Opioid Receptors Modulate Firing and Synaptic Transmission in the Paraventricular Nucleus of the Thalamus.

The paraventricular nucleus of the thalamus (PVT) is involved in drug addiction-related behaviors, and morphine is a widely used opioid for the relief of severe pain. Morphine acts via opioid receptors, but the function of opioid receptors in the PVT has not been fully elucidated. Here, we used in vitro electrophysiology to study neuronal activity and synaptic transmission in the PVT of male and female mice. Activation of opioid receptors suppresses the firing and inhibitory synaptic transmission of PVT neurons in brain slices. On the other hand, the involvement of opioid modulation is reduced after chronic morphine exposure, probably because of desensitization and internalization of opioid receptors in the PVT. Overall, the opioid system is essential for the modulation of PVT activities.SIGNIFICANCE STATEMENT Opioid receptors modulate the activities and synaptic transmission in the PVT by suppressing the firing rate and inhibitory synaptic inputs. These modulations were largely diminished after chronic morphine exposure.

A circuit from lateral septum neurotensin neurons to tuberal nucleus controls hedonic feeding.

Feeding behavior is regulated by both the homeostatic needs of the body and hedonic values of the food. Easy access to palatable energy-dense foods and the consequent obesity epidemic stress the urgent need for a better understanding of neural circuits that regulate hedonic feeding. Here, we report that neurotensin-positive neurons in the lateral septum (LSNts) play a crucial role in regulating hedonic feeding. Silencing LSNts specifically promotes feeding of palatable food, whereas activation of LSNts suppresses overall feeding. LSNts neurons project to the tuberal nucleus (TU) via GABA signaling to regulate hedonic feeding, while the neurotensin signal from LSNts→the supramammillary nucleus (SUM) is sufficient to suppress overall feeding. In vivo calcium imaging and optogenetic manipulation reveal two populations of LSNts neurons that are activated and inhibited during feeding, which contribute to food seeking and consumption, respectively. Chronic activation of LSNts or LSNts→TU is sufficient to reduce high-fat diet-induced obesity. Our findings suggest that LSNts→TU is a key pathway in regulating hedonic feeding.

Structural Studies of Hydrographenes.

As a result of the unique physical and electrical properties, graphene continues to attract the interest of a large segment of the scientific community. Since graphene does not occur naturally, the ability to exfoliate and isolate individual layers of graphene from graphite is an important and challenging process. The interlayer cohesive energy of graphite that results from van der Waals attractions has been determined experimentally to be 61 meV per carbon atom (61 meV/C atom). This requires the development of a method to overcome the strong attractive forces associated with graphite. The exfoliation process that we, and others, have investigated involves electron transfer into bulk graphite from intercalated lithium to yield lithium graphenide. The resulting graphenide can be reacted with various reagents to yield functionalized graphene. As a part of our interest in the functionalization of graphene, we have explored the Birch reduction as a route to hydrographenes. The addition of hydrogen transforms graphene into an insulator, leading to the prediction that important applications will emerge. This Account focuses mainly on the characterization of the hydrographenes that are obtained from different types of graphite including synthetic graphite powder, natural flake graphite, and annealed graphite powder. Analysis by solid state 13C NMR spectroscopy proved to be important since it was shown that the hydrographenes are composed of interior, isolated aromatic (predominantly fully substituted benzene) rings surrounded by saturated rings. The expected clusters of benzene rings were not found. NMR spectroscopy also offers strong evidence for the presence of tert-butyl alcohol and ethanol (workup solvent) that could not be removed in vacuo from the samples. These compounds could be observed to move freely within the layers of the hydrographene. High-resolution transmission electron microscopy images revealed a remarkable change in morphology that results when hydrogen is added to the graphenide. The appearance of edge and circular dislocations and increased distances between graphitic layers are most visible in the case of the hydrographenes that are formed from annealed graphite. The repetitive hydrogenation of synthetic graphite powder leads to an increase in the distances between the graphitic layers in the (002) direction from 3.4 Å for the initial graphite to 4.11 Å after the first reduction and to 4.29 Å after a third reduction of the same material. Defect-free graphite is formed when the hydrographenes are heated. The distance between carbon layers decreases from 4.11 to 3.44 Å after heating the samples to 1200 °C. This trend toward the spacing of graphite confirms the reversibility of the functionalization process. The C-H bonds have been broken yielding hydrogen, and the exposed carbon orbitals are in close enough proximity to have reverted to graphite. This Account introduces only a narrow area of materials chemistry, and many applications of graphene and its derivatives can be expected as researchers exploit this burgeoning field.

