Biomedical subjects

Wei Cheng

Publications and source records attributed to Wei Cheng.

At least 19 recordsLinked to original sources

PubMed2025

Proteomic-based identification of novel EV-derived protein antibodies biomarkers for melioidosis diagnosis.

Melioidosis, caused by Burkholderia pseudomallei (Bp), is a life-threatening disease characterized by diverse clinical manifestations and limited diagnostic capabilities. Extracellular vesicles (EVs) have emerged as critical carriers of novel antibody targets for serodiagnosis. In this study, we established a Bp-infected BEAS-2B cell model (Bp/BEAS-2B) and isolated EV from both Bp and Bp/BEAS-2B cells to generate EV proteome, identifying potential antigenic biomarkers for melioidosis diagnosis. Bioinformatics analysis identified PPEP and POMCR proteins as candidate antigens, with BLF1 and omp A serving as positive controls. Using a self-developed IgM-ELISA, serum samples from 43 melioidosis patients and 47 healthy volunteers were analyzed to detect antibodies against these antigens. Anti-POMCR IgM demonstrated exceptional diagnostic performance, with an AUC of 0.9872 (95% CI: 0.9713-1.003), sensitivity of 93.02% and specificity of 97.92% at a cutoff value of OD450 = 0.118. Similarly, IgM against PPEP, BLF1, and omp A also showed high diagnostic accuracy, with AUC values of 0.969, 0.9621, and 0.976, respectively. The accuracy of anti-POMCR and anti-PPEP were 96.43% and 95.54%, respectively, equivalent to anti-omp A (93.75%) and anti-BLF1 (91.96%). Antibodies to EV-derived proteins effectively differentiated melioidosis patients from other bacterial infections and healthy volunteers, highlighting their clinical potential as diagnostic tools for melioidosis.

Humans↗

PubMed2024

Contribution of copy number variations to education, socioeconomic status and cognition from a genome-wide study of 305,401 subjects.

Educational attainment (EA), socioeconomic status (SES) and cognition are phenotypically and genetically linked to health outcomes. However, the role of copy number variations (CNVs) in influencing EA/SES/cognition remains unclear. Using a large-scale (n = 305,401) genome-wide CNV-level association analysis, we discovered 33 CNV loci significantly associated with EA/SES/cognition, 20 of which were novel (deletions at 2p22.2, 2p16.2, 2p12, 3p25.3, 4p15.2, 5p15.33, 5q21.1, 8p21.3, 9p21.1, 11p14.3, 13q12.13, 17q21.31, and 20q13.33, as well as duplications at 3q12.2, 3q23, 7p22.3, 8p23.1, 8p23.2, 17q12 (105 kb), and 19q13.32). The genes identified in gene-level tests were enriched in biological pathways such as neurodegeneration, telomere maintenance and axon guidance. Phenome-wide association studies further identified novel associations of EA/SES/cognition-associated CNVs with mental and physical diseases, such as 6q27 duplication with upper respiratory disease and 17q12 (105 kb) duplication with mood disorders. Our findings provide a genome-wide CNV profile for EA/SES/cognition and bridge their connections to health. The expanded candidate CNVs database and the residing genes would be a valuable resource for future studies aimed at uncovering the biological mechanisms underlying cognitive function and related clinical phenotypes.

Humans↗

PubMed2006

DeltaNp63 plays an anti-apoptotic role in ventral bladder development.

The bladder, the largest smooth-muscle organ in the human body, is responsible for urine storage and micturition. P63, a homolog of the p53 tumor-suppressor gene, is essential for the development of all stratified epithelia, including the bladder urothelium. The N-terminal truncated isoform of p63, DeltaNp63, is known to have anti-apoptotic characteristics. We have established that DeltaNp63 is not only the predominant isoform expressed throughout the bladder, but is also preferentially expressed in the ventral bladder urothelium during early development. We observed a host of ventral defects in p63-/- embryos, including the absence of the abdominal and ventral bladder walls. This number of ventral defects is identical to bladder exstrophy, a congenital anomaly exhibited in human neonates. In the absence of p63, the ventral urothelium was neither committed nor differentiated, whereas the dorsal urothelium was both committed and differentiated. Furthermore, in p63-/- bladders, apoptosis in the ventral urothelium was significantly increased. This was accompanied by the upregulation of mitochondrial apoptotic mediators Bax and Apaf1, and concurrent upregulation of p53. Overexpression of DeltaNp63gamma and DeltaNp63beta in p63-/- bladder primary cell cultures resulted in a rescue, evidenced by significantly reduced expressions of Bax and Apaf1. We conclude that DeltaNp63 plays a crucial anti-apoptotic role in normal bladder development.

