PO-134 Optogenetics Active SNc DA Neurons Improve Locomotor Activity on Exercise-Induced fatigue Rats

Objective After optogenetics activing SNc DANs, locomotor activity ability of exercise-induced fatigue rats were recorded to research the role of nigra-striatum DA system in central mechanism of motor control. Methods Used male SD rats (220~240g), randomly divided into 6 groups: sham control group (SCG), optogenetics control group (OCG), fatigue group (FG), sham fatigue group (SFG) and optogenetics fatigue group (OFG). Virus ware injected in the right SNc at coordinates (AP:-5.30 mm, R: 2.00 mm, H-8.00 mm). The SCG/SFG injected 1 μ l saline, OCG/OFG injected 1 μl mixed virus(ChR2 with TH Cre,1:1), the fiber implantation site was deeper than the virus injection about 1 mm. Three weeks after surgery, rats attend 7D exhaustive treadmill exercise. After fatigue running, OCG/OFG/SCG/SFG were in the open field. We used two different light delivery schedules: 10 ms pulses at 20 Hz (10s) and 10 ms pulses at 3 Hz (10s). Sampling time were quiet state, 1D exhaustion, 7D exhaustion and recovery 24h. Animals were euthanized after completion of the behavioral tests. Brains were sectioned coronally in 50-μm slices, images were taken using a fluorescence microscope and determined the anatomical location of the optical fiber. Results (1) OCG/OFG obtain expression of ChR2 in DANs, this was not observed in SCG/SFG; Activation of OCG DANs with 20Hz increased the normalized mean global activity (laser on/laser off), and a significant increment in normalized mean global activity (laser on/laser off) when DANs were activated with 3Hz/20Hz in OFG (p<0.05), showing successful transfection of OCG/OFG. (2) Stimulation at 20 Hz was sufficient to improve global activity, the effects of 3 Hz did not significant, showing 20Hz stimulation possibility be related to motor regulation. (3)The global activity and total distance of rats after 7D exhaustion ware significantly lower than of quiet state (p<0.05), the difference from the quiet state and after 24h recovery is not significant, indicating that the decline in locomotor ability caused by exercise induced-fatigue is reversible. (4) The 20 Hz stimulation significantly improved the global activity of 1D and 7D exhausted rats (p<0.05), indicating that 20 Hz stimulation can effectively improve the rats locomotor activity with exercise-induced fatigue compared with 3 Hz stimulation. Conclusions (1) ChR2 virus transfection can effectively active the nigra-striatum DA system, causing changes in motor performance and increasing the locomotor ability of rats; (2) The locomotor ability of rats with exercise-induced fatigue to decrease. The total distance and global activity decreased significantly with exercise-induced fatigue; (3) Photoactivation of SNc DANs can improve the locomotor activity of rats with exercise-induced fatigue. From the perspective of stimulating effect, 20Hz is the most obvious activation reference point (NSFC: 31401018, SKXJX: 2014014, Corresponding [email protected])

PO-147 Effect of Exercise-induced Fatigue on the Electrical Activity of the External Globus Pallidus Neurons in rats

Objective The motor cortex (MC) stimulation-induced unitary responses of globus pallidus external segment (GPe) neurons in control and exercise induced-fatigue rats were recorded in vivo to examine the role of cortical-striatum-external globus pallidal pathway in the mechanism of central fatigue. Methods 32 Clean healthy male Wistar rats (260~300g), were randomly divided into 4 groups: control group (Control), 1-day fatigue group (1FG), 3-day fatigue group (3FG) and 7-day fatigue group (7FG). Rats were subjected to a 5-day adaptive treadmill training. Modified Bedford treadmill exercise with progressively increasing load was used to creat the exercise fatigue model. （3 levels:8.2 m/min, 15 min; 15m/min, 15 min; 20 m/min, lasting till exhaustion） The spontaneous unit activity and responses to MC stimulation of GPe neurons were recorded by the electrophysiological technique of extracellular recording of glass microelectrodes. Results The results showed that the firing frequency of high-frequency firing with pause (HFP) and low frequency firing with burst (LFB) in the GPe of 1FG was comparable with that of control group (P>0.05). However in 3FG and 7FG , the percentage of HFP neuron was significantly decreased (P<0.05), while the proportion of LFB was significantly increased (P<0.05), and the average firing rate of LFB was higher and inter spike intervals (ISI) was significantly lower than that of the control group. With 200μA electrical stimulation, the explosive discharge of GPe neurons was attenuated after fatigue in rats. The response of GPe neurons to variable frequency stimulation in exhausted model groups was stronger than that of the control group.MC-stimulation typically induced a triphasic response composed of early excitation, inhibition, and late excitation in GPe neurons. The population of neurons showing a short inhibition slightly increased in 3FG and 7FG. Conclusions 1. The results confirmed that GPe is an important nucleus of basal ganglia involved in the regulation of exercise-induced fatigue by the change of spontaneous activity. Electrical stimulation on the cortex can alter response patterns of GPe neurons in exercise-induced fatigue rats, the results confirmed that the Ctx-Str-GPe neural pathway is involved in the regulation of exercise fatigue, and the indirect pathway is over-activated