The moderating roles of resilience and social support in the relationships between bullying victimization and well-being among Chinese adolescents: Evidence from PISA 2018.

Bullying victimization can undermine adolescents' well-being. However, few studies have comprehensively investigated the contributions of various victimization forms to well-being and compared which forms were more harmful than others. Evidence on whether resilience and social support moderate such associations is also limited. Using a sample of 12,058 Chinese adolescents in the Programme for International Student Assessment (PISA) 2018, this cross-sectional study aimed to (1) investigate the associations of physical, verbal and relational victimization with well-being; (2) compare the strengths of these associations; and (3) examine the moderating roles of resilience and teacher and parent support in these associations. Results showed that three victimization forms were associated with poorer well-being. Relational and physical victimization were more harmful to most studied well-being outcomes than verbal victimization. Furthermore, resilience weakened the negative effects of physical victimization on negative affect and life satisfaction but aggravated the negative effects of verbal victimization on both outcomes and the negative effect of relational victimization on school belonging. Teacher support intensified the negative effects of physical victimization on school belonging. Parent support was not effective in regulating the victimization-well-being association. The findings underscored the detrimental effects of bullying victimization on adolescents' well-being and the potentially harmful sides of resilience and social support. Implications for bullying prevention were discussed.

Neuronal activity in the anterior paraventricular nucleus of thalamus positively correlated with sweetener consumption in mice.

Although the brain can discriminate between various sweet substances, the underlying neural mechanisms of this complex behavior remain elusive. This study examines the role of the anterior paraventricular nucleus of the thalamus (aPVT) in governing sweet preference in mice. We fed the mice six different diets with equal sweetness for six weeks: control diet (CD), high sucrose diet (HSD), high stevioside diet (HSSD), high xylitol diet (HXD), high glycyrrhizin diet (HGD), and high mogroside diet (HMD). The mice exhibited a marked preference specifically for the HSD and HSSD. Following consumption of these diets, c-Fos expression levels in the aPVT were significantly higher in these two groups compared to the others. Utilizing fiber photometry calcium imaging, we observed rapid activation of aPVT neurons in response to sucrose and stevioside intake, but not to xylitol or water. Our findings suggest that aPVT activity aligns with sweet preference in mice, and notably, stevioside is the sole plant-based sweetener that elicits an aPVT response comparable to that of sucrose.

Zona incerta mediates early life isoflurane-induced fear memory deficits.

The potential long-term effects of anesthesia on cognitive development, especially in neonates and infants, have raised concerns. However, our understanding of its underlying mechanisms and effective treatments is still limited. In this study, we found that early exposure to isoflurane (ISO) impaired fear memory retrieval, which was reversed by dexmedetomidine (DEX) pre-treatment. Measurement of c-fos expression revealed that ISO exposure significantly increased neuronal activation in the zona incerta (ZI). Fiber photometry recording showed that ZI neurons from ISO mice displayed enhanced calcium activity during retrieval of fear memory compared to the control group, while DEX treatment reduced this enhanced calcium activity. Chemogenetic inhibition of ZI neurons effectively rescued the impairments caused by ISO exposure. These findings suggest that the ZI may play a pivotal role in mediating the cognitive effects of anesthetics, offering a potential therapeutic target for preventing anesthesia-related cognitive impairments.

