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Jian Ma

Publications and source records attributed to Jian Ma.

At least 19 recordsLinked to original sources
PubMed2026

Ancient DNA unveils distinctive ancestries in the Bronze and Iron Ages of East Tianshan.

The East Tianshan Mountains occupy a key corridor between Central and East Asia, but their population history remains poorly understood. Here we report genome-wide data from 135 ancient individuals from 11 archaeological sites. We identify a previously unrecognized Bronze Age admixture between populations related to Yellow River millet farmers and steppe pastoralists associated with the Chemurchek culture. In contrast, we find little genetic contribution from contemporaneous middle-to-late Bronze Age steppe pastoralists, despite their eastward expansion across the Eurasian Steppe. By the Iron Age, regional populations had become more heterogeneous, incorporating additional eastern and steppe-related sources while retaining variable contributions from Early Bronze Age groups. These results reveal sustained demographic interactions in eastern Central Asia nearly 1800 years preceding the establishment of the historic Silk Road.

DNA, Ancient↗
PubMed2026

Dual HBV cccDNA-linked HiBiT reporter hepatocyte models for screening of candidate cccDNA modulators.

Chronic hepatitis B remains difficult to cure because the viral covalently closed circular DNA (cccDNA) minichromosome can persist and sustain viral transcription, creating a need for scalable, reporter readouts that facilitate early discovery of cccDNA-modulating agents. Here, we developed two complementary hepatocyte HiBiT reporter models: a replication-competent HBV reporter in HepaRG cells (HepaRG-Hibit16), in which a secreted split-NanoLuc HiBiT signal is linked to cccDNA-associated expression, and a Cre/Lox-based recombinant cccDNA (rcccDNA) reporter in HepG2 cells (HepG2-Rccc1a) that rapidly generates rcccDNA with a matched HiBiT readout. Screening of 1,403 FDA-approved compounds across both models identified 13 concordant, non-cytotoxic hits. Palovarotene, a retinoic acid receptor-γ agonist, was selected as an exemplar concordant hit and reduced HBV antigens, HBV DNA, and cccDNA and inhibited HBV infection in multiple hepatocyte-based in vitro systems without overt cytotoxicity at the tested concentrations. Together, this dual-reporter strategy supports efficient cross-model triage of candidate cccDNA modulators for subsequent orthogonal validation.

Humans↗
PubMed2026

pH Tunes the DNA Repair Efficiency and Strand Preference of the AlkB Family Enzymes.

AlkB-family Fe(II)/2-oxoglutarate-dependent dioxygenases repair alkylated nucleic acid lesions through oxidative dealkylation and play important roles in genome maintenance. 1-Methyl-2'-deoxyadenosine (1mA) and 3-methyl-2'-deoxycytidine (3mC) are well-established substrates of AlkB, ALKBH2, and ALKBH3. Although these enzymes have been extensively studied, the influence of proton concentration (pH) on their catalytic behavior and strand preference remains poorly defined. Here, we systematically examined how pH modulates the activity of the prototypical bacterial AlkB and the human homologues ALKBH2 and ALKBH3 using defined DNA substrates in both single-stranded (ssDNA) and double-stranded (dsDNA) contexts containing 1mA and 3mC lesions. Across a broad pH range, all three enzymes mainly exhibit bell-shaped activity profiles with distinct optima. The prevailing view in the field is that AlkB preferentially repairs these lesions in ssDNA, ALKBH2 favors dsDNA, and ALKBH3 prefers ssDNA. However, our results demonstrate that pH influences the catalytic efficiency and strand utilization in a substrate- and enzyme-dependent manner. AlkB maintains a consistent ssDNA preference for 3mC but exhibits variable strand preference for 1mA at different pH values. ALKBH2 retains a strong dsDNA preference for 1mA across all conditions but shows a clear pH-dependent strand switch for 3mC, favoring ssDNA under acidic conditions and preferring dsDNA at neutral to alkaline pH conditions. In contrast, ALKBH3 consistently favors ssDNA for 3mC but exhibits pH-dependent strand preference for 1mA. Our results show that the reported strand preferences largely hold at pH 7.0-8.0 but are not complete, as strand utilization and pH optima vary by enzyme and substrate. The observations demonstrate that proton availability strongly influences AlkB-family catalysis and is an important factor in how these enzymes process damaged DNA. These findings may also aid the optimization of AlkB-based protein engineering and sequencing technologies.

