Biomedical subjects

Yu Lu

Publications and source records attributed to Yu Lu.

At least 19 recordsLinked to original sources

PubMed2025

ClinGen recuration of hearing loss-associated genes demonstrates significant changes in gene-disease validity over time.

PURPOSE: The Clinical Genome Resource (ClinGen) Hearing Loss Gene Curation Expert Panel was assembled in 2016 and has since curated 174 gene-disease relationships (GDRs) using ClinGen's semiquantitative framework. ClinGen mandates the timely recuration of all GDRs classified as Disputed, Limited, Moderate, and Strong every 2 to 3 years. METHODS: Thirty-five GDRs met the criteria for recuration within 2 years of original curation. Previous evidence was reevaluated using the latest curation guidelines, and a comprehensive literature review was performed to obtain new evidence. Recurations were approved by the Gene Curation Expert Panel and published on the ClinGen website (www.clinicalgenome.org). RESULTS: Eight of 35 GDRs (22%) changed their classification. Two Moderate and 5 Strong GDRs were upgraded to Definitive because of new case evidence. One Strong was subsumed under another Definitive GDR after evaluation of the lumping/splitting of disease entities. Twenty-seven of 35 patients remained unchanged, with little to no new evidence reported. CONCLUSION: Genes classified as Moderate and Strong were likely to build evidence and change their classification over time, whereas Limited were unlikely to gain evidence. These findings highlight the critical role of recuration in ensuring that genetic tests and research studies incorporate the most recent evidence into their efforts.

Humans↗

PubMed2024

Genotype-phenotype spectrum and correlation of PHARC Syndrome due to pathogenic ABHD12 variants.

BACKGROUND: A comprehensive understanding of the genetic basis of rare diseases and their regulatory mechanisms is essential for human molecular genetics. However, the genetic mutant spectrum of pathogenic genes within the Chinese population remains underrepresented. Here, we reported previously unreported functional ABHD12 variants in two Chinese families and explored the correlation between genetic polymorphisms and phenotypes linked to PHARC syndrome. METHODS: Participants with biallelic pathogenic ABHD12 variants were recruited from the Chinese Deafness Genetics Cohort. These participants underwent whole-genome sequencing. Subsequently, a comprehensive literature review was conducted. RESULTS: Two Han Chinese families were identified, one with a compound heterozygous variant and the other with a novel homozygous variant in ABHD12. Among 65 PHARC patients, including 62 from the literature and 3 from this study, approximately 90% (57 out of 63) exhibited hearing loss, 82% (50 out of 61) had cataracts, 82% (46 out of 56) presented with retinitis pigmentosa, 79% (42 out of 53) experienced polyneuropathy, and 63% (36 out of 57) displayed ataxia. Seventeen different patterns were observed in the five main phenotypes of PHARC syndrome. A total of 33 pathogenic variants were identified in the ABHD12. Compared with other genotypes, individuals with biallelic truncating variants showed a higher incidence of polyneuropathy (p = 0.006), but no statistically significant differences were observed in the incidence of hearing loss, ataxia, retinitis pigmentosa and cataracts. CONCLUSIONS: The diagnosis of PHARC syndrome is challenging because of its genetic heterogeneity. Therefore, exploring novel variants and establishing genotype-phenotype correlations can significantly enhance gene diagnosis and genetic counseling for this complex disease.

Humans↗

PubMed2006

Histologic evaluation of direct pulp capping with a self-etching adhesive and calcium hydroxide in beagles.

OBJECTIVE: To evaluate the pulpal response of beagles following direct pulp capping with Clearfil SE Bond (SB), a self-etching adhesive. STUDY DESIGN: One hundred thirty sound teeth from 6 male beagles were used. One hundred twenty teeth had their pulp mechanically exposed at the bottom of the class V cavities and were divided into 2 groups. In group 1, teeth were capped with SB; group 2 teeth were capped with calcium hydroxide cement (CH). Ten teeth were kept intact as an untreated control group. After 7, 30, and 90 days, 40 teeth from 2 beagles were extracted and processed for light microscopic examination. RESULTS: After the 7-day observation period, inflammatory reaction in the SB group was similar to that of the CH group (P > .05). After the 30-day and 90-day observation periods, inflammatory reaction was slight in both groups, but less dentin bridge formation was observed in specimens from the SB group than in those from the CH group (P < .05). CONCLUSION: SB showed good biocompatibility with pulp, but its ability to induce reparative dentin was lower than that of CH.

