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Biomedical subjects

Jing Li

Publications and source records attributed to Jing Li.

At least 415 records · Page 23Linked to original sources

Exchange-coupled nanocomposite magnets by nanoparticle self-assembly.

Exchange-spring magnets are nanocomposites that are composed of magnetically hard and soft phases that interact by magnetic exchange coupling. Such systems are promising for advanced permanent magnetic applications, as they have a large energy product--the combination of permanent magnet field and magnetization--compared to traditional, single-phase materials. Conventional techniques, including melt-spinning, mechanical milling and sputtering, have been explored to prepare exchange-spring magnets. However, the requirement that both the hard and soft phases are controlled at the nanometre scale, to ensure efficient exchange coupling, has posed significant preparation challenges. Here we report the fabrication of exchange-coupled nanocomposites using nanoparticle self-assembly. In this approach, both FePt and Fe3O4 particles are incorporated as nanometre-scale building blocks into binary assemblies. Subsequent annealing converts the assembly into FePt-Fe3Pt nanocomposites, where FePt is a magnetically hard phase and Fe3Pt a soft phase. An optimum exchange coupling, and therefore an optimum energy product, can be obtained by independently tuning the size and composition of the individual building blocks. We have produced exchange-coupled isotropic FePt-Fe3Pt nanocomposites with an energy product of 20.1 MG Oe, which exceeds the theoretical limit of 13 MG Oe for non-exchange-coupled isotropic FePt by over 50 per cent.

Journal Article↗

Crystal of semiconducting quantum dots built on covalently bonded t5 [in(28)cd(6)s(54)](-12): the largest supertetrahedral cluster in solid state.

Periodic array of nanoparticles is essential for practical applications in optical devices. Periodic dot arrays often exhibit very interesting collective phenomenon. We report a periodic crystal of InCdS pseudo-T5 nanocluster, the largest supertetrahedral cluster found thus far in solid state. Each InCdS cluster behaves like a nanoparticle with the same size. Unlike the array of colloidal dots in which the dot-dot separation is large ( approximately 5 nm), the neighboring T5 clusters in [In28Cd6S54].[(CH3)4N]12[(HSCH2COOH)2]3.5 crystal form a natural point contact by sharing covalently bonded S atoms. Both experimental and theoretical studies show that this crystal is a semiconductor with a band gap of 3.0 eV.

Journal Article↗

[Impact of islet alpha cell loss on insulin secretion].

OBJECTIVE: To investigate the impact of islet alpha cell loss on insulin secretion. METHODS: Human pancreatic tissues underwent over-digestion of collagenase. Digestion was terminated in half of the tissue suspension, and half of the suspension was put into solution of collagenase to undergo over-digestion so as to cause loss of islet alpha cells. The tissues of digested human pancreas and over-digested human pancreas were fixed and immunohistochemical staining was made to observe the loss of islet alpha cells. The contents of insulin and glucagon in solutions of normal human pancreas, human islet of pancreas with normal enzyme secretion, and over-digested human islet were measured by radioimmunoassay. The ratios of insulin/glucagon in these three solutions were calculated so as to analyze the loss of alpha cells. Different human pancreatic tissues were inoculated in 24-well plate. Glucose solutions of different concentrations were added into the suspensions. The concentration of insulin in the supernatant was measured after incubation. C57/BL Normal human pancreas and human pancreas with islet alpha cell loss were transplanted into the renal capsules of two groups of 5 C57/BL mice with experimental diabetes mellitus respectively. The blood insulin was measured for two days. On the 3(rd) day, the left kidneys of the mice were taken to undergo insulin/glucagon immunohistochemical staining to observe the loss of alpha cells. Human islets with alpha cell loss were transplanted into the renal capsules of another 10 mice. Then 5 of them received injection of normal saline and the other 5 received glucagon for 7 days, then glucagon was injected into the mice of normal saline group, and vise versa. The blood sugar was measured every day. RESULTS: Glucagon immunohistochemistry showed alpha cell loss from islet periphery in over-digested human pancreas. The insulin/glucagons ratios were 100:2.34 and 100:2.05 in the normal pancreas and isolated normal islets respectively, and was 100:0.314 in the over-digested islets, showing a loss of > 80% of alpha cells. As compared with normal islets, glucose-induced insulin secretion was significantly decreased. The insulin concentration was 222.7 micro U/ml +/- 32.1 micro U/ml in the suspension of cultured normal pancreatic cells and was 124.6 micro U/ml +/- 12.6 micro U/ml in the supernatant of suspension of pancreatic islets with alpha cell loss (P < 0.01). The average blood sugar was 8.9 micro U/ml +/- 1.98 micro U/ml in mice grafted with normal islets and was 21.3 micro U/ml +/- 2.2 micro U/ml in mice grafted with alpha cell deficient islets (P < 0.01). However, insulin secretion in islets with alpha cell loss was significantly improved by exogenous glucagon in vitro and in vivo. CONCLUSION: The function of insulin secretion in islets with alpha cell loss is significantly decreased. Insulin secretion of islets with alpha cell loss can be improved by exogenous glucagon.

