Modeling and simulation of drug disposition has emerged as an important tool in drug development, clinical study design and regulatory review, and the number of physiologically based pharmacokinetic ...(PBPK) modeling related publications and regulatory submissions have risen dramatically in recent years. However, the extent of use of PBPK modeling by researchers, and the public availability of models has not been systematically evaluated. This review evaluates PBPK-related publications to 1) identify the common applications of PBPK modeling; 2) determine ways in which models are developed; 3) establish how model quality is assessed; and 4) provide a list of publically available PBPK models for sensitive P450 and transporter substrates as well as selective inhibitors and inducers. PubMed searches were conducted using the terms "PBPK" and "physiologically based pharmacokinetic model" to collect published models. Only papers on PBPK modeling of pharmaceutical agents in humans published in English between 2008 and May 2015 were reviewed. A total of 366 PBPK-related articles met the search criteria, with the number of articles published per year rising steadily. Published models were most commonly used for drug-drug interaction predictions (28%), followed by interindividual variability and general clinical pharmacokinetic predictions (23%), formulation or absorption modeling (12%), and predicting age-related changes in pharmacokinetics and disposition (10%). In total, 106 models of sensitive substrates, inhibitors, and inducers were identified. An in-depth analysis of the model development and verification revealed a lack of consistency in model development and quality assessment practices, demonstrating a need for development of best-practice guidelines.
Graphene nanosheets are impermeable to chemical molecules and electrical conductivity. Thus, they are attractive candidates to enhance an epoxy zinc rich coating with a significant anticorrosion ...performance. Several studies focus on investigating the role of graphene in reinforcing the corrosion resistance of the coatings. However, there is a paucity of study that analyzing the anticorrosion relationship between the feature of graphene and epoxy zinc rich coating. The present study reported on epoxy zinc rich coatings with enhanced anticorrosion performance via embedding reduced graphene oxide/graphene oxide (rGO/GO) nanosheets. Thus, rGO and GO were prepared from natural graphite powder via the modified Hummers method. The results of Raman, XPS, FT-IR, SPM, and TEM analyses revealed the quintessential structure and morphology of rGO and GO. In addition, results from electrochemical measurements and the scanning vibrating electrode technique indicated that rGO effectively enhanced the cathodic protection duration of epoxy zinc rich coatings. rGO nanosheets exhibited dual functions that were identified in two aspects. First, the impermeable barrier role was exerted by including prepared rGO nanosheets into the polymer matrix. Second, superior electrical conductivity was utilized since the rGO nanosheets improved the efficiency of the electrical connection between the zinc particles and steel substrate.
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•Well-designed rGO nanosheets were used for enhancing anticorrosion.•rGO can enhance the cathodic protection duration of epoxy zinc rich coating.•rGO endowed composite coating exhibited optimal anticorrosion capability.•SVET confirmed the cathodic protection property of the coating.
Insufficient tumor accumulation and distribution of photosensitizers as well as low antitumor immunity severely restrict the therapeutic efficacy of photothermal therapy (PTT). Cancer-associated ...fibroblasts (CAFs) play a key role in tumor extracellular matrix (ECM) remodeling and immune evasion. Reshaping tumor microenvironment via CAF regulation might provide a potential approach for complete tumor elimination in combination with PTT. Here, tumor cell-derived microparticles co-delivering calcipotriol and Indocyanine green (Cal/ICG@MPs) are developed to modulate CAFs for improved PTT efficacy. Cal/ICG@MPs efficiently target tumor tissues and regulate CAFs to reduce tumor ECM, resulting in enhanced tumor accumulation and penetration of ICG to generate strong PTT efficacy and activate CD8
T cell-mediated antitumor immunity. In addition, Cal/ICG@MPs-triggered CAF regulation enhances tumor infiltration of CD8
T cells and ameliorates CAF-induced antigen-mediated activation-induced cell death of tumor-specific CD8
T cells in response to PTT, eliciting long-term antitumor immune memory to inhibit tumor recurrence and metastasis. Our results support Cal/ICG@MPs as a promising drug to improve PTT efficacy in cancer treatment.
•A phenols-based DES is easily prepared for extraction of sesame lignans.•This DES can extract non-polar lignans due to the π–π interaction.•The method is efficient for simultaneous determination of ...all the lignans.
