Hydrogen bonding network dynamics of 1,2-propanediol-water binary solutions by Raman spectroscopy and stimulated Raman scattering.

Raman spectroscopy and stimulated Raman scattering (SRS) were used to investigate the hydrogen bonding (HB) network in 1,2-propanediol (1,2-PD)-water binary solutions. Abnormal changes in hydrogen bonds (HBs) were detected when V1,2-PD (volume fraction of the1,2-PD) was 0.4. In the case of Raman spectroscopy, the HB strength of water is weakened and then strengthened with the increase of 1,2-PD volume fraction. In the case of SRS, two new peaks at 3283 cm-1 and 3319 cm-1 were appeared, which demonstrated the appearance of ice-like structures near the methyl group and the weakening of HBs. Based on these phenomena, the HB structure of this binary system underwent a transition from H2O-H2O to H2O-1,2-PD when the V1,2-PD was 0.4 as V1,2-PD increased. This work serves as a reference value for the study of HB networks in alcohol-water binary solutions.

Research on the Relationship Between Meckel's Cavity Shape, Balloon Shape, and Intracapsular Pressure During Percutaneous Balloon Compression.

OBJECTIVE: Percutaneous balloon compression is a safe, effective, and minimally invasive therapeutic method for trigeminal neuralgia. Intraoperatively precise compression after the formation of the pear-shaped balloon is the key to the expected effect. In this study, we assessed the relationship between the structure of Meckel's cavity and the shape and intracapsular pressure of the balloon by preoperative magnetic resonance. METHODS: We respectively analyzed 58 patients with typical trigeminal neuralgia who underwent percutaneous balloon compression surgery in our department. Reconstruction of magnetic resonance imaging 3-dimensional fast imaging employing steady-state acquisition thin-layer scanning sequence was also performed before the operation to analyze the sagittal features of Meckel's cavity. The pressure was recorded continuously when a pear-shaped balloon was forming during the operation. Meanwhile, the balloon height/length (h/l) ratio was measured. The relationship between Meckel's cavity shape, balloon shape, and pressure was analyzed by mentioned parameters. RESULTS: The pain of 57 patients was relieved immediately after the operation, and the effective rate was 98.27% (57 of 58); Recurrence in 2 cases within the median follow-up time (7.5 months). Meckel's cavity classification on magnetic resonance showed that the clubbing type, oval type, and flat type accounted for 31.1% (18 of 58), 58.6% (34 of 58), and 10.3% (6 of 58), respectively. The results demonstrated that the intracapsular pressure was low, while the h/l ratio of Meckel's cavity was relatively high. We also found the corresponding pressure results when the ratio was low. However, no significant difference was found between the balloon h/l ratio and Meckel's cavity h/l ratio. CONCLUSIONS: Intracapsular pressure of balloon is negatively correlated with the h/l ratio of Meckel's cavity. The individually differentiated formation of the pear-shaped balloon has little correlation with the sagittal shape of Meckel's cavity.

How Learners' Corrective Feedback Beliefs Modulate Their Oral Accuracy: A Comparative Study on High- and Low-Accuracy Learners of Chinese as a Second Language.

This paper explores the differences in high-accuracy and low-accuracy learners' beliefs about corrective feedback when learning Chinese as a second language (henceforth, CSL). In this study, we collected data through a questionnaire survey and an oral test with 76 CSL learners in a Chinese university. The analysis revealed that both high- and low-accuracy CSL learners shared the same beliefs in whether and how the learner errors should be corrected but differed in their beliefs about when is the best time to correct, which error should be corrected, and who the corrector should be. Specifically, the discrepancy between high- and low-accuracy groups' beliefs about corrective feedback was found to be related to the participants' oral accuracy. Our results confirm that learners' CF beliefs can modulate their language accuracy. The corrective feedback beliefs held by high-accuracy groups have implications for improving low-accuracy groups' oral accuracy. Through comparison with findings on corrective feedback beliefs of English as a foreign/second language (henceforth, EFL/ESL) learners, this study suggested that language pedagogies developed from the research of EFL/ESL learners' CF beliefs should be able to shed light on this area and have significance for CSL learners. Implications for correcting learner errors in teaching CSL are also provided in the paper.