Animals↗

PRC17, a novel oncogene encoding a Rab GTPase-activating protein, is amplified in prostate cancer.

We used cDNA-based genomic microarrays to examine DNA copy number changes in a panel of prostate tumors and found a previously undescribed amplicon on chromosome 17 containing a novel overexpressed gene that we termed prostate cancer gene 17 (PRC17). When overexpressed in 3T3 mouse fibroblast cells, PRC17 induced growth in low serum, loss of contact inhibition, and tumor formation in nude mice. The PRC17 gene product contains a GTPase-activating protein (GAP) catalytic core motif found in various Rab/Ypt GAPs, including RN-Tre. Similar to RN-Tre, we found that PRC17 protein interacts directly with Rab5 and stimulates its GTP hydrolysis. Point mutations that alter conserved amino acid residues within the PRC17 GAP domain abolished its transforming abilities, suggesting that GAP activity is essential for its oncogenic function. Whereas PRC17 is amplified in 15% of prostate cancers, it is highly overexpressed in approximately one-half of metastatic prostate tumors. The potent oncogenic activity of PRC17 is likely to influence the tumorigenic phenotype of these prostate cancers.

3T3 Cells↗

Signaling intermediates required for NF-kappa B activation and IL-8 expression in CF bronchial epithelial cells.

Ligation of the asialoGM1 Pseudomonas aeruginosa pilin receptor has been demonstrated to induce IL-8 expression in airway epithelial cells via an NF-kappaB-dependent pathway. We examined the signaling pathways required for asialoGM1-mediated NF-kappaB activation in IB3 cells, a human bronchial epithelial cell line derived from a cystic fibrosis (CF) patient, and C-38 cells, the rescued cell line that expresses a functional CF transmembrane regulator. Ligation of the asialoGM1 receptor with specific antibody induced greater IL-8 expression in IB3 cells than C-38 cells, consistent with the greater density of asialoGM1 receptors in CF phenotype cells. AsialoGM1-mediated activation of NF-kappaB, IkappaB kinase (IKK), and ERK was also greater in IB3 cells. With the use of genetic inhibitors, we found that IKK-beta and NF-kappaB-inducing kinase are required for maximal NF-kappaB transactivation and transcription from the IL-8 promoter. Finally, although ERK activation was required for maximal asialoGM1-mediated IL-8 expression, inhibition of ERK signaling had no effect on IKK or NF-kappaB activation, suggesting that ERK regulates IL-8 expression in an NF-kappaB-independent manner.

Antibodies↗

The effect of malignant effusions on methotrexate disposition.

