Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma

Recent studies have shown that circulating microRNAs are a potential biomarker in various types of malignancies. The aim of this study was to investigate the feasibility of using serum exosomal microRNAs as novel serological biomarkers for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We measured the serum exosomal microRNAs and serum circulating microRNAs in patients with CHB (n=20), liver cirrhosis (LC) (n=20) and HCC (n=20). Serum exosomal microRNA was extracted from 500 μl of serum using an Exosome RNA Isolation kit. The expression levels of microRNAs were quantified by real-time PCR. The expression levels of selected microRNAs were normalized to Caenorhabditis elegans microRNA (Cel-miR-39). The serum levels of exosomal miR-18a, miR-221, miR-222 and miR-224 were significantly higher in patients with HCC than those with CHB or LC (P<0.05). Further, the serum levels of exosomal miR-101, miR-106b, miR-122 and miR-195 were lower in patients with HCC than in patients with CHB (P=0.014, P<0.001, P<0.001 and P<0.001, respectively). There was no significant difference in the levels of miR-21 and miR-93 among the three groups. Additionally, the serum levels of circulating microRNAs showed a smaller difference between HCC and either CHB or LC. This study suggests that serum exosomal microRNAs may be used as novel serological biomarkers for HCC.     

DNA-templated preparation of gold nanoparticles

DNA-mediated gold nanoparticles were prepared by chemical reduction of DNA-Au(III) complex. The DNA-Au(III) was first formed by reacting DNA with HAuCl? at a pH of 5.6. The complex in solution was reacted with hydrazine reducing Au(III) to Au. The reduced Au formed nanodimensional aggregates. The particle distributions were obtained by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). This method resulted in a rather uniform dispersion of Au nanoparticles of near-spherical shape and 45~80 nm in diameter. Gold nanoparticles were embedded and stabilized by DNA.     

Identification of a lacosamide binding protein using an affinity bait and chemical reporter strategy: 14-3-3 ζ

We have advanced a useful strategy to elucidate binding partners of ligands (drugs) with modest binding affinity. Key to this strategy is attaching to the ligand an affinity bait (AB) and a chemical reporter (CR) group, where the AB irreversibly attaches the ligand to the receptor upon binding and the CR group is employed for receptor detection and isolation. We have tested this AB&CR strategy using lacosamide ((R)-1), a low-molecular-weight antiepileptic drug. We demonstrate that using a (R)-lacosamide AB&CR agent ((R)-2) 14-3-3 ζ in rodent brain soluble lysates is preferentially adducted, adduction is stereospecific with respect to the AB&CR agent, and adduction depends upon the presence of endogenous levels of the small molecule metabolite xanthine. Substitution of lacosamide AB agent ((R)-5) for (R)-2 led to the identification of the 14-3-3 ζ adduction site (K120) by mass spectrometry. Competition experiments using increasing amounts of (R)-1 in the presence of (R)-2 demonstrated that (R)-1 binds at or near the (R)-2 modification site on 14-3-3 ζ. Structure-activity studies of xanthine derivatives provided information concerning the likely binding interaction between this metabolite and recombinant 14-3-3 ζ. Documentation of the 14-3-3 ζ-xanthine interaction was obtained with isothermal calorimetry using xanthine and the xanthine analogue 1,7-dimethylxanthine.     

Decarboxylative cross-couplings of 2-aminopyrimidine-5-carboxylic acids

Decarboxylative CC cross-couplings of 2-aminopyrimidine-5-carboxylic acids under a Pd/Ag-based catalytic system opens a new platform for the introduction of diverse C5 substituents. The reaction methods proceeded efficiently with a wide range of the acids and the coupling partners of aryl iodides, alkenes, bromoalkynes, and azoles. Considering ready availability of 2-aminopyrimidine-5-carboxylic acid from the oxidative dehydrosulfurative CN cross-coupling of the 3,4-dihydropyrimidin-1H-2-thiones, this reaction method unambiguously pave a shortcut to densely substituted 2-aminopyrimidine derivatives with unprecedented diversity.     

Hydrophobic Shielding of Outer Surface: Enhancing the Chemical Stability of Metal–Organic Polyhedra

Metal–organic polyhedra (MOP) are a promising class of crystalline porous materials with multifarious potential applications. Although MOPs and metal–organic frameworks (MOFs) have similar potential in terms of their intrinsic porosities and physicochemical properties, the exploitation of carboxylate MOPs is still rudimentary because of the lack of systematic development addressing their chemical stability. Herein we describe the fabrication of chemically robust carboxylate MOPs via outer‐surface functionalization as an a priori methodology, to stabilize those MOPs system where metal–ligand bond is not so strong. Fine‐tuning of hydrophobic shielding is key to attaining chemical inertness with retention of the framework integrity over a wide range of pH values, in strong acidic conditions, and in oxidizing and reducing media. These results are further corroborated by molecular modelling studies. Owing to the unprecedented transition from instability to a chemically ultra‐stable regime using a rapid ambient‐temperature gram‐scale synthesis (within seconds), a prototype strategy towards chemically stable MOPs is reported.     