The Long Non-Coding RNA HOXC-AS3 Promotes Glioma Progression by Sponging miR-216 to Regulate F11R Expression.

HOXC cluster antisense RNA 3 (HOXC-AS3) is a long noncoding RNA (lncRNA) that plays a crucial role in various tumors; nevertheless, its role in glioma and its mechanism have not been completely elucidated. In this research, we discovered that HOXC-AS3 was over-expression in glioma cells and tissues and was associated with prognosis. Next, we determined that HOXC-AS3 targeted miR-216 as a sponge and that the F11 receptor (F11R) was the target of miR-216 by online databases analysis, qRT-PCR, and luciferase reporter assay. In addition, the rescue experiments confirmed that HOXC-AS3 regulated the expression of F11R by competitively binding miR-216 and functioning as a competing endogenous RNA (ceRNA). The intracranial glioblastoma mouse model suggested that HOXC-AS3 could promote glioma malignant progression in vivo. In summary, our study shows that the HOXC-AS3/miR-216/F11R axis plays an important role in the malignant progression of glioma, and may provide new ideas for the treatment of glioma.

Determination of temperature-dependent Fermi resonance in acetonitrile-water binary solution by two-dimensional correlation Raman spectroscopy.

Acetonitrile (AN), as an organic solvent, has a wide range of applications. The C≡N stretching vibration mode (ν2) and the combination mode (ν3 + ν4) are coupled by Fermi resonance (FR). In this work, the phase transition and the interaction mechanism of the 60% AN-water binary solution (AN-Water) were analyzed by calculating FR parameters and two-dimensional correlation Raman spectroscopy (2DCRS). The change in the ν2 band and the base bands ν3 and ν4 caused energy transfer by anharmonic interaction, which led to a change in FR parameters. With a reduced temperature, the energy transfer was caused by microheterogeneity and the energy transfer effect (293-273 K), the phase separation (263-233 K), and the phase transition of AN (223-173 K). The 2DCRS and Gaussian deconvolution provided more information on FR, which revealed the interaction mechanism of the Fermi doublet. The polarity and binding modes of molecules provided a new perspective for analyzing the transmission of electrons and ions in the electrolyte at different temperatures.

Study on hydrogen bonding network in aqueous methanol solution by Raman spectroscopy.

The Raman spectra of aqueous methanol solution with various concentrations were measured at room temperature and atmospheric pressure. We found that the CO stretching vibration mode of methanol showed a significant blue shift at Vm (Vm represents the volume fraction of methanol) >0.4, while the CH symmetric and asymmetric stretching vibration modes exhibited red shift under the same conditions. These results illustrate that the variation of hydrogen bond between methanol and water molecules lead to a phase transition of the methanol-water complex at Vm = 0.4. Furthermore, the red shift of the CH vibration mode indicates that there is no hydrogen bond formed between the CH3 group of methanol and water molecules. In addition, we found that the frequency shift of C-H is affected by the hydrogen bond C-O…H-O formed between methanol and water molecules, and the corresponding theoretical discussion is given. Finally, the phase transition process of methanol-water complex in methanol-water binary solution was given by theoretical analysis.

Investigation of hydrogen bonding in Water/DMSO binary mixtures by Raman spectroscopy.

Raman spectra of water/dimethyl sulfoxide (DMSO) mixtures have been observed at room temperature and atmospheric pressure. We find that the Raman peaks corresponding to the symmetric and asymmetric O-H stretching vibration mode of water rapidly move to lower wavenumber with increasing DMSO concentration. These results indicate that the strong hydrogen bond between DMSO-water complexes helps to strengthen the tetrahedral structure of water when the volume fraction of DMSO is less than 0.6. Moreover, the blue/red shifts of SO and C-H are obvious when the concentration of DMSO reaches 0.6, which may be due to changes in the structure of the DMSO-water complex. Furthermore, the frequency shift of the C-H group indicates that the non-polar methyl group of DMSO forms a hydrophobic hydrated structure. Finally, the frequency shift of the Raman peaks of SO and C-H exhibited a highly consistent concentration dependence due to the cooperation effect of the C-H⋯O with the O-H⋯OS.