PURPOSE: The purpose of this study was to evaluate the effect of malignant effusions on the pharmacokinetics of methotrexate (MTX). METHODS: Simulated drug concentrations in blood, tissues and effusion fluid spaces were generated using a previously published physiologically based pharmacokinetic (PBPK) model for MTX in humans. The model was expanded to incorporate effusion spaces with permeability rate-limited drug transport. The model was used first to simulate MTX plasma concentrations in patients without effusions. Then the effects of cardiac, peritoneal and pleural effusions on MTX plasma concentrations were investigated followed by an examination of the influence of effusion volume, binding in the effusate, and effusion space permeability clearance (PA) on MTX plasma pharmacokinetics. In addition, the effect of the disposition characteristics (e.g. volume of distribution) of the anticancer drug on the overall influence of an effusate was evaluated. Finally, the simulations were compared with MTX concentrations observed in the plasma and pleural fluid of a patient with a pleural effusion treated with MTX. RESULTS: There was good agreement between the PBPK-simulated MTX plasma concentrations and observed values in patients without effusions. There was also a remarkable similarity between simulated and measured plasma and effusion MTX concentrations in a pediatric patient with a malignant pleural effusion. The physiological characteristics of an effusion, i.e. fluid volume, protein binding and membrane permeability clearance, modulate the influence of an effusion on the drug plasma concentration-time course. In general, effusions cause an increase in the steady-state volume of distribution but no change in the overall clearance of a drug. Malignant effusions were noticeable only in the disposition phase of MTX resulting in an apparent "third space." This was most prominent when the effusion fluid volume was large, the binding of MTX in the effusion fluid was greater than in plasma and the PA value was low. The percentage change in terminal half-life due to an effusion is significant for drugs with small volumes of distribution (332%) but not for those with large volumes of distribution (1.29%). In the case of MTX, and probably other anticancer drugs, the resulting increase in half-life may be associated with unanticipated toxicity.

Antimetabolites, Antineoplastic↗

Fabrication and optical properties of metastable Cu-Ag alloys.

A series of single-phase metastable Cu-Ag solid solutions was deposited by magnetron sputtering at liquid-nitrogen temperature. The lattice constant increases with increasing Ag content. The spectroscopic ellipsometer measurements clearly show that with increasing Ag content, the Cu-like and Ag-like absorption edges in the visible wavelength range shift continuously toward the high-energy and the low-energy sides, respectively.

Journal Article↗

[Pulmonary function in first generation children of chronic obstructive pulmonary disease (COPD) patients: assessment of related predicting factors].

OBJECTIVE: To study whether familial aggregation exists in pulmonary function impairment and COPD. METHODS: Pulmonary function, smoking habits, history of occupational dust exposure and clinical manifestation among 117 children of 59 smokers with COPD and 55 children of 28 control smokers without COPD. A multivariate linear regression analysis was carried out to study FEV1 among the children. Logistic regression analysis was conducted to study the factors influencing the FEV1 < 70% pred. RESULTS: Height and male gender were positively correlated to children's FEV1 (ml); whereas age, clinical symptoms, history of occupational dust exposure and being children of diseased probands were negatively correlated to children's FEV1 (ml). With other relevant factors adjusted, the FEV1 (ml) was lower among those being children of COPD patients; the more severe the COPD conditions of the parents, the lower the FEV1 of the children. Cigarette consumption having clinical symptoms, and being children of COPD probands showed increased risk of FEV1 below 70% predicted (OR = 1.987). Height, age, and history of occupational dust exposure were not correlated to FEV1 < 70% pred among children. CONCLUSION: Being children of COPD parents is the independent risk factor for lower FEV1 (ml) and FEV1 below 70% pred, which demonstrates the presence of familial aggregation of COPD and pulmonary function impairment.

Body Height↗

Reactions of cysteines substituted in the amphipathic N-terminal tail of a bacterial potassium channel with hydrophilic and hydrophobic maleimides.

Single cysteine-substitution mutants of KcsA, a K(+) channel from Streptomyces lividans, were expressed in Escherichia coli, and inner membranes were isolated. The rate constants for the reactions of these cysteines with three maleimides of increasing hydrophobicity, 4-(N-maleimido)phenyltrimethylammonium, N-phenylmaleimide, and N-(1-pyrenyl)maleimide, were determined by back titration of the remaining cysteines with methoxypolyethylene glycol-2-pyridine disulfide (M(r) 3,000) and quantitation of the fraction of gel-shifted KcsA as a function of reaction time. The patterns of the rate constants for the reactions of all three reagents with eight consecutive cysteines in the partially lipid-immersed amphipathic N-terminal tail helix were the same, with cysteines on the hydrophilic side of the helix reacting faster than Cys on the hydrophobic side. The results are consistent with the tail helix lying with its long axis in the lipid-water interface and with the orientation of the helix fluctuating around this axis. The patterns of the rate constants for the three reagents were similar to the pattern of the probabilities that the substituted cysteines were exposed to water, based on the sum of the free energies of transfer from water to octanol of all of the residues exposed to lipid in each orientation of the helix.

