Biomedical subjects

Yi Pan

Publications and source records attributed to Yi Pan.

At least 19 recordsLinked to original sources

PubMed2026

Multiple metabolic factors and kidney dysfunction: Causal evidence and translational insights from a mendelian randomization study.

Chronic kidney disease is a major global public health burden. This study investigated the causal effects of systolic blood pressure (SBP), apolipoprotein B (ApoB), and serum urate on renal function and albuminuria, and explored potential mechanistic implications. Two-sample Mendelian randomization (MR) analyses were conducted using large-scale genome-wide association study summary statistics from European populations. Univariable MR estimated total causal effects on estimated glomerular filtration rate (eGFR) and albuminuria. Multivariable MR assessed independent effects of correlated exposures, and 2-step MR evaluated albuminuria as a mediator. Cis-MR analyses were performed to explore target-proximal genetic evidence for lipid-related drug targets. Genetically predicted SBP was causally associated with reduced eGFR, while ApoB was inversely associated with albuminuria risk. serum urate showed no significant causal effects. Multivariable and mediation analyses supported distinct roles of SBP and ApoB, with albuminuria partially mediating the SBP-eGFR association. Cis-MR analyses indicated heterogeneous renal effects of lipid-lowering targets. These findings provide genetic evidence linking SBP to renal dysfunction, suggest that albuminuria may partially mediate the association between SBP and renal function, and highlight the complex renal relevance of lipid-related pathways.

Mendelian Randomization Analysis↗

PubMed2007

Homocysteine-mediated reactivity and assembly of gold nanoparticles.

This paper reports the findings of an investigation of the reactivity and assembly of gold nanoparticles mediated by homocysteine (Hcys), a thiol-containing amino acid found in plasma. The aim is to gain insight into the interparticle interaction and reactivity, which has potential application for the detection of thiol-containing amino acids. By monitoring the evolution of the surface plasmon resonance absorption and the dynamic light scattering of gold nanoparticles in the presence of Hcys, the assembly was shown to be dependent on the nature and concentration of the electrolytes, reflecting an effective screening of the diffuse layer around the initial citrate-capped nanoparticles that decreases the barrier to the Hcys adsorption onto the surface, and around the subsequent Hcys-capped nanoparticles that facilitate the zwitterion-type electrostatic interactions between amino acid groups of Hcys bound to different nanoparticles. A key element of the finding is that the interparticle zwitterion interaction of the Hcys-Au system is much stronger than the expectation for a simple Hcys or Au solution, a new phenomenon originating from the unique nanoscale interparticle interaction. The strength and reversibility of the interparticle zwitterion-type electrostatic interactions between amino acid groups are evidenced by the slow disassembly upon increasing pH at ambient temperatures and its acceleration at elevated temperature. These findings provide new insight into the precise control of interfacial interactions and reactivities between amino acids anchored to nanoparticles and have broad implications in the development of colorimetric nanoprobes for amino acids.

Chemistry, Physical↗

PubMed2007

Heparan sulfate Ndst1 gene function variably regulates multiple signaling pathways during mouse development.

Disruption of heparan sulfate (HS) synthesis in vertebrate development causes malformations that are composites of those caused by mutations of multiple HS binding growth factors and morphogens. We previously reported severe developmental defects of the forebrain and the skull in mutant mice bearing a targeted disruption of the heparan sulfate-generating enzyme GlcNAc N-deacetylase/GlcN N-sulfotransferase 1 (Ndst1). Here, we further characterize the molecular mechanisms leading to frontonasal dysplasia in Ndst1 mutant embryos and describe additional malformations, including impaired spinal and cranial neural tube fusion and skeletal abnormalities. Of the numerous proteins that bind HS, we show that impaired fibroblast growth factor, Hedgehog, and Wnt function may contribute to some of these phenotypes. Our findings, therefore, suggest that defects in HS synthesis may contribute to multifactor types of congenital developmental defects in humans, including neural tube defects.

