Tyrosinase (TYR) plays a pivotal role in the biosynthesis of melanin, and its activity level holds critical implications for vitiligo, melanoma cancer, and food nutritional value. The sensitive determination of TYR activity is of great significance for both fundamental research and clinical investigations. In this work, we successfully synthesized silicon-doped carbon quantum dots (Si-CQDs) through a one-pot hydrothermal method with trans-aconitic acid as carbon source and N-[3-(Trimethoxysilyl)propyl]ethylenediamine as the dopant, exhibiting remarkable fluorescence quantum yield (QY) and photostability. Correspondingly, Si-CQDs were used as a probe to construct a sensitive, rapid, and user-friendly fluorescence method for TYR detection. The method relied on the oxidation of isoprenaline (ISO) by TYR, where Si-CQDs were employed as a highly efficient probe. The testing mechanism was the internal filtering effect (IFE) observed between Si-CQDs and the oxidative system of ISO and TYR. Under the optimized conditions, the fluorescence strategy exhibited a detection range of 0.05-2.0 U/mL for TYR with a limit of detection (LOD) of 0.041 U/mL. Furthermore, we successful demonstrated the accurate determination of TYR levels in human serum, showcasing the promising potential of this method in various practical scenarios.

Background: Lamotrigine plays a crucial role in the treatment of epilepsy and bipolar disorder in adults and children. However, its pharmacokinetic (PK) behavior in first or long-term treatment in pediatric patients and the changes in drug exposure in patients with renal impairment are not well characterized. The purpose of the research was to build a robust physiologically based pharmacokinetic (PBPK) model of lamotrigine for the prediction of drug exposure in diverse populations to facilitate therapeutic drug monitoring (TDM) and guide dosing regimens. Methods: The physicochemical parameter values of lamotrigine were integrated to establish and validate the model in an adult population in PK-sim. This adult PBPK model can be extrapolated to children and patients with renal impairment to predict PK changes. Results: Most of the observed data were within the 5th and 95th percentile intervals of the variability around the predicted plasma concentrations. The model predicted pharmacokinetic thresholds and exposure values for clinically safe and effective doses recommended by the FDA for initial and long-term treatment of epilepsy in adults and children aged 2–12 years. Notably, patients with severe renal impairment and end-stage renal disease experienced an average increase in the area under the curve of 1.51 folds and 1.62 folds, respectively. This scenario necessitates further lamotrigine dose adjustments. Conclusions: The developed lamotrigine PBPK model offers a strategy for assisting clinicians in TDM and dose adjustment for special populations, thereby offering a reference (PK parameters, as well as peak and valley concentrations to reach a steady state) for a safer administration regimen in clinical treatment.