Animals↗

PubMed2006

Metabolic monitoring of the electrically stimulated single heart cell within a microfluidic platform.

A device based on five individually addressable microelectrodes, fully integrated within a microfluidic system, has been fabricated to enable the real-time measurement of ionic and metabolic fluxes from electrically active, beating single heart cells. The electrode array comprised one pair of pacing microelectrodes, used for field-stimulation of the cell, and three other microelectrodes, configured as an electrochemical lactate microbiosensor, that were used to measure the amounts of lactate produced by the heart cell. The device also allowed simultaneous in-situ microscopy, enabling optical measurements of cell contractility and fluorescence measurements of extracellular pH and cellular Ca2+. Initial experiments aimed to create a metabolic profile of the beating heart cell, and results show well defined excitation-contraction (EC) coupling at different rates. Ca2+ transients and extracellular pH measurements were obtained from continually paced single myocytes, both as a function of the rate of cell contraction. Finally, the relative amounts of intra- and extra-cellular lactate produced during field stimulation were determined, using cell electroporation where necessary.

Aerobiosis↗

PubMed2006

Observation and tuning of hypersonic bandgaps in colloidal crystals.

Composite materials with periodic variations of density and/or sound velocities, so-called phononic crystals, can exhibit bandgaps where propagation of acoustic waves is forbidden. Phononic crystals are the elastic analogue of the well-established photonic crystals and show potential for manipulating the flow of elastic energy. So far, the experimental realization of phononic crystals has been restricted to macroscopic systems with sonic or ultrasonic bandgaps in the sub-MHz frequency range. In this work, using high-resolution Brillouin spectroscopy we report the first observation of a hypersonic bandgap in face-centred-cubic colloidal crystals formed by self-assembly of polystyrene nanoparticles with subsequent fluid infiltration. Depending on the particle size and the sound velocity in the infiltrated fluid, the frequency and the width of the gap can be tuned. Promising technological applications of hypersonic crystals, ranging from tunable filters and heat management to acousto-optical devices, are anticipated.

Journal Article↗

PubMed2006

HNF factors form a network to regulate liver-enriched genes in zebrafish.

Defects in some of liver-enriched genes in mammals will cause liver- and/or blood-related diseases. However, due to the fact that embryogenesis happens intrauterinally in the mammals, the function of these liver-enriched genes during liver organogenesis is poorly studied. We report here the identification of 129 genuine liver-enriched genes in adult zebrafish and show that, through in situ hybridization, 69 of these genes are also enriched in the embryonic liver. External embryogenesis coupled with the well-established morpholino-mediated gene knock-down technique in zebrafish offers us a unique opportunity to study if this group of genes plays any role during liver organogenesis in the future. As an example, preliminary study using morpholino-mediated gene knock-down method revealed that a novel liver-enriched gene leg1 is crucial for the liver expansion growth. We also report the analysis of promoter regions of 51 liver-enriched genes by searching putative binding sites for Hnf1, Hnf3, Hnf4 and Hnf6, four key transcription factors enriched in the liver. We found that promoter regions of majority of liver-enriched genes contain putative binding sites for more than one HNF factors, suggesting that most of liver-enriched genes are likely co-regulated by different combination of HNF factors. This observation supports the hypothesis that these four liver-enriched transcription factors form a network in controlling the expression of liver-specific or -enriched genes in the liver.

Amino Acid Sequence↗

PubMed2006

GFP-based FRET analysis in live cells.

Fluorescence resonance energy transfer (FRET) is a widely utilized optical technique for measuring small distances of 1-10 nm in live cells. In recent years, its application has been greatly popularized by the discovery of green fluorescent protein (GFP) and many improved variants which make good donor-acceptor fluorophore pairs. GFP-based proteins are structurally stable, relatively inert, and can be reliably attached to points of interest. The combination of easy access to the GFP-based FRET technique and its obvious usefulness in many applications can lead to complacency. Potential problems such as light contaminants, e.g., bleed-through and cross-talk, and inconsistent donor and acceptor concentrations are easily overlooked and can lead to errors in FRET calculation and data interpretation. In this article, we outline possible pitfalls of GFP-based FRET and approaches that address these issues, including a "Spectra FRET" technique that can be easily applied to live cell studies.

Animals↗

PubMed2006

Fabrication and characterization of polysulfone-dicalcium silicate composite films.

