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The ε-polylysine (ε-PL) is a food-grade antimicrobial substance. The cationic ε-PL molecules may interact with anionic components of food matrix causing turbidity, sedimentation, and hampering the antimicrobial activity. Herein, sodium alginate (SA) was used as wall material to encapsulate ε-PL, thereby to synthesize ε-PL-SA nanoparticles (ε-PL-SA-NPs). Monosaccharide composition and molecular weight of SA were characterized. The synthetic scheme is optimized and physicochemical characteristics and antimicrobial potential was investigated. Findings indicate that SA primarily consisted of mannuronic acid (95.25 %), weight average molecular weight (Mw) of SA was 176.464 kDa, and the molecular configuration of SA was irregular line clusters. The encapsulation efficiency (EE) of ε-PL in ε-PL-SA-NPs made under optimum strategy (at pH 6.0, mass ratio of ε-PL to SA is 0.14, and SA concentration is 6 mg/mL) is about 99.74 %. The particle size of ε-PL-SA-NPs is ∼541.86 nm. The SEM image showed that the ε-PL-SA-NPs had a nearly spherical morphology. Zeta-potential and FTIR data reveal the interaction between ε-PL and SA was electrostatic and the hydrogen bonding. Agar diffusion assay exhibit that ε-PL-SA-NPs had antimicrobial activity against Escherichia coli and Staphylococcus aureus. The salmon preservation experiments reveal sustained antimicrobial efficacy of ε-PL-SA-NPs., Competing Interests: Declaration of competing interest The authors declare no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The ongoing outbreak of the novel coronavirus disease 2019 (COVID-19) draws worldwide concerns due to its long incubation period and strong infectivity. Although RT-PCR-based methods are being widely applied for clinical diagnosis, timely and accurate diagnosis towards COVID-19 causing virus, the SARS-CoV-2, is still limited due to labor-intensive and time-consuming operations. Herein, we report a new viral RNA extraction method based on poly-(amino ester) with carboxyl group (PC)-coated magnetic nanoparticles (pcMNPs) for the sensitive detection of SARS-CoV-2. This method combines the lysis and binding steps into one step, and refines multiple washing steps into one step, giving a turnaround time of less than 9 min. Furthermore, the extracted pcMNP-RNA complexes can be directly introduced into subsequent RT-PCR reactions without elution. This simplified viral RNA method could be well adapted in fast manual and automated high-throughput nucleic acids extraction protocols suitable for different scenarios. A high sensitivity down to 100 copies/mL and a linear correlation between 100 and 10 6 copies/mL of SARS-CoV-2 pseudovirus particles are achieved in both protocols. Benefitting from the simplicity and excellent performances, this new method can dramatically improve the efficiency and reduce operational requirements for the early clinical diagnosis and large-scale SARS-CoV-2 nucleic acid screening., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The development of cereal foods with slow starch digestibility is important for the general improvement of human health. In this study, the quality properties of noodles with added okara, in vitro starch digestibility, and the underlying mechanisms of the influence of okara on noodles were studied. Low concentrations (5 and 10 %) of okara improved the texture, cooking, and sensory properties of the noodles. Okara decreased the rapidly digestible starch (RDS) content, increased the resistant starch (RS) content, and reduced the predicted glycaemic index (pGI) of noodles. The pasting viscosity, thermal stability, and dynamic rheological results indicated that okara improved the starch crystallite stability of wheat flour and viscoelasticity of dough. Moreover, Fourier transform infrared (FTIR) spectroscopy showed that okara promoted the formation of starch-lipid complexes and improved the short-range structural order of starch. Additionally, microstructure imaging and protein network analysis (PNA) indicated that low addition of okara promoted the compactness of the okara-gluten-starch matrix, thus reducing the contact between starch and hydrolytic enzymes. These results reveal the effect of okara on the quality properties and starch