GLP-1R-positive neurons in the lateral septum mediate the anorectic and weight-lowering effects of liraglutide in mice.

Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, is approved for obesity treatment, but the specific neuronal sites that contribute to its therapeutic effects remain elusive. Here, we show that GLP-1 receptor-positive (GLP-1R-positive) neurons in the lateral septum (LSGLP-1R) play a critical role in mediating the anorectic and weight-loss effects of liraglutide. LSGLP-1R neurons were robustly activated by liraglutide, and chemogenetic activation of these neurons dramatically suppressed feeding. Targeted knockdown of GLP-1 receptors within the LS, but not in the hypothalamus, substantially attenuated liraglutide's ability to inhibit feeding and lower body weight. The activity of LSGLP-1R neurons rapidly decreased during naturalistic feeding episodes, while synaptic inactivation of LSGLP-1R neurons diminished the anorexic effects triggered by liraglutide. Together, these findings offer critical insights into the functional role of LSGLP-1R neurons in the physiological regulation of energy homeostasis and delineate their instrumental role in mediating the pharmacological efficacy of liraglutide.

Cellular and circuit architecture of the lateral septum for reward processing.

The lateral septum (LS) is composed of heterogeneous cell types that are important for various motivated behaviors. However, the transcriptional profiles, spatial arrangement, function, and connectivity of these cell types have not been systematically studied. Using single-nucleus RNA sequencing, we delineated diverse genetically defined cell types in the LS that play distinct roles in reward processing. Notably, we found that estrogen receptor 1 (Esr1)-expressing neurons in the ventral LS (LSEsr1) are key drivers of reward seeking via projections to the ventral tegmental area, and these neurons play an essential role in methamphetamine (METH) reward and METH-seeking behavior. Extended exposure to METH increases the excitability of LSEsr1 neurons by upregulating hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, thereby contributing to METH-induced locomotor sensitization. These insights not only elucidate the intricate molecular, circuit, and functional architecture of the septal region in reward processing but also reveal a neural pathway critical for METH reward and behavioral sensitization.

Hypothalamic CRF neurons facilitate brain reward function.

Aversive stimuli activate corticotropin-releasing factor (CRF)-expressing neurons in the paraventricular nucleus of hypothalamus (PVNCRF neurons) and other brain stress systems to facilitate avoidance behaviors. Appetitive stimuli also engage the brain stress systems, but their contributions to reward-related behaviors are less well understood. Here, we show that mice work vigorously to optically activate PVNCRF neurons in an operant chamber, indicating a reinforcing nature of these neurons. The reinforcing property of these neurons is not mediated by activation of the hypothalamic-pituitary-adrenal (HPA) axis. We found that PVNCRF neurons send direct projections to the ventral tegmental area (VTA), and selective activation of these projections induced robust self-stimulation behaviors, without activation of the HPA axis. Similar to the PVNCRF cell bodies, self-stimulation of PVNCRF-VTA projection was dramatically attenuated by systemic pretreatment of CRF receptor 1 or dopamine D1 receptor (D1R) antagonist and augmented by corticosterone synthesis inhibitor metyrapone, but not altered by dopamine D2 receptor (D2R) antagonist. Furthermore, we found that activation of PVNCRF-VTA projections increased c-Fos expression in the VTA dopamine neurons and rapidly triggered dopamine release in the nucleus accumbens (NAc), and microinfusion of D1R or D2R antagonist into the NAc decreased the self-stimulation of these projections. Together, our findings reveal an unappreciated role of PVNCRF neurons and their VTA projections in driving reward-related behaviors, independent of their core neuroendocrine functions. As activation of PVNCRF neurons is the final common path for many stress systems, our study suggests a novel mechanism underlying the positive reinforcing effect of stressful stimuli.

Distinct reward processing by subregions of the nucleus accumbens.

