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A two-dimensional molybdenum disulfide (MoS2) nanosheet, as a new type of inorganic material with high hydrophobicity and excellent physicochemical stability, holds great application potential in t...

PurposeWhile numerous epidemiological studies have indicated that omega-3 polyunsaturated fatty acids have anticancer properties in various cancers, the effects and mechanisms of eicosapentaenoic acid (EPA) in ovarian cancer cell growth are poorly understood.Materials and MethodsES2 ovarian clear cell carcinoma cells and SKOV3 adenocarcinoma cells were treated with palmitic acid or EPA, followed by flow cytometry and cell counting to measure apoptosis and proliferation, respectively. A modified protein lipid overlay assay was used to further verify whether EPA was a ligand of G protein–coupled receptor 30 (GPR30) in ES2 cells. The levels of apoptosis-related genes, phosphorylated AKT, and phosphorylated ERK1/2 were detected to explore the underlying mechanism. Finally, inhibitory effect of EPA on tumor growth via GPR30 was determined in vitro and in vivo.ResultsEPA suppressed ES2 ovarian clear cell carcinoma cells growth via GPR30, a novel EPA receptor, by inducing apoptosis. As a ligand of GPR30, EPA activated the GPR30-cAMP– protein kinase A signaling pathway. When GPR30 was suppressed by siRNA or its inhibitor G15, the antiproliferative action of EPA was impaired. Furthermore, EPA inhibited tumor growth by blocking the activation of AKT and ERK. In the mouse xenograft model, EPA decreased tumor volume and weight through GPR30 by blocking tumor cell proliferation.ConclusionThese results confirm that EPA is a tumor suppressor in human ovarian clear cell carcinoma cells and functions through a novel fatty acid receptor, GPR30, indicating a mechanistic linkage between omega-3 fatty acids and cancers.

This study aims to investigate the relationship between breast white adipose tissue (WAT) inflammation and being overweight or obese, menopausal status, and metabolic syndrome-related indicators in breast cancer patients as well as the association between adipocyte size and the severity of WAT inflammation and body mass index (BMI). The crown-like structures (CLS-B) formed by macrophages surrounding dying or dead adipocytes can be used to identify breast WAT inflammation. In this study, breast WAT and fasting blood from 136 Chinese women with breast cancer were collected for analysis. Cluster of differentiation 68 (CD68) immunohistochemical staining was performed to identify CLS-B, and the adipocyte size was measured by hematoxylin and eosin staining. The results showed that breast WAT inflammation usually occurs in overweight/obese breast cancer patients, and the severity of inflammation is positively correlated with adipocyte hypertrophy. We did not observe a direct association between WAT inflammation and menopausal status. In addition, the presence of WAT inflammation is associated with abnormalities in circulating factors associated with metabolic syndrome such as higher serum lipid, glucose, and C-reactive protein levels. Overweight/obese breast cancer patients may be more prone to breast WAT inflammation and may be associated with abnormalities in circulatory markers associated with metabolic syndrome.

A Gram-negative, aerobic, non-flagellated and ovoid- or rod-shaped bacterium, designated strain SM1902T, was isolated from the sediment sampled at the Jia River estuary, Yantai, PR China. The strain grew at 10–37 °C (optimum, 25–30 °C), pH 6.0–10.0 (pH 7.0) and with 0.5–13.0 % (w/v) NaCl (2.5%). It reduced nitrate to nitrite, but did not produce bacteriochlorophyll a. The results of phylogenetic analysis based on 16S rRNA gene sequences revealed that strain SM1902T constituted a separated lineage within the family Rhodobacteraceae and was closely related to Meridianimarinicoccus roseus TG-679T and Phycocomes zhengii LMIT002T with 96.1 and 94.3 % 16S rRNA gene sequence similarities, respectively. The predominant cellular fatty acid was summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, an unidentified aminolipid and an unidentified lipid. The sole respiratory quinone was ubiquinone-10. The in silico DNA–DNA hybridization values between strain SM1902T and Meridianimarinicoccus roseus TG-679T and Phycocomes zhengii LMIT002T were 19.6 and 19.5 %, respectively; and the average nucleotide identity values between them were 76.1 and 74.2 %, respectively. The genomic DNA G+C content of strain SM1902T was 58.2 mol%. Based on the phylogenetic, chemotaxonomic and phenotypic data obtained in this study, strain SM1902T is considered to represent a novel species in a new genus within the family Rhodobacteraceae , for which the name Fluviibacterium aquatile gen. nov., sp. nov. is proposed. The type strain is SM1902T (=KCTC 72045T=MCCC 1K03596T=CCTCC AB 2018346T).