Hydrogen-Ion Concentration↗
PubMed2026

Seed-type vacuolar processing enzymes recognize the 619th asparagine residue to posttranslationally cleave the HMW-GS 1Dy10-m619SN allele.

High molecular weight glutenin subunits (HMW-GSs) are critical grain storage proteins in wheat, which govern its unique processing quality. A HMW-GS 1Dy10 allele variant (1Dy10-m619SN), carrying a serine-to-asparagine substitution at the 619th residue, undergoes partial posttranslational cleavage. This modification leads to improved cookie-making quality. However, the enzymes mediating this cleavage remain unknown. In this study, we identified vacuolar processing enzymes (VPEs) as candidates for 1Dy10-m619SN processing using TurboID-based proximity labeling and RNA-seq analysis. In vitro cleavage assays confirmed that VPEs catalyzed 1Dy10-m619SN cleavage. Phylogenic analysis revealed that there are two seed-type VPEs in wheat, TaVPEI and TaVPEII, with TaVPEI being further subdivided into TaVPEI-1, TaVPEI-2, and TaVPEI-3. Despite sharing conserved catalytic domains, these isoforms display distinct temporal expression patterns, with TaVPEI-1 expression showing the strongest correlation with the posttranslational cleavage of 1Dy10-m619SN. TaVPEI-1 protein is localized to the vacuole, the well-known deposition site for HMW-GSs. Overexpression of TaVPEI-1 in wheat enhances the 1Dy10-m619SN cleavage. Collectively, these findings demonstrate that the seed-type VPEs in wheat are responsible for the posttranslational cleavage of 1Dy10-m619SN, which provides new insights into the molecular basis of wheat's unique processing quality.

Triticum↗
PubMed2006

Linear ablation of left atrium for the treatment of atrial fibrillation guided by double Lasso catheters and three dimensional electroanatomical mapping.

BACKGROUND: Linear ablation of left atrium (LA) guided by three dimensional (3-D) electroanatomical mapping (Carto) has been used in many centres worldwide for the treatment of atrial fibrillation (AF) instead of pure anatomical approaches. There were little data about linear ablation of LA guided by Carto and double Lasso catheters in China. We report the results of linear ablation of LA guided by both Carto and double Lasso catheters. METHODS: After the anatomical model of LA and all pulmonary veins (PVs) had been established, circumferential ablations of the left pulmonary vein antrum and the right pulmonary vein antrum were performed with 2 circumferential mapping catheters (Lasso) placed within the ipsilateral superior and inferior PVs. The endpoint of ablation was abolishment or dissociation of the pulmonary vein potentials (PVPs). Oral amiodarone or propafenone was taken for at least 3 months by patients with persistent AF, permanent AF or those whose PVPs had not been isolated completely. The recurrence of atrial tachyarrhythmias was observed 3 months after the procedure. RESULTS: There were 106 patients (mean age, 51.4 +/- 9.9 years). Seventy-eight patients had paroxysmal AF, 12 persistent AF and 16 permanent AF. Onset of atrial fibrillation occurred in 52 patients during ablation procedure. Thirty-two patients restored to sinus rhythm eventually after the procedure. Abolishment or dissociation of PVPs was accomplished during the procedure in 94 patients (88.7%). The duration of procedure and exposure to X-ray were (213 +/- 45) minutes and (32.5 +/- 12.8) minutes, respectively. Among the 87 patients followed up for over 3 months, 62 were free of atrial tachyarrhythmias (including 8 patients who were still taking oral amiodarone). The success rate was 71.3% in the first procedure. Two patients had pericardial effusion treated by pericardial puncture and effusion drainage. No pulmonary vein stenosis, atrioesophageal fistula, stroke or procedural death occurred. CONCLUSIONS: Combination of double Lasso catheters with 3-D electroanatomical mapping to guide the linear ablation of left atrium procedure can confirm the isolation of PVPs.

