Biomedical subjects

Gang Yu

Publications and source records attributed to Gang Yu.

At least 19 recordsLinked to original sources

PubMed2026

Identification of Two Novel Compound Heterozygous ADAMTS17 Variants Associated With Weill-Marchesani Syndrome 4.

PURPOSE: Weill-Marchesani syndrome 4 (WMS4) is frequently underdiagnosed when standard exome sequencing fails to detect noncoding pathogenic variants. We aimed to identify the genetic cause in a patient with suspected WMS4 and to characterize the splicing-altering mechanism of a deep intronic variant in ADAMTS17. MATERIALS AND METHODS: Whole-exome sequencing combined with whole-genome sequencing was conducted in the proband, who presented with ocular and skeletal manifestations of WMS4. A minigene splicing assay was applied to verify the splicing abnormality caused by the deep intronic variant. RESULTS: The patient showed high myopia, brachydactyly, accelerated growth velocity, and advanced bone age. Two novel compound heterozygous variants in ADAMTS17, c.1655G>A and c.450+38C>A, were identified. The deep intronic variant c.450+38C>A was confirmed by minigene assay to disrupt normal pre-messenger RNA splicing by inducing retention of a 35-base pair intronic segment, leading to a frameshift and premature termination (p.G152Lfs*23). CONCLUSIONS: This study broadens the mutational spectrum of ADAMTS17. Whole-genome sequencing combined with functional splicing validation is essential for resolving molecularly undiagnosed cases of WMS4, particularly when deep intronic variants are suspected, and supports clinical genetic testing and genetic counseling of hereditary connective tissue disorders.

ADAMTS17↗

PubMed2025

Midkine attenuates amyloid-β fibril assembly and plaque formation.

Proteomic profiling of Alzheimer disease (AD) brains has identified numerous understudied proteins, including midkine (MDK), that are highly upregulated and correlated with amyloid-β (Aβ) from the early disease stage but their roles in disease progression are not fully understood. Here, we present that MDK attenuates Aβ assembly and influences amyloid formation in the 5xFAD amyloidosis mouse model. MDK protein mitigates fibril formation of both Aβ40 and Aβ42 peptides according to thioflavin T fluorescence, circular dichroism, negative-stain electron microscopy and nuclear magnetic resonance analyses. Knockout of the Mdk gene in 5xFAD increased amyloid formation and microglial activation in the brain. Further comprehensive mass-spectrometry-based profiling of the whole proteome and detergent-insoluble proteome in these mouse models indicated significant accumulation of Aβ and Aβ-correlated proteins, along with microglial components. Thus, our structural and mouse model studies reveal a protective role of MDK in counteracting amyloid pathology in AD.

Animals↗

PubMed2006

Electrocatalytic hydrodechlorination of 4-chlorobiphenyl in aqueous solution using palladized nickel foam cathode.

The electrocatalytic hydrodechlorination of 4-chlorobiphenyl on palladized nickel foam with high porous structure in an aqueous solution containing MeOH, bromide of hexadecyltrimethylammonium (CTAB), sodium acetate, and acetic acid were investigated in a membrane-separated flow-through cell. The Pd/Ni foam electrode was prepared by electroless deposition method, on which the Pd particles dispersed finely over Ni foam surface indicated by SEM-EDX analysis. The effects of current density, organic cosolvent, initial concentration, temperature, and flow rate on the hydrodechlorination of 4-chlorobiphenyl were examined. Methanol was among the best cosolvents and was used in preferential concentration of 50 vol%. Moderate current density (e.g., 2.23 mA cm(-2)), relatively high initial concentration, temperature, and flow rate were beneficial to improve the hydrodechlorination of 4-chlorobiphenyl. The current efficiencies for the conversion of 1mM 4-MCB decreased with increasing current density and range from 37.2% at 0.74 mA cm(-2) to 14.1% at 5.21 mA cm(-2) after 20 min electrolysis cut. Under the optimized conditions, 1mM of 4-MCB could be removed rapidly with the rate of 94.6% after 2h electrolysis, which gave current efficiencies and energy consumptions in range of 8.1-24.6% and 1.7-5.2 kW h kg(-1), respectively.