Animals↗

PubMed2006

Off-line form of the Michaelis-Menten equation for studying the reaction kinetics in a polymer microchip integrated with enzyme microreactor.

We firstly transformed the traditional Michaelis-Menten equation into an off-line form which can be used for evaluating the Michaelis-Menten constant after the enzymatic reaction. For experimental estimation of the kinetics of enzymatic reactions, we have developed a facile and effective method by integrating an enzyme microreactor into direct-printing polymer microchips. Strong nonspecific adsorption of proteins was utilized to effectively immobilize enzymes onto the microchannel wall, forming the integrated on-column enzyme microreactor in a microchip. The properties of the integrated enzyme microreactor were evaluated by using the enzymatic reaction of glucose oxidase (GOx) with its substrate glucose as a model system. The reaction product, hydrogen peroxide, was electrochemically (EC) analyzed using a Pt microelectrode. The data for enzyme kinetics using our off-line form of the Michaelis-Menten equation was obtained (K(m) = 2.64 mM), which is much smaller than that reported in solution (K(m) = 6.0 mM). Due to the hydrophobic property and the native mesoscopic structure of the poly(ethylene terephthalate) film, the immobilized enzyme in the microreactor shows good stability and bioactivity under the flowing conditions.

Enzyme Stability↗

PubMed2006

Temperature dependence of human ether-a-go-go-related gene K+ currents.

The function of voltage-gated human ether-à-go-go related gene (hERG) K(+) channels is critical for both normal cardiac repolarization and suppression of arrhythmias initiated by premature excitation. These important functions are facilitated by their unusual kinetics that combine relatively slow activation and deactivation with rapid and voltage-dependent inactivation and recovery from inactivation. The thermodynamics of these unusual features were examined by exploring the effect of temperature on the activation and inactivation processes of hERG channels expressed in Chinese hamster ovary cells. Increased temperature shifted the voltage dependence of activation in the hyperpolarizing direction but that of inactivation in the depolarizing direction. This increases the relative occupancy of the open state and contributes to the marked temperature sensitivity of hERG current magnitude observed during action potential voltage clamps. The rates of activation and deactivation also increase with higher temperatures, but less markedly than do the rates of inactivation and recovery from inactivation. Our results also emphasize that one cannot extrapolate results obtained at room temperature to 37 degrees C by using a single temperature scale factor.

Action Potentials↗

PubMed2006

[Controlled observation on Guan-moxibustion and suspended moxibustion for treatment of herpes simplex virus facial neuritis].

OBJECTIVE: To evaluate clinical therapeutic effect of Guan-moxibustion on herpes simplex virus facial neuritis. METHODS: One hundred and sixty cases were enrolled in 3 centers and 157 cases were completed the study. All he patients were randomly divided into 2 groups, a Guan-moxibustion group and a suspended moxibustion plus acupuncture group. All of them were treated with basic acupuncture, and the Guan-moxibustion group were added with Guan-moxibustion and the suspended moxibustion group with suspended moxibustion. They were treated for 8 weeks, and facial disability index (FDI) and House-Brackmann facial nerve grading system were used to assess therapeutic effects. RESULTS: The effective rate was 91.0% in the Guan-moxibustion group and 72.2% in the suspended moxibustion group with a significant difference between the two groups (P < 0.05), the Guan-moxibustion being better than the suspended moxibustion group. CONCLUSION: The therapeutic effect of Guan-moxibustion plus acupuncture on herpes simplex virus facial neuritis is better than that of suspended moxibustion plus acupuncture.

Acupuncture Therapy↗

PubMed2006

[Effects of osmoconditioning on membrane lipid components and fatty acid content of cold-sensitive soybean seeds].

Cold-sensitive soybean (Glycisne max Zhonghuang No.22) seeds were used to investigate the effects of osmoconditioning for invigoration of seeds chilling tolerance and the changes in membrane lipid by thin layer chromatography and gas chromatography to disclose the role of membrane lipid played in imbibitional chilling resistance capacity. Results are as follows: being treated with 33% PEG6000, seeds germination index, vigor index and root dry weight presented the trend of upward as the osmocondition time prolonged. In 72 h, the percentage of unsaturated phospholipid (e.g. PC and PE) in soybean seed increased, composition of lipid fatty acid changed: the saturated fatty acid 16:0 content in PC, PE, PI significantly decreased, while unsaturated fatty acid 18:2 increased greatly, which led to increase index of unsaturation fatty acid of lipid. These changes were positively corrected with osmoconditioning time. After treated with PEG, membrane fluidity increased to provide precondition for preventing imbibitional chilling, keeping the integrity of membrane system and normal metabolism.