Study of molecular association in acetic acid-water binary solution by Raman spectroscopy.

Raman spectra of acetic acid-water binary solutions with different concentrations have been measured in order to study molecular association of acetic acid. We find that the symmetric and asymmetric OH stretching vibration of water (3242 and 3443 cm-1) have marked changes of Raman shift when the volume fraction of acetic acid (VAA) is 0.3 and 0.8, respectively, which demonstrates that the hydrogen bonding of the water is affected, causing association molecule (acetic acid-water structure) to undergo two phase transitions. Furthermore, the peak of the HCH bending vibration is blue-shifted at VAA = 0.8, which shows that the acetic acid-acetic acid structure undergoes a phase transition and the acetic acid side-on dimer is formed. These results also indicate that the CH vibration mode in CH⋯O is HCH bending vibration. Finally, the phase transition process of association molecules (hydrated monomer, linear dimer, acetic acid side-on dimer and water-separated dimer) has been obtained in acetic acid-water binary solutions through theoretical analysis.

C11, a novel fibroblast growth factor receptor 1 (FGFR1) inhibitor, suppresses breast cancer metastasis and angiogenesis.

The fibroblast growth factor receptors (FGFRs) are increasingly considered attractive targets for therapeutic cancer intervention due to their roles in tumor metastasis and angiogenesis. Here, we identified a new selective FGFR inhibitor, C11, and assessed its antitumor activities. C11 was a selective FGFR1 inhibitor with an IC50 of 19 nM among a panel of 20 tyrosine kinases. C11 inhibited cell proliferation in various tumors, particularly bladder cancer and breast cancer. C11 also inhibited breast cancer MDA-MB-231 cell migration and invasion via suppression of FGFR1 phosphorylation and its downstream signaling pathway. Suppression of matrix metalloproteinases 2/9 (MMP2/9) was associated with the anti-motility activity of C11. Furthermore, the anti-angiogenesis activity of C11 was verified in endothelial cells and chicken chorioallantoic membranes (CAMs). C11 inhibited the migration and tube formation of HMEC-1 endothelial cells and inhibited angiogenesis in a CAM assay. In sum, C11 is a novel selective FGFR1 inhibitor that exhibits potent activity against breast cancer metastasis and angiogenesis.

Discovery of natural estrogen receptor modulators with structure-based virtual screening.

Eleven compounds were identified as estrogen receptor modulators from an in-house natural product database (NPD) by structure-based virtual screening for ERα and ERß. Among them, 3 compounds were confirmed as ER agonists and 8 compounds were confirmed as ER antagonists by yeast two-hybrid (Y2H) assay, with EC50 values ranging from several micromolar to 100 micromolar. In this study, a novel series of cycloartane triterpenoids isolated from Schisandra glaucescens Diels was found to have ER antagonistic effect, the most potent antagonist of which exhibited activity with EC50 value of 2.55 and 4.68 µM for ERα and ERß, respectively. Moreover, the types of modulation and subtype selectivity were also investigated through molecular docking simulation.

PTID: an integrated web resource and computational tool for agrochemical discovery.