Polysulfone (PSU) composite films filled with Beta-dicalcium silicate (Beta-Ca(2)SiO(4)) particles are prepared by the solvent casting-evaporation method. The surface morphologies and mechanical properties of the films are determined. The bioactivity of the composite films is evaluated by soaking them in simulated body fluid (SBF) and the results show that the composites are bioactive as they induce the formation of hydroxyapatite (HAp) on the surface of the composite films. The measurement of the water contact angles suggests that the incorporation of Beta-Ca(2)SiO(4) particles into PSU matrix can improve the hydrophilicity of the composite. PSU composite films filled with modified Beta-dicalcium silicate (Beta-mCa(2)SiO(4)) particles are also prepared after Beta-Ca(2)SiO(4) particles are treated with dodecyl alcohol through surface esterification reactions. The infrared spectra of the Beta-mCa(2)SiO(4) particles before and after aging in water indicate that the surface modification is reversible. The scanning electron microscope (SEM) images (micrographs) of both composites show that the dispersion of inorganic particles in the polymer matrix improves after surface modification. The PSU-Beta-mCa(2)SiO(4) composite is still bioactive and exhibits the same water contact angle after aging in water as compared to that of the PSU-Beta-Ca(2)SiO(4) composite. All these results suggest that the incorporation of Beta-Ca(2)SiO(4) particles is a useful method to prepare composites with improved bioactivity and hydrophilicity, and the surface modification of Beta-Ca(2)SiO(4) particles can improve the dispersion while retaining the bioactivity and hydrophilicity.

Biocompatible Materials↗

PubMed2006

RNA translocation and unwinding mechanism of HCV NS3 helicase and its coordination by ATP.

Helicases are a ubiquitous class of enzymes involved in nearly all aspects of DNA and RNA metabolism. Despite recent progress in understanding their mechanism of action, limited resolution has left inaccessible the detailed mechanisms by which these enzymes couple the rearrangement of nucleic acid structures to the binding and hydrolysis of ATP. Observing individual mechanistic cycles of these motor proteins is central to understanding their cellular functions. Here we follow in real time, at a resolution of two base pairs and 20 ms, the RNA translocation and unwinding cycles of a hepatitis C virus helicase (NS3) monomer. NS3 is a representative superfamily-2 helicase essential for viral replication, and therefore a potentially important drug target. We show that the cyclic movement of NS3 is coordinated by ATP in discrete steps of 11 +/- 3 base pairs, and that actual unwinding occurs in rapid smaller substeps of 3.6 +/- 1.3 base pairs, also triggered by ATP binding, indicating that NS3 might move like an inchworm. This ATP-coupling mechanism is likely to be applicable to other non-hexameric helicases involved in many essential cellular functions. The assay developed here should be useful in investigating a broad range of nucleic acid translocation motors.

Adenosine Triphosphate↗

PubMed2006

The role of conservative management in congenital tracheal stenosis: an evidence-based long-term follow-up study.

BACKGROUND/PURPOSE: Surgery has been the management of choice for severe congenital tracheal stenosis (CTS). The role of conservative management of CTS however is not clear. The aim of this study is to characterize the natural history of CTS, review the radiologic evidence of tracheal growth, and evaluate the clinical outcome and selection criteria of conservative management of CTS. METHODS: A retrospective study was carried out on 22 consecutive children with symptomatic CTS admitted into a single institution between 1982 and 2001. The patients were categorized into operation (n = 11) and observation (n = 11) groups. Six patients of the observation group were followed up with serial computed tomography scan. Their tracheal growth was compared with that of healthy children of the same age. RESULTS: The mortality rates of observation and operation groups were 9% and 27%, respectively, although the latter group consisted of more severely affected patients. The pathologic categorization of the CTS influenced the survival rates (P = .046, chi2), with the long segment type having the worst prognosis (67%). Serial computed tomography scans of 6 conservatively managed patients revealed that all stenotic tracheas continued to grow (P = .039, 2-tailed paired Student's t test). Of the 6 stenotic tracheas, 5 grew at a faster-than-normal rate, and the stenotic tracheal diameters approached those of normal diameters by the age of 9 years. CONCLUSIONS: The management of patients with symptomatic CTS should be individualized. A selected group of patients with CTS can be safely managed nonoperatively.

Disease Progression↗

PubMed2006

[Fractionation and high performance capillary electrophoretic analysis of phospholipids].

