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Biomedical subjects

Q Sun

Publications and source records attributed to Q Sun.

At least 37 records · Page 2Linked to original sources

Ferromagnetic GaN--Cr Nanowires.

Using first-principles theory, we predict ferromagnetism in Cr-doped GaN nanowires irrespective of the sites that the Cr atoms occupy. This is in contrast to Mn-doped GaN nanowires in which the magnetic coupling between the Mn atoms is sensitive to the Mn--Mn and Mn--N distances, although the ground state of Mn-doped GaN nanowires is ferromagnetic. Each Cr atom carries a magnetic moment of about 2.5 micro(B). The magnetic moment at the N site, however, is small and is aligned antiferromagnetically to the moments at the Cr atom. The magnetization axis is perpendicular to the axis of the wire, but the anisotropy energy is rather small. The easy solubility of Cr in GaN and the lack of sensitivity of ferromagnetic coupling to Cr distribution suggest that Cr-doped GaN nanowires may be a more suitable system for applications in spintronics than Mn-doped GaN nanowires.

Chromium↗

Antiangiogenic gene therapy: disruption of neovascular networks mediated by inducible caspase-9 delivered with a transcriptionally targeted adenoviral vector.

The activation of an inducible caspase (iCaspase-9) mediates apoptosis of neovascular endothelial cells, and overcomes the prosurvival effect of vascular endothelial growth factor or basic fibroblast growth factor. The potential utilization of direct activation of caspases as an antiangiogenic strategy for treatment of angiogenesis-dependent diseases (eg cancer) requires expression of the inducible caspase primarily in the tumor endothelium. The objective of this work was to develop and characterize a transcriptionally targeted adenoviral vector that mediates expression of iCaspase-9 specifically in neovascular endothelial cells. We observed that adenoviral vectors containing the human VEGFR2 promoter induced reporter gene expression primarily in proliferating human dermal microvascular endothelial cells (HDMEC). HDMEC transduced with recombinant adenoviral vectors containing iCaspase-9 under regulation of the VEGFR2 promoter (Ad-hVEGFR2-iCaspase-9) and exposed to a cell-permeable dimerizer drug (AP20187), presented higher caspase-3 activity and apoptosis than controls (P < or = 0.05). Using the SCID Mouse Model of Human Angiogenesis, we observed that local delivery of Ad-hVEGFR2-iCaspase-9 followed by intraperitoneal injection of AP20187 resulted in endothelial cell apoptosis and local ablation of microvessels. We believe that this constitutes the first report of a transcriptionally targeted antiangiogenic adenoviral vector that mediates neovascular disruption upon activation of a caspase-based artificial death switch.

Adenoviridae↗

Atrial natriuretic peptide inhibits the actions of FSH and forskolin in meiotic maturation of pig oocytes via different signalling pathways.

Atrial natriuretic peptide (ANP) as well as its receptors is found in mammalian ovary and follicular cells and its function in oocyte meiotic maturation has also been reported in Xenopus, hamster and rat. But the results are controversial and the physiological mechanism of ANP on oocyte maturation is not clear, especially the relationship between gonadotrophin and ANP as well as the signal transduction, and these need further study. The present study conducted experiments to examine these questions by using drug treatment and Western blot analysis and focused on pig oocyte meiotic maturation and cumulus expansion in vitro. The results revealed that ANP could inhibited FSH-induced pig oocyte maturation and cumulus expansion and prevent the full phosphorylation of mitogen-activated protein kinase in both oocytes and cumulus cells, and that these inhibitory effects could be mimicked by 8-Br-cyclic guanosine 5'-monophosphate (8-Br-cGMP), but blocked by a protein kinase G (PKG) inhibitor KT5823. Zaprinast, a cGMP-specific phosphodiesterase inhibitor, could enhance the inhibitory effect of ANP on oocyte maturation. A specific analogue of ANP, C-ANP-(4-23), which binds to the natriuretic peptide receptor-C (NPRC), had no effect in either FSH-induced or spontaneous oocyte maturation. Treatment with forskolin, a stimulator of adenylate cyclase, had a biphasic effect; 44 h treatment induced cumulus expansion but inhibited oocyte maturation while 2 h treatment induced maturation of cumulus-enclosed oocytes (CEOs). Both ANP and C-ANP-(4-23) could inhibit the effect of forskolin on CEO maturation, and these inhibitory effects of ANP/C-ANP-(4-23) could be blocked by preincubation with pertussis toxin (PT), consistent with mediation by a Gi protein(s) in the cumulus cells. All these results suggest that ANP is a multifunctional regulator of FSH and forskolin on pig CEO maturation by two signalling mechanisms: one is via a cGMP/PKG pathway, the other is via NPRC receptors in cumulus cells and the activation of the PT-sensitive Gi protein(s).

