Aristolochic acid I aggravates oxidative stress-mediated apoptosis by inhibiting APE1/Nrf2/HO-1 signaling.

Nephrotoxicity induced by aristolochic acid I (AAI) is related to redox stress and apoptosis. Apurinic/apyrimidine endonuclease 1 (APE1) has antioxidant and anti-apoptotic effects. This study investigated the potential role of APE1 in AAI-induced nephrotoxicity. Renal injury was successfully induced in C57BL/6J mice by intraperitoneal injection of AAI every other day for 28 days. Expressions of APE1, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) in renal tissues of the model mice was inhibited, accompanied by oxidative damage and apoptosis. Similar results were obtained in vitro in human proximal tubular (HK-2) cells damaged by AAI. In the presence of a low concentration of the APE1 inhibitor E3330, expression of Nrf2 and HO-1 proteins in HK-2 cells was decreased and AAI-induced apoptosis was aggravated. Overexpression of APE1 in HK-2 cells promoted the expression of Nrf2 and HO-1, and alleviated apoptosis and renal injury induced by AAI. The collective findings demonstrate that AAI can inhibit the induction of oxidative stress and apoptosis by the APE1/Nrf2/HO-1 axis, leading to AAI renal injury. Targeting APE1 may be an effective therapeutic strategy to treat AA nephrotoxicity.

MicroRNA-143-3p ameliorates collagen-induced arthritis by polarizing naive CD4+ T cells into Treg cells.

BACKGROUND: Rheumatoid arthritis (RA) is a persistent and systemic autoimmunity disease. The abnormal differentiation of Treg cells is important in pathogenesis. Despite previous studies showed that microRNAs (miRNAs, miR) are pivotal modulators of Treg cells, the effect of miRNAs on Treg cell differentiation and function is not clear. Our study wants to reveal the relationship of miR-143-3p with the differentiative ability and biofunction of Treg cells during the development of RA. METHODS: The Expressing level of miR-143-3p and cell factor generation in peripheral blood (PB) of RA sufferers were identified by ELISA or RT-qPCR. The roles of miR-143-3p in Treg cell differentiation were studied via ShRNA/lentivirus transfection. Male DBA/1 J mice were separated into control, model, control mimics, and miR-143-3p mimics groups to analyze the anti-arthritis efficacy, the differentiative ability of Treg cells, and the expression level of miR-143-3p. RESULTS: Our team discovered that the Expressing level of miR-143-3p was related to RA disease activities in a negative manner, and remarkably related to antiinflammation cell factor IL-10. In vitro, the expression of miR-143-3p in the CD4+ T cells upregulated the percentage of CD4+ CD25+ Fxop3+ cells (Tregs) and forkhead box protein 3 (Foxp3) mRNA expression. Evidently, miR-143-3p mimic intervention considerably upregulated the content of Treg cells in vivo, validly avoided CIA progression, and remarkably suppressed the inflammatory events of joints in mice. CONCLUSION: Our findings indicated that miR-143-3p could ameliorate CIA through polarizing naive CD4+ T cells into Treg cells, which may be a novel strategy to treat autoimmune diseases such as RA.

Panax notoginseng saponins (PNS) attenuate Th17 cell differentiation in CIA mice via inhibition of nuclear PKM2-mediated STAT3 phosphorylation.

