Biomedical subjects

Feng Yan

Publications and source records attributed to Feng Yan.

At least 19 recordsLinked to original sources

PubMed2026

Genomic insights into low-level rifampicin resistance mediated by borderline rpoB mutations in Mycobacterium tuberculosis: prevalence and phylogeny in Northeast China.

The emergence of low-level rifampicin (RIF) resistance in Mycobacterium tuberculosis poses a challenge to tuberculosis (TB) control, as it often leads to discordance between genotypic resistance detected by molecular assays (e.g., Xpert MTB/RIF) and phenotypic susceptibility in conventional drug susceptibility testing (DST). In this study, we performed whole-genome sequencing (WGS) on 17 clinical isolates from Changchun, Northeast China, which exhibited such discordance. All isolates harbored functional borderline mutations in the rpoB RRDR region, predominantly Leu452Pro and Leu430Pro (29% each), followed by His445Asn (18%). RIF minimum inhibitory concentration (MIC) values ranged from ≤0.25 to 1.0 mg/L, confirming low-level resistance. Notably, 53% (9/17) of the isolates were co-resistant to fluoroquinolones and 24% (4/17) to isoniazid (INH). According to WHO classification, 59% (10/17) were pre-extensively drug-resistant TB (Pre-XDR-TB) or multidrug-resistant TB (MDR-TB). Phylogenetic analysis revealed that 94% (16/17) belonged to the East Asian Beijing lineage (Lineage 2.2.1), with no evidence of recent local transmission. These findings underscore the complexity of low-level RIF resistance and its frequent association with broader drug resistance in a dominant lineage, highlighting the need for integrating MIC and WGS into diagnostic algorithms to guide appropriate treatment and surveillance.IMPORTANCEThe accurate detection of RIF resistance is critical for the management of TB, yet standard phenotypic methods often fail to identify strains with low-level resistance conferred by borderline rpoB mutations. This study provides the first genomic characterization of such discordant isolates in Northeast China, revealing a high prevalence of co-resistance to other key drugs and a strong association with the locally dominant Beijing lineage. The findings emphasize that reliance on phenotypic DST alone may lead to underestimation of drug resistance and inappropriate treatment, potentially contributing to the emergence and spread of Pre-XDR-TB and MDR-TB. Incorporating MIC determination and WGS into routine diagnostics could enhance detection, inform tailored therapy, and improve surveillance of these clinically significant strains.

Mycobacterium tuberculosis↗

PubMed2026

Epigenetic and immunological alterations in umbilical cord blood of overweight/obese women with gestational diabetes mellitus: insights into DNA methylation signatures and immune cell dysregulation.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy complication associated with adverse maternal and neonatal outcomes. Epigenetic modifications may reflect intrauterine metabolic exposure and contribute to immune and metabolic alterations. This study aimed to explore DNA methylation profiles in umbilical cord blood from overweight and obese women with and without GDM. METHODS: Umbilical cord blood samples from 30 overweight/obese pregnant women (with and without GDM) were analyzed using the Illumina 850 K methylation array to identify differentially methylated positions (DMPs) and regions (DMRs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to assess the functional relevance of methylation changes. Immune cell composition was estimated using deconvolution analysis and further examined in an independent single-cell RNA sequencing (scRNA-seq) cohort. Lasso regression was applied to identify CpG sites associated with GDM status and construct a preliminary methylation-based classification model. RESULTS: A total of 23,331 hypermethylated and 29,501 hypomethylated DMPs were identified between women with and without GDM, with hypomethylation predominating. Enrichment analyses indicated associations with neurodevelopmental pathways, metabolic processes, immune regulation, and epigenetic modification. Immune deconvolution analysis suggested reduced proportions of CD4+ T cells (p < 0.05) and a trend toward decreased NK cells in the GDM group, alongside increased CD8+ T cells and neutrophils. Seven CpG sites were selected for model construction and demonstrated strong discriminatory performance within this cohort. CONCLUSION: This exploratory study identifies distinct cord blood DNA methylation patterns associated with GDM in overweight/obese pregnancies. The findings suggest potential links between epigenetic alterations and immune cell composition in GDM-exposed offspring. The identified CpG signature warrants further validation in larger, prospective cohorts to determine its clinical applicability.