Alkaline Phosphatase↗

PubMed2006

A novel approach to phylogenetic tree construction using stochastic optimization and clustering.

BACKGROUND: The problem of inferring the evolutionary history and constructing the phylogenetic tree with high performance has become one of the major problems in computational biology. RESULTS: A new phylogenetic tree construction method from a given set of objects (proteins, species, etc.) is presented. As an extension of ant colony optimization, this method proposes an adaptive phylogenetic clustering algorithm based on a digraph to find a tree structure that defines the ancestral relationships among the given objects. CONCLUSION: Our phylogenetic tree construction method is tested to compare its results with that of the genetic algorithm (GA). Experimental results show that our algorithm converges much faster and also achieves higher quality than GA.

Algorithms↗

PubMed2006

An improved ant colony algorithm with diversified solutions based on the immune strategy.

BACKGROUND: Ant colony algorithm has emerged recently as a new meta-heuristic method, which is inspired from the behaviours of real ants for solving NP-hard problems. However, the classical ant colony algorithm also has its defects of stagnation and premature. This paper aims at remedying these problems. RESULTS: In this paper, we propose an adaptive ant colony algorithm that simulates the behaviour of biological immune system. The solutions of the problem are much more diversified than traditional ant colony algorithms. CONCLUSION: The proposed method for improving the performance of traditional ant colony algorithm takes into account the polarization of the colonies, and adaptively adjusts the distribution of the solutions obtained by the ants. This makes the solutions more diverse so as to avoid the stagnation and premature phenomena.

Algorithms↗

PubMed2006

Heparan sulfate biosynthetic gene Ndst1 is required for FGF signaling in early lens development.

Multiple signaling molecules, including bone morphogenic proteins (BMP) and fibroblast growth factors (FGF), play important roles in early lens development. However, how these morphogens are regulated is still largely unknown. Heparan sulfate participates in both morphogen transport and morphogen-receptor interaction. In this study, we demonstrate that inactivation of the heparan sulfate biosynthetic gene Ndst1 resulted in invagination defects of the early lens and in the disruption of lens-determination gene expression, leading to severe lens hypoplasia or anophthalmia. Ndst1 mutants exhibited reduced sulfation of heparan sulfate, but both BMP- and Wnt-signaling remained unchanged. Instead, these embryos showed diminished binding of a subset of FGF proteins to FGF receptors. Consistent with disruption of FGF signaling, expression of phospho-Erk and ERM were also downregulated in Ndst1-mutant lenses. Taken together, these results establish an important role of Ndst1 function in FGF signaling during lens development.

Animals↗

PubMed2006

Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro.

Prolyl hydroxylation of hypoxible-inducible factor alpha (HIF-alpha) proteins is essential for their recognition by pVHL containing ubiquitin ligase complexes and subsequent degradation in oxygen (O(2))-replete cells. Therefore, HIF prolyl hydroxylase (PHD) enzymatic activity is critical for the regulation of cellular responses to O(2) deprivation (hypoxia). Using a fusion protein containing the human HIF-1alpha O(2)-dependent degradation domain (ODD), we monitored PHD activity both in vivo and in cell-free systems. This novel assay allows the simultaneous detection of both hydroxylated and nonhydroxylated PHD substrates in cells and during in vitro reactions. Importantly, the ODD fusion protein is regulated with kinetics identical to endogenous HIF-1alpha during cellular hypoxia and reoxygenation. Using in vitro assays, we demonstrated that the levels of iron (Fe), ascorbate, and various tricarboxylic acid (TCA) cycle intermediates affect PHD activity. The intracellular levels of these factors also modulate PHD function and HIF-1alpha accumulation in vivo. Furthermore, cells treated with mitochondrial inhibitors, such as rotenone and myxothiazol, provided direct evidence that PHDs remain active in hypoxic cells lacking functional mitochondria. Our results suggest that multiple mitochondrial products, including TCA cycle intermediates and reactive oxygen species, can coordinate PHD activity, HIF stabilization, and cellular responses to O(2) depletion.