Biphenyl Compounds↗

PubMed2006

Design and preliminary evaluation of a portable device for the measurement of bioimpedance spectroscopy.

Portable bioimpedance spectroscopy (BIS) devices are of great value for monitoring the pathological status of biological tissues in clinical and home environments. The two traditional techniques for measuring complex bioimpedance, the bridge method and quadrature demodulation method, are either time-consuming or often associated with high cost, high power consumption, and large board space, and therefore are not ideally suitable for designing a portable device for BIS measurement. This paper describes a novel design of a portable BIS device based on the magnitude-ratio and phase-difference detection method and its implementation using the newest generation of analog electronic products which greatly decrease the complexity of both hardware and software. In order to improve the accuracy of the device, a three-reference calibration algorithm was applied. Experimental sweep-frequency measurements on RC circuits were carried out to preliminarily evaluate the performances of the device. The results obtained by the device were found to be in good agreement with the results measured by a commercial impedance analyzer HP4194, with an overall mean error of 0.014% in magnitude and 0.136 degrees in phase over a frequency range of 20 kHz to 1 MHz.

Adult↗

PubMed2006

Ubiquitin-proteasome pathway mediates degradation of APH-1.

Gamma-secretase catalyzes intramembraneous proteolysis of several type I transmembrane proteins, including beta-amyloid precursor protein (APP), to generate amyloid beta protein (Abeta), a key player in the pathogenesis of Alzheimer's disease (AD). The critical components of the gamma-secretase complex include presenilin (PS), nicastrin (NCT), presenilin enhancer-2 (PEN-2) and anterior pharynx defective-1 (APH-1). Abnormalities of the ubiquitin-proteasome pathway have been implicated in the pathogenesis of AD; while PS and PEN-2 turnover is regulated by this pathway, it is unknown whether the ubiquitin-proteasome pathway is also involved in the degradation of APH-1 protein. In this study, we found that the expression of endogenous and exogenous APH-1 significantly increased in cells treated with proteasome-specific inhibitors. The effect of the proteasome inhibitors on APH-1 was dose- and time-dependent. APH-1 protein was ubiquitinated. Pulse-chase metabolic labeling experiments showed that the degradation of newly synthesized radiolabeled APH-1 proteins was inhibited by lactacystin. Disruption of the PS1 and PS2 genes did not affect the degradation of APH-1 by the ubiquitin-proteasome pathway. Furthermore, over-expression of APH-1 and inhibition of proteasomal APH-1 degradation facilitated gamma-secretase cleavage of APP to generate Abeta. These results demonstrate that the degradation of APH-1 protein is mediated by the ubiquitin-proteasome pathway.

Acetylcysteine↗

PubMed2006

Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder. Mutations in presenilins 1 and 2 (PS1 and PS2) account for approximately 40% of familial AD (FAD) cases. FAD mutations and genetic deletions of presenilins have been associated with calcium (Ca(2+)) signaling abnormalities. We demonstrate that wild-type presenilins, but not PS1-M146V and PS2-N141I FAD mutants, can form low-conductance divalent-cation-permeable ion channels in planar lipid bilayers. In experiments with PS1/2 double knockout (DKO) mouse embryonic fibroblasts (MEFs), we find that presenilins account for approximately 80% of passive Ca(2+) leak from the endoplasmic reticulum. Deficient Ca(2+) signaling in DKO MEFs can be rescued by expression of wild-type PS1 or PS2 but not by expression of PS1-M146V or PS2-N141I mutants. The ER Ca(2+) leak function of presenilins is independent of their gamma-secretase activity. Our data suggest a Ca(2+) signaling function for presenilins and provide support for the "Ca(2+) hypothesis of AD."

Alzheimer Disease↗

PubMed2006

Thienorphine is a potent long-acting partial opioid agonist: a comparative study with buprenorphine.