Chromatography, Gas↗

PubMed2005

Optofluidic control using photothermal nanoparticles.

Photothermal metallic nanoparticles have attracted significant attention owing to their energy-conversion properties. Here, we introduce an optofluidic application based on a direct optical-to-hydrodynamic energy conversion using suspended photothermal nanoparticles near the liquid-air interface. Using light beams with submilliwatt power, we can drive and guide liquid flow in microfluidic channels to transport biomolecules and living cells at controlled speeds and directions. Previously, a variety of methods for controlling microscale liquid flow have been developed owing to the increasing interest for microfluidics-based biochemical analysis systems. However, our method dispenses with the need for complex pump and valve devices, surface chemistry and electrode patterning, or any other further effort towards substrate fabrication. Instead, our optofluidic control method will allow the fabrication of all-optical large-scale integrated microfluidic circuits for biomolecular and cellular processing without any physical valve or mechanical pumping device.

Electrochemistry↗

PubMed2005

A negative regulatory element-dependent inhibitory role of ITF2B on IL-2 receptor alpha gene.

Despite the fact that the negative regulatory element (NRE) within the upstream regulatory region of human IL-2 receptor alpha (IL-2Ralpha) gene has been identified two decades ago, mechanisms of the NRE function on the gene are hitherto unknown. In this paper, we report for the first time that the immunoglobulin transcription factor 2B (ITF2B) encoded by transcription factor 4 (TCF4) gene is a NRE binding protein. The full-length TCF4 cDNA clone was obtained from a HTLV-1 transformed human peripheral T cell MACHERMAKER cDNA library with NRE as the bait in yeast one-hybrid system. The NRE binding ability of ITF2B was further confirmed in chromatin-immunoprecipitation assay. Competitive RT-PCR-based promoter activity assay showed that over-expression of ITF2B protein inhibited the expression of IL-2Ralpha gene in Jurkat cells in an NRE-dependent manner. The function of ITF2B on the inhibition of both the IL-2Ralpha and the 5'LTR activity of HIV-1 shed light on the essence of NRE binding protein as a potential target for immune therapy and treatment in AIDS patients.

Base Sequence↗

PubMed2005

Identification of kinectin as a novel Behçet's disease autoantigen.

There has been some evidence that Behçet's disease (BD) has a significant autoimmune component but the molecular identity of putative autoantigens has not been well characterized. In the initial analysis of the autoantibody profile in 39 Chinese BD patients, autoantibodies to cellular proteins were uncovered in 23% as determined by immunoblotting. We have now identified one of the major autoantibody specificities using expression cloning. Serum from a BD patient was used as a probe to immunoscreen a lambdaZAP expression cDNA library. Candidate autoantigen cDNAs were characterized by direct nucleotide sequencing and their expressed products were examined for reactivity to the entire panel of BD sera using immunoprecipitation. Reactivity was also examined with normal control sera and disease control sera from patients with lupus and Sjögren's syndrome. Six independent candidate clones were isolated from the cDNA library screen and were identified as overlapping partial human kinectin cDNAs. The finding that kinectin was an autoantigen was verified in 9 out of 39 (23%) BD patient sera by immunoprecipitation of the in vitro translation products. Sera from controls showed no reactivity. The significance of kinectin as a participant in autoimmune pathogenesis in BD and the potential use of autoantibody to kinectin in serodiagnostics are discussed.

Adult↗

PubMed2005

Rapid method for design and fabrication of passive micromixers in microfluidic devices using a direct-printing process.

We developed a facile and rapid one-step technique for design and fabrication of passive micromixers in microfluidic devices using a direct-printing process. A laser printing mechanism was dexterously adopted to pattern the microchannels with different gray levels using vector graphic software. With the present method, periodically ordered specific bas-relief microstructures can be easily fabricated on transparencies by a simple printing process. The size and shape of the resultant microstructures are determined by the gray level of the graphic software and the resolution of the laser printer. Patterns of specific bas-relief microstructures on the floor of a channel act as obstacles in the flow path for advection mixing, which can be used as efficient mixing elements. The mixing effect of the resultant micromixer in microfluidic devices was evaluated using CCD fluorescence spectroscopy. We found that the mixing performance depends strongly on the gray level values. Under optimal conditions, fast passive mixing with our periodic ordered patterns in microfluidic devices has been achieved at the very early stages of the laminar flow. In addition, fabrication of micromixers using the present versatile technique requires less than an hour. The present method is promising for fabrication of micromixers in microfluidic devices at low cost and without complicated devices and environment, providing a simple solution to mixing problems in the micro-total-analysis-systems field.

