Biomedical subjects

Miao Zhang

Publications and source records attributed to Miao Zhang.

At least 19 recordsLinked to original sources

PubMed2026

Interkingdom remodeling of the intestinal bacteriome and virome during Toxoplasma gondii infection in rats.

Toxoplasma gondii infection is associated with intestinal microbiome disruption, but its effects on genome-resolved bacterial populations, the gut virome, and bacteriome-virome relationships remain poorly understood. Using previously generated shotgun metagenomic datasets from 36 intestinal samples collected from 18 Sprague-Dawley rats across control, acute, and chronic infection groups, we reconstructed 294 quality-filtered, non-redundant bacterial metagenome-assembled genomes (MAGs) and identified 899 medium-to-high-quality viral operational taxonomic units (vOTUs) from assembled metagenomic contigs. Infection was associated with reduced bacterial richness in the small intestine during both acute and chronic stages and lower Shannon diversity during chronic infection. In contrast, large-intestinal α-diversity remained stable despite significant compositional reorganization. Taxonomic changes included increased Lactobacillus intestinalis, Limosilactobacillus reuteri, and Prevotella sp900547005, together with decreased Rothia sp002492045 and Akkermansia muciniphila. Functional profiling revealed region- and stage-specific changes in predicted bacterial metabolic potential, including reduced energy-related pathways and carbohydrate-active enzyme abundance. The virome also showed significant compositional changes in both intestinal regions. Quimbyviridae and Podoviridae_crAss-like viruses decreased in the small intestine during chronic infection, while Quimbyviridae, Flandersviridae, and Podoviridae_crAss-like viruses showed stage-specific decreases in the large intestine. Predicted bacterial hosts were assigned to 48.39% of vOTUs, with Lachnospiraceae and Ruminococcaceae being the most frequently linked families. Trans-kingdom networks further revealed region-specific positive and negative abundance correlations between bacterial and viral taxa. These findings extend previous microbiota-metabolome observations by integrating genome-resolved bacteriome analysis with contig-based virome profiling, providing a foundation for future mechanistic studies of toxoplasmosis-associated microbiome remodeling.

Gut virome↗

PubMed2026

Mechanism exploration of divergent partial denitrification performance under tetracycline stress: Insights from functional gene, electron transport and molecular docking.

Nitrates and antibiotics like tetracycline (TC) coexist in wastewater and inhibit nitrite (NO₂--N) accumulation during partial denitrification (PD), restricting anammox coupling. A moving bed biofilm reactor (PD-MBBR) and a sequencing batch reactor (PD-SBR) were compared under TC stress (0-8 mg/L). The PD-MBBR proved more robust, sustaining a high nitrate transformation ratio (NTR) of 95.11% and ∼53% TC removal. Metagenomic sequencing, quantitative polymerase chain reaction (qPCR), and molecular docking revealed this tolerance stemmed from physical shielding and metabolic compensation. Carrier-attached growth promoted extracellular polymeric substances (EPS) overproduction, forming a dense barrier preventing TC from binding to key denitrifying enzymes. The biofilm maintained stable nitrate reductase (NAR) activity via high narG and napA gene abundances, while nitrite reductase (NIR) was inhibited, ensuring efficient NO₂--N accumulation. This was supported by hyperactivated electron transport chain components, with complex III relative abundance increasing 15.08% and peak enzymatic activity reaching 149.02%. While IntI1-mediated horizontal gene transfer fortified community defense, concentrated antibiotic resistance genes (ARGs) within the biofilm pose a secondary dissemination risk. Thus, PD-MBBR provides an efficient pretreatment strategy for anammox, though downstream ARGs management is warranted.

Denitrification↗

PubMed2006

Activation of protein kinase C zeta by peroxynitrite regulates LKB1-dependent AMP-activated protein kinase in cultured endothelial cells.