digestibility in a starch-gluten complex system., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Uranium is a radioactive heavy metal and a significant public health concern; however, its associated underlying toxicological mechanisms remain largely unknown. In this work, the uptake and efflux processes of uranium in CHO-k1 cells were studied and the cytotoxicity effects were explored. It was found that both the uptake and efflux processes took place rapidly and half of the internalized uranium was expelled within 8 h. The uranium exposure caused a decrease of cell viability and adhesion ability in a dose-dependent manner and blocked the cell cycle at the G1 stage. In addition, gene expression analysis revealed relative changes in the transcription of metabolism related genes. Further studies revealed that the cytotoxicity of uranium could be alleviated by exposing cells to a lower temperature or by the addition of amantadine-HCl, an endocytosis inhibitor. Interestingly, after uranium exposure, needle-like precipitates were observed in both intracellular and extracellular regions. These findings collectively suggest that the cellular transport of uranium is a rapid process that disturbs cell metabolism and induces cytotoxicity, and this impact could be reduced by slowing down endocytic processes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

N-isopropylbenzylamine, an isomer of methamphetamine, has been used to adulterate methamphetamine, and distributed as fake "Ice" methamphetamine by illicit manufacturers, leading to a world problem of N-isopropylbenzylamine exposure. Though it is unclear whether N-isopropylbenzylamine has addictive potential like methamphetamine, N-isopropylbenzylamine users reported side effects such as headaches and confusion. However, the pharmacological targets and cytotoxicity of this chemical remained unknown. In this study, in vitro toxicity of N-isopropylbenzylamine and its toxicity-related targets were investigated in SN4741, SH-SY5Y or PC12 cell lines that model neurons. The cell viability was analyzed by using MTT assay after incubation with N-isopropylbenzylamine for 24 h in cells. N-isopropylbenzylamine caused cell death with IC 50 values at around 1-3 mM in these cell lines. N-isopropylbenzylamine time- and concentration-dependently facilitated the expression of neuronal nitric oxide synthase (nNOS), and increased intracellular nitric oxide (NO) in SN4741 cells. Furthermore, 7-nitroindazole, a specific inhibitor of nNOS, significantly prevented N-isopropylbenzylamine-induced toxicity in vitro. These results suggested that N-isopropylbenzylamine-induced toxicity is at least partially related to the increased intracellular NO levels and the activated nNOS. Considering the circumstances that N-isopropylbenzylamine was used to adulterate and mimic methamphetamine, and the side effects associated with N-isopropylbenzylamine in abusers, our findings sounded an alarm for abuser and warn the dangerousness of N-isopropylbenzylamine for public health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Native broken-rice starch was used to create starch nanoparticles (StNPs) with particle sizes ranging from 100 nm to 800 nm. The fluorescent isothiocyanate poly-l-lysine StNPs (FITC-PLL-StNPs) were created in two steps. First, the StNPs were electrostatically modified by poly-l-lysine (PLL) molecules rich in amino acids. Second, fluorescein isothiocyanate reacted with some amino groups on PLL molecules (FITC). Fluorescence spectrophotometry was used to determine the degree of substitution (DS) and fluorescent properties of fluorescent starches. The study found that FITC-PLL-StNP-200 has higher fluorescence stability, more phagocytic cells, and a better and clearer fluorescence detecting effect than FITC-PLL-St, FITC-PLL-StNP-100, FITC-PLL-StNP-400, and FITC-PLL-StNP-800. The biological evaluation results showed that FITC-PLL-StNP-200 did not affect the viability of HeLa cells at the lysosome labeling concentration. These findings suggest that FITC-PLL-StNP-200 has strong and stable fluorescence, indicating that FITC-PLL-StNP-200 can be used as a fluorescent probe and lysosome marker in a variety of applications, particularly in biomedicine., (Copyright © 2022. Published by Elsevier B.V.)