SUMMARY: Although in silico drug discovery approaches are crucial for the development of pharmaceuticals, their potential advantages in agrochemical industry have not been realized. The challenge for computer-aided methods in agrochemical arena is a lack of sufficient information for both pesticides and their targets. Therefore, it is important to establish such knowledge repertoire that contains comprehensive pesticides' profiles, which include physicochemical properties, environmental fates, toxicities and mode of actions. Here, we present an integrated platform called Pesticide-Target interaction database (PTID), which comprises a total of 1347 pesticides with rich annotation of ecotoxicological and toxicological data as well as 13 738 interactions of pesticide-target and 4245 protein terms via text mining. Additionally, through the integration of ChemMapper, an in-house computational approach to polypharmacology, PTID can be used as a computational platform to identify pesticides targets and design novel agrochemical products. AVAILABILITY: http://lilab.ecust.edu.cn/ptid/. CONTACT: hlli@ecust.edu.cn; xhqian@ecust.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Insulin-like growth factor-1 receptor (IGF-1R) kinase inhibitors in cancer therapy: advances and perspectives.

The insulin-like growth factors (IGF) and their receptors play pivotal roles in cellular signaling transduction and thus regulate cell growth, differentiation, apoptosis, transformation and other important physiological progresses. The insulin-like growth factor 1 receptor (IGF-1R) mainly engages in the Ras/mitogen-activated protein kinase (MAPK) pathway and the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, and also forms cross-talk with the epidermal growth factor receptor (EGFR) pathway. Currently, it draws more attention since its overexpression has been demonstrated in various human cancers, such as colorectal cancer, breast cancer, prostate cancer and lung tumors, thus the strategy targeting the IGF-1R would be promising in treatment of these cancers. There are already dozens of agents developed for the inhibition of IGF-1R, which are categorized into monoclonal antibodies, small molecule inhibitors and so on. While in this review, small molecule inhibitors would be the focus for detailed discussion. Herein, we updated previously reported research papers and reviews in this field and summarized developments of small molecule inhibitors up to 2011. Finally, we proposed the application of network pharmacology methods to reconsider the clinical use of inhibitors with concomitant IR inhibition or other kinases inhibition, hoping that more optimal combinations would be obtained for cancer therapy.

New thiazole carboxamides as potent inhibitors of Akt kinases.

A new series of 2-substituted thiazole carboxamides were identified as potent pan inhibitors against all three isoforms of Akt (Akt1, Akt2 and Akt3) by systematic optimization of weak screening hit N-(1-amino-3-phenylpropan-2-yl)-2-phenylthiazole-5-carboxamide (1). One of the most potent compounds, 5m, inhibited the kinase activities of Akt1, Akt2 and Akt3 with IC(50) values of 25, 196 and 24nM, respectively. The compound also potently inhibited the phosphorylation of downstream MDM2 and GSK3ß proteins, and displayed strongly antiproliferative activity in prostate cancer cells. The inhibitors might serve as lead compounds for further development of novel effective anticancer agents.

SHAFTS: a hybrid approach for 3D molecular similarity calculation. 2. Prospective case study in the discovery of diverse p90 ribosomal S6 protein kinase 2 inhibitors to suppress cell migration.

We described a prospective application of ligand-based virtual screening program SHAFTS to discover novel inhibitors for p90 ribosomal S6 protein kinase 2 (RSK2). Taking the putative 3D conformations of two weakly binding RSK2 NTKD inhibitors as query templates, SHAFTS was used to perform 3D similarity based virtual screening because of a lack of crystal structure of RSK2 protein, thus leading to the identification of several novel scaffolds that would have been missed by conventional 2D fingerprint methods. The most potent hit compounds show low micromolar inhibitory activities against RSK2. In particular, one of the hit compounds exhibits potent antimigration activity against the MDA-MB-231 tumor cell. The results exemplified SHAFTS' application in active enrichment and scaffold hopping, which is of general interest for lead identification in drug discovery endeavors and also provides novel scaffolds that lay the foundation for uncovering new RSK2 regulatory mechanisms.

Acenaphtho[1,2-b]pyrrole-based selective fibroblast growth factor receptors 1 (FGFR1) inhibitors: design, synthesis, and biological activity.

