An Indirubin Derivative, Indirubin-39-MonoximeSuppresses Oral Cancer Tumorigenesis through theDownregulation of Survivin

Oral cancer is the fourth most common cause of death from cancer in Taiwanese men. Indirubin-3′-monoxime (I3M), a potent cyclin-dependent kinase inhibitor, has therapeutic effects in other cancer cells. In this study, we carried out in vitro assays to test cell viability, cell cycle progression, apoptosis, cell migration and invasion in this cancer type. In addition, using an oral tumorigenic animal model, we examined target gene and protein expression using real time qPCR, immunoblotting and immunohistochemical staining. Our results demonstrate that I3M has an anti-proliferative effect in both Cal-27 and HSC-3 oral cancer cell lines and that treatment of Cal-27 and HSC-3 cells with I3M results in apoptosis through the activation of cytochrome c. In addition, I3M interrupts the cell cycle in Cal-27 cells in a dose-dependent manner by arresting cells in the G2/M phase. We also found that I3M suppresses migration and invasion in Cal-27 cells by inhibiting the expression of focal adhesion kinase, urokinase-type plasminogen inhibitor, and matrix metalloproteinase 9. Moreover, we identified survivin as a target protein in I3M-treated oral cancer cells. Using an oral cancer mouse model, we demonstrate that topical application of an adhesive gel composed of I3M and poly(vinyl alcohol) (I3M/PVA) has dose-dependent anti-tumorigenic effects. Following treatment, the expression of survivin protein and mRNA was downregulated in cancerous tissues. Furthermore, plasma survivin levels were also reduced in the I3M-treated mice. These results suggest that topical application of I3M, a drug synthesized from indirubin, which is found in Qing-Dai – has therapeutic potential for treating oral cancer

Exploring Concurrent Relationships between Economic Factors and Student Mobility in Expanding Higher Education Achieving 2030

Student mobility is one of the most important indicators to reflect institutional internationalization in a sustainable higher education system. Student mobility issues have been addressed in previous studies, and the phenomenon was discussed in association with related factors persistently. Since higher education sustainable development has received much scholarly attention, monitoring student mobility flows to adjust international strategies is necessary. This study explored practical approaches to detect student mobility flows in the process of higher education expansion. Targeting Taiwan’s higher education system as an example, we addressed the topic of system expansion and the core issues of student mobility. Target series data were collected from 1950 to 2021, including the economic growth ratio, GDP per capita, higher education enrollment, gross enrollment ratio (GER), and the number of inbound and outbound students. The data were transformed with index formats, for example, the economic growth ratio, enrollment increasing ratio (IR), and net flow ratio. The cross-correlation function (CCF) and autoregressive integrated moving average (ARIMA) were used to determine the correlations of the series data and their future trends. The findings suggested that the system expansion, with GER and IR, might reflect fluctuated student mobility in economic growth. This study confirmed that the time series approaches work well in detecting the phenomena of higher education expansion and their effects on student mobility flow in the future

Strategic Analysis and Model Construction on Conflict Resolution with Motion Game Theory

This research uses the “Participating Observation Method” to observe the interaction between manufacturer and distributor negotiation strategies, determine the preference and expectation of participants, and establish a framework for this type of research. Then it sets up the “analysis framework of negotiation strategies” between the manufacturer and the distributor based on an analysis of the respective conditions, advantages, and disadvantages of the manufacturer and distributor. Thirdly, this study sets up a reward matrix of the strategy action game between the manufacturer and the distributor. Then establishes a set of feasible “negotiation models” based on the reward matrix of the strategy game between the both parties to observe how the manufacturer and the distributor make their own bargaining decisions in the situation of information asymmetry or exterior opportunity/threat. Finally, this study establishes a “multi-agent strategy game protocol system model” to solve the conflict resulting from the self-strategizing of both parties for their own interests, and to achieve the utmost efficiency in the negotiation

Quantum Impurity in Luttinger Liquid: Universal Conductance with Entanglement Renormalization

We study numerically the universal conductance of Luttinger liquids wire with a single impurity via the Muti-scale Entanglement Renormalization Ansatz (MERA). The scale invariant MERA provides an efficient way to extract scaling operators and scaling dimensions for both the bulk and the boundary conformal field theories. By utilizing the key relationship between the conductance tensor and ground-state correlation function, the universal conductance can be evaluated within the framework of the boundary MERA. We construct the boundary MERA to compute the correlation functions and scaling dimensions for the Kane-Fisher fixed points by modeling the single impurity as a junction (weak link) of two interacting wires. We show that the universal behavior of the junction can be easily identified within the MERA and argue that the boundary MERA framework has tremendous potential to classify the fixed points in general multi-wire junctions.Comment: 14 pages, 18 figure

Integrin-mediated membrane blebbing is dependent on the NHE1 and NCX1 activities.

Integrin-mediated signal transduction and membrane blebbing have been well studied to modulate cell adhesion, spreading and migration^1-6^. However, the relationship between membrane blebbing and integrin signaling has not been explored. Here we show that integrin-ligand interaction induces membrane blebbing and membrane permeability change. We found that sodium-proton exchanger 1 (NHE1) and sodium-calcium exchanger 1 (NCX1) are located in the membrane blebbing sites and inhibition of NHE1 disrupts membrane blebbing and decreases membrane permeability change. However, inhibition of NCX1 enhances cell blebbing to cause cell swelling which is correlated with an intracellular sodium accumulation induced by NHE17. These data suggest that sodium influx induced by NHE1 is a driving force for membrane blebbing growth, while sodium efflux induced by NCX1 in a reverse mode causes membrane blebbing retraction. Together, these data reveal a novel function of NHE1 and NCX1 in membrane permeability change and blebbing and provide the link for integrin signaling and membrane blebbing

San-Huang-Xie-Xin-Tang Protects against Activated Microglia- and 6-OHDA-Induced Toxicity in Neuronal SH-SY5Y Cells

San-Huang-Xie-Xin-Tang (SHXT), composed of Coptidis rhizoma, Scutellariae radix and Rhei rhizoma, is a traditional Chinese herbal medicine used to treat gastritis, gastric bleeding and peptic ulcers. This study investigated the neuroprotective effects of SHXT on microglia-mediated neurotoxicity using co-cultured lipopolysaccharide (LPS)-activated microglia-like BV-2 cells with neuroblastoma SH-SY5Y cells. Effects of SHXT on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity were also examined in SH-SY5Y cells. Results indicated SHXT inhibited LPS-induced inflammation of BV-2 cells by downregulation of iNOS, NO, COX-2, PGE2, gp91phox, iROS, TNF-α, IL-1β, inhibition of IκBα degradation and upregulation of HO-1. In addition, SHXT increased cell viability and down regulated nNOS, COX-2 and gp91phox of SH-SY5Y cells co-cultured with LPS activated BV-2 cells. SHXT treatment increased cell viability and mitochondria membrane potential (MMP), decreased expression of nNOS, COX-2, gp91phox and iROS, and inhibited IκBα degradation in 6-OHDA-treated SH-SY5Y cells. SHXT also attenuated LPS activated BV-2 cells- and 6-OHDA-induced cell death in differentiated SH-SY5Y cells with db-cAMP. Furthermore, SHXT-inhibited nuclear translocation of p65 subunit of NF-κB in LPS treated BV-2 cells and 6-OHDA treated SH-SY5Y cells. In conclusion, SHXT showed protection from activated microglia- and 6-OHDA-induced neurotoxicity by attenuating inflammation and oxidative stress