Humans↗

PubMed2007

Sensitive reagentless electrochemical immunosensor based on an ormosil sol-gel membrane for human chorionic gonadotrophin.

A new organically modified silicate (ormosil) material was synthesized as a matrix to encapsulate enzyme labeled antibody for preparation of immunosensors. The ormosil matrix was prepared by hydrolyzing tetraethyoxysilane and (3-aminopropyl)triethoxysilane in weak alkali solution. It possessed three-dimensional ordered nanoporous structure with high electrical conductivity and good mechanical stability. Its hydrophilicity provided a microenvironment for retaining the biological activity of the immobilized protein. Particularly, using horseradish peroxidase-labeled human chorionic gonadotrophin antibody (HRP-anti-hCG) as a model, the immobilized HRP showed direct electron transfer at about -35 mV with a rate constant of 15.8+/-3.8s(-1). By a simple one-step immunoreaction between human serum chorionic gonadotrophin (hCG) in sample solution and the immobilized HRP-anti-hCG, the differential pulse voltammetric peak current of HRP decreased linearly with an increasing hCG concentration from 0.5 to 50 mIU/ml with a relatively low limit of detection of 0.3 mIU/ml at 3sigma. Excellent analytical performance, fabrication reproducibility and operational stability of the proposed biosensor indicated its promising application in clinical diagnostics.

Biosensing Techniques↗

PubMed2007

Polymerization of and in mesophases.

The use of surfactant mesophases such as vesicular and lyotropic mesophases as templates for the preparation of nanostructured polymers by polymerization is reviewed. Recent developments using polymerizable and polymeric surfactants in mesophase formation and polymerization are also represented with examples. The formations of various novel materials including nanocapsules, vesicle-polymer architecture, mesoporous polymers and functional nano-composites which would be unobtainable through conventional techniques are highlighted. The effects of reaction thermodynamics and kinetics on templated polymerizations are also discussed.

Journal Article↗

PubMed2007

Effect of silica nanoparticles with different sizes on the catalytic activity of glucose oxidase.

In this work we present a strategy for the covalent immobilization of periodate oxidized glucose oxidase (IO(4)(-) - GOx) to aminated silica nanoparticles (ASNPs) modified on gold electrodes. Silica nanoparticles greatly enhanced the catalytic ability of GOx toward the oxidation of glucose and improved the electron transfer between the GOx and the electrode surface. ASNPs of varying size--that is 100, 80, 60, and 30 nm--were prepared, and they were used to fabricate biosensors. Electrochemical impedance spectroscopy (EIS) of ferrocyanide followed the assembly process and verified the successful immobilization of IO(4)(-) - GOx on ASNPs modified on gold electrodes. From the analysis of catalytic signals of biosensors using different sizes of ASNPs under the same conditions, the surface concentration of electrically wired enzyme (Gamma (ET)) was estimated and was found to increase with decreasing ASNPs size. Therefore, the sensitivity of biosensors using smaller ASNPs was higher than that using larger particles. Specifically, we utilized the ASNPs with optimal size (30 nm) to fabricate the glucose biosensor. The resulting electrodes showed a wide linear response to glucose at least to 6 mM and reached 95% of the steady-state current in less than 4 s with a sensitivity of 5.02 microA mM(-1) cm(-2) and a detection limit of 0.01 mM. The biosensor also showed excellent stability and good reproducibility.

Amination↗

PubMed2006

Self-renewal of embryonic stem cells by a small molecule.

