[Daily NO Simulation Research Based on Automatic Machine Learning Ensemble Models].

To understand the spatial distribution of NO near the surface, we utilized measured data from NO monitoring stations and combined it with column concentration data from the Tropospheric Monitoring Instrument （TROPOMI）, taking the Yangtze River Delta region as the study area. We considered the impact of factors such as population, elevation, and meteorological conditions on NO levels. We used automated machine learning to select five machine-learning algorithms with high simulation accuracy, namely ET, RF, XGBoost, LightGBM, and Catboost, and then integrated these five algorithms using the Stacking model to simulate the daily NO concentration in the Yangtze River Delta region from March 2020 to February 2021.

Prediction of tissue exposures of polymyxin-B, amikacin and sulbactam using physiologically-based pharmacokinetic modeling.

Background: The combination antimicrobial therapy consisting of amikacin, polymyxin-B, and sulbactam demonstrated synergy against multi-drug resistant .

Objectives: The objectives were to predict drug disposition and extrapolate their efficacy in the blood, lung, heart, muscle and skin tissues using a physiologically-based pharmacokinetic (PBPK) modeling approach and to evaluate achievement of target pharmacodynamic (PD) indices against .

Methods: A PBPK model was initially developed for amikacin, polymyxin-B, and sulbactam in adult subjects, and then scaled to pediatrics, accounting for both renal and non-renal clearances.

Predict the Drug-Drug Interaction of a Novel PI3Kα/δ Inhibitor, TQ-B3525, and Its Two Metabolites Using Physiologically Based Pharmacokinetic Modeling.

A novel dual PI3K α/δ inhibitor, TQ-B3525, has been developed for the targeted treatment of lymphoma and solid tumors. TQ-B3525 is primarily metabolized by CYP3A4 and FOM3, while also serving as a substrate for the P-glycoprotein transporter. The aim of this study was to anticipate the drug-drug interaction (DDI) of TQ-B3525 and its two metabolites with CYP3A4 enzyme potent inducer (rifampicin) and CYP3A4/P-gp inhibitor (itraconazole) utilizing a physiologically based pharmacokinetic (PBPK) modeling approach.

Metabolomics revealed mechanism for the synergistic effect of sulbactam, polymyxin-B and amikacin combination against .

Introduction: The emergence of multidrug-resistant (MDR) prompts clinicians to consider treating these infections with polymyxin combination.

Methods: Metabolomic analysis was applied to investigate the synergistic effects of polymyxin-B, amikacin and sulbactam combination therapy against MDR harboring OXA-23 and other drug resistant genes. The drug concentrations tested were based on their clinical breakpoints: polymyxin-B (2 mg/L), amikacin (16 mg/L), polymyxin-B/amikacin (2/16 mg/L), and polymyxin-B/amikacin/sulbactam (2/16/4 mg/L).

Physiologically-based pharmacokinetic modeling to inform dosing regimens and routes of administration of rifampicin and colistin combination against Acinetobacter baumannii.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to major antibiotics such as penicillin, cephalosporin, fluoroquinolone and aminoglycoside, and has become a significant nosocomial pathogen. The efficacy of rifampicin and colistin combination against CRAB could be dependent on the administration routes and drug concentrations at the site of infection.

Objective: The objective is to predict drug disposition in biological tissues.

Pharmacokinetic/Pharmacodynamic Evaluation of Aztreonam/Amoxicillin/Clavulanate Combination against New Delhi Metallo-β-Lactamase and Serine-β-Lactamase Co-Producing and .

This study aimed to examine specific niches and usage for the aztreonam/amoxicillin/clavulanate combination and to use population pharmacokinetic simulations of clinical dosing regimens to predict the impact of this combination on restricting mutant selection. The in vitro susceptibility of 19 New-Delhi metallo-β-lactamase (NDM)-producing clinical isolates to amoxicillin/clavulanate and aztreonam alone and in co-administration was determined based on the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC). The fractions of a 24-h duration that the free drug concentration was within the mutant selection window (fTMSW) and above the MPC (fT>MPC) in both plasma and epithelial lining fluid were determined from simulations of 10,000 subject profiles based on regimens by renal function categories.

The combination effect of meropenem/sulbactam/polymyxin-B on the pharmacodynamic parameters for mutant selection windows against carbapenem-resistant .

The objective of this study was to evaluate whether combinations of sulbactam, meropenem, and polymyxin-B could reduce or close the gap of mutant selection window (MSW) of individual antibiotics against harboring OXA-23. MICs of three antimicrobials used alone and in combination (meropenem/polymyxin-B or meropenem/polymyxin-B/sulbactam) were obtained in 11 clinical isolates and mutant prevention concentrations were determined in 4 of the 11 isolates. All isolates were resistant to meropenem or polymyxin-B.

Effects of amikacin, polymyxin-B, and sulbactam combination on the pharmacodynamic indices of mutant selection against multi-drug resistant .