Anomalous size effects of effective stiffnesses in bistable counter-rotating mechanical metamaterials

Counter-rotating mechanical metamaterials have previously been found to have anomalous characteristics or functions such as auxetics effects, shape changers, and soliton transports, which are all under monostable conditions. The properties of counter-rotating mechanical metamaterials under bistable conditions have not yet been explored. Here, we found that for a bistable counter-rotating metamaterial chain, the effective stiffnesses of the two steady states are different in the chain with even-numbered nodes. For the chain with odd-numbered nodes, the effective stiffnesses corresponding to the two steady states are exactly the same. This special property is not characterized by the characteristic attenuation lengths of the underlying mechanism, but depends on the different symmetries of the underlying mechanism of the chains with odd and even nodes. In addition, the relationship between the abnormal non-monotonic size effect and equilibrium angle are clarified. More interestingly, for one-dimensional chains with even-numbered nodes, the size effect of effective stiffness bifurcates at a specific equilibrium angle, and the according mechanisms are revealed

PL - 022 Effects of exercise-induced fatigue on autonomic activity and dopamine metabolism in rats after D2DR modulation

Objective Objective:  After injection of D2DR antagonist and agonist, the autonomic activity and striatal neurons electrical activity of rats with exercise-induced fatigue were recorded to explore the role of DA receptors in the central mechanism of exercise-induced fatigue. Methods Methods: Used male Wistar rats, randomly divided into 7 groups: control group (CG), one-time exhaustive exercise group (1FG), 3D repetitive exhaust group (3FG), and 7D repetitive exhaustion group (7FG), 7D repeated exhaustive 24h recovery group (24RG) and 7D repeated exhaustive 48h recovery group (48RG). After 1 week adaptive training in rats, rats attend 7D exhaustive treadmill exercise. Subsequently, the autonomic activity changes of each group with D2DR antagonists and agonists were observed in open filed. Used glass microelectrode extracellular recording technique to observe the dorsolateral striatum neurons change of the rats injected with D2DR antagonist spiperone. Real-time PCR (RT-PCR) molecular biology methods were used to measure the expression of D1DR and D2DR in the striatum after exercise-induced fatigue. To investigate the role of DA neurotransmitter and receptor on central mechanism of exercise-induced fatigue. Results Results: (1) With the increase of treadmill exercise load, the total distance of each group became shorter, and the recovery phase gradually recovered to a quiet level. The maximum exercise speed of rats in 7FG was significantly higher than 1FG (P<0.05).The average exercise speed of rats in each group was significantly lower than CG (P<0.05).The average speed of 7FG and 24RG were significantly lower than 1FG(P<0.05). the average movement speed of the 48RG was higher than 7FG;(2) After D2DR antagonist injection, the exhaustive time of rats was significantly lower than CG(P<0.01), while the exhaustive time of D2DR agonist intervention was significantly increased (P<0.01).The active areas of the rats in the open field were concentrated in the corners and margins. The distance of normal rats in 60 min was about 159 m. The activity of rats decreased after D2DR antagonist intervention, the movement distance of rats in CG、1FG and 48RG were significant reduced;(3) After injection of D2DR antagonist, The excitability of dorsolateral striatum neurons were affected by 56.10%, 9.76% (4/41) increased excitability, and 46.34% (19/41) decreased, the inhibitory effect of D2DR agonist was higher than excitatory effects (P<0.05);(4) RT-PCR data showed that there was no significant change in the expression of D1DR in the striatum after exercise-induced fatigue, and D2DR was significantly higher than the CG (P<0.01). Conclusions Conclusion:(1) With the increase of fatigue in rats, the total distance of exercise in each group gradually decreased;(2) Exercise-induced fatigue affects the expression of DA receptors in the striatum;(3) D2DR antagonists and agonists can affect the locomotor ability of rats;(4) D2DR antagonist can inhibit striatal neurons in rats with exercise-induced fatigue, suggesting that D2DR may be one of the drug intervention targets of exercise-induced fatigue.(NSFC: 31401018, SKXJX: 2014014)

Predictors of Virologic Failure in HIV‐1–Infected Adults Receiving First‐Line Antiretroviral Therapy in 8 Provinces in China

Despite poor primary healthcare systems, free antiretroviral therapy (ART) has been available in China for over 5 years. Virologic outcomes of Chinese patients receiving ART have not been described at a national level

