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Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.p.) significantly impaired ORM retrieval in mice. Fiber photometry recording in METH-treated mice revealed that the activity of prelimbic cortex glutamatergic neurons (PrLGlu) was significantly reduced during ORM retrieval. Chemogenetic activation of PrLGluor glutamatergic projections from ventral CA1 to PrL (vCA1Glu-PrL) rescued ORM retrieval impairment. Fiber photometry recording revealed that dopamine (DA) levels in PrL of METH-treated mice were significantly increased, and micro-infusion of the D2 receptor (D2R) antagonist sulpiride (0.25 μg/side) into PrL rescued ORM retrieval impairment. Whole-cell recordings in brain slices containing the PrL revealed that PrLGluintrinsic excitability and basal glutamatergic synaptic transmission were significantly reduced in METH-treated mice, and the decrease in intrinsic excitability was reversed by micro-infusion of Sulpiride into PrL in METH-treated mice. Thus, the impaired ORM retrieval caused by single-dose METH administration may be attributed to reduced PrLGluactivity, possibly due to excessive DA activity on D2R. Selective activation of PrLGluor vCA1Glu-PrL may serve as a potential therapeutic strategy for METH-induced cognitive dysfunction.

We previously reported that pseudoginsenoside-F11 (PF11), an ocotillol-type saponin, significantly ameliorated Alzheimer’s disease (AD)-associated cognitive defects in APP/PS1 and SAMP8 mice by inhibiting Aβ aggregation and tau hyperphosphorylation, suggesting a potential therapeutic effect of PF11 in the treatment of AD. In the present study we further evaluated the therapeutic effects of PF11 on relieving cognitive impairment in a rat model of sporadic AD (SAD). SAD was induced in rats by bilateral icv infusion of streptozotocin (STZ, 3 mg/kg). The rats were treated with PF11 (2, 4, 8 mg·kg−1·d−1, ig) or a positive control drug donepezil (5 mg·kg−1·d−1, ig) for 4 weeks. Their cognitive function was assessed in the nest building, Y-maze, and Morris water maze tests. We showed that STZ icv infusion significantly affected the cognitive function, tau phosphorylation, and insulin signaling pathway in the hippocampus. Furthermore, STZ icv infusion resulted in significant upregulation of the calpain I/cyclin-dependent protein kinase 5 (CDK5) signaling pathway in the hippocampus. Oral administration of PF11 dose-dependently ameliorated STZ-induced learning and memory defects. In addition, PF11 treatment markedly reduced the neuronal loss, protected the synapse structure, and modulated STZ-induced expression of tau phosphorylation by regulating the insulin signaling pathway and calpain I/CDK5 signaling pathway in the hippocampus. Donepezil treatment exerted similar beneficial effects in STZ-infused rats as the high dose of PF11 did. This study highlights the excellent therapeutic potential of PF11 in managing AD.

In this paper, we examine the effect of a nascent venture's speed to legal registration during its formation on the initial venture performance in an emerging economy. Quickly obtaining legitimacy via legal registration in the early stages of a new venture's formation accelerates its resources acquisition and transition to other start‐up activities, facilitating the venture to seize dynamic entrepreneurial opportunities; however, in an emerging economy, quick legal registration also incurs substantial costs and compliance activities that may inhibit the venture's engagement in other start‐up activities. A nascent venture in an emerging economy suffers from being either too fast (early) or too slow (late) in registering its business during the formation process, and the relationship between the speed to registration and nascent venture performance is best reflected by an inverse U‐shape. Moreover, the inverse U‐relationship becomes more pronounced when the entrepreneurial opportunity is more innovative. Based on analyzing 145 nascent entrepreneurs from the event history data set of the China Panel Study of Entrepreneurial Dynamics (CPSED), we found strong support for our arguments.