A two-dimensional molybdenum disulfide (MoS2) nanosheet, as a new type of inorganic material with high hydrophobicity and excellent physicochemical stability, holds great application potential in the preparation of a high separation performance organic–inorganic hybrid membrane. In this work, high hydrophobic MoS2 was embedded in hydrophobic polyether copolymer block amide (PEBA) to prepare PEBA/MoS2 organic–inorganic hybrid membranes. The structure, morphology, and hydrophobicity of the hybrid membrane were characterized by scanning electron microscopy, thermogravimetric analysis, contact angle goniometry, X-ray diffraction, infrared spectroscopy analysis, and atomic force microscopy. The effect of embedding of MoS2 on the swelling degree and pervaporation separation performance of the PEBA/MoS2 hybrid membrane was studied with a 1.0 wt % pyridine dilute solution. The results indicated that with increasing the MoS2 content, the separation factor of PEBA/MoS2 increased first and then decreased, while it showed a downward trend in the permeation flux. When the MoS2 content in the PEBA/MoS2 hybrid membrane was 10.0 wt %, the permeation flux was 83.4 g m–2 h–1 (decreased by 21.5% compared with the pure PEBA membrane), and the separation factor reached a maximum value of 11.11 (increased by 37.6% compared with the pure PEBA membrane). Meanwhile, the effects of feed temperature on the pervaporation separation performance of PEBA/MoS2 hybrid membranes were also studied. In addition, as the PEBA/MoS2 hybrid membrane has excellent thermal stability, it is expected to be a promising material for recovering pyridine from wastewater.

Bromodomain testis-specific factor (BRDT) is a member of the bromodomain and extra-terminal (BET) family proteins. Its expression and potential functions in ovarian cancer were examined. We show that BRDT is overexpressed in human ovarian cancer tissues and in established (CaOV3)/primary ovarian cancer cells. However, its expression is low in ovarian epithelial tissues and cells. Significantly, shRNA-induced silencing or CRISPR/Cas9-mediated knockout of BRDT inhibited ovarian cancer cell growth, viability, proliferation and migration, and induced significant apoptosis activation. Conversely, exogenous overexpression of BRDT, by a lentiviral construct, augmented CaOV3 cell proliferation and migration. In CaOV3 cells expression of two key BRDT target genes, polo-like kinase 1 (PLK1) and aurora kinase C (AURKC), was downregulated by BRDT shRNA or knockout, but upregulated with BRDT overexpression. In vivo, xenograft tumors-derived from BRDT-knockout CaOV3 cells grew significantly slower than control tumors in severe combined immunodeficient (SCID) mice. Furthermore, intratumoral injection of BRDT shRNA lentivirus potently inhibited the growth of primary ovarian cancer xenografts in SCID mice. Downregulation of PLK1 and AURKC was detected in BRDT-knockout and BRDT-silenced tumor tissues. Collectively, BRDT overexpression promotes ovarian cancer cell progression. Targeting BRDT could be a novel strategy to treat ovarian cancer.

MoS2, a typical two-dimensional transition metal sulfide nanomaterial, has attracted much attention for supercapacitor electrode materials due to its high theoretical capacity. Herein, MoS2 nanosheets grown on a hierarchical porous carbon (HPGC) derived from pomelo peel are prepared via hydrothermal method. The curled MoS2 nanosheets grow and uniformly distribute on the conductive hierarchical porous carbon matrix, which made the electrodes materials possess a high specific surface area (320.2 m2 g−1). Simultaneously, the novel structure enhances the conductivity of MoS2, alleviates capacity attenuation and guarantees the interface stability. Furthermore, the MoS2/HPGC shows a great enhancement in supercapacitor performance and deliver a remarkable specific capacitance of 411.4 F g−1 at the current density of 0.5 A g−1. The initial capacitance retention rate is approximately 94.3% after 2000 cycles. It turns out that the synergistic effects between the MoS2 nanosheets and HPGC contribute to high specific capacity, excellent rate performance and ultra-long cycle life. This work provides a new idea for the design and development of MoS2 composites as the electrode materials of supercapacitors.

The bicyclic 1-aza-2-azoniaallenium salt intermediates, generated from the azoester species upon treatment with a Lewis acid, have been demonstrated to participate in Huisgen-type cycloaddition with nitriles to result in the formation of fused 6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-d][1,4]diazepinium salts. This transformation is interpreted as a regular [3++2] cycloaddition between intermediates as the reactive 1,3-monopole reactants and nitriles as the nucleophilic reagents followed by spontaneous [1,2]-cationic rearrangement. The azoester precursors were easily accessible via oxidation of the corresponding hydrazones using hypervalent iodine oxidant PhI(OAc)2 under mild conditions. The [1,2,4]triazolodiazepine compounds represent a class of N-containing biologically important heterocycles with a new type of scaffold.

To investigate the associations between serum levels of matrix metalloproteinase 7 (MMP7), surfactant protein D (SPD), interleukin 18 (IL-18) and chemokine ligand 18 (CCL18) with dermatomyositis and polymyositis-associated interstitial lung disease (DM/PM-ILD) and evaluate their prognostic values in the disease.Seventy-eight patients with multiple disciplinary team diagnosis of DM/PM-ILD were enrolled and classified as anti-melanoma differentiation-associated protein 5 antibody (MDA5)-ILD, anti-synthetase antibodies (ARS)-ILD and other antibodies-ILD upon autoantibodies profiles. Clinical data were collected and serum levels of four biomarkers were analysed. The primary endpoint was 3-month mortality. The cut-off values of biomarkers for mortality were figured out by receiver operating characteristic (ROC) analysis. Cox regression was performed to evaluate predictive values.Serum levels of MMP7 (p=0.036), SPD (p0.001), IL-18 (p0.001) and CCL18 (p0.001) in patients with DM/PM-ILD were significantly higher than healthy controls with levels of MMP7 (p=0.029) and SPD (p=0.029) in patients with MDA5-ILD significantly lower than patients with ARS-ILD. The 3-month mortality in MDA5-ILD was 54.5% (12/22). Multivariate analysis showed that age (p=0.001, HR 1.151, 95% CI 1.063-1.247) and an increased level of SPD (75.90ng/ml, p=0.005, HR 16.411, 95% CI 2.369-113.711) were significant predictors for 3-month mortality in patients with MDA5-ILD.Elevated serum biomarkers were associated with DM/PM-ILD with differential levels between MDA5-ILD and ARS-ILD. Age and an increased SPD had prognostic values for predicting short-term mortality in patients with MDA5-ILD. Our study was important in providing a clue for understanding the classification and prognosis of DM/PM-ILD.

The development of inexpensive and effective adsorbents for the highly efficient removal of arsenic (As) and antimony (Sb) from water is of great importance for the environment and human health. In the present study, magnetic bio-sludge (MS) containing activated sludge and magnetite (Fe3O4) nanoparticles (diameter: 2–25 nm) was investigated as an adsorbent. MS was synthesized by a facile co-precipitation method and characterized using various physicochemical methods. MS featured a macroporous structure with a surface area of 78 m2 g−1 and a pore volume of 0.53 cm3 g−1. MS could be readily and easily separated from water using an external magnetic field. Importantly, MS could be applied for the removal of As(V) and Sb(V) contaminants from water. It exhibited high stability, ultrafast adsorption/separation rates, and a large adsorption capacity. Moreover, it achieved near-complete removal of As(V) and Sb(V) in 10 μg L−1 solutions. Its high adsorption performance was almost unaffected by the presence of ion interferents in solution. Thus, the present study demonstrates the potential of MS as an adsorbent for the removal of As(V) and Sb(V) from groundwater to meet environmental and public health standards.

The effects of grain sizes and oxygen impurities on thermal conductivity in aluminum nitride (AlN) ceramics has been calculated by density functional perturbation theory (DFPT) and quasi-harmonic approximation (QHA) combined with Debye theory in the paper. From 300K up to 1000K, the predicted thermal properties are compared with experimental data. The agreements with experiment suggest that the theoretical method used in the paper is an effective approach. From our theoretical study, the reduction of thermal conductivity is greater between grain sizes of 1μm and 5μm, while it’s smaller between 8μm and 10μm. Oxygen defects bring about greater influence on thermal conductivity at low temperature than at high temperature. The influence of the oxygen defect is not as significant as the grain sizes when the oxygen concentrations are less than 0.70 at. %, so it’s more important to increase the grain sizes than reduce the oxygen contents in the preparation process to achieve high thermal conductivity AlN ceramics.

