Enhancement of lateral Casimir force on a rotating particle near hyperbolic metamaterial.

Enhancement of weak Casimir forces is extremely important for their practical detection and subsequent applications in variety of scientific and technological fields. We study the lateral Casimir forces acting on the rotating particles with small radius of 50 nm as well as that with large radius of 500 nm near the hyperbolic metamaterial made of silicon carbide (SiC) nanowires. It is found that the lateral Casimir force acting on the small particle of 50 nm near hyperbolic metamaterial with appropriate filling fraction can be enhanced nearly four times comparing with that acting on the same particle near SiC bulk in the previous study. Such enhancement is caused by the coupling between the resonance mode excited by nanoparticle and the hyperbolic mode supported by hyperbolic metamaterial. The results obtained in this study provide an efficient method to enhance the interaction of nanoscale objects.

Docking and molecular dynamics study on the inhibitory activity of novel inhibitors on epidermal growth factor receptor (EGFR).

EGFR is the cell-surface receptor. Its overexpression or overactivity has been associated with a number of cancers, including breast, lung, ovarian, and anal cancers. Many therapeutic approaches are aimed at the EGFR. A series of 2, 7-diamino-thiazolo [4,5-d] pyrimidine analogues are among the most highly potent and selective inhibitors of EGFR described to date. For in-depth investigation into the structural and chemical features responsible for the binding recognition mechanism concerned, as well as for exploring the binding pocket of these compounds, we performed a series of automated molecular docking operations. It was revealed that the binding site consisted of three main areas (P1, P2 and P3) composed of most of the hydrophobic amino acids able to accommodate the lipophilic arms of the compounds investigated. However, the solvent interface did not make much contribution to the binding of the inhibitors. The presence of residues Met793 and Asp855 may also be responsible for the binding recognition through H-bond interactions, with Phe856 through a T-shape π-π stacking interaction. The interaction model and pharmacophore of EGFR inhibitors were derived that can be successfully used to explain the different biologic activities of these inhibitors. Moreover, the docking results were quite robust as further validated by molecular dynamics. It is anticipated that the findings reported here may provide very useful information or clue for designing effective drugs for the therapeutic treatment of EGFR-related cancer.

Identification of ligand binding site on RXRγ using molecular docking and dynamics methods.

Retinoid X receptors (RXRα, ß and γ) are recently known to be cancer chemotherapies targets. The ligand binding domains of RXRs have been crystallized, but the information of RXRγ ligand binding site is not yet available due to the lack of liganded complex. A thorough understanding of the ligand binding sites is essential to study RXRs and may result in cancer therapeutic breakthrough. Thus we aimed to study the RXRγ ligand binding site and find out the differences between the three subtypes. Alignment and molecular simulation were carried out for identifying the RXRγ ligand binding site, characterizing the RXRγ ligand binding mode and comparing the three RXRs. The result has indicated that the RXRγ ligand binding site is defined by helices H5, H10, ß-sheet s1 and the end loop. Besides hydrophobic interactions, the ligand 9-cis retinoic acid interacts with RXRγ through a hydrogen bond with Ala106, a salt bridge with Arg95 and the π-π interactions with Phe217 and Phe218. The binding modes exhibit some similarities among RXRs, such as the interactions with Arg95 and Ala106. Nonetheless, owing to the absence of Ile47, Cys48, Ala50, Ala51 and residues 225∼237 in the active site, the binding pocket in RXRγ is two times larger than those of RXRα and RXRß. Meanwhile, spatial effects of Trp84, Arg95, Ala106, Phe217 and Phe218 help to create a differently shaped binding pocket as compared to those of RXRα and RXRß. Consequently, the ligand in RXRγ undergoes a "standing" posing which is distinct from the other two RXRs.

Docking and molecular dynamics study on the inhibitory activity of N, N-disubstituted-trifluoro-3-amino-2-propanols-based inhibitors of cholesteryl ester transfer protein.

