Physiologically based pharmacokinetic modelling of cefoperazone in paediatrics.

Aims: Cefoperazone is commonly used off-label in the treatment of bacterial meningitis and sepsis in children, and the pharmacokinetic (PK) data are limited in this vulnerable population. The goal of this study was to develop a physiologically based pharmacokinetic (PBPK) model to predict pediatric cefoperazone exposure for rational dosing recommendations.

Methods: A cefoperazone PBPK model for adults was first constructed using Simcyp V22 simulator.

Evaluation of Various Approaches to Estimate Transplacental Clearance of Vancomycin for Predicting Fetal Concentrations using a Maternal-Fetal Physiologically Based Pharmacokinetic Model.

Background: Evaluating drug transplacental clearance is vital for forecasting fetal drug exposure. Ex vivo human placenta perfusion experiments are the most suitable approach for this assessment. Various in silico methods are also proposed.

Simulated drug disposition in critically ill patients to evaluate effective PK/PD targets for combating resistance to meropenem.

Bacterial infections, including those caused by , often lead to sepsis, necessitating effective antibiotic treatment like carbapenems. The key pharmacokinetic/pharmacodynamic (PK/PD) index correlated to carbapenem efficacy is the fraction time of unbound plasma concentration above the minimum inhibitory concentration (MIC) of the pathogen (% > MIC). While multiple targets exist, determining the most effective one for critically ill patients remains a matter of debate.

Potential prognosis and immunotherapy predictor TFAP2A in pan-cancer.

Background: TFAP2A is critical in regulating the expression of various genes, affecting various biological processes and driving tumorigenesis and tumor development. However, the significance of TFAP2A in carcinogenesis processes remains obscure.

Methods: In our study, we explored multiple databases including TCGA, GTEx, HPA, cBioPortal, TCIA, and other well-established databases for further analysis to expound TFAP2A expression, genetic alternations, and their relationship with the prognosis and cellular signaling network alternations.

Development and validation of a UPLC-PDA method for quantifying ceftazidime in dried blood spots.

Bacterial infection is a leading cause of neonatal death. Ceftazidime, commonly used for neonatal infections, is often used off-label. Blood sampling limits pharmacokinetic (PK) studies in neonatal patients.

A novel method to estimate the absorption rate constant for two-compartment model fitted drugs without intravenous pharmacokinetic data.

The performances of most drugs after extravascular administration are fitted well with the two-compartment pharmacokinetic (PK) model, but the estimation of absorption rate constant (k) for these drugs becomes difficult during unavailability of intravenous PK data. Herein, we developed a novel method, called the direct method, for estimating the k values of drugs without using intravenous PK data, by proposing a new PK parameter, namely, maximum apparent rate constant of disposition (k). The accuracy of the direct method in k estimation was determined using the setting parameters (k, k, and k values at high, medium, and low levels, respectively) and clinical data.

Combinatorial Polydopamine-Liposome Nanoformulation as an Effective Anti-Breast Cancer Therapy.

Introduction: Drug delivery systems (DDSs) based on liposomes are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve biosafe, accurate, and efficient cancer therapy of liposomes with single function or single mechanism. To solve this problem, we designed a multifunctional and multimechanism nanoplatform based on polydopamine (PDA)-coated liposomes for accurate and efficient combinatorial cancer therapy of chemotherapy and laser-induced PDT/PTT.

NIR light-activatable dissolving microneedle system for melanoma ablation enabled by a combination of ROS-responsive chemotherapy and phototherapy.

Background: As a consequence of the aggressive and recurrent nature of melanoma, repeated, multimodal treatments are often necessary to cure the disease. While microneedle (MN)-based transdermal drug delivery methods can allow drugs to avoid first-pass metabolism and overcome the stratum corneum barrier, the main challenges of these delivery methods entail the lack of controlled drug release/activation and effective imaging methods to guide the entire treatment process.