Cysteine↗

A conserved Tyr residue is required for sugar selectivity in a Pol alpha DNA polymerase.

Many DNA polymerases select their natural substrates, deoxy- as opposed to ribonucleoside triphosphates, with a selectivity greater than 10000-fold. The function of a highly conserved residue, Tyr416, in the palm domain of the parental enzyme, an exo(-) derivative of RB69 DNA polymerase (gp43), a member of the pol alpha DNA polymerase family, was examined for its role in helping the polymerase discriminate between ribo-, dideoxyribo-, and deoxyribonucleoside triphosphates. The parental enzyme selected dNTPs vs rNTPs with about the same preference as dNTPs vs ddNTPs. Pre-steady-state kinetic analysis was carried out with the parental enzyme and two mutants, Y416A and Y416F. The Y416A mutant incorporated ribonucleotide residues much more efficiently than the parental enzyme, whereas the Y416F mutant was more permissive toward ddNTP vs rNTP utilization than either the Y416A mutant or the parental enzyme. We also found that both dCDP and rCDP inhibited dCTP incorporation by the Y416A mutant, while only dCDP but not rCDP inhibited dCTP incorporation by the parental enzyme and the Y416F mutant. The parental enzyme and the Y416A and Y416F mutants were all able to add araCTP (1-beta-D-arabinofuranosylcytosine-5'-triphosphate) to a primer but with reduced efficiency relative to dCTP. Based on our kinetic results, interpreted in the context of the crystal structure of the RB69 gp43 ternary complex, we suggest that sugar discrimination is provided mainly by the Tyr416 side chain which can sterically block the 2'-OH group of an incoming rNTP.

Alanine↗

Modulation of radiation response and tumor-induced angiogenesis after epidermal growth factor receptor inhibition by ZD1839 (Iressa).

ZD1839 ("Iressa") is an orally-active, selective epidermal growth factor receptor-tyrosinekinase inhibitor. We evaluated the antitumor activity of ZD1839 in combination with radiation in human squamous cell carcinomas (SCCs) of the head and neck. ZD1839 produced a dose-dependent inhibition of cellular proliferation in human SCCs grown in culture. Flow cytometry analysis of cell cycle progression confirmed the accumulation of cells in G(1) phase after exposure to ZD1839. Clonogenic analysis demonstrated that treatment of SCCs with ZD1839 reduced cell survival after radiation exposure. Flow cytometric analysis further demonstrated that treatment of SCCs with ZD1839 amplified radiation-induced apoptosis. Tumor xenograft studies confirmed that oral administration of ZD1839, or focal radiation, resulted in partial and transient tumor regression in both SCC-1 and SCC-6 xenografts. In contrast, profound tumor regression and regrowth delay was observed in mice treated with the combination of ZD1839 and radiation. To examine antiangiogenic effects, we studied the impact of ZD1839 on human umbilical vascular endothelial cells (HUVECs). In the presence of reconstituted Matrigel matrix, HUVECs established a capillary-like network structure (tube formation). Treatment with ZD1839 reduced the cell-to-cell interaction of HUVECs, resulting in disruption of tube formation. The effect of ZD1839 was further examined using an in vivo tumor xenograft model of angiogenesis (Matrigel plug) in athymic mice. Systemic treatment with ZD1839 significantly inhibited tumor-induced neovascularization across the Matrigel plug. Taken together, these results suggest that the antitumor activity of ZD1839 in combination with radiation appears to derive from not only proliferative growth inhibition (with associated cell cycle arrest and enhancement of radiation-induced apoptosis) but also from inhibition of tumor angiogenesis.

Animals↗

[Effect of low-dosage aspirin combined with perindopril on prostacyclin, thromboxone A2, and norepinephrine in rabbits' blood].

