Predicting tissue distribution and tumor delivery of nanoparticles in mice using machine learning models.

Nanoparticles (NPs) can be designed for targeted delivery in cancer nanomedicine, but the challenge is a low delivery efficiency (DE) to the tumor site. Understanding the impact of NPs' physicochemical properties on target tissue distribution and tumor DE can help improve the design of nanomedicines. Multiple machine learning and artificial intelligence models, including linear regression, support vector machine, random forest, gradient boosting, and deep neural networks (DNN), were trained and validated to predict tissue distribution and tumor delivery based on NPs' physicochemical properties and tumor therapeutic strategies with the dataset from Nano-Tumor Database.

A physiologically based pharmacokinetic/pharmacodynamic model to determine dosage regimens and withdrawal intervals of aditoprim against .

Streptococcus suis () is a zoonotic pathogen threatening public health. Aditoprim (ADP), a novel veterinary medicine, exhibits an antibacterial effect against . In this study, a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was used to determine the dosage regimens of ADP against and withdrawal intervals.

Ceftiofur in swine manure contributes to reducing pathogens and antibiotic resistance genes during composting.

Aerobic composting is a common way for the disposal of feces produced in animal husbandry, and can reduce the release of antibiotic resistance genes (ARGs) from feces into the environment. In this study, we collected samples from two distinct treatments of swine manure compost with and without ceftiofur (CEF), and identified the ARGs, mobile genetic elements (MGEs), and bacterial community by metagenomic sequencing. The impacts of CEF on the bacterial community composition and fate of ARGs and MGEs were investigated.

Bacterial Efflux Pump Inhibitors Reduce Antibiotic Resistance.

Bacterial resistance is a growing problem worldwide, and the number of deaths due to drug resistance is increasing every year. We must pay great attention to bacterial resistance. Otherwise, we may go back to the pre-antibiotic era and have no drugs on which to rely.

Metagenomic analysis reveals impact of acyl homoserine endolipid-like signaling molecules on the aqueous sediment resistome under florfenicol stress.

Quorum sensing potentially helps microorganisms adapt to antibiotic stress encountered in the environment. This experiment investigated the effect of acyl homoserine endolipid-like signaling molecules on microbial antibiotic resistance gene structures in aqueous sediments under florfenicol stress. Additional acyl homoserine endolipid-like signaling molecules (AHLs) alter the structure of multidrug resistance genes in florfenicol-stressed sediments, particularly the multidrug resistance efflux pump gene family.

Co-selection mechanism for bacterial resistance to major chemical pollutants in the environment.

Bacterial resistance is an emerging global public health problem, posing a significant threat to animal and human health. Chemical pollutants present in the environment exert selective pressure on bacteria, which acquire resistance through co-resistance, cross-resistance, co-regulation, and biofilm resistance. Resistance genes are horizontally transmitted in the environment through four mechanisms including conjugation transfer, bacterial transformation, bacteriophage transduction, and membrane vesicle transport, and even enter human bodies through the food chain, endangering human health.

The Relationship Between Theta Power, Theta Asymmetry and the Effect of Escitalopram in the Treatment of Depression.

Objective: Only about one-third of depressed patients respond to initial antidepressant treatment. Therefore, it is crucial to find effective predictors of antidepressants. The purpose of our study was to learn the relationship between EEG theta power, theta asymmetry, and the efficacy of escitalopram.

Pharmacokinetic and Pharmacodynamic Drug-Drug Interactions: Research Methods and Applications.

Because of the high research and development cost of new drugs, the long development process of new drugs, and the high failure rate at later stages, combining past drugs has gradually become a more economical and attractive alternative. However, the ensuing problem of drug-drug interactions (DDIs) urgently need to be solved, and combination has attracted a lot of attention from pharmaceutical researchers. At present, DDI is often evaluated and investigated from two perspectives: pharmacodynamics and pharmacokinetics.

