Sorafenib is the only and standard systematic chemotherapy drug for treatment of advanced hepatocellular carcinoma (HCC) at the current stage. Although sorafenib showed survival benefits in large randomized phase III studies, its clinical benefits remain modest and most often consist of temporary tumor stabilization, indicating that more effective first-line treatment regimens or second-line salvage therapies are required. The molecular pathogenesis of HCC is very complex, involving hyperactivated signal transduction pathways such as RAS/RAF/MEK/ERK and PI3K/AKT/mTOR and aberrant expression of molecules such as receptor tyrosine kinases and histone deacetylases. Simultaneous or sequential abrogation of these critical pathways or the functions of these key molecules involved in angiogenesis, proliferation, and apoptosis may yield major improvements in the management of HCC. In this review, we summarize the emerging sorafenib-based combined molecule targeting for HCC treatment and analyze the rationales of these combinations.
Background Breast cancer (BC) is a common cancer in women worldwide. Emerging evidence has indicated that circular RNA hsa‐circ_0007255 (circ_0007255) is a prognostic mediator in BC progression. However, the functional role of circ_0007255 needs to be determined. Methods The expression of circ_0007255, microRNA (miR)‐335‐5p, and SIX Homeobox 2 (SIX2) was evaluated using quantitative real‐time polymerase chain reaction (qRT‐PCR) or western blot assay. Actinomycin D and RNase R treatment was performed to analyze the stability of circ_0007255. Additionally, Seahorse extracellular flux, colony formation and transwell analyses were carried out to detect oxygen consumption ratio (OCR), colony formation and cell mobility, respectively. The interaction between miR‐335‐5p and circ_0007255 or SIX2 was confirmed via dual‐luciferase reporter assay. A xenograft tumor model was established to explore the role of circ_0007255 in vivo. Results Circ_0007255 and SIX2 were overexpressed, but miR‐335‐5p was diminished in BC tissues and cells. Circ_0007255 absence inhibited oxygen consumption, colony formation, cell migration and invasion, and these effects were particularly abrogated via miR‐335‐5p upregulation in BC cells. Moreover, SIX2 deficiency eliminated the promotion effects of miR‐335‐5p inhibitor on oxygen consumption, colony formation, and cell mobility in BC cells. Importantly, circ_0007255 inhibited tumor growth in vivo. Mechanically, circ_0007255 was a sponge of miR‐335‐5p to regulate SIX2 expression in BC progression. Conclusion Circ_0007255 functioned as a novel oncogene in the progression of BC by regulating miR‐335‐5p/SIX2 axis, and might be a promising biomarker for BC treatment. Key points Significant findings of the study: Levels of circ_0007255 and SIX2 were upregulated, but miR‐335‐5p was diminished in BC tissues and cells. Circ_0007255 was an oncogene in BC development and exerted its function via miR‐335‐5p/SIX2 axis in BC. Tumor growth was reduced by circ_0007255 absence. What this study adds: Circ_0007255 functioned as a novel oncogene in the progression of BC by regulating miR‐335‐5p/SIX2 axis, and might be a promising biomarker for BC treatment.
Lasers have long been used in the field of mass spectrometric analysis for characterization of condensed matter. However, emission of neutrals upon laser irradiation surpasses the number of ions. Typically, only one in about one million analytes ejected by laser desorption/ablation is ionized, which has fueled the quest for postionization methods enabling ionization of desorbed neutrals to enhance mass spectrometric detection schemes. The development of postionization techniques can be an endeavor that integrates multiple disciplines involving photon energy transfer, electrochemistry, gas discharge, etc. The combination of lasers of different parameters and diverse ion sources has made laser desorption/ablation postionization (LD/API) a growing and lively research community, including two‐step laser mass spectrometry, laser ablation atmospheric pressure photoionization mass spectrometry, and those coupled to ambient mass spectrometry. These hyphenated techniques have shown potentials in bioanalytical applications, with major inroads to be made in simultaneous location and quantification of pharmaceuticals, toxins, and metabolites in complex biomatrixes. This review is intended to provide a timely comprehensive view of the broadening bioanalytical applications of disparate LD/API techniques. We also have attempted to discuss these applications according to the classifications based on the postionization methods and to encapsulate the latest achievements in the field of LD/API by highlighting some of the very best reports in the 21st century. © 2020 John Wiley & Sons Ltd.
The traditional gas sensor array has been viewed as a simple apparatus for information acquisition in chemosensory systems. Gas sensor arrays frequently undergo impairments in the form of sensor failures that cause significant deterioration of the performance of previously trained pattern recognition models. Reliability monitoring of gas sensor arrays is a challenging and critical issue in the chemosensory system. Because of its importance, we design and implement a status self-validating gas sensor array prototype to enhance the reliability of its measurements. A novel fault detection, isolation, and diagnosis (FDID) strategy is presented in this paper. The principal component analysis-based multivariate statistical process monitoring model can effectively perform fault detection by using the squared prediction error statistic and can locate the faulty sensor in the gas sensor array by using the variables contribution plot. The signal features of gas sensor arrays for different fault modes are extracted by using ensemble empirical mode decomposition (EEMD) coupled with sample entropy (SampEn). The EEMD is applied to adaptively decompose the original gas sensor signals into a finite number of intrinsic mode functions (IMFs) and a residual. The SampEn values of each IMF and the residual are calculated to reveal the multi-scale intrinsic characteristics of the faulty sensor signals. Sparse representation-based classification is introduced to identify the sensor fault type for the purpose of diagnosing deterioration in the gas sensor array. The performance of the proposed strategy is compared with other different diagnostic approaches, and it is fully evaluated in a real status self-validating gas sensor array experimental system. The experimental results demonstrate that the proposed strategy provides an excellent solution to the FDID of status self-validating gas sensor arrays.
It is suggested that the lateral septum may receive afferent information from the gastrointestinal tract and promote gastric motility. Ghrelin plays an important role in promoting gastric motility in the lateral septum. The ARC may be involved in the regulation of the lateral septum's influence on gastric motility.
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