Control-value appraisals and academic emotions: An intensive longitudinal examination of reciprocal effects.

This study examined the reciprocal relation between lesson-specific perceived cognitive appraisals and academic emotions on an intra-individual level. A daily diary study was conducted using a sample of 266 Chinese Han students (Grades 7-8; 56.8% boys; Mage = 13.70, SDage = 0.52) during 10 mathematics lessons in 2022. Standardized questionnaires were also administered to these students before the daily diary study. The results of the dynamic structural equation modeling revealed significant reciprocal relations between cognitive appraisals and academic emotions within early adolescents and highlighted the role of emotions in guiding cognitive appraisals. Additionally, the study identified similarities and differences in the inter-individual relation between appraisals and emotions across self-reported questionnaires and daily diary measures.

Reliability, validity, and measurement invariance of a Chinese handwriting legibility scale among primary students in central China.

Background: Chinese handwriting has a close relationship with spatial cognition, and the legibility dimension is prominent with its spatial-oriented characteristics. However, handwriting evaluation focusing on the detailed spatial aspects of the legibility dimension in the Chinese context is rare. Aims and methods: We aimed to develop a Chinese Handwriting Legibility Scale (CHLS) and examine its reliability, validity, and measurement invariance among Chinese primary students of different grades. A total of 684 students aged 8-12 years were recruited from a mainstream primary school in central China and were asked to copy a Chinese template as legibly as possible within 4 min. The developed CHLS was used to assess these students' legibility performance. Results: The seven-criteria CHLS favored content validity. The inter-rater reliability was good; however, the scoring instructions need to be refined. Principal component analysis (PCA) revealed a one-factor solution explaining 62.336% of the variance of the seven-criteria CHLS, and confirmatory factor analysis (CFA) confirmed its appropriateness. There was a high internal consistency (α = 0.902). In terms of measurement invariance, the factor structures and loadings of the CHLS were consistent across students of different grades; however, significant intercept variations were detected between students of Grades 2 and 4. Conclusion: CHLS may be effective for evaluating Chinese handwriting legibility performance in the Chinese primary school context in the central region. Students' Chinese handwriting legibility performance may have developmental specificity in different grades.

Differential associations between scale-free neural dynamics and different levels of cognitive ability.

As indicators of cognitive function, scale-free neural dynamics are gaining increasing attention in cognitive neuroscience. Although the functional relevance of scale-free dynamics has been extensively reported, one fundamental question about its association with cognitive ability remains unanswered: is the association universal across a wide spectrum of cognitive abilities or confined to specific domains? Based on dual-process theory, we designed two categories of tasks to analyze two types of cognitive processes-automatic and controlled-and examined their associations with scale-free neural dynamics characterized from resting-state electroencephalography (EEG) recordings obtained from a large sample of human adults (N = 102). Our results showed that resting-state scale-free neural dynamics did not predict individuals' behavioral performance in tasks that primarily engaged the automatic process but did so in tasks that primarily engaged the controlled process. In addition, by fitting the scale-free parameters separately in different frequency bands, we found that the cognitive association of scale-free dynamics was more strongly manifested in higher-band EEG spectrum. Our findings indicate that resting-state scale-free dynamics are not universal neural indicators for all cognitive abilities but are mainly associated with high-level cognition that entails controlled processes. This finding is compatible with the widely claimed role of scale-free dynamics in reflecting properties of complex dynamic systems.

Physiologically based pharmacokinetic modeling framework for quantitative prediction of an herb-drug interaction.

Herb-drug interaction predictions remain challenging. Physiologically based pharmacokinetic (PBPK) modeling was used to improve prediction accuracy of potential herb-drug interactions using the semipurified milk thistle preparation, silibinin, as an exemplar herbal product. Interactions between silibinin constituents and the probe substrates warfarin (CYP2C9) and midazolam (CYP3A) were simulated. A low silibinin dose (160 mg/day × 14 days) was predicted to increase midazolam area under the curve (AUC) by 1%, which was corroborated with external data; a higher dose (1,650 mg/day × 7 days) was predicted to increase midazolam and (S)-warfarin AUC by 5% and 4%, respectively. A proof-of-concept clinical study confirmed minimal interaction between high-dose silibinin and both midazolam and (S)-warfarin (9 and 13% increase in AUC, respectively). Unexpectedly, (R)-warfarin AUC decreased (by 15%), but this is unlikely to be clinically important. Application of this PBPK modeling framework to other herb-drug interactions could facilitate development of guidelines for quantitative prediction of clinically relevant interactions.CPT Pharmacometrics Syst. Pharmacol. (2014) 3, e107; doi:10.1038/psp.2013.69; advance online publication 26 March 2014.

Pharmacokinetics, disposition and lipid-modulating activity of 5-{2-[4-(3,4-difluorophenoxy)-phenyl]-ethylsulfamoyl}-2-methyl-benzoic acid, a potent and subtype-selective peroxisome proliferator-activated receptor alpha agonist in preclinical species and human.

5-{2-[4-(3,4-Difluorophenoxy)-phenyl]-ethylsulfamoyl}-2-methyl-benzoic acid (1) is a novel, potent, and selective agonist of the peroxisome proliferator-activated receptor alpha (PPAR-alpha). In preclinical species, compound 1 demonstrated generally favourable pharmacokinetic properties. Systemic plasma clearance (CLp) after intravenous administration was low in Sprague-Dawley rats (3.2 +/- 1.4 ml min(-1) kg(-1)) and cynomolgus monkeys (6.1 +/- 1.6 ml min(-1) kg(-1)) resulting in plasma half-lives of 7.1 +/- 0.7 h and 9.4 +/- 0.8 h, respectively. Moderate bioavailability in rats (64%) and monkeys (55%) was observed after oral dosing. In rats, oral pharmacokinetics were dose-dependent over the dose range examined (10 and 50 mg kg(-1)). In vitro metabolism studies on 1 in cryopreserved rat, monkey, and human hepatocytes revealed that 1 was metabolized via oxidation and phase II glucuronidation pathways. In rats, a percentage of the dose (approximately 19%) was eliminated via biliary excretion in the unchanged form. Studies using recombinant human CYP isozymes established that the rate-limiting step in the oxidative metabolism of 1 to the major primary alcohol metabolite M1 was catalysed by CYP3A4. Compound 1 was greater than 99% bound to plasma proteins in rat, monkey, mouse, and human. No competitive inhibition of the five major cytochrome P450 enzymes, namely CYP1A2, P4502C9, P4502C19, P4502D6 and P4503A4 (IC50's > 30 microM) was discerned with 1. Because of insignificant turnover of 1 in human liver microsomes and hepatocytes, human clearance was predicted using rat single-species allometric scaling from in vivo data. The steady-state volume was also scaled from rat volume after normalization for protein-binding differences. As such, these estimates were used to predict an efficacious human dose required for 30% lowering of triglycerides. In order to aid human dose projections, pharmacokinetic/pharmacodynamic relationships for triglyceride lowering by 1 were first established in mice, which allowed an insight into the efficacious concentrations required for maximal triglyceride lowering. Assuming that the pharmacology translated in a quantitative fashion from mouse to human, dose projections were made for humans using mouse pharmacodynamic parameters and the predicted human pharmacokinetic estimates. First-in-human clinical studies on 1 following oral administration suggested that the human pharmacokinetics/dose predictions were in the range that yielded a favourable pharmacodynamic response.