A strategy in the development of new treatment for opioid addiction is to find partial opioid agonists with properties of long duration of action and high oral bioavailability. In a search for such compounds, thienorphine, a novel analog of buprenorphine, was synthesized. Here, we reported that, like buprenorphine, thienorphine bound potently and nonselectively to mu-, delta-, and kappa-opioid receptors stably expressed in CHO (Chinese hamster ovary) cells and behaved as a partial agonist at mu-opioid receptor. However, some differences were observed between the pharmacological profiles of thienorphine and buprenorphine. In vitro, thienorphine was more potent than buprenorphine in inhibiting [3H]diprenorphine and stimulating guanosine 5'-O-(3-[35S]thio)triphosphate binding to rat mu-opioid receptor stably expressed in CHO cells. In vivo, thienorphine exhibited a less potent but more efficacious antinociceptive effect with an ED50 value of 0.25 mg/kg s.c. and more potent antimorphine effect with an ED50 value of 0.64 mg/kg intragastric, compared with buprenorphine. Additionally, the bioavailability of thienorphine was greatly higher than that of buprenorphine after oral administration. Moreover, compared with buprenorphine, thienorphine showed a similar long-lasting antinociceptive effect but a much longer antagonism of morphine-induced lethality (more than 15 days). These results indicate that thienorphine is a potent, long-acting partial opioid agonist with high oral bioavailability and may have possible application in treating addiction.

Analgesics, Opioid↗

PubMed2006

sorLA: sorting out APP.

The accumulation of amyloid-beta peptides in the brain is a major factor of Alzheimer Disease. Central to the production of the amyloid-beta peptides are the proteolytic secretases, which, recently, have been important targets of drug discovery. Newly published results indicate that the sorting protein-related receptor sorLA/LR11 regulates processing and trafficking of the precursor of the amyloid-beta peptides, revealing an alternative target for developing molecular clinical therapeutic compounds for Alzheimer Disease.

Alzheimer Disease↗

PubMed2006

[Assessment of adenoid size in children by flexible fibrescope examination].

OBJECTIVE: To assess the adenoid size in children by flexible fibrescope examination and outline an effective therapeutic program according to the examination. METHOD: In this study, the flexible fibrescope examination of the nasal cavity and nasopharynx and a lateral skull radiograph examination were performed in 130 children with snoring and the same examinations were performed in another 30 children without snoring. RESULT: The size of adenoid was negatively associated with the degree of snoring. (P < 0.01). There is a high correlation between the flexible fibrescope examination and the lateral skull radiograph examination (r = 0.435, P < 0.01). CONCLUSION: The application of the flexible fibrescope examination of the nasal cavity and nasopharynx has proved to be of great clinical value, especially in the selection of children for adenoidectomy. It is an examination with minor invasion which can be well tolerated by most children, giving more information than a lateral skull radiograph and avoiding unnecessary radiation.

Adenoids↗

PubMed2006

[Study of poly (3,4-ethylene dioxythiophene) : poly (styrene sulfonate) by in-situ resonance Raman spectroscopy].

Poly (3,4-ethylene dioxythiophene) (PEDOT): Poly (styrene sulfonate) (PSS) has attracted a lot of interest for application in organic electronics due to good stability and high electronic conductivity in its doped state. Indeed, thin layers of PEDOT:PSS was regularly used in light emitting diodes (PLEDs) as hole injection and transportation layer. Here, Doping and dedoping states of PEDOT:PSS were studied by absorbance spectra and Raman spectra. A new absorption band centered at 620 nm was observed on dedoped PEDOT:PSS. Consistently, Raman signals of dedoped PEDOT:PSS are resonantly intensified since the Raman excitation wavelength (633 nm) is set in the enhanced absorption band. So it gives a sensitive way to study the doping and dedoping states of PEDOT:PSS. Furthermore, for the encapsulated polymer light-emitting diodes, Raman spectroscopy is a powerful way to study the polymer layers inside the devices.

English Abstract↗

PubMed2005

Quantitative structure-property relationships on photodegradation of polybrominated diphenyl ethers.

