SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis

Increased dependence on aerobic glycolysis is characteristic of most cancer cells, whereas the mechanism underlying the promotion of aerobic glycolysis in metastatic breast cancer cells under ambient oxygen has not been well understood. Here, we demonstrated that aberrant expression of signal-induced proliferation-associated 1 (SIPA1) enhanced aerobic glycolysis and altered the main source of ATP production from oxidative phosphorylation to glycolysis in breast cancer cells. We revealed that SIPA1 promoted the transcription of EPAS1, which is known as the gene encoding hypoxia-inducible factor-2α (HIF-2α) and up-regulated the expression of multiple glycolysis-related genes to increase aerobic glycolysis. We also found that blocking aerobic glycolysis by either knocking down SIPA1 expression or oxamate treatment led to the suppression of tumor metastasis of breast cancer cells both in vitro and in vivo. Taken together, aberrant expression of SIPA1 resulted in the alteration of glucose metabolism from oxidative phosphorylation to aerobic glycolysis even at ambient oxygen levels, which might aggravate the malignancy of breast cancer cells. The present findings indicate a potential target for the development of therapeutics against breast cancers with dysregulated SIPA1 expression.

The Proliferation of Pre-Pubertal Porcine Spermatogonia in Stirred Suspension Bioreactors Is Partially Mediated by the Wnt/β-Catenin Pathway

Male survivors of childhood cancer are at risk of suffering from infertility in adulthood because of gonadotoxic chemotherapies. For adult men, sperm collection and preservation are routine procedures prior to treatment; however, this is not an option for pre-pubertal children. From young boys, a small biopsy may be taken before chemotherapy, and spermatogonia may be propagated in vitro for future transplantation to restore fertility. A robust system that allows for scalable expansion of spermatogonia within a controlled environment is therefore required. Stirred suspension culture has been applied to different types of stem cells but has so far not been explored for spermatogonia. Here, we report that pre-pubertal porcine spermatogonia proliferate more in bioreactor suspension culture, compared with static culture. Interestingly, oxygen tension provides an avenue to modulate spermatogonia status, with culture under 10% oxygen retaining a more undifferentiated state and reducing proliferation in comparison with the conventional approach of culturing under ambient oxygen levels. Spermatogonia grown in bioreactors upregulate the Wnt/ β-catenin pathway, which, along with enhanced gas and nutrient exchange observed in bioreactor culture, may synergistically account for higher spermatogonia proliferation. Therefore, stirred suspension bioreactors provide novel platforms to culture spermatogonia in a scalable manner and with minimal handling.

A Simple Sensor System for Onsite Monitoring of O2 in Vacuum-Packed Meats during the Shelf Life

Vacuum packaging (VP) is used to reduce exposure of retail meat samples to ambient oxygen (O2) and preserve their quality. A simple sensor system produced from commercial components is described, which allows for non-destructive monitoring of the O2 concentration in VP raw meat samples. Disposable O2 sensor inserts were produced by spotting small aliquots of the cocktail of the Pt–benzoporphyrin dye and polystyrene in ethyl acetate onto pieces of a PVDF membrane and allowing them to air-dry. These sensor dots were placed on top of the beef cuts and vacuum-packed. A handheld reader, FirestinGO2, was used to read nondestructively the sensor phase shift signals (dphi°) and relate them to the O2 levels in packs (kPa or %). The system was validated under industrial settings at a meat processing plant to monitor O2 in VP meat over nine weeks of shelf life storage. The dphi° readings from individual batch-calibrated sensors were converted into the O2 concentration by applying the following calibration equation: O2 (%) = 0.034 * dphi°2 − 3.413 * dphi° + 85.02. In the VP meat samples, the O2 levels were seen to range between 0.12% and 0.27%, with the sensor dphi signals ranging from 44.03° to 56.02°. The DIY sensor system demonstrated ease of use on-site, fast measurement time, high sample throughput, low cost and flexibility.

Effects of Oxygen Content on Operational Characteristics and Stability of High-Mobility IGTO Thin-Film Transistors during Channel Layer Deposition

In this study, we investigated the effects of oxygen content on the transfer characteristics and stability of high-mobility indium-gallium-tin oxide (IGTO) thin-film transistors (TFTs) during channel layer deposition. The IGTO thin films were deposited through direct current sputtering at different ambient oxygen percentages of 10%, 20%, 30%, 40%, and 50%. The experimental results indicate that the drain currents were hardly modulated by the gate-to-source voltage in the IGTO TFT prepared at 10% ambient oxygen. However, as the oxygen content increased from 20% to 50%, the transfer curves shifted to the positive direction with a decrease in field-effect mobility (μFE). The IGTO TFTs exhibited deteriorated positive bias stress (PBS) stability as the oxygen content increased. However, the stabilities of the IGTO TFTs under negative bias illumination stress (NBIS) improved with an increase in the ambient oxygen percentage during the channel layer deposition. Furthermore, to understand the mechanism of the observed phenomena, we performed X-ray photoelectron spectroscopy (XPS) analysis of the IGTO thin films prepared at different oxygen percentages. The XPS results demonstrate that the deteriorated PBS stability and enhanced NBIS stability of the IGTO TFTs prepared at higher oxygen percentages were mainly ascribed to the larger amount of oxygen interstitials resulting from the excess oxygen and the smaller number of oxygen vacancies within the IGTO, respectively. The obtained results suggest that the oxygen percentages of 30% in the sputtering ambient is the most suitable oxygen percentage for optimizing the electrical properties (μFE = 24.2 cm2/V·s, subthreshold swing = 0.43 V/dec, and threshold voltage = −2.2 V) and adequate PBS and NBIS stabilities of IGTO TFTs.