Extensive studies suggest direct links between cholesteryl ester transfer protein (CETP), high-density lipoproteins-cholesterol level and cardiovascular diseases. Many therapeutic approaches are aimed at the CETP. A series of N, N-disubstituted-trifluoro-3-amino-2-propanol analogues are among the most highly potent and selective inhibitors of CETP described to date. For in-depth investigation into the structural and chemical features responsible for exploring the binding pocket of these compounds, as well as for the binding recognition mechanism concerned, we performed a series of automated molecular docking operations. Moreover, the docking results were quite robust as further validated by molecular dynamics. The docking results reveal that the binding site mainly consists of two hydrophobic regions (P1 and P2 site) which are able to accommodate the lipophilic arms of the compounds investigated. Val421 in P1 site and Met194 in P2 site could be considered to be two important residues in forming the two hydrophobic regions. The presence of residues Phe197 and Phe463 in P2 site may be responsible for the binding recognition through π-π stacking interactions. The hydrophobic 3-phenoxy substituent may be important in creating the preferable inhibitive capability for increasing the binding potency. The hydrophobic character of the tetrafluoroethoxybenzyl group at position 3 displays better hydrophobicity than a shorter hydrophobic substituent. An interaction model of CETP-inhibitors is derived that can be successfully used to explain the different biologic activities of these inhibitors. It is anticipated that the findings reported here may provide very useful information or clues for designing effective drugs for the therapeutic treatment of CETP-related cardiovascular diseases.

[A survey on AIDS discrimination among medical college students].

OBJECTIVE: To understand the related knowledge, discrimination attitudes toward HIV/AIDS among medical college students, and to provide scientific evidence for further HIV/AIDS anti-discrimination intervention. METHODS: By means of stratified cluster sampling to classes, 2844 undergraduate students were randomly selected from medical colleges. A self-designed and self-administered questionnaire survey was conducted, and SPSS 13.0 software was used for data analysis. RESULTS: 2501 valid questionnaires had been collected. The overall HIV/AIDS knowledge coverage rate of the respondents was 73.1% (1828/2501); The HIV/AIDS discrimination rates in different questions were varying, the discrimination rate of infected with AIDS by bad sex and sharing needles was 83.1% (2078/2501) and 77.7% (1943/2501) respectively, the discrimination rates in term of contacting with HIV patients and their daily necessities, sharing desks, personal social were all exceeding 40%. CONCLUSION: The medical students held serious discrimination attitudes to HIV infected persons and patients; it is necessary to strengthen anti-discrimination education about HIV/AIDS among medical students.

[Study of BRCA1 and BRCA2 gene mutations in human sporadic breast cancers].

OBJECTIVE: To detect the mutations of BRCA1 and BRCA2 in sporadic breast cancer and study the relationship between BRCA1 and BRCA2 mutations and breast cancer. METHODS: Breast cancer tissues of 144 patients and breast tissues of 30 cases of healthy people who were treated from December 2000 to September 2005 were studied. DNA was extracted by the phenol-chloroform method. Fragments of exon 2, exon 3, exon 5, exon 6, exon 7, exon 8, exon 9, exon 10, exon 11, exon 12, exon 13, exon 14, exon 15, exon 16, exon 17, exon 18, exon 19, exon 20, exon 21, exon 22, exon 23 and exon 24 in the BRCA1 gene and exon 10 and exon 14 in the BRCA2 gene were amplified by polymerase chain reaction. Mutation screening was performed by single-strand conformation polymorphism analysis and alterations were confirmed by DNA sequencing. RESULTS: A total of 20 single nucleotide changes in BRCA1 were detected in the 144 cases of breast cancer patients. The total mutation rate was 13.9% and missense mutation rate was 11.1%. No mutation was detected in the BRCA2 and controls. CONCLUSIONS: Mutations in BRCA1 may play an important role in evaluation of sick risk, earlier diagnosis and gene therapy of breast cancer in southern Chinese populations.

[Comparative study on clinical effect of postoperative arterial infusion chemotherapy and systemic chemotherapy in gastric cancer].

OBJECTIVE: To compare the clinical effect of postoperative arterial infusion chemotherapy and systemic chemotherapy in gastric cancer. METHODS: From July 1997 to July 2002, the patients undergoing radical gastric resection were randomly divided into two groups, and received systemic or arterial infusion chemotherapy three weeks after radical resection. Systemic chemotherapy was carried out for two courses with 5-fluorouracil (5-FU), pirarubicin (THP), and mitomycin (MMC) administered according to FAM program, while arterial infusion chemotherapy for four courses with the same anticancer drugs infused via the celiac artery. The outcomes were compared. RESULTS: Systemic chemotherapy was carried out in 188 cases, and arterial infusion chemotherapy in 180 cases. There were no significant differences in sex, age, tumor location, histological type, TNM stage and surgical procedure between the two groups (P > 0.05). The 1, 3, 5 year survival rates were 87.2%, 53.7% and 43.1% in systemic chemotherapy, and 93.3%, 72.2% and 53.6% in arterial infusion chemotherapy respectively (P< 0.01). CONCLUSION: The survival rate of the patients with arterial infusion chemotherapy is higher than that with systemic chemotherapy, which indicates that arterial infusion chemotherapy can remarkably improve the prognosis of the patients with gastric cancer.