MiR-146b-5p/SEMA3G regulates epithelial-mesenchymal transition in clear cell renal cell carcinoma.

OBJECTIVE: The primary purpose was to unveil how the miR-146b-5p/SEMA3G axis works in clear cell renal cell carcinoma (ccRCC). METHODS: ccRCC dataset was acquired from TCGA database, and target miRNA to be studied was further analyzed using survival analysis. We performed miRNA target gene prediction through the database, and those predicted miRNAs were intersected with differential mRNAs. After calculating the correlation between miRNAs and mRNAs, we completed the GSEA pathway enrichment analysis on mRNAs. MiRNA and mRNA expression was examined by qRT-PCR. Western blot was introduced to detect SEMA3G, MMP2, MMP9 expression, epithelial-mesenchymal transition (EMT) marker proteins, and Notch/TGF-ß signaling pathway-related proteins. Targeted relationship between miRNA and mRNA was validated using a dual-luciferase test. Transwell assay was employed to assess cell migration and invasion. Wound healing assay was adopted for evaluation of migration ability. The effect of different treatments on cell morphology was observed by a microscope. RESULTS: In ccRCC cells, miR-146b-5p was remarkably overexpressed, yet SEMA3G was markedly less expressed. MiR-146b-5p was capable of stimulating ccRCC cell invasion, migration and EMT, and promoting the transformation of ccRCC cell morphology to mesenchymal state. SEMA3G was targeted and inhibited via miR-146b-5p. MiR-146b-5p facilitated ccRCC cell migration, invasion, morphology transforming to mesenchymal state and EMT process by targeting SEMA3G and regulating Notch and TGF-ß signaling pathways. CONCLUSION: MiR-146b-5p regulated Notch and TGF-ß signaling pathway by suppressing SEMA3G expression, thus promoting the growth of ccRCC cells, which provides a possible target for ccRCC therapy and prognosis prediction.

Deubiquitinase Ubp3 regulates ribophagy and deubiquitinates Smo1 for appressorium-mediated infection by Magnaporthe oryzae.

The Ubp family of deubiquitinating enzymes has been found to play important roles in plant-pathogenic fungi, but their regulatory mechanisms are still largely unknown. In this study, we revealed the regulatory mechanism of the deubiquitinating enzyme Ubp3 during the infection process of Magnaporthe oryzae. AUBP3 deletion mutant was severely defective in appressorium turgor accumulation, leading to the impairment of appressorial penetration. During appressorium formation, the mutant was also defective in glycogen and lipid metabolism. Interestingly, we found that nitrogen starvation and rapamycin treatment induced the ribophagy process in M. oryzae, which is closely dependent on Ubp3. In the ∆ubp3 mutant, the ribosome proteins and rRNAs were not well degraded on nitrogen starvation and rapamycin treatment. We also found that Ubp3 interacted with the GTPase-activating protein Smo1 and regulated its de-ubiquitination. Ubp3-dependent de-ubiquitination of Smo1 may be required for Smo1 to coordinate Ras signalling. Taken together, our results showed at least two roles of Ubp3 in M. oryzae: it regulates the ribophagy process and it regulates de-ubiquitination of GTPase-activating protein Smo1 for appressorium-mediated infection.

Endocytic protein Pal1 regulates appressorium formation and is required for full virulence of Magnaporthe oryzae.

Endocytosis plays key roles during infection of plant-pathogenic fungi, but its regulatory mechanisms are still largely unknown. Here, we identified a putative endocytosis-related gene, PAL1, which was highly expressed in appressorium of Magnaporthe oryzae, and was found to be important for appressorium formation and maturation. Deletion of PAL1 significantly reduced the virulence of M. oryzae due to defects in appressorial penetration and invasive growth in host cells. The Pal1 protein interacted and colocalized with the endocytosis protein Sla1, suggesting it is involved in endocytosis. The Δpal1 mutant was significantly reduced in appressorium formation, which was recovered by adding exogenous cAMP and 3-isobutyl-1-methylxanthine (IBMX). Moreover, the phosphorylation level of Pmk1 in Δpal1 was also reduced, suggesting Pal1 functions upstream of both the cAMP and Pmk1 signalling pathways. As a consequence, the utilization of glycogen and lipid, appressorial autophagy, actin ring formation, localization of septin proteins, as well as turgor accumulation were all affected in the Δpal1 mutant. Taken together, Pal1 regulates cAMP and the Pmk1 signalling pathway for appressorium formation and maturation to facilitate infection of M. oryzae.

Ultralow-noise broadband source for interferometric fiber optic gyroscopesemploying a semiconductor optical amplifier.

A novel scheme of an ultralow relative intensity noise (RIN) broadband source module employing a double pumped backward (DPB) Er-doped superfluorescence fiber source (EDSFS) and a semiconductor optical amplifier for interferometric fiber optic gyroscopes (IFOGs) is proposed. With optimized parameters, the optimal twin-peak output profile of the source is obtained. The effective optical spectrum width of the source is 38.6 nm, and the output power is about 12.5 mW. Compared with the DPB EDSFS with a similar spectrum, the ultralow RIN broadband source proposed demonstrates a lower RIN of about 8.4 dB. A high-precision IFOG utilizing the ultralow RIN broadband source is set up, and the performance of the IFOG is experimentally studied. An angle random walk coefficient of 6.93×10-5o/h1/2 is demonstrated, which is reduced by about 31.5% compared with the same IFOG system utilizing conventional DPB EDSFS with a similar spectrum profile. The ultralow RIN broadband source module proposed is quite feasible for high-precision IFOGs used in strategic-grade navigation systems and satellites.

The Mechanisms of Action of Curcumin in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder of the elderly. As the prevalence of AD rises in the 21st century, there is an urgent need for the development of effective pharmacotherapies. Currently, drug treatments target the symptoms of the disease and do not modify or halt the disease progress. Thus, natural compounds have been investigated for their ability to treat AD. This review examines the efficacy of curcumin, a polyphenol derived from turmeric herb, to treat AD. We summarize the in vivo and in vitro research describing the mechanisms of action in which curcumin modifies AD pathology: curcumin inhibits the formation and promotes the disaggregation of amyloid-ß plaques, attenuates the hyperphosphorylation of tau and enhances its clearance, binds copper, lowers cholesterol, modifies microglial activity, inhibits acetylcholinesterase, mediates the insulin signaling pathway, and is an antioxidant. In conclusion, curcumin has the potential to be more efficacious than current treatments. However, its usefulness as a therapeutic agent may be hindered by its low bioavailability. If the challenge of low bioavailability is overcome, curcumin-based medications for AD may be in the horizon.