Relationships Between Prenatal Cocaine Exposure, Cannabis-Use Onset and Emotional and Related Characteristics in Young/Emerging Adults.

Background: Exposure to substances in utero may have significant early-life consequences. Less is known about the effects in emerging adulthood, particularly regarding patterns of substance use and related characteristics.Objectives: In this study, we recruited emerging adults, followed since birth, who had been prenatally exposed, or not, to cocaine. Individuals reported on their cannabis, alcohol, and tobacco use, and measures of impulsivity, anhedonia, emotional regulation, and mental health were obtained. Comparisons were made between emerging adults with prenatal cocaine exposure and those without. Correlations were performed between psychological measures and substance use, and regression analyses were conducted to determine potential pathways by which such measures may relate to prenatal exposure or substance use.Results: Individuals with prenatal cocaine exposure (vs. those without) used cannabis at younger ages, reported greater cannabis-use severity, and demonstrated higher impulsivity, state anxiety, and alexithymia. Earlier age of onset of cannabis use was associated with higher impulsivity, state anxiety, alexithymia, and social and physical anhedonia. Cannabis-use age-of-onset mediated the relationship between prenatal cocaine-exposure status and state anxiety and between prenatal cocaine-exposure status and cannabis-use severity in emerging adulthood but not relationships between prenatal cocaine-exposure status and impulsivity or alexithymia in emerging adulthood. Findings suggest that adults with prenatal cocaine exposure may use cannabis at younger ages, which may relate to increased anxiety and more severe use.Conclusions: These findings suggest both mechanisms and possible intervention targets to improve mental health in emerging adults with prenatal cocaine exposure.

Graphitic Armor: A Natural Molecular Sieve for Robust Hydrogen Electroxidation.

Carbon coating layers have been found to improve the catalytic performance of transition metals, which is usually explained as an outcome of electronic synergistic effect. Herein we reveal that the defective graphitic carbon, with a unique interlayer gap of 0.342 nm, can be a highly selective natural molecular sieve. It allows efficient diffusion of hydrogen molecules or radicals both along the in-plane and out-of-plane direction, but sterically hinders the diffusion of molecules with larger kinetic diameter (e.g., CO and O2) along the in-plane direction. As a result, poisonous species lager than 0.342 nm are sieved out, even when their adsorption on the metal is thermodynamically strong; at the same time, the interaction between H2 and the metal is not affected. This natural molecular sieve provides a very chance for constructing robust metal catalysts for hydrogen-relevant processes, which are more tolerant to chemical or electrochemical oxidation or CO-relevant poisoning.

Reconstructing 3d-Metal Electrocatalysts through Anionic Evolution in Zinc-Air Batteries.

As one of the promising sustainable energy storage systems, academic research on rechargeable Zn-air batteries has recently been rejuvenated following development of various 3d-metal electrocatalysts and identification of their dynamic reconstruction toward (oxy)hydroxide, but performance disparity among catalysts remains unexplained. Here, this uncertainty is addressed through investigating the anionic contribution to regulate dynamic reconstruction and battery behavior of 3d-metal selenides. Comparing with the alloy counterpart, anionic chemistry is identified as a performance promoter and further exploited to empower Zn-air batteries. Based on theoretical modeling, Se-resolved operando spectroscopy, and advanced electron microscopy, a three-step Se evolution is established, consisting of oxidation, leaching, and recoordination. The process generates an amorphous (oxy)hydroxide with O-sharing bonded Se motifs that triggers charge redistribution at metal sites and lowers the energetic barrier of their current-driven redox. A pervasive concept of Se back-feeding is then proposed to describe the underlying chemistry for 3d-metal selenides with diversity in crystals or compositions, and the feasibility to fine-tune their behavior is also presented.

LiMgPO4 -Coating-Induced Phosphate Shell and Bulk Mg-Doping Enables Stable Ultra-High-Voltage Cycling of LiCoO2 Cathode.