CONTEXT: Rheumatoid arthritis (RA) is an autoimmune disease with aberrant Th17 cell differentiation. Panax notoginseng (Burk.) F. H. Chen (Araliaceae) saponins (PNS) have an anti-inflammatory effect and can suppress Th17 cell differentiation. OBJECTIVE: To investigate mechanisms of PNS on Th17 cell differentiation in RA, and the role of pyruvate kinase M2 (PKM2). MATERIALS AND METHODS: Naive CD4+T cells were treated with IL-6, IL-23 and TGF-ß to induce Th17 cell differentiation. Apart from the Control group, other cells were treated with PNS (5, 10, 20 µg/mL). After the treatment, Th17 cell differentiation, PKM2 expression, and STAT3 phosphorylation were measured via flow cytometry, western blots, or immunofluorescence. PKM2-specific allosteric activator (Tepp-46, 50, 100, 150 µM) and inhibitor (SAICAR, 2, 4, 8 µM) were used to verify the mechanisms. A CIA mouse model was established and divided into control, model, and PNS (100 mg/kg) groups to assess an anti-arthritis effect, Th17 cell differentiation, and PKM2/STAT3 expression. RESULTS: PKM2 expression, dimerization, and nuclear accumulation were upregulated upon Th17 cell differentiation. PNS inhibited the Th17 cells, RORγt expression, IL-17A levels, PKM2 dimerization, and nuclear accumulation and Y705-STAT3 phosphorylation in Th17 cells. Using Tepp-46 (100 µM) and SAICAR (4 µM), we demonstrated that PNS (10 µg/mL) inhibited STAT3 phosphorylation and Th17 cell differentiation by suppressing nuclear PKM2 accumulation. In CIA mice, PNS attenuated CIA symptoms, reduced the number of splenic Th17 cells and nuclear PKM2/STAT3 signaling. DISCUSSION AND CONCLUSIONS: PNS inhibited Th17 cell differentiation through the inhibition of nuclear PKM2-mediated STAT3 phosphorylation. PNS may be useful for treating RA.

Triptolide inhibits Th17 differentiation via controlling PKM2-mediated glycolysis in rheumatoid arthritis.

CONTEXT: Rheumatoid arthritis (RA) is an autoimmune disease with the aberrant differentiation of T helper 17 (Th17) cells. Pyruvate kinase M2 (PKM2), a key enzyme of glycolysis, was associated with Th17 cell differentiation. AIM: To investigate the potential therapeutic effects of triptolide (TP) in collagen-induced arthritis (CIA) and Th17 cell differentiation, and elucidated the underlying mechanisms. METHODS: PKM2 expression and IL-17A production in peripheral blood of RA patients were detected by RT-qPCR or ELISA. Flow cytometry and ELISA were employed to assess the effect of Th17 cell differentiation by TP. PKM2 expression and other glycolysis-related factors were detected using RT-qPCR and Western Blot. PKM2 specific inhibitor Compound 3 K was used to verify the mechanisms. Male DBA/1J mice were divided into control, model, and TP (60 µg/kg) groups to assess the anti-arthritis effect, Th17 cell differentiation and PKM2 expression. RESULTS: PKM2 expression positively correlated with IL-17A production in RA patients. PKM2 expression was increased upon Th17 cell differentiation. Down-regulating PKM2 expression could strongly reduce Th17 cell differentiation. Molecular docking analysis predicted that TP targeted PKM2. TP treatment significantly reduced Th17 cell differentiation, PKM2 expression, pyruvate, and lactate production. In addition, compared with down-regulating PKM2 alone (Compound 3 K treatment), co-treatment with TP and Compound 3 K further significantly decreased PKM2-mediated glycolysis and Th17 cell differentiation. In CIA mice, TP repressed the PKM2-mediated glycolysis and attenuated joint inflammation. CONCLUSION: TP inhibited Th17 cell differentiation through the inhibition of PKM2-mediated glycolysis. We highlight a novel strategy for the use of TP in RA treatment.

RBF Neural Network Sliding Mode Control for Passification of Nonlinear Time-Varying Delay Systems with Application to Offshore Cranes.

This paper is devoted to studying the passivity-based sliding mode control for nonlinear systems and its application to dock cranes through an adaptive neural network approach, where the system suffers from time-varying delay, external disturbance and unknown nonlinearity. First, relying on the generalized Lagrange formula, the mathematical model for the crane system is established. Second, by virtue of an integral-type sliding surface function and the equivalent control theory, a sliding mode dynamic system can be obtained with a satisfactory dynamic property. Third, based on the RBF neural network approach, an adaptive control law is designed to ensure the finite-time existence of sliding motion in the face of unknown nonlinearity. Fourth, feasible easy-checking linear matrix inequality conditions are developed to analyze passification performance of the resulting sliding motion. Finally, a simulation study is provided to confirm the validity of the proposed method.