We previously reported the phosphoinositide 3-kinase-dependent activation of the 5'-AMP-activated kinase (AMPK) by peroxynitrite (ONOO-) and hypoxia-reoxygenation in cultured endothelial cells. Here we show the molecular mechanism of activation of this pathway. Exposure of bovine aortic endothelial cells to ONOO- significantly increased the phosphorylation of both Thr172 of AMPK and Ser1179 of endothelial nitric-oxide synthase, a known downstream enzyme of AMPK. In addition, activation of AMPK by ONOO- was accompanied by increased phosphorylation of protein kinase Czeta (PKCzeta) (Thr410/403) and translocation of cytosolic PKCzeta into the membrane. Further, inhibition of PKCzeta abrogated ONOO- -induced AMPK-Thr172 phosphorylation as that of endothelial nitric-oxide synthase. Furthermore, overexpression of a constitutively active PKCzeta mutant enhanced the phosphorylation of AMPK-Thr172, suggesting that PKCzeta is upstream of AMPK activation. In contrast, ONOO- activated PKCzeta in LKB1-deficient HeLa-S3 but affected neither AMPK-Thr172 nor AMPK activity. These data suggest that LKB1 is required for PKCzeta-enhanced AMPK activation. In vitro, recombinant PKCzeta phosphorylated LKB1 at Ser428, resulting in phosphorylation of AMPK at Thr172. Further, direct mutation of Ser428 of LKB1 into alanine, like the kinase-inactive LKB1 mutant, abolished ONOO- -induced AMPK activation. In several cell types originating from human, rat, and mouse, inhibition of PKCzeta significantly attenuated the phosphorylation of both LKB1-Ser428 and AMPK-Thr172 that were enhanced by ONOO-. Taken together, we conclude that PKCzeta can regulate AMPK activity by increasing the Ser428 phosphorylation of LKB1, resulting in association of LKB1 with AMPK and consequent AMPK Thr172 phosphorylation by LKB1.

AMP-Activated Protein Kinase Kinases↗

PubMed2006

B cell antigen receptor signaling and internalization are mutually exclusive events.

Engagement of the B cell antigen receptor initiates two concurrent processes, signaling and receptor internalization. While both are required for normal humoral immune responses, the relationship between these two processes is unknown. Herein, we demonstrate that following receptor ligation, a small subpopulation of B cell antigen receptors are inductively phosphorylated and selectively retained at the cell surface where they can serve as scaffolds for the assembly of signaling molecules. In contrast, the larger population of non-phosphorylated receptors is rapidly endocytosed. Each receptor can undergo only one of two mutually exclusive fates because the tyrosine-based motifs that mediate signaling when phosphorylated mediate internalization when not phosphorylated. Mathematical modeling indicates that the observed competition between receptor phosphorylation and internalization enhances signaling responses to low avidity ligands.

Amino Acid Motifs↗

PubMed2006

Negative photoconductivity and memory effects of germanium nanocrystals embedded in HfO2 dielectric.

A metal-insulator-semiconductor (MIS) structure containing an HfO2/SiO2 stack tunnel layer, isolated Germanium (Ge) nanocrystals, and an HfO2 capping layer, was obtained by an electron-beam evaporation method. A high-resolution transmission electron microscopy (HRTEM) study revealed that uniform and pronounced Ge nanocrystals had formed after annealing. Raman spectroscopy provided evidence for the formation of Ge-Ge bonds and the optimal annealing temperature for the crystallization ratio of the Ge. The electric properties of the MIS structure were characterized by capacitance-voltage (C-V) and current-voltage (I-V) measurements at room temperature. Negative photoconductivity was observed when the structure was under a forward bias, which screened the bias voltage, resulting in a decrease in the current at a given voltage and a negative shift in flat band voltage. A relatively high stored charge density of 3.27 x 10(12) cm 2 was also achieved.

Electrochemistry↗

PubMed2005

Improved spliced alignment from an information theoretic approach.

MOTIVATION: mRNA sequences and expressed sequence tags represent some of the most abundant experimental data for identifying genes and alternatively spliced products in metazoans. These transcript sequences are frequently studied by aligning them to a genomic sequence template. For existing programs, error-prone, polymorphic and cross-species data, as well as non-canonical splice sites, still present significant barriers to producing accurate, complete alignments. RESULTS: We took a novel approach to spliced alignment that meaningfully combined information from sequence similarity with that obtained from PSSM splice site models. Scoring systems were chosen to maximize their power of discrimination, and dynamic programming (DP) was employed to guarantee optimal solutions would be found. The resultant program, EXALIN, performed better than other popular tools tested under a wide range of conditions that included detection of micro-exons and human-mouse cross-species comparisons. For improved speed with only a marginal decrease in splice site prediction accuracy, EXALIN could perform limited DP guided by a result from BLASTN. AVAILABILITY: The source code, binaries, scripts, scoring matrices and splice site models for human, mouse, rice and Caenorhabditis elegans utilized in this study are posted at http://blast.wustl.edu/exalin. The software (scripts, source code and binaries) is copyrighted but free for all to use.

Algorithms↗

PubMed2005

[Influence of combined spinal-epidural analgesia and epidural analgesia on the progress of labor].