Amikacin and polymyxins as monotherapies are ineffective against multidrug-resistant at the clinical dose. When polymyxins, aminoglycosides, and sulbactam are co-administered, the combinations exhibit synergistic activities. The minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined in 11 and 5 clinical resistant isolates of harboring OXA-23, respectively, in order to derive the fraction of time over the 24-h wherein the free drug concentration was within the mutant selection window (T) and the fraction of time that the free drug concentration was above the MPC (T) from simulated pharmacokinetic profiles.

Metabolomic profiling of polymyxin-B in combination with meropenem and sulbactam against multi-drug resistant .

Empirical therapies using polymyxins combined with other antibiotics are recommended in the treatment of infections. In the present study, the synergistic activities of polymyxin-B, meropenem, and sulbactam as combination therapy were investigated using metabolomic analysis. The metabolome of was investigated after treatment with polymyxin-B alone (2 mg/l), meropenem (2 mg/l) alone, combination of polymyxin-B/meropenem at their clinical breakpoints, and triple-antibiotic combination of polymyxin-B/meropenem and 4 mg/l sulbactam.

Prediction of Tissue Exposures of Meropenem, Colistin, and Sulbactam in Pediatrics Using Physiologically Based Pharmacokinetic Modeling.

Background: The combination of polymyxins, meropenem, and sulbactam demonstrated efficacy against multi-drug-resistant bacillus Acinetobacter baumannii. These three antibiotics are commonly used against major blood, skin, lung, and heart muscle infections.

Objective: The objective of this study was to predict drug disposition and extrapolate the efficacy in these tissues using a physiologically based pharmacokinetic modeling approach that linked drug exposures to their target pharmacodynamic indices associated with antimicrobial activities against A.

Florfenicol/Chlortetracycline Effect on Pharmacodynamic Indices for Mutant Selection of in Ducks.

can cause septicemia and death in ducks and geese, leading to significant economic losses to animal farms. The emergence of resistance of to commonly used antibiotics increases the difficulty of treating infection. The aim of this study was to evaluate the utility of antibiotic combination to restrict mutant selection of multidrug-resistant (MDR) isolates.

Aztreonam/avibactam effect on pharmacodynamic indices for mutant selection of Escherichia coli and Klebsiella pneumoniae harbouring serine- and New Delhi metallo-β-lactamases.

Objectives: Ceftazidime/avibactam is not active against MBL-producing bacteria. Combining ceftazidime/avibactam or avibactam with aztreonam can counter the resistance of MBL-producing Enterobacterales. The aim of this study was to evaluate whether the addition of avibactam could reduce or close the mutant selection window (MSW) of aztreonam in Escherichia coli and Klebsiella pneumoniae harbouring MBLs; MSW is a pharmacodynamic (PD) parameter for the selection of emergent resistant mutants.

LC-MS/MS Determination of Apigenin in Rat Plasma and Application to Pharmacokinetic Study.

Background: Apigenin, a natural plant flavone, has been shown to possess a variety of biological properties.

Objective: In this report, a highly selective and sensitive LC-MS/MS method was developed and validated for the determination of apigenin in rat plasma.

Methods: Analysts were separated on the HSS T3 column (1.

Pharmacokinetics and tissue distribution of eupatilin and its metabolite in rats by an HPLC-MS/MS method.

Eupatilin, a major pharmacologically active ingredient in Stillen, has been known to possess anti-peptic, anti-cancer and anti-allergy activities. A rapid, simple, sensitive and specific high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous determination of eupatilin and its main metabolite (eupatilin-7β-O-glucuronide, E-7-G) in rat plasma and tissues was established and validated. The linear range of eupatilin and E-7-G was 0.

Decimetre-scale multicellular eukaryotes from the 1.56-billion-year-old Gaoyuzhuang Formation in North China.

Fossils of macroscopic eukaryotes are rarely older than the Ediacaran Period (635-541 million years (Myr)), and their interpretation remains controversial. Here, we report the discovery of macroscopic fossils from the 1,560-Myr-old Gaoyuzhuang Formation, Yanshan area, North China, that exhibit both large size and regular morphology. Preserved as carbonaceous compressions, the Gaoyuzhuang fossils have statistically regular linear to lanceolate shapes up to 30 cm long and nearly 8 cm wide, suggesting that the Gaoyuzhuang fossils record benthic multicellular eukaryotes of unprecedentedly large size.

Ultrastructural Heterogeneity of Carbonaceous Material in Ancient Cherts: Investigating Biosignature Origin and Preservation.

Opaline silica deposits on Mars may be good target sites where organic biosignatures could be preserved. Potential analogues on Earth are provided by ancient cherts containing carbonaceous material (CM) permineralized by silica. In this study, we investigated the ultrastructure and chemical characteristics of CM in the Rhynie chert (c.