Dietary Supplementation of Vine Tea Ameliorates Glucose and Lipid Metabolic Disorder via Akt Signaling Pathway in Diabetic Rats.

A traditional Chinese tea with many pharmacological effects, vine tea (VT) is considered a potential dietary supplement to improve type 2 diabetes (T2D). To investigate the effect and mechanism of VT on glucose and lipid metabolic disorders in T2D rats, Wistar rats fed a normal diet served as the normal control, while rats fed a high-fat diet combined with low-dose streptozotocin (STZ)-induced T2D were divided into three groups: The model group (MOD); the positive control group (MET, metformin at 200 mg/kg/d); and the VT-treated group (VT500, allowed to freely drink 500 mg/L VT). After four weeks of intervention, biochemical metrics indicated that VT significantly ameliorated hyperglycemia, hyperlipidemia and hyperinsulinemia in T2D rats. Metabolomics research indicated that VT regulated the levels of metabolites closely related to glucose and lipid metabolism and promoted glycogen synthesis. Furthermore, VT had a significant influence on the expression of key genes involved in the Akt signaling pathway, inhibited gluconeogenesis through the Akt/Foxo1/Pck2 signaling pathway, and reduced fatty acid synthesis via the SREBP1c/Fasn signaling pathways. In conclusion, VT has great potential as a dietary supplement to ameliorate glucose and lipid metabolic disorders via the Akt signaling pathway in T2D rats.

[Research strategy of traditional Chinese medicine proteomics].

The application of proteomics in the research of traditional Chinese medicine (TCM) is very extensive, and there have been many successful cases. In this paper, the previous studies on the complex system of TCM by using proteomics technology were reviewed, and the authors proposed to set up a special subject on proteomics in TCM, which is called TCM proteomics. In this paper, the research strategies and the future research directions of TCM proteomics were reviewed and discussed, which may provide some ideas for the researchers of TCM proteomics.

Cajaninstilbene acid prevents corticosterone-induced apoptosis in PC12 cells by inhibiting the mitochondrial apoptotic pathway.

BACKGROUND/AIMS: Cajaninstilbene acid (3-hydroxy-4-prenyl-5-methoxystilben-2 -carboxylic acid, CSA), a natural stilbene isolated from the leaves of Cajanus cajan, has attracted considerable attention for its wide range of pharmacological activities. This study investigated whether CSA protects against corticosterone (CORT)-induced injury in PC12 cells and examined the potential mechanisms underlying this protective effect. METHODS: Cell viability and cytotoxicity were detected using a 3-(4,5-desethyithiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and a lactate dehydrogenase (LDH) assay kit, respectively. PC12 cell apoptosis was measured using Hoechst 33342 staining and a DNA fragmentation assay kit, and intracellular Ca(2+) concentrations were assessed by fluorescent labelling. Next, the mitochondrial permeability transition pores (mPTPs) and mitochondrial membrane potentials (∆Ψm) were detected using a colorimetric mPTP detection kit and a 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) kit, respectively. Finally, cytochrome c, caspase-3 and inhibitor of caspase-activated deoxyribonuclease (ICAD) expression levels were monitored by western blot analysis. RESULTS: Treatment with 100 µmol/l CORT induced cytotoxicity in PC12 cells. However, CSA dose-dependently increased cell viability and decreased LDH release as well as CORT-induced apoptosis. Mechanistically, compared with the CORT-treated group, CSA strongly attenuated intracellular Ca(2+) overload and restored mitochondrial functions, including mPTPs and ∆Ψm. Furthermore, the down-regulation of cytochrome c and ICAD protein expression and the blockage of caspase-3 activity were observed upon CSA treatment. CONCLUSIONS: In summary, our data are the first to show that the in vitro antidepressant-like effect of CSA may be attributed to the cytoprotection of neurons and that such neuroprotective mechanisms are correlated with intracellular Ca(2+) homeostasis and mitochondrial apoptotic pathways.