Animals↗

Appearance of bulk properties in small tungsten oxide clusters.

Contrary to the conventional understanding that atomic clusters usually differ in properties and structure from the bulk constituents of which they are comprised, we show that even a dimer of tungsten oxide (WO(3))(2) possesses bulklike features and the geometry of a small cluster containing only 4 tungsten and 12 oxygen atoms bears the hallmarks of crystalline tungsten oxide, WO(3). This observation, based on a synergistic approach involving mass distributions under quasisteady state conditions, photoelectron spectroscopy, and first principles molecular orbital theory, not only illustrates the existence of a class of strongly covalent or ionic materials whose embryonic forms are tiny clusters but also lends the possibility that a fundamental understanding of complex processes such as catalytic reactions on surfaces may be achieved on an atomic scale with clusters as model systems.

Journal Article↗

An autosomal genomic scan for loci linked to type 2 diabetes in northern Han Chinese.

We report the results of a genome-wide scan conducted in 219 individuals from 34 large multiplex nuclear pedigrees from the northern Han Chinese population at an average resolution of about 10 cM. Nonparametric two-point and multipoint linkage analyses were performed to detect evidence of linkage with type 2 diabetes in this study. On chromosome 1 four regions showed evidence of linkage with type 2 diabetes in northern Han Chinese. Of these regions a marker D1S193 (73 cM) showed evidence of linkage (two-point nonparametric linkage 2.409), and another region (around 190 cM) was a replication of several other studies performed in different ethnic populations. Evidences of linkage have been confirmed by typing additional markers (average distance 1-5 cM) flanking these two positive regions on chromosome 1. We also found indication of linkage with type 2 diabetes on chromosomes 2, 10, 12, 18, 20, and 22 by two-point linkage analyses.

Adult↗

Electronic structure and bonding of Au on a SiO2 cluster: a nanobullet for tumors.

The binding of gold atoms to a small silica cluster has been studied by using density functional theory with generalized gradient approximation for exchange and correlation. It is shown that gold atoms bind to silicon atoms with dangling bonds and serve as seeds for the growth of Au islands. The large electron affinity of gold causes a significant change in the electronic structure of silica resulting in a substantial reduction in the highest occupied and the lowest unoccupied molecular orbital and the optical gap, thus allowing it to absorb near infrared radiation. This suggests that a small cluster can have a similar functionality in the treatment of cancer as the large size nanoshell, but for a different mechanism.

Breast Neoplasms↗

Antiferromagnetic coupling driven by bond length contraction near the Ga1-xMnxN film surface.

Using first principles calculations based on gradient corrected density functional theory we show that Mn atoms, which couple ferromagnetically in bulk Ga1-xMnxN, couple antiferromagnetically on its surface. This change in magnetic behavior is brought about by a contraction of the Mn-Mn and Mn-N bond lengths, which is significantly greater on the surface than in the bulk. The present study provides new insight to the numerous conflicting experimental observations in Mn doped GaN systems.

Journal Article↗

Comparison of effects of acetylcholine on electromechanical characteristics in guinea-pig atrium and ventricle.