A Synthetic Algorithm for Tracking a Moving Object in a Multiple-Dynamic Obstacles Environment Based on Kinematically Planar Redundant Manipulators

This paper presents a synthetic algorithm for tracking a moving object in a multiple-dynamic obstacles environment based on kinematically planar manipulators. By observing the motions of the object and obstacles, Spline filter associated with polynomial fitting is utilized to predict their moving paths for a period of time in the future. Several feasible paths for the manipulator in Cartesian space can be planned according to the predicted moving paths and the defined feasibility criterion. The shortest one among these feasible paths is selected as the optimized path. Then the real-time path along the optimized path is planned for the manipulator to track the moving object in real-time. To improve the convergence rate of tracking, a virtual controller based on PD controller is designed to adaptively adjust the real-time path. In the process of tracking, the null space of inverse kinematic and the local rotation coordinate method (LRCM) are utilized for the arms and the end-effector to avoid obstacles, respectively. Finally, the moving object in a multiple-dynamic obstacles environment is thus tracked via real-time updating the joint angles of manipulator according to the iterative method. Simulation results show that the proposed algorithm is feasible to track a moving object in a multiple-dynamic obstacles environment

T cell-related ubiquitination genes as prognostic indicators in hepatocellular carcinoma

BackgroundT lymphocytes, integral to the adaptive immune system, wield pivotal influence in bolstering anti-tumor responses, and are strictly regulated by ubiquitination modification. The objective of this investigation was to devise a novel prognostic and immunotherapeutic efficacy predictor for hepatocellular carcinoma patients utilizing T cell-related ubiquitination genes (TCRUG).MethodThe single-cell RNA sequencing (scRNA-seq) data and bulk RNA data of HCC patients are derived from the GEO database and TCGA database. Based on the processing of scRNA-seq, T cell marker genes are obtained and TCRUG is obtained. Further combined with WGCNA, differential analysis, univariate Cox regression analysis, LASSO analysis, and multivariate Cox regression analysis to filter and screen TCRUG. Finally construct a riskscore for predicting the prognosis of HCC patients, the predictive effect of which is validated in the GEO dataset. In addition, we also studied the correlation between riskscore and immunotherapy efficacy. Finally, the oncogenic role of UBE2E1 in HCC was explored through various in vitro experiments.ResultBased on patients’ scRNA-seq data, we finally obtained 3050 T cell marker genes. Combined with bulk RNA data and clinical data from the TCGA database, we constructed a riskscore that accurately predicts the prognosis of HCC patients. This riskscore is an independent prognostic factor for HCC and is used to construct a convenient column chart. In addition, we found that the high-risk group is more suitable for immunotherapy. Finally, the proliferation, migration, and invasion abilities of HCC cells significantly decreased after UBE2E1 expression reduction.ConclusionThis study developed a riskscore based on TCRUG that can accurately and stably predict the prognosis of HCC patients. This riskscore is also effective in predicting the immune therapy response of HCC patients

Decreasing Excess Mortality of HIV-Infected Patients Initiating Antiretroviral Therapy: Comparison with Mortality in General Population in China, 2003–2009

To evaluate excess mortality across calendar time comparing HIV-infected patients receiving cART with the general Chinese population

Attrition among Human Immunodeficiency Virus (HIV)- Infected Patients Initiating Antiretroviral Therapy in China, 2003–2010

BACKGROUND: Mortality and morbidity from HIV have dramatically decreased in both high- and low-income countries. However, some patients may not benefit from combination antiretroviral therapy (cART) because of inadequate access to HIV care, including attrition after care initiation. METHODOLOGY/PRINCIPAL FINDINGS: The study population included all HIV-infected patients receiving cART through the Chinese National Free Antiretroviral Treatment Program from 1 January 2003 to 31 December 2010 (n = 106,542). We evaluated retention in HIV care and used multivariable Cox proportional hazard models to identify independent factors predictive of attrition. The cumulative probability of attrition from cART initiation was 9% at 12 months, 13% at 18 months, 16% at 24 months and 24% at 60 months. A number of factors were associated with attrition, including younger age, male gender, and being single or divorced. Patients with higher CD4 cell counts at cART initiation were more likely to drop out of HIV care. The proportion of patients remaining in HIV care increased in more recent calendar years and among patients who initiated modern cART regimens. CONCLUSIONS/SIGNIFICANCE: Retention in HIV care is essential for optimizing individual and public health outcomes. Attrition, even the degree observed in our study, can lead to premature morbidity and mortality, and possibly affect further transmission of HIV and HIV resistant drug variants. Effective strategies to promote retention in HIV care programs are needed. In China these strategies may include focusing particularly on younger male patients and those with higher CD4 cell counts at therapy initiation