Propofol, an intravenous short-acting anesthetic, has the potential to induce craving and relapse. Accumulated evidence demonstrates that extracellular signal-regulated kinase (ERK) plays an essential role in drug reward and relapse. In the previous study, we demonstrated that the ERK signaling pathways in the Nucleus accumbens (NAc) were involved in propofol reward. However, the role of the ERK signaling pathways in propofol relapse is still unknown. We first trained rats to self-administer propofol for 14 days, then evaluated propofol-seeking behavior of relapse induced by a contextual cues and conditioned cues after 14-day withdrawal. Meanwhile, MEK inhibitor U0126 was used to investigate the role of the ERK signal pathways in propofol-seeking behavior induced by contextual cues and conditioned cues. Results showed that the number of active nose-poke responses in propofol-seeking behavior induced by conditioned cues was much higher compared to contextual cues. U0126 (5.0 μg/side, Lateral Ventricle (LV)) pretreatment significantly decreased the active responses induced by conditioned cues, which was associated with a large decline in the expression of p-ERK in the NAc. Moreover, microinjectionofU0126 (2.0 μg/side) in the NAc also attenuated the active responses of propofol-seeking behavior. Additionally, microinjections with U0126 in the LV (5.0 μg/side) or NAc (2.0 μg/side) both failed to alter sucrose self-administration or locomotor activity of rats. Therefore, we conclude that ERK phosphorylation in the NAc maybe involved in propofol relapse., Competing Interests: Declaration of competing interest The research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Methamphetamine (METH) use disorder has been shown to be in high comorbidity with cognitive deficits. METH-induced cognitive deficits are accompanied by neurotoxicity which could result from neuroinflammation. The potential role of NLRP1 inflammasome (NLRP1) and the downstream signalling pathway in METH-induced cognitive impairment was explored in the current study. Cognitive functions and the changes of NLRP1/Caspase-1/GSDMD signalling pathway were firstly determined in rats receiving daily injections of METH. Subsequently, the effects of aspirin-triggered-lipoxin A4 (ATL), a potent anti-inflammatory mediator, and NLRP1 siRNA was investigated were investigated in both METH-treated rats and HT22 cells. METH induces significant cognitive deficits in rats, using the NOR test. METH-induced cognitive impairment was in line with increased activities of NLRP1, cleaved-Caspase-11, IL-1β and TNF-α and the presence of GSDMD-mediated pyroptosis in the hippocampus of rats. NLRP1 inhibition by ATL significantly attenuated METH-induced cognitive impairment, in conjunction with the decreased activities of NLRP1 and cleaved-Caspase-1, IL-1β and TNF-α. ATL and NLRP1 siRNA also prevented the presence of apoptosis in the hippocampus of METH-treated rats and the cell death in METH-treated HT22 cells. These results reveal a novel role of NLRP1 and the downstream signaling pathways in the complex actions of METH-induced cognitive deficits., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The molecular and behavioral aspects of α-pyrrolidinopentiophenone (α-PVP) have been characterized; however, how the structural modification of α-PVP affects its abuse potential is still unknown. In this study, we investigated the abuse potential of two pyrrolidinylated second-generation cathinones:4-chloro-α-pyrrolidinopentiophenone (4cl-α-PVP) and 4-chloro-α-pyrrolidinopropiophenone (4cl-α-PPP). Male Sprague-Dawley rats were trained to self-administer methamphetamine (METH, 0.05 mg·kg -1 ·infusion -1 ), α-PVP (0.05 mg·kg -1 ·infusion -1 ), 4cl-α-PVP (0.05 mg·kg -1 ·infusion -1 ), and 4cl-α-PPP (0.5 mg·kg -1 ·infusion -1 ) under a fixed ratio (FR) 1 reinforcement schedule for 10 sessions. The discriminative-stimulus effect of METH (0.8 mg/kg) from saline was tested under an FR10 schedule of food delivery. α-PVP, 4cl-α-PVP and 4cl-α-PPP produced reinforcement behaviors and presented an inverted U-shaped dose effect. The reinforcing potency was displayed with a rank order of α-PVP (0.029 mg·kg -1 ·infusion -1 ) > METH (0.040 mg·kg -1 ·infusion -1 ) > 4cl-α-PVP (0.094 mg·kg -1 ·infusion -1 ) > 4cl-α-PPP (0.51 mg·kg -1 ·infusion -1 ). All three drugs were fully substituted for the discriminative-stimulus effects of METH in rats. The substitution potency for discriminative-stimulus effects of α-PVP (ED 50  = 0.4 mg/kg) was approximately equal to that of METH (ED 50  = 0.3 mg/kg), while the discriminative potency of 4cl-α-PVP (ED 50  = 1.0 mg/kg) and 4cl-α-PPP (ED 50  = 5 mg/kg) was approximately 3 and 16-fold less than that of METH. The rank order of potency was α-PVP ≈ METH >4cl-α-PVP > 4cl-α-PPP. The present data demonstrated that 4cl-α-PVP