The direct negative effects of acetylcholine (ACh) on guinea-pig atria and ventricles were investigated using standard microelectrodes, a force transducer and a video edge-detection system. It was found that: (1) ACh (at 0.001-100 microm) decreased the force of contraction and shortened the action potential duration (APD) in both atria and ventricles in a concentration-dependent manner, and that the atria were more sensitive to ACh than the ventricles; and (2) the direct negative inotropic effect of ACh (1 microm) on an isolated cardiac cell was similar to that on the isolated myocardium. But this effect was not present in all isolated ventricular cells, while all the atrial cells responded to ACh. In conclusion, ACh had direct inhibitory effects on both atrial and ventricular tissue and myocytes, although the effects were greater in atria than in ventricles; and the negative inotropic effect of ACh was closely related to the shortening of the APD.

Acetylcholine↗

Inhibitory effects of flavonoids from Hypericum perforatum on nitric oxide synthase.

The inhibitory effects of six flavonoids from Hypericum perforatum were assessed spectrophotometrically using nitric oxide synthase (NOS) in blood and cerebral homogenate of rats. Of the assayed compounds, quercetin and hyperoside showed concentration-dependent enzyme inhibitory actions. The IC50 values of quercetin for inhibiting NOS in rat cerebral homogenate and blood were 63.06 and 57.54 microM, and those of hyperoside 56.23 and 158.49 microM, respectively. The competitive patterns were discerned with the inhibition of the two flavonoids on NOS in serum and cerebral homogenate (except a mixed type inhibition was observed with quercetin in inhibiting cerebral NOS). Furthermore, similar inhibitions were found for quercetin upon NOS in cerebral homogenate and blood. However, a stronger inhibitory effect of hyperoside on the enzyme was discerned in cerebrum than in blood. These results suggested that the galactose moiety in hyperoside may be associated with the selectivity of the NOS inhibition.

Animals↗

Current perspectives on the therapeutic utility of VR1 antagonists.

This review gives a brief overview of the expression patterns, molecular pharmacology and physiological roles of the vanilloid receptor 1 (VR1). Particular emphasis is given to the therapeutic utility of VR1 modulators. Small molecule agonists of VR1, including capsaicin and RTX, are currently utilized for a number of clinical syndromes, including intractable neuropathic pain, spinal detrusor hyperreflexia, and bladder hypersensitivity; however, antagonists of VR1 have yet to reach the clinic. While the classic VR1 antagonist, capsazepine has proven a useful tool for unraveling the molecular pharmacology of VR1, in vivo studies with this compound have had limited success due to poor pharmacokinetic properties and species selectivity issues. With the cloning of VR1 in 1997, the pharmaceutical community has been provided a molecular target for high throughput screening and small molecule lead discovery and optimization. As a result, resurgence in the interest of VR1 antagonists has given way to many new pharmacological agents that may provide better tools to probe VR1 physiology, and ultimately yield promising therapeutic agents.

Animals↗

Stabilization of Si60 cage structure.

A comprehensive search for the stable geometries of bare Si60 and Si60 supported on a C60 fullerene was carried out using first principles calculations based on density functional theory. In contrast to previous theoretical studies and in agreement with recent experiments, we show that Si60 and C(60)@Si(60) clusters are unstable in the fullerenelike cage structure. However, Si60 cage can be stabilized by including within it, as endohedral units, small magic clusters such as Al12X (X=Si, Ge, Sn, Pb) and Ba@Si(20).

Journal Article↗

Two inbred rat strains that differ substantially in hip fragility.

One approach to identifying the genetic influences on skeletal phenotypes involves the creation and genetic mapping of a population of the second filial (F2) offspring derived from a cross of two inbred strains of rodents. The two inbred strains should be chosen based upon a large difference in the phenotype of interest, e.g., bone fragility. We found previously that considerable variation exists in fragility phenotypes among inbred strains of rats, and the phenotypic variation was site specific. In particular, two inbred rat strains, Copenhagen 2331 (COP) and Dark Agouti (DA), were found to differ significantly in femoral neck geometry and strength. The aim of this study was to further characterize hip fragility in COP and DA rats at 6 months of age using peripheral quantitative computed tomography (pQCT), microcomputed tomography (mCT), and biomechanical tests. COP rats had a significantly wider femoral head (P = 0.04) and neck (P = 0.007), significantly larger bone area and cortical bone area in femoral neck (P = 0.03 and P = 0.02, respectively), significantly greater total bone mineral content (BMC) and cortical BMC in femoral neck (P = 0.01 and P = 0.001, respectively), and 65% greater femoral neck cross-sectional moment of inertia (P = 0.02), as compared with DA rats. As a result, COP rats had 22% higher ultimate force (Fu), 68% higher ultimate displacement (du), and 81% higher work to failure (U) than DA rats in the femoral neck biomechanical test (P = 0.04, P = 0.01, and P = 0.02, respectively). The biomechanical properties for the femoral midshaft and lumbar vertebrae were virtually the same in the two rat strains, suggesting a hip-specific genetic effect on bone strength. These data indicate that significant phenotypic variation at the femoral neck site exists between these two inbred strains, and COP rats appear to have genes that specifically enhance the femoral neck structural properties and strength. Therefore these two inbred strains, COP with DA, may facilitate effective genetic studies of hip fragility.

