agent. [ABSTRACT FROM AUTHOR]

Traditional identification methods make it difficult to accurately determine the parameters of the friction model. Based on the LuGre friction model, a hybrid optimization algorithm (HO) is presented to address such aspects. This algorithm combines the genetic algorithm (GA) and particle swarm optimization algorithm (PSO) to obtain the globally optimal solutions. It incorporates three main improvements: introducing selection and crossover operations into the PSO algorithm, utilizing a variable inertia weight coefficient, and applying variable learning coefficients for enhanced performance. Compared to the static optimal solutions of the GA and PSO algorithms, the HO algorithm can improve the optimal solution by 40.68 % and 35.89 % respectively. The HO algorithm can achieve the highest model accuracy: the maximum identified friction error with the HO algorithm is only 1.70 kN, compared to 3.69 kN with the GA method and 8.52 kN with the PSO algorithm. Furthermore, a novel adaptive friction compensation controller (AC) is introduced based on the identification results to improve the stability and accuracy of the electro-hydraulic proportional systems of a 23-ton robotic excavator. Comparisons with existing proportional integral differential (PID) and feedforward compensation controllers (FC) highlight the superiority of the proposed adaptive controller in terms of trajectory accuracy and robustness. In sinusoidal trajectory tracking experiments, the AC method can achieve the highest tracking performance among the three controllers, and the maximum tracking error is only 11.56 mm. Compared to the FC controller, the control accuracy with the AC controller can be improved by 43.38 %. Experiments and simulations have shown that the friction compensation controller can effectively mitigate friction and other disturbances. As a result, the phenomena of crawling and flat peak phenomena can be eliminated. [ABSTRACT FROM AUTHOR]

Abstract: Human choriogonadotropin (hCG) and follitropin (hFSH) have been shown to contact different regions of the extracellular domains of G-protein coupled lutropin (LHR) and follitropin (FSHR) receptors. We report here that hCG and hFSH analogs interact with different regions of an FSHR/LHR chimera having only two unique LHR residues and that binds both hormones with high affinity. hCG and hFSH analogs dock with this receptor chimera in a manner similar to that in which they bind LHR and FSHR, respectively. This shows that although the FSHR does not normally bind hCG, it contains a cryptic lutropin binding site that has the potential to recognize hCG in a manner similar to the LHR. The presence of this cryptic site may explain why equine lutropins bind many mammalian FSHR and why mutations in the transmembrane domain distant from the extracellular domain enable the FSHR to bind hCG. The leucine-rich repeat domain (LRD) of the FSHR also appears to contain a cryptic FSH binding site that is obscured by other parts of the extracellular domain. This will explain why contacts seen in crystals of hFSH complexed with an LRD fragment of the human FSHR are hard to reconcile with the abilities of FSH analogs to interact with membrane G-protein coupled FSHR. We speculate that cryptic lutropin binding sites in the FSHR, which are also likely to be present in thyrotropin receptors (TSHR), permit the physiological regulation of ligand binding specificity. Cryptic FSH binding sites in the LRD may enable alternate spliced forms of the FSHR to interact with FSH. [Copyright &y& Elsevier]

• The improved Stribeck model is used to establish the non-linear friction model of a electro-hydraulic system. • The improved genetic algorithm is used to identify four unknown parameters in the friction model. • A dynamic friction feedforward compensation method is designed based on the velocity observer and the structural invariance principle. • Effectiveness of the friction model and the friction feedforward compensation method is validated by experiment. It is necessary to identify and compensate the non-linear friction to improve the performances of the electro-hydraulic system of robotic excavators. The mathematical model of the electro-hydraulic system is established first, and the non-linear friction are described by the improved Stribeck model. The actual friction force is calculated by measuring the pressures of the two chambers of the hydraulic cylinder at different constant velocities. The fitness, crossover and mutation probabilities of the genetic algorithm are improved to overcome the shortcomings of stagnation and premature convergence. Four unknown parameters in the friction model are identified and verified by the improved genetic algorithm. According to the displacement signal from the sensor, a velocity observer is used to estimate the velocity signal in real time. Based on the principle of structural invariance, a dynamic friction feedforward compensation method is designed. On this basis, the experiments of friction compensation (FC) under three working conditions of sinusoidal trajectory, low and high velocities tracking were carried out for the arm electro-hydraulic system. The results show that the proposed Stribeck model and friction compensation control method effectively eliminates the low velocity crawling and amplitude flattening phenomena, and improves the control performances of the system. [ABSTRACT FROM AUTHOR]