OBJECTIVE: To investigate the influence of combined spinal-epidural analgesia (CSEA) and epidural analgesia (EA) and patient-controlled epidural analgesia (PCEA) on labor progress. METHODS: The partograms of 722 healthy vaginal delivery nulliparas were retrospectively analyzed in Department of Obstetric and Gynecology, First Hospital of Peking University. Three groups were divided among all subjects: CSEA group (259 cases) receiving CSEA + PCEA, EA group (215 cases) receiving EA + PCEA and control group (248 cases) without any analgesia method. RESULTS: The duration of active phase in the first stage and the second stage in the CSEA group [(272 +/- 127) min and (57 +/- 36) min] and in the EA group [(305 +/- 133) min and (59 +/- 39) min] were significantly longer than that of control group [(188 +/- 110) min and (45 +/- 32) min]. No significant difference was found in the three groups in the duration of the third stage [CSEA: (9 +/- 6) min; EA: (8 +/- 6) min; CONTROL: (9 +/- 6) min. P > 0.05]. The dilatation curve of the cervix in CSEA group and EA group was plotted on the right side of the Friedman curve while that of the control group on the left, reflecting a slower progress in the former two groups than the control during the active phase. The average speed of cervical dilatation in CSEA and EA groups (1.5 cm and 1.4 cm) was significantly slower than that of the control (1.8 cm) in the active phase (P < 0.01). CONCLUSIONS: CSEA + PCEA or EA + PCEA during labor might slow down the progress of the active phase and lead to a prolonged labor in the end. Therefore, the management of these parturients may vary based on Friedman partogram.

Adult↗

PubMed2004

Impaired Ca2+ store functions in skeletal and cardiac muscle cells from sarcalumenin-deficient mice.

Sarcalumenin (SAR), specifically expressed in striated muscle cells, is a Ca2+-binding protein localized in the sarcoplasmic reticulum (SR) of the intracellular Ca2+ store. By generating SAR-deficient mice, we herein examined its physiological role. The mutant mice were apparently normal in growth, health, and reproduction, indicating that SAR is not essential for fundamental muscle functions. SAR-deficient skeletal muscle carrying irregular SR ultrastructures retained normal force generation but showed slow relaxation phases after contractions. A weakened Ca2+ uptake activity was detected in the SR prepared from mutant muscle, indicating that SAR contributes to Ca2+ buffering in the SR lumen and also to the maintenance of Ca2+ pump proteins. Cardiac myocytes from SAR-deficient mice showed slow contraction and relaxation accompanied by impaired Ca2+ transients, and the mutant mice exhibited a number of impairments in cardiac performance as determined in electrocardiography, ventricular catheterization, and echocardiography. The results obtained demonstrate that SAR plays important roles in improving the Ca2+ handling functions of the SR in striated muscle.

Animals↗

PubMed2004

Procom: a web-based tool to compare multiple eukaryotic proteomes.

UNLABELLED: Each organism has traits that are shared with some, but not all, organisms. Identification of genes needed for a particular trait can be accomplished by a comparative genomics approach using three or more organisms. Genes that occur in organisms without the trait are removed from the set of genes in common among organisms with the trait. To facilitate these comparisons, a web-based server, Procom, was developed to identify the subset of genes that may be needed for a trait. AVAILABILITY: The Procom program is freely available with documentation and examples at http://ural.wustl.edu/~billy/Procom/ CONTACT: billy@ural.wustl.edu.

Animals↗

PubMed2004

B-cell antigen receptor signaling requirements for targeting antigen to the MHC class II presentation pathway.

The ability of B lymphocytes to capture, process and present antigens to T cells is requisite for normal humoral immune responses and contributes to the pathogenesis of both B- and T-cell-mediated autoimmune diseases. B lymphocytes preferentially capture polyvalent antigens, which are capable of eliciting a coordinated series of cellular responses that ensure that even low-affinity antigens are productively captured. Polyvalency not only accelerates transit through the endocytic pathway but also induces a reorganization of the antigen-processing compartment, activates degradative pathways and determines how antigenic peptides are presented to T cells. Similar changes are observed in maturing dendritic cells, indicating that some cellular responses to foreign antigens are conserved.

Animals↗

PubMed2003

Molecular mechanisms of B cell antigen receptor trafficking.

