Characterization of the G-quadruplexes in the transthyretin gene and its role in silencing transthyretin mRNA transcription.

Transthyretin Amyloidosis arises from the misfolding of monomers or oligomers of the normal transthyretin protein. Our investigation revealed that certain guanine-rich regions within the 5' UTR sequence of the transthyretin gene possess the ability to form G2-quadruplex structures, as determined through analysis with QGRS mapper. We demonstrated that small molecule ligands, including TMPyP4, Braco-19, NMM, and TO, have a significant impact on the stabilization of transthyretin G-quadruplexes. The objective of this study was to confirm the effect of ligands on transthyretin gene transcription through the stabilization of G-quadruplexes. To comprehend the interaction between ligands and transthyretin G-quadruplexes, a range of analytical techniques were employed, includingUV titration, fluorescence titration assays, circular dichroism, quantitative RT-PCR and cytotoxicity tests. The results revealed the presence of four putative G2-quadruplex sequences, which formed stable anti-parallel, parallel, and hybrid G2-quadruplex structures. Notably, Ttrg 3 (5'-GGAAGGAAGGGAGGGAGGG-3') exhibited the highest stability to form G-quadruplex. Furthermore, TmPyP4, Braco-19, NMM and TO were found to stabilize the parallel topology of Ttrg 3. After 48 h of incubation, the RT-PCR experiments revealed a significant reduction in transthyretin mRNA transcription in HepG2 cells when treated with 20 µM TmPyP4 and Braco-19, without inducing apoptosis. Our findings suggested that ligand-mediated stabilization of G-quadruplexes within the 5'-UTR can effectively silence transthyretin expression, highlighting the potential of G-quadruplex as a novel therapeutic target for Transthyretin Amyloidosis. This study might shed valuable lights for the development of innovative therapeutic approach against Transthyretin Amyloidosis.

The Relationship between Postural Stability and Lower-Limb Muscle Activity Using an Entropy-Based Similarity Index.

The aim of this study is to see if the centre of pressure (COP) measurements on the postural stability can be used to represent the electromyography (EMG) measurement on the activity data of lower limb muscles. If so, the cost-effective COP data measurements can be used to indicate the level of postural stability and lower limb muscle activity. The Hilbert-Huang Transform method was used to analyse the data from the experimental designed to examine the correlation between lower-limb muscles and postural stability. We randomly selected 24 university students to participate in eight scenarios and simultaneously measured their COP and EMG signals during the experiments. The Empirical Mode Decomposition was used to identify the intrinsic-mode functions (IMF) that can distinguish between the COP and EMG at different states. Subsequently, similarity indices and synchronization analyses were used to calculate the correlation between the lower-limb muscle strength and the postural stability. The IMF5 of the COP signals and the IMF6 of the EMG signals were not significantly different and the average frequency was 0.8 Hz, with a range of 0-2 Hz. When the postural stability was poor, the COP and EMG had a high synchronization with index values within the range of 0.010-0.015. With good postural stability, the synchronization indices were between 0.006 and 0.080 and both exhibited low synchronization. The COP signals and the low frequency EMG signals were highly correlated. In conclusion, we demonstrated that the COP may provide enough information on postural stability without the EMG data.

Multiheteroatom-Doped Porous Carbon Catalyst for Oxygen Reduction Reaction Prepared using 3D Network of ZIF-8/Polymeric Nanofiber as a Facile-Doping Template.

We report a facile and versatile method for fabrication of multiheteroatom-doped hierarchically porous carbon with a large specific surface area, using the 3D network constructed by ZIF-8 coated wormlike micelles as template. The uniform and highly pure wormlike micelles developed in our laboratory is essential, because they not only are responsible for the formation of hierarchical porosity, but also play as a versatile platform for multiheteroatoms doping. In a primary experiment, S, N, B, and P heteroatoms were doped conveniently and the resultant porous carbons have the excellent oxygen reduction reaction performance comparable to the commercial 20% Pt/C.