Zeolitic imidazolate framework-8 (ZIF-8) has a “gate-opening” framework with narrow pore apertures that swing open by reorientation of 2-methylimidazolate (MeIM) linkers enforced by guest adsorption. The present study aimed to employ free energy analysis to provide insight into the mechanism of the adsorption-induced structural transition that results from the reorientation of the MeIM linkers. We combined experimental Ar adsorption at cryogenic temperatures with grand canonical Monte Carlo simulations to determine the free energy profiles as functions of the rotational angle of the MeIM linker (θIM) and bulk gas pressure. We also estimated the energy fluctuation of the system, which is crucial to discussing the structural transition from a metastable state. The results from the free energy analysis, for example, at 91 K, suggest the following conclusions: A gradual reorientation of the MeIM linkers up to θIM = 10.5° occurs with increasing gas pressure that is followed by a spontaneous structural transition to θIM = 25.5° during the adsorption process (gate opening), and then, during the desorption process, an equilibrium structural transition occurs with the opposite reorientation of the MeIM linkers from θIM = 25.5° to θIM = 10.5° (gate closing).

Apoptosis is a form of programmed cell death characterized by nuclear chromatin condensation, cell shrinkage, membrane blebbing, and DNA fragmentation. [1][2][3] The relationship between intracellular acidification and apoptosis has been studied. [4][5][6][7][8][9] In recent studies, the intracellular acidification may lead to activation of endonucleases and induce apoptosis in tumor cells. 6,8,9 In addition, the role of intracellular pH (pHi) in apoptosis and cell proliferation has been investigated. 10,11 The pHi of cancer cells has been reported to be more alkaline than that of normal cells, and the maintenance of a neutral or slightly alkaline pHi is required for cell growth, transformation, and metabolism. 10,11 Therefore, increasing the intracellular acidity by inhibiting the pHi regulatory mechanisms is cytotoxic and suggests that the pHi regulatory mechanisms may serve as targets for tumor therapy. 6,8,9 Prodigiosins (prodigiosin, metacycloprodigiosin, and prodigiosin 25-C) are red pigments produced as chromophores by various bacteria including Serratia marcescens, Pseuodomonas magnesiorubera, and others. 12 Among the prodigiosin family, prodigiosin 25-C inhibited H ϩ translocation by vacuolar-type H ϩ -ATPase (V-ATPase) without any effect on its ATP hydrolytic activity and suppressed the growth of neoplastic Chinese hamster ovary cells. 13 We previously reported that cycloprodigiosin hydrochloride (cPrG-HCl), which is a member of the prodigiosin family and is more pure and stable than the others, inhibited H ϩ translocation by V-ATPase in the same manner as other prodigiosins. 14 Recently, it was found that prodigiosins promote H ϩ /Cl Ϫ symport across vesicular membranes, resulting in an uncoupling of V-ATPase. 13,15,16 Therefore, these reports suggested that prodigiosins are useful pH regulators and may be promising anticancer drugs.To date, the nature of the interaction between the alteration of pHi and apoptosis induced by cPrG-HCl has not been investigated. Therefore, in this study, we have shown that cPrG-HCl suppressed the cellular proliferation and induced apoptosis as a result of a decrease of pHi on liver cancer cell lines. MATERIALS AND METHODSCell Culture. Six liver cancer cell lines (Huh-7, HCC-M, and HCC-T, human hepatocellular carcinoma; HepG2, human hepatoAbbreviations: pHi, intracellular pH; V-ATPase, vacuolar-type H ϩ -ATPase; cPrG-HCl, cycloprodigiosin hydrochloride; DMEM, Dulbecco' s modified Eagle minimum essential medium; FBS, fetal bovine serum; DMSO, dimethylsulfoxide; PBS, phosphate-buffered saline; MTT, 3-(4,5-dimethylthiazol-2-2-yl), 5 diphenyltetrazolium bromide; IC 50 , 50% inhibitory concentration; BCECF-AM, 2Ј,7Ј-bis-(Carboxyethyl)-5(6Ј)-carboxyfluorescein acetoxymethyl ester; TUNEL, terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling.From the