B lymphocytes are among the most efficient cells of the immune system in capturing, processing, and presenting MHC class II restricted peptides to T cells. Antigen capture is essentially restricted by the specificity of the clonotypic antigen receptor expressed on each B lymphocyte. However, receptor recognition is only one factor determining whether an antigen is processed and presented. The context of antigen encounter is crucial. In particular, polyvalent arrays of repetitive epitopes, indicative of infection, accelerate the delivery of antigen to specialized processing compartments, and up-regulate the surface expression of MHC class II and co-stimulatory molecules such as B7. Recent studies have demonstrated that receptor-mediated signaling and receptor-facilitated peptide presentation to T cells are intimately related. For example, rapid sorting of endocytosed receptor complexes through early endosomes requires the activation of the tyrosine Syk. This proximal kinase initiates all BCR-dependent signaling pathways. Subsequent entry into the antigen-processing compartment requires the tyrosine phosphorylation of the BCR constituent Igalpha and direct recruitment of the linker protein BLNK. Signals from the BCR also regulate the biophysical and biochemical properties of the targeted antigen-processing compartments. These observations indicate that the activation and recruitment of signaling molecules by the BCR orchestrate a complex series of cellular responses that favor the presentation of even rare or low-affinity antigens if encountered in contexts indicative of infection. The requirement for BCR signaling provides possible mechanisms by which cognate B:T cell interactions can be controlled by the milieu in which antigen engagement occurs.

Peptides↗

PubMed2003

[Comparison of curative effect of autologous peripheral blood stem cell transplantation versus bone marrow transplantation for acute leukemia].

To compare the clinical outcome of autologous peripheral blood stem cell transplantation (APBSCT) and autologous bone marrow transplantation (ABMT) in treatment of patients with acute leukemia in first remission, 41 patients received APBSCT, 17 patients received unpurged ABMT and 30 patients received purged ABMT. The results showed that hematopoietic recovery was significantly earlier after APBSCT than that after purged or unpurged ABMT. The 3-year disease-free survival (DFS), relapse rate (RR) and transplant-related mortality (TRM) for all patients of 3 groups were 51.7%, 41.7% and 6.8%, respectively. DFS and RR were significantly influenced by disease types (ALL or AML) and intervals between diagnosis and CR(1) or CR(1) and transplant. The main causes of transplant-related death were infection and hemorrhage. After APBSCT, DFS, RR and TRM were 48.4%, 43.9% and 4.9%, respectively, and did not differ significantly from those found in unpurged ABMT (47.1%, 45.6% and 11.8%) or purged ABMT (66.5%, 29.6% and 6.7%). It is concluded that the clinical outcome of APBSCT is similar to unpurged or purged ABMT but APBSCT allows faster recovery of hematopoiesis and needs less transfusion support.

Acute Disease↗

PubMed2003

[New targets for drug therapeutics: receptors for purines and pyrimidines].

Endogenous nucleoside and nucleotide mediate a lot of functions via cell surface P receptors (receptors for purines and pyrimidines) in many organs. Nucleoside and nucleotide have protective roles in the events such as cancer, apoptosis, ischemia, wound healing, osteoporosis, drug toxicity, inflammation and pain. Moreover, the development of selective agonists and antagonists for P1, P2 receptors and P receptor subtypes may provide novel drugs in therapeutic strategies.

Animals↗

PubMed2002

[An analysis of double autologous hemopoietic stem cell transplantation for hematological malignancies].

OBJECTIVE: To analyse the clinical efficacy of the double autologous hemopoietic stem cell transplantation (DAHSCT) for hematological malignancies. METHODS: 19 hematological malignant disease patients received the first AHSCT within 12 months after diagnosis. The first conditioning regimen was VP-16 or Ara-C, CTX +, TBI, nine of them received BCNU additionally. All patients received the second AHSCT in 4 to 10 months after the first AHSCT. The second conditioning regimen was VP-16 (or Ara-C), CTX +, Mel. RESULTS: All patients had rapidly hemopoietic reconstitution, the first hemopoietic reconstitution is faster than the second. There was no AHSCT related death. The median follow up duration was 1078 days. 12 of the 19 patients were still alive during the analysis. The 3-year disease-free suvival (DFS) was 63% +/- 10%. Those patients who had more blasts in bone marrow at the second AHSCT than the first AHSCT had greater probability to relapse. CONCLUSION: DAHSCT can be safety performed as an important treatment method in hematological malignancies.

Adolescent↗

PubMed2002

Fusion of RDC1 with HMGA2 in lipomas as the result of chromosome aberrations involving 2q35-37 and 12q13-15.

Rearrangements of chromosome bands 12q13-15 are frequent in various benign mesenchymal and epithelial tumors, and the gene HMGA2 seems to be the most common target within this chromosome region. In the majority of cases, the rearrangements result in a fusion of the first three exons of HMGA2 with different translocation partners. Despite the large number of HMGA2 mutations that have been reported, very little is known about the fusion partners. In this study, we have characterized a recurrent fusion of the first three exons of HMGA2 5' to the G protein-coupled receptor gene (RDC1) in lipomas with rearrangements involving chromosome bands 2q35-37 and 12q13-15, one of several recurrent chromosomal rearrangements in lipomas. The functional impact of the fusion is truncation of HMGA2, because the RDC1 part contributes with a stop codon one amino acid downstream of the breakpoint. The breakpoint within RDC1 was localized in a previously uncharacterized exon of the gene, and our data suggest that RDC1 is subject to alternative splicing.