Adult↗
PubMed2006

Eicosapentaenoic acid modifies lipid composition in caveolae and induces translocation of endothelial nitric oxide synthase.

Endothelial nitric oxide synthase (eNOS) plays a crucial role in the regulation of a variety of cardiovascular functions. Many studies have shown that dietary n-3 polyunsaturated fatty acids (PUFAs) have beneficial effects on coronary atherosclerosis. However, the mechanisms of n-3 PUFAs regulation in eNOS activation remain unknown. In the present study we investigated the effects of eicosapentaenoic acid (EPA, 20:5 n-3) on subcellular distribution of eNOS and lipid composition of caveolae. We demonstrated for the first time that EPA treatment profoundly altered lipid composition and fatty acyl substitutions of phospholipids in caveolae. We found that caveolin-1 was solely located in caveolae fractions in control cells, and EPA treatment displaced caveolin-1 from caveolae. eNOS was detected in the caveolin-enriched fractions and noncaveolae fractions in control cells. EPA treatment induced the translocation of eNOS from caveolae fractions to soluble fractions. P-eNOS was also distributed in both fractions. After EPA treatment, the level of p-eNOS in each fraction was increased but the distribution of which was unaffected. Moreover, the results of immunofluorescence confirmed that EPA could redistribute caveolin-1 and eNOS in plasma membrane. eNOS activity in HUVEC cells was increased after EPA treatment, which was in a dose dependent manner. And incubation with 50 microM EPA had the maximum effect on eNOS activity. Our results suggested that eNOS translocation was paralleled by a stimulated capacity for NO production in the cells. We found that total Akt and p-Akt were primarily presented in heavy membranes in control cells, and the relative level of p-Akt increased but the distribution did not change after EPA treatment. The distribution of CaM was slightly changed after EPA treatment. Our results indicated that n-3 PUFAs profoundly altered caveolae microenvironment, thereby modifying location and function of proteins in caveolae. EPA-induced alterations of lipid and proteins in caveolae may be an important mechanism in the pathophysiologic process of atherosclerosis.

Blotting, Western↗
PubMed2006

Reconstructing contiguous regions of an ancestral genome.

This article analyzes mammalian genome rearrangements at higher resolution than has been published to date. We identify 3171 intervals, covering approximately 92% of the human genome, within which we find no rearrangements larger than 50 kilobases (kb) in the lineages leading to human, mouse, rat, and dog from their most recent common ancestor. Combining intervals that are adjacent in all contemporary species produces 1338 segments that may contain large insertions or deletions but that are free of chromosome fissions or fusions as well as inversions or translocations >50 kb in length. We describe a new method for predicting the ancestral order and orientation of those intervals from their observed adjacencies in modern species. We combine the results from this method with data from chromosome painting experiments to produce a map of an early mammalian genome that accounts for 96.8% of the available human genome sequence data. The precision is further increased by mapping inversions as small as 31 bp. Analysis of the predicted evolutionary breakpoints in the human lineage confirms certain published observations but disagrees with others. Although only a few mammalian genomes are currently sequenced to high precision, our theoretical analyses and computer simulations indicate that our results are reasonably accurate and that they will become highly accurate in the foreseeable future. Our methods were developed as part of a project to reconstruct the genome sequence of the last ancestor of human, dogs, and most other placental mammals.

Algorithms↗
PubMed2006

Identification of nuclear localization signal that governs nuclear import of BRD7 and its essential roles in inhibiting cell cycle progression.

BRD7, a novel bromodomain gene, is identified to be associated with nasopharyngeal carcinoma (NPC). Decreased or loss of expression of BRD7 was detected in NPC biopsies and cell lines. Overexpression of BRD7 could inhibit NPC cell growth and arrest cells in cell cycle by transcriptionally regulating some important molecules involved in ras/MEK/ERK and Rb/E2F pathway, and downregulate the promoter activity of E2F3. In the present study, the subcellular localