A novel pH activatable near-infrared fluorescence probe was developed, which successfully visualized acidosis in tumors. This probe holds promise to non-invasively predict the tumor metastasis potential and evaluate the therapeutic response.

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Vancomycin, a glycopeptide antibiotic for the treatment of grampositive infections, is mainly eliminated via glomerular filtration. Thus, its therapeutic effects are affected predominantly by renal function. The aim of this study was to develop a population pharmacokinetic model of vancomycin for Chinese adult patients and to investigate the influence of different renal function descriptors on the predictability of the model. A retrospective analysis was performed based on the blood concentrations of vancomycin in 218 Chinese adult patients. Among these patients, the data from 160 were used to establish the population pharmacokinetic model, and the data from the remaining 58 patients were used for external model validation. A simulation was employed to determine the appropriate initial vancomycin dosage regimens in adult Chinese patients for reaching the target steady-state trough concentrations of 10–15 mg/L and 15–20 mg/L. We developed a one-compartment model with first-order absorption to characterize the concentration-time profile of vancomycin. There was a positive correlation between the body clearance of vancomycin and renal function; both creatinine clearance (CL_Cr) and age were the covariates that influenced the PK of vancomycin, and the excretion of vancomycin decreased as renal function diminishing with age. The typical clearance (CL) value was 2.829 L/h for 75-year-old patients with CL_Cr values of 80 mL/min, and the rate constant of CL with the CL_Cr changing at 1 mL/min was 0.00842. The influence coefficient of age on CL was 0.08143. The external validation results revealed that the current different descriptors of renal function behaved similarly to the predicted performance of the models. In conclusion, the developed model is appropriate for Bayesian dose predictions of vancomycin concentrations in the population of Chinese adult patients. Furthermore, the simulation provides a reference for clinical optimized antibacterial therapy with vancomycin.

Background and Purpose: Receptor internalisation is by nature kinetic. Application of a standard equilibrium dose response model to describe the properties of a ligand inducing internalisation, while commonly used, are therefore problematic. Here, we propose two quantitative approaches to address this issue—(a) a model‐free method and (b) a kinetic modelling approach—and systematically evaluate the performance of these methods against traditional equilibrium methods to characterise the internalisation profiles of cannabinoid CB₁ receptor agonists.Experimental Approach: Kinetic internalisation assays were conducted using a concentration series of six CB₁ receptor ligands. Internalisation rate analysis and snapshot equilibrium analysis were performed. A model‐free method was developed based on the mean residence time of internalisation. A kinetic internalisation model was developed under the quasi‐steady state assumption.Key Results: Rates of receptor internalisation depended on both agonist and concentration. Agonist potencies from snapshot equilibrium analysis increased with stimulation time, and there was no single time point at which internalisation profiles could infer agonist properties in a comparative manner. The model‐free method yielded a time‐invariant measure of potency/efficacy for internalisation. The kinetic model adequately described the internalisation of CB₁ receptors over time and provided robust estimates of both potency and efficacy.Conclusion and Implications: Applying equilibrium analysis to a non‐equilibrium pathway cannot provide a reliable estimate of agonist potency. Both the model‐free and kinetic modelling approaches characterised the internalisation profiles of CB₁ receptor agonists. The kinetic model provides additional advantages as a method to capture changes in receptor number during other functional assays.

The outbreak and spread of coronavirus disease 2019 (COVID-19) highlighted the importance and urgency of the research and development of therapeutic drugs. Very early into the COVID-19 pandemic, China has begun developing drugs, with some notable progress. Herein, we summarizes the anti-COVID-19 drugs and promising drug candidates originally developed and researched in China. Furthermore, we discussed the developmental prospects, mechanisms of action, and advantages and disadvantages of the anti-COVID-19 drugs in development, with the aim to contribute to the rational use of drugs in COVID-19 treatment and more effective development of new drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the variants. Neutralizing antibody is an effective approach to overcome COVID-19. However, drug resistance induced by rapid virus mutation will likely to challenge neutralizing antibodies. Taking into account current epidemic trends, small molecule drugs have a crucial role in fighting COVID-19 due to their significant advantage of convenient administration and affordable and broad-spectrum. Traditional Chinese medicines, including natural products and traditional Chinese medicine prescriptions, contribute to the treatment of COVID-19 due to their unique mechanism of action. Currently, the research and development of Chinese anti-COVID-19 drugs have led to some promising achievements, thus prompting us to expect even more rapidly available solutions.