Stable cycling of LiCoO2 (LCO) cathode at high voltage is extremely challenging due to the notable structural instability in deeply delithiated states. Here, using the sol-gel coating method, LCO materials (LMP-LCO) are obtained with bulk Mg-doping and surface LiMgPO4 /Li3 PO4 (LMP/LPO) coating. The experimental results suggest that the simultaneous modification in the bulk and at the surface is demonstrated to be highly effective in improving the high-voltage performance of LCO. LMP-LCO cathodes deliver 149.8 mAh g-1 @4.60 V and 146.1 mAh g-1 @4.65 V after 200 cycles at 1 C. For higher cut-off voltages, 4.70 and 4.80 V, LMP-LCO cathodes still achieve 144.9 mAh g-1 after 150 cycles and 136.8 mAh g-1 after 100 cycles at 1 C, respectively. Bulk Mg-dopants enhance the ionicity of CoO bond by tailoring the band centers of Co 3d and O 2p, promoting stable redox on O2- , and thus enhancing stable cycling at high cut-off voltages. Meanwhile, LMP/LPO surface coating suppresses detrimental surface side reactions while allowing facile Li-ion diffusion. The mechanism of high-voltage cycling stability is investigated by combining experimental characterizations and theoretical calculations. This study proposes a strategy of surface-to-bulk simultaneous modification to achieve superior structural stability at high voltages.

Analyzing molecular typing and clinical application of immunogenic cell death-related genes in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is considered one of the most common cancers, characterized by low early detection and high mortality rates, and is a global health challenge. Immunogenic cell death (ICD) is defined as a specific type of regulated cell death (RCD) capable of reshaping the tumor immune microenvironment by releasing danger signals that trigger immune responses, which would contribute to immunotherapy. METHODS: The ICD gene sets were collected from the literature. We collected expression data and clinical information from public databases for the HCC samples in our study. Data processing and mapping were performed using R software to analyze the differences in biological characteristics between different subgroups. The expression of the ICD representative gene in clinical specimens was assessed by immunohistochemistry, and the role of the representative gene in HCC was evaluated by various in vitro assays, including qRT-PCR, colony formation, and CCK8 assay. Lasso-Cox regression was used to screen prognosis-related genes, and an ICD-related risk model (ICDRM) was constructed. To improve the clinical value of ICDRM, Nomograms and calibration curves were created to predict survival probabilities. Finally, the critical gene of ICDRM was further investigated through pan-cancer analysis and single-cell analysis. RESULTS: We identified two ICD clusters that differed significantly in terms of survival, biological function, and immune infiltration. As well as assessing the immune microenvironment of tumors in HCC patients, we demonstrate that ICDRM can differentiate ICD clusters and predict the prognosis and effectiveness of therapy. High-risk subpopulations are characterized by high TMB, suppressed immunity, and poor survival and response to immunotherapy, whereas the opposite is true for low-risk subpopulations. CONCLUSIONS: This study reveals the potential impact of ICDRM on the tumor microenvironment (TME), immune infiltration, and prognosis of HCC patients, but also a potential tool for predicting prognosis.

Improved A* Algorithm for Path Planning of Spherical Robot Considering Energy Consumption.

Spherical robots have fully wrapped shells, which enables them to walk well on complex terrains, such as swamps, grasslands and deserts. At present, path planning algorithms for spherical robots mainly focus on finding the shortest path between the initial position and the target position. In this paper, an improved A* algorithm considering energy consumption is proposed for the path planning of spherical robots. The optimization objective of this algorithm is to minimize both the energy consumption and path length of a spherical robot. A heuristic function constructed with the energy consumption estimation model (ECEM) and the distance estimation model (DEM) is used to determine the path cost of the A* algorithm. ECEM and DCM are established based on the force analysis of the spherical robot and the improved Euclidean distance of the grid map, respectively. The effectiveness of the proposed algorithm is verified by simulation analysis based on a 3D grid map and a spherical robot moving with uniform velocity. The results show that compared with traditional path planning algorithms, the proposed algorithm can minimize the energy consumption and path length of the spherical robot as much as possible.

Cross-substance patterns of alcohol, cigarette, and cannabis use initiation in Black and White adolescent girls.

