Bovine Induced Pluripotent Stem Cells Are More Resistant to Apoptosis than Testicular Cells in Response to Mono-(2-ethylhexyl) Phthalate

Although the androgen receptor (AR) has been implicated in the promotion of apoptosis in testicular cells (TSCs), the molecular pathway underlying AR-mediated apoptosis and its sensitivity to environmental hormones in TSCs and induced pluripotent stem cells (iPSCs) remain unclear. We generated the iPSCs from bovine TSCs via the electroporation of OCT4. The established iPSCs were supplemented with leukemia inhibitory factor and bone morphogenetic protein 4 to maintain and stabilize the expression of stemness genes and their pluripotency. Apoptosis signaling was assessed after exposure to mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate. Here, we report that iPSCs were more resistant to MEHP-induced apoptosis than were original TSCs. MEHP also repressed the expression of AR and inactivated WNT signaling, and then led to the commitment of cells to apoptosis via the cyclin dependent kinase inhibitor p21^CIP1. The loss of the frizzed receptor 7 and the gain of p21^CIP were responsible for the stimulatory effect of MEHP on AR-mediated apoptosis. Our results suggest that testicular iPSCs can be used to study the signaling pathways involved in the response to environmental disruptors, and to assess the toxicity of environmental endocrine disruptors in terms of the maintenance of stemness and pluripotency.     

Triac Speed Control of Three-Phase Induction Motor with Phase-Locked Loop Regulation

The speed control of a three-phase squirrel cage induction motor by employing triacs in the lines which operate in the normal phase control mode is described. The inherent limitation of low circuit commutated (dv/dt), which makes the triac circuit somewhat unreliable, has been overcome by suitably designing the snubber circuit. The closed-loop speed regulation of the system is then investigated by employing digital phase-locked loop scheme. Compared to the conventional method with antiparallel SCR's and analog servo, the present scheme is somewhat simpler, more economical, and extreme precision in speed control is possible. A complete model of the speed control system has been designed and experimentally evaluated in the laboratory.     

FOXM1-CD44 Signaling Is Critical for the Acquisition of Regorafenib Resistance in Human Liver Cancer Cells

Regorafenib is a multikinase inhibitor that was approved by the US Food and Drug administration in 2017. Cancer stem cells (CSCs) are a small subset of cancer-initiating cells that are thought to contribute to therapeutic resistance. The forkhead box protein M1 (FOXM1) plays an important role in the regulation of the stemness of CSCs and mediates resistance to chemotherapy. However, the relationship between FOXM1 and regorafenib resistance in liver cancer cells remains unknown. We found that regorafenib-resistant HepG2 clones overexpressed FOXM1 and various markers of CSCs. Patients with hepatocellular carcinoma also exhibited an upregulation of FOXM1 and resistance to regorafenib, which were correlated with a poor survival rate. We identified a close relationship between FOXM1 expression and regorafenib resistance, which was correlated with the survival of patients with hepatocellular carcinoma. Thus, a strategy that antagonizes FOXM1–CD44 signaling would enhance the therapeutic efficacy of regorafenib in these patients.