Gender difference in the pharmacokinetics and metabolism of VX-548 in rats.

VX-548 is a sodium channel blocker, which acts as an analgesic. This study aims to investigate the gender differences in the pharmacokinetics and metabolism of VX-548 in rats. After intravenous administration, the area under the curve (AUC0-t) of VX-548 was much higher in female rats (1505.8 ± 47.3 ng·h/mL) than in male rats (253.8 ± 6.3 ng·h/mL), and the clearance in female rats (12.5 ± 0.8 mL/min/kg) was much lower than in male rats (65.1 ± 1.7 mL/min/kg). After oral administration, the AUC0-t in female rats was about 50-fold higher than that in male rats. The oral bioavailability in male rats was 11% while it was 96% in female rats. An in vitro metabolism study revealed that the metabolism of VX-548 in female rat liver microsomes was much slower than in male rats. Further metabolite identification suggested that the significant gender difference in pharmacokinetics was attributed to demethylation. The female rat liver microsomes showed a limited ability to convert VX-548 into desmethyl VX-548. Phenotyping experiments indicated that the formation of desmethyl VX-548 was mainly catalyzed by CYP3A2 and CYP2C11 using rat recombinant CYPs. Overall, we revealed that the pharmacokinetics and metabolism of VX-548 in male and female rats showed significant gender differences.

Mitochondrial phosphoenolpyruvate carboxylase contributes to carbon fixation in the diatom Phaeodactylum tricornutum at low inorganic carbon concentrations.

Photosynthetic carbon fixation is often limited by CO2 availability, which led to the evolution of CO2 concentrating mechanisms (CCMs). Some diatoms possess CCMs that employ biochemical fixation of bicarbonate, similar to C4 plants, but whether biochemical CCMs are commonly found in diatoms is a subject of debate. In the diatom Phaeodactylum tricornutum, phosphoenolpyruvate carboxylase (PEPC) is present in two isoforms, PEPC1 in the plastids and PEPC2 in the mitochondria. We used real-time quantitative polymerase chain reaction, Western blots, and enzymatic assays to examine PEPC expression and PEPC activity, under low and high concentrations of dissolved inorganic carbon (DIC). We generated and analyzed individual knockout cell lines of PEPC1 and PEPC2, as well as a PEPC1/2 double-knockout strain. While we could not detect an altered phenotype in the PEPC1 knockout strains at ambient, low or high DIC concentrations, PEPC2 and the double-knockout strains grown under ambient air or lower DIC availability conditions showed reduced growth and photosynthetic affinity for DIC while behaving similarly to wild-type (WT) cells at high DIC concentrations. These mutants furthermore exhibited significantly lower 13 C/12 C ratios compared to the WT. Our data imply that in P. tricornutum at least parts of the CCM rely on biochemical bicarbonate fixation catalyzed by the mitochondrial PEPC2.

Fish-mussel-algae-bacteria model remedied eutrophication pollution: Application in Dongxiang district reservoir.

Eutrophication pollution has become an important ecological problem in China. Biological treatment is a common means to repair eutrophication pollution. Therefore, based on the biological manipulation technology, we put forward a fishing scheme for the Xiaoxiangshan and Shizishan reservoirs in Dongxiang District, which have been in a serious eutrophication pollution level for a long time, that is, to improve the quality and control water by operating fish, mussel, algae, and bacteria. The monitoring results in the middle stage of treatment showed that the structure of phytoplankton changed, and the degree of eutrophication pollution improved. In the later stage of treatment, the plankton diversity and richness of the two reservoirs increased significantly, the density and biomass of Cyanobacteria decreased significantly, and the degree of eutrophication pollution decreased to mesotrophic type. Overall, our research puts forward new ideas for the prevention and control of water eutrophication pollution and provides a reference for other kinds of water body treatment.

The Influence of Authoritarian-Benevolent Leadership on Subordinates' Work Engagement: A Social Information Processing Perspective.

Purpose: The dynamic and complex external environment calls for leaders to be both benevolent and authoritarian to cope with the mutually exclusive demands in the management process. But few research paid attention to the dark side of leaders' inconsistent behaviors on employees' work outcomes. Based on social information processing theory, this study investigated the impact of authoritarian-benevolent leadership on subordinates' work engagement and explored the mediating role of leader-member exchange ambivalence and the moderating role of trait mindfulness. Methods: A two-wave time-lagged survey approach was employed and data from 309 employees from three Chinese companies were collected. R 4.2.1 and SPSS 26.0 were used to test our hypotheses. Results: The findings demonstrated how subordinates were influenced in their work engagement by authoritarian-benevolent leadership and leader-member exchange ambivalence and emphasized the value of maintaining a high level of trait mindfulness. This study indicated that (1) authoritarian-benevolent leadership was negatively associated with work engagement, which was mediated by leader-member exchange ambivalence; (2) subordinates' trait mindfulness moderated the relationship between leader-member exchange ambivalence and work engagement; (3) the indirect effect of authoritarian-benevolent leadership on subordinates' work engagement through leader-member exchange ambivalence was moderated by subordinates' trait mindfulness. Conclusion: This study reveals the dark side of authoritarian-benevolent leadership and deepens our understanding of the mechanism underlying the effect of authoritarian-benevolent leadership on subordinates' work engagement from a new theoretical perspective. Practical implications are provided for managers to effectively develop authoritarian-benevolent leadership skills and improve subordinates' work engagement.