Thermal management is one of the major challenges in the development of high powered LEDs. The effects on thermal conductivity of impurity concentration and thickness are studied in Cu doped AlN (AlN:Cu) phosphor in the paper. Density functional perturbation theory (DFPT) and quasi-harmonic approximation (QHA) combined with Debye model are used in the calculation. The results show that thermal conductivity of AlN:Cu is higher than that of Nd doped ytterbium aluminum garnet (YAG:Nd) from 300K up to 1000K thus the temperature of LEDs can be controlled efficiently. Thermal conductivity increases with the rising of thickness while it decreases with the addition of Cu concentration. The influence of Cu concentration on thermal conductivity depends on temperature. The lower the temperature is, the bigger the influence.

Thermal conductivity of aluminum nitride (AlN) has been calculated by density functional perturbation theory (DFPT) and quasi-harmonic approximation (QHA) combined with Debye theory in the paper. Debye temperature is evaluated respectively from sound velocity and heat capacity. From 300K up to 1000K, the predicted thermal properties in pure crystal AlN based on these two Debye temperatures are compared with each other and the latter shows excellent agreement with Slack’s experimental data. The relative difference based on Debye temperature from heat capacity is within the limits of ±5.5%. This agreement with experiment is due to the Debye temperature derived from capacity contains the temperature effect while describe the three phonon process.

Background:Cervical cancer is one of the leading causes of cancer mortality in women, which seriously threatens the health of women worldwide. Platelet (PLT)-related parameters, including PLT count, mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW), are correlated with tumor prognosis.Methods:In total, 110 patients with cervical carcinoma were recruited in this study. The patients were divided into 2 groups according to the receiver operating characteristic analysis cutoff values of PLT, MPV, PCT, or PDW. The post-/preradiotherapy ratios were defined as the rate of preradiotherapy PLT-related parameters counts and the corresponding ones obtained after radiotherapy.Results:Higher pretreatment PLT level was correlated with Higher Federation of Gynecology and Obstetrics (FIGO) stage (II). Higher pretreatment PLT level was correlated with worse progression-free survival (PFS) and overall survival (OS). Increased post-/preradiotherapy ratio of PLT was correlated with worse PFS and OS. Changes in PCT, MPV, or PDW levels had no effects on PFS or OS. Cox regression analysis model indicated that larger tumor size, higher pretreatment PLT level, and increased post-/preradiotherapy PLT ratio were independently associated with worse PFS; higher FIGO stage (II) and increased post-/preradiotherapy PLT ratio were independently associated with worse OS.Conclusion:Pretreatment PLT level and increased post-/preradiotherapy PLT ratio are correlated with outcomes of cervical cancer.

In this paper, we carry out linear response calculation to determine the phonon density of states and the thermodynamic properties of the wurtzite and zinc-blende AlN by using the norm-conserving pseudo-potential method. The optimized lattice constant is in good agreement with the available experimental data. The internal energies increase almost linearly with temperature and the phonon free energy curves move down with increasing temperature in both structures. The zero value of the lattice vibration free energy appears at temperature 707K in wurtzite and 728K in zinc-blende AlN respectively. The specific heat capacity of the wurtzite AlN is higher than that of the zinc-blende AlN at room temperature owing to the difference of the phonon spectra.

The mechanisms of the title reactions between 1-aza-2-azoniaallene cations and carbodiimides in the gas phase have been examined using the Becke-3-parameter-Lee-Yang-Parr (B3LYP) at 6-31++G** level. The theoretical results revealed that the reaction is a domino reaction that comprises two consecutive reactions: an ionic [3+2] cycloaddition reaction between 1-aza-2-azoniallene cation and carbodiimide to yield the cycloadduct 3 and then a [1,2]-shift to yield the thermodynamically more stable adduct 4. Both stepwise and concerted pathways are accessible in the first cycloaddition in the model reaction. The activation barriers of them are almost equivalent. For the [1,2]-shift reactions, both of the electron-withdrawing chlorine substituent and the electron-releasing methyl substituent on the 1-aza-2-azoniaallene cation can facilitate the reaction but have little effects when substituted in the carbodiimide moiety. The model reaction has also been investigated at the QCISD (quadratic configuration interaction using single and double substitutions)/6-31++G** and CCSD(T) (coupled cluster calculations with single and double excitations and a perturbative estimate of triple contributions calculations)/6-31++G** levels as well as by the density functional theory. In addition, solvent effects with the isodensity-surface polarized continuum model are also reported for all the reactions. In solvent dichloromethane, the cycloadducts of all the reactions, except model reaction and reaction d, were obtained from reactants directly as the result of the solvent effect. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011