By partial least squares (PLS) regression, quantitative structure-property relationship (QSPR) models were developed for photodegradation rates (k(p)) and quantum yields (Phi) of polybrominated diphenyl ethers (PBDEs) in methanol/water (8:2), and photodegradation rates in pure methanol by UV light in the sunlight region, respectively. Quantum chemical descriptors computed by PM3 Hamiltonian were used as predictor variables. The cross-validated Q(cum)(2) values for three optimal QSPR models of PBDEs are above 0.90 (remarkably higher 0.50), indicating good predictive abilities for logk(p) and logPhi values of PBDEs. The QSPR results show that logk(p) values of PBDEs in methanol/water (8:2) and in pure methanol are governed by different molecular structural descriptors, respectively, which implies that photodegradation rates of PBDEs are affected by the characteristics of solution in which it takes place.

Environmental Pollutants↗

PubMed2005

Combined effect of microwave and activated carbon on the remediation of polychlorinated biphenyl-contaminated soil.

The application of microwave and activated carbon for the treatment of polychlorinated biphenyl (PCB) contaminated soil was explored in this study with a model compound of 2,4,5-trichlorobiphenyl (PCB29). PCB-contaminated soil was treated in a quartz reactor by microwave irradiation at 2450MHz with the addition of granular activated carbon (GAC). In this procedure, GAC acted as microwave absorbent for reaching high temperature and reductant for dechlorination. A sheltered type-K thermocouple was applied to record the temperature rising courses. It was shown that the addition of GAC could effectively promote the temperature rising courses. The determination of PCB residues in soil by gas chromatography (GC) revealed that rates of PCB removal were highly dependent on microwave power, soil moisture content, and the amount of GAC added. GC with mass spectrum (MS) detector and ion chromatography were employed for the analysis of degradation intermediates and chlorine ions, respectively. It was suggested that microwave irradiation with the assistance of activated carbon might be a potential technology for the remediation of PCB-contaminated soil.

Carbon↗

PubMed2005

An investigation of the treatment of particulate matter from gasoline engine exhaust using non-thermal plasma.

A plasma reactor with catalysts was used to treat exhaust gas from a gasoline engine in order to decrease particulate matter (PM) emissions. The effect of non-thermal plasma (NTP) of the dielectric discharges on the removal of PM from the exhaust gas was investigated experimentally. The removal efficiency of PM was based on the concentration difference in PM for particle diameters ranging from 0.3 to 5.0 microm as measured by a particle counter. Several factors affecting PM conversion, including the density of plasma energy, reaction temperature, flow rate of exhaust gas, were investigated in the experiment. The results indicate that PM removal efficiency ranged approximately from 25 to 57% and increased with increasing energy input in the reactor, reaction temperature and residence time of the exhaust gas in the reactor. Enhanced removal of the PM was achieved by filling the discharge gap of the reactor with Cu-ZSM-5 catalyst pellets. In addition, the removal of unburned hydrocarbons was studied. Finally, available approaches for PM conversion were analyzed involving the interactions between discharge and catalytic reactions.

Air Pollution↗

PubMed2005

Nicastrin functions as a gamma-secretase-substrate receptor.

gamma-secretase catalyzes the intramembrane cleavage of amyloid precursor protein (APP) and Notch after their extracellular domains are shed by site-specific proteolysis. Nicastrin is an essential glycoprotein component of the gamma-secretase complex but has no known function. We now show that the ectodomain of nicastrin binds the new amino terminus that is generated upon proteolysis of the extracellular APP and Notch domains, thereby recruiting the APP and Notch substrates into the gamma-secretase complex. Chemical- or antibody-mediated blocking of the free amino terminus, addition of purified nicastrin ectodomain, or mutations in the ectodomain markedly reduce the binding and cleavage of substrate by gamma-secretase. These results indicate that nicastrin is a receptor for the amino-terminal stubs that are generated by ectodomain shedding of type I transmembrane proteins. Our data are consistent with a model where nicastrin presents these substrates to gamma-secretase and thereby facilitates their cleavage via intramembrane proteolysis.

Amyloid Precursor Protein Secretases↗

PubMed2005

Quantitative structure-property relationships on photolysis of PCDD/Fs adsorbed to spruce (Picea abies (L.) Karst.) needle surfaces under sunlight irradiation.