and 4cl-α-PPP produced reinforcing effects and fully and dose-dependently substituted for the subjective effects of METH, suggesting that both 4cl-α-PVP and 4cl-α-PPP have abuse potential that may be similar to METH., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Fast pyrolysis biofuel is considered as one of the promising alternative fuels for future transportation. The authors' research group has improved a pyrolysis biofuel production method for obtaining a biofuel from rice husk. Preliminary research published in Fuel reveals that it has the potential of being used as a gasoline blending component. Before this biofuel can be widely used in real combustors or engines at a large scale, its explosion characteristics should be investigated for the safety consideration during production, transport and storage. This paper quantitatively evaluates explosion pressure, deflagration index, maximum pressure rise rate and combustion duration of this biofuel in the constant volume combustion chamber (CVCC). At the same time, the effects of initial pressure, initial temperature and equivalence ratio on explosion characteristics of this biofuel was also qualitatively analyzed. Linear relationships between explosion pressure, deflagration index, maximum pressure rise rate and combustion duration versus initial pressure and explosion pressure versus initial temperature are given. Results show that explosion pressure is a linear relationship with the initial temperature. However, deflagration index, maximum pressure rise rate and combustion duration are insensitive to the temperature variation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Heroin addiction is a disorder that stems from maladaptive plasticity within neural circuits and produces broad cognitive deficits. Despite considerable advances in psychotherapy and pharmacotherapy for heroin relapse and addiction, effective treatments for heroin use disorder are still lacking. Increasing preclinical evidence indicates that heroin seeking behavior is persistent after withdrawal, while cognitive dysfunctions associated with chronic heroin use are an important contributing factor to risk of heroin relapse and addiction. Cognitive enhancers may be used to stimulate treatment success and enhance treatment efficacy. The purpose of this review is to outline the literature that demonstrates the cognitive deficits during the development of heroin addiction and withdrawal process, and several factors that underline the efficacy of cognitive enhancers for heroin use disorders. The review, then, examines the potential use and pharmacological mechanisms of cognitive enhancers that act on cholinergic, glutamatergic, dopaminergic or adrenergic pathways. It also examines the effects of compounds that alter CREB signaling and epigenetic mechanisms in animal model of heroin relapse. The current body of research reveals the new insights into the pharmacological mechanisms underlying heroin addiction and holds a significant promise for cognitive enhancers as an improved approach to treat heroin use disorder in a more efficient and persistent way., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The plateau pika (Ochotona curzoniae), one of the indigenous animals of the Qinghai-Tibet Plateau, is adapted to life in a cold and hypoxic environment. We conducted a series of genomic, proteomic and morphological studies to investigate whether changes in energy metabolism contribute to adaptation of the plateau pika to cold stress by analyzing summer and winter cohorts. The winter group showed strong morphological and histological features of brown adipose tissue (BAT) in subcutaneous white adipose tissue (sWAT). To obtain molecular evidence of browning of sWAT, we performed reverse transcription and quantitative real-time PCR, which revealed that BAT-specific genes, including uncoupling protein 1 (UCP-1) and PPAR-γ coactivator 1α (PGC-1α), were highly expressed in sWAT from the winter group. Compared with the summer group, Western blot analysis also confirmed that UCP-1, PGC-1α and Cox4 protein levels were significantly increased in sWAT from the winter group. Increased BAT mass in the inter-scapular region of the winter group was also observed. These results suggest that the plateau pika adapts to cold by browning sWAT and increasing BAT in order to increase thermogenesis. These changes are distinct from the previously reported adaptation of highland deer mice. Understanding the regulatory mechanisms underlying this adaptation may lead to novel therapeutic strategies for treating obesity and metabolic disorders., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Because of consistent demand for identification of molecular targets for diagnosis and treatment, ancillary tests are increasingly being developed for cytology specimens. One