Background
Oral submucous fibrosis (OSF) is a potentially malignant lesion characterized by epithelial‐mesenchymal transition (EMT). Bone morphogenetic protein 4 (BMP4) promotes EMT in fibrotic diseases, but the underlying mechanisms and its potential role in OSF are unclear. This study investigates whether BMP4 plays a role in the pathogenesis of OSF and explores the underlying mechanisms.
Methods
The expression of BMP4 and the EMT proteins E‐cadherin and vimentin was investigated in OSF specimens by immunohistochemical staining. Pearson's correlation analysis was conducted to explore the correlation between BMP4 and the EMT markers. Western blotting and RT‐PCR assays were used to analyze the effect of arecoline (a known EMT‐promoting pathogenic factor in OSF) on BMP4 and identify the transcription factor involved. Confocal microscopy was used to observe the intracellular sublocalization of the identified transcription factor, Yes‐associated protein 1 (YAP1). Finally, siRNA silencing of BMP4 was used to determine its effect on YAP1 activation and arecoline‐induced EMT.
Results
BMP4 is overexpressed in OSF and plays a role in EMT, as its expression correlates with the expression of E‐cadherin and vimentin. Arecoline induces BMP4 expression via the activation of YAP1 (through its nuclear translocation). Furthermore, the YAP1/BMP4 mechanism is the main molecular event in arecoline‐induced EMT, as knockdown of BMP4 expression affects expression of the EMT markers and inhibits extracellular matrix accumulation.
Conclusions
Arecoline induces EMT in OSF via the YAP1/BMP4 pathway. Thus, BMP4 could be considered as a potential therapeutic target for the treatment of OSF.
A 0.5-6 GHz CMOS vector-sum phase shifter with a full 360° phase ran g e is presented. Emplo y in g phase reversible variable g ain amplifiers (VGAs), for simultaneous amplitude and polarit y control, the phase shifter realizes a continuousl y tunable phase shift of 360° with onl y one DC control volta g e and sin g le-ended 1-and Q-si g nals. A maximum g ain of 11 dB is measured with a 2-dB g ain variation over the 0.5-6 GHz band. The root-mean-square (RMS) amplitude and phase error are less than 0.95 dB and 7°. The measured in-band noise fi g ure (NF) is better than 13 dB. Wideband input and output matching are also achieved throughout the entire band. Operating at 1.5 V, the entire circuit consumes 27.5 mW. To the best of the authors' knowled g e, it is the first time the phase-reversible VGA is used to realize a full-360° vector sum phase shifter, which eliminates the need for an input balun and a complicated control circuit.Index Terms -CMOS active phase shifter, wideband vector sum phase shifter, phase-reversible VGA.
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