A cell-based screen of chemical libraries was carried out to identify small molecules that control the self-renewal of ES cells. A previously uncharacterized heterocycle, SC1, was discovered that allows one to propagate murine ES cells in an undifferentiated, pluripotent state under chemically defined conditions in the absence of feeder cells, serum, and leukemia inhibitory factor. Long-term SC1-expanded murine ES cells can be differentiated into cells of the three primary germ layers in vitro and also can generate chimeric mice and contribute to the germ line in vivo. Biochemical and cellular experiments suggest that SC1 works through dual inhibition of RasGAP and ERK1. Molecules of this kind may not only facilitate practical applications of stem cells in research and therapy, but also provide previously undescribed insights into the complex biology of stem cells.

Animals↗

PubMed2006

Biosynthesis of fosfomycin, re-examination and re-confirmation of a unique Fe(II)- and NAD(P)H-dependent epoxidation reaction.

(S)-2-Hydroxypropylphosphonic acid epoxidase (HppE) catalyzes the epoxide ring closure of (S)-HPP to form fosfomycin, a clinically useful antibiotic. Early investigation showed that its activity can be reconstituted with Fe(II), FMN, NADH, and O2 and identified HppE as a new type of mononuclear non-heme iron-dependent oxygenase involving high-valent iron-oxo species in the catalysis. However, a recent study showed that the Zn(II)-reconstituted HppE is active, and HppE exhibits modest affinity for FMN. Thus, a new mechanism is proposed in which the active site-bound Fe2+ or Zn2+ serves as a Lewis acid to activate the 2-OH group of (S)-HPP and the epoxide ring is formed by the attack of the 2-OH group at C-1 coupled with the transfer of the C-1 hydrogen as a hydride ion to the bound FMN. To distinguish between these mechanistic discrepancies, we re-examined the bioautography assay, the basis for the alternative mechanism, and showed that Zn(II) cannot replace Fe(II) in the HppE reaction and NADH is indispensable. Moreover, we demonstrated that the proposed role for FMN as a hydride acceptor is inconsistent with the finding that FMN cannot bind to HppE in the presence of substrate. In addition, using a newly developed HPLC assay, we showed that several non-flavin electron mediators could replace FMN in the HppE-catalyzed epoxidation. Taken together, these results do not support the newly proposed "nucleophilic displacement-hydride transfer" mechanism but are fully consistent with the previously proposed iron-redox mechanism for HppE catalysis, which is unique within the mononuclear non-heme iron enzyme superfamily.

Chromatography, High Pressure Liquid↗

PubMed2006

Highly sensitive visible-blind extreme ultraviolet Ni/4H-SiC Schottky photodiodes with large detection area.

Ni/4H-SiC Schottky photodiodes of 5 mm x 5 mm area have been fabricated and characterized. The photodiodes show less than 0.1 pA dark current at -4 V and an ideality factor of 1.06. A quantum efficiency (QE) between 3 and 400 nm has been calibrated and compared with Si photodiodes optimized for extreme ultraviolet (EUV) detection. In the EUV region, the QE of SiC detectors increases from 0.14 electrons/photon at 120 nm to 30 electrons/photon at 3 nm. The mean energy of electron-hole pair generation of 4H-SiC estimated from the spectral QE is found to be 7.9 eV.

Journal Article↗

PubMed2006

Surfactant ionic liquid-based microemulsions for polymerization.

Surfactants based on imidazolium ionic liquids (ILs), including polymerizable surfactant ILs, have been synthesized and used to stabilize polymerizable microemulsions useful for producing polymer nanoparticles, gels, and open-cell porous materials.

Journal Article↗

PubMed2006

Multilayered construction of glucose oxidase and silica nanoparticles on Au electrodes based on layer-by-layer covalent attachment.