time-consuming step in this procedure is glass coverslip removal by xylene. Here we describe a method for rapid coverslip removal using liquid nitrogen., Materials and Methods: Direct smears were prepared from residual pleural fluid, Diff-Quik stained, then covered with a glass coverslip. Coverslips were then removed by either immersing the slides in xylene for 3 to 4 days, or by a razor blade after rapidly freezing the slides in liquid nitrogen. The DNA or RNA was extracted, and the quantities of DNA and RNA were evaluated. The amplifiability of the DNA and RNA was also evaluated by real-time polymerase chain reaction (PCR) and real time reverse transcription (RT)-PCR., Results: The concentrations of DNA isolated using the two procedures are not significantly different (2.79 μg/mL with liquid nitrogen method versus 2.56 μg/mL with xylene method, n = 5). Similar results were observed for RNA concentration (13.28 μg/mL versus 12.22 μg/mL). The DNA extracted from the two procedures can be amplified without significant difference. Similar results were obtained from real time RT-PCR for RNA samples., Conclusions: By removing the coverslip from the cytology slides using the liquid nitrogen method, DNA and RNA can be extracted from the slides without affecting the quantity and quality of the nucleic acids, and is equivalent to the xylene coverslip removal method., (Copyright © 2016 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Polydimethylsiloxane(PDMS) is a common industrial polymer with advantages such as ease of fabrication, tunable hardness, and other desirable properties, but the basic (-OSi(CH 3 ) 2 -) n structure in PDMS is inherently hydrophobic thereby hampering application to biomedical engineering. In this study, plasma immersion ion implantation (PIII) is conducted on PDMS to improve the biological properties. PIII forms wrinkled "herringbone" patterns and abundant O-containing functional groups on PDMS to alter the surface hydrophilicity. The biocompatibility of the modified PDMS is assessed with Chinese hamster ovarian cells and compared to that of the untreated PDMS. Our results reveal that the PDMS samples after undergoing PIII have better cytocompatibility and lower genotoxicity. PIII which is a non-line-of-sight technique extends the application of PDMS to the biomedical field., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Rationale: The role of glycogen synthase kinase-3 (GSK-3) has recently been implicated in the neurochemical mechanism underlying ketamine-induced neuronal toxicity and behavioral disturbance., Objectives: The primary goal of the present study was to determine the role of GSK-3β in ketamine self-administration (SA) and relapse to drug-seeking behavior after abstinence., Methods: In Experiment 1, the level of phosphorylated GSK-3β (p-GSK-3β) and total GSK-3β (t-GSK-3β) was determined in various brain areas following 14 days of ketamine SA. In Experiments 2 and 3, the effects of a GSK-3β inhibitor, SB216763 (2 and 4 mg/kg) and a GSK-3 inhibitor, lithium (LiCl, 100mg/kg) on the responding maintained by 0.5mg/kg/infusion ketamine SA were evaluated. In Experiments 4 and 5, rats underwent ketamine SA for 14 days followed by a 10-day abstinence period. The animals were treated with 2 or 4 mg/kg GSK-3β inhibitor, or 100mg/kg LiCl during the cue-induced relapse test. Seven days later, animals received the same drug treatment and underwent the drug-induced relapse test. Finally, the effect of saline and DMSO on locomotor activity was evaluated in Experiment 6., Results: Ketamine SA significantly decreased the ratio p-GSK-3β and t-GSK-3β (p-GSK-3β:t-GSK-3β) in the caudate putamen, nucleus accumbens, and ventral tegmental area. Both SB216763 and LiCl decreased responding on a progressive ratio schedule, but not on a fixed ratio schedule. Cue-induced relapse was suppressed only by 4mg/kg SB216763, whereas drug-induced relapse was inhibited by 2, 4 mg/kg SB216763 and LiCl. However, inactive responses were also suppressed by LiCl during progressive ratio and drug-induced relapse testing., Conclusions: SB216763 was effective at decreasing ketamine SA under the PR schedule and reducing drug-seeking behavior after abstinence., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

