Search

Autophagy is a form of programmed cell degradation that enables the maintenance of homeostasis in response to extracellular stress stimuli. Autophagy is primarily activated by starvation and mediates the degradation, removal, or recycling of cell cytoplasm, organelles, and intracellular components in eukaryotic cells. Autophagy is also involved in the pathogenesis of human diseases, including several cancers. Human uveal melanoma (UM) is the primary intraocular malignancy in adults and has an extremely poor prognosis; at present there are no effective therapies. Several studies have suggested that autophagy is important in UM. By understanding the mechanisms of activation of autophagy in UM it may be possible to develop biomarkers to provide more definitive disease prognoses and to identify potential drug targets for the development of new therapeutic strategies. This article reviews the current information regarding autophagy in UM that could facilitate biomarker and drug development.

The spacer grid models are important models for simulating the thermal-hydraulics phenomena during reflooding process. The spacer grid pressure drop model, wall heat transfer enhancement model, interfacial heat transfer enhancement model, droplet breakup model, spacer grid re-wet model and grid temperature model are integrated in COSINE multiphase sub-channel code. In this paper, the typical rod bundle heat transfer (RBHT) reflooding tests were selected to assess the spacer grid model in the code. The calculation results show that the spacer grid models can significantly enhance the code predicted heat transfer capacity, accelerate the quench rate and reduce the peak cladding temperature (PCT) during the reflooding process, and the calculated results are in good agreement with the experimental measurements. In addition, the deviation of the PCT predicted by the code is reduced from 10% to 7% due to the adoption of the spacer grid models. The spacer grid models have the ability to enhance the interfacial heat transfer between vapor and droplet, therefore the calculated results with the spacer grid models show a significantly faster decrease in vapor temperature than that without the spacer grid models. And the calculated vapor temperatures with spacer grid models are in good agreement with the experimental measurements. The trend of the code predicted spacer grid temperature agrees well with the experimental results, but the code predicted spacer grid temperature is slightly higher than the experimental measurements. Furthermore, the early wetting of the temperature probe located on the spacer grid in the experiment results in a rapid decrease in the spacer grid temperature, however，the code predicted spacer grid temperature does not show as sharp a decrease as the experimental results due to the interpolation method in the calculation of the spacer grid temperature. The spacer grid models adopted in the code can simulate the breakup of droplets across the spacer grid, the diameter ratio of the shattered droplets predicted by the code is in good agreement with the experimental measurements, and the calculation results of the Cheung model are more accurate than those of the Paik model in the test case 7151. In addition to this, the code can predict the trend of droplet velocity near the spacer grid during reflooding process, but the calculated droplet velocity decreases significantly faster than the experimental measurements, and it needs more work in future. In general, the calculated results with the spacer grid models are in good agreement with the experimental results, and the spacer grid models adopted in the code are reasonable and reliable.

COSINE software package provides various functions in thermal-hydraulic analysis of pressurized water reactor (PWR) after years of development. In order to meet the engineering design and safety analysis requirements of the advanced passive reactor CAP1400, the multiphase field sub-channel code with higher calculation accuracy was developed based on the homogeneous sub-channel program (cosSUBC) in COSINE software package. The multiphase sub-channel code contained 11 basic equations including the mass conservation equations of the vapor, continuous liquid, and droplet, the axial momentum conservation equations of the gas, continuous liquid phase, droplet phase, the transverse momentum conservation equation of the gas, continuous liquid, and droplet, and the energy conservation equations of the gas and total liquid phases. The continuous liquid and the droplet were in energy equilibrium states in one cell was assumed, therefore the continuous liquid and droplet were merged into total liquid phases in energy conservation equation. The constitutive relation models between different phases were introduced in the code to realize the closure of the basic equations, the staggered discrete format in space and a semi-implicit time discrete format were adopted in multiphase field sub-channel code. The typical test cases and representative experiments were modeled and calculated in this paper to verify the calculation capability of the code. First, the test of droplet behavior was modeled to verify the correctness of droplet model adopted in the code. Then the turbulent mixing experiment was modeled to verify the correctness of turbulent mixing model used in the code. In the end, the wall heat transfer experiment and the reflooding process experiment were modeled to verify the simulation ability in the heat transfer regime especially in the post critical heat flux (post-CHF) condition. The results show that the droplet behaviors including the generation and the flow distribution of droplet phase are in good agreement with the reference code. And the code can well simulate the flow distribution phenomenon according the comparison between the calculation results and experimental data in flow distribution experiment and the turbulent mixing experiment. Besides, the code can well simulate the distribution of the wall temperature and the reflooding process in the post-CHF and heat transfer condition. Therefore, the calculation of the thermal-hydraulic phenomena in the core of reactor by the multiphase field sub-channel code is reasonable and right, and the code has the ability to calculate and simulate the thermal-hydraulic conditions in the core of PWR.