A feasible approach to construct multilayer films of aminated silica nanoparticles/glucose oxidase (ASNPs/GOx) on the Au electrode surface using a glutaraldehyde as a covalent attachment cross-linker is described. The covalent attachment processes were followed and confirmed by electrochemical impedance spectroscopy (EIS), which demonstrated that the ASNPs/GOx multilayer films are formed in a progressive and uniform manner. The gold electrodes modified with the ASNPs/GOx multilayer films were studied by cyclic voltammetry (CV) and showed excellent electro-catalytical response to the oxidation of glucose when ferrocenemethanol was used as an artificial redox mediator. From the analysis of voltammetric signals, the coverage of active enzyme on the electrode was estimated, which showed a linear relationship with the number of ASNPs/GOx bilayers. This suggests that the analytical performance such as sensitivity, detection limit is tunable by controlling the number of attached bilayers. The linear response range of the biosensor constructed with four bilayers of ASNPs/GOx to the concentration of glucose can extend at least to 8mM and reached 95% of the steady-state current in less than 4s with the sensitivity of 5.11 microA/mM cm(2) and the detection limit of 9 microm. In addition, the sensor exhibited good stability and long-term life.

Biosensing Techniques↗

PubMed2006

A disposable electrochemical immunosensor for flow injection immunoassay of carcinoembryonic antigen.

A new simple immunoassay method for carcinoembryonic antigen (CEA) detection using a disposable immunosensor coupled with a flow injection system was developed. The immunosensor was prepared by coating CEA/colloid Au/chitosan membrane at a screen-printed carbon electrode (SPCE). Using a competitive immunoassay format, the immunosensor inserted in the flow system with an injection of sample and horseradish peroxidase (HRP)-labeled CEA antibody was used to trap the labeled antibody at room temperature for 35 min. The current response obtained from the labeled HRP to thionine-H(2)O(2) system decreased proportionally to the CEA concentration in the range of 0.50-25 ng/ml with a correlation coefficient of 0.9981 and a detection limit of 0.22 ng/ml (S/N=3). The immunoassay system could automatically control the incubation, washing and current measurement steps with good stability and acceptable accuracy. Thus, the proposed method proved its potential use in clinical immunoassay of CEA.

Biosensing Techniques↗

PubMed2006

Bioisosteric modification of salvinorin A, a potent and selective kappa-opioid receptor agonist.

Salvinorin A ((2S,4aR,6aR,7R,9S,10aS, 10bR)-2H-naphtho[2,1-c]pyran-7-carboxylic acid, 9-(acetyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10-dioxo methyl ester, 1, CAS 83729-01-5) has been shown to bind with high affinity and selectivity to the kappa-opioid receptor (KOR) as an agonist. Bioisosteres of 1 were developed and biologically evaluated in binding and functional assays. The C-2 thioacetate isoster produced comparable activity to 1, but nitrogen substitution had a diminishing effect. Intermediates, which lack a beta-carbonyl at C-2, displayed moderate affinity. The derivatives were tested against all opioid subtypes and were selective towards KOR.

Binding, Competitive↗

PubMed2006

[cDNA microarray-based screening of differentially expressed genes in macrophages in the spleen of patients with portal hypertension and hypersplenism].

OBJECTIVE: To identify the differentially expressed genes associated with hypersplenism in patients with portal hypertension. METHODS: The total RNA were extracted from the macrophages isolated from normal spleen and the spleen of patients with portal hypertension and reversely transcribed to cDNA with the incorporation of fluorescent (cy3 and cy5)-labeled dCTP to prepare the hybridization probes. After hybridization of Biostar-H140s chip containing 14,112 spots of cDNAs with the prepared probes, the gene chip was scanned for fluorescence intensity to screen the differently expressed genes. Three gene chips were used for hybridization and only the genes with differential expression in all the three chips were considered to associate with hypersplenism in patients with portal hypertension. RESULTS: Totaling 896, 1330 and 898 genes were identified to be differentially expressed by the three chips, respectively, and 121 genes (0.86%) showed differential expression in all the three chips, including 21 up-regulated known genes and 73 down-regulated known genes. The differently expressed genes were functionally related with ion channels and transport proteins, cyclins, cytoskeleton, cell receptors, cell signal transduction, metabolism, immunity, and so forth. These genes might be involved in hypersplenism in the condition of portal hypertension. CONCLUSION: cDNA microarray-based screening of differentially expressed genes in the macrophages in the spleen may provide new insights into the pathogenesis of hypersplenism in patients with portal hypertension.