For simultaneous determination of lignans (i.e. sesamin, sesamolin and sesamol) in sesame oils, a highly efficient ultrasonic-assisted liquid–liquid microextraction (UALLME) technique was developed based on deep eutectic solvents (DESs) composed of choline chloride and p-cresol. Compared with the common polyols-based DESs (i.e. choline chloride-ethylene glycol), the phenolic DESs exhibited higher extraction efficiency for both polar lignans (i.e. sesamol) and non-polar lignans (i.e. sesamin and sesamolin) due to the π-π interaction between lignans and DES. After the UALLME process, DES phase was analyzed by HPLC-UV. Under optimized condition, all three lignans showed good linear calibration curves and low limit of detection. The recoveries were in the range of 97.3–120%, and the intra-day and inter-day precisions were less than 0.97%. Moreover, this method was used for simultaneous determination of lignans in 15 commercial oil samples. The results showed that the new microextraction technique achieved similar efficiency as the conventional liquid-liquid extraction method.
The main challenges for programmed cell death 1(PD-1)/PD-1 ligand (PD-L1) checkpoint blockade lie in a lack of sufficient T cell infiltration, tumor immunosuppressive microenvironment, and the ...inadequate tumor accumulation and penetration of anti-PD-1/PD-L1 antibody. Resetting tumor-associated macrophages (TAMs) is a promising strategy to enhance T-cell antitumor immunity and ameliorate tumor immunosuppression. Here, mannose-modified macrophage-derived microparticles (Man-MPs) loading metformin (Met@Man-MPs) are developed to efficiently target to M2-like TAMs to repolarize into M1-like phenotype. Met@Man-MPs-reset TAMs remodel the tumor immune microenvironment by increasing the recruitment of CD8
T cells into tumor tissues and decreasing immunosuppressive infiltration of myeloid-derived suppressor cells and regulatory T cells. More importantly, the collagen-degrading capacity of Man-MPs contributes to the infiltration of CD8
T cells into tumor interiors and enhances tumor accumulation and penetration of anti-PD-1 antibody. These unique features of Met@Man-MPs contribute to boost anti-PD-1 antibody therapy, improving anticancer efficacy and long-term memory immunity after combination treatment. Our results support Met@Man-MPs as a potential drug to improve tumor resistance to anti-PD-1 therapy.
Advanced glycation end products (AGEs) and heterocyclic amines (HAs) are two kinds of important harmful products formed simultaneously during the thermal processing of proteinaceous food. In this ...paper, the effect of roasting conditions on the formation of AGEs and HAs, as well as active carbonyl intermediates in common peanut (C−peanut) and high-oleic acid peanut (HO−peanut) was studied simultaneously for the first time. In general, with the increase in roasting temperature (160–200 °C) and time, the contents of AGEs, HAs and active carbonyl intermediates (i.e., glyoxal (GO) and methylglyoxal (MGO)) significantly increased in peanuts. Four kinds of HAs (i.e., AαC, DMIP, Harman and Norharman) were observed in roasted peanuts, of which Harman and Norharman accounted for about 93.0% of the total HAs content after roasting for 30 min at 200 °C. Furthermore, a correlation analysis among AGEs (i.e., Nε-(1-Carboxymethyl)-L-lysine (CML) and Nε-(1-Carboxyethyl)-L-lysine (CEL)), HAs, GO and MGO was conducted. Most of these compounds showed an excellent positive linear relationship (p ≤ 0.001) with each other. The evident increase in GO and MGO contents implied an increase in not only the content of AGEs but also HAs. However, contents of AGEs and HAs showed no significant difference between roasted HO−peanut and C−peanut. This study would provide a theoretical basis for simultaneously controlling the levels of AGEs and HAs in thermal processed peanut foods.
The development and application of seismic technology in civil engineering structures is of great significance to extend the service life of buildings and improve the overall quality of buildings, so ...it is necessary to further strengthen the research on it. Geographic Information System (GIS) is a new subject integrating computer science, informatics, geography and other sciences. Because of its rapid and convenient management of massive data, GIS has been widely used in the fields of resource development, environmental protection, urban planning and construction, disaster monitoring and evaluation, etc. GIS is used to manage and analyze the data, and the damage detection module in the system is used to realize the structural damage identification. And use that special thematic analysis function of GIS to display the data on the map in the form of statistical graph, so that users can find the damage position more directly and clearly.