A novel series of acenaphtho[1,2-b]pyrrole derivatives as potent and selective inhibitors of fibroblast growth factor receptor 1 (FGFR1) were designed and synthesized. In silico target prediction revealed that tyrosine kinases might be the potential targets of the representative compound 2, which was subsequently validated by enzyme-linked immunosorbent assay (ELISA) for its selective and active FGFR1 inhibition of various tyrosine kinases. The structure-activity relationship (SAR) analysis aided by molecular docking simulation in the ATP-binding site demonstrated that acenaphtho[1,2-b]pyrrole carboxylic acid esters (2-5) are potent inhibitors of FGFR1 with IC(50) values ranging from 19 to 77 nM. Furthermore, these compounds exhibited favorable growth inhibition property against FGFR-expressing cancer cell lines with IC(50) values ranging from micromolar to submicromolar. Western blotting analysis showed that compounds 2, 3, and 2b inhibited activation of FGFR1 and extracellular-signal regulated kinase 1/2 (Erk1/2).

A stable and sensitive testing system for potential carcinogens based on DNA damage-induced gene expression in human HepG2 cell.

In order to analyze potential carcinogenic and genotoxic responses caused by exposure to pollutants existing in environment, a screening method has been established in our laboratory that uses a stably transfected HepG2 cell lines containing gadd153 promoter regions which drive a luciferase reporter gene. Activation of the exogenous gadd153 promoter was quantified using the luciferase activity following drug exposure. Twenty four agents were used to evaluate this screening assay. We selected the agents, ranging from DNA alkylating agents, oxidative agent, radiation, DNA cross-linking agent, nongenotoxic carcinogens, precarcinogenic agents, which included cadmium chloride, chromium trichloride, mercuric chloride, lead nitrate, dichloro-diphenyl-trichloroethane, deltamethrin, biphenylamine, 2-aminofluorene, benzo[a]pyrene, 2,3,7,8,-tetracblorodibenzo-p-dioxin, diethyl-stilbestrol, carbon tetrachloride, mitomycin C, hydroxycamptothecin, UV, sodium fluoride, acrylamide, hydrogen peroxide. In addition, two complex genotoxic agents (water samples) existing in the environment were selected. The results showed that all 20 tested known carcinogenic and genotoxic agents were able to induce gadd153-Luc expression at a sublethal dose. In contrast, four tested non-carcinogens, included 4-acetylaminofluorene, pyrene, benzylpenicillin sodium and vitamin C, were unable to induce gadd153-Luc expression. In conclusion, this reporter system can facilitate in vitro screening for potential carcinogens. Therefore, the gadd153-Luc test system we have developed appears to be a useful and complementary system to existing genotoxic and mutagenic tests.

In vitro toxicity of surface water disinfected by different sequential treatments.

The in vitro toxicity of extracts of Hanjiang water disinfected by different sequential treatments was evaluated. Hanjiang water was disinfected using ozone, chloride dioxide or chlorine as the primary disinfectant followed by chlorine as the secondary disinfectant. HepG(2) cells were exposed to extracts corresponding to concentrations of 0.2, 1, 5, 25 and 125 mL water/mL medium. Compared with control, HepG(2) cells exposed to extracts of raw water and all disinfected water for 24h increased oxidative stress level, DNA damage and micronuclei frequency, and decreased cell viability. Water disinfected by Cl(2)+Cl(2) had the highest DNA double-strand breaks. All disinfected water and raw water increased micronuclei frequency via clastogenic and aneugenic effects. Oxidative stress induced DNA strand breaks and micronuclei frequency and therefore reduced cell viability either in disinfected water or raw water. Compared with raw water, water after disinfection increased DNA strand breaks, decreased cell viability and changed oxidative stress potential. Compared with chlorination, sequential treatment using O(3) or ClO(2) as primary disinfectant followed by chlorine disinfection reduced chlorinated by-products, DNA double-strand breaks and cell viability, but did not decrease micronuclei frequency and other DNA damage such as DNA single-strand break, alkali liable sites and incomplete excision sites. Sequential treatments did not significantly reduce in vivo toxicity of disinfected Hanjiang water.