Search Results (12,098)

Background/Objectives: Coated drug pellets enjoy widespread use in hard gelatine capsules. In heterogeneous pellets, the drug substance is layered onto core pellets. Coatings are often applied to generate a retarded release or an enteric coating. Methods: In the present study, the thickness of a polymer coating layer on drug pellets was correlated to the drug release kinetics. Results: The question should be answered whether it is possible to stop the coating process when a layer thickness referring to an intended drug release is achieved. Inert pellets were first coated with sodium benzoate and second with different amounts of water insoluble polyacrylate in a fluidized bed apparatus equipped with a Wurster inlet. The whole process was controlled in-line and at-line with process analytical technology by the measurement of the particle size and the layer thickness. The in-vitro sodium benzoate release was investigated, and the data were linearized by different standard models and compared with the polyacrylate layer thickness. With increasing polyacrylate layer thickness the release rate diminishes. The superposition of several processes influencing the release results in release profiles corresponding approximately to first order kinetics. The coating layer thickness corresponds to a determined drug release profile. Conclusions: The manufacturing of coated drug pellets with intended drug release is possible by coating process control and layer thickness measurement. Preliminary investigations are necessary for different formulations. Full article

Protein kinases have essential responsibilities in controlling several cellular processes, and their abnormal regulation is strongly related to the development of cancer. The implementation of protein kinase inhibitors has significantly transformed cancer therapy by modifying treatment strategies. These inhibitors have received substantial FDA clearance in recent decades. Protein kinases have emerged as primary objectives for therapeutic interventions, particularly in the context of cancer treatment. At present, 69 therapeutics have been approved by the FDA that target approximately 24 protein kinases, which are specifically prescribed for the treatment of neoplastic illnesses. These novel agents specifically inhibit certain protein kinases, such as receptor protein-tyrosine kinases, protein-serine/threonine kinases, dual-specificity kinases, nonreceptor protein-tyrosine kinases, and receptor protein-tyrosine kinases. This review presents a comprehensive overview of novel targets of kinase inhibitors, with a specific focus on cyclin-dependent kinases (CDKs) and epidermal growth factor receptor (EGFR). The majority of the reviewed studies commenced with an assessment of cancer cell lines and concluded with a comprehensive biological evaluation of individual kinase targets. The reviewed articles provide detailed information on the structural features of potent anticancer agents and their specific activity, which refers to their ability to selectively inhibit cancer-promoting kinases including CDKs and EGFR. Additionally, the latest FDA-approved anticancer agents targeting these enzymes were highlighted accordingly. Full article

Abstract: Prefabricated construction (PC) is increasingly promoted in the construction sector for its potential benefits, including reduced resource assumption and improved quality. Accordingly, Lean methods are popularly applied to PC projects for optimizing operational processes and enhancing their performance in line with strategic objectives. A key factor in effectively implementing Lean to improve strategic control is developing specific strategies and planning that consider their complex interactions. Thus, this paper aims to propose a quantitative network-based model by integrating Interpretive Structural Modeling (ISM) and Matrix Impact Cross-Reference Multiplication Applied to a Classification (MICMAC) under complex network theory to develop a Lean implementation framework for effective strategy formulation. Specifically, 17 Lean implementation strategies for PC in the context of the Chinese prefabrication industry were identified via an extensive literature review and expert interviews. Then, ISM-MICMAC quantitatively identifies the direct and indirect relationships among strategies, while subsequent analysis of Topological Structure Weight (TSW) and Structural Degree Weight (SDW), as complex network parameters, is used to evaluate the importance of each strategy. The findings show that the strategic planning for Lean implementation in PC consists of four levels, i.e., foundation, organizational, technical, and control. Selecting appropriate Lean tools and technologies is crucial for PC implementation, which must be built on a top-level management team and foster a Lean culture. Moreover, it involves building a standardized system of processes and activities, enhancing both internal and external collaboration, and continuously improving processes in response to changes. On one hand, this in-depth network-based analysis offers practical insights for PC stakeholders, particularly in China, on Lean implementation in line with PC performance and strategic control and objectives. On the other hand, the network-based model can be future-implemented globally. Additionally, this study expands the current body of knowledge on Lean in PC by exploring the interrelationships of Lean implementation strategies. Full article