Characterizing variations in the timing of alcohol, cigarette, and cannabis use onset both among and between Black and White youth can inform targeted prevention. The current study aimed to capture cross-substance initiation patterns in Black and White girls and characterize these patterns with respect to substance use related socioeconomic, neighborhood, family, community, and individual level factors. Data were drawn from interviews conducted at ages 8 through 17 in an urban sample of girls (n = 2172; 56.86% Black, 43.14% White). Discrete-time multiple event process survival mixture modeling was used to identify patterns (i.e., classes) representing timing of alcohol, cigarette, and cannabis use initiation, separately by race. Class characteristics were compared using multinomial logistic regression. Among both Black and White girls, four classes, including abstainer and cross-substance early onset classes, emerged. Two classes characterized by mid-adolescence onset (Black girls) and variation in onset by substance (White girls) were also observed. Class differences centered around cannabis for Black girls (e.g., preceding or following cigarette use) and alcohol for White girls (e.g., (in)consistency over time in greater likelihood of initiation relative to cigarette and cannabis use). Several factors distinguishing the classes were common across race (e.g., externalizing behaviors, friends' cannabis use); some were specific to Black girls (e.g., intentions to smoke cigarettes) or White girls (e.g., primary caregiver problem drinking). Findings underscore the need to recognize a more complex picture than a high-risk/low-risk dichotomy for substance use initiation and to attend to nuanced differences in markers of risky onset pathways between Black and White girls.

General psychiatric symptoms among Bangladeshi people approximately one year after the onset of the COVID-19 pandemic.

BACKGROUND: Coronavirus disease-2019 (COVID-19) has had negative physical and mental impacts on people globally. The current study examined general psychiatric symptoms (fear, anxiety, depression, and insomnia) and loneliness, and their interrelationships and correlates among Bangladeshi individuals approximately 1 year after the onset of the COVID-19 outbreak. METHODS: An internet-based cross-sectional survey was conducted among 1004 Bangladeshi people (51.8% male; mean age: 25.41 ± 7.80; age range: 18-60 years). Data were collected using a semi-structured e-questionnaire including informed consent, socio-demographics, lifestyle measures, and psychometric tools assessing loneliness, anxiety, depression, insomnia, and fear of COVID-19. RESULTS: Sizeable participants screened positive for loneliness (63.5%), anxiety (26.3%), depression (46.4%), and insomnia (50.7%). Considerable numbers of respondents also reported fear of COVID-19. In hierarchical regression analyses, loneliness, anxiety, depression, insomnia, and fear of COVID-19 were associated with socio-demographic and lifestyle factors. Loneliness, anxiety, depression, insomnia, and fear of COVID-19 were positively correlated with each other (p < 0.001). In exploratory path analyses, anxiety, depression, and insomnia mediated the relationship between loneliness and fear of COVID-19. CONCLUSIONS: The findings indicate that many people in Bangladesh have experienced psychiatric concerns approximately 1 year after the onset of the COVID-19 outbreak. Investigation into empirically supported interventions and their implementation is needed.

SHCBP1 interacting with EOGT enhances O-GlcNAcylation of NOTCH1 and promotes the development of pancreatic cancer.

O-GlcNAcylation is important in the development and progression of pancreatic ductal adenocarcinoma (PDAC). The glycosyltransferase EGF domain-specific O-linked GlcNAc transferase (EOGT) acts as a key participant in glycosylating NOTCH1. High-throughput sequencing of specimens from 30 advanced PDAC patients identified SHCBP1 and EOGT as factors of poor prognosis. We hypothesized that they could mediate PDAC progression by influencing NOTCH1 O-GlcNAcylation. Thus, 186 PDAC tissue specimens were immunostained for EOGT and SHCBP1. Pancreatic cancer cell lines and nude mouse models were used for in vitro and in vivo experiments. Respectively, The protein expression of EOGT and SHCBP1 was significantly elevated and correlated with worse prognosis in PDAC patients. In vitro, SHCBP1 overexpression promoted pancreatic cancer cell proliferation, migration and invasion, while knocking down SHCBP1 and EOGT inhibited these malignant processes. In vivo data showed that SHCBP1 overexpression promoted xenograft growth and lung metastasis and shortened survival in mice, whereas knocking down either EOGT or SHCBP1 expression suppressed xenograft growth and metastasis and prolonged survival. We further clarified the molecular mechanisms by which EOGT and SHCBP1 enhance the O-GlcNAcylation of NOTCH1, Subsequently promoting the nuclear localization of the Notch intracellular domain (NICD) and inhibiting the transcription of E-cadherin and P21 in pancreatic cancer cells.

