High Electrochemical Sensitivity of TiO2- x Nanosheets and an Electron-Induced Mutual Interference Effect toward Heavy Metal Ions Demonstrated Using X-ray Absorption Fine Structure Spectra.

Mutual interference is a severe issue that occurs during the electrochemical detection of heavy metal ions. This limitation presents a notable drawback for its high sensitivity to specific targets. Here, we present a high electrochemical sensitivity of ∼237.1 µA cm-2 µM-1 toward copper(II) [Cu(II)] based on oxygen-deficient titanium dioxide (TiO2- x) nanosheets. We fully demonstrated an atomic-level relationship between electrochemical behaviors and the key factors, including the high-energy (001) facet percentage, oxygen vacancy concentration, surface -OH content, and charge carrier density, is fully demonstrated. These four factors were quantified using Raman, electron spin resonance, X-ray photoelectron spectroscopy spectra, and Mott-Schottky plots. In the mutual interference investigation, we selected cadmium(II) [Cd(II)] as the target ion because of the significant difference in its stripping potential (∼700 mV). The results show that the Cd(II) can enhance the sensitivity of TiO2- x nanosheets toward Cu(II), exhibiting an electron-induced mutual interference effect, as demonstrated by X-ray absorption fine structure spectra.

Surface-Electronic-State-Modulated, Single-Crystalline (001) TiO2 Nanosheets for Sensitive Electrochemical Sensing of Heavy-Metal Ions.

Intrinsically low conductivity and poor reactivity restrict many semiconductors from electrochemical detection. Usually, metal- and carbon-based modifications of semiconductors are necessary, making them complex, expensive, and unstable. Here, for the first time, we present a surface-electronic-state-modulation-based concept applied to semiconductors. This concept enables pure semiconductors to be directly available for ultrasensitive electrochemical detection of heavy-metal ions without any modifications. As an example, a defective single-crystalline (001) TiO2 nanosheet exhibits high electrochemical performance toward Hg(II), including a sensitivity of 270.83 µA µM-1 cm-2 and a detection limit of 0.017 µM, which is lower than the safety standard (0.03 µM) of drinking water established by the World Health Organization (WHO). It has been confirmed that the surface oxygen vacancy adsorbs an O2 molecule while the Ti3+ donates an electron, forming the O2•- species that facilitate adsorption of Hg(II) and serve as active sites for electron transfer. These findings not only extend the electrochemical sensing applications of pure semiconductors but also stimulate new opportunities for investigating atom-level electrochemical behaviors of semiconductors by surface electronic-state modulation.

[Association between parental MTHFR gene polymorphism 677C/T and nonsyndromic cleft lip and palate in offspring].

OBJECTIVE: To explore the association between parental genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) 677C/T and occurrence of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in offspring in Shandong Province. METHODS: MTHFR genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Parents of 89 NSCL/P patients treated at Qilu Hospital from August, 2006 to August, 2008 and those of 64 healthy children were recruited in this case-control study. RESULTS: Frequencies of T and C alleles in mothers of patients and healthy children were 65.73% and 46.09%, and 34.27% and 53.91%, respectively (Chi-square=13.663, P<0.01). Offspring whose mothers had T alleles were 2.243 times more likely to develop NSCL/P (95%CI: 1.408-3.572). Frequencies of T and C alleles in fathers of patients and healthy children were 62.92% and 55.47%, and 37.08% and 44.53%, respectively (Chi-square=2.222, P>0.05). The chance for parents of the patient and control groups to bear an affected fetus carrying homozygous mutations were 43% and 29%, respectively (P>0.05). CONCLUSION: In Shandong Province, maternal genotype for the MTHFR 677C/T polymorphism has a significant impact on the occurrence of NSCL/P in their offspring, whilst paternal genotype for this polymorphism may not be a risk factor for NSCL/P in their offspring.

Parts per billion-level detection of benzene using SnO2/graphene nanocomposite composed of sub-6 nm SnO2 nanoparticles.

In the present work, the SnO(2)/graphene nanocomposite composed of 4-5 nm SnO(2) nanoparticles was synthesized using a simple wet chemical method for ppb-level detection of benzene. The formation mechanism of the nanocomposite was investigated systematically by means of simultaneous thermogravimetry analysis, X-ray diffraction, and X-ray photoelectron spectroscopy cooperated with transmission electron microscopy observations. The SnO(2)/graphene nanocomposite showed a very attractive improved sensitivity to toxic volatile organic compounds, especially to benzene, compared to a traditional SnO(2). The responses of the nanocomposite to benzene were a little higher than those to ethanol and the detection limit reached 5 ppb to benzene which is, to our best knowledge, far lower than those reported previously.