A LC-MS-based serum pharmacochemistry approach to reveal the compatibility features of mutual promotion/assistance herb pairs in Xijiao Dihuang decoction.

Xijiao Dihuang decoction (XDT), a famous formula, was usually used to improve the prognosis of patients with blood-heat and blood-stasis syndrome-related diseases. There were some mutual promotion and mutual assistance herb pairs in XDT. However, the exact functions of these herb pairs in the compatibility of XDT were not elucidated due to the lack of appropriate methodologies. Based on the theory of serum pharmacochemistry, a systematic method was established for the qualitative and quantitative analysis of characteristic components in the extracts and drug-containing plasma samples of XDT and its relational mutual promotion/assistance herb pairs. For qualitative analysis, 85 characteristic components were identified using the liquid chromatography with triple time-of-flight mass/mass spectrometry (LC-Triple QTOF-MS/MS) based on the mass defect filtering, product ion filtering, neutral loss filtering and isotope pattern filtering techniques. For quantitative detection, a relative quantitation assay using an extract ion chromatogram (EIC) of the full scan MS experiment was validated and employed to assess the quantity of the 85 identified compounds in the test samples of single herb, herb pairs and XDT. The results of multivariate statistical analyses indicated that both the assistant and guide herbs could improve the solubilization of active compounds from the sovereign and minister herbs in XDT in vitro, might change the trans-membrane transportation, and regulate metabolism in vivo. The methods used in present study might be also valuable for the investigation of multiple components from other classic TCM formulas for the purpose of compatibility feature study.

Identifying potential Q-markers for quality evaluation of Zhenyuan capsule by integrating chemical analysis, network pharmacology, molecular docking, and molecular dynamics simulations.

Quality markers (Q-markers) are of great significance for quality evaluation of herbal medicines. Zhenyuan Capsule (ZYC) is a kind of Chinese patent medicine used to treat cardiovascular diseases. However, reliable and effective Q-markers for ZYC are still lacking. Herein, a UHPLC-Q/Orbitrap-MS/MS was performed to characterise the preliminary chemical profile of ZYC. A total of 86 components were characterised among which 20 constituents were unambiguously identified by reference compounds. Based on network pharmacology, seven major ginsenosides with great importance in the network were identified as Q-markers among which ginsenoside Re with the highest betweenness was screened to inhibit the development of coronary heart disease (CHD) by binding with vascular endothelial growth factor A (VEGFA). Docking and molecular dynamics simulation studies suggested that ginsenoside Re stably bound to VEGFA. Quantitative determination and chemical fingerprinting analysis were performed using HPLC-DAD. The results showed that ginsenosides screened might function as potential Q-markers for ZYC.

Robot path planning based on artificial potential field with deterministic annealing.

In the context of motion planning in robotics, the problem of path planning based on artificial potential fields has been examined using different algorithms to avoid trapping in local minima. With this objective, this paper proposes a novel method based on a deterministic annealing strategy to improve the potential field function by introducing a temperature parameter to increase the robot's obstacle avoidance efficiency. The annealing and tempering strategies prevent the robot from being trapped at the local minima and allow it to continue towards its destination. The initial path is optimised using an annealing algorithm to enhance the overall performance. The time, length and success rate of the planned path measures the quality of the solution. Simulation results and comparative experiments demonstrate that the proposed algorithm can solve path planning in different environments. The proposed algorithm is suitable for complex environments with convex or non-convex polygon obstacles.

Adaptive neural-network-based sliding mode control of switching distributed delay systems with Markov jump parameters.