Animals↗

PubMed2006

Grazing angle mirror-backed reflection (GMBR) for infrared analysis of monolayers on silicon.

An easy handling infrared measurement, grazing angle mirror-backed reflection (GMBR), has been established to analyze the silicon-based organic monolayer. Theoretical prediction gave the optimal configuration with p-polarized irradiation near a grazing angle 78.1 degrees of incidence. Experimental measurement of hydrogen-terminated, undecylenic acid (UA) and N-hydroxysuccinimide (NHS) functionalized silicon (111) surfaces showed good signal peaks and reproducibility.

Letter↗

PubMed2006

Pax6 is regulated by Meis and Pbx homeoproteins during pancreatic development.

Pancreatic development depends on the transcription factor Pax6, which controls islet cell differentiation and hormone production. To understand the regulation of Pax6 pancreatic expression, we have identified a minimal Pax6 pancreatic enhancer and show that it contains a composite binding site for Meis and Pbx homeoproteins. We further show that Meis proteins are expressed during pancreatic development, and together with Pbx, are able to form a synergistic binding complex on the Pax6 pancreatic enhancer. When tested in transgenic mice, both the Meis and Pbx sites are essential for Pax6 pancreatic enhancer activity, and the composite site can be functionally replaced by a consensus Meis-Pbx sequence. In addition, analysis of Pbx1 and Pbx2 knockout mice demonstrates that, during pancreatic islet formation, Pax6 expression becomes dependent upon Pbx1 and Pbx2 function. As Meis homeoproteins have been previously demonstrated to regulate Pax6 expression during lens development, these results suggest a conserved mechanism of Pax6 regulation by Meis homeoproteins in two different organs.

Animals↗

PubMed2006

Random assembly of GABA rho1 and rho2 subunits in the formation of heteromeric GABA(C) receptors.

1. Various combinations of the rho subunits (rho(1A), rho(1B), rho(2A), rho(2B)) of GABA(C) receptors cloned from white perch retina were expressed in Xenopus oocytes, and electrophysiological and pharmacological methods were used to test their ability to co-assemble into heteromeric receptors. Simultaneous injection of the two subunits, irrespective of their relative proportions, led invariably to the formation of a preponderance of heteromeric receptors. 2. The GABA deactivation responses elicited from these cells could be described by a single exponential decay, and their pharmacological responses deviated significantly from those expected of a simple mixture of two homomeric rho(1) and rho(2) receptors. In contrast, a double exponential function comprising fast and slow components was required to fit the GABA deactivation responses elicited from oocytes sequentially expressing rho(1) and rho(2) subunits, a condition that favors the formation of a mixture of homomeric rho(1) and rho(2) receptors. 3. Both the GABA-response kinetics and the sensitivity to picrotoxin of the heteromeric perch rho(1B)rho(2A) receptor varied with the proportion of the subunit RNA injected, indicating there is no fixed stoichiometry for their co-assembly into heteromeric rho(1)rho(2) receptors. 4. If native GABA(C) receptors in retinal neurons behave in a similar manner as in the oocyte expression system, these finding suggest that the properties of their GABA(C) receptors are likely to be influenced by the transcription/translation efficiency of GABA rho subunit genes.

Animals↗

PubMed2006

Water-soluble CdSe and CdSe/CdS nanocrystals: a greener synthetic route.