Observation of negative charge trapping and investigation of its physicochemical origin in newly synthesized poly(tetraphenyl)silole siloxane thin films

A new kind of organic-inorganic hybrid polymer, poly(tetraphenyl)silole siloxane, was invented and synthesized for realization of its unique charge trap properties. The organic portions consisting of (tetraphenyl)silole rings were responsible for negative charge trapping, while the Si-O-Si inorganic linkages provided the intrachain energy barrier for controlling electron transport. The polysilole siloxane dielectric thin films were fabricated by spin-coating and curing of the polymers, followed by characterization with spectroscopic ellipsometry (SE), near edge X-ray absorption fine structure spectroscopy (NEXAFS), and photoemission spectroscopy (PES). The abrupt increase in density and decrease in thickness of the thin film at a curing temperature of 100 °C was attributed to a thermodynamically preferred state in the nanoscopic arrangement of the polymer chains; this was due to cofacial π-π interactions in a skewed manner between peripheral phenyl groups of the (tetraphenyl)silole rings of the adjacent polymer chains. Using the NEXAFS spectrum to assess high electron affinity, the LUMO energy level of the dielectric thin film cured at 150 °C was positioned 1 eV above the Fermi energy level (E(F)). The electron trapping of the dielectric thin films was confirmed from the positive flat band shift (ΔV(FB)) in the capacitance-voltage (C-V) measurements performed within the metal-insulator-semiconductor (MIS) device structure, which strongly verified the polymer design concept. From the simple kinetics model of the electron transport, it was proposed that the flat band shift (ΔV(FB)) or trap density of the negative charges (|ρ|) was logarithmically proportional to the decay constant (β) for the electron-tunneling process. When a phenyl group of a silole ring in a polymer chain was inserted into the two available phenyl groups of another silole ring in another polymer chain, the electron transfer between the groups was enhanced, decreasing the trap density of the negative charges (|ρ|). For the thermodynamically preferred state generating the high refractive index, the distance between the two phenyl groups of the adjacent polymer chains was estimated to be in the range of 0.27-0.36 nm.     

Synthesis and antitumor activity of DNA binding cationic porphyrin-platinum(II) complexes

A new series of DNA binding 5,10,15-tri(N-methyl-4-pyridiniumyl)porphyrin (TrisMPyP)-platinum(II) conjugates was synthesized, in which different spacer ligands were used for appropriate coordination to platinum(II) complexes. Compound 9b exhibited in vivo antitumor activity (T/C%, 294) superior to cisplatin (T/C%, 184) against the leukemia L1210 cell line.     

Blue Luminescence of Dendrimer‐Encapsulated Gold Nanoclusters

Direct evidence for the blue luminescence of gold nanoclusters encapsulated inside hydroxyl‐terminated polyamidoamine (PAMAM) dendrimers was provided by spectroscopic studies as well as by theoretical calculations. Steady‐state and time‐resolved spectroscopic studies showed that the luminescence of the gold nanoclusters consisted largely of two electronic transitions. Theoretical calculations indicate that the two transitions are attributed to the different sizes of the gold nanoclusters (Au₈ and Au₁₃). The luminescence of the gold nanoclusters was clearly distinguished from that of the dendrimers.     

Mass spring lattice modeling of the scanning laser source technique

The scanning laser source (SLS) technique is a promising new laser ultrasonic tool for the detection of small surface-breaking defects. The SLS approach is based on monitoring the changes in laser generated ultrasound as a laser source is scanned over a defect. Changes in amplitude and frequency content have been observed for ultrasound generated by the laser over uniform and defective areas. In this paper, the SLS technique is simulated numerically using the mass spring lattice model. Thermoelastic laser generation of ultrasound in an elastic material is modeled using a shear dipole distribution. The spatial and temporal energy distribution profiles of typical pulsed laser sources are used to model the laser source. The amplitude and spectral variations in the laser generated ultrasound as the SLS scans over a large aluminum block containing a small surface-breaking crack are observed. The experimentally observed SLS amplitude and spectral signatures are shown to be captured very well by the model. In addition, the possibility of utilizing the SLS technique to size surface-breaking cracks that are sub-wavelength in depth is explored.