A novel pentaheterocyclic ring system derived from (5α)-cholestan-3-one, i.e. [1R-[1α(R*),3aβ,3bα,5aβ,12aα,12bβ,14aα]]-1-(1,5-dimethylhexyl)-1,2,3,3a,3b,4,5,11,12,12a,12b,13,14,14a-tetradecahydro-8,12a,14a-trimethyl-9-(2,4,6-trichlorophenyl)-cyclopenta[5,6]naphtho[2,1-d][1,2,4]triazolo[1,5-a]azepinium hexachloroantimonate (6) has been synthesized via the reverse-electron-demand 1,3-dipolar cycloaddition of the 1-aza-2-azoniaallene cation 4 to the triple bond of acetonitrile followed by ring enlargement. The structure of 6 was determined by NMR, IR and high-resolution mass spectra, and unequivocally confirmed by X-ray crystallographic analysis. The title compound crystallizes in monoclinic class under the space group P2-1 with a = 8.163(3) A, b = 11.214(4) A, c = 24.191(9) A, α = 90°, β = 97.740(5)°, and γ = 90°. The five-membered triazole ring is essentially planar and aromatic, while the seven-membered azepine ring is not planar, but adopts a chair-like conformation. [1R-[1α(R*),3aβ,3bα,5aβ,12aα,12bβ,14aα]]-1-(1,5-dimethylhexyl)-1,2,3,3a,3b,4,5,11,12,12a,12b,13,14,14a-tetradecahydro-8,12a,14a-trimethyl-9-(2,4,6-trichlorophenyl)-cyclopenta[5,6]naphtho[2,1-d][1,2,4]triazolo[1,5-a]azepinium hexachloroantimonate (6) has been synthesized and unequivocally confirmed by X-ray crystallographic analysis.

In this paper, 5-pair InAs/GaAs QDIPs with tunable dark current blocking barrier resulting from a p-type doped GaAs layer are fabricated. With a proper choice of the p-type doping density, temperature- insensitive detectivities up to 110 K at low applied voltage 0.8 V are obtained. The phenomenon is attributed to the one order of magnitude increase of photocurrent with increasing temperature resulting from the increase of transition probability with more available empty excited states at higher temperature. The results have shown superior high-temperature operation of the asymmetric QDIP structure than the symmetric device.

In this study, we develop a novel way to fabricate InGaN/GaN LED chips with special shape for improving the output power. Crack-free shaped GaN islands were first prepared on c-axis sapphire substrate by using HVPE selective area growth. By doing so, GaN islands with flat top surface and inclined side faces are obtained. Then, the InGaN/GaN LED structure was grown on the top surface of the GaN island subsequently. The output powers of the p-side up and the p-side down shaped LED chip are 1.4 and 2.2 times the output power of the cubic chip, respectively. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The mechanism of the samarium-catalyzed 1,5-regioselective azide-alkyne [3 + 2]-cycloaddition (SmAAC) reaction has been examined with quantum mechanical calculations at the B3LYP/6-31+G(d,p) level of theory with ECP51MWB on Sm. Four stepwise pathways were located, with two leading to the 5-endocyclic 1,5-disubstituted 1,2,3-triazole product PSmL2 (paths 1 and 2) and the other two to the exocyclic product ExoPSmCl2 (path 3) as well as 1,4-disubstituted 1,2,3-triazole RegPSmL2 (path 4), respectively. Among them, path 2 (R-COM1-TS12-COM2-TS23-COM3-TS3P-PSmL2) is the most favored one both in the gas phase and in toluene solution, which is in good agreement with the experimental data. Moreover, 1,1-insertion forming COM2 in path 2 is the rate-determining step. The computational results also infer that the participation of samarium catalyst changes the distribution of the electrostatic potential on the reactants' surface, which determines the polarization direction of the reactants and formation of different intermediates (COM1 and RegCOM1), and finally affects the regioselectivity. When solvent corrections for toluene are considered, the 1,1-insertion process is discouraged, while the intramolecular [1,3]-shift reaction is facilitated.

