Aim: The objects of this study originated from the experimental observations, whereby the HIV -1 gp120 V3 loop is a high-affinity ligand for immunophilins, and consisted in generating the structural complex of cycloph...Aim: The objects of this study originated from the experimental observations, whereby the HIV -1 gp120 V3 loop is a high-affinity ligand for immunophilins, and consisted in generating the structural complex of cyclophilin (Cyc) B belonging to immunophilins family with the virus subtype A V3 loop (SA-V3 loop) as well as in specifying the Cyc B segment forming the binding site for V3 synthetic copy of which, on the assumption of keeping the 3D peptide structure in the free state, may present a forwardlooking basic structure for anti-AIDS drug development. Methods: To reach the objects of view, molecular docking of the HIV-1 SA-V3 loop structure determined previously with the X-ray conformation of Cyc B was put into practice by Hex 4.5 program (http://www.loria.fr/~ritchied/ hex/) and the immunophilin stretch responsible for binding to V3 (Cyc B peptide) was identified followed by examination of its 3D structure and dynamic behavior in the unbound status. To design the Cyc B peptide, the X-ray conformation for the identical site of the native protein was involved in the calculations as a starting model to find its best energy structural variant. The search for this most preferable structure was carried out by consecutive use of the molecular mechanics and simulated annealing methods. The molecular dynamics computations were implemented for the Cyc B peptide by the GROMACS computer package (http:// www.gromacs.org/). Results: The overmolecular structure of Cyc B with V3 was built by computer modeling tools and the immunophilinderived peptide able to mask effectively the structurally invariant V3 segments embracing the functionally crucial amino acids of the HIV-1 gp120 envelope protein was constructed and analyzed. Conclusions: Starting from the joint analysis of the results derived with those of the literature, the generated peptide was suggested to offer a promising basic structure for making a reality of the protein engineering projects aimed at developing the anti-AIDS drugs able to stop the HIV’s spread.展开更多
In this work, Bioactive-functionalized interpenetrating network (IPNs) hydrogel (BIOF-INPs) were prepared and investigated in vitro for the free radical detection/defense, therapeutic release as well as shear bond str...In this work, Bioactive-functionalized interpenetrating network (IPNs) hydrogel (BIOF-INPs) were prepared and investigated in vitro for the free radical detection/defense, therapeutic release as well as shear bond strength to dentine, ability to re-mineralize surface of the dentin after application of these bio-inspired materials using a biologically inspired mineralization process in vitro as well as investigating antimicrobial properties of the BIOF-INPs against S. aureous. The aim of this investigation was to evaluate the suitability and flexibility of the designer materials to act as an “in vitro” probe to gain insights into molecular origin of TMD and associated disorders.展开更多
Gordon Life Science Institute is the first Internet Research Institute ever established in the world. It is a non-profit institute. Those scientists who really dedicate themselves to science and loving science more th...Gordon Life Science Institute is the first Internet Research Institute ever established in the world. It is a non-profit institute. Those scientists who really dedicate themselves to science and loving science more than anything else can become its member. In the friendly door-opened Institute, they can maximize their time and energy to engage in their scientific creativity. They have also believed that science would be more truthful and wonderful if scientists do not have to spend a lot of time on funding application, and that great scientific findings and creations in history were often made by those who were least supported or funded but driven by interesting imagination and curiosity. Recollected in this review article is its establishing and developing processes, as well as its philosophy and accomplishments. Particularly, its productive and by-productive outcomes have covered the following five very hot topics in bioinformatics and drug development: 1) PseAAC and PseKNC;2) Disported key theory;3) Wenxiang diagram;4) Multi-label system prediction;5) 5-steps rule. Their impacts on the proteomics and genomics as well as drug development are substantially and awesome.展开更多