We report a new green synthetic route of CdSe and core-shell CdSe/CdS nanoparticles (NPs) in aqueous solutions. This route is performed under water-bath temperature, using Se powder as a selenium source to prepare CdSe NPs, and H(2)S generated by the reaction of Na(2)SH(2)SO(4) as a sulfur source to synthesize core-shell CdSe/CdS NPs at 25-35 degrees C. The synthesis time of every step is only 20 min. After illumination with ambient natural light, photoluminescence (PL) intensities of CdSe NPs enhanced up to 100 times. The core-shell CdSe/CdS NPs have stronger photoactive luminescence with quantum yields over 20%. The obtained CdSe NPs exhibit a favorable narrow PL band (FWHM: 50-37 nm) with increasing molar ratio of Cd/Se from 4:1 to 10:1 at pH 9.1 in the crude solution, whereas PL band of corresponding CdSe/CdS NPs is slightly narrower. The emission maxima of nanocrystals can be tuned in a wider range from 492 to 592 nm in water by changing synthesis temperature of CdSe core than those reported previously. The resulting new route is of particular interest as it uses readily-available reagents and simple equipment to synthesize high-quality water-soluble CdSe and CdSe/CdS nanocrystals.

Journal Article↗

PubMed2006

Efficacy of omega-3 fatty acids in preventing age-related macular degeneration: a systematic review.

TOPIC: What is the evidence for efficacy of dietary and/or supplemental omega-3 fatty acids in preventing age-related macular degeneration (AMD)? CLINICAL RELEVANCE: Age-related macular degeneraion is the leading cause of blindness and vision impairment in persons older than 50 years living in North America. There is no cure for AMD, and treatment does not usually restore vision but only prevents disease progression to a modest degree. omega-3 fatty acids are considered potentially important antioxidants and are being considered as an arm of the Age-Related Eye Disease Study II clinical trial. METHODS/LITERATURE REVIEWED: Keywords were searched in Medline, Pre-Medline, Embase, and the Cochrane Library on Ovid. There was no restriction on the year or language of publication. RESULTS: There were 6 observational studies found, but the specific outcomes, exposures, and covariates studied all varied greatly. CONCLUSION: There is some clinical evidence for protection of AMD from omega-3 fatty acids. However, the results are not consistent. Hence, our conclusion is that this issue is neither clearly supported nor refuted by the present world literature. This is an intriguing and extremely important question but needs further study first with prospective cohort designs and, if positive, randomized clinical trials.

Antioxidants↗

PubMed2006

Trabeculectomy and phacotrabeculectomy, with mitomycin-C, show similar two-year target IOP outcomes.

BACKGROUND: To determine the efficacy and safety of trabeculectomy with mitomycin-C (trabMMC) compared with that of single-site phacotrabeculectomy with mitomycin-C (phacotrabMMC) in glaucoma patients at increased risk for filtering surgery failure. METHODS: Eighty-five consecutive eyes that underwent trabMMC and 105 consecutive eyes that underwent phacotrabMMC were retrospectively compared up to 2 years postoperatively with respect to intraocular pressure (IOP), number of glaucoma medications, and surgical complication rates. The primary outcome was the difference in the cumulative proportion of patients meeting the target IOP range at 2 years. Secondary outcomes included mean postoperative IOP, mean IOP drop from baseline, mean number of glaucoma medications, and surgical complication rates. RESULTS: Baseline characteristics were similar in the 2 groups and most patients had advanced glaucoma with a similar upper limit of the target IOP range (15.5 +/- 2.6 mm Hg for trabMMC vs. 15.3 +/- 2.1 mm Hg for phacotrabMMC, p = 0.56). Loss to follow-up was significant in both groups (almost 50% over 2 years). A statistically similar proportion of patients achieved their target IOP range at 1 and 2 years in both groups: the cumulative success rate at 2 years was 29.04% and 22.91% (p = 0.44) without add-on glaucoma therapy, 25.38% and 25.22% (p = 0.60) with the use of up to 2 glaucoma medications, and 30.01% and 25.17% (p = 0.81) with the use of any number of glaucoma medications, in the trabMMC and phacotrabMMC groups, respectively. Mean postoperative IOP was also similar between the 2 groups at almost all follow-up times up to 2 years (13.56 +/- 4.92 mm Hg in trabMMC vs. 13.98 +/- 4.74 mm Hg in phacotrabMMC at 2 years, p = 0.67). The mean IOP drop from baseline was significantly greater in the trabMMC group throughout the study period (-10.87 +/- 8.33 mm Hg in trabMMC vs. -6.15 +/- 7.01 mm Hg in phacotrabMMC at 2 years, p = 0.003); however, baseline IOP was also higher in the trabMMC group (26.1 mm Hg vs. 20.3 mm Hg, p < 0.0001). Serious postoperative complication rates were similarly low between the 2 groups. INTERPRETATION: TrabMMC and phacotrabMMC may be equally safe and effective in bringing IOP to within an acceptable target range over 2 years in advanced glaucoma patients at increased risk for filtering surgery failure, although trabMMC appears to be associated with greater IOP lowering from baseline.