Phosphatidylcholine of high purity (PC, content 92.80%) was prepared from market soybean power phospholipids (PC content 14.05%) by using solvent extraction and column chromatography. As the main objective, micellar electrokinetic capillary chromatography (MECC) was established for the separation and analysis of phospholipids. MECC conditions such as surfactant and its concentration, pH of running buffer solution, organic modifier and its volume content, concentration of buffer solution, temperature etc were optimized to provide good separation and larger peak area of phospholipids. The optimum MECC conditions were as follows: running buffer system of 35 mmol/L sodium deoxycholate (SDC)-1 mmol/L borax buffer solution/n-propanol (57 : 43, v/v) with pH 8.30, column temperature of 44 degrees C, applied voltage of 25 kV and ultraviolet (UV) detection at 200 nm. Addition of standards was used to identify the components of phospholipids. External standard method was used to determine PC content. As the results shown, five components of phospholipids could be effectively separated under the optimum MECC conditions. Correlation coefficient within 0.1 - 1 g/L PC concentration reached 0.999 0. The average recovery of PC was 98.0%. The intra-day relative standard deviation (RSD) and inter-day RSD of peak area of PC were 1.36% and 3.27%, respectively. The qualitative result of PC obtained by MECC was consistent with that determined by thin layer chromatography and infrared analysis, respectively. So MECC can be used as an effective tool for the separation, analysis and quality control of phospholipids.

Buffers↗

PubMed2006

A technique for retrograde intubation in mice.

Endrotracheal intubation is critical for some experimental studies in mice, but the animals' small size makes the procedure difficult. The authors describe a new, easily learned retrograde intubation method using angioplasty guide wire. They twice intubated anesthetized mice successfully with no airway complications caused by puncture of the trachea.

Anesthesia↗

PubMed2006

[Expressions of L-type calcium channel and potassium channel Kv4.3 in rapid paced primary cultured atrial myocytes].

OBJECTIVE: To study the expressions of L-type calcium channel alpha1c and potassium channel Kv4.3 at early stages of atrial fibrillation in a rapid paced primary cultured atrial myocyte model. METHODS: Primary rat atrial myocytes were cultured and a rapid paced cell model was established. The atrial cells were divided into five groups with pacing durations within 0 and 24 h. Reverse transcription-polymerase chain reaction and Western blot were applied to detect the messenger ribonucleic acid (mRNA) and proteins of L-type calcium channel alpha1c and potassium channel Kv4.3, respectively. RESULTS: mRNA expression of L-type calcium channel alpha1c reduced after 6 h of rapid pacing and continued to decline as the pacing process. The decrease of L-type calcium channel alpha1c protein was paralleled with mRNA expression and reached the lowest levels at 24 h. Similarly, changes of potassium channel Kv4.3 protein and mRNA were paralleled. Kv4.3 mRNA was not altered within the first 6 h. It was reduced after 12 h. However, longer pacing periods did not further decrease mRNA and protein expression levels of potassium channel Kv4.3. CONCLUSIONS: Expressions of L-type calcium channel alpha1c and potassium channel Kv4.3 were both reduced at different levels in early phase of rapid pacing atrial myocytes. It implicates the occurrence of ion channel remodeling of atrial myocytes, which may serve as molecular mechanism of electrical remodeling in the development of atrial fibrillation.

Animals↗

PubMed2006

[A preliminary study on the effect of prepubertal exposure of male rats to diethylstilbestrol on the apoptosis of spermatogenic cells after sexual maturation and its mechanism].

OBJECTIVE: To preliminarily study the effect of prepubertal exposure of male SD (Sprague-Dawley) rats to diethylstilbestrol (DES) on the apoptosis of spermatogenic cells after sexual maturation and its mechanism. METHODS: Thirty 21-day-old male SD rats were randomly divided into 4 experimental groups, DES 0.01, 0.1, 1.0 and 10.0 microg/(kg x d) and 1 control group. The experimental groups were injected (s.c.) with different doses of DES (dissolved in corn oil) during prepuberty [from postnatal day (PND) 22 to PND 35] and the control group with medium only. The apoptosis and related proteins Bcl-2 and Bax expressions of testicular spermatogenic cells were studied with TUNEL and immunohistochemistry after the rats sexual maturation (at PND 64). RESULTS: Compared with the control group, the apoptosis of testicular spermatogenic cells in the DES 0.01 microg/kg group had no difference, but significantly increased in the DES 0.1, 1.0 and 10.0 microg/kg groups and the apoptosis increased with the increase of DES dose. In the control and DES 0.01 microg/kg groups, Bax protein expressed weakly but Bcl-2 protein strongly in spermatogenic cells. With the increase of DES exposure, Bax protein expression in spermatogenic cells increased but Bcl-2 protein expression decreased. CONCLUSION: Prepubertal exposure of SD rats to inappropriate dose of DES can make the apoptosis of spermatogenic cells increase after sexual maturation. Bax and Bcl-2 proteins participate in the apoptotic course caused by prepubertal DES exposure.