Influenza A(A/H_(x)N_(y))is a significant public health concern due to its high infectiousness and mortality.Neuraminidase,which interacts with sialic acid(SIA)in host cells,has become an essential target since its hi...Influenza A(A/H_(x)N_(y))is a significant public health concern due to its high infectiousness and mortality.Neuraminidase,which interacts with sialic acid(SIA)in host cells,has become an essential target since its highly conserved catalytic center structure,while resistance mutations have already generated.Here,a detailed investigation of the drug resistance mechanism caused by mutations was performed for subtype N9(A/H7N9).Molecular dynamics simulation and alanine-scanning-interaction-entropy method(ASIE)were used to explore the critical differences between N9 and Zanamivir(ZMR)before and after R294K mutation.The results showed that the mutation caused the hydrogen bond between Arg294 and ZMR to break,then the hydrogen bonding network was disrupted,leading to weakened binding ability and resistance.While in wild type(A/H7N9^(WT)),this hydrogen bond was initially stable.Meanwhile,N9 derived from A/H11N9 was obtained as an R292K mutation.Then the relative binding free energy of N9 with five inhibitors(SIA,DAN,ZMR,G28,and G39)was predicted,basically consistent with experimental values,indicating that the calculated results were reliable by ASIE.In addition,Arg292 and Tyr406 were hot spots in the A/H11N9^(WT)-drugs.However,Lys292 was not observed as a favorable contributing residue in A/H11N9^(R292K),which may promote resistance.In comparison,Tyr406 remained the hotspot feature when SIA,ZMR,and G28 binding to A/H11N9^(R292K).Combining the two groups,we speculate that the resistance was mainly caused by the disruption of the hydrogen bonding network and the transformation of hotspots.This study could guide novel drug delivery of drug-resistant mutations in the treatment of A/H_(x)N9.展开更多
Differently substituted benzimidazoles have been synthesized in very good yields in solvent-free conditions from o-phenylenediamine and aldehydes in the presence of BF3·OEt2 as a catalyst. The method is applicabl...Differently substituted benzimidazoles have been synthesized in very good yields in solvent-free conditions from o-phenylenediamine and aldehydes in the presence of BF3·OEt2 as a catalyst. The method is applicable to aromatic, unsaturated and aliphatic aldehydes and to substituted o-phenylenediamines without significant differences.展开更多
Recent interest by physicists in social networks and disease transmission factors has prompted debate over the topology of degree distributions in sexual networks. Social network researchers have been critical of “sc...Recent interest by physicists in social networks and disease transmission factors has prompted debate over the topology of degree distributions in sexual networks. Social network researchers have been critical of “scale-free” Barabasi-Albert approaches, and largely rejected the preferential attachment, “rich-get-richer” assumptions that underlie that model. Instead, research on sexual networks has pointed to the importance of homophily and local sexual norms in dictating degree distributions, and thus disease transmission thresholds. Injecting Drug User (IDU) network topologies may differ from the emerging models of sexual networks, however. Degree distribution analysis of a Brooklyn, NY, IDU network indicates a different topology than the spanning tree configurations discussed for sexual networks, instead featuring comparatively short cycles and high concurrency. Our findings suggest that IDU networks do in some ways conform to a “scale-free” topology, and thus may represent “reservoirs” of potential infection despite seemingly low transmission thresholds.展开更多
Epigenetic changes of DNA, including methylation, have long been recognized as key indicators of various diseases, including aging, cancer, and neurological disorders. Biomarker discoveries based on distinct methylati...Epigenetic changes of DNA, including methylation, have long been recognized as key indicators of various diseases, including aging, cancer, and neurological disorders. Biomarker discoveries based on distinct methylation patterns for both hypermethylation and hypomethylation lead the way in discovery of novel diagnosis and treatment targets. Many different approaches are present to detect the level of methylation in whole genome (whole genome bisulfite sequencing, microarray) as well as at specific loci (methylation specific PCR). Cell-free DNA (cf-DNA) found in body fluids like blood provides information about DNA methylation and serves as a less invasive approach for genetic screening. Cell-free DNA and methylation screening technologies, when combined, have the potential to transform the way we approach genetic screening and personalized therapy. These technologies can help enhance disease diagnostic accuracy and inform the development of targeted therapeutics by providing a non-invasive way for acquiring genomic information and identifying disease-associated methylation patterns. We highlight the clinical benefits of using cell-free DNA (cf-DNA) liquid biopsy analysis and available methylation screening technologies that have been crucial in identifying biomarkers for disease from patients using a non-invasive way. Powering such biomarker discoveries are various methods of cf-DNA methylation analysis such as Bisulfite Sequencing and most recently, Methylation-Specific Restriction Enzyme (MSRE-seq) Analysis, paving the way for novel epigenetic biomarker discoveries for more robust diagnosis such as early disease detection, prognosis, monitoring of disease progression and treatment response as well as discovery of novel drug targets.展开更多