The main challenge of this scientific work was the implementation on an industrial olive oil extraction plant of an NIR device for the multispectral analysis of pomace to predict the percentage of humidity and oil contained in it. Subsequent to the implementation of the NIR device on the oil extraction line on the solid’s outlet from the decanter, NIRS interaction measurements in the 761–1081 nm region were used to probe the pomace. NIRS calibration models for the prediction of water and oil content in the pomace were obtained and successfully tested and validated. The correlations of calibration results for oil and water content were 0.700 and 0.829, while the correlations of validation were 0.773 and 0.676, respectively. Low values of root mean square error were found for both the prediction and validation set. The results highlight the good robustness of an NIR approach based on a PLS calibration model to monitor the industrial olive oil process. The results obtained are a first step toward the large-scale implementation of NIR devices for monitoring pomace in oil mills. The possibility of knowing the oil lost in the pomace, moment by moment, would open a new frontier towards system control and the sustainability of the olive oil extraction process. Full article

Our previous studies demonstrated the modulatory effects of new synthetic thio-chalcone derivatives in dishes on the Nrf2, NF-κB, and STAT3 signaling pathways in colon cancer cells. This study aimed to evaluate the effect of four selected active chalcone thio-derivatives on the NF-κB and STAT3 signaling pathways involved in inflammatory processes and cell proliferation in human liver cancer cells. Cell survival was assessed for cancer (HepG2) and normal (THLE-2) cell lines. Activation of NF-κB and STAT3 signaling pathways and the expression of proteins controlled by these pathways were estimated by Western blot, and qRT-PCR assessed the expression of NF-κB and STAT3 target genes. We also evaluated the impact on the selected kinases responsible for the phosphorylation of the studied transcription factors by MagneticBead-Based Multiplex Immunoassay. Among the thio-derivatives tested, especially derivatives 1 and 5, there was an impact on cell viability, cell cycle, apoptosis, and activation of NF-κB and STAT3 pathways in hepatocellular carcinoma (HCC), which confirms the possibilities of using them in combinatorial molecular targeted therapy of HCC. The tested synthetic thio-chalcones exhibit anticancer activity by initiating proapoptotic processes in HCC while showing low toxicity to non-cancerous cells. These findings confirm the possibility of using chalcone thio-derivatives in molecularly targeted combination therapy for HCC. Full article

Precast concrete components have attracted a lot of attention due to their efficient production on off-site production lines. However, in the precast component production process, unreasonable production sequence and mold layout will reduce production efficiency and affect the workload balance between each process. Due to the multi-species and small-lot production characteristics of precast concrete components, the number of molds corresponding to each precast concrete component is generally limited. In this paper, a production sequence and layout optimization model for assembling precast concrete components under a limited number of molds is proposed, aiming to improve the comprehensive utilization efficiency of the mold tables and balance the workload between each production process of precast components. In order to obtain a better production sequence and a richer combination of mold layout schemes, a multi-objective teaching-learning-based optimization algorithm based on the Pareto dominance relation is developed, and an enhancement mechanism is embedded in the proposed algorithm. To verify the superior performance of the enhanced teaching-learning-based optimization algorithm in improving the comprehensive utilization efficiency of the mold tables and balancing the workload between various processes, three different sizes of precast concrete component production cases are designed. The research results show that the proposed model and optimization algorithm can help production managers to efficiently formulate more reasonable precast component production sequence and layout schemes, especially for those enterprises that are struggling to improve the efficiency of precast concrete component production. Full article

