Hanoi University of Pharmacy

This study evaluated the probability of pharmacokinetic/pharmacodynamic efficacy target attainment and developed a dosing interval identification nomogram to minimize toxicity risks of high-dose amikacin. Therapeutic drug monitoring was performed in critically ill patients receiving high-dose (30 mg/kg) amikacin intravenously. Population pharmacokinetic modeling and Monte Carlo simulation were performed in NONMEM® 7.5.1. The probability of target attainment and the cumulative fraction of response for the local Klebsiella pneumoniae population were assessed using maximum concentration/minimum inhibitory concentration ≥ 8 as the efficacy target. Nomograms stratified by the renal function group were established to guide dosing intervals to avoid exceeding the toxicity minimum concentration threshold of 2.5 mg/L. A total of 251 patients with 488 amikacin concentrations were included. The amikacin pharmacokinetics was best described by a two-compartment model. The creatinine clearance and adjusted body weight were significant covariates for clearance and the central volume of distribution, respectively. Amikacin 30 mg/kg achieved a probability of target attainment > 90% for minimum inhibitory concentrations < 8 mg/L and around 80% for minimum inhibitory concentrations of 8 mg/L. This regimen showed a cumulative fraction of response of 63.5% for K. pneumoniae, while attaining a cumulative fraction of response of 96.8% for susceptible isolates. The 30-mg/kg nomograms in patients with creatinine clearance < 60 and ≥ 60 mL/min showed accurate dosing intervals with around 90% of virtual patients for the post-infusion period from 20 to 32 h and from 6 to 32 h, respectively. Nomogram-aided dosing interval adjustment of high-dose amikacin (30 mg/kg) maximized the efficacy and safety target attainment for critically ill patients with infections caused by susceptible K. pneumoniae.

The imidazole-[1,5-a]-pyridine derivatives were recently synthesized and showed remarkable bioactivity against three cancer cell lines, but an understanding of their activities is still missing. To prompt a detailed investigation into their molecular binding mechanisms, we carried out a comprehensive computational workflow for structure-based drug design. The protocol encompasses (i) ligand polarization using quantum chemical calculations, (ii) docking algorithms to generate initial protein-ligand conformations, (iii) molecular dynamics simulations to evaluate ligand diffusion within the protein pocket, and (iv) binding free energy calculations through the umbrella sampling molecular dynamics method. The inherent flexibility of the epidermal growth factor receptor (EGFR) kinase protein in an aqueous environment challenges the stability of ligand-protein associations. Of the 15 imidazole-pyridine compounds considered, after completing a total simulation time of 1.1 μs, only three compounds have been found to possess strong interactions with critical residues in the allosteric pocket of the EGFR inactive conformation in which the electrostatic potential energies play an important role. Notably, the compound named 3h389 carries out an exceptionally large binding free energy, outperforming the well-known allosteric inhibitor EAI045 considered a reference. More interestingly, the EGFR conformational changes under both 3h389 and EAI045 binding are similar. These results promote the imidazole-[1,5-a] compound denoted as 3h389 to be a highly strong candidate for a preclinical evaluation in cancer therapy. If such an evaluation can be performed, it underlines the utility of our computational pipeline for drug discovery efforts.

In the context of agricultural digital transformation, this study proposes a PLC-based smart livestock management system that integrates multi-gas environmental sensing, automated control, and cloud-based monitoring within a unified architecture. The system employs a wireless sensor network to simultaneously monitor temperature, humidity, light intensity, wind speed, and key gases (O₂, CO, CO₂, and NH₃), enabling comprehensive assessment of barn microclimate conditions. Sensor data are processed in real time by a Programmable Logic Controller (PLC) to execute automatic and semi-automatic control of ventilation, cooling, lighting, and roof mechanisms, ensuring stable and safe environments for livestock. The use of nanomaterial-based sensing elements enhances gas sensitivity and response time, improving microclimate regulation accuracy compared with conventional sensors. A cloud-connected platform further enables remote monitoring, data storage, scenario-based operation, and real-time alerts via web and mobile applications. The system was experimentally deployed in a commercial poultry farm in Hung Yen, Vietnam, demonstrating improved environmental stability, reduced labor demand, and increased poultry survival rates. These results confirm the novelty, feasibility, and scalability of the proposed nanomaterial–PLC integrated approach.

Antimicrobial peptides (AMPs) represent promising scaffolds for therapeutic development, but many natural sequences show limited potency or poor selectivity. Among them, Cn-AMP1, a coconut-derived peptide, exhibits excellent biocompatibility but weak antibacterial and anticancer activities owing to low hydrophobicity and minimal cationic charge. Here, we rationally designed a series of Cn-AMP1 derivatives with systematic modulation of charge and hydrophobicity to probe structure-activity relationships. Among them, CAP10, displayed 2-4-fold stronger antibacterial potency than earlier analogs while maintaining hemolysis below 10%. CAP10 also achieved measurable cytotoxicity toward cancer cells, representing a clear improvement over the other Cn-AMP1 derivatives. Molecular dynamics simulations revealed that CAP10 penetrates deeply into bacterial and cancer membranes, inducing local bilayer thinning and density depletion, whereas Cn-AMP1 remained surface-bound with limited disruption. These results establish that simultaneous optimization of hydrophobicity and charge enhances membrane-active selectivity and dual functionality. Our findings provide structural principles for the rational design of next-generation AMPs with improved efficacy and safety profiles.