Alternative Splicing↗

PubMed2002

Distribution of functional P2X1-like receptor in isolated rabbit arteries.

AIM: To clarify the distribution of functional P2X1-like receptors in rabbit arteries. METHODS: Isometric contractile responses to noradrenaline (NA) and alpha, beta-methylene ATP (alpha, beta-meATP) were observed in the arteries isolated from rabbit renal (Re), femoral (Fe), saphenous (Sa), mesenteric (Me), splenic (Sp), and ear (Ea). RESULTS: The maximal responses to NA (E(max.NA)) varied among the arteries in an order of Re>Fe>Sa>Me>Sp>Ea. After standardization by the maximal response to KCl (E(max.KCl)), however, the values of E(max.NA)/E(max.KCl) in the six kinds of arteries were almost the same. EC50 values of NA in arteries were different, and the EC50 value of NA in Me artery was 54 times that of Fe artery (P<0.01). The maximal response to alpha, beta-meATP (E(max.alpha, beta-meATP) ) varied among the arteries in an order of Re>Sa=Fe>Ea>Sp=Me, and the values of E max.alpha, beta-meATP /E(max.KCl) were still different (Fe<Re<Sa=Ea=Sp=Me). The EC50 values of alpha, beta-meATP in regional arteries were almost the same (0.23-0.77 mmol/L). The vasoconstrictive responses induced by alpha, beta-meATP in the Re,Fe,Sa,Me,Sp, and Ea arteries were subject to tachyphylaxis. CONCLUSION: There are functional P2X1-like receptors in the six kinds of arteries used, and the vasoconstrictive responses regulated via the receptors are Fe<Re<Sa=Ea=Sp=Me, which is consistent with the sympathetic innervation of the arteries.

Animals↗

PubMed2002

[The effect of separating red blood cells from bone marrow graft in vitro by methylcellulose].

It has need to separate red blood cells (RBC) from marrow graft in ABO group unmatched BMT and auto-BMT with purging tumor cells, the separating effect of methylcellulose was observed. The mixture of 0.5% methylcellulose and bone marrow was laid up in an open transfusion system, and then sedimentation of RBC was performed in the transfusion tube. The separating results of 18 marrow grafts showed that the recovery rates of mononuclear cells and CD34(+) cells were (83.8 +/- 55.2)% and (90.3 +/- 7.2)%, respectively. RBC residual rate was (4.3 +/- 1.5)%. The yield of CFU-GM was (60.8 +/- 22.4)/2 x 10(5) MNC, and there was no difference to [(69.8 +/- 23.4)/2 x 10(5) MNC] yielded from same marrow samples, separated by Ficoll-Hypaque separation. It is concluded that this method could be used for bone marrow transplantation.

Bone Marrow Transplantation↗

PubMed2002

[Change of adhesion molecule expression on CD34(+) cells from bone marrow and peripheral blood during mobilization with combination of chemotherapy and G-CSF].

To explore the dynamic change of CD34(+) cell expressing adhesion molecules in bone marrow and peripheral blood during mobilization with combination of chemotherapy and G-CSF and its clinical significance, mononuclear cells of bone marrow and peripheral blood from malignant hematopathy cases before and after mobilization with G-CSF were labeled by CD45-CY-Chrome, PE conjugated anti-CD34, and FITC conjugated anti-CD44, anti-CD49d, anti-CD62L and anti-CXCR4. For three-color fluorescence analysis by flow cytometry was performed on a FACScalibur. Also the relationship between the number of subpopulations in different expressions of adhesion molecules infused and the time of recovery in different blood cells after transplantation was evaluated. Results showed that a significantly lower expression of CD44(+) and CD49d(+) on CD34(+) cells in bone marrow after mobilization compared to that before mobilization, whereas great higher expression of CD44(+), CD49d(+), anti-CD62L(+) and lower of anti-CXCR4(+) in peripheral blood were observed after mobilization. No significant relations were found between expression of different adhesion molecules on CD34(+) cells infused and the time of reconstitution in blood cells after transplantation. It was concluded that this mobilizing regimen could downregulate the expressions of CD44, CD49d, CD62L, and anti-CXCR4 on CD34(+) cells in bone marrow, it may related to mobilization of CD34(+) cells from marrow to blood, and homing of blood CD34(+) cells into marrow.

Adolescent↗