The common use of hydrogel materials in 3D bioprinting techniques is dictated by the unique properties of hydrogel bioinks, among which some of the most important in terms of sustaining vital cell functions in vitro in 3D cultures are the ability to retain large amounts of liquid and the ability to modify rigidity and mechanical properties to reproduce the structure of the natural extracellular matrix. Due to their high biocompatibility, non-immunogenicity, and the possibility of optimizing rheological properties and bioactivity at the same time, one of the most commonly used hydrogel bioink compositions are polymer solutions based on sodium alginate and gelatin. In 3D bioprinting techniques, it is necessary for hydrogel printouts to feature an appropriate geometry to ensure proper metabolic activity of the cells contained inside the printouts. The desired solution is to obtain a thin-walled printout geometry, ensuring uniform nutrient availability and gas exchange during cultivation. Within this study’s framework, tubular bioprinted structures were developed based on sodium alginate and gelatin, containing cells of the immortalized fibroblast line NIH/3T3 in their structure. Directly after the 3D printing process, such structures are characterized by extremely low mechanical strength. The purpose of this study was to perform a comparative analysis of the viability and spreading ability of the biological material contained in the printouts during their incubation for a period of 8 weeks while monitoring the effect of cellular growth on changes in the mechanical properties of the tubular structures. The observations demonstrated that the cells contained in the 3D printouts reach the ability to grow and spread in the polymer matrix after 4 weeks of cultivation, leading to obtaining a homogeneous, interconnected cell network inside the hydrogel after 6 weeks of incubation. Analysis of the mechanical properties of the printouts indicates that with the increasing time of cultivation of the structures, the degree of their overgrowth by the biological material contained inside, and the progressive degradation of the polymer matrix process, the tensile strength of tubular 3D printouts varies. Full article

Most unmanned aerial vehicle (UAV) ground control station (GCS) solutions today are either web-based or native applications, primarily designed to support a single UAV. In this paper, our research aims to provide an open, universal framework intended for rapid prototyping, addressing these objectives by developing a Web Real-Time Communication (WebRTC)-based multi-UAV monitoring and control system for applications such as automated power line inspection (APOLI). The APOLI project focuses on identifying damage and faults in power line insulators through real-time image processing, video streaming, and flight data monitoring. The implementation is divided into three main parts. First, we configure UAVs for hardware-accelerated streaming using the GStreamer framework on the NVIDIA Jetson Nano companion board. Second, we develop the server-side application to receive hardware-encoded video feeds from the UAVs by utilizing a WebRTC media server. Lastly, we develop a web application that facilitates communication between clients and the server, allowing users with different authorization levels to access video feeds and control the UAVs. The system supports three user types: pilot/admin, inspector, and customer. Our research aims to leverage the WebRTC media server framework to develop a web-based GCS solution capable of managing multiple UAVs with low latency. The proposed solution enables real-time video streaming and flight data collection from multiple UAVs to a server, which is displayed in a web application interface hosted on the GCS. This approach ensures efficient inspection for applications like APOLI while prioritizing UAV safety during critical scenarios. Another advantage of the solution is its integration compatibility with platforms such as cloud services and native applications, as well as the modularity of the plugin-based architecture offered by the Janus WebRTC server for future development. Full article

There is growing evidence that the body’s energy expenditures constitute a significant risk factor for the development of most deadly diseases, including cancer. Our aim was to investigate the impact of basal metabolic rate (BMR) on the growth and progression of colorectal cancer (CRC). To do so, we used a unique model consisting of three lines of laboratory mice (Mus musculus) artificially selected for high (HBMR) and low (LBMR) basal metabolic rate and randomly bred individuals (non-selected, NSBMR). The experimental individuals were implanted with human colorectal cancer cells DLD-1. The variation in BMR between the lines allowed for testing the impact of whole-body metabolism on oxidative and antioxidant parameters in the liver throughout the cancerogenesis process. We investigated the dependence between metabolic values, reactive oxygen species (ROS) levels, and Kelch-like ECH-associated protein 1-based E3 ligase complexes (Keap1) gene activity in these animals. We found that the HBMR strain had a higher concentration of oxidative enzymes compared to the LBMR and NSBMR. Furthermore, the growth rate of CRC tumors was associated with alterations in the levels of oxidative stress enzymes and Keap1 expression in animals with a high metabolic rate. Our results indicate that a faster growth and development of CRC line DLD-1 is associated with enzymatic redox imbalance in animals with a high BMR. Full article

