Electrochemical Deposition and Etching of Quasi-Two-Dimensional Periodic Membrane Structure.

In this paper, two experimental procedures are reported, namely electro-deposition in the ultrathin liquid layer and chemical micro-etching. Firstly, a large area quasi-two-dimensional periodic membrane with adjustable density is deposited on a Si substrate driven by half-sinusoidal voltage, which is composed of raised ridges and a membrane between the ridges. The smaller the voltage frequency is, the larger the ridge distance is. The height of a raised ridge changes synchronously with the amplitude. The grain density distribution of membrane and raised ridge is uneven; the two structures change alternately, which is closely related to the change of growth voltage and copper ion concentration during deposition. The structural characteristics of membrane provide favorable conditions for micro-etching; stable etching speed and microscope real-time monitoring are the keys to achieve accurate etching. In the chemical micro-etching process, the membrane between ridges is removed, retaining the raised ridges, thus a large scale ordered micro-nano wires array with lateral growth was obtained. This method is simple and controllable, can be applied to a variety of substrates, and is the best choice for designing and preparing new functional materials. This experiment provides a basis for the extension of this method.

Treatment of refractory giant macular hole by vitrectomy with internal limiting membrane transplantation and autologous blood.

AIM: To investigate the effect of internal limiting membrane transplantation and autologous blood on treating refractory giant macular hole. METHODS: Thirty-seven eyes with giant macular hole of the smallest hole diameter >700 µm, the maximum diameter of the substrate >1000 µm and hole formation factor <0.6 underwent surgical treatment. The patients were randomly divided into two groups. Nineteen eyes with surgical flip of the internal limiting membrane in group A, 18 eyes with internal limiting membrane transplantation in group B who underwent the tamponade of internal limiting membrane into the hole, autologous plasma was used to seal the hole. The patients were followed up for 3mo, optical coherence tomography and best corrected visual acuity (BCVA) were recorded before and after operation, and the results were statistically analyzed. RESULTS: At 3mo after operation, BCVA of the two groups was significantly improved compared with that before operation (tA=4.192, tB=4.374, P<0.05). But there was no significant difference in visual acuity between the two groups (χ2=0.128, P>0.05). At 3mo after operation, the closure rate of group A was 68.4%, and 100% in group B. (χ2=5.628, P<0.05). The defect diameter of inner segment/outer segment at 3mo after the operation was significantly lower than that before operation (tA=12.287, tB=15.481, P<0.05), and the difference was statistically significant (t=2.552, P<0.05). CONCLUSION: Internal limiting membrane transplantation combined with autologous whole blood can improve the postoperative closure rate of the refractory large aperture, and can effectively improve the postoperative visual acuity.

Synthesis, biological evaluation and molecular modeling studies of psammaplin A and its analogs as potent histone deacetylases inhibitors and cytotoxic agents.

In this study, a concise synthetic method of psammaplin A was achieved from 3-bromo-4-hydroxybenzaldahyde and hydantoin through a four-step synthesis via Knoevenagel condensation, hydrolysis, oximation and amidation in 37% overall yield. A collection of novel psammaplin A analogs focused on the variations of substituents at the benzene ring and modifications at the oxime moiety were synthesized. Among all the synthesized compounds, 5d and 5e showed better HDAC inhibition than psammaplin A and comparable cytotoxicity against four cancer cell lines (PC-3, MCF-7, A549 and HL-60). Molecular docking and dynamics simulation revealed that (i) hydrogen atom of the oxime group interacts with Asp99 of HDAC1 through a water bridged hydrogen bond and (ii) a hydroxyl group is optimal attached on the para-position of benzene, interacting with Glu203 at the entrance to the active site tunnel.

Synthesis and biological evaluation of quinoline derivatives as potential anti-prostate cancer agents and Pim-1 kinase inhibitors.

In this work, a series of quinoline derivatives were designed and synthesized as antitumor agents. Most quinolines showed potent anti-proliferative activity against human prostatic cancer PC-3 cell line. Among which, 9d, 9f and 9g were the most effective compounds with GI50 values of 2.60, 2.81 and 1.29 µM, respectively. Structure-activity relationship analysis indicated that the secondary amine linked quinoline and pyridine ring played an important role in the anti-proliferative effects. Mechanistic studies revealed that 9g was a potential Pim-1 kinase inhibitor with abilities of cell cycle arrest and apoptosis induction. Considering of the increased activity of Pim-1 in prostate cancer, such compounds have potential to be developed as anti-prostate cancer agents.