Adult↗

PubMed2006

Rule generation for protein secondary structure prediction with support vector machines and decision tree.

Support vector machines (SVMs) have shown strong generalization ability in a number of application areas, including protein structure prediction. However, the poor comprehensibility hinders the success of the SVM for protein structure prediction. The explanation of how a decision made is important for accepting the machine learning technology, especially for applications such as bioinformatics. The reasonable interpretation is not only useful to guide the "wet experiments," but also the extracted rules are helpful to integrate computational intelligence with symbolic AI systems for advanced deduction. On the other hand, a decision tree has good comprehensibility. In this paper, a novel approach to rule generation for protein secondary structure prediction by integrating merits of both the SVM and decision tree is presented. This approach combines the SVM with decision tree into a new algorithm called SVM_ DT, which proceeds in three steps. This algorithm first trains an SVM. Then, a new training set is generated through careful selection from the output of the SVM. Finally, the obtained training set is used to train a decision tree learning system and to extract the corresponding rule sets. The results of the experiments of protein secondary structure prediction on RS126 data set show that the comprehensibility of SVM_DT is much better than that of the SVM. Moreover, the generalization ability of SVM_DT is better than that of C4.5 decision trees and is similar to that of the SVM. Hence, SVM_DT can be used not only for prediction, but also for guiding biological experiments.

Algorithms↗

PubMed2006

The Rx-like homeobox gene (Rx-L) is necessary for normal photoreceptor development.

PURPOSE: The retinal homeobox (Rx) gene plays an essential role in retinal development. An Rx-like (Rx-L) gene from Xenopus laevis has been identified. The purpose of this study was to analyze the function of Rx-L in the developing retina. METHODS: DNA-binding properties of Rx-L were analyzed by electrophoretic mobility shift assay (EMSA), with in vitro-translated proteins and radiolabeled oligonucleotide probe. The Rx-L expression pattern was analyzed by in situ hybridization using whole or sectioned embryos and digoxigenin-labeled antisense riboprobes. Rx-L loss of function was studied by using antisense morpholino oligonucleotides targeted to the Rx-L translation initiation site. Embryos injected with control or Rx-L morpholinos were analyzed at stage 41 or 45. RESULTS: Rx-L shares homology with Rx at the homeo-, OAR, and Rx domains, but lacks an octapeptide motif. Rx-L is expressed in the developing retina beginning in the early tailbud stage. In the maturing retina, Rx-L expression is restricted primarily to the developing photoreceptor layer and the ciliary marginal zone. Rx-L can bind a photoreceptor conserved element-1 (PCE-1) oligonucleotide, an element conserved among all known photoreceptor gene promoters. In a promoter activity assay, Rx-L functions as a stronger transcriptional activator than Rx. Antisense morpholino-mediated knockdown of Rx-L expression resulted in a decrease in rhodopsin and red cone opsin expression levels in Xenopus retinas. Injection of the Rx-L antisense morpholino oligonucleotide also resulted in a decrease in the length of both rod and cone outer segments. CONCLUSIONS: The results suggest that Rx-L functions to regulate rod and cone development by activating photoreceptor-specific gene expression.