Animals↗

PubMed2005

Excess l-arginine restores endothelium-dependent relaxation impaired by monocrotaline pyrrole.

The pyrrolizidine alkaloid plant toxin monocrotaline pyrrole (MCTP) causes pulmonary hypertension in experimental animals. The present study aimed to examine the effects of MCTP on the endothelium-dependent relaxation. We constructed an in vitro disease model of pulmonary hypertension by overlaying MCTP-treated bovine pulmonary artery endothelial cells (CPAEs) onto pulmonary artery smooth muscle cell-embedded collagen gel lattice. Acetylcholine (Ach) induced a relaxation of the control CPAEs-overlaid gels that were pre-contracted with noradrenaline, and the relaxation was inhibited by L-NAME, an inhibitor of NO synthase (NOS). In contrast, when MCTP-treated CPAEs were overlaid, the pre-contracted gels did not show a relaxation in response to Ach in the presence of 0.5 mM l-arginine. Expression of endothelial NOS protein, Ach-induced Ca2+ transients and cellular uptake of l-[3H]arginine were significantly smaller in MCTP-treated CPAEs than in control cells, indicating that these changes were responsible for the impaired NO production in MCTP-treated CPAEs. Since cellular uptake of l-[3H]arginine linearly increased according to its extracellular concentration, we hypothesized that the excess concentration of extracellular l-arginine might restore NO production in MCTP-treated CPAEs. As expected, in the presence of 10 mM l-arginine, Ach showed a relaxation of the MCTP-treated CPAEs-overlaid gels. These results indicate that the impaired NO production in damaged endothelial cells can be reversed by supplying excess l-arginine.

Animals↗

PubMed2005

Mechanical strength of amorphous CaCO3 colloidal spheres.

Amorphous glassy CaCO3 colloidal spheres of monomodal size distribution were studied by high-resolution Brillouin light scattering. The Young modulus of 37 GPa and shear modulus of 14 GPa of glassy CaCO3 at a density of 1.9 g/cm3 were extracted from the particle vibration frequencies by employing acoustic wave scattering cross-section calculations. The line shape of the low-frequency modes is a sensitive index of the particle polydispersity.

Journal Article↗

PubMed2005

Autoinhibition of Escherichia coli Rep monomer helicase activity by its 2B subdomain.

DNA helicases catalyze separation of double-helical DNA into its complementary single strands, a process essential for DNA replication, recombination, and repair. The Escherichia coli Rep protein, a superfamily 1 DNA helicase, functions in DNA replication restart and is required for replication of several bacteriophages. Monomers of Rep do not display helicase activity in vitro; in fact, DNA unwinding requires Rep dimerization. Here we show that removal of the 2B subdomain of Rep to form RepDelta2B activates monomer helicase activity, albeit with limited processivity. Although both full length Rep and RepDelta2B monomers can translocate with 3' to 5' directionality along single-stranded DNA, the 2B subdomain inhibits the helicase activity of full length Rep. This suggests an autoregulatory mechanism for Rep helicase, which may apply to other nonhexameric helicases, whereby helicase activity is regulated by the rotational conformational state of the 2B subdomain; formation of a Rep dimer may relieve autoinhibition by altering the 2B subdomain orientation.

Adenosine Triphosphatases↗

PubMed2005

Control of local ionization and charge transfer in the bifunctional molecule 2-phenylethyl-N,N-dimethylamine using Rydberg fingerprint spectroscopy.

Local photoionization pathways and charge-transfer dynamics of 2-phenylethyl-N,N-dimethylamine (PENNA) are explored using the recently developed Rydberg fingerprint spectroscopy. PENNA, a molecule that derives its biological significance from its relation to neurotransmitters, has two ionization centers that are separated by an ethyl group. We ionize the molecule in various multiphoton ionization processes using different laser wavelengths. The Rydberg fingerprint spectrum reveals the local nature of the ionization process and identifies the center of charge. We discovered that the laser wavelength provides substantial control over the activation of the individual ionization centers. The resonant (2+1) ionization with 400-nm radiation is dominated by the ejection of an electron from the amine moiety. In contrast, the resonant (1+1) ionization with 266-nm radiation leads predominantly to an ion with the charge in the phenyl group. The clean separation of the two ionization processes allows the exploration of ultrafast charge-transfer dynamics ensuing from a specific starting state characterized by a charged phenyl moiety. The width of the corresponding spectral features suggests that the charge transfer proceeds on a femtosecond time scale, suggesting a strong coupling between the two lowest-energy electronic surfaces of the PENNA cation.

Journal Article↗