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Biomedical subjects

Jiang Zhou

Publications and source records attributed to Jiang Zhou.

At least 19 recordsLinked to original sources
PubMed2026

G-quadruplex upstream of PAX9 TSS acts as a 3D-genome scaffold to remotely silence X-linked genes and modulate cell-cycle progression.

G-quadruplexes (G4s) are non-canonical DNA secondary structures that act as local replication barriers and transcriptional regulators. Whether G4 can simultaneously influence splicing, DNA replication, and long-range, trans-chromosomal gene regulation remains untested. Here we combined in vitro biophysics, CRISPR mutagenesis and multi-omics to dissect a conserved G4 motif (QS1) located ~173 bp upstream of the PAX9 transcription start site. CD spectroscopy confirmed that the wild-type, but not the G-to-T mutant sequence, folds into a stable parallel G4 under physiological K+. In human cells, disruption of the QS1 G4 changed chromatin accessibility, remotely down-regulated a cohort of X-linked genes, accelerated migration and delayed G1/S progression. Integrative analysis of ATAC-seq, RNA-seq profiling reveals that the QS1 G4 acts as a three-dimensional genome scaffold linking PAX9 to cell-cycle and metabolic networks. Our findings establish a pleiotropic role for a single promoter G4 in coordinating DNA replication stress, chromatin architecture and trans-chromosomal transcriptional control.

G-Quadruplexes↗
PubMed2026

Comprehensive transcriptomics and proteomics analysis of neointima formation in human saphenous vein: implications for bypass graft disease.

Human saphenous veins (SVs) are widely used as grafts in coronary artery bypass (CABG) surgery but often fail due to neointima formation. Little is known, however, regarding the cellular, transcriptomic, and proteomic dynamics of neointima formation in human veins. Here, we performed transcriptomics and proteomics analysis in an ex vivo tissue culture model of neointima formation in human SVs procured for CABG surgery. Histological examination demonstrated significant elastin degradation and neointima formation (indicated by increased neointima area and neointima-to-media ratio) in SVs subjected to tissue culture. Analysis of data from 72 patients suggests that the progression of SV remodeling and neointima formation differs according to sex and body mass index, which is negatively associated with neointima formation in males only. RNA sequencing demonstrated upregulation of proinflammatory and proliferation-related genes during neointima formation and identified novel processes, including increased cellular stress and DNA damage responses, reflecting tissue trauma associated with vein harvesting. Proteomic analysis identified upregulated extracellular matrix-related and coagulation/thrombosis proteins and downregulated metabolic proteins. Spatial transcriptomics, used to infer regionally enriched gene expression, suggested dynamic alterations in fibroblast and vascular smooth muscle cell (VSMC) states during neointima formation. Specifically, we identified the emergence of HES1+ and matrix metalloproteinase 2- and 14-positive (MMP2+/MMP14+) expression in VSMCs and fibroblasts, respectively, during neointima formation. Furthermore, our data suggest that MIR647, identified through screening, maintains VSMC contractile gene expression. Our findings suggest dynamic transcriptomic and proteomic changes during neointima formation in human veins and provide useful mechanistic information for the pathogenesis of SV graft disease.NEW & NOTEWORTHY Using multiomics and spatial transcriptomics, we uncover dynamic molecular and cellular changes driving neointima proliferation in human saphenous veins, the most common conduit for bypass surgery. Our study highlights sex- and body mass index-associated differences, novel fibroblast and smooth muscle cell states, and a role for microRNA-647 in preserving vascular contractile phenotype. These findings provide new insight into the mechanisms of vein graft failure and may guide future strategies to improve coronary bypass outcomes.

Humans↗
PubMed2007

Formation and stability of G-quadruplexes self-assembled from guanine-rich strands.

Electrospray ionization mass spectrometry (ESI-MS) was utilized to investigate the formation and stability of G-quadruplexes. For the 15 6-nt oligonucleotides tested, ESI-MS indicated that formation of a parallel tetramer quadruplex requires at least four continuous guanines in the 6-nt sequence. In addition, the G-rich strands prefer to employ "self-association" in the formation of the G-quadruplex rather than hybridized integration, and the thermodynamic-stability order of these three G-quadruplexes is Q(2)>Q(1)>Q(3).