Animals↗

Congenic mice reveal sex-specific genetic regulation of femoral structure and strength.

Genetic linkage studies in C3H/HeJ (C3H) and C57BL/6J (B6) mice identified several chromosomal locations or quantitative trait loci (QTL) linked to femoral volumetric bone mineral density (vBMD). From QTL identified on chromosomes (chr) 1, 4, 6, 13, and 18, five congenic mouse strains were developed. In each of these mice, genomic DNA from the QTL region of the donor C3H strain was transferred into the recipient B6 strain. Here we report the effects of donated C3H QTL on femoral structure, cortical vBMD and bending strength. Femoral structure was quantified by the polar moment of inertia (Ip) at the mid-diaphysis, which reflects the bending or torsional rigidity of the femur. Although the C3H progenitor mice have a smaller Ip than B6 progenitor mice, the congenic mice carrying the C3H segment at Chr 4 had significantly increased Ip in both males and females, giving these mice stronger femora. In female mice from the congenic Chr 1 strain, Ip was increased whereas male mice from the Chr 1 strain had smaller femoral cross-sections and significantly reduced Ip. This sex-specific effect on femoral structure was seen to a lesser extent in Chr 18 congenic mice. In addition, cortical vBMD was measured using peripheral quantitative computed tomography. Cortical vBMD was similar among most congenic strains except in Chr 6 congenic mice, where cortical vBMD was significantly less in females, but not in males. We conclude that (1) chromosomal QTL from C3H mice, which are genetically linked to total femoral vBMD, also regulate femoral structure; (2) the QTL on Chr 4 improves femoral structure and strength; (3) QTL on Chr 1 and 18 impart sex-specific effects on femoral structure; and (4) the QTL on Chr 6 imparts a sex-specific effect on cortical vBMD and femoral strength.

Animals↗

Downregulation of mafB expression in T-helper cells during early differentiation in vitro.

We have studied the expression of a human homologue of mafB (maf-1), a member of the family of large maf transcription factors. In support of the suggested key role that mafB expression plays in differentiating macrophages, we found mafB to be expressed at a very high level in monocytic U937 and THP-1 cell lines. However, we show here that mafB transcription is not restricted to myeloid cells but can also be detected in lymphoid cells, indicating transcriptional plasticity during haematopoiesis. In conclusion, strong proliferative signals mediated by T-cell activation and interleukins (IL-4 and IL-12) downregulate the mafB messenger RNA transcript level when resting naïve CD4+ T-helper cells enter the differentiation pathway in vitro.

Avian Proteins↗

Computer-integrated finite element modeling of human middle ear.

The objective of this study was to produce an improved finite element (FE) model of the human middle ear and to compare the model with human data. We began with a systematic and accurate geometric modeling technique for reconstructing the middle ear from serial sections of a freshly frozen temporal bone. A geometric model of a human middle ear was constructed in a computer-aided design (CAD) environment with particular attention to geometry and microanatomy. Using the geometric model, a working FE model of the human middle ear was created using previously published material properties of middle ear components. This working FE model was finalized by a cross-calibration technique, comparing its predicted stapes footplate displacements with laser Doppler interferometry measurements from fresh temporal bones. The final FE model was shown to be reasonable in predicting the ossicular mechanics of the human middle ear.

Acoustic Stimulation↗