This paper is devoted to the issue of observer-based adaptive sliding mode control of distributed delay systems with deterministic switching rules and stochastic jumping process, simultaneously, through a neural network approach. Firstly, relying on the designed Lebesgue observer, a sliding mode hyperplane in the integral form is put forward, on which a desired sliding mode dynamic system is derived. Secondly, in consideration of complexity of real transition rates information, a novel adaptive dynamic controller that fits to universal mode information is designed to ensure the existence of sliding motion in finite-time, especially for the case that the mode information is totally unknown. In addition, an observer-based neural compensator is developed to attenuate the effectiveness of unknown system nonlinearity. Thirdly, an average dwell-time approach is utilized to check the mean-square exponential stability of the obtained sliding mode dynamics, particularly, the proposed criteria conditions are successfully unified with the designed controller in the type of mode information. Finally, a practical example is provided to verify the validity of the proposed method.

An event-triggered mechanism to observer-based sliding mode control of fractional-order uncertain switched systems.

This paper is dealing with the problem of observer-based event-triggered sliding mode control for fractional-order uncertain switched systems with a positive order less than one. Firstly, a fractional-order state observer is designed, based on which a fractional-order integral sliding surface function is proposed. Then, utilizing the estimated observer error and sliding mode error vectors, an event-triggered condition is constructed to decide whether the current control signal should be updated or not. Besides, sufficient conditions are derived in the forms of linear matrix inequalities (LMIs) to ensure finite-time stability of the augmented closed-loop system by adopting an average dwell time approach. Thereafter, to avoid the occurrence of infinite triggers within finite time, this paper also discusses the Zeno behavior and refines the results in the previous literature. Finally, to illustrate the effectiveness and superiority of the proposed method, three numerical simulations are provided.

Aircraft route recovery based on distributed integer programming method.

In order to further promote the application and development of unmanned aviation in the manned field, and reduce the difficulty that airlines cannot avoid due to unexpected factors such as bad weather, aircraft failure, and so on, the problem of restoring aircraft routes has been studied. To reduce the economic losses caused by flight interruption, this paper divides the repair problem of aircraft operation plans into two sub problems, namely, the generation of flight routes and the reallocation of aircraft. Firstly, the existing fixed-point iteration method proposed by Dang is used to solve the feasible route generation model based on integer programming. To calculate quickly and efficiently, a segmentation method that divides the solution space into mutually independent segments is proposed as the premise of distributed computing. The feasible route is then allocated to the available aircraft to repair the flight plan. The experimental results of two examples of aircraft fault grounding and airport closure show that the method proposed in this paper is effective for aircraft route restoration.

Association between the systemic immune-inflammation index and outcomes among atrial fibrillation patients with diabetes undergoing radiofrequency catheter ablation.

PURPOSE: To investigate the relationship between the incidence of atrial fibrillation (AF) recurrence and the levels of the systemic immune-inflammatory index (SII, platelet × neutrophil/lymphocyte ratio) in patients with AF and diabetes mellitus (DM) undergoing after radiofrequency catheter ablation (RFCA). PATIENTS AND METHODS: Preoperative SII levels were determined in AF patients with DM undergoing RFCA. Restricted cubic splines were used to determine the correlation between SII and the risk of AF recurrence. Multivariate-adjusted logistic regression models were constructed to determine the relationship between SII levels and AF recurrence. The predictive value of the clinical model and combined with the SII index was estimated by the area under the receiver-operating characteristic curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: A total of 204 patients with AF and DM who underwent RFCA in our hospital were included. Seventy-seven patients had AF recurred during a mean follow-up of 20 months. Restricted cubic spline analysis showed that when SII ≥ 444.77 × 109 /L, there was a positive correlation with the incidence of AF recurrence. In addition, adding the SII to the predictive model for AF recurrence after RFCA in patients with DM and AF could contribute to an increase in C-statistics (0.798 vs. 0.749, p = .034). After SII was incorporated into the clinical model, the comprehensive discrimination and net reclassification tended to improve (IDI and NRI > 0, p < .05). CONCLUSION: SII was independently and positively associated with recurrence after the first catheter ablation in patients with DM and AF.

miR-125b-5p-MAPK1-C/EBPα feedback loop regulates all-trans retinoic acid resistance in acute promyelocytic leukemia.