A physiologically based pharmacokinetic model to optimize the dosage regimen and withdrawal time of cefquinome in pigs.

Cefquinome is widely used to treat respiratory tract diseases of swine. While extra-label dosages of cefquinome could improve clinical efficacy, they might lead to excessively high residues in animal-derived food. In this study, a physiologically based pharmacokinetic (PBPK) model was calibrated based on the published data and a microdialysis experiment to assess the dosage efficiency and food safety.

antimicrobials inherited and the non-inherited resistance: mechanisms and alternative therapeutic strategies.

spp. is one of the most important foodborne pathogens. Typhoid fever and enteritis caused by are associated with 16-33 million infections and 500,000 to 600,000 deaths annually worldwide.

Emerging roles of endoplasmic reticulum stress in the cellular plasticity of cancer cells.

Cellular plasticity is a well-known dynamic feature of tumor cells that endows tumors with heterogeneity and therapeutic resistance and alters their invasion-metastasis progression, stemness, and drug sensitivity, thereby posing a major challenge to cancer therapy. It is becoming increasingly clear that endoplasmic reticulum (ER) stress is a hallmark of cancer. The dysregulated expression of ER stress sensors and the activation of downstream signaling pathways play a role in the regulation of tumor progression and cellular response to various challenges.

The Application of Hollow Fiber Cartridge in Biomedicine.

The hollow fiber cartridge has the advantages of good semi-permeability, high surface area to volume ratio, convenient operation, and so on. Its application in chemical analysis, drug in vitro experiment, hemodialysis, and other fields has been deeply studied. This paper introduces the basic structure of hollow fiber cartridge, compares the advantages and disadvantages of a hollow fiber infection model constructed by a hollow fiber cartridge with traditional static model and animal infection model and introduces its application in drug effects, mechanism of drug resistance, and evaluation of combined drug regimen.

Prognostic and incremental value of computed tomography-based radiomics from tumor and nodal regions in esophageal squamous cell carcinoma.

Objective: This study aimed to evaluate the prognostic value of preoperative radiomics and establish an integrated model for esophageal squamous cell cancer (ESCC).

Methods: A total of 931 patients were retrospectively enrolled in this study (training cohort, n=624; validation cohort, n=307). Radiomics features were obtained by contrast-enhanced computed tomography (CT) before esophagectomy.

Fate and exposure risk of florfenicol, thiamphenicol and antibiotic resistance genes during composting of swine manure.

Livestock manure is an important source of antibiotic resistance genes (ARGs) spreading to the environment, posing a potential threat to human health. Here, we investigated the dissipation of florfenicol (FF) and thiamphenicol (TAP), and their effects on the bacterial community, mobile genetic elements (MGEs), and ARGs during composting. The results indicated that FF and TAP dissipated rapidly in compost, with half-life values of 5.

Optimization and Validation of Dosage Regimen for Ceftiofur against in Swine by Physiological Based Pharmacokinetic-Pharmacodynamic Model.

Model informed drug development is a valuable tool for drug development and clinical application due to its ability to integrate variability and uncertainty of data. This study aimed to determine an optimal dosage of ceftiofur against by ex vivo pharmacokinetic/pharmacodynamic (PK/PD) model and validate the dosage regimens by Physiological based Pharmacokinetic-Pharmacodynamic (PBPK/PD) model. The pharmacokinetic profiles of ceftiofur both in plasma and bronchoalveolar lavage fluid (BALF) are determined.

Application of Semi-Mechanistic Pharmacokinetic and Pharmacodynamic Model in Antimicrobial Resistance.

Antimicrobial resistance is a major public health issue. The pharmacokinetic/pharmacodynamic (PK/PD) model is an essential tool to optimize dosage regimens and alleviate the emergence of resistance. The semi-mechanistic PK/PD model is a mathematical quantitative tool to capture the relationship between dose, exposure, and response, in terms of the mechanism.