Recent studies demonstrate that the neuropeptide VGF (nonacronymic)-derived peptide is regulated in the hippocampus by antidepressant therapies. Brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), cAMP response element-binding protein (CREB) signaling, and monoamine transmitter pathways mediate the behavioral effects of antidepressants, but it is not known if these pathways also contribute to the antidepressant-like effects of VGF-derived peptide TLQP62. Here the antidepressant-like effects of TLQP62 were evaluated by measuring immobility time in the forced swimming and tail suspension tests (FST and TST) following acute microinjection of the TLQP62 (0.25, 0.5 and 1 nmol/side) into the hippocampal CA1 regions. This treatment dose-dependently reduced immobility in the FST and TST compared to phosphate-buffered saline (PBS) infusion without affecting locomotor activity in the open field test (OFT). In addition, daily intrahippocampal microinfusion of TLQP62 (1 nmol/side/day; 21 days) also upregulated the expression of BDNF and the phosphorylation of CREB (pCREB) and TrkB (pTrkB) without altering CREB or TrkB. Blocking tissue plasminogen activator (tPA) by microinfusion of tPASTOP or TrkB activation by microinfusion of K252a 60 min prior to TLQP62 infusion almost completely abolished TLQP62-induced antidepressant-like effects, BDNF upregulation, and CREB/TrkB phosphorylation. In contrast, none of these effects were diminished by pretreatment with the non-specific 5-HT receptor antagonist metergoline, the selective 5-HT1A receptor antagonist NAN-190, the 5-HT synthase inhibitor parachlorophenylalanine, the selective α1-adrenoceptor antagonist prazosin, the β receptor antagonist propranolol, or the D2 receptor antagonist raclopride. Moreover, our study was also to investigate the antidepressant-like effects of TLQP62 (50, 250 and 500 nmol/kg; i.p.) on depression-related behaviors in comparison with fluoxetine (10mg/kg; i.p.). While TLQP62 and fluoxetine showed similar antidepressant-like behavioral effects in the FST of mice. Our present results strongly suggest that activation of BDNF/TrkB/CREB signaling may be involved in the antidepressant-like effects of TLQP62., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Surgical ablation of select brain areas has been frequently used to alleviate psychological dependence on opiate drugs in certain countries. However, ablative brain surgery was stopped in China in 2004 due to the related ethical controversy and possible side effects. Deep brain stimulation (DBS), a less invasive, reversible and adjustable process of neuromodulation, was adopted to attenuate relapses in studies of drug addiction., Methods: Preclinical experiments were designed to assess the long-term effects of DBS of the nucleus accumbens (NAc) on cue- and heroin-induced reinstatement of drug seeking behaviors. After a rat self-administration model of heroin relapse was established, DBS was administered bilaterally or unilaterally to the NAc core through concentric bipolar electrodes. A 1-h long continuous stimulation (130 Hz, 100 μs, 0-150 μA) was given daily for 7 days during the abstinence session. Drug seeking behaviors were elicited by conditioned cues or a small dose of heroin., Results: 75 μA and 150 μA bilateral NAc DBS attenuated cue- and heroin-induced reinstatement of drug seeking, and unilateral DBS of the right NAc achieved effects almost equivalent to bilateral DBS. Additional experiments showed that DBS had no long-term influence on locomotor activity and spatial learning and retention capabilities in Morris water maze tasks. Subsequent immunohistochemistry measurements revealed that the behavioral consequences were associated with a significant increase in the expression of pCREB and a reduction in the expression of ΔFosB in the NAc., Conclusions: These findings indicate that the NAc DBS could be an effective and safe therapeutic option for preventing relapse to heroin addiction., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Curcumin, a major active component of Curcuma longa, possesses antidepressant effects that are mediated by the 5-HT system. However, little is known about the effect of curcumin on the behavioral consequences of methamphetamine (METH)., Methods: The subjects were male, adult Sprague-Dawley rats. In Experiment 1, the effects of 20 and 40 mg/kg curcumin (i.p.) on response rates and breakpoints of 0.06 mg/kg/infusion METH were evaluated. In Experiment 2, rats were self-administering METH for 10 days followed by a 14-day abstinence period. During the abstinence period, the animals were treated with DMSO, 20 or 40 mg/kg curcumin. All rats were then tested for extinction responding and cue-induced reinstatement. In Experiment 3, rats were treated with DMSO, 20, or 40 mg/kg curcumin 15 min before a METH-induced locomotor activity test for 14 consecutive days. In Experiment 4, rats were pretreated with DMSO or curcumin (20 mg/kg or 40 mg/kg) for 13 days and were subsequently tested for METH-induced locomotor activity on the 14th day. In Experiment 5, three groups were tested for locomotor activity after an injection of DMSO, 20, or 40 mg/kg curcumin. The test was repeated for 14 days., Results: Curcumin produced little effect on response rates and breakpoints maintained by METH. Chronic treatment of only 40 mg/kg curcumin during the abstinence phase enhanced cue-induced reinstatement of METH