BACKGROUND: Various studies have highlighted the significance of miR-125b-5p in tumour chemotherapy resistance; However, whether miR-125b-5p is associated with all-trans retinoic acid (ATRA) resistance in acute promyelocytic leukemia (APL) has not been reported. METHODS: Drug-resistance-related factors in APL were predicted using the DRESIS database. The expression levels of miR-125b-5p in ATRA-sensitive and ATRA-resistant APL cells were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR). A nitrotetrazolium blue (NBT) reduction assay and flow cytometry (FCM) were used to detect the effect of miR-125b-5p on ATRA resistance in APL cells. An APL xenograft tumour mouse model was established to determine the effect of miR-125b-5p on ATRA resistance. A dual-luciferase gene reporter assay, qRT-PCR, and western blotting verified the regulation by miR-125b-5p of its target gene, MAPK1, and the MAPK1 downstream factor, C/EBPα. An NBT reduction assay and FCM were used to detect the effect of C/EBPα on ATRA resistance in APL cells. Western blotting and qRT-PCR were used to assess the regulation of miR-125b-5p and MAPK1 by C/EBPα. RESULTS: miR-125b-5p expression levels were dramatically increased in ATRA-resistant APL cells. Both in vitro and in vivo experiments revealed that miR-125b-5p overexpression enhanced ATRA resistance in APL. miR-125b-5p promoted ATRA resistance by sponging MAPK1. C/EBPα was negatively regulated by miR-125b-5p, which in addition, regulated ATRA resistance in APL cells. C/EBPα also regulated the miR-125b-5p-MAPK1 axis. CONCLUSION: The findings of this study indicate that the miR-125b-5p-MAPK1-C/EBPα feedback loop regulated ATRA resistance in APL. Thus, miR-125b-5p may be a promising target for treating ATRA resistance in APL.

Integration of network pharmacology, transcriptomics and molecular docking reveals two novel hypoglycemic components in snow chrysanthemum.

Our previous studies uncovered the glucose-lowering properties of snow chrysanthemum tea, however, the active ingredients and underlying mechanisms were yet to be uncovered. Flavonoids are the most active and abundant components in snow chrysanthemum tea. In this study, we treated leptin-deficient diabetic ob/ob or high-fat diet (HFD)-induced C57BL/6 J obese mice with or without total flavonoids of snow chrysanthemum (TFSC) for 14 weeks. Results indicated that TFSC ameliorated dyslipidemia and fatty liver, thereby reducing hyperlipidemia. Further mechanism experiments, including RNA-seq and experimental validation, revealed TFSC improved glycolipid metabolism primarily by activating the AMPK/Sirt1/PPARγ pathway. Additionally, by integrating UPLC, network pharmacology, transcriptomics, and experimental validation, we identified two novel hypoglycemic compounds, sulfuretin and leptosidin, in TFSC. Treatment with 12.5 µmol/L sulfuretin obviously stimulated cellular glucose consumption, and sulfuretin (3.125, 6.25 and 12.5 µmol/L) significantly mitigated glucose uptake damage and reliably facilitated glucose consumption in insulin-resistant HepG2 cells. Remarkably, sulfuretin interacted with the ligand-binding pocket of PPARγ via three hydrogen bond interactions with the residues LYS-367, GLN-286 and TYR-477. Furthermore, a concentration of 12.5 µmol/L sulfuretin effectively upregulated the expression of PPARγ, exhibiting a comparable potency to a renowned PPARγ agonist at 20 µmol/L. Taken together, our findings have identified two new hypoglycemic compounds and revealed their mechanisms, which significantly expands people's understanding of the active components in snow chrysanthemum that have hypoglycemic effects.