The mechanism of the Lewis acid-catalyzed oxy-2-azonia-Cope rearrangement between β,γ-unsaturated ketones and imines leading to the formation of homoallylic amides and lactams has been theoretically studied using the B3LYP density functional theory methods enhanced with a polarized continuum solvation model. It was predicted that the SnCl 4 -catalyzed tandem dimerization/oxy-2-azonia- Cope rearrangement mechanism is highly preferred over the uncatalyzed version as well as the plausible tandem dimerization/Prins rearrangement mechanism. A two-step pathway was found for the overall reaction, involving the initial nucleophilic dimerization followed by the (3,3)-sig- matropic rearrangement. The latter phase was considered to be the rate-limiting step. Particularly, the transition states account for the experimentally observed stereoselectivities and Z/E selectivities. The high stereoselectivity and Z/E selectivity for the chiral cyclic substrates can be attributed to the relative conformational stabilities of TSs. Moreover, distortion-interaction analysis has been performed in an attempt to quantify the various contributions to the reac- tion transition states, and it revealed that interaction energy E II and distortion energy ∆Ed associated with the forma- tion of the 2COM2 complex are the determining factors to

In addition to the typical size, Cryptococcus neoformans can enlarge its size to form titan cells during infection, and its diameter can reach up to 100 μm. Clinical reports about cryptococcal titan cells are rare. Most studies focus on aspects of animal models of infection with titan cells. Herein, we report the clinical and imaging characteristics and histopathologic features of 3 patients with titan cells and 27 patients with pathogens of typical size, and describe the morphological characteristics of titan cells in details. Histologically, 3 patients with titan cells show necrosis, fibrosis and macrophage accumulation. The titan cells appear in necrotic tissue and between macrophages, and have thick wall with unstained halo around them and diameters range from 20 to 80 μm with characteristic of narrow-necked single budding. There are also organisms with typical size. All 27 patients with normal pathogens show epithelioid granulomatous lesions. There is no significantly difference in clinical and imaging feature between the two groups. Cryptococcus neoformans exhibits a striking morphological change for the formation of titan cells during pulmonary infection, which will result in misdiagnosis and under diagnosis. The histopathological changes may be new manifestation, which need to be further confirmed by the study with animal models of infection and the observation of more clinical cases. Careful observation of the tissue sections is necessary.

In the title compound, C23H27NO4, the γ-lactam ring adopts an envelope conformation. An O—H⋯O hydrogen bond links the mol­ecules into a chain which runs parallel to the c axis.

The mechanisms of cycloaddition reactions between 1-aza-2-azoniaallene cations 1 and acetylenes 2 have been investigated using the global electrophilicity and nucleophilicity of the corresponding reactants as global reactivity indexes defined within the conceptual density functional theory. The reactivity and regioselectivity of these reactions were predicted by analysis of the energies, geometries, and electronic nature of the transition state structures. The theoretical results revealed that the reaction features a tandem process: an ionic 1,3-dipolar cycloaddition to produce the cycloadducts 3 H-pyrazolium salts 3 followed by a [1,2]-shift affording the thermodynamically more stable adducts 4 or 5. The mechanism of the cycloaddition reactions can be described as an asynchronous concerted pathway with reverse electron demand. The model reaction has also been investigated at the QCISD/6-31++G(d,p) and CCSD(T)/6-31++G(d,p)//B3LYP/6-31++G(d,p) levels as well as by the DFT. The polarizable continuum model, at the B3LYP/6-31++G(d,p) level of theory, was used to study solvent effects on all the studied reactions. In solvent dichloromethane, all the initial cycloadducts 3 were obtained via direct ionic process as the result of the solvent effect. The consecutive [1,2]-shift reaction, in which intermediates 3 are rearranged to the five-membered heterocycles 4/5, is proved to be a kinetically controlled reaction, and the regioselectivity can be modulated by varying the migrant. The LOL function and RDG function based on localized electron analysis were used to analysis the covalent bond and noncovalent interactions in order to unravel the mechanism of the title reactions.