self-administration. Chronic administration of curcumin increased METH-induced sensitization of locomotor activity at the lower (20 mg/kg) but not higher (40 mg/kg) dose. However pretreatment of curcumin alone showed no significant effect on acute locomotor responses to METH and locomotor responses per se., Conclusions: Curcumin enhanced, rather than inhibited the behavioral effects of METH., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Little is known about the effect of different rearing conditions on the effects of methamphetamine and whether the introduction of enriched rearing conditions at different stages of development could produce different behavioral outcomes., Methods: In Experiment 1, rats were reared in either enriched (EE) or isolated environments (IE) from PND 21 to 60. In Experiment 2, two groups of animals were handled in the same fashion as those in Experiment 1. Additional two groups were housed in IE during the first 20 or 30 days and then housed under EE for the remaining 20 or 10 days respectively. Locomotor activity and Morris Water Maze were tested. The effects of rearing conditions on methamphetamine (METH) self-administration were investigated., Results: IE animals exhibited higher levels of locomotion than EE animals, but EE animals showed enhanced Morris water maze performance. Animals reared in IE for 30 and 40 days more readily acquired METH self-administration, compared to those reared in IE for 20 and in EE for 40 days respectively. However, the effect of rearing conditions was only seen at the lowest dose tested under FR schedule and breakpoints obtained from PR schedule were not significantly affected. Those reared in IE for 20 and EE for 40 days animals produced significantly fewer responses during the extinction and cue-induced reinstatement of METH self-administration, compared with animals reared in IE for 30 and 40 days, respectively., Conclusion: Rearing condition plays a significant role in locomotor activity, spatial memory and behavioral effects of METH., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

In the wake of the deteriorating situation of drug addiction and related infectious diseases among injecting drug users (IDUs) in China in recent years, the Standing Committee of the National People's Congress of China adopted the new Drug Control Law which came into force in June 1, 2008. This law is part of a broad reform movement in China where drug addiction is no longer understood as simply a legal or moral issue but rather, as a complicated medical condition requiring comprehensive therapeutic strategies. Although the Drug Control Law draws a distinct line from previous Drug Control regulations in the country, there have still been dilemmas along the implementation process. This paper is intended to elaborate on the general principles of China's latest Drug Control Law from the point of view of scholars who are involved in the field of drug addiction research and treatment in China. This paper will also discuss the challenges we are currently facing, based on the observations and practical experiences the authors have obtained in China. It is hoped that by addressing these issues, we will be able to implement the new Drug Control Law more successfully and ensure that we deal more effectively with drug addiction in China., (Copyright 2009. Published by Elsevier B.V.)

Severe deficiency of ADAMTS13, a plasma metalloprotease, leads to thrombotic thrombocytopenic purpura. ADAMTS13 contains 10 putative N-glycosylation sites in or near its metalloprotease sequence, spacer region, thrombospondin type 1 repeat no. 4 (TSR no. 4), and CUB domains. Tunicamycin treatment markedly decreased the secretion of ADAMTS13 into the culture medium of transfected cells. Nevertheless, the protease was efficiently secreted from N-acetylglucosaminyltransferase I-deficient Lec1 Chinese hamster ovary cells, indicating that N-glycosylation in the endoplasmic reticulum, but not the conversion of oligomannose to complex N-glycans in the Golgi complex, is important for secretion. However, ADAMTS13 with oligomannose N-glycans cleaved its substrate, von Willebrand factor (VWF) multimers, less effectively, with a higher K(m) but similar k(cat) value. In mutagenesis analysis, decreased secretion and VWF cleaving activity was observed with the N146Q and N828Q mutants, while decreased secretion only was observed with the N552Q mutant of ADAMTS13. Enzymatic removal of N-glycans from ADAMTS13 did not affect its VWF cleaving activity. Thus, N-glycosylation is necessary for efficient secretion of ADAMTS13, while conversion of the N-glycans from oligomannose to complex type in the Golgi complex enhances the proteolytic activity of the protease toward VWF multimers. After its secretion, ADAMTS13 does not require N-glycans for its VWF cleaving activity.