Metabolite Identification and Pharmacokinetic Behavior of Diaveridine in the Plasma of Pigs and Chickens Based on Radioactive Tracing Coupled With LC/MS-IT-TOF Assay.

Diaveridine (DVD) is widely used for the prevention and treatment of coccidiosis and leucocytozoonosis infections in food-producing animals. To gain a better understanding of DVD metabolism and pharmacokinetics in healthy Landrace/Doric Cross castrated male pigs and both female and male Cobb 500 broiler chickens, a method involving radioactive tracing coupled with LC/MS-IT-TOF was developed for the identification and quantitation of DVD and its metabolites in pig and chicken plasma, and then was applied to investigate DVD pharmacokinetics. A simple MCX solid phase extraction procedure was adopted for sample preparation.

Excretion and Residual Concentration Correlations of Salbutamol Between Edible Tissues and Living Samples in Pigs and Goats.

Illegal use of salbutamol (SAL), a β-adrenergic leanness-enhancing agent, has posed potential threat to human health in China. The excretion and depletion of SAL in pigs and goats were investigated, and the concentration correlations between edible tissues and living samples were analyzed to find out a suitable living sample for pre-slaughter monitoring of SAL in pigs and goats. After a single oral dosage of 1.

Dose Optimization of Aditoprim-Sulfamethoxazole Combinations Against From Patients With Clinical Endometritis by Using Semi-mechanistic PK/PD Model.

Combinations of two and more drugs with different target sites are being used as a new treatment regimen for resistant clones of bacteria. Though, achieving the right combination of the drugs for optimal dosage regimen is challenging. In our study, we studied the antimicrobial effect of aditoprim, a novel dihydrofolate reductase inhibitor, and its synergistic effect with sulfamethoxazole.

Determination of Susceptibility Breakpoint for Cefquinome against in Pigs.

(), a zoonotic pathogen, causes severe diseases in both pigs and human beings. Cefquinome can display excellent antibacterial activity against gram-negative and gram-positive bacteria. The aim of this study was to derive an optimal dosage of cefquinome against with a pharmacokinetic/pharmacodynamic (PK/PD) integration model in the target infection site and to investigate the cutoffs monitoring the changes of resistance.

Apply a Physiologically Based Pharmacokinetic Model to Promote the Development of Enrofloxacin Granules: Predict Withdrawal Interval and Toxicity Dose.

Enrofloxacin (ENR) granules were developed to prevent and control the infections caused by foodborne zoonotic intestinal pathogens in our previous studies. To promote the further development of ENR granules and standardize their usage in pigs, a physiologically based pharmacokinetic (PBPK) model of the ENR granule in pigs was built to determine the withdrawal time (WT) and evaluate the toxicity to pigs. Meanwhile, the population WT was determined by a Monte Carlo analysis to guarantee pork safety.

Adsorption/desorption and degradation of doxycycline in three agricultural soils.

Veterinary antibiotics are widely used in animal agriculture. Owing to its good absorption in the gastrointestinal tract, strong tissue permeability, and long biological half-life, doxycycline (DOX) is widely used to treat bacterial infections; however, this use can pose an environmental risk. The adsorption/desorption and degradation of DOX in three agricultural soils were investigated.

Exploration of Clinical Breakpoint of Danofloxacin for in Plasma and in PELF.

In order to establish the clinical breakpoint (CBP) of danofloxacin against , three cutoff values, including epidemiological cutoff value (ECV), pharmacokinetic-pharmacodynamic (PK-PD) cutoff value (CO) and clinical cutoff value (CO), were obtained in the present study. The ECV was calculated using ECOFFinder base on the MIC distribution of danfloxacin against 347 collected from disease pigs. The CO was established based on in vivo and ex vivo PK-PD modeling of danofloxacin both in plasma and pulmonary epithelial lining fluid (PELF) using Hill formula and Monte Carlo analysis.