Binding Sites↗
PubMed2006

Essential roles for GSK-3s and GSK-3-primed substrates in neurotrophin-induced and hippocampal axon growth.

Glycogen synthase kinase-3beta (GSK-3beta) is thought to mediate morphological responses to a variety of extracellular signals. Surprisingly, we found no gross morphological deficits in nervous system development in GSK-3beta null mice. We therefore designed an shRNA that targeted both GSK-3 isoforms. Strong knockdown of both GSK-3alpha and beta markedly reduced axon growth in dissociated cultures and slice preparations. We then assessed the role of different GSK-3 substrates in regulating axon morphology. Elimination of activity toward primed substrates only using the GSK-3 R96A mutant was associated with a defect in axon polarity (axon branching) compared to an overall reduction in axon growth induced by a kinase-dead mutant. Consistent with this finding, moderate reduction of GSK-3 activity by pharmacological inhibitors induced axon branching and was associated primarily with effects on primed substrates. Our results suggest that GSK-3 is a downstream convergent point for many axon growth regulatory pathways and that differential regulation of primed versus all GSK-3 substrates is associated with a specific morphological outcome.

Animals↗
PubMed2006

A novel method for the in situ determination of concentration gradients in the electrolyte of Li-ion batteries.

An electrochemical method has been developed for the in situ determination of concentration gradients in the electrolyte of sealed Li-ion batteries by measuring the potential difference between microreference electrodes. Formulas relating the concentration gradient and the potential difference between the microreference electrodes were derived from the Nernst-Planck equation. The concentration gradients in Li-ion batteries are theoretically and experimentally proven to be linear at steady state under galvanostatic charging and discharging conditions. Based on this finding, both the diffusion coefficient of the lithium ions in the electrolyte and the diffusion overpotential related to the concentration gradient have been calculated. It was found that the concentration gradient is proportional to the applied current over a wide current range and that the obtained diffusion coefficient of lithium ions is almost constant. For the batteries studied in this work, the diffusion overpotential is already noticeable at 0.30 A and the limiting current is estimated to be 1.1 A, corresponding to a C-rate of 3.7.

Journal Article↗
PubMed2006

Neurotrophins support regenerative axon assembly over CSPGs by an ECM-integrin-independent mechanism.

Chondroitin sulfate proteoglycans (CSPGs) and myelin-based inhibitors are the most studied inhibitory molecules in the adult central nervous system. Unlike myelin-based inhibitors, few studies have reported ways to overcome the inhibitory effect of CSPGs. Here, by using regenerating adult dorsal root ganglion (DRG) neurons, we show that chondroitin sulfate proteoglycans inhibit axon assembly by a different mechanism from myelin-based inhibitors. Furthermore, we show that neither Rho inhibition nor cAMP elevation rescues extracellular factor-induced axon assembly inhibited by CSPGs. Instead, our data suggest that CSPGs block axon assembly by interfering with integrin signaling. Surprisingly, we find that nerve growth factor (NGF) promotes robust axon growth of regenerating DRG neurons over CSPGs. We have found that, unlike naive neurons that require simultaneous activation of neurotrophin and integrin pathways for axon assembly, either neurotrophin or integrin signaling alone is sufficient to induce axon assembly of regenerating neurons. Thus, our results suggest that the ability of NGF to overcome CSPG inhibition in regenerating neurons is probably due to the ability of regenerating neurons to assemble axons using an integrin-independent pathway. Finally, our data show that the GSK-3beta-APC pathway, previously shown to mediate developing axon growth, is also necessary for axon regeneration.

Aggrecans↗
PubMed2006

Lewis acid promoted preparation of isomerically pure fullerenols from fullerene peroxides C60(OOt-Bu)6 and C60(O)(OOt-Bu)6.

Fullerene mixed peroxides C60(t-BuOO)6 and C60(O)(t-BuOO)6 react with Lewis acids to form various fullerenols through the partial fragmentation of t-BuOO groups. Two monohydroxyl fullerenols with the general formula C60(OH)(t-BuOO)5 and six monohydroxyl fullerenols with the general formula C60(O)(OH)(t-BuOO)5 were prepared, which are essentially the same except the location of the OH group. An additional reaction of the monohydroxyl fullerenols gave bis- and trishydroxyl fullerenols. Single-crystal X-ray structures have been obtained for the two monohydroxyl fullerenols. Other compounds are characterized by chemical correlation and their spectroscopic data. Cuprous bromide could protect the most reactive t-BuOO group from being attacked by stronger Lewis acids. The proposed mechanism mainly involves Lewis acid induced heterolysis of the peroxo O-O bond.