Biomedical Technology↗

PubMed2005

Nanophotonic crescent moon structures with sharp edge for ultrasensitive biomolecular detection by local electromagnetic field enhancement effect.

We present novel gold nanophotonic crescent moon structures with a sub-10 nm sharp edge, which can enhance local electromagnetic field at the edge area. The formation of unconventional nanophotonic crescent moon structure is accomplished by using a sacrificial nanosphere template and conventional thin film deposition method, which allows an effective batch nanofabrication and precise controls of nanostructure shapes. Unique multiple scattering peaks are observed in a single gold nanocrescent moon with dark-field white light illumination. A 785 nm near-infrared (NIR) diode laser was used as the excitation source to induce the amplified scattering field on the sharp edge of the single gold nanocrescent moon. The Raman scattering spectrum of Rhodamine 6G molecules adsorbed on the single gold nanocrescent moon are characterized, and the Raman enhancement factor of single gold nanocrescent moon is estimated larger than 10(10), which suggests the potential applications of gold nanocrescent moons in ultrasensitive biomolecular detection and cellular imaging using surface enhanced Raman spectroscopy.

Electromagnetic Fields↗

PubMed2005

High-density silver nanoparticle film with temperature-controllable interparticle spacing for a tunable surface enhanced Raman scattering substrate.

The formation of high-density silver nanoparticles and a novel method to precisely control the spacing between nanoparticles by temperature are demonstrated for a tunable surface enhanced Raman scattering substrates. The high-density nanoparticle thin film is accomplished by self-assembling through the Langmuir-Blodgett (LB) technique on a water surface and transferring the particle monolayer to a temperature-responsive polymer membrane. The temperature-responsive polymer membrane allows producing a dynamic surface enhanced Raman scattering substrate. The plasmon peak of the silver nanoparticle film red shifts up to 110 nm with increasing temperature. The high-density particle film serves as an excellent substrate for surface-enhanced Raman spectroscopy (SERS), and the scattering signal enhancement factor can be dynamically tuned by the thermally activated SERS substrate. The SERS spectra of Rhodamine 6G on a high-density silver particle film at various temperatures is characterized to demonstrate the tunable plasmon coupling between high-density nanoparticles.

Acrylic Resins↗

PubMed2005

[Apoptosis of human carcinoma of mouth floor KB cells and multidrug resistant KBv200 cells induced by azide methyl anthraquinone derivative].

AIM: To determine the effects of azide methyl anthraquinone derivative (AMAD) on growth inhibition and inducing apoptosis of multidrug resistant (MDR) KBv200 cells and parental drug-sensitive KB cells. METHODS: Cytotoxicity was determined by tetrazolium (MTF) assay. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (deltapsi(m)) in cells were labeled with DCFH-DA and DiOC6 and tested by flow cytometry. Annexin V stain and DNA ladder were used to examine the apoptosis of KB and KBv200 cells induced by AMAD. RESULTS: AMAD was shown to inhibit the growth of KB and KBv200 cells significantly in a concentration-dependent manner, with mean IC50 of 0.36 and 0.45 micromol x L(-1), respectively. The generation of ROS increased obviously after the cells were treated with AMAD for 12 h, up to the peak in 24 h, meanwhile the levels of deltapsi(m) were time-dependently decreased. DNA fragmentation appeared on the agarose gel. Annexin V stain showed AMAD induced apoptosis of KB and KBv200 cells also in a concentration-dependent manner. CONCLUSION: AMAD showed inhibitory effect on both MDR KBv200 cells and parental drug-sensitive KB cells. The mechanism of action was associated with the increase of the cellular ROS level and the decrease of the mitochondrial membrane potential induced by AMAD, which result in cell apoptosis.

Anthraquinones↗

PubMed2005

[High expression of alpha-D-galactosidase gene (aga1) of Bifidobacterium breve 203 in Escherichia coli].