C-X-C chemokine receptor type 4 (CXCR4), also known as fusin or CD184, is a 7-transmembrane helix G-protein-coupled receptor that is encoded by the CXCR4 gene. Involved in various physiological ...processes, CXCR4 could form an interaction with its endogenous partner, chemokine ligand 12 (CXCL12), which is also named SDF-1. In the past several decades, the CXCR4/CXCL12 couple has attracted a large amount of research interest due to its critical functions in the occurrence and development of refractory diseases, such as HIV infection, inflammatory diseases, and metastatic cancer, including breast cancer, gastric cancer, and non-small cell lung cancer. Furthermore, overexpression of CXCR4 in tumor tissues was shown to have a high correlation with tumor aggressiveness and elevated risks of metastasis and recurrence. The pivotal roles of CXCR4 have encouraged an effort around the world to investigate CXCR4-targeted imaging and therapeutics. In this review, we would like to summarize the implementation of CXCR4-targeted radiopharmaceuticals in the field of various kinds of carcinomas. The nomenclature, structure, properties, and functions of chemokines and chemokine receptors are briefly introduced. Radiopharmaceuticals that could target CXCR4 will be described in detail according to their structure, such as pentapeptide-based structures, heptapeptide-based structures, nonapeptide-based structures, etc. To make this review a comprehensive and informative article, we would also like to provide the predictive prospects for the CXCR4-targeted species in future clinical development.
Background
There is a lack of evidence related to physical activity and risk of cesarean section (CS) by age and/or weight in pregnant women.
Objectives
To evaluate the effect of physical activity on ...the incidence of CS and explore the relationship of age and body mass index (BMI) with incidence of CS.
Search Strategy
A systematic search was conducted in CNKI, WANGFANG, Web of Science, and PubMed from inception to 31 August 2021.
Selection Criteria
Experimental studies were included if the participants were pregnant, if intervention included physical activity and controls received routine prenatal care only, and if primary outcome was CS.
Data Collection and Analysis
Meta‐analysis included a heterogeneity test, data combination, subgroup analysis, forest plot, sensitivity analysis, and dose–response regression analysis.
Main Results
Sixty‐two studies were included. Physical activity during pregnancy decreased the incidence of CS (relative risk RR 0.81, 95% confidence interval CI 0.74–0.88, P < 0.001). The incidence of CS was lower among the overweight/obese group (RR 0.78, 95% CI 0.65–0.93) compared with the normal weight group (RR 0.82, 95% CI 0.74–0.90). The incidence of CS was lowest among the young age group (RR 0.61, 95% CI 0.46–0.80) compared with the middle age group (RR 0.74, 95% CI 0.64–0.85) and the older age group (RR 0.90, 95% CI 0.82–1.00). The critical value, when age becomes a risk factor for CS, was 31.7 years in the intervention group and 28.5 years in the control group.
Conclusions
Physical activity during pregnancy can reduce the incidence of CS, especially among obese people, and prolong the gestational age span.
Synopsis
Physical activity during pregnancy can significantly prolong the appropriate gestational age span of pregnant women, particularly among those with a normal pre‐pregnancy BMI.
Abstract The issue of academic procrastination is highly prevalent among university students. It not only has a deterimental effect on students' academic performance but also poses a risk to their ...physical and mental well-being. Anxiety, as a negative emotion, has attracted researchers’ attention in relation to academic procrastination. Research indicates a correlation between state anxiety and academic procrastination, but the underlying mechanisms that drive this association remain unclear. When individuals experience ego-depletion, it can lead to psychological exhaustion, subsequently leading to procrastination. Gender role conceptions, shaped by sociocultural and psychological mechanisms, have profound implications on individuals’ cognition, emotions, and behaviors. This study primarily aims to explore the relationship between state anxiety and academic procrastination among university students, with a particularly focus on the mediating role of ego-depletion and the moderating role of gender. A survey using the State Anxiety Scale, Ego-Depletion Scale, and Irrational Procrastination Scale was administered to 3370 undergraduates. State anxiety shows positive correlations with ego depletion and academic procrastination ( r = 0.665, p < 0.01; r = 0.491, p < 0.01), while ego depletion is also positively linked to academic procrastination ( r = 0.500, p < 0.01). State anxiety serves as a positive predictor of academic procrastination, with a confidence interval of 95% 0.626, 0.696; additionally, ego depletion partially mediates the relationship between state anxiety and academic procrastination, with a confidence interval of 95% 0.168, 0.251. Gender acts as a moderator in directly predicting the impact of state anxiety on academic procrastination and in the latter stage of mediating the effect of ego depletion. State anxiety can significantly and positively predict academic procrastination among university students. Ego-depletion partially mediates the relationship between state anxiety and academic procrastination. The direct predictive effect of state anxiety on academic procrastination, as well as the mediating role of ego-depletion, is moderated by gender. This provides educators and university students themselves with reference for addressing the issue of academic procrastination.
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