Introduction: Our study aims to provide a comprehensive overview of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in drug delivery research, focusing on the period between 2013 and 2023. Given the increasing global interest in this field, we utilized bibliometric tools to explore publication trends, key contributors, and thematic research clusters. Methods: Data was collected from the Web of Science (WoS) database, and an in-depth bibliometric analysis was conducted using VOSviewer. The analysis encompassed bibliographic coupling, co-citation, co-authorship, and co-occurrence trends, offering a structured insight into global research activity. We also employed Citespace to further analyze thematic clusters in this domain. Results: Our analysis revealed a total of 1,045 publications related to MSC-EVs in drug delivery over the past decade, showing a steady increase in research output. China led in publication count, H-index, prolific authors, and research funding, while the United States ranked highest in total citations, average citation counts, and H-index performance. Pharmaceutics emerged as the leading journal by publication volume, with the Journal of Controlled Release having the strongest total link strength. Top institutions driving research included Shanghai Jiao Tong University, Zhejiang University, and Harvard University. VOSviewer analysis identified four major research clusters: tissue engineering, cancer, neurological diseases, and targeted delivery. Citespace analysis refined this further into ten thematic areas, including differentiation, tissue regeneration, and drug resistance. Discussion: This bibliometric assessment provides a holistic visualization of the research landscape for MSC-EVs in drug delivery, underlining the significant contributions of China and the United States. Our findings underscore the increasing global importance of MSC-EV research and highlight emerging themes that will likely guide future research directions. The insights from this study offer a foundational framework for identifying nascent frontiers in MSC-EV-based drug delivery. [ABSTRACT FROM AUTHOR]

Background: Diabetic gastrointestinal dysfunction (DGD) is a common complication in diabetic patients, and enteric glial cells (EGCs) found in the gastrointestinal tract have been shown to play an essential role in gastrointestinal dysfunction. Thus, targeting EGCs may be helpful for the control of DGD. This study aimed to evaluate the protective effect of Ginkgo biloba extract (GBE) from G. biloba dropping pills against hyperglycaemic stress-induced EGCs injury and its underlying mechanism. Methods: In vitro, the protective effect of GBE on CRL-2690 cells was evaluated by MTT assay and TUNEL assay. The expression of related markers was evaluated by RNA sequencing and validated by using western blotting. In vivo, STZ-induced C57BL/6J WT mice were used as models to evaluate the effects of GBE on blood glucose, body weight, and EGCs' activity and relevant signalling pathways were validated by immunofluorescence. Results: The results showed that GBE (25 μg/ml) treatment significantly attenuated hyperglycaemic stress-induced cytotoxicity and cell apoptosis in CRL-2690 cells, which was verified in an STZ-induced (100 mg/kg, 3 days) diabetic mouse model with continuous GBE administration (25/100 mg/kg/day, 6/12 weeks). Further mechanistic study based on transcriptomic data revealed that GBE exerted its beneficial effect by regulating immune-related pathways, and TLR2/BTK/NF-κB/IL-1α/IL-10 comprised the main targets of this drug. Conclusions: This study demonstrates the protective effect of GBE against hyperglycaemic stress-induced EGCs injury using both in vitro and in vivo models and further reveals that the effect was achieved by targeting TLR2 and its downstream molecules BTK/NF-κB/IL-1α/IL-10. This study may be helpful for expanding the clinical application of GBE in treating DGD. [ABSTRACT FROM AUTHOR]