Investigating the chemical profile of Rheum lhasaense and its main ingredient of piceatannol-3'-O-ß-D-glucopyranoside on ameliorating cognitive impairment.

Rheum lhasaense A. J. Li et P. K. Hsiao, a stout herb plant from the Polygonaceae, is a typical Tibetan folk herb with heat-clearing and detoxifying effects, but does not have the typical laxative effect compared with other rhubarb plants. Nevertheless, its chemical composition and pharmacological activities still lack in-depth research. The present study endeavored to analyze the possible phytochemical constituents in R. lhasaense and explore the main compound piceatannol-3'-O-ß-D-glucopyranoside (PG) effect on cognitive impairment and its underlying mechanism. The chemical profile of R. lhasaense discovered 46 compounds, including 27 stilbenoids and 13 gallotannins using UPLC-Q-TOF-MS/MS. The UPLC determined the contents of 6 main stilbenoids, among which the content of PG was the highest, up to 61.06 mg/g. Moreover, behavioral tests showed that PG (40 mg/kg and 160 mg/kg) administration markedly ameliorated memory impairments of scopolamine-induced mice. Biochemical parameters showed that PG treatment alleviated the levels of Ach, AchE, and inflammatory factors while elevating the levels of antioxidants in mice. In addition, network pharmacology was performed to reveal PG exert an mild cognitive impairment effect by participating in neurodegenerative disease pathways, proliferation and apoptosis-, and inflammation-related pathways. Eventually, the results of molecular docking and the qRT-PCR revealed that PG down-regulated the mRNA expressions of MMP3, MMP9 and BACE1 in cognitive impairment mice brain tissue. In conclusion, our results demonstrated that PG mitigated scopolamine-induced cognitive dysfunction in mice by targeting the BACE1-MMP3/9 pathway, and PG might be a promising mild AD drug candidate.

[Neuroprotective effect of longistyline A against corticosterone-induced neurotoxicity in PC12 cells].

This study is to investigate the protective effect of longistyline A against corticosterone-induced neurotoxicity in PC12 cells. While PC12 cells were exposed to 100 micromol x L(-1) corticosterone for 48 h, cell survival rate was reduced and lactate dehydrogenase (LDH) release increased. In parallel, corticosterone caused significant elevations of DNA fragmentation, [Ca2+]i and caspase-3 activity. However, when the PC12 cells were incubated with longistyline A (4.0, 8.0 and 16.0 micromol x L(-1)) in the presence of 100 micromol x L(-1) corticosterone for 48 h, the effects were evidently alleviated, but dose-dependent manner was not obvious. In summary, longistyline A could generate a neuroprotective effect against corticosterone-induced neurotoxicity in PC12 cells possibly by decreasing [Ca2+]i and caspase-3 activity.

Sliding-mode controller synthesis of robotic manipulator based on a new modified reaching law.

In this study, an adaptive modified reaching law-based switch controller design was developed for robotic manipulator systems using the disturbance observer (DO) approach. Firstly, a standard DO is employed to estimate the unknown disturbances of the plant, from which the control signal could be compensated. Then, an adaptive modified reaching law is established to dynamically adapt the switching gain of the sliding mode robust term and further guarantee the finite-time arrival of the established sliding surface. Additionally, the convergence of the error system is analyzed via the Lyapunov method. At last, the feasibility and effectiveness of the proposed control scheme are verified by using a two-joint robotic manipulator model. The simulation results show that the developed controller can achieve rapid tracking, reduce system chattering and improve the robustness of the plant. The main innovations of the work are as follows. 1) A new adaptive reaching law is proposed; it can reduce chattering effectively, and it has a fast convergence speed. 2) Regarding the nonlinear robotic manipulator model, a novel adaptive sliding-mode controller was synthesized based on the DO to estimate the unknown disturbance and ensure effective tracking of the desired trajectory.