Alpha-D-galactosidase gene (agal) of Bifidobacterium breve 203 was cloned into temperature expression vector pBV220 and transformed into E. coli. The recombinant plasmid pBVagal was induced to express with temperature. The specific activities of recombinant enzyme Agal in E. coli DH5alpha, E. coli DH10B and E. coli BL21 were 28.08 U/mg, 19.44 U/mg and 13.85 U/mg, respectively. The recombinant plasmid pBVagal is more stable in E. coli BL21. The molecular weight of Agal as determined by SDS-PAGE was about 67 kD. The optimum pH of Agal was pH 4.0-4.4, and it was stable between pH 3.6 and 6.0 (kept at 4 degrees C overnight). The optimum temperature of Agal was 45 degrees C, and it was stable below 40 degrees C (incubated for 30 min). Km-values for p-nitrophenyl-alpha-galactopyranoside (pNPGal) and melibiose were calculated with 1.43 mmol/L and 261 mmol/L, respectively. No transgalactosylation activity was found when Agal hydrolyzed melibiose or raffinose. The results suggest that Agal is much different from reported alpha-D-galactosidase from Bi. breve 203. Agal is another kind of alpha-D-galactosidase in the same bifidobacteria strain.

Bifidobacterium↗

PubMed2005

[Histological evaluation of direct pulp capping with a self-etching adhesive and calcium hydroxide].

OBJECTIVE: To evaluate the beagles' pulp response following direct pulp capping with Clearfil SE BOND (SB). METHODS: 130 sound teeth were used. 120 had their pulps mechanically exposed and were divided in two groups. In group A, teeth were capped with SB. In group B, teeth were capped with calcium hydroxide (CH). The left 10 teeth were used as control. After 7, 30 and 90 days, the teeth were extracted and processed for light microscopical examination. RESULTS: In 7 day observation period, inflammatory reaction in SB group was slighter than that of CH group, but the difference was statistical insignificant. In the 30 day and 90 day observation period, inflammatory reaction was slight in both groups, but specimens with dentin bridge formation was significantly less in SB group than in CH group (P < 0.05). CONCLUSION: SB showed acceptable biocompatibility with pulp, but its ability to induce hard tissue barrier on pulp exposure is weaker than CH.

Adhesives↗

PubMed2004

Prevalence and risk factors of knee osteoarthritis in Huang-Pu District, Shanghai, China.

OBJECTIVES: A community-based survey on the prevalence of knee osteoarthritis (OA) and associated factors was carried out in Shanghai, People's Republic of China. METHODS: Of 2,305 registered residents >or=40 years of age, 2,093 were examined by interview and questionnaire. One hundred ninety knee pain-positive and 510 knee pain-negative subjects received radiography. RESULTS: Radiographic knee OA (RKOA) was found in 72.1% (137/190) of symptomatic and 41.6% (212/510) of asymptomatic subjects (SKOA and AsKOA, respectively). The estimated prevalences of symptomatic and asymptomatic knee OA in the community were 7.2% and 37.4%, respectively. Women had higher SKOA prevalence than men (9.8% vs 3.7%, P<0.01). Compared with Caucasians, the urban Shanghai population had a higher prevalence of tibiofemoral joint OA. CONCLUSIONS: There was a higher proportion of SKOA than AsKOA (72.1% vs 41.6%), and SKOA was significantly more associated with disability (81.0% vs 26.9%, P<0.01). The prevalence of SKOA increased with age, from 1.3% in the 40-49-year-old age group to 13.2% in the 70+ group. Age, body mass index, and female gender were associated risk factors for knee OA.

China↗

PubMed2004

Absolute quantification of specific proteins in complex mixtures using visible isotope-coded affinity tags.

The identification of proteins in complex mixtures is most useful when quantitative information is also obtained. We describe a new type of protein tagging reagent called the visible isotope-coded affinity tag (VICAT) which allows the absolute amount of a target protein or proteins to be quantified in a complex biological sample such as a eukaryotic cell lysate. VICAT reagents tag thiol groups of cysteines or thioacetylated amino groups and introduce into the tryptic peptide a biotin affinity handle, a visible moiety for tracking the chromatographic location of the target peptide by a method other than mass spectrometry, a photocleavable linker for removing a portion of the tag, and an isotope tag for distinguishing sample and internal standard peptides. We demonstrate the use of VICAT reagents together with isoelectric focusing of peptides on an immobilized gel strip followed by combined micro-liquid chromatography/electrospray ionization mass spectrometry operating in selected reaction monitoring mode to determine the absolute abundance of a specific protein, human group V phospholipase A(2), in eukaryotic cell lysates. It is found that human lung macrophages contain 66 fmol of this protein per 100 microg of cell protein. Western blot analysis of human group V phospholipase A(2) in macrophages gave inconclusive data. VICAT reagents should be useful for numerous applications including the analysis of candidate disease markers in complex mixtures such as serum.

Amino Acid Sequence↗