Background: Previous studies show that the acute administration of N-acetylcysteine (NAC) inhibits the desire for cocaine in addicts and cocaine-seeking in animals., Methods: Rats were trained to self-administer heroin, and the reinstatement model of drug seeking was used to determine whether chronic NAC treatment inhibited heroin-seeking., Results: Daily NAC administration inhibited cue- and heroin-induced seeking. Moreover, repeated NAC administration during extinction training reduced extinction-responding and inhibited cue- and heroin-induced reinstatement for up to 40 days after discontinuing daily NAC injection., Conclusions: These data show that daily NAC inhibits heroin-induced reinstatement and produces an enduring reduction in cue- and heroin-induced drug seeking for over 1 month after the last injection of NAC. Both the inhibitory effect of NAC on the reinstatement of heroin-seeking and the ability of NAC to reduce extinction-responding support clinical evaluation of repeated NAC administration to decrease in drug-seeking in heroin addicts.

Severe deficiency of ADAMTS13, a von Willebrand factor (VWF)-cleaving metalloprotease, causes thrombotic thrombocytopenic purpura. When analyzed with VWF multimers, but not with an abbreviated VWF peptide (VWF73) as the substrate, the plasma ADAMTS13 activity levels of mouse strains segregated into a high and a low group that differed by approximately 10 fold. Low ADAMTS13 activity was detected in mice containing 2 alleles of intracisternal A-type particle (IAP) retrotransposon sequence in the ADAMTS13 gene. Molecular cloning of mouse ADAMTS13 identified 2 truncated variants (IAP-a and IAP-b) in the low-activity mice. Both of the IAP variants lacked the 2 carboxyl terminus thrombospondin type 1 repeat (TSR) and CUB domains of full-length ADAMTS13. The IAP-b variant also had splicing abnormalities affecting the spacer domain sequence and had miniscule enzymatic activity. Compared with full-length ADAMTS13, the IAP-a variant was approximately one ninth as active in cleaving VWF multimers but was only slightly less active in cleaving VWF73 peptide. Recombinant human ADAMTS13 was also less effective in cleaving VWF multimers than VWF73 when the C-terminal TSR sequence was deleted. In summary, the carboxyl terminus TSR sequence is important for cleaving VWF multimers. Assay results should be interpreted with caution when peptide substrates are used for analysis of variant ADAMTS13 proteins.

Conditioned stimuli (CSs) previously associated with heroin are critically involved in activating long-lasting relapse and compulsive drug seeking. This study examined the magnitude of heroin seeking induced by drug-related cues in relation to the total amount of drug exposure during training. Five groups of male Sprague-Dawley rats (n=6/group) were trained by the nose-poking response to self-administer different doses of heroin (0, 0.01, 0.025, 0.05, and 0.1 mg/kg per infusion respectively, one 4-h session daily, limited to 25 infusions per session) under an identical progressive ratio schedule with gradual incremental response requirements. All the rats established stable heroin self-administration within 14 days of self-administration training, and the time needed to obtain all the 25 heroin infusions decreased across sessions. After 14 days of abstinence, heroin seeking elicited by contextual cues (self-administration chamber) or discrete contingent CSs previously associated with heroin infusions was measured in two consecutive 1-h test phases. During both test phases, the rats trained with heroin even at the lowest dose (0.01 mg/kg) showed higher active responses than saline controls, and the active responses were also higher in rats trained with doses of 0.025, 0.05, and 0.10 mg/kg in comparison with those trained with a dose of 0.01 mg/kg. There was no observable dose-dependence increase of responses at doses above 0.025 mg/kg. The results suggested that an increased motivation to seek heroin induced by drug-related cues is associated with the total amount of heroin intake.