Research Summary:We examine the value of political ties on firm performance in an emerging economy. Using social exchange theory, we posit that political connections propel firms to engage more in proself and prosocial activities, which mediate the relationship between political ties and firm performance. The institutional environment moderates the dual mediations such that as the institutional environment improves, the mediation effect through proself engagement weakens, whereas the mediation effect through prosocial engagement strengthens. We found support for these propositions by analyzing two samples of firms in China: A surveyed sample of 363 small‐ and medium‐sized firms and data from 2,780 publicly listed firms from 1999 to 2014. Our findings shed light on the strategic value of political ties, coinciding with the development of institutional environments. Managerial Summary:Political ties have been considered important for firm survival and performance in emerging economies, as they enable firms to obtain critical information and resources to buffer uncertainty and build up competitive advantages. Our study demonstrates that what truly matters may not be a firm’s political ties themselves but the firm’s strategic engagement in both proself and prosocial activities in order to maintain social exchange with governments. Also, our study reveals that the development of institutional environments alters the business–government exchange and influences a firm’s proself and prosocial engagement differently, making the value of political ties on a firm’s performance difficult to predict.

Methamphetamine (METH) abuse is a serious social and health problem worldwide. At present, there are no effective medications to treat METH addiction. Here, we report that aggregated single-walled carbon nanotubes (aSWNTs) significantly inhibited METH self-administration, METH-induced conditioned place preference and METH- or cue-induced relapse to drug-seeking behaviour in mice. The use of aSWNTs alone did not significantly alter the mesolimbic dopamine system, whereas pretreatment with aSWNTs attenuated METH-induced increases in extracellular dopamine in the ventral striatum. Electrochemical assays suggest that aSWNTs facilitated dopamine oxidation. In addition, aSWNTs attenuated METH-induced increases in tyrosine hydroxylase or synaptic protein expression. These findings suggest that aSWNTs may have therapeutic effects for treatment of METH addiction by oxidation of METH-enhanced extracellular dopamine in the striatum.

Gambogic acid (GA) has been approved by the Chinese Food and Drug Administration for the treatment of lung cancer in clinical trials. However, whether GA has chemosensitizing properties when combined with other chemotherapy agents in the treatment of lung cancer is not known. Here we investigated the effects of GA combined with adriamycin (ADM), a common chemotherapy agent, in regard to their activities and the possible mechanisms against lung cancer in vitro and in vivo. Cell viability results showed that sequential GA-ADM treatment was synergistic, while the reverse sequence and simultaneous treatments were antagonistic or additive, in lung cancer cells and ADM resistant cells, but not in normal cells. The combined use of GA and ADM synergistically displayed apoptosis-inducing activities in lung cancer cells. Moreover, GA in combination with ADM could promote PARP cleavage, enhance caspases activation and decrease the expression of anti-apoptotic proteins in lung cancer cells. The combined use of GA and ADM decreased the expression of P-glycoprotein and increased the accumulation of ADM in lung cancer cells. Furthermore, it was found that, prior to ADM treatment, GA could inhibit NF-B signaling pathways, which have been validated to confer ADM resistance. The critical role of NF-B was further confirmed by using PDTC, a NF-B inhibitor, which significantly increased apoptosis induction by the combination of GA and ADM and inhibited ADM-induced ABCB1 upregulation. Importantly, our results indicated that the combination of GA and ADM exerted enhanced anti-tumor effects on A549 xenograft models through inhibiting NF-B and P-glycoprotein, and attenuated ADM-induced cardiotoxicity. Collectively, these findings indicate that GA sensitizes lung cancer cells to ADM in vitro and in vivo, providing a rationale for the combined use of GA and ADM in lung cancer chemotherapy.

In this paper, we first present intuitionistic fuzzy sets with time parameter (IFSTP). Compared with intuitionistic fuzzy set (IFS), IFSTP can provide membership function with time parameter, non-membership function with time parameter, and hesitancy function with time parameter. Thus, IFSTP is more suitable for real-time controller than IFS. Then we propose a type of score function according to IFS and IFSTP. The results of pattern recognition show that the score function method is more effective than conventional distance measure method and similarity measure method. Finally, using the score function of IFSTP, we design a dynamic real time controller, which is more comprehensive and flexible than the intuitionistic fuzzy controller.