Background/Objectives: To date, nearly 300 lentiviral-based gene therapy clinical trials have been conducted, with eight therapies receiving regulatory approval for commercialization. These advances, along with the increased number of advanced-phase clinical trials, have prompted contract development and manufacturing organizations (CDMOs) to develop innovative strategies to address the growing demand for large-scale batches of lentiviral vectors (LVVs). Consequently, manufacturers have focused on optimizing processes under good manufacturing practices (GMPs) to improve cost-efficiency, increase process robustness, and ensure regulatory compliance. Nowadays, the LVV production process mainly relies on the transient transfection of four plasmids encoding for the lentiviral helper genes and the transgene. While this method is efficient at small scales and has also proven to be scalable, the industry is exploring alternative processes due to the high cost of GMP reagents, and the batch-to-batch variability predominantly attributed to the transfection step. Methods: Here, we report the development and implementation of a reliable and clinical-grade envisioned platform based on the generation of stable producer cell lines (SCLs) from an initial well-characterized lentiviral packaging cell line (PCL). Results: This platform enables the production of VSV-G-pseudotyped LVVs through a fully transfection-free manufacturing process. Our data demonstrate that the developed platform will facilitate successful technological transfer to large-scale LVV production for clinical application. Conclusions: With this simple and robust stable cell line generation strategy, we address key concerns associated with the costs and reproducibility of current manufacturing processes. Full article

Testing was carried out in this study to evaluate the friction and wear performance of 45# steel inner liner pipes with cladding, along with four different types of centralizing materials (45# steel, nylon, polytetrafluoroethylene (PTFE), and surface alloy coating) in oil field conditions. Under dry-friction conditions, the coefficients of friction and rates of wear are significantly higher than their counterparts in aqueous solutions. This is attributed to the lubricating effect provided by the aqueous solution, which reduces direct friction between contact surfaces, thereby lowering wear. As the degree of mineralization in the aqueous solution increases, the coefficient of friction tends to decrease, indicating that an elevated level of mineralization enhances the lubricating properties of the aqueous solution. The wear pattern in an aqueous solution is similar to that in dry-friction conditions under different loads, but with a lower friction coefficient and wear rate. The coating has played an important role in protecting the wear process of 45# steel, and the friction coefficient and wear rate of tubing materials under various environmental media have been significantly reduced. In terms of test load, taking into account the friction coefficient and wear rate, the suggested order for centralizing materials for lining oil pipes with the surface alloy coating is as follows: (i) surface alloy coating, (ii) nylon, (iii) PTFE, and (iv) 45# steel. Full article

Platelets are essential blood components that maintain hemostasis, prevent excessive bleeding, and facilitate wound healing. Reduced platelet counts are implicated in various diseases, including leukemia, hepatitis, cancer, and Alzheimer’s disease. Enhancing megakaryocytic differentiation is a promising strategy to increase platelet production. Compound K (CK), a major bioactive metabolite of ginsenosides from Panax ginseng, has demonstrated anti-cancer and neuroprotective properties. In this study, we investigated the effects of CK on megakaryocytic differentiation and apoptosis in chronic myeloid leukemia (CML) cell lines K562 and Meg-01. CK treatment significantly upregulated the mRNA expression of key megakaryocytic differentiation markers, including CD61, CD41, and CD42a, and promoted the formation of large, multinucleated cells in K562 cells. Additionally, flow cytometry analysis revealed that CK at 5 µM induced apoptosis, a critical process in thrombocytopoiesis, in both K562 and Meg-01 cells. RT² Profiler PCR array analysis further identified a marked increase in the expression of genes associated with the activation of the NLRP3 inflammasome in CK-treated K562 and Meg-01 cells. This study is the first to demonstrate that CK promotes megakaryocytic differentiation and apoptosis through the activation of the ERK/EGR1 and NLRP3 inflammasome pathways. These findings suggest that CK may enhance platelet production, indicating its potential as a therapeutic candidate for platelet-related disorders and other associated diseases. Full article