In order to improve the trajectory tracking accuracy and robustness of a typical heavy electro-hydraulic position system, a fuzzy adaptive sliding mode controller is proposed. A potential-like function is introduced to design a new sliding surface with non-linear integral term. An adaptive controller is designed to approximate the equivalent controller in sliding mode control. Stability of the controller is demonstrated by Lyapunov method, and the chattering phenomenon caused by the nonlinear switching term is reduced by using the fuzzy switching method, 25 fuzzy rules are given to adjust the sliding mode switching controller. Simulations with sinusoidal, ramp and step signals, and experiments with leveling operation at different speeds are carried out. The proposed controller can follow the reference trajectory quickly and smoothly, and has certain anti-interference ability. Compared with the traditional sliding mode controller, the proposed controller has small tracking error, fast response and good tracking performances. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurological condition that progresses with age. Amyloid-β (Aβ) aggregation has been suggested to be a key pathogenic process in Alzheimer's disease. Ginseng polysaccharides (GP), the main biologically active components isolated from Panax ginseng C. A. Meyer (ginseng), may act as neuroprotective agents with potential benefits for AD patients. However, GP effects on Aβ pathology and AD symptoms are still unclear. Here, a 4.7-kDa GP termed GP4 was purified and subjected to basic physicochemical characterization. The biological effects of GP4 to prevent Aβ aggregation were then assessed with cross-species AD models, including Aftin-5-treated SH-SY5Y cells and cerebral organoids, and transgenic C. elegans overexpressing the full-length human Aβ 42 peptide. These analyses ultimately demonstrated that GP4 was capable of inhibiting Aβ accumulation both in vivo and vitro , and with early intervention of GP4 being sufficient to alleviate Aβ 42 -associated aging phenotypes and memory loss in C. elegans model of AD. Furthermore, neuroinflammation was significantly down-regulated in human cells and cerebral organoids. From a mechanistic perspective, the ability of GP4 to inhibit Aβ aggregation was found to be related to its ability to promote neuronal mitophagic activity. This finding offers a robust theoretical foundation for the further development of GP4 as a candidate drugs with the potential to treat AD. [Display omitted] • A 4.7-kDa ginseng polysaccharides termed GP4 was purified from Panax ginseng and subjected to basic physicochemical characterization using HPGPC, HPLC, FT-IR and NMR analyses. • GP4 was capable of inhibiting Aβ accumulation in cross-species AD models, including Aftin-5-treated SH-SY5Y cells and cerebral organoids, and transgenic C. elegans overexpressing the full-length human Aβ 42 peptide. • Early intervention of GP4 being sufficient to alleviate Aβ 42 -associated aging phenotypes and memory loss in vivo. • Neuroinflammation was significantly down-regulated in vitro models of AD. • GP4 repressed Aβ accumulation via promoting neuronal mitophagic activity. [ABSTRACT FROM AUTHOR]

This paper describes the deposition of SnO 2 and WO 3 thin films and WO 3 -SnO 2 dual-layer thin films using the sol-gel process. The microstructure and morphology of these three thin films were analyzed with FE-SEM and X-ray diffraction. The H 2 response characteristics, including response magnitude, time and transients of the three samples, were investigated at different operation temperatures and H 2 gas concentrations. Although the maximum response magnitude of 29.31 towards 1000 ppm H 2 gas appeared at 225 °C，the WO 3 -SnO 2 dual-layer films still had a response magnitude of 24.23 at 175 °C, which is much higher than those of the SnO 2 (4.19) and WO 3 (6.73) thin films. The linear response magnitude profile of the WO 3 -SnO 2 dual-layer thin films toward H 2 gas concentration was obtained. The mechanism of the enhanced gas response characteristics was explained by the band bending theory. [ABSTRACT FROM AUTHOR]

