Unique properties exist in nanofluidic channels. In this paper, we report a new phenomenon, ion enrichment/depletion, associated with nanochannel structures. As a voltage is applied across a nanochannel, ions are rapidly enriched at one end and depleted at the other end of the nanochannel. The degree of this enrichment and depletion is directly related to the extent of double-layer overlap. A simple model is presented to qualitatively interpret this phenomenon.

Adenosine analogues modified at the 5'-position as uronamides and/or as N6-benzyl derivatives were synthesized. These derivatives were examined for affinity in radioligand binding assays at the newly discovered rat brain A3 adenosine receptor and at rat brain A1 and A2a receptors. 5'-Uronamide substituents favored A3 selectivity in the order N-methyl > N-ethyl approximately unsubstituted carboxamide > N-cyclopropyl. 5'-(N-Methylcarboxamido)-N6-benzyladenosine was 37-56-fold more selective for A3 receptors. Potency at A3 receptors was enhanced upon substitution of the benzyl substituent with nitro and other groups. 5'-N-Methyluronamides and N6-(3-substituted-benzyl)adenosines are optimal for potency and selectivity at A3 receptors. A series of 3-(halobenzyl)-5'-N-ethyluronamide derivatives showed the order of potency at A1 and A2a receptors of I approximately Br > Cl > F. At A3 receptors the 3-F derivative was weaker than the other halo derivatives. 5'-N-Methyl-N6-(3-iodobenzyl)adenosine displayed a Ki value of 1.1 nM at A3 receptors and selectivity versus A1 and A2a receptors of 50-fold. A series of methoxybenzyl derivatives showed that a 4-methoxy group best favored A3 selectivity. A 4-sulfobenzyl derivative was a specific ligand at A3 receptors of moderate potency. An aryl amino derivative was prepared as a probe for radioiodination and receptor cross-linking.

Hollow, spherical nitrogen-rich porous carbon shells were prepared as supercapacitor electrode materials through the carbonization of structure-controlled porous organic frameworks at high temperature. The structure and electrochemical properties of the resulting carbonized materials were systematically characterized. Experimental results revealed that the nitrogen-rich hollow carbon spheres obtained at 800 °C were a kind of amorphous carbon with micropores on the shell frame and with specific surface areas as high as 525 m2 g(-1). The prepared porous carbon possessed a specific capacitance of 230 F g(-1) at a current density of 0.5 A g(-1) and could retain ∼98% of the initial capacitance after 1500 successive charge-discharge cycles. Electrochemical impedance spectroscopy indicated that the material has a small equivalent series resistance (0.62 Ω). All of these values demonstrated that the prepared porous carbon is a promising supercapacitor material. The proposed method represents a simple approach towards the preparation of unique structures of nitrogen-containing porous carbon that exhibit the advantages of having a simple preparation process, a wide availability of precursors, flexible control of the structure, and an easier adjustment of the amount of heteroatoms.

The apparent proton conductivity inside a nanochannel can be enhanced by orders of magnitude due to the electric double layer overlap. A nanochannel filled with an acidic solution is thus a micro super proton conductor, and an array of such nanochannels forms an excellent proton conductive membrane. Taking advantage of this effect, a new class of proton exchange membrane is developed for micro fuel cell applications.

Interleukin-6 (IL-6) has been demonstrated to be involved in Hepatitis B virus (HBV)-associated hepatocarcinogenesis through activation of the STAT3 pathway. The sustained activation of the IL-6/STAT3 pathway is frequently associated with repression of SOCS3, which is both a target gene and a negative regulator of STAT3. However, the silencing mechanism of SOCS3 in hepatocellular carcinoma (HCC) remains to be elucidated. Here, we showed that the repression of SOCS3 and sustained activation of IL-6/STAT3 pathway in HBV-producing HCC cells were caused by HBV-induced mitochondrial ROS accumulation. Mechanistic studies revealed that ROS-mediated DNA methylation resulted in the silencing of SOCS3. Decreased SOCS3 expression significantly promoted the proliferation of HCC cells and growth of tumor xenografts in mice. Further studies revealed that HBVinduced ROS accumulation upregulated the expression of the transcription factor, Snail, which bound to the E-boxes of SOCS3 promoter and mediated the epigenetic silencing of SOCS3 in association with DNMT1 and HDAC1. In addition, we found that the expression of Snail and SOCS3 were inversely correlated in HBV-associated HCC patients, suggesting that SOCS3 and/or Snail could be used as prognostic markers in HCC pathogenesis. Taken together, our data show that HBV-induced mitochondrial ROS production represses SOCS3 expression through Snail-mediated epigenetic silencing, leading to the sustained activation of IL-6/STAT3 pathway and ultimately contributing to hepatocarcinogenesis. Cell Death and Differentiation (2016) 23, 616-627; doi:10.1038/cdd.2015.129; published online 22 January 2016 Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer death in the world.1 Chronic HBV infection and chronic liver disease that progress from hepatitis to cirrhosis are major risk factors for the development of HCC. Options for the treatment of HCC are quite limited because the molecular, cellular and environmental mechanisms that drive HBV-associated HCC pathogenesis are poorly understood.Pro-inflammatory cytokines contribute significantly to the pathogenesis of many tumor types.2 Among them, elevated IL-6 is closely related to HCC development and progression.3 Elevated IL-6 was found in patients with viral and alcoholic hepatitis and liver cirrhosis. In these conditions, IL-6 is expressed mainly by myeloid cells/leukocytes. 4 Recent studies have confirmed that upregulation of IL-6 in human HCC, where it is expressed by the cancer cells, also has a central role in a gene expression network via an autocrine signaling pathway that drives tumor development and progression.5 However, it remains unknown whether IL-6 autocrine signaling can be stimulated by HBV during hepatocarcinogensis.Reactive oxygen species (ROS) are continuously generated by cells to regulate cellular responses such as proliferation, differentiation and apoptosis. 6 Chronic virus infection may enhance ROS production and cause oxidative stress in host cells.7 Continued oxidative...

