The molecular mechanism for inhibiting the growth of nasopharyngeal carcinoma cells using polymethoxyflavonoids purified from pericarp of Citrus reticulata ‘Chachi’ via HSCCC

Polymethoxyflavonoids (PMFs), the main bioactive compounds naturally occurring in the pericarp of Citrus reticulata ‘Chachi’ (CRCP), possess significant antitumor action. However, the action of PMFs in nasopharyngeal carcinoma (NPC) is currently unknown. The present research study was conducted to investigate the inhibitory mechanisms of PMFs from CRCP on NPC growth in vivo and in vitro. In our research, we used high-speed counter-current chromatography (HSCCC) to separate four PMFs (nobiletin (NOB), 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), tangeretin (TGN), and 5-hydroxy-6,7,8,3′,4′-pentamethoxyflavone (5-HPMF)) from CRCP. CCK-8 assay was used to preliminarily screen cell viability following exposure to the four PMFs. Colony formation, Hoechst-33258 staining, transwell, and wound scratch assays were performed to assess the anti-proliferation, invasion, migration, and apoptosis-inducing effects of HMF on NPC cells. NPC tumors in xenograft tumor transplantation experiments were also established to explore the effect of HMF (100 and 150 mg/kg/day) on NPC. The histopathological changes in the treated rats were observed by H&E staining and Ki-67 detection by immunohistochemical techniques. The expressions of P70S6K, p-P70S6K, S6, p-S6, COX-2, p53, and p-p53 were measured by Western blot. The four PMFs were obtained with high purity (>95.0%). The results of the preliminary screening by CCK-8 assay suggested that HMF had the strongest inhibitory effect on NPC cell growth. The results of the colony formation, Hoechst-33258 staining, transwell, and wound scratch assays indicated that HMF had significant anti-proliferation, invasion, migration, and apoptosis-inducing ability in NPC cells. Moreover, HMF suppressed NPC tumor growth in xenograft tumor transplantation experiments. Further investigation suggested that HMF regulated NPC cells proliferation, apoptosis, migration, and invasion by activating AMPK-dependent signaling pathways. In conclusion, HMF-induced AMPK activation inhibited NPC cell growth, invasion, and metastatic potency by downregulating the activation of the mTOR signaling pathway and COX-2 protein levels, as well as enhancing the p53 phosphorylation level. Our study provides a crucial experimental basis for the clinical treatment of NPC, as well as the development and utilization of PMFs from CRCP

Designing Flexible-Bus System with Ad-Hoc Service Using Travel-Demand Clustering

Providing direct and affordable transit services for travelers is the goal of the evolving flexible-bus (FB) system. In this study, we design an FB system with an ad-hoc service, to supplement traditional public transit and provide a better FB service. We first build up a mathematical model to optimize bus-stop sites, routes, and schedules, where the unmet travel demand is served by an ad-hoc service with relatively high cost. Then, we cluster travel demand spatially and temporarily, using the ST-DBSCAN algorithm. We use the simulated-annealing algorithm, which has better convergence and diversity than other heuristic algorithms, to solve the suggested model in large-scale networks. To demonstrate the effectiveness of the proposed model, we run experiments on a small network and a large real-world network of Shenzhen airport, which shows that the FB system with ad-hoc service can reduce overall cost and improve social welfare, compared to taxies and FB only. In addition, it provides affordable transit services with shorter walking distances and lower waiting times, which can be deployed in airports or high-speed railway stations with massive, irregular travel demands

Designing Flexible-Bus System with Ad-Hoc Service Using Travel-Demand Clustering

Providing direct and affordable transit services for travelers is the goal of the evolving flexible-bus (FB) system. In this study, we design an FB system with an ad-hoc service, to supplement traditional public transit and provide a better FB service. We first build up a mathematical model to optimize bus-stop sites, routes, and schedules, where the unmet travel demand is served by an ad-hoc service with relatively high cost. Then, we cluster travel demand spatially and temporarily, using the ST-DBSCAN algorithm. We use the simulated-annealing algorithm, which has better convergence and diversity than other heuristic algorithms, to solve the suggested model in large-scale networks. To demonstrate the effectiveness of the proposed model, we run experiments on a small network and a large real-world network of Shenzhen airport, which shows that the FB system with ad-hoc service can reduce overall cost and improve social welfare, compared to taxies and FB only. In addition, it provides affordable transit services with shorter walking distances and lower waiting times, which can be deployed in airports or high-speed railway stations with massive, irregular travel demands

Large-Scale and Highly Efficient Production of Ultrafine PVA Fibers by Electro-Centrifugal Spinning for NH₃ Adsorption

Ultrafine Polyvinyl alcohol (PVA) fibers have an outstanding potential in various applications, especially in absorbing fields. In this manuscript, an electrostatic-field-assisted centrifugal spinning system was designed to improve the production efficiency of ultrafine PVA fibers from PVA aqueous solution for NH3 adsorption. It was established that the fiber production efficiency using this self-designed system could be about 1000 times higher over traditional electrospinning system. The produced PVA fibers establish high morphology homogeneity. The impact of processing variables of the constructed spinning system including rotation speed, needle size, liquid feeding rate, and voltage on fiber morphology and diameter was systematically investigated by SEM studies. To acquire homogeneous ultrafine PVA fiber membranes, the orthogonal experiment was also conducted to optimize the spinning process parameters. The impact weight of different studied parameters on the spinning performance was thus provided. The experimental results showed that the morphology of micro/nano-fibers can be well controlled by adjusting the spinning process parameters. Ultrafine PVA fibers with the diameter of 2.55 μm were successfully obtained applying the parameters, including rotation speed (6500 rpm), needle size (0.51 mm), feeding rate (3000 mL h−1), and voltage (20 kV). Furthermore, the obtained ultrafine PVA fiber mat was demonstrated to be capable of selectively adsorbing NH3 gas relative to CO2, thus making it promising for NH3 storage and other environmental purification applications