Sorafenib has become the standard therapy for patients with advanced hepatocellular carcinoma (HCC). Unfortunately, most patients eventually develop acquired resistance. Therefore, it is important to identify potential biomarkers that could predict the efficacy of sorafenib. To identify target proteins associated with the development of sorafenib resistance, we applied stable isotope labelling with amino acids in cell culture (SILAC)-based quantitative proteomic approach to analyze differences in protein expression levels between parental HuH-7 and sorafenib-acquired resistance HuH-7 (HuH-7 R ) cells in vitro, combined with an isobaric tags for relative and absolute quantitation (iTRAQ) quantitative analysis of HuH-7 and HuH-7 R tumors in vivo. In total, 2,450 quantified proteins were identified in common in SILAC and iTRAQ experiments, with 81 showing increased expression (>2.0-fold) with sorafenib resistance and 75 showing decreased expression (<0.5-fold). In silico analyses of these differentially expressed proteins predicted that 10 proteins were related to cancer with involvements in cell adhesion, migration, and invasion. Knockdown of one of these candidate proteins, galectin-1, decreased cell proliferation and metastasis in HuH-7 R cells and restored sensitivity to sorafenib. We verified galectin-1 as a predictive marker of sorafenib resistance and a downstream target of the AKT/mTOR/HIF-1␣ signaling pathway. In addition, increased galectin-1 expression in HCC patients' serum was associated with poor tumor control and low response rate. We also found that a high serum galectin-1 level was an independent factor associated with poor progression-free survival and overall survival. In conclusion, these results suggest that galectin-1 is a possible biomarker for predicting the response of HCC patients to treatment with sorafenib. As such, it may assist in the stratification of HCC and help direct personalized therapy. Molecular & Cellular

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Obstructive sleep apnea (OSA), which is caused by obstructions of the upper airway, is a syndrome with rising prevalence. Mandibular advancement splints (MAS) are oral appliances for potential treatment of OSA. This work proposes a highly-sensitive pressure sensing array integrated with a system-on-chip (SoC) embedded in a MAS. The device aims to measure tongue pressure distribution in order to determine the efficacy of the MAS for treating OSA. The flexible sensing array consists of an interdigital electrode pair array assembled with conductive polymer films and an SoC capable of retrieving/storing data during sleep, and transmitting data for analysis after sleep monitoring. The surfaces of the conductive polymer films were patterned with microdomed structures, which effectively increased the sensitivity and reduced the pressure sensing response time. The measured results also show that the crosstalk effect between the sensing elements of the array was negligible. The sensitivity of the sensing array changed minimally after the device was submerged in water for up to 100 h.

This work proposes a miniaturized respiratory transducer array that utilizes the sharp temperature dependence of the resistivity characteristic of acrylate-based composites with a positive temperature coefficient. The proposed device employs an array configuration consisting of three sensing elements with the composites of different glass transition temperatures to achieve a wide operational temperature range. The temperature transient responses caused by different breathing conditions were clearly resolved by the device, and the corresponding respiration rates were easily extracted. The transducer array was characterized in a room temperature range from 23 °C to 29 °C. In addition, the device effectively detected the respiration rate up to a distance of 30 cm. It was also demonstrated that the device is capable of quantifying the breathing rate over a practical range of frequencies (from 0.1 Hz to 2 Hz). The respiration rates measured by the proposed device were also in good agreement with the results measured simultaneously by using a commercially available nasal pressure transducer. Comparison of the results demonstrated an excellent linear correlation (r=0.953 and P &lt; 0.001). The measured results suggest the feasibility of using this miniaturized device to monitor patients' respiration rates in clinical institutes and in other point-of-care applications.

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