From bulk to interface: electrochemical phenomena and mechanism studies in batteries via electrochemical quartz crystal microbalance.

Understanding the bulk and interfacial behaviors during the operation of batteries (e.g., Li-ion, Na-ion, Li-O2 batteries, etc.) is of great significance for the continuing improvement of the performance. Electrochemical quartz crystal microbalance (EQCM) is a powerful tool to this end, as it enables in situ investigation into various phenomena, including ion insertion/deinsertion within electrodes, solid nucleation from the electrolyte, interphasial formation/evolution and solid-liquid coordination. As such, EQCM analysis helps to decipher the underlying mechanisms both in the bulk and at the interface. This tutorial review will present the recent progress in mechanistic studies of batteries achieved by the EQCM technology. The fundamentals and unique capability of EQCM are first discussed and compared with other techniques, and then the combination of EQCM with other in situ techniques is also covered. In addition, the recent studies utilizing EQCM technologies in revealing phenomena and mechanisms of various batteries are reviewed. Perspectives regarding the future application of EQCM in battery studies are given at the end.

Lottery-Purchasing Adolescents: Gambling Perceptions, Problems, and Characteristics.

Gambling on the lottery is a prevalent behavior, and lottery products are increasingly available in online and electronic formats. As lottery-purchasing is prevalent in adolescents, this study systematically examined relationships between lottery-purchasing and problem-gambling severity and gambling perceptions and attitudes, as well as differences in the relationships between problem-gambling severity and measures of health/functioning and gambling characteristics among lottery-purchasing groups. Participants were 1517 Connecticut high-school adolescents with past-year gambling. Chi-square and logistic regression models were conducted, and interactions between problem-gambling severity and lottery-purchasing status on multiple outcomes were determined. Lottery-purchasing, compared to non-lottery-purchasing, adolescents had greater problem-gambling severity and reported more permissive gambling attitudes and greater parental approval of gambling. Significant between-group differences were observed, with at-risk/problem-gambling more strongly associated with having friends and adult gambling partners among non-lottery-purchasing adolescents, and machine and online gambling, and gambling alone more strongly associated among lottery-purchasing adolescents. Greater problem-gambling severity, permissive gambling attitudes, and parental approval of gambling in lottery-purchasing adolescents suggest that parenting contexts are important considerations in prevention efforts targeting problem gambling in youths. Between-group differences in associations between problem-gambling severity and gambling types and partners may identify high-risk groups associated with more solitary gambling behaviors for whom targeted interventions may be adapted.

CHD1L promotes EOC cell invasiveness and metastasis via the regulation of METAP2.

Chromodomain helicase DNA binding protein 1-like (CHD1L) gene has been proposed to play an oncogenic role in human hepatocellular carcinoma. Previously we reported that CHD1L overexpression is significantly associated with the metastasis proceeding of epithelial ovarian cancer (EOC), and may predict a poor prognosis in EOC patients. However, the potential oncogenic mechanisms by which CHD1L acts in EOC remain unclear. To elucidate the oncogenic function of CHD1L, we carried out a series of in vitro assays, with effects of CHD1L ectogenic overexpression and silencing being determined in EOC cell lines (HO8910, A2780 and ES2). Real-time PCR and Western blotting analyses were used to identify potential downstream targets of CHD1L in the process of EOC invasion and metastasis. In ovarian carcinoma HO8910 cell lines, ectopic overexpression of CHD1L substantially induced the invasive and metastasis ability of the cancer cells in vitro. In contrast, knockdown of CHD1L using shRNA inhibited cell invasion in vitro in ovarian carcinoma A2780 and ES2 cell lines. We also demonstrated that methionyl aminopeptidase 2 (METAP2) was a downstream target of CHD1L in EOC, and we found a significant, positive correlation between the expression of CHD1L and METAP2 in EOC tissues (P<0.05). Our findings indicate that CHD1L plays a potential role in the inducement of EOC cancer cell invasion and/or metastasis via the regulation of METAP2 expression and suggests that CHD1L inhibition may provide a potential target for therapeutic intervention in human EOC.