The impact of culture systems on the gut microbiota and gut metabolome of bighead carp (Hypophthalmichthys nobilis).

BACKGROUND: The gut microbiota of fish confers various effects on the host, including health, nutrition, metabolism, feeding behaviour, and immune response. Environment significantly impacts the community structure of fish gut microbiota. However, there is a lack of comprehensive research on the gut microbiota of bighead carp in culture systems. To demonstrate the impact of culture systems on the gut microbiome and metabolome in bighead carp and investigate a potential relationship between fish muscle quality and gut microbiota, we conducted a study using 16S ribosomal ribonucleic acid sequencing, gas chromatography-mass spectrometry, and liquid chromatography-mass spectrometry techniques on bighead carp in three culture systems. RESULTS: Our study revealed significant differences in gut microbial communities and metabolic profiles among the three culture systems. We also observed conspicuous changes in muscle structure. The reservoir had higher gut microbiota diversity indices than the pond and lake. We detected significant differences in phyla and genera, such as Fusobacteria, Firmicutes, and Cyanobacteria at the phylum level, Clostridium sensu stricto 1, Macellibacteroides, Blvii28 wastewater sludge group at the genus level. Multivariate statistical models, including principal component analysis and orthogonal projections to latent structures-discriminant analysis, indicated significant differences in the metabolic profiles. Key metabolites were significantly enriched in metabolic pathways involved in "arginine biosynthesis" and "glycine, serine, and threonine metabolism". Variation partitioning analysis revealed that environmental factors, such as pH, ammonium nitrogen, and dissolved oxygen, were the primary drivers of differences in microbial communities. CONCLUSIONS: Our findings demonstrate that the culture system significantly impacted the gut microbiota of bighead carp, resulting in differences in community structure, abundance, and potential metabolic functions, and altered the host's gut metabolism, especially in pathways related to amino acid metabolism. These differences were influenced substantially by environmental factors. Based on our study, we discussed the potential mechanisms by which gut microbes affect muscle quality. Overall, our study contributes to our understanding of the gut microbiota of bighead carp under different culture systems.

Observing Leadership as and in Networks: A Multilevel Investigation of Shared Leadership, Discrete Emotions, and Knowledge Behaviors.

Purpose: With an increasing demand for shared leadership to address complex, dynamic, and diverse knowledge situations, more attention should be paid to the knowledge behaviors of emergent leaders in teams. However, there is thus far a lack of research into the multilevel nature of shared leadership. Using a dual network lens, this study considers two aspects of shared leadership: "shared leadership as networks" (SLAN) and "shared leadership in networks" (SLIN). Based on emotion appraisal theory, this study investigated the impact of SLIN on leaders' productive and counterproductive knowledge behaviors through discrete emotions (pride and fear of losing power) and the moderating role of SLAN in guiding their emotions and subsequent behaviors. Methods: A social network approach was employed to obtain data among 431 employees from 72 teams in China. We identified 350 emergent leaders via leadership sociograms. Statistical analysis methods, including multilevel regression analysis, Monte Carlo simulation, and simple slope analysis, were utilized to test our hypotheses. Results: This study indicates that (1) SLIN is positively associated with pride (B = 0.33, p < 0.001), which in turn increases knowledge sharing (B = 0.37, p < 0.001); (2) SLIN is positively related to fear of losing power (B = 0.21, p < 0.05), which in turn is negatively associated with knowledge sharing (B = -0.23, p < 0.001) and positively associated with knowledge hiding (B = 0.19, p < 0.001); (3) SLAN moderated these aforementioned indirect effects. Conclusion and Originality: First, by defining and differentiating between SLAN and SLIN, this study expands a new perspective on SLIN and facilitates the further development of multilevel shared leadership. Second, this study responds to recent calls for more research on leadership networks and individual-level outcomes of shared leadership. Moreover, it offers a novel theoretical framework to illustrate the impact of SLIN on their knowledge behaviors. Finally, the focus on the moderating role of SLAN identifies a significant contextual factor that prevents the dysfunctional effects of SLIN. These original discoveries enrich the literature on team leadership, emotions, and knowledge management. Further, our novel findings may be of interest to practitioners as they help organizations and teams manage the complex impacts of SLIN on knowledge behaviors in the contexts of an ongoing "affective revolution" and team-based organizational structures.

Author Correction: Predicting the Dispersion Relations of One-Dimensional Phononic Crystals by Neural Networks.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Predicting the Dispersion Relations of One-Dimensional Phononic Crystals by Neural Networks.

In this paper, deep back propagation neural networks (DBP-NNs) and radial basis function neural networks (RBF-NNs) are employed to predict the dispersion relations (DRs) of one-dimensional (1D) phononic crystals (PCs). The data sets generated by transfer matrix method (TMM) are used to train the NNs and detect their prediction accuracy. In our work, filling fractions, mass density ratios and shear modulus ratios of PCs are considered as the input values of NNs. The results show that both the DBP-NNs and the RBF-NNs exhibit good performances in predicting the DRs of PCs. For one-parameter prediction, the RBF-NNs have shorter training time and remarkable prediction accuracy, for two- and three-parameter prediction, the DBP-NNs have more stable performance. The present work confirms the feasibility of predicting the DRs of PCs by NNs, and provides a useful reference for the application of NNs in the design of PCs and metamaterials.