Amino Acid Sequence↗

PubMed2006

[Nuclear expression of Survivin in glioma and its correlation to prognosis].

BACKGROUND & OBJECTIVE: Survivin, an inhibitor of apoptosis protein, is correlated to aggressive behavior, resistance to chemotherapy and radiotherapy, and prognosis of human cancers. It is expressed in both nuclei and cytoplasm. Recent research revealed that the nuclear expression of survivin is an important prognostic factor of human cancers. This study was to investigate the nuclear expression of Survivin in human glioma, and its correlations to clinicopathologic characteristics and prognosis. METHODS: The nuclear expression of Survivin in 88 specimens of glioma (33 at grade I-II, and 55 at grade III-IV) was detected by tissue microarray and immunohistochemistry. Its correlations to clinicopathologic characteristics and prognosis were analyzed. RESULTS: The positive rate of nuclear Survivin was 27.3% in the whole group. It was significantly lower in grade I-II gliomas than in grade III-IV gliomas (12.1% vs. 36.4%, P=0.013). Nuclear expression of Survivin had no correlation to patient's age (P=0.053), sex (P=0.376), Karnofsky performance status (P=0.486), and clinical stage (P=0.359). The 5-year overall survival rate and 3-year disease-freely survival rate were significantly lower in nuclear Survivin-positive group than in nuclear Survivin-negative group (22.7% vs. 47.7%, P=0.005; 13.7% vs. 39.5%, P=0.015). The median survival was slightly lower in high nuclear Survivin expression group than in low nuclear Survivin expression group (14.9 months vs. 20.2 months, P=0.089). CONCLUSIONS: The nuclear expression of Survivin is related to the pathologic grade of glioma, and might be a negative prognostic factor of glioma.

Adolescent↗

PubMed2006

[Comparison between PET/CT and MRI in diagnosing lymph node metastasis and N staging of nasopharyngeal carcinoma].

OBJECTIVE: To compare the clinical significance of PET/CT and MRI in diagnosing lymph node metastasis and N staging of nasopharyngeal carcinoma (NPC). METHODS: 116 NPC patients had undergone PET/CT and MRI before therapy. The findings of PET/CT and MRI in diagnosing lymph node metastasis and N staging were compared according to the results of follow-up. RESULTS: A total of 614 lymph nodes in 116 patients were analyzed. 340 positive nodes and 274 negative nodes interpreted by image findings were verified during follow-up. The sensitivity, specificity and accuracy of PET/CT in diagnosing node metastasis was 93.2%, 98.2% and 95.4%, while that of MRI was 88.8%, 91.2% and 89.9%, respectively, with statistically significant difference in each between PET/CT and MRI (P < 0.05). Based on Fuzhou Staging System, 109 patients (94.0%) were correctly staged by PET/CT, and 103 patients (88.8%) by MRI, while according to UICC Staging System, 108 patients (93.1%) were correctly staged by PET/CT, and 100 patients (86.2%) by MRI. CONCLUSION: PET/CT is superior to MRI in diagnosing lymph node metastasis and N staging of nasopharyngeal carcinoma. The false-positive and false-negative assessment based on PET-CT scan findings may be caused by: (1) inflammatory hyperplastic node; (2) node with large areas of necrosis; (3) node in diameter less than spatial resolution limitation of PET.

Adolescent↗

PubMed2005

Diffusion of hydrosilanes from the control layer to the vinylsilane-rich flow membrane during the fabrication of microfluidic chips.

During the fabrication of poly(dimethylsiloxane) (PDMS)-based microfluidic chips, polymethylhydrosiloxane (PMHS) species in the control layer diffuse into the flow membrane, which contains polymethylvinylsiloxane (PMVS), and the components cross-link together to form the mechanically enhanced membrane. The diffusion course was investigated by using attenuated total reflectance FTIR and the improvement of mechanical properties of the flow membrane was studied by measuring the Young's modulus and the tensile strength.

Journal Article↗