The present paper reviews new findings in redoxproperties of the active constituent of Chinese herbalmedicine(CHM),a kind of CHM or a compoundprescription as an antioxidant.Firstly,we have studiedtheir antioxidant and...The present paper reviews new findings in redoxproperties of the active constituent of Chinese herbalmedicine(CHM),a kind of CHM or a compoundprescription as an antioxidant.Firstly,we have studiedtheir antioxidant and prooxidant actions with electronspin resonance(ESR).The results show that the activecomponents from over 10 kinds of CHM are able toscavenge the oxygen free radicals but propyl gallate展开更多
文摘Aim: The objects of this study originated from the experimental observations, whereby the HIV -1 gp120 V3 loop is a high-affinity ligand for immunophilins, and consisted in generating the structural complex of cyclophilin (Cyc) B belonging to immunophilins family with the virus subtype A V3 loop (SA-V3 loop) as well as in specifying the Cyc B segment forming the binding site for V3 synthetic copy of which, on the assumption of keeping the 3D peptide structure in the free state, may present a forwardlooking basic structure for anti-AIDS drug development. Methods: To reach the objects of view, molecular docking of the HIV-1 SA-V3 loop structure determined previously with the X-ray conformation of Cyc B was put into practice by Hex 4.5 program (http://www.loria.fr/~ritchied/ hex/) and the immunophilin stretch responsible for binding to V3 (Cyc B peptide) was identified followed by examination of its 3D structure and dynamic behavior in the unbound status. To design the Cyc B peptide, the X-ray conformation for the identical site of the native protein was involved in the calculations as a starting model to find its best energy structural variant. The search for this most preferable structure was carried out by consecutive use of the molecular mechanics and simulated annealing methods. The molecular dynamics computations were implemented for the Cyc B peptide by the GROMACS computer package (http:// www.gromacs.org/). Results: The overmolecular structure of Cyc B with V3 was built by computer modeling tools and the immunophilinderived peptide able to mask effectively the structurally invariant V3 segments embracing the functionally crucial amino acids of the HIV-1 gp120 envelope protein was constructed and analyzed. Conclusions: Starting from the joint analysis of the results derived with those of the literature, the generated peptide was suggested to offer a promising basic structure for making a reality of the protein engineering projects aimed at developing the anti-AIDS drugs able to stop the HIV’s spread.
文摘In this work, Bioactive-functionalized interpenetrating network (IPNs) hydrogel (BIOF-INPs) were prepared and investigated in vitro for the free radical detection/defense, therapeutic release as well as shear bond strength to dentine, ability to re-mineralize surface of the dentin after application of these bio-inspired materials using a biologically inspired mineralization process in vitro as well as investigating antimicrobial properties of the BIOF-INPs against S. aureous. The aim of this investigation was to evaluate the suitability and flexibility of the designer materials to act as an “in vitro” probe to gain insights into molecular origin of TMD and associated disorders.
文摘Gordon Life Science Institute is the first Internet Research Institute ever established in the world. It is a non-profit institute. Those scientists who really dedicate themselves to science and loving science more than anything else can become its member. In the friendly door-opened Institute, they can maximize their time and energy to engage in their scientific creativity. They have also believed that science would be more truthful and wonderful if scientists do not have to spend a lot of time on funding application, and that great scientific findings and creations in history were often made by those who were least supported or funded but driven by interesting imagination and curiosity. Recollected in this review article is its establishing and developing processes, as well as its philosophy and accomplishments. Particularly, its productive and by-productive outcomes have covered the following five very hot topics in bioinformatics and drug development: 1) PseAAC and PseKNC;2) Disported key theory;3) Wenxiang diagram;4) Multi-label system prediction;5) 5-steps rule. Their impacts on the proteomics and genomics as well as drug development are substantially and awesome.