Identification of N-(6-mercaptohexyl)-3-(4-pyridyl)-1H-pyrazole-5-carboxamide and its disulfide prodrug as potent histone deacetylase inhibitors with in vitro and in vivo anti-tumor efficacy.

In this study, a collection of N-(6-mercaptohexyl)-3-substituted-1H-pyrazole-5-carboxamide HDAC inhibitors was developed. Among them, 15k was identified as the most potent inhibitor against total HDACs with IC50 of 0.008 µM. Further isoenzyme assays revealed that 15k and its analogs have a preference for HDAC1-3 (class I) and HDAC6 (class IIb) isoforms. The enzyme-based potencies of 15k were 2- to 11-fold higher than those of Vorinostat. The disulfide prodrug 18 was found to be potent cytotoxic agent against a panel of seven tumor cells, causing hyper-acetylation of histone and non-histone proteins in cellular level. In addition, 18 demonstrated a notable in vivo anti-tumor activity in HCT-116 xenografted model. This study provides further possibility of developing novel thiol-based HDAC inhibitors for the treatment of cancer.

Design and synthesis of substituted pyrido[3,2-d]-1,2,3-triazines as potential Pim-1 inhibitors.

A novel series of substituted pyrido[3,2-d]-1,2,3-triazines were designed and synthesized as Pim-1 inhibitors through scaffold hopping. Most of the derivatives showed potent in vitro Pim-1 inhibitory activities and anti-proliferative effects toward prostate cancer cells. Among them, 6b, 6h and 6m showed the best Pim-1 inhibitory activity with IC50 values of 0.69, 0.60 and 0.80 µM, respectively. Furthermore, compounds 6b, 6i, 6j and 6m showed strong inhibitory activity to human prostate cancer LNcap and PC-3 cell lines with IC50 values at low micromolar level. Structure-activity relationship analysis revealed that appropriate substitutions at C-6 positions contributed to the kinase inhibition and antiproliferative effects. Moreover, western blot assay suggested that 6j could decrease the levels of p-BAD and p-4E-BP1 in a dose-dependent manner in PC-3 cells. Docking studies showed that 3-N of the scaffold formed a hydrogen bond with Lys67, aromatic 4-aniline formed a key π-π stack with Phe49. Taken together, this study might provide the first sight for developing the pyrido[3,2-d]-1,2,3-triazine scaffold as novel Pim-1 inhibitors.

Novel thiol-based histone deacetylase inhibitors bearing 3-phenyl-1H-pyrazole-5-carboxamide scaffold as surface recognition motif: Design, synthesis and SAR study.

A series of novel thiol-based histone deacetylase (HDAC) inhibitors bearing 3-phenyl-1H-pyrazole-5-carboxamide scaffold as surface recognition motif was designed, synthesized, and evaluated for their HDAC inhibition activity. Among them, 15j (IC50=0.08µM) was identified as a better inhibitor than Vorinostat (IC50=0.25µM) against total HDACs. In addition, Structure-activity relationships (SAR) analyses indicated that (i) compounds with different substituents on pyrazole N-1 position exhibited superior activities than those on pyrazole N-2 position, (ii) variation of functional groups on N-1'-alkyl chain terminus followed the trends of carboxyl group>hydroxyl group≫alkyl group, and (iii) methylation on pyrazole C-4 position diminished the HDAC inhibition activity. The SAR will guide us to further refine compounds bearing 3-phenyl-1H-pyrazole-5-carboxamide scaffold to achieve better HDAC inhibitors.

Synthesis of dense, single-crystalline CrO2 nanowire arrays using AAO template-assisted chemical vapor deposition.

High-density, vertically aligned CrO(2) nanowire arrays were obtained via atmospheric-pressure CVD assisted by AAO templates. The CrO(2) nanowire arrays show remarkably enhanced coercivity compared with CrO(2) films or bulk. It was found that the length of the nanowires is greatly influenced by the pore diameter of the AAO template used. The growth mechanism and the pore size dependence of the CrO(2) nanowire arrays are discussed. The present method provides a useful approach for the synthesis of CrO(2) nanowire arrays. Such highly ordered nanowire arrays within an AAO template may have important applications in ultrahigh-density perpendicular magnetic recording devices and the mass production of spintronic nanodevices.