This study was performed to investigate the reactivity of azocarbenium salts derived from 5α-cholestan-3-one towards 1,3-dipolar cycloaddition reactions with inverse electron-demand to produce unprecedented steroidal heterocyclic derivatives, i.e. [1,2,4]-triazolo-annulated 3-aza-A-homocholestanes 8 and 11 and picrates 12. The synthetic steps were comprised of oxidizing hydrazones 3 with tert-butyl hypochlorite to germinal chloroazo compounds 4, generation of the 1-aza-2-azoniaallene cations 5 by action with equimolar antimony pentachloride and interception with nitrile and alkyne molecules by cycloaddition to the triple bond followed by ring enlargement. The structure of the compounds was principally established on the basis of the analytical and spectral data along with the previously published X-ray diffraction analysis on 8a.

AIM: To explore germline hypermethylation of the tumor suppressor genes MLH1, CDH1 and P16INK4a in suspected cases of hereditary gastric cancer (GC). METHODS: A group of 140 Chinese GC patients in whom the primary cancer had developed before the age of 60 or who had a familial history of cancer were screened for germline hypermethylation of the MLH1, CDH1 and P16INK4a tumor suppressor genes. Genomic DNA was extracted from peripheral blood leukocytes and modified by sodium bisulfite. The treated DNA was then subjected to bisulfite DNA sequencing for a specific region of the MLH1 promoter. The methylation status of CDH1 or P16INK4a was assayed using methylation-specific PCR. Clonal bisulfite allelic sequencing in positive samples was performed to obtain a comprehensive analysis of the CpG island methylation status of these promoter regions. RESULTS: Methylation of the MLH1 gene promoter was detected in the peripheral blood DNA of only 1/140 (0.7%) of the GC patient group. However, this methylation pattern was mosaic rather than the allelic pattern which has previously been reported for MLH1 in hereditary non-polyposis colorectal cancer (HNPCC) patients. We found that 10% of the MLH1 alleles in the peripheral blood DNA of this patient were methylated, consistent with 20% of cells having one methylated allele. No germline promoter methylation of the CDH1 or P16INK4a genes was detected. CONCLUSION: Mosaic germline epimutation of the MLH1 gene is present in suspected hereditary GC patients in China but at a very low level. Germline epimutation of the CDH1 or P16INK4a gene is not a frequent event.

Using the National Highway transportation hub system planning of Beijing as the background, and based on the system functions of highway transportation hubs, this article analyzes the different operational requirements to hub systems on primary functions for different users. Basic principles of transport system planning, system theory and control theory will be used on putting forward a program. This program will have multi-level hierarchical control as the oriented control work, feedback control as the auxiliary control work and high quality service as the core. This article establishes an overall model of highway passenger transport hub systems, and a structure model with the organization and management, production and service, communication and information and ancillary service of it. These methods and models can be used as advices to other highway traffic hub systems.

Up to date, there is few satisfactory pharmacotherapy, except for aspirin and heparin, to stop the preeclampsia progression. Although the mechanism of preeclampsia is poorly understood, it has been proven to be associated with coagulation activation. Researches on prophylactic and therapeutic application of anticoagulants may benefit the clinical aspects of preeclampsia individuals. This study aimed to evaluate the effects of Danshensu on maternal syndrome in phosphatidylserine/phosphatidylcholine (PS/PC) microvesicle induced-mouse model.Sixty-six preeclampsia-like pregnant mice, induced by PS/PC microvesicle administration, were randomly divided into six groups. From days 5.5 to 16.5 of pregnancy, each group was respectively treated as follows: a) mice in group C (n = 12, control group) were injected with 100 microl of filtered phosphate-buffered saline into the tail vein every day; b) group PE (n = 15, preeclampsia model group) were injected in the same way with 100 microl of filtered PS/PC vesicle suspension; c) group H (n = 9, group treated with heparin) were injected with 1 unit heparin together with PS/PC vesicle suspension; d) group A (n = 10, group treated with aspirin) were injected with 20 microg/g aspirin-DL lysine as well; e) group LD (n = 10, group treated with low-dose Danshensu) were injected with 10 microg/g Danshensu; and f) group HD (n = 10, group treated with high-dose Danshensu) were injected with 30 microg/g Danshensu. Systolic blood pressure, total urinary protein levels, blood tests for some hemostatic function parameters (mean platelet counts, plasma antithrombin III activity (AT-III), D-D dimmer levels, and thrombin time), fibrin deposition by phosphotungstic acid hematoxylin staining, and thrombomodulin expression by immunohistochemistry staining in placentas were examined as indices for maternal syndrome.Heparin showed significant effects on maternal syndrome of preeclampsia such as hypertension and proteinuria, and different doses of Danshensu also presented the certain effects. High-dose Danshensu and aspirin all demonstrated better effects than low-dose Danshensu on decreasing blood pressure to normal level, while high-dose Danshensu demonstrated better effects than aspirin and low-dose Danshensu on decreasing proteinuria to normal level. As to Danshensu's effects on hemostatic function, high- and low-dose Danshensu's marked effects on increasing the plasma AT-III activity were the same as that of aspirin and inferior to that of heparin. High-dose Danshensu's better effect on elevating the platelet counts was superior to low-dose Danshensu and aspirin. Low-dose Danshensu's obvious effect on decreasing D-D levels was close to heparin and superior to high-dose Danshensu and aspirin. High- and low-dose Danshensu's significant effects on reduced thrombin time level are same to heparin. Different anticoagulants all played improvement roles in placental fibrin depositions, but heparin and high-dose Danshensu's roles on lowering thrombomodulin expression in placentas were superior to low-dose Danshensu and aspirin. However, anticoagulant function of high-dose Danshensu was still inferior to heparin. We found long-term use of heparin and aspirin, in spite of low-dose administration, could raise the risk of bleeding such as placental abruption and intestinal hemorrhage. But no any side effect was observed in mice treated with different doses of Danshensu in our study.Danshensu has proven to be effective and safe in ameliorating the prognosis of maternal syndrome in a preeclampsia mouse model. We suggest long-term provision of low-dose Danshensu in pregnancy, leading to an improvement of preeclampsia syndrome with considerable maternal safety.