Female↗

PubMed2005

Tuftsin binds neuropilin-1 through a sequence similar to that encoded by exon 8 of vascular endothelial growth factor.

Tuftsin, Thr-Lys-Pro-Arg (TKPR), is an immunostimulatory peptide with reported nervous system effects as well. We unexpectedly found that tuftsin and a higher affinity antagonist, TKPPR, bind selectively to neuropilin-1 and block vascular endothelial growth factor (VEGF) binding to that receptor. Dimeric and tetrameric forms of TKPPR had greatly increased affinity for neuropilin-1 based on competition binding experiments. On endothelial cells tetrameric TKPPR inhibited the VEGF(165)-induced autophosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2) even though it did not directly inhibit VEGF binding to VEGFR-2. Homology between exon 8 of VEGF and TKPPR suggests that the sequence coded for by exon 8 may stabilize VEGF binding to neuropilin-1 to facilitate signaling through VEGFR-2. Given the overlap between processes involving neuropilin-1 and tuftsin, we propose that at least some of the previously reported effects of tuftsin are mediated through neuropilin-1.

Amino Acid Sequence↗

PubMed2005

A gold nanoparticles/sol-gel composite architecture for encapsulation of immunoconjugate for reagentless electrochemical immunoassay.

A highly hydrophilic, non-toxic and conductive colloidal gold nanoparticle/titania sol-gel composite membrane with a low contact angle was prepared on a glassy carbon electrode via a vapor deposition method. With human chorionic gonadotrophin (hCG) as a model antigen and encapsulation of horseradish peroxidase-labeled hCG antibody (HRP-anti-hCG) in the composite architecture, this membrane could be used for reagentless electrochemical immunoassay. It displayed a porous and homogeneous composite architecture without the aggregation of the immobilized protein molecules. The presence of gold nanoparticles provided a congenial microenvironment for adsorbed biomolecules and decreased the electron transfer impedance, leading to a direct electrochemical behavior of the immobilized HRP. The formation of immunoconjugate by a simple one-step immunoreaction between hCG in sample solution and the immobilized HRP-anti-hCG introduced a barrier of direct electrical communication between the immobilized HRP and the electrode surface. Under optimal conditions, the hCG analyte could be determined in two linear ranges from 0.5 to 5.0 mIU/mL and 5.0 to 30 mIU/mL with a relatively low detection limit of 0.3 mIU/mL at 3sigma. The hCG immunosensor exhibited good precision, high sensitivity, acceptable stability, accuracy and reproducibility. This composite membrane could be used efficiently for the entrapment of different biomarkers and clinical applications.

Biomarkers↗

PubMed2005

Site-directed mutagenesis and spectroscopic studies of the iron-binding site of (S)-2-hydroxypropylphosphonic acid epoxidase.

(S)-2-Hydroxylpropanylphosphonic acid epoxidase (HppE) is a novel type of mononuclear non-heme iron-dependent enzyme that catalyzes the O2 coupled, oxidative epoxide ring closure of HPP to form fosfomycin, which is a clinically useful antibiotic. Sequence alignment of the only two known HppE sequences led to the speculation that the conserved residues His138, Glu142, and His180 are the metal binding ligands of the Streptomyces wedmorensis enzyme. Substitution of these residues with alanine resulted in significant reduction of metal binding affinity, as indicated by EPR analysis of the enzyme-Fe(II)-substrate-nitrosyl complex and the spectral properties of the Cu(II)-reconstituted mutant proteins. The catalytic activities for both epoxidation and self-hydroxylation were also either eliminated or diminished in proportion to the iron content in these mutants. The complete loss of enzymatic activity for the E142A and H180A mutants in vivo and in vitro is consistent with the postulated roles of the altered residues in metal binding. The H138A mutant is also inactive in vivo, but in vitro it retains 27% of the active site iron and nearly 20% of the wild-type activity. Thus, it cannot be unequivocally stated whether H138 is an iron ligand or simply facilitates iron binding due to proximity. The results reported herein provide initial evidence implicating an unusual histidine/carboxylate iron ligation in HppE. By analogy with other well-characterized enzymes from the 2-His-1-carboxylate family, this type of iron core is consistent with a mechanism in which both oxygen and HPP bind to the iron as a first step in the in the conversion of HPP to fosfomycin.