OBJECTIVE: To explore the interaction of low-dosage aspirin combined with angiotensin-converting enzyme (ACE) inhibitors by prostacyclin (PGI2), thromboxone A2 (TXA2) and norepinephrine (NE)) levels in rabbits' blood. METHODS: Forty healthy New Zealand rabbits were divided into four groups. Blood samples were drawn from the rabbits' heart before and after a consecutive four-week. NE was measured by high performance liquid chromatography, and PGI2 and TXA2 were measured by radioimmunoassay. RESULTS: ACE inhibitors increased PGI2 levels (P < 0.05, P < 0.01); low-dosage aspirin suppressed TXA2 productions (P < 0.05, P < 0.01) after the four-week administration. Aspirin combined with ACE inhibitors led to a significant increase in PGI2/TXA2(P < 0.01), together with a significant decrease in NE levels in the rabbits' blood (P < 0.001). CONCLUSION: Neither low-dosage aspirin nor ACE inhibitors influence NE levels alone. The ratio of PGI2 to TXA2 increased, and NE levels decreased significantly during the administration of aspirin combined with ACE inhibitors. The results suggest that there is a synergis-action between low-dosage aspirin and ACE inhibitors due to increased PGI2/TXA2 and decreased NE levels.

Angiotensin-Converting Enzyme Inhibitors↗

Mapping of electrostatic potential in deep submicron CMOS devices by electron holography.

Quantitative two-dimensional maps of electrostatic potential in device structures are obtained using off-axis electron holography with a spatial resolution of 6 nm and a sensitivity of 0.17 V. Estimates of junction depth and variation in electrostatic potential obtained by electron holography, process simulation, and secondary ion mass spectroscopy show close agreement. Measurement artifacts due to sample charging and surface "dead layers" do not need to be considered provided that proper care is taken with sample preparation. The results demonstrate that electron holography could become an effective method for quantitative 2D analysis of dopant diffusion in deep-submicron devices.

Journal Article↗

Controlled synthesis and magnetic properties of 2D and 3D iron azide networks infinity2[Fe(N3)2(4,4'-bpy)] and infinity3[Fe(N3)2(4,4'-bpy)].

Controlled synthesis of transition metal complexes with mixed ligands has led to two new compounds with the same empirical formula [Fe(N3)2(4,4'-bpy)] (4,4'-bpy=4,4'- bipyridine). The compound 2D-[Fe(N3)2(4,4'-bpy)] (I) contains end-on (EO) bridging azido ligands. It crystallizes in the orthorhombic crystal system, space group Cmmm (No. 65): a=11.444(2) A, b=15.181(3) A, c=3.458(1) A, V=600.8(2) A(3), and Z=2. The compound 3D-[Fe(N3)2(4,4'-bpy)] (II) contains end-to-end (EE) azido bridges. It belongs to the tetragonal crystal system, space group P4(1)2(1)2 (No. 92): a=8.132(1) A, b=8.132(1) A, c=16.708(3) A, V=1104.9(5) A(3), and Z=4. Crystals of I and II have been grown by the diffusion method. Phase-pure samples of both compounds have been obtained by means of an optimal solution synthesis. Spontaneous long-range magnetic ordering was found in both I and II, with I being a metamagnet, and II being a ferromagnet. For I, in the low-field region, multiple transitions at TN1=20 K and TN2=5 K were observed, and these indicated the existence of Fe moment reorientation. Heat capacity measurements on II confirmed ferromagnetic transition at TC=20 K.

Journal Article↗

Analytical study of the principal angle used in optical experiments.

An analytical method has been developed for directly calculating the principal angle theta(p) at which the phase difference between the two reflection coefficients is equal to 90 degrees and at which the ratio of /r(p)/ to /r(s)/ is equal or close to a minimum. The equations given here can be used in many optical applications. For example, ellipsometric data measured at an incidence angle theta(p) will have higher precision than data measured at other incidence angles. theta(p) is the principal angle. Instead of three principal angles, there is only one principal angle, which can be found in the region of 0 < or = theta(p) < or = 90 degrees for most metallic materials used in applications. Results show good agreement between the measured and the calculated spectra of delta(p) and rho(po).

Journal Article↗