Metal oxide nanostructures and their gas sensing properties: a review.

Metal oxide gas sensors are predominant solid-state gas detecting devices for domestic, commercial and industrial applications, which have many advantages such as low cost, easy production, and compact size. However, the performance of such sensors is significantly influenced by the morphology and structure of sensing materials, resulting in a great obstacle for gas sensors based on bulk materials or dense films to achieve highly-sensitive properties. Lots of metal oxide nanostructures have been developed to improve the gas sensing properties such as sensitivity, selectivity, response speed, and so on. Here, we provide a brief overview of metal oxide nanostructures and their gas sensing properties from the aspects of particle size, morphology and doping. When the particle size of metal oxide is close to or less than double thickness of the space-charge layer, the sensitivity of the sensor will increase remarkably, which would be called "small size effect", yet small size of metal oxide nanoparticles will be compactly sintered together during the film coating process which is disadvantage for gas diffusion in them. In view of those reasons, nanostructures with many kinds of shapes such as porous nanotubes, porous nanospheres and so on have been investigated, that not only possessed large surface area and relatively mass reactive sites, but also formed relatively loose film structures which is an advantage for gas diffusion. Besides, doping is also an effective method to decrease particle size and improve gas sensing properties. Therefore, the gas sensing properties of metal oxide nanostructures assembled by nanoparticles are reviewed in this article. The effect of doping is also summarized and finally the perspectives of metal oxide gas sensor are given.

SNX-2112, a novel Hsp90 inhibitor, induces G2/M cell cycle arrest and apoptosis in MCF-7 cells.

SNX-2112 is a heat shock protein 90 (Hsp90) inhibitor with anticancer properties currently in clinical trials. This study investigated the effects of SNX-2112 on inhibition of cell growth, the cell cycle, and apoptosis in MCF-7 human breast cancer cells, in addition to the various molecular mechanisms. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis suggest that SNX-2112 inhibits cell growth in a time- and dose-dependent manner more potently than 17-(allylamino)-17-demethoxygeldanmycin (17-AAG), a traditional Hsp90 inhibitor, probably as a result of cell-cycle arrest at the G2/M phase and the induction of apoptosis. Downregulation of Bcl-2 and Bcl-xL, upregulation of Bax, cleavage of caspase-9 and poly (ADP-ribose) polymerase (PARP), and degradation of the breast cancer-related Hsp90 client proteins human epidermal growth factor receptor-2 (HER2), Akt, Raf-1, and nuclear factor kappa-B kinase (IKK) were observed in SNX-2112 treated cells by Western blot assay. These findings suggest that the molecular mechanisms of cell-growth inhibition by SNX-2112 involve activation of the mitochondrial apoptotic pathway and the degradation of breast cancer-related proteins.

In-vitro antitumor activity evaluation of hyperforin derivatives.

The derivatives of hyperforin, namely hyperforin acetate (2), 17,18,22,23,27,28,32,33-octahydrohyperforin acetate (3), and N,N-dicyclohexylamine salt of hyperforin (4), have been investigated for their antitumor properties. In-vitro studies demonstrated that 2 and 4 were active against HeLa (human cervical cancer), A375 (human malignant melanoma), HepG2 (human hepatocellular carcinoma), MCF-7 (human breast cancer), A549 (human nonsmall cell lung cancer), K562 (human chronic myeloid leukemia), and K562/ADR (human adriamycin-resistant K562) cell lines with IC(50) values in the range of 3.2-64.1 µM. The energy differences between highest occupied molecular orbital and lowest unoccupied molecular orbital of 2-4 were calculated to be 0.39778, 0.43106, and 0.30900 a.u., respectively, using the Gaussian 03 software package and ab initio method with the HF/6-311 G* basis set. The result indicated that the biological activity of 4 might be the strongest and that of 3 might be the weakest, which was in accordance with their corresponding antiproliferative effects against the tested tumor cell lines. Compound 4 caused cell cycle arrest at G2/M phase in flow cytometry experiment and induced apoptosis by 4',6-diamidino-2-phenylindole staining and Annexin V-FITC/PI (propidium iodide) double-labeled staining in HepG2 cells. The results indicated a potential for N,N-dicyclohexylamine salt of hyperforin as a new antitumor drug.

BJ-B11, a novel Hsp90 inhibitor, induces apoptosis in human chronic myeloid leukemia K562 cells through the mitochondria-dependent pathway.