The nucleus accumbens (NAc) plays an important role in motivation and reward processing. Recent studies suggest that different NAc subnuclei differentially contribute to reward-related behaviors. However, how reward is encoded in individual NAc neurons remains unclear. Using in vivo single-cell resolution calcium imaging, we find diverse patterns of reward encoding in the medial and lateral shell subdivision of the NAc (NAcMed and NAcLat, respectively). Reward consumption increases NAcLat activity but decreases NAcMed activity, albeit with high variability among neurons. The heterogeneity in reward encoding could be attributed to differences in their synaptic inputs and transcriptional profiles. Specific optogenetic activation of Nts-positive neurons in the NAcLat promotes positive reinforcement, while activation of Cartpt-positive neurons in the NAcMed induces behavior aversion. Collectively, our study shows the organizational and transcriptional differences in NAc subregions and provides a framework for future dissection of NAc subregions in physiological and pathological conditions.

Investigating career-related teacher support for Chinese secondary school students in Hong Kong.

Teachers play a critical role in facilitating the career and life planning of secondary school students. This paper describes the development of the Career-Related Teacher Support Scale (Hong Kong Secondary Students Form). Based on data obtained from 493 students in Hong Kong, five types of career-related teacher support were identified with the most important form of support being teachers' knowledge about the world of work and study path requirements. A correlation model yielded the best fit to the data. No variance in response pattern appeared across genders, and the new scale was found to have good validity and reliability.

Enquête sur le soutien des enseignant·e·s lié à la carrière pour les étudiant·e·s chinois du secondaire à Hong Kong Les enseignant·e·s jouent un rôle essentiel en facilitant la planification de la carrière et de la vie des élèves du secondaire. Cet article décrit le développement de l'échelle Career-Related Teacher Support Scale (Hong Kong Secondary Students Form). Sur la base des données obtenues auprès de 493 étudiantes à Hong Kong, cinq types de soutien des enseignantes liés à la carrière ont été identifiés, la forme de soutien la plus importante étant les connaissances des enseignantes sur le monde du travail et les exigences des filières d'études. Un modèle de corrélation s'est avéré le mieux adapté aux données. Aucune variance dans le modèle de réponse n'est apparue entre les sexes, et la nouvelle échelle s'est avérée avoir une bonne validité et fiabilité.

Investigando el Apoyo Docente al Desarrollo de la Carrera para estudiantes chinos de secundaria en Hong Kong Los profesores desempeñan un papel fundamental a la hora de facilitar la planificación de la carrera y la vida de los estudiantes de secundaria. Este artículo describe el desarrollo de la Escala de Apoyo Docente al Desarrollo de la Carrera (Cuestionario para Estudiantes de Secundaria de Hong Kong). Sobre la base de los datos obtenidos de 493 estudiantes en Hong Kong, se identificaron cinco tipos de apoyo de los docentes relacionados con la carrera, siendo la forma más importante de apoyo el conocimiento de los docentes sobre el mundo del trabajo y los requisitos de las trayectorias educativas. El mejor ajuste para los datos fue aportado por un modelo de correlación. No apareció ninguna variabilidad en el patrón de respuesta relacionada con el género, y se encontró que la nueva escala tiene buena validez y fiabilidad.

How the brain processes negative emotions.

A new brain circuit that contributes to aversive states, such as fear or anxiety, has been characterized in mice.

Promoting college students' systems thinking in asynchronous discussions: Encouraging students initiating questions.