The notion of intuitionistic fuzzy sets with parameters (IFSP) is first introduced in this paper. Compared with conventional intuitionistic fuzzy sets (IFS), IFSP can improve the recognition accuracy when it is applied to pattern recognition. By analyzing the degree of hesitancy, this paper concentrates on the construction and application of intuitionistic fuzzy sets with double parameters (IFSDP). Finally, a pattern recognition example applied to automatic control system is given to demonstrate the application of IFSDP. The simulation results show that the method of IFSDP is more comprehensive and flexible than that of the traditional intuitionistic fuzzy sets.

A high accuracy rotation angle estimation algorithm based on Local Upsampling Fourier Transform (LUFT) is developed in this paper. The LUFT uses a hierarchical strategy to estimate the rotation, which consists of a transformation of rotation to translation, a fast coarse rotation estimation and a robust refinement stage as well. The coarse rotation is estimated through the conventional Phase Only Correlation (POC), then, it is refined by the resampling technique within a local neighborhood in frequency domain. Furthermore, as will be shown in many experiments, the LUFT can achieve high accuracy rotation estimation, where the accuracy is tunable to some extent. Specially, it is efficient and robust to noise.

A robot monocular localization method based on 4-DOF ego-motion model and RANdom SAmple Consensus (RANSAC) in country road environment is introduced in this paper. The algorithm uses as input only those images provided by a single camera mounted on the roof of the vehicle. Given the image motion, the stable localization of vehicle is computed by the 4-DOF ego-motion model and RANSAC algorithm, which can efficiently estimate the instantaneous steering angle and traveling distance even if the vehicle runs on bumpy road. The proposed algorithms are successfully validated on videos from an automotive platform. Furthermore, the localization results from our method are compared to the ground truth measured with a GPS/INS joint system, and the trajectory recovered from the estimated localization parameters is superimposed onto a digital map. These experimental results indicate that the algorithms are efficient and encouraging.

Background: Ethanol abuse, especially binge drinking, can be toxic to human organs. However, there have been few studies on the genotoxicity induced by ethanol in human peripheral lymphocytes under binge drinking conditions. The purpose of this study was to investigate the oxidative DNA damage induced by ethanol in human peripheral lymphocytes in vitro and the possible mechanism associated with ethanol metabolism. The concentrations of ethanol investigated in this study were 50 and 100 mM, which are equal to the ethanol concentrations in blood after binge drinking. The maximum concentration we used was 150 mM although it is not the typical blood ethanol concentration seen during binge drinking, and most people may die at such a high concentration. The purpose of using this maximum concentration was to obtain more detailed evidence about the genotoxicity induced by ethanol. The DNA repair process was also studied.

Eleven new monoterpenes, paeonidangenin (1), paeonidanin A (2), paeonidanin B (3), paeonidanin C (4), paeonidanin D (5), paeonidanin E (6), paeoniflorone (7), 4-O-methylbenzoylpaeoniflorin (8), 4-O-methylgalloylpaeoniflorin (9), 4-O-methyldebenzoylpaeoniflorin (10), and 4-O-methylalbiflorin (11), were isolated from the 60% ethanol extract of the roots of Paeonia albiflora. Their structures were determined primarily on the basis of 1D and 2D NMR techniques and MS studies. Paeonidanins D (5) and E (6) are unprecedented examples of “cage-like” monoterpene dimers. The inhibitory effects of the isolated compounds on nitric oxide production by lipopolysaccharide (LPS)-activated N9 microglia were evaluated.

