PDE12 disrupts mitochondrial oxidative phosphorylation and mediates mitochondrial dysfunction to induce oral mucosal epithelial barrier damage in oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a chronic oral mucosal disease. The pathological changes of OSF include epithelial damage and subepithelial matrix fibrosis. This study aimed to reveal the epithelial injury mechanism of OSF. A histopathological method was used to analyze oral mucosal tissue from OSF patients and OSF rats. The expression of PDE12 in the oral epithelium was analyzed by immunohistochemistry. The epithelial-mesenchymal transition (EMT) and tight junction proteins in arecoline-treated HOKs were explored by western blotting. Epithelial leakage was assessed by transepithelial electrical resistance and lucifer yellow permeability. The expression of PDE12 and the mitochondrial morphology, mitochondrial permeability transition pore opening, mitochondrial membrane potential, and mitochondrial reactive oxygen species (mtROS) were evaluated in arecoline-induced HOKs. Oxidative phosphorylation (OXPHOS) complexes and ATP content were also explored in HOKs. The results showed significant overexpression of PDE12 in oral mucosal tissue from OSF patients and rats. PDE12 was also overexpressed and aggregated in mitochondria in arecoline-induced HOKs, resulting in dysfunction of OXPHOS and impaired mitochondrial function. An EMT, disruption of tight junctions with epithelial leakage, and extracellular matrix remodeling were also observed. PDE12 overexpression induced by PDE12 plasmid transfection enhanced the mtROS level and interfered with occludin protein localization in HOKs. Interestingly, knockdown of PDE12 clearly ameliorated arecoline-induced mitochondrial dysfunction and epithelial barrier dysfunction in HOKs. Therefore, we concluded that overexpression of PDE12 impaired mitochondrial OXPHOS and mitochondrial function and subsequently impaired epithelial barrier function, ultimately leading to OSF. We suggest that PDE12 may be a new potential target against OSF.

Fucoxanthin ameliorated myocardial fibrosis in STZ-induced diabetic rats and cell hypertrophy in HG-induced H9c2 cells by alleviating oxidative stress and restoring mitophagy.

Diabetic cardiomyopathy (DCM) is one of the leading causes of death in diabetic patients, and is accompanied by increased oxidative stress and mitochondrial dysfunction. Fucoxanthin (FX), as a marine carotenoid, possesses strong antioxidant activity. The main purpose of our study was to explore whether FX could attenuate experimental cardiac hypertrophy by affecting mitophagy and oxidative stress. We found that FX improved lipid metabolism, myocardial damage, myocardial fibrosis and hypertrophy in the myocardial tissue of STZ-induced diabetic rats. Additionally, FX upregulated Nrf2 signaling to reduce the level of reactive oxygen species (ROS). FX also promoted Bnip3/Nix signaling to improve mitochondrial function and reduced the levels of mitochondrial and intracellular ROS, thereby reversing HG-induced H9c2 cell hypertrophy. However, treatment with the autophagy inhibitor CQ abolished the anti-hypertrophic effect of FX, accompanied by impaired mitochondrial function and increased ROS levels. In conclusion, we found that FX reduced the accumulation of TGF-ß1, FN and α-SMA to relieve myocardial fibrosis in STZ-induced diabetic rats, and FX up-regulated Bnip3/Nix to promote mitophagy and enhanced Nrf2 signaling to alleviate oxidative stress, thereby inhibiting hypertrophy in HG-induced H9c2 cells. These results imply that FX may be developed as a functional food for DCM.

A Fine-Tuned Positioning Algorithm for Space-Borne GNSS Timing Receivers.

To maximize the usage of limited transmission power and wireless spectrum, more communication satellites are adopting precise space-ground beam-forming, which poses a rigorous positioning and timing requirement of the satellite. To fulfill this requirement, a space-borne global navigation satellite system (GNSS) timing receiver with a disciplined high-performance clock is preferable. The space-borne GNSS timing receiver moves with the satellite, in contrast to its stationary counterpart on ground, making it tricky in its positioning algorithm design. Despite abundant existing positioning algorithms, there is a lack of dedicated work that systematically describes the delicate aspects of a space-borne GNSS timing receiver. Based on the experimental work of the LING QIAO (NORAD ID:40136) communication satellite's GNSS receiver, we propose a fine-tuned positioning algorithm for space-borne GNSS timing receivers. Specifically, the proposed algorithm includes: (1) a filtering architecture that separates the estimation of satellite position and velocity from other unknowns, which allows for a first estimation of satellite position and velocity incorporating any variation of orbit dynamics; (2) a two-threshold robust cubature Kalman filter to counteract the adverse influence of measurement outliers on positioning quality; (3) Reynolds averaging inspired clock and frequency error estimation. Hardware emulation test results show that the proposed algorithm has a performance with a 3D positioning RMS error of 1.2 m, 3D velocity RMS error of 0.02 m/s and a pulse per second (PPS) RMS error of 11.8ns. Simulations with MATLAB show that it can effectively detect and dispose outliers, and further on outperforms other algorithms in comparison.