Amino Acid Sequence↗

PubMed2005

Surface modification of liposomes by saccharides: vesicle size and stability of lactosyl liposomes studied by photon correlation spectroscopy.

The cell glycocalyx is an attractive model for surface modification of liposomes, because its hydrated oligosaccharide layer inhibits nonspecific protein adsorption and can provide specificity towards desired sites. Here, we report on the use of lactose as a model saccharide to modify the liposome surface and examine the vesicle size and stability. Two kinds of lactosyl lipids, including lactosyl ether-lipid (6a) and lactosyl ester-lipid (6b), which contain octadecyl and octadecanoyl as the lipid tails, respectively, were synthesized and their liposomes were prepared by the extrusion method. The effects of glycolipid structure, concentration, and the pore size of the extrusion membrane on vesicle size and stability were investigated at room temperature by photon correlation spectroscopy (PCS). All liposomes with 5 or 10 mol% of lactosyl lipids had a narrow size distribution and remained stable at room temperature for at least one month, which is comparable to 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)- and poly(ethylene glycol) (PEG)-liposomes. The maximum incorporation of lactosyl ester-lipid into liposomes was 15 mol%, compared with only 10 mol% for the lactosyl ether-lipid. The lactosyl ester-liposomes had better stability and exhibited less size change than the lactosyl ether-liposomes at 15 or 20 mol% of lactosyl lipids incorporated. This may be attributed to the better structural compatibility of lactosyl ester-lipid with DSPC. The PCS results show that the glycolipid structure and concentrations are major factors that affect vesicle stability, while the pore size of extrusion membranes has no influence.

Carbohydrate Conformation↗

PubMed2005

Human and mouse mast cells use the tetraspanin CD9 as an alternate interleukin-16 receptor.

Interleukin-16 (IL-16) induces the chemotaxis and activation of mast cells (MCs) and other cell types. While it has been concluded that CD4 is the primary IL-16 receptor on T cells, at least one other IL-16 receptor exists. We now show that the IL-16-responsive human MC line HMC-1 lacks CD4, and that the IL-16-mediated chemotactic and Ca2+ mobilization responses of this cell can be blocked by anti-CD9 monoclonal antibodies (mAbs) but not by mAbs directed against CD4 or other tetraspanins. Anti-CD9 mAbs also inhibited the IL-16-mediated activation of nontransformed human cord blood-derived MCs and mouse bone marrow-derived MCs by 50% to 60%. The chemotactic response of HMC-1 cells to IL-16, as well as the binding of the cytokine to the cell's plasma membrane, was inhibited by CD9-specific antisense oligonucleotides. CD9 is therefore essential for the IL-16-mediated chemotaxis and activation of the HMC-1 cell line. In support of this conclusion, IL-16 bound to CD9-expressing CHO cell transfectants. The ability of wortmannin and xestopongin C to inhibit the IL-16-mediated chemotactic response of these cells suggests that the cytokine activates a phosphatidylinositol 3-kinase (PI3K)/inositol trisphosphate-dependent signaling pathway in MCs. This is the first report of a tetraspanin that plays a prominent role in a cytokine-mediated chemotactic response of human MCs.

Animals↗