Alexithymia, Emotion-Regulation Strategies, and Traumatic Experiences in Prenatally Cocaine-Exposed Young Adults.

BACKGROUND AND OBJECTIVES: Exposure to early-life trauma may lead to maladaptive characteristics such as alexithymia, and thus to poorer emotional regulation. This relationship may also be influenced by exposure to substances prenatally. We hypothesized that increased alexithymia would be seen in those with prenatal cocaine exposure (PCE). Additionally, we hypothesized that early-life trauma would be associated with alexithymia, and that alexithymia would be associated with poor emotional reappraisal and emotional suppression. METHODS: A moderated mediation model was developed to examine whether the hypothesized indirect relationship between trauma and emotional reappraisal through alexithymia was different in young adults with and without PCE (Total N = 57). Thirty-seven young adults with PCE and 20 with no such exposure, all of whom were members of a longitudinal cohort, were recruited for the study, and data concerning childhood trauma, alexithymia, and emotional regulation were collected. Intercorrelations were performed between the scores on each measure and moderated mediation models were constructed separately with emotional neglect or emotional abuse as the independent variable and emotional reappraisal or emotional suppression as the dependent variable. RESULTS: PCE status was associated with alexithymia, and alexithymia mediated the relationship between emotional neglect and emotional reappraisal in individuals with PCE but not those without. DISCUSSION AND CONCLUSIONS: The data suggest that alexithymia is a mechanism underlying poor use of emotional reappraisal in PCE individuals. SCIENTIFIC SIGNIFICANCE: Individuals with early-life trauma and substance exposure may represent a vulnerable population, and alexithymia may play a key role in the development of emotional regulation skills in this population. (Am J Addict 2020;29:492-499).

Gambling, Substance Use and Violence in Male and Female Adolescents.

The study systematically examined the link between history of gambling, and substance-use and violence-related measures in male and female adolescents, and compared association differences between genders in representative youth risk behavior surveillance data. An anonymous survey was administered to 2425 9th- to 12th-grade students in the state of Connecticut to assess risk behaviors that impact health. Reported past-12-months gambling was the independent variable of interest. Chi squares and adjusted odds-ratios were computed to determine gambling associations with demographic variables, substance-use, and violence-related measures, and whether associations were different between genders. Among students, 18.6% reported gambling. Reported gambling in males and females associated with lifetime use of any drugs, marijuana, cocaine, inhalants, heroin, methamphetamines, ecstasy, synthetic marijuana, non-medical pain-relievers, and injected drugs, in addition to past-30-days cigarette smoking, alcohol and heavy alcohol drinking, and marijuana use. Gambling associated with reported weapon-carrying, being threatened or injured with a weapon, forced sexual intercourse, bullying, and electronic bullying in males; physical dating violence in females; and physical fighting and sexual dating violence in both groups. Gambling and gender interaction terms did not associate with outcome measures except synthetic marijuana use, which trended towards significance (P = 0.052). Gambling in adolescence was similarly linked to risk behaviors involving substance-use in males and females, though gambling relationships with different violence-measures varied between genders. Assessing gambling behavior may be important for targeted preventions focused on adolescents at risk for substance-use disorder and physical violence.

Childhood trauma moderates inhibitory control and anterior cingulate cortex activation during stress.

OBJECTIVE: The anterior cingulate cortex (ACC) is critical for both stress and inhibitory control processes and has been implicated in childhood trauma. This prospective study tested the hypothesis that early trauma moderates the association between inhibitory control during late childhood and ACC stress reactivity during adolescence. METHOD: Sixty-four adolescents were stratified into higher- or lower-childhood-trauma groups. Inhibitory control was indicated by fewer errors on a Stroop Color-Word task. Personalized stress cues during functional magnetic resonance imaging assessed neural correlates of stress in adolescents. RESULTS: Using a priori-defined anterior (rCZa) and posterior rostral cingulate zones of the ACC, associated with Stroop Color-Word task performance in prior meta-analyses, Stroop errors correlated inversely with activation in the rCZa during stress-cue exposure (r = -.23, p = .04). Childhood trauma moderated the association between Stroop errors and rCZa stress reactivity (interaction = -1.26, p = .02, 95%CI = -2.33,-0.20), where Stroop errors were inversely associated with brain activation among those with higher childhood trauma (simple slopes = -.83, p = .007, 95%CI = -1.40,-0.25). Low stress-related rCZa activation inversely (R2 = 0.19, b = -0.43, p = .001, 95%CI = -4.11,-1.06) and Stroop errors directly (R2 = 0.09, b = 0.27, p = .048, 95%CI = 0.02, 5.8) associated with baseline subjective anxiety while controlling for childhood trauma. CONCLUSIONS: This is the first study to demonstrate a moderating role of childhood trauma on the relationship between inhibitory control and stress-related ACC activation. Childhood trauma may portend neurodevelopmental changes that impede recruitment of control-associated ACC-functioning during distress, which may relate to dysregulation of stress-induced affective responses. Further work is needed to elucidate relationships between childhood trauma and addictive behaviors precipitated by stress.