Introduction: Systems thinking is one of the most important thinking skills for medical students. Most of the studies focused on designing technological-rich learning environments which usually take several weeks or months to implement. However, the occurring of COVID-19 health crisis does not allow extensive period of time to implement classroom interventions. How to support students' systems thinking in fully online environments remains an issue. This study examines if encouraging students initiating questions on asynchronous discussion forum supports their systems thinking development. Methods: Twenty-two junior students participated in this study. We compared if and how students developed systems thinking when they were encouraged asking questions in asynchronous discussion forums in one unit with another unit in which traditional method was used. Multiple analytical methods were applied in this study, including, social network analysis, epistemic network analysis, inferential statistical analysis and qualitative analysis. Results: Quantitative results showed that all students improved systems thinking compared with traditional teaching unit among which leader students improved most. Further analysis on students' discussion posts suggested leader students asked high systems thinking level questions and provided high level responses. Epistemic network analysis unpacked how leader, regular and peripheral students engaged in initiating questions and providing responses differently. Discussion: This study provides methodological and practical contributions. Methodologically, this study extends prior methods of applying network analysis beyond its original preservice teacher training contexts; practically, this study provides strategies to practitioners to support students' asynchronous forum discussions.

Trajectories of Idea Emergence in Dialogic Collaborative Problem Solving: Toward a Complex Dynamic Systems Perspective.

According to the complex dynamic systems (CDS) perspective, learning emerges at various system levels. This study built a coherent theoretical framework based on CDS and Bakhtinian dialogic theory and further employed the concept of attractor (i.e., certain stable states that recur over time) in CDS theory to investigate the trajectories of idea emergence and how they diversified group outcomes in dialogic collaborative problem solving (D-CPS). Two contrasting groups were compared using visual and qualitative analysis approaches. The analysis based on idea tree diagrams showed that new ideas emergent in group discussion tended to attract local utterances and performed features of attractors in CDS in both high-performing and low-performing groups. The analysis based on idea hierarchy diagrams revealed how ideas emerged at various system levels. It was also found that status problems were likely to affect the functioning of regulative feedback loops, which might give rise to different structures of idea evolution. This study proposed CDS theory as an alternative perspective, augmented by the ethical considerations of Bakhtinian dialogism, for examining the dynamics of D-CPS.

A systematic review and meta-analysis of parent-mediated intervention for children and adolescents with autism spectrum disorder in mainland China, Hong Kong, and Taiwan.

LAY ABSTRACT: The ideal dosage for early intensive interventions for autism spectrum disorder has been suggested to be at least 25-hour per week to reach optimal effects. However, insufficient service use and unmet needs among families with children with autism spectrum disorder are frequently reported worldwide. Helping parents to develop strategies for interaction and management of behavior through parent training has been demonstrated to be a prominent way to supplementing service insufficiency for autism spectrum disorder, which is particularly crucial in less-resourced areas. This review included 21 parent-mediated intervention programs conducted in China, the most populated developing country. Among them, we were able to combine outcome information from 12 randomized controlled trials to increase confidence in the results. We also rated the quality of methodology and evidence for all included studies, which was taken into account in making conclusions. The included programs varied in the content, length, and delivery method of trainings. Although targeting different training outcomes, the majority of the studies aimed to help parents be more competent and responsive during interactions with their child in order to decrease symptom severity. Overall, results showed sufficient evidence that parent training did improve child outcomes as intended. However, the quality of more than half (14/21) of the included studies were below satisfactory. Identified programs lack the capacity to be further transported in the Chinese societies due to the lack of solid theoretical foundations, implementation manuals, and appropriate cultural adaptations. This review reinforces the need for promotion and improvement of parent-mediated interventions in low-resource context.

Retrospective analysis of the development history of the Chinese food additive standards system based on the CODEX principles.

In 1984, China joined the Codex Alimentarius Commission (CAC), which was established by the United Nations' World Health Organization (WHO) and the Food and Agriculture Organization (FAO), which consists of 188 member states and one member organization. Since then, China has taken an active role in various initiatives organized by the Codex Committee on Food Additives (CCFA) and has shared resources and experience with its Codex member states, thus effectively promoting the development of the Chinese food additive standards system. Instead of a country where almost no systematic food additive standard were available, China has become the host country of the CCFA's sessions. China's food additive industry is the only one that is supported by international standards, out of the industries of the International Standard Industrial Classification and China's national economy. Based on this case, four strategic milestones are summarized by retrospectively analyzing the history of the development of Chinese food additive standards from 1978 to the present. China is expected to share its valuable experience and provide references for the improvement of food additive standards systems in multiple developing countries, so promoting food safety and trade harmonization. With the advances in core technologies in the food industry, the future development of food additive standardization is also forecast in this review.

