Media 1: Pulse bursts with a controllable number of pulses from a mode-locked Yb-doped all fiber laser system

Originally published in Optics Express on 24 March 2014 (oe-22-6-6699

Mirror-Image Thymidine Discriminates against Incorporation of Deoxyribonucleotide Triphosphate into DNA and Repairs Itself by DNA Polymerases

DNA polymerases are known to recognize preferably d-nucleotides over l-nucleotides during DNA synthesis. Here, we report that several general DNA polymerases catalyze polymerization reactions of nucleotides directed by the DNA template containing an l-thymidine (l-T). The results display that the 5′–3′ primer extension of natural nucleotides get to the end at chiral modification site with Taq and Phanta Max DNA polymerases, but the primer extension proceeds to the end of the template catalyzed by Deep Vent (exo^–), Vent (exo^–), and Therminator DNA polymerases. Furthermore, templating l-nucleoside displays a lag in the deoxyribonucleotide triphosphate (dNTP) incorporation rates relative to natural template by kinetics analysis, and polymerase chain reactions were inhibited with the DNA template containing two or three consecutive l-Ts. Most interestingly, no single base mutation or mismatch mixture corresponding to the location of l-T in the template was found, which is physiologically significant because they provide a theoretical basis on the involvement of DNA polymerase in the effective repair of l-T that may lead to cytotoxicity

Media 1: Flexible operability and amplification of gray pulses

Originally published in Optics Letters on 15 July 2014 (ol-39-14-4116

Media 3: Different polarization dynamic states in a vector Yb-doped fiber laser

Originally published in Optics Express on 20 April 2015 (oe-23-8-10747

Effects of Conformational Alteration Induced by d‑/l‑Isonucleoside Incorporation in siRNA on Their Stability in Serum and Silencing Activity

We report here that all of the d- or l-isonucleoside (isoNA) modified siRNAs investigated showed the characteristic A-form conformation in the circular dichroism (CD) spectra compared to native siRNA. The d-isoNA modification had less influence on the thermal stability of siRNAs, but all l-isoNA modification displayed a significant tendency to decrease the thermal stability of siRNA. It was also found that the stabilities of d-/l-isoNA modified siMek1 in serum were different and d-isoNA modification was more potent, i.e., increase of serum stability of siRNA, than l-isoNA modification. When d-isoNA incorporated at position 4 and position 5 at antisense strand of siMek1 showed obvious improvement on serum stability, however, l-isoNA incorporated at positions 11 and 12 at antisense strand and position 9 at sense strand made the siMek1 duplex formed very unstable in serum. The silencing activities of modified siMek1s with d-/l-isoNA at position 1 of antisense strand also dropped dramatically; however, the modification at 3′-terminal of the sense strand with d- or l-isoNA significantly enhanced the silencing activity targeting the antisense strand as reporter and minimized the passenger strand-specific off-target effect. IsoNA modified in the seed area of siMek1, <b>siMek1 A04D</b> and <b>siMek1 A05L</b>, showed similar activity to the native one and better target selectivity. In the case of modification at the position near the cleavage area, it was found that d- or l-isoNA modified sense strand at position 8, 9, or 15 of siMek1 could retain the silencing activities targeting the antisense strand as reporter. Especially, both <b>siMek1 S15D</b> and <b>siMek1 S15L</b> showed good silencing activity and high target selectivity compared to native siMek1. The effects of conformational alteration of such isoNA modification of siRNA on their stability in serum and silencing activity are discussed based on computer simulation. Systematic investigation of the relationship between modified siRNA conformation and their physical and biological properties should provide a useful guideline for chemical modification and optimization of siRNA for further clinical application

Media 1: Different polarization dynamic states in a vector Yb-doped fiber laser

Originally published in Optics Express on 20 April 2015 (oe-23-8-10747

Biological Properties of a 3′,3″-Bis-Peptide-siRNA Conjugate in Vitro and in Vivo

This study proposes an effective melanoma small interfering RNA (siRNA), named siMB3, which targets the mRNA of mutant BRAF protein. We found that Bis-pep-siMB3, with peptide KALLAL-conjugated siMB3 at the 3′-termini of both strands, inhibited translation of the target genes and expression of the related protein as effectively as siMB3, but for substantially longer, and the conjugates could alleviate off-target effects. Further studies on the mechanisms of action showed that the stability of Bis-pep-siMB3 in fetal bovine serum improved and the half-life period of Bis-pep-siMB3 was increased 21-fold over that of siMB3. Peptide conjugation could improve the combination of siRNA and cationic lipid vectors. Bis-pep-siMB3 is likely to reach the lysosome earlier and stay longer, and appears to increase the release of siRNA from the endosome. At the animal level, application of Bis-pep-siMB3 showed good therapeutic potential, inhibiting the growth of xenograft tumors in athymic mice slightly better than siMB3 and greatly prolonging the circulating time in vivo. Moreover, it distributed widely in mice. These results show the promising potential of Bis-pep-siRNA conjugates as therapeutic siRNAs for cancer treatment