Crystallography, X-Ray↗
PubMed2006

Preparation of fullerendione through oxidation of vicinal fullerendiol and intramolecular coupling of the dione to form hemiketal/ketal moieties.

[reaction: see text] Vicinal fullerendiol is oxidized to fullerendione in good yield by (diacetoxy)iodobenzene. The resulting cage-opened fullerendione reacts with oxygen nucleophiles in the presence of BF(3).Et(2)O to form fullerene hemiketal/ketal derivatives through coupling of the two carbonyl groups. Fullerene-mixed peroxide derivatives are involved in all these reactions. The compounds are characterized by spectroscopic data and single-crystal X-ray analysis.

Journal Article↗
PubMed2005

Investigation of noncovalent complexes between beta-cyclodextrin and polyamide acids containing N-methylpyrrole and N-methylimidazole by electrospray ionization mass spectrometry.

Electrospray ionization (ESI) mass spectrometry was utilized to investigate noncovalent complexes between beta-cyclodextrin (beta-CD) and five novel polyamide acids containing N-methylpyrrole and N-methylimidazole. The 1:1 binding mode was specified by examining the binding stoichiometry from ESI mass spectra. It found that polyamide acids with beta-CD have binding affinities in the order: ImImImbetaCOOH > ImPyImbetaCOOH > ImPyPybetaCOOH > PyPyPybetaCOOH > NO(2)PyPyPybetaCOOH. The method gives, simultaneously, the binding constants between beta-CD and polyamide acids based on a novel linear equation.

Algorithms↗
PubMed2005

Studies on electrochemical oxidation mechanisms of polyamides containing N-methylpyrrole and N-methylimidazole by electrospray ionization tandem mass spectrometry.

Electrochemical oxidization mechanism of polyamides containing N-methylpyrrole and N-methylimidazole was investigated by electrospray ionization tandem mass spectrometry (ESI-MS(n)). The spectra of the oxidization products unambiguously revealed that one or two oxygen atoms are added to the polyamide after the bulk electrolysis. It was found that electrochemical oxidation preferably takes place on the imidazole ring of the polyamide with both imidazole and pyrrole to produce a carbonyl group on the rings. ESI tandem mass spectrometry has proven to be an excellent method for the structural identification of electrochemical oxidation products of DNA-recognizing polyamides.

Electrochemistry↗
PubMed2005

Preparation of [5,6]- and [6,6]-oxahomofullerene derivatives and their interconversion by Lewis acid assisted reactions of fullerene mixed peroxides.

[60]Fullerene mixed peroxides C60(O)(OOtBu)4 exhibit chemo- and regioselective reactions under mild conditions. The epoxy moiety is opened by ferric chloride to form vicinal hydroxy chloride C60Cl(OH)(OOtBu)4. BF3 is also effective in opening the epoxy moiety. The O-O bond of the fullerene mixed peroxide is cleaved by aluminum chloride to form both [5,6]- and [6,6]-fullerene hemiketals (oxohomo[60]fullerenes). A Hock-type rearrangement is proposed for the formation of the hemiketals, in which a fullerene C-C bond is cleaved. Lewis acids and/or visible light can initiate isomerization of the hemiketal isomers. Single-crystal X-ray analysis and theoretical calculations confirmed the results.

Journal Article↗
PubMed2005

Regiochemistry of [70]fullerene: preparation of C70(OOtBu)n (n = 2, 4, 6, 8, 10) through both equatorial and cyclopentadienyl addition modes.