Some of the most prominent "neutral losses" in peptide ion fragmentation are the loss of ammonia and water from N-terminal glutamine. These processes are studied by electrospray ionization mass spectrometry in singly-and doubly-protonated peptide ions undergoing collision-induced dissociation in a triple quadrupole and in an ion trap instrument. For this study, four sets of peptides were synthesized: (1) QLLLPLLLK and similar peptides with K replaced by R, H, or L, and Q replaced by a number of amino acids, (2) QL n K (n ϭ 0, 1, 3, 5, 7, 9, 11), (3) QL n R (n ϭ 0, 1, 3, 5, 7, 9), and (4) QL n (n ϭ 1, 2, 3, 4, 8). The results for QLLLPLLLK and QLLLPLLLR show that the singly protonated ions undergo loss of ammonia and to a smaller extent loss of water, whereas the doubly protonated ions undergo predominant loss of water. The fast fragmentation next to P (forming the y 5 ion) occurs to a larger extent than the neutral losses from the singly protonated ions but much less than the water loss from the doubly protonated ions. The results from these and other peptides show that, in general, when N-terminal glutamine peptides have no "mobile protons", that is, the number of charges on the peptide is no greater than the number of basic amino acids (K, R, H), deamination is the predominant neutral loss fragmentation, but when mobile protons are present the predominant process is the loss of water. Both of these processes are faster than backbone fragmentation at the proline. These results are rationalized on the basis of resonance stabilization of the two types of five-membered ring products that would be formed in the neutral loss processes; the singly protonated ion yields the more stable neutral pyrrolidinone ring whereas the doubly protonated ion yields the protonated aminopyrroline ring (see Schemes). The generality of these trends is confirmed by analyzing an MS/MS spectra library of peptides derived from tryptic digests of yeast. In the absence of mobile protons, glutamine deamination is the most rapid neutral loss process. For peptides with mobile protons, dehydration from glutamine is far more rapid than from any other amino acid. Most strikingly, end terminal glutamine is by far the most labile source of neutral loss in excess-proton peptides, but not highly exceptional when mobile protons are not available. In addition, rates of deamination are faster in lysine versus arginine C-terminus peptides and 20 times faster in positively charged than negatively charged peptides, demonstrating that these formal neutral loss reactions are not "neutral reactions" but depend on charge state and stability. (J Am Soc Mass Spectrom 2007, 18, 27-36)

This paper reports on the surface modification of plastic microfluidic channels to prepare different biomolecule micropatterns using ultraviolet (UV) photografting methods. The linkage chemistry is based upon UV photopolymerization of acryl monomers to generate thin films (0.01-6 microm) chemically linked to the organic backbone of the plastic surface. The commodity thermoplastic, cyclic olefin copolymer (COC) was selected to build microfluidic chips because of its significant UV transparency and easiness for microfabrication by molding techniques. Once the polyacrylic films were grafted on the COC surface using photomasks, micropatterns of proteins, DNA, and biotinlated conjugates were readily obtained by surface chemical reactions in one or two subsequent steps. The thickness of the photografted films can be tuned from several nanometers up to several micrometers, depending on the reaction conditions. The micropatterned films can be prepared inside the microfluidic channel (on-chip) or on open COC surfaces (off-chip) with densities of functional groups about 10(-7) mol/cm2. Characterization of these films was performed by attenuated-total-reflectance IR spectroscopy, fluorescence microscopy, profilometry, atomic force microscopy, and electrokinetic methods.

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