We synthesized size-controlled zeolitic imidazolate framework (ZIF-8) nanoparticles using a T-type micromixer. The nanocrystallization of ZIF-8 proceeds by a rapid coordination reaction of Zn 2+ ions and 2-methylimidazole (2-MeIM) in a highly concentrated solution. Therefore, a rapid mixing of the raw materials is required to control the size and morphology of ZIF-8 nanoparticles. First, we prepared ZIF-8 nanoparticles at various flow rates of raw materials to investigate the mixing performance of a T-type micromixer. The size of the ZIF-8 nanoparticles decreased with an increase in flow rates at Reynolds number (Re) < 2000 (regarded as laminar flow). However, the size and shape of the resultant nanoparticles did not depend on the flow rates at Re > 2000 (transition state between laminar flow and turbulent flow), demonstrating the high mixing performance. Further, we systematically examined the effects of temperatures and [2-MeIM]/[Zn 2+ ] ratios on the resultant ZIF-8 nanoparticles to elucidate the formation mechanism and to optimize the conditions for the synthesis of smaller ZIF-8 nanoparticles. Through a detailed analysis, we concluded that the requisite conditions are lower temperatures and higher [2-MeIM]/[Zn 2+ ] ratios, which affect the nucleation process and the particle growth process, respectively. Finally, we examined the adsorption properties of the resultant smaller ZIF-8 nanoparticles. We found that the amount of adsorbed N 2 gas for the ZIF-8 nanoparticles synthesized by our method is higher than the amount for a conventional ZIF-8 sample, and the adsorption rate is faster because of the

Ductography and fiberoptic ductoscopy are useful procedure in guiding subsequent breast surgery in the treatment of nipple discharge.

No abstract

A case of hepatoid carcinoma of the ovary in a 61-year-old Japanese woman, who showed high serum levels of alpha-fetoprotein and CA125, is reported. Grossly, the left ovarian tumor, which measured 12 x 9 cm, was solid and multinodular. Histologically, the tumor resembled hepatocellular carcinoma by its architectural and cytological features. Liver cell differentiation was indicated functionally by the immunohistochemical detection of alpha-fetoprotein and protein induced by vitamin K absence or antagonist II (PIVKA-II) and by positive bile production, and the hepatocellular differentiation was structurally in accord with keratin 7, 8 and 18 expression. CA125 expression, commonly present in ovarian surface epithelial carcinomas, suggested that this neoplasm originated from ovarian common epithelial cells. There are only nine such cases in the literature. A review of these cases reveals that hepatoid carcinoma of the ovary occurs exclusively in postmenopausal women (mean age, 62.7 years) and that the prognosis is poor.

Genistein, a prominent isoflavone in soy products, produced dose- and time-dependent in vitro growth inhibition at high concentrations (at least 185 microM) with an IC50 of 7.0-274.2 microM after 72 h incubation in four breast cancer cell lines (DD-762, Sm-MT, MCF-7 and MDA-MB-231) and one breast epithelial cell line (HBL- 100) of human and animal origin; it stimulated estrogen-receptor-positive MCF-7 cells at low concentrations (3.7 nM-37 microM). Genistein-exposed cells underwent apoptosis, confirmed by G2/M arrest followed by the appearance of a sub-G1 fraction in cell-cycle progression, and by a characteristic cell ultrastructure. The apoptosis cascade was due to up-regulation of Bax protein, down-regulation of Bcl-XL protein, and activation of caspase-3. Genistein acted in synergism with eicosapentaenoic acid (EPA), a fish oil component, on human breast cancer MCF-7 cells (genistein > 93.2 microM and EPA > 210.9 microM) and on MDA-MB-231 cells (genistein > 176.1 microM and EPA > 609.3 microM). Dietary intake of genistein in combination with EPA may be beneficial for breast cancer control.

The design of dynamically self-assembled systems is of high interest in science and technology. Here, we report a unique cascade in the self-ordering of droplets accompanied by a dewetting transition. The dynamic self-emergent droplets are observed when a thin liquid layer of an immiscible fluorocarbon oil (perfluorooctyl bromide, PFOB) is placed on a water surface. Due to the gradual evaporation of PFOB, a circular PFOB-free domain appears as a result of a local dewetting transition. A circular pearling structure is generated at the rim with the growth of the dewetting hole. As the next stage, linear arrays of droplets are generated in a radial manner from the centre of the hole. These one-dimensional arrangements then evolve into two-dimensional hexagonal arrays of microdroplets through collective rhythmical shrinking/expanding motions. The emergence of such dynamic patterns is discussed in terms of the nonlinear kinetics of the dewetting transition under thermodynamically dissipative conditions.