Presentation1_Causal effects of homocysteine levels on the components of sarcopenia: A two-sample mendelian randomization study.pdf

Background: Currently, it is unclear whether there is a causal association between genetically predicted plasma homocysteine (Hcy) levels and the risk of sarcopenia. We performed a Mendelian randomization (MR) study to assess the association between circulating Hcy levels and the components [grip strength, walking pace, and appendicular lean mass (ALM)] of sarcopenia.Methods: Independent single nucleotide polymorphisms (SNPs) significantly associated with plasma Hcy levels served as instrumental variables. Summary-level data regarding the components of sarcopenia. Were obtained from the UK Biobank. Inverse variance weighted (IVW) as the primary method was used for Mendelian randomization (MR) analysis. We also use four models, weighted median, MR-Egger regression, Maximum likelihood, and Penalised weighted median, as supplementary methods to IVW. The MR-Egger intercept test, Cochran’s Q test, and “leave-one-out” sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of the causal association between Hcy levels and the components of sarcopenia.Results: The IVW-MR analysis suggested significant negative associations of increased plasma Hcy levels with grip strength (right: effect = −0.036, SE = 0.032, p = 5.53E-4; left: effect = −0.045, SE = 0.010, p = 1.45E-5), walking pace (effect = −0.038, SE = 0.011, p = 3.18E-4), and ALM (effect = −0.058, 0.013, p = 1.03E-5). However, there were no significant associations of decreased plasma Hcy levels with grip strength (right: effect = 0.005, SE = 0.021, p = 0.82; left: effect = −0.006, SE = 0.014, p = 0.64), walking pace (effect = 0.01, 0.020, p = 0.61), or ALM (effect = -0.034, SE = 0.018, p = 0.06).The accuracy and robustness of these findings were confirmed by sensitivity tests.Conclusion: Increased circulating Hcy levels were associated with lower grip strength, slower walking pace, and decreased ALM.</p

Synthesis of cholesterol-peptide conjugates.

<p>Synthesis of cholesterol-peptide conjugates.</p

Luciferase expression levels induced by Ch-R5H5/DNA, Ch-R3H3/DNA, Ch-R5, and Ch-R3 complexes in mammalian cells.

<p>DNA and PEI/DNA complex at an N/P ratio of 10 are used as negative and positive controls respectively. Error bars represent standard deviation of 4 replicates. Panel A. HEK-293 cell line. Panel B. MCF-7 cell line.</p

Critical micelle concentration of cholesterol-peptide hybrids in PBS at 25°C.

<p>Panel A. Ch-R5H5. Panel B. Ch-R3H3. Panel C. Ch-R5. Panel D. Ch-R3.</p

Hydrodynamic size and zeta potential of Ch-R5H5/DNA, Ch-R3H3/DNA, Ch-R5/DNA, Ch-R3/DNA and R10/DNA complexes.

<p>Hydrodynamic size and zeta potential of Ch-R5H5/DNA, Ch-R3H3/DNA, Ch-R5/DNA, Ch-R3/DNA and R10/DNA complexes.</p

Cell viability of mammalian cells after incubation with Ch-R5H5-DNA, Ch-R3H3-DNA, Ch-R5, and Ch-R3 complexes at different N/P ratios compared to DNA and PEI/DNA complex at an N/P ratio of 10.

<p>Error bars represent standard deviation of 8 replicates. Panel A. HEK-293 cell line. Panel B. MCF-7 cell line.</p

Total ion chromatogram(TIC) and Major intermediates ion mass spectra(P1~P7) of SMN from Photocatalytic degradation of sulfamethazine in aqueous solution using ZnO with different morphologies

Fig.S

Dextran–Peptide Hybrid for Efficient Gene Delivery

Gene therapy has drawn significant interest in the past two decades since it provides a promising strategy to treat both genetic disorders and acquired diseases. However, the transfer of gene therapy to clinical applications is troubled with many difficulties, since many current systems are of toxicity, low transfection efficiency and low biodegradability. To address these challenges, we developed a dextran–peptide hybrid system as a safe and efficient vector for gene therapy and investigated the structure–function–cytotoxicity relationship of this dextran–peptide hybrid system. Dextrans (Dex10, Dex20, and Dex70) with different molecular weights (10, 20 and 70 kDa) were conjugated with a cationic peptide, R5H5, at various degrees of substitution. Gene expression and cytotoxicity mediated by this delivery system were evaluated against SKOV-3 human ovarian carcinoma cells and compared to 25 kDa branched poly­(ethylenimine) (PEI). The results showed that Dex10–R5H5 and Dex20–R5H5 hybrids derived from low molecular weight dextrans induced higher gene expression and lower cytotoxicity than Dex70–R5H5 hybrid from higher molecular weight dextran. The best performance on gene expression was achieved by Dex10–R5H5 at 40% substitution of R5H5, which induced greater gene expression than PEI at a low N/P ratio of 5. Dex10–R5H5/DNA complexes at 40% substitution of R5H5 also showed much higher cell viability (93%) than PEI/DNA (66%) at the same N/P ratio. These results indicate that the Dex–R5H5 hybrid with the low molecular weight of dextran and the high degree of substitution of R5H5 is a very promising material for safe and efficient gene therapy

Hepatic contents of total lipid, triacylglycerol and cholesterol.

<p>Values are mean ±SEM. The means marked with superscript letters are significantly different relative to others.</p