We have investigated the influences of the light–dark cycle and the pineal gland on the hypnotic activity of melatonin in rats and mice. The results showed that melatonin significantly shortened time to sleep onset and wakefulness time, increased slow wave sleep, paradoxical sleep, and total sleep time in rats during the light phase of a 12‐h light: 12‐h dark cycle, by electroencephalogram recording. However, during the dark phase it had almost no significant sleep‐promoting effect except shortened time to sleep onset. Melatonin exhibited more potent sleep‐promoting effect in rats exposed to constant light compared with rats exposed to 12:12‐h light:dark at 2000 h. Melatonin markedly prolonged sleeping time in the mice exposed to constant illumination. It was found that pinealectomy was an important factor that influenced the hypnotic activity of melatonin. When melatonin was administered to pinealectomized mice, the hypnotic activity of melatonin was more intense compared with sham‐operated mice. These results demonstrated that the hypnotic activity of melatonin displayed a light‐dependence manner. These results suggested that light exposure and the functional state of the pineal gland could substantially impact the hypnotic activity of melatonin at pharmacological dosage.

We have investigated the influences of the light–dark cycle and the pineal gland on the hypnotic activity of melatonin in rats and mice. The results showed that melatonin significantly shortened time to sleep onset and wakefulness time, increased slow wave sleep, paradoxical sleep, and total sleep time in rats during the light phase of a 12-h light: 12-h dark cycle, by electroencephalogram recording. However, during the dark phase it had almost no significant sleep-promoting effect except shortened time to sleep onset. Melatonin exhibited more potent sleep-promoting effect in rats exposed to constant light compared with rats exposed to 12:12-h light:dark at 2000 h. Melatonin markedly prolonged sleeping time in the mice exposed to constant illumination. It was found that pinealectomy was an important factor that influenced the hypnotic activity of melatonin. When melatonin was administered to pinealectomized mice, the hypnotic activity of melatonin was more intense compared with sham-operated mice. These results demonstrated that the hypnotic activity of melatonin displayed a light-dependence manner. These results suggested that light exposure and the functional state of the pineal gland could substantially impact the hypnotic activity of melatonin at pharmacological dosage.

The anti‐seizure effect of oleamide, an endogenous sleep‐inducing fatty acid amide, was studied in mice. Oleamide, in the dose range 43.7–700.0 mg kg−, significantly and dose‐dependently inhibited the seizures induced by pentylenetetrazole. However, oleamide showed no inhibitory action on the seizures induced by picrotoxin, strychnine, caffeine or semicarbazide. These results provide the first evidence for the anti‐seizure effect of oleamide, and suggest that this effect may be selective to the seizure model induced by pentylenetetrazole.

The anti-seizure effect of oleamide, an endogenous sleep-inducing fatty acid amide, was studied in mice. Oleamide, in the dose range 43.7–700.0 mg kg−, significantly and dose-dependently inhibited the seizures induced by pentylenetetrazole. However, oleamide showed no inhibitory action on the seizures induced by picrotoxin, strychnine, caffeine or semicarbazide. These results provide the first evidence for the anti-seizure effect of oleamide, and suggest that this effect may be selective to the seizure model induced by pentylenetetrazole.

In this paper we view the optimal set of discriminant vectors as a global transform, and consider its separability from a global view point. Based on this idea, the concept of a generalised Fisher discriminant criterion and that of a generalised optimal set of discriminant vectors is introduced. After that, a new algorithm is given to calculate the generalised optimal set of discriminant vectors defined in this paper, which is particularly suited to the case of a small number of samples where the scatter matrix is singular. It is then applied to an experiment on human facial recognition, and the results show that the new algorithm is superior to existing methods in terms of correct classification rate.

Three novel compounds, genkwanines M (I), N (II) and optically active genkwanine O (III) are isolated.

At present, the research on robot team cooperation is still in qualitative analysis phase and lacks the description model that can quantitatively describe the dynamical evolution of team cooperative relationships with constantly changeable task demand in Multi-robot field. First this paper whole and static describes organization model HWROM of robot team, then uses Markov course and Bayesian theorem for reference, dynamical describes the team cooperative relationships building. Finally from cooperative entity layer, ability layer and relative layer we research team formation and cooperative mechanism, and discuss how to optimize relative action sets during the evolution. The dynamic evolution model of robot team and cooperative relationships between robot teams proposed and described in this paper can not only generalize the robot team as a whole, but also depict the dynamic evolving process quantitatively. Users can also make the prediction of the cooperative relationship and the action of the robot team encountering new demands based on this model.