基金supported by the National Natural Science Foundation of China(No.11774207)。
文摘Influenza A(A/H_(x)N_(y))is a significant public health concern due to its high infectiousness and mortality.Neuraminidase,which interacts with sialic acid(SIA)in host cells,has become an essential target since its highly conserved catalytic center structure,while resistance mutations have already generated.Here,a detailed investigation of the drug resistance mechanism caused by mutations was performed for subtype N9(A/H7N9).Molecular dynamics simulation and alanine-scanning-interaction-entropy method(ASIE)were used to explore the critical differences between N9 and Zanamivir(ZMR)before and after R294K mutation.The results showed that the mutation caused the hydrogen bond between Arg294 and ZMR to break,then the hydrogen bonding network was disrupted,leading to weakened binding ability and resistance.While in wild type(A/H7N9^(WT)),this hydrogen bond was initially stable.Meanwhile,N9 derived from A/H11N9 was obtained as an R292K mutation.Then the relative binding free energy of N9 with five inhibitors(SIA,DAN,ZMR,G28,and G39)was predicted,basically consistent with experimental values,indicating that the calculated results were reliable by ASIE.In addition,Arg292 and Tyr406 were hot spots in the A/H11N9^(WT)-drugs.However,Lys292 was not observed as a favorable contributing residue in A/H11N9^(R292K),which may promote resistance.In comparison,Tyr406 remained the hotspot feature when SIA,ZMR,and G28 binding to A/H11N9^(R292K).Combining the two groups,we speculate that the resistance was mainly caused by the disruption of the hydrogen bonding network and the transformation of hotspots.This study could guide novel drug delivery of drug-resistant mutations in the treatment of A/H_(x)N9.
文摘Differently substituted benzimidazoles have been synthesized in very good yields in solvent-free conditions from o-phenylenediamine and aldehydes in the presence of BF3·OEt2 as a catalyst. The method is applicable to aromatic, unsaturated and aliphatic aldehydes and to substituted o-phenylenediamines without significant differences.
文摘Recent interest by physicists in social networks and disease transmission factors has prompted debate over the topology of degree distributions in sexual networks. Social network researchers have been critical of “scale-free” Barabasi-Albert approaches, and largely rejected the preferential attachment, “rich-get-richer” assumptions that underlie that model. Instead, research on sexual networks has pointed to the importance of homophily and local sexual norms in dictating degree distributions, and thus disease transmission thresholds. Injecting Drug User (IDU) network topologies may differ from the emerging models of sexual networks, however. Degree distribution analysis of a Brooklyn, NY, IDU network indicates a different topology than the spanning tree configurations discussed for sexual networks, instead featuring comparatively short cycles and high concurrency. Our findings suggest that IDU networks do in some ways conform to a “scale-free” topology, and thus may represent “reservoirs” of potential infection despite seemingly low transmission thresholds.
文摘Epigenetic changes of DNA, including methylation, have long been recognized as key indicators of various diseases, including aging, cancer, and neurological disorders. Biomarker discoveries based on distinct methylation patterns for both hypermethylation and hypomethylation lead the way in discovery of novel diagnosis and treatment targets. Many different approaches are present to detect the level of methylation in whole genome (whole genome bisulfite sequencing, microarray) as well as at specific loci (methylation specific PCR). Cell-free DNA (cf-DNA) found in body fluids like blood provides information about DNA methylation and serves as a less invasive approach for genetic screening. Cell-free DNA and methylation screening technologies, when combined, have the potential to transform the way we approach genetic screening and personalized therapy. These technologies can help enhance disease diagnostic accuracy and inform the development of targeted therapeutics by providing a non-invasive way for acquiring genomic information and identifying disease-associated methylation patterns. We highlight the clinical benefits of using cell-free DNA (cf-DNA) liquid biopsy analysis and available methylation screening technologies that have been crucial in identifying biomarkers for disease from patients using a non-invasive way. Powering such biomarker discoveries are various methods of cf-DNA methylation analysis such as Bisulfite Sequencing and most recently, Methylation-Specific Restriction Enzyme (MSRE-seq) Analysis, paving the way for novel epigenetic biomarker discoveries for more robust diagnosis such as early disease detection, prognosis, monitoring of disease progression and treatment response as well as discovery of novel drug targets.
文摘The present paper reviews new findings in redoxproperties of the active constituent of Chinese herbalmedicine(CHM),a kind of CHM or a compoundprescription as an antioxidant.Firstly,we have studiedtheir antioxidant and prooxidant actions with electronspin resonance(ESR).The results show that the activecomponents from over 10 kinds of CHM are able toscavenge the oxygen free radicals but propyl gallate