Indole-3-carbinol (I3C), a hydrolysis product of indole-3-methylglucosinolate, is toxic to herbivorous insects and pathogens. In mammals, I3C is extensively studied for its properties in cancer prevention and treatment. Produced in Brassicaceae, I3C reversibly inhibits root elongation in a concentration-dependent manner. This inhibition is partially explained by the antagonistic action of I3C on auxin signaling through TIR1. To further elucidate the mode of action of I3C in plants, we have employed a forward-genetic amiRNA screen that circumvents functional redundancy. We identified and characterized two amiRNA lines with impaired I3C response. The first line, ICT2, targets the phosphatidylinositol 4-phosphate 5-kinase family (PIP5K), exhibiting tolerance to I3C, while the second line, ICS1, targets the Wall-Associated Kinases (WAK1–3) family, showing susceptibility to I3C. Both lines maintain I3C-induced antagonism of auxin signaling, indicating that their phenotypes are due to auxin-independent mechanisms. Transcript profiling experiments reveal that both lines are transcriptionally primed to respond to I3C treatment. Physiological, metabolomic, and transcriptomic analysis reveal that these kinases mediate numerous developmental processes and are involved in abiotic and biotic stress responses. Full article

Several microRNAs (miRNAs), including miR-221-5p, Let-7b-5p, miR-21-5p, miR-9-5p, miR-126-3p, and miR-222-3p, were recently found to be enriched in circulating exosomes of patients with non-small cell lung cancers (NSCLCs). These miRNAs distinguished cancer cases from controls with high precision and were predicted to modulate the expression of genes within the oncogenic LINE-1 regulatory network. To test this hypothesis, plasma exosomes from controls, early, and late-stage NSCLC patients were co-cultured with non-tumorigenic lung epithelial cells for 72 h and processed for measurements of gene expression. Exosomes from late-stage NSCLC patients markedly increased the mRNA levels of LINE-1 ORF1 and ORF2, as well as the levels of target miRNAs in naïve recipient cells compared to saline or control exosomes. Late-stage exosomes also modulated the expression of oncogenic targets within the LINE-1 regulatory network, namely, ICAM1, AGL, RGS3, RGS13, VCAM1, and TGFβ1. In sharp contrast, exosomes from controls or early-stage NSCLC patients inhibited LINE-1 expression, along with many of the genetic targets within the LINE-1 regulatory network. Thus, late-stage NSCLC exosomes activate LINE-1 and miRNA-regulated oncogenic signaling in non-tumorigenic, recipient lung bronchial epithelial cells. These findings raise important questions regarding lung cancer progression and metastasis and open the door for the exploration of new therapeutic interventions. Full article

Background/Objectives: Irinotecan, a camptothecin (CPT) derivative, is commonly used as a first-line therapy for colorectal cancer (CRC), but resistance remains a significant challenge. This study aims to explore the therapeutic potential of FL118, another CPT derivative, with a focus on overcoming resistance to irinotecan. Methods: The effects of FL118 on CRC cells were evaluated, and bioinformatics analysis was performed on RNA-seq data. Transfection was conducted to observe the knockdown effect of survivin, and the in vivo efficacy of FL118 was assessed using a xenograft model. Results: FL118 induces apoptosis, G2/M arrest, and DNA damage. A notable mechanism of action of FL118 is a reduction in survivin levels, which downregulates the expression of RAD51, a key marker of homologous recombination, and attenuates DNA repair processes. Given that SN38 is the active metabolite of irinotecan, FL118 reduces cell viability and RAD51 in SN38-resistant LOVO cells. Conclusions: Our findings provide effective insights into the antitumor activity of FL118 and its potential as a therapeutic agent for overcoming irinotecan resistance in CRC. Full article