Adsorption of hydrogen arsenate and dihydrogen arsenate ions from neutral water by UiO-66-NH2.

The metal-organic framework (MOF) UiO-66-NH2 was synthesized with different substrate to solvent ratios and its morphology, surface area, pore distributions, and NMR, XRD, and TGA-FTIR patterns were obtained. Adsorption tests at pH 7 and 25 °C showed that the produced UiO-66-NH2 has a hydrogen arsenate adsorption capacity of 76.9 mg/g. With the affinity onto Zr clusters, this MOF also can adsorb phosphate ions from water. Treatment with 1-4 M hydrochloric acid (HCl) protonated the amine groups in the MOF. Treatment with 1 M HCl at 25 °C for 6 h maximized the adsorption capacity of UiO-66-NH2 to 161.3 mg/g, such that the protonated amine groups accounted for 53.7% of the adsorption of arsenate from the water. The use of excessively strong acid at elevated temperature reduced the adsorption capacity.

Substance-use initiation moderates the effect of stress on white-matter microstructure in adolescents.

BACKGROUND: While childhood stress may contribute risk to substance-use initiation and differences in brain white-matter development, understanding of the potential impact of substance-use initiation on the relationship between experienced stress and white-matter microstructure remains limited. OBJECTIVES: This study examined whether substance-use initiation moderated the effect of perceived stress on white-matter differences using measures of primary white-matter fiber anisotropy. METHODS: Forty adolescents (age 14.75 ± .87 years) were assessed on the Perceived Stress Scale, and 50% were determined to have presence of substance-use initiation. White-matter microstructure was examined using primary-fiber orientations anisotropy, which may reflect white-matter integrity, modeled separately from other fiber orientations in the same voxels. Analyses were conducted on regions of interest previously associated with childhood stress and substance use. RESULTS: Lower perceived stress and presence of substance-use initiation were related to greater right cingulum primary-fiber measures. Substance-use-initiation status moderated the association between perceived stress and right cingulum primary-fiber measures, such that higher perceived stress was associated with lower right cingulum primary-fiber anisotropy in adolescents without substance-use initiation, but not in those with substance-use initiation. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Findings in primary-fiber anisotropy suggest differences in right cingulum white-matter integrity is associated with substance-use initiation in higher-stress adolescents. This reflects a possible pre-existing risk factor, an impact of early substance use, or a combination thereof. Examination of potential markers associated with substance-use initiation in white-matter microstructure among stress-exposed youth warrant additional investigation as such biomarkers may inform efforts relating to tailored interventions. (Am J Addict 2018;27:217-224).

Relationships Between Perceived Family Gambling and Peer Gambling and Adolescent Problem Gambling and Binge-Drinking.