[reaction: see text] tert-Butylperoxy radicals add to [70]fullerene to form a mixture of adducts C(70)(OO(t)()Bu)(n)() (n = 2, 4, 6, 8, 10). Four isomers were isolated for the bis-adduct with the two tert-butylperoxo groups attached at 1,2-, 5,6-, 7,23-, and 2,5-positions, respectively. Two isomers were isolated for the tetrakis-adduct with the tert-butylperoxo groups located along the equator in C(s)() symmetry and on the side in C(1) symmetry, respectively. Similarly, two isomers were isolated for the hexakis-adducts with a structure related to the tetrakis-adducts, one of which has the cyclopentadienyl substructure. No isomer was detected for the octakis- and decakis-adducts. The C(s)()-symmetric octakis- and C(2)-symmetric decakis-adducts have all the tert-butylperoxo groups located along the equator. The decakis-adduct is the major product under optimized conditions. The compounds were characterized by their spectroscopic data. Chemical correlation through further addition of tert-butylperoxy radicals to isolated pure derivatives confirmed the structure assignment. Mechanisms of the tert-butylperoxy radical addition to C(70) follow two pathways: equatorial addition along the belt and cyclopentadienyl addition on the side.

Cyclopentanes↗
PubMed2005

Disruption of Smad5 gene induces mitochondria-dependent apoptosis in cardiomyocytes.

Our previous studies have shown that SMAD5, an important intracellular mediator of transforming growth factor beta (TGF-beta) family, is required for normal development of the cardiovascular system in vivo. In the current study, we reported that the lack of the Smad5 gene resulted in apoptosis of cardiac myocytes in vivo. To further investigate the mechanism of the Smad5 gene in cardiomyocyte apoptosis, the embryonic stem (ES) cell differentiation system was employed. We found that the myotubes that differentiated from the homozygous Smad5ex6/ex6 mutant ES cells underwent collapse and degeneration during the late stages of in vitro differentiation, mimicking the in vivo observation. By electron microscopy, abnormal swollen mitochondria were observed in cardiomyocytes both from Smad5-deficient embryos and from ES-differentiated cells. There was also a significant reduction in mitochondrial membrane potential (Deltapsi m) and a leakage of cytochrome c from mitochondria into the cytosol of myocytes differentiated from Smad5 mutant ES cells. The expression of p53 and p21 was found to be elevated in the differentiated Smad5 mutant myocytes, and this was accompanied by an up-regulation in caspase 3 expression. These results suggest that the Smad5-mediated TGF-beta signals may protect cardiomyocytes from apoptosis by maintaining the integrity of the mitochondria, probably through suppression of p53 mediated pathways.

Animals↗
PubMed2005

Analysis of noncovalent complexes between human telomeric DNA and polyamides containing N-methylpyrrole and N-methylimidazole by using electrospray ionization mass spectrometry.

Electrospray ionization mass spectrometry (ESI-MS) was used to investigate noncovalent complexes formed between four novel polyamides containing N-methylpyrrole (Py) and N-methylimidazole (Im), and human telomeric DNA. Of the four polyamides investigated, PyPyPygammaImImImbetaDp (3) had the highest binding affinity towards the duplex d(TTAGGGTTAGGG/CCCTAACCCTAA) (D1). Results of competition analysis showed that the polyamides had binding affinities with D1 in the order PyPyPygammaImImImbetaDp (3)>PyPyPyPygammaPyImImPybetaDp (4)>PyPyPybetaImImImbetaDp (2)>>ImImImbetaDp (1). MS/MS spectra confirmed that binding between D1 and the hairpin polyamides is more stable than that with the three-ring polyamides. By contrast, in the case of single-stranded d(TTAGGGTTAGGG)(D2), the binding order changes to ImImImbetaDp (1)>PyPyPygammaImImImbetaDp (3)>PyPyPybetaImImImbetaDp (2).

DNA↗
PubMed2004

NGF-induced axon growth is mediated by localized inactivation of GSK-3beta and functions of the microtubule plus end binding protein APC.

Little is known about how nerve growth factor (NGF) signaling controls the regulated assembly of microtubules that underlies axon growth. Here we demonstrate that a tightly regulated and localized activation of phosphatidylinositol 3-kinase (PI3K) at the growth cone is essential for rapid axon growth induced by NGF. This spatially activated PI3K signaling is conveyed downstream through a localized inactivation of glycogen synthase kinase 3beta (GSK-3beta). These two spatially coupled kinases control axon growth via regulation of a microtubule plus end binding protein, adenomatous polyposis coli (APC). Our results demonstrate that NGF signals are transduced to the axon cytoskeleton via activation of a conserved cell polarity signaling pathway.

Adenomatous Polyposis Coli↗