In the past few years heat shock protein 90 (Hsp90) inhibitors have been reported to possess significant antitumor activity. We investigated, for the first time, the antitumor activity of a novel Hsp90 inhibitor 2-(4-acetyloxycyclohexylamino)-4-(3, 6, 6-trimethyl-4-oxo-4, 5, 6, 7-tetrahydro-1H-indazol-1-yl)-benzamide (BJ-B11) and the molecular mechanism underlying the apoptosis it induces in human chronic myeloid leukemia K562 cells. The results revealed that BJ-B11 triggered growth inhibition in K562 cells and other malignant cell lines in vitro with only minor toxicity in a normal human cell line. BJ-B11 inhibited the proliferation of K562 cells in a concentration- and time-dependent manner, with IC(50) values of 1.1 ± 0.2 µM and 0.4 ± 0.1 µM after 48 and 72 h incubations respectively. This most likely results from cell cycle arrest at the G(0)/G(1) phase and the induction of apoptosis. In addition, BJ-B11 degraded the Hsp90 client proteins Bcr-Abl and Akt, induced activation of caspase-9 and caspase-3, and subsequent cleavage of PARP. The caspase signals may originate from mitochondrial dysfunction, which is supported by the finding of cytochrome c release. In addition, inactivation of the Akt signaling pathway may be involved in the process of BJ-B11-induced apoptosis. Taken together, our data provide a putative molecular mechanism for the anticancer effect of BJ-B11 on K562 cells, and suggest a potential application for BJ-B11 in chronic myeloid leukemia therapy.

Induction of apoptosis in K562 cells by dicyclohexylammonium salt of hyperforin through a mitochondrial-related pathway.

Hyperforin is an abundant phloroglucinol-type constituent isolated from the extract of the flowering upper portion of the plant Hypericum perforatum L. The dicyclohexylammonium salt of hyperforin (DCHA-HF) has exhibited antitumor and antiangiogenic activities in various cancer cells. Here, the antitumor effects of DCHA-HF on the chronic myeloid leukemia K562 cell line were investigated for the first time. DCHA-HF exhibited dose- and time-dependent inhibitory activities against K562 cells, with IC(50) values of 8.6 and 3.2 µM for 48 h and 72 h of treatment, respectively, which was more effective than that of the hyperforin. In contrast, little cytotoxic activity was observed with DCHA-HF on HUVECs. DCHA-HF treatment resulted in induction of apoptosis as evidenced from DNA fragmentation, nuclear condensation and increase of early apoptotic cells by DAPI staining analysis, TUNEL assay and Annexin V-FITC/PI double-labeled staining analysis, respectively. Moreover, DCHA-HF elicited dissipation of mitochondrial transmembrane potential that commenced with the release of cytochrome c through down-regulation of expression of anti-apoptotic proteins and up-regulation of expression of pro-apoptotic proteins. DCHA-HF treatment induced activation of the caspase 3, 8, and 9 cascade and subsequent PARP cleavage, and DCHA-HF-induced apoptosis was significantly inhibited by caspase inhibitors. Treated cells were arrested at the G1 phase of the cell cycle and the expression of p53 and p27(Kip1), two key regulators related to cell cycle and apoptosis, was up-regulated. These results suggest that DCHA-HF inhibits K562 cell growth by inducing caspase-dependent apoptosis mediated by a mitochondrial pathway and arresting the cell cycle at the G1 phase. Therefore, DCHA-HF is a potential chemotherapeutic antitumor drug for chronic myeloid leukemia therapy.

[Comparative study on chemcial composition between cultivated and wild Scutellariae radix].

OBJECTIVE: To do some comparative study on chemical composition between the cultivated and wild samples of Radix Scutellariae. METHOD: Thirty three samples of Radix Scutellariae were collected from different habitats. An HPLC method for fingerprint identification and simultaneous determination of baicalin, baicalein and wogonin was established, and the content of ethanolic extractive was measured according to the method in Chinese Pharmacopoeia. RESULT: The number of chromatographic peaks in fingerprint of wild sample was more than that of cultivated sample in Hebei and Inner Mongolia. In 95% confidence intervals, the contents of baicalin, baicalein and wogonin were (15.89 +/- 1.52)%, (1.04 +/- 0.26)% and (0.27 +/- 0.07)%, respectively in the cultivated samples and (11.93 +/- 1.62)%, (1.03 +/- 0.26)% and (0.27 +/- 0.06)%, respectively in wild samples. The content of ethanolic extractive was 52.07 +/- 3.05% in the cultivated and (41.21 +/- 2.86)% in the wild within 95% confidence interval. CONCLUSION: Slight difference between the fingerprint of the cultivated and wild samples was found, and the contents of baicalin and ethanolic extraction in the cultivated were higher than those in the wild.