Methods: To enable a transdermal delivery method with controllable drug release/activation and effective imaging guidance, we designed a near-infrared (NIR) photoactivatable, dissolving MN system comprising dissolvable polyvinylpyrrolidone MNs arrays (MN-pB/I) containing liposomes that were co-loaded with the photosensitizer indocyanine green (ICG) and the reactive oxygen species (ROS)-activatable prodrug of doxorubicin (pB-DOX).

Identification of CPT2 as a prognostic biomarker by integrating the metabolism-associated gene signature in colorectal cancer.

Background: The incidence of colorectal cancer (CRC) is considered to be the third-highest malignant tumor among all carcinomas. The alterations in cellular bioenergetics (metabolic reprogramming) are associated with several malignant phenotypes in CRC, such as tumor cell proliferation, invasion, metastasis, chemotherapy resistance, as well as promotes its immune escape. However, the expression pattern of metabolism-associated genes that mediate metabolic reprogramming in CRC remains unknown.

Facial Emotion Recognition Using a Novel Fusion of Convolutional Neural Network and Local Binary Pattern in Crime Investigation.

The exploration of facial emotion recognition aims to analyze psychological characteristics of juveniles involved in crimes and promote the application of deep learning to psychological feature extraction. First, the relationship between facial emotion recognition and psychological characteristics is discussed. On this basis, a facial emotion recognition model is constructed by increasing the layers of the convolutional neural network (CNN) and integrating CNN with several neural networks such as VGGNet, AlexNet, and LeNet-5.

Symptomatic plaque enhancement is associated with early-onset post-stroke depression.

Background: The association between imaging features closely associated with symptomatic intracranial atherosclerotic plaques and early-onset post-stroke depression (PSD) is currently unclear.

Materials And Methods: 76 ischemic stroke patients who underwent high-resolution vessel wall magnetic resonance imaging (HR-VWI) were divided into PSD and non-PSD groups according to their DSM-V diagnoses and HAMD-17 scores at 14 days after onset. Clinical data and the imaging features associated with symptomatic plaques (including the enhancement index (EI), remodeling index, and plaque surface irregularity) were compared between groups.

ROS-responsive liposomes with NIR light-triggered doxorubicin release for combinatorial therapy of breast cancer.

Background: Reactive oxygen species (ROS)-responsive drug delivery systems (DDSs) are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve spatially and temporally controllable and accurate drug release in tumor sites based on ROS-responsive DDSs. To solve this problem, we designed a nanosystem combined photodynamic therapy (PDT) and ROS-responsive chemotherapy.

A spermine conjugated stearic acid-g-chitosan oligosaccharide polymer with different types of amino groups for efficient p53 gene therapy.

The effect of various amino groups on gene vector is different. In order to combine their effect in one vector and finally promote the transfection efficiency, a biogenic tetra-amine spermine was introduced to modify the stearic acid-grafted chitosan oligosaccharide (CSOSA) polymer to build a new gene delivery system. The spermine linked CSOSA (SP-CSOSA) polymer consists two types of amino groups with 73.

Effect of anionic PEGylated polypeptide on gene transfection mediated by glycolipid conjugate micelles.

To improve the gene transfection efficiency mediated by chitosan-g-stearic acid (CS) micelles, poly(ethylene glycol)-b-poly(γ-glutamic acid) (PG) was incorporated into a CS-based gene delivery system. CS/PG/pDNA complexes were prepared by ionic interaction. CS and PEGylated CS (PCS) micelles were introduced to prepare binary complexes for use as controls.

TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting.

Nowadays, a real challenge in cancer therapy is to design drug delivery systems that can achieve high concentrations of drugs at the target site for improved therapeutic effect with reduced side effects. In this research, we designed and synthesized a homing peptide-(TNYLFSPNGPIA, TNYL) modified chitosan-g-stearate (CS) polymer micelle (named T-CS) for targeting delivery. The peptide displayed specific binding affinity to EphB4 which is a member of the Eph family of receptor tyrosine protein kinases.