By partial least squares (PLS) regression, quantitative structure-property relationship (QSPR) models were developed for photolysis half-life (t1/2) of PCDD/Fs and PAHs sorbed to spruce (Picea abies (L.) Karst.) needle surfaces and irradiated by sunlight. Quantum chemical descriptors computed by PM3 Hamiltonian were used predictor variables. PLS analysis for the PCDDs and PAHs respectively resulted in no correlation by our statistical methods. The cross-validated Qcum2 value for the optimal QSPR model of PCDFs is 0.722, indicating a good predictive ability for logt1/2 of PCDFs adsorbed to spruce needle surfaces. The QSPR results show that the number of chlorine atoms bonded to the parent structure and (E(LUMO)-E(HOMO))2 has a dominant effect on t1/2 values of PCDFs. Increasing the number of chlorine atoms and (E(LUMO)-E(HOMO))2 values leads to increase of logt1/2 values of PCDFs.

Adsorption↗

PubMed2005

Production of a bioflocculant by Aspergillus parasiticus and its application in dye removal.

Aspergillus parasiticus was found to produce a bioflocculant with high flocculating activity for Kaolin suspension and water-soluble dyes. Results showed that the carbon and nitrogen sources favorable for the production of the bioflocculant were corn starch and peptone, and an optimal condition of 28 degrees C, initial pH 5-6 and shaking speed of 150 rpm. The highest flocculating efficiency achieved for Kaolin suspension was 98.1%, after 72 h cultivation. The bioflocculant was mainly composed of sugar (76.3%) and protein (21.6%), and an average molecular weight of 3.2x10(5) Da. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectra showed that amino, amide and hydroxyl groups were present in the bioflocculant molecules. The bioflocculant was effective in flocculating some soluble anionic dyes in aqueous solution, in particular Reactive Blue 4 and Acid Yellow 25 with a decolorization efficiency of 92.4 and 92.9%, respectively. The decolorization efficiency was dependent on the flocculant dosage and solution pH. XPS result shows that the amine groups in the bioflocculant were protonated at pH 5, and thus the positive bioflocculant was attracted to the negatively charged dye molecules. The amino and amide groups in the bioflocculant molecule are believed to play an important role in flocculation from the viewpoint of electrostatic interaction.

Aspergillus↗

PubMed2005

Aph-1 interacts at the cell surface with proteins in the active gamma-secretase complex and membrane-tethered Notch.

The activity of the gamma-secretase complex is critical for the processing of a number of transmembrane proteins, including Notch. Functional gamma-secretase activity can be reconstituted from four proteins--presenilin, nicastrin, Pen-2 and Aph-1--but the role of the individual proteins remains unclear. In this report we describe the cellular localization and protein interactions of Aph-1, with particular regard to Notch receptor processing. We found that Aph-1 is present at the cell surface, where it interacts with Pen-2, the mature forms of presenilin and nicastrin, and full-length Notch. Aph-1 also interacts with a truncated form of Notch, which is a direct substrate for gamma-secretase, but not with the Notch intracellular domain. Immunoprecipitation data for Notch and Aph-1 showed that the Notch-containing gamma-secretase complexes most likely form a small subset of the total number of gamma-secretase complexes. In conclusion, these data demonstrate that Aph-1 is present at the cell surface, presumably in active gamma-secretase complexes, and interacts with the Notch receptor, both before and after ligand activation.

Amyloid Precursor Protein Secretases↗

PubMed2005

[Application of depth-analysis of confocal Raman micro-spectroscopy to chirography identification].

Depth analysis of confocal Raman micro-spectroscopy was applied to chirography identification. The result indicated that depth analysis has potential application to forensic science field, especially in longitudinal identification of ink and inkpad. No matter what the spatial distributions of the signature pen and inkpad are, confocal Raman micro-spectroscopy can longitudinally distinguish those spatial differences. All those suggested that confocal Raman micro-spectroscopy is a fast, simple, high sensitive and non-destructive technique.

Forensic Medicine↗