The study systematically examined the relative relationships between perceived family and peer gambling and adolescent at-risk/problem gambling and binge-drinking. It also determined the likelihood of at-risk/problem gambling and binge-drinking as a function of the number of different social groups with perceived gambling. A multi-site high-school survey assessed gambling, alcohol use, presence of perceived excessive peer gambling (peer excess-PE), and family gambling prompting concern (family concern-FC) in 2750 high-school students. Adolescents were separately stratified into: (1) low-risk, at-risk, and problem/pathological gambling groups; and, (2) non-binge-drinking, low-frequency-binge-drinking, and high-frequency-binge-drinking groups. Multinomial logistic regression showed that relative to each other, FC and PE were associated with greater likelihoods of at-risk and problem/pathological gambling. However, only FC was associated with binge-drinking. Logistic regression revealed that adolescents who endorsed either FC or PE alone, compared to no endorsement, were more likely to have at-risk and problem/pathological gambling, relative to low-risk gambling. Adolescents who endorsed both FC and PE, compared to PE alone, were more likely to have problem/pathological gambling relative to low-risk and at-risk gambling. Relative to non-binge-drinking adolescents, those who endorsed both FC and PE were more likely to have low- and high-frequency-binge-drinking compared to FC alone or PE alone, respectively. Family and peer gambling individually contribute to adolescent at-risk/problem gambling and binge-drinking. Strategies that target adolescents as well as their closely affiliated family and peer members may be an important step towards prevention of harm-associated levels of gambling and alcohol use in youths.

Inhibition of acid-sensing ion channels by levo-tetrahydropalmatine in rat dorsal root ganglion neurons.

Levo-tetrahydropalmatine (l-THP), a main bioactive Chinese herbal constituent from the genera Stephania and Corydalis, has been in use in clinical practice for years in China as a traditional analgesic agent. However, the mechanism underlying the analgesic action of l-THP is poorly understood. This study shows that l-THP can exert an inhibitory effect on the functional activity of native acid-sensing ion channels (ASICs), which are believed to mediate pain caused by extracellular acidification. l-THP dose dependently decreased the amplitude of proton-gated currents mediated by ASICs in rat dorsal root ganglion (DRG) neurons. l-THP shifted the proton concentration-response curve downward, with a decrease of 40.93% ± 8.45% in the maximum current response to protons, with no significant change in the pH0.5 value. Moreover, l-THP can alter the membrane excitability of rat DRG neurons to acid stimuli. It significantly decreased the number of action potentials and the amplitude of the depolarization induced by an extracellular pH drop. Finally, peripherally administered l-THP inhibited the nociceptive response to intraplantar injection of acetic acid in rats. These results indicate that l-THP can inhibit the functional activity of ASICs in dissociated primary sensory neurons and relieve acidosis-evoked pain in vivo, which for the first time provides a novel peripheral mechanism underlying the analgesic action of l-THP.

De novo transcriptome sequencing and digital gene expression analysis predict biosynthetic pathway of rhynchophylline and isorhynchophylline from Uncaria rhynchophylla, a non-model plant with potent anti-alzheimer's properties.

BACKGROUND: The major medicinal alkaloids isolated from Uncaria rhynchophylla (gouteng in chinese) capsules are rhynchophylline (RIN) and isorhynchophylline (IRN). Extracts containing these terpene indole alkaloids (TIAs) can inhibit the formation and destabilize preformed fibrils of amyloid ß protein (a pathological marker of Alzheimer's disease), and have been shown to improve the cognitive function of mice with Alzheimer-like symptoms. The biosynthetic pathways of RIN and IRN are largely unknown. RESULTS: In this study, RNA-sequencing of pooled Uncaria capsules RNA samples taken at three developmental stages that accumulate different amount of RIN and IRN was performed. More than 50 million high-quality reads from a cDNA library were generated and de novo assembled. Sequences for all of the known enzymes involved in TIAs synthesis were identified. Additionally, 193 cytochrome P450 (CYP450), 280 methyltransferase and 144 isomerase genes were identified, that are potential candidates for enzymes involved in RIN and IRN synthesis. Digital gene expression profile (DGE) analysis was performed on the three capsule developmental stages, and based on genes possessing expression profiles consistent with RIN and IRN levels; four CYP450s, three methyltransferases and three isomerases were identified as the candidates most likely to be involved in the later steps of RIN and IRN biosynthesis. CONCLUSION: A combination of de novo transcriptome assembly and DGE analysis was shown to be a powerful method for identifying genes encoding enzymes potentially involved in the biosynthesis of important secondary metabolites in a non-model plant. The transcriptome data from this study provides an important resource for understanding the formation of major bioactive constituents in the capsule extract from Uncaria, and provides information that may aid in metabolic engineering to increase yields of these important alkaloids.