A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats.

A major cause of repeated relapses is a craving for the drug. Drug craving increases progressively during the abstinence period, a phenomenon termed incubation of drug craving. Here, we describe a morphine conditioned place preference (CPP) protocol for measuring the incubation of craving in rats. In this protocol, a CPP paradigm mainly employing somatosensory cues is used to establish a long-term reward memory of morphine. A three-chamber CPP box that differs in the texture of the chamber floor is constructed. First, the animals are tested for their baseline preference to the two side chambers for three consecutive days. Then, they are injected intraperitoneally with morphine/saline and put into their non-preferred/preferred chamber for 45 min. After 6 days of conditioning, their preference to the side chambers is tested for 15 min at different time points after the last conditioning session. With this paradigm, the reward memory of morphine could last for at least 18 days. To test whether the above-mentioned protocol can model increased craving, the number of entrances into the two side chambers are counted during the abstinence period. The results show that the entrances increased, suggesting that the CPP paradigm could mimic the incubation of craving. Future studies can employ this model to study neural mechanisms underlying long-term memory and incubation of craving.

The triarchic model of grit is linked to academic success and well-being among Filipino high school students.

Previous investigations mostly relied on the two-factor model of grit (with perseverance of effort and consistency of interests as major dimensions) which received a number criticisms in the extant literature. Recent studies have provided promising lines of evidence regarding the triarchic model of grit (TMG) which posits three dimensions of grit in a collectivist setting: perseverance of effort, consistency of interests, and adaptability to situations. However, little is known about how this model of grit may be linked to various indicators of positive educational and psychological functioning. The present research filled this gap through examining the association of the TMG with academic (Study 1) and well-being outcomes (Study 2) among Filipino high school students. Results demonstrated that grit positively predicted academic agentic, behavioral, cognitive, and emotional engagement. Findings of multiple mediation analyses showed that grit had indirect effects on academic engagement via the intermediate variable autonomous motivation even after controlling for age, gender, and conscientiousness. Study 2 showed grit positively predicted life satisfaction, positive affect, and interdependent happiness even after controlling for demographic covariates and neuroticism. Grit negatively predicted psychological distress. Theoretical and practical implications are discussed. (PsycINFO Database Record

Controlled synthesis of Pt nanoparticles via seeding growth and their shape-dependent catalytic activity.

Through a seed-mediated growth route, Pt nanoparticles (NPs) with tunable shape and size were prepared, such as octahedral, cuboctahedral, branched and rice-like. Three nanometer Pt NPs were prepared and dispersed in oleyl amine to form seed solution and then Pt precursor (platinum acetylacetonate (Pt(acac)(2))) was added. Under high temperature, oleyl amine as both reducing and protective agents can reduce Pt precursor to Pt atoms which selectively deposit on seeds surface to form variously structured Pt NPs. By adjusting the reactive conditions (the molar ratio of Pt metals from Pt(acac)(2) and seed (PPS), the seed diameter, the addition route of Pt(acac)(2)), the NPs growth could be controlled to fall into kinetic or thermodynamic regime, producing variously shaped NPs. On the basis of observed results, a reaction mechanism in which the resulting NP shape had strong dependence on c/s (c=precursor concentration, s=available deposition surface area) was figured out. The obtained NPs were supported on black carbon to act as Pt/C catalysts for oxidization of methanol and results show that the catalysts from branched NPs had higher catalytic activity and stability than ones from polyhedral NPs.