The title compound, C(24)H(41)NO, is a new derivative of the anti-HIV steroid 17β-(N-tert-butyl-amino-carbon-yl)androst-4-en-3-one. There are four rings in the structure and these are trans-fused. The three six-membered rings exhibit chair conformations, while the five-membered ring adopts an envelope conformation.

AIM: To give a comprehensive report of E-cadherin gene (CDH1) variations in a population at a high risk for gastric cancer (GC). METHODS: The samples consisted of 178 men and 58 women with a mean age of 62.3 ± 9.4 years and an age range of 30-84 years. A total of 240 cancer-free controls were recruited (mean age of 61.8 ± 10.1 years, age range of 26-82 years). Samples were screened for CDH1 germline mutations by high-resolution melting analysis or directly sequencing. Luciferase reporter assay, RNA splicing assay and bioinformatic analysis were used to evaluate the effect of mutations. RESULTS: Four novel CDH1 sequence alterations were identified in GC patients including a G>T transition 49 bp before the start codon; a three-nucleotide deletion, c.44_46del TGC; one missense mutation, c.604G>A (V202I); and one variation in the intron, c.1320+7A>G. In addition, polymorphism frequencies were observed for CDH1-164delT, -161C>A, -73A>C, c.48+6C>T, c.48+62_48+63delinsCGTGCCCCAGCCC, c.894C>T (A298A), c.1224G>A (A408A), c.1888C>G (L630V), c.2076T>C (A692A), and c.2253C>T (N751N) which is similar to the data reported in http://www.ncbi.nlm.nih.gov/projects/SNP/. RNA splicing analysis suggested that the c.1320+7A>G and c.1224G>A variations did not affect exon splicing ability. Luciferase reporter assay demonstrated that the c.-49T variation might be helpful for E-cadherin transcription, though the increase in transcription activity is limited (only 33%). SIFT score and PolyPhen analysis both demonstrated that the L630V missense mutation probably damages protein function, while the V202I variant does not. CONCLUSION: This study reveals novel mutations in sporadic GC patients which had been poorly investigated for susceptibility genes.

The title compound, C21H28N4, was synthesized. It is an unusual example of a Z′ = 4 structure without obvious pseudosymmetry. The mol­ecules are linked by numerous C—H⋯N and C—H⋯π hydrogen bonds; there are many H⋯H short contacts.

The title steroid, C29H44O7, is a new androgen derivative and a key intermediate for synthesizing novel anti-HIV steroid agents. There are fourtrans-fused rings in the structure. The three six-membered rings exhibit chair conformations, while the five-membered ring adopts an envelope conformation.

In the molecule of the title compound, C17H18N2O2, the piperidine ring adopts a half-chair form. The two benzene rings are individually planar and make a dihedral angle of 53.90°. The crystal structure is stabilized by intermolecular N—H...N hydrogen bonds and π–π stacking interactions (centroid–centroid distance = 3.962 Å).