CREATION OF TRANSPORT PATHWAYS ACROSS SKIN BY MICRONEEDLES FOR DRUG DELIVERY

Ph.DDOCTOR OF PHILOSOPH

The role of AMPK/mTOR/S6K1 signaling axis in mediating the physiological process of exercise-induced insulin sensitization in skeletal muscle of C57BL/6 mice

AbstractThe crosstalk between mTORC1/S6K1 signaling and AMPK is emerging as a powerful and highly regulated way to gauge cellular energy and nutrient content. The aim of the current study was to determine the mechanism by which exercise training reverses lipid-induced insulin resistance and the role of AMPK/mTOR/S6K1 signaling axis in mediating this response in skeletal muscle. Our results showed that high-fat feeding resulted in decreased glucose tolerance, which was associated with decreased Akt expression and increased intramuscular triglyceride deposition in the skeletal muscle of C57BL/6 mice. Impairments in lipid metabolism were accompanied by increased total protein and phosphorylation of S6K1, SREBP-1c cleavage, and decreased AMPK phosphorylation. Exercise training reversed these impairments, resulting in improved serum lipid profiles and glucose tolerance. C2C12 myotubes were exposed to palmitate, resulting in an increased insulin-dependent Akt Ser473 phosphorylation, associated with a significant increase in the level of phosphorylation of S6K1 on T389. All these changes were reversed by activation of AMPK. Consistent with this, inhibition of AMPK by compound C induced an enhanced phosphorylation of both S6K1 and Akt, and silencing of S6K1 with siRNA showed no effect on Akt phosphorylation in both the absence and presence of palmitate cultured myotubes. In addition, compound C led to an elevated SREBP-1c cleavage but was blocked by S6K1 siRNA. In summary, exercise training inhibits SREBP-1c cleavage through AMPK/mTOR/S6K1 signaling, resulting in decreased intramyocellular lipid accumulation. Our results provide new insights into the mechanism by which AMPK/mTOR/S6K1 signaling axis mediates the physiological process of exercise-induced insulin sensitization

On-Line Monitoring and Fault Diagnosis of Box Transformer Substation Based on VPRS-RBFNN

Box transformer substation (BTS) is an important power distribution environment. To ensure the safe and stable operation of the power distribution system, it is critical to monitor the BTS operation and diagnose its faults in a reliable manner. In the Internet of Things (IoT) environment, this paper aims to develop a real-time and accurate online strategy for BTS monitoring and fault diagnosis. The framework of our strategy was constructed based on the IoT technique, including a sensing layer, a network layer and an application layer. On this basis, a BTS fault diagnosis method was established with variable precision rough set (VPRS) as the pre-network and the radial basis function neural network (RBFNN) as the back-fed network. The VPRS and the RBFNN were selected, because the BTS faults have many characteristic parameters, with complex nonlinear relationship with fault modes. Finally, a prototype of our strategy was developed and applied to the fault diagnosis of an actual BTS. The results fully demonstrate the effectiveness and feasibility of our strategy

Astaxanthin production by Phaffia rhodozyma fermentation of cassava residues substrate

Cassava residues as main materials were fermented with Phaffia rhodozyma to produce astaxanthin.  Using the Box-Behnken design, the effects of sugar content, initial pH and nitrogen content were studied with the yield of astaxanthin as response value, which was evaluated to optimize the fermentation conditions of astaxanthin production.  The optimal fermentation conditions have been reached by the study: sugar content was 40 g/L, the initial pH was at 4 and nitrogen content was 8 g/L.  By validation test, the astaxanthin yield under the optimal condition, which was basically corresponded to the model prediction, was 96.83%.Keywords: astaxanthin, cassava recidues, Phaffia rhodozym

Ultrahigh Piezoelectric Performance through Synergistic Compositional and Microstructural Engineering

Piezoelectric materials enable the conversion of mechanical energy into electrical energy and vice-versa. Ultrahigh piezoelectricity has been only observed in single crystals. Realization of piezoelectric ceramics with longitudinal piezoelectric constant (d33) close to 2000 pC N–1, which combines single crystal-like high properties and ceramic-like cost effectiveness, large-scale manufacturing, and machinability will be a milestone in advancement of piezoelectric ceramic materials. Here, guided by phenomenological models and phase-field simulations that provide conditions for flattening the energy landscape of polarization, a synergistic design strategy is demonstrated that exploits compositionally driven local structural heterogeneity and microstructural grain orientation/texturing to provide record piezoelectricity in ceramics. This strategy is demonstrated on [001]PC-textured and Eu3+-doped Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT) ceramics that exhibit the highest piezoelectric coefficient (small-signal d33 of up to 1950 pC N–1 and large-signal d33* of ≈2100 pm V–1) among all the reported piezoelectric ceramics. Extensive characterization conducted using high-resolution microscopy and diffraction techniques in conjunction with the computational models reveals the underlying mechanisms governing the piezoelectric performance. Further, the impact of losses on the electromechanical coupling is identified, which plays major role in suppressing the percentage of piezoelectricity enhancement, and the fundamental understanding of loss in this study sheds light on further enhancement of piezoelectricity. These results on cost-effective and record performance piezoelectric ceramics will launch a new generation of piezoelectric applications

SMA1, a homolog of the splicing factor Prp28, has a multifaceted role in miRNA biogenesis in Arabidopsis

MicroRNAs (miRNAs) are a class of small non-coding RNAs that repress gene expression. In plants, the RNase III enzyme Dicer-like (DCL1) processes primary miRNAs (pri-miRNAs) into miRNAs. Here, we show that SMALL1 (SMA1), a homolog of the DEADbox pre-mRNA splicing factor Prp28, plays essential roles in miRNA biogenesis in Arabidopsis. A hypomorphic sma1-1 mutation causes growth defects and reduces miRNA accumulation correlated with increased target transcript levels. SMA1 interacts with the DCL1 complex and positively influences primiRNA processing. Moreover, SMA1 binds the promoter region of genes encoding pri-miRNAs (MIRs) and is required for MIR transcription. Furthermore, SMA1 also enhances the abundance of the DCL1 protein levels through promoting the splicing of the DCL1 pre-mRNAs. Collectively, our data provide new insights into the function of SMA1/Prp28 in regulating miRNA abundance in plants