Marine umbilical provides the remote control function for offshore oil and gas exploitation, which is usually integrated by different functional components that vary widely in their mechanical properties. Under the action of external load, unreasonable cross-sectional layouts may lead to large cross-sectional deformation and contact pressure between components thus affecting the service life of an umbilical. Therefore, how to design the cross-sectional layout is a very necessary research work in order to improve service life of the umbilical to withstand various loads during operation. At present, the research on the cross-sectional layout of an umbilical is not sufficient, and there is no standardized design method in the design specification. Considering the mechanical and geometrical properties as the quantitative design objectives, the mathematical optimization model of the cross-sectional layout of an umbilical is proposed. Meanwhile, the layering strategy is introduced because of the processing and manufacturing factors. Then, the genetic algorithm (GA) with good global search performance and the generalized Lagrange multiplier (GLM) with fast convergence speed are combined to solve the above model. Finally, taking an umbilical as an example, the optimal cross-sectional layout is obtained and the effectiveness of the algorithm is verified by the numerical simulation. The results show that the optimization method proposed in this paper can quickly obtain the optimal design cross-sectional layout, and supply a specific way for the fast design of an umbilical, which has the certain engineering application value. • The cross-sectional layout design of the umbilical is a typical multi-objective optimization problem. • The quantifiable multi-objective optimization model for the cross-sectional layout of the umbilical is proposed. • The GA-GLM optimization algorithm with good global search ability and fast convergence speed is introduced. • The effectiveness of the optimization algorithm GA-GLM is verified by the numerical simulation. • The proposed multi-objective optimization algorithm can improve the design efficiency and avoid the manual process. [ABSTRACT FROM AUTHOR]

C. albicans is the most prevalent opportunistic fungal and can cause life-threatening systemic infections under certain circumstances. The inefficiency and resistance of traditional therapy make the development of novel techniques indispensable. The main components, proteins and glycoproteins, of the C. albicans cell wall are highly immunogenic and very different from those of the host, making it an ideal source of targets for antifungal drug development. This study aimed to screen and identify specific peptides that bind to the C. albicans cell wall using a phage-display peptide library, and to develop a peptide-based therapy targeted to C. albicans. After four rounds of screening, JC-1 ScFv was found to bind to the C. albicans cell wall specifically, inhibit C. albicans growth and viability in vitro , and protect mice from C. albicans infection in vivo. Further study showed that JC-1 could provoke an immune response in C. albicans -infected mice. These results indicated that JC-1 ScFv screened from a phage-display peptide library had the potential to be developed as a vector for targeting C. albicans. • After four rounds of screening, JC-1 ScFv was able to bind to C. albicans cell wall specifically • JC-1 mAb protect mice from C. albicans infection in vivo. • JC-1 provoked an immune response in C. albicans -infected mice. • JC-1 had the potential to be developed as a vector for targeting C. albicans. [ABSTRACT FROM AUTHOR]

Abstract: In this study, seedlings of tomato were treated with salt stress or alkali stress. The growth, photosynthesis and concentrations of solutes and inorganic ions in tissue sap of stressed seedlings were measured to investigate the physiological adaptive mechanisms by which tomato tolerates alkali stress. The alkali stress clearly inhibited growth and photosynthesis. With increasing salinity, the Na+ concentration and Na+/K+ ratio in leaves increased, with greater degrees of increase under alkali than under salt stress. This indicated that high-pH caused by alkali stress might affect the control of roots on Na+ uptake and increased the intracellular Na+ to a toxic level, which might be the main cause of reductions of stomatal conductance and net photosynthetic rates under alkali stress. Under salt stress, organic acids (OAs), Na+, K+ and Cl− were the main osmolytes in both roots and leaves. Under alkali stress, roots and leaves revealed different mechanisms of ion balance and osmotic regulation. Under alkali stress, in roots, OAs and Na+ were the main osmolytes, and the osmotic role of K+ was small; however, in leaves, OAs, Na+ and K+ all played important osmotic roles. The mechanisms governing ionic balance under both stresses were different. Under salt stress, the contribution of inorganic ions to keep ion balance was greater than that of OAs. However, under alkali stress, Cl−, H2PO4 − and SO4 2− concentrations decreased, and tomato might have enhanced OA synthesis to compensate for the shortage of inorganic anions. [Copyright &y& Elsevier]

Abstract: The N-linked oligosaccharides on human choriogonadotropin (hCG) and follitropin (hFSH) α-subunit loop 2 (α2) have a dominant influence on hormone efficacy. hCG analogs lacking this oligosaccharide retain approximately 40% the efficacy of the fully glycosylated hormone in cyclic AMP accumulation assays. Previous efforts to reduce efficacy further have involved removing the other N-linked oligosaccharides. We found that some intersubunit disulfide crosslinks reduced the efficacies of hCG analogs lacking only the α2 oligosaccharide. The least active analog was an hCG/hFSH chimera containing hFSH residues 95–108 in place of hCG residues 101–114 and a disulfide bond between α-subunit residue 37 and β-subunit residue 33. While it bound lutropin receptors 2- to 3-fold better than hCG and follitropin receptors 10–30% as well as hFSH, it had less than 10% and 5% the efficacies of either hormone. This suggests that complete deglycosylation will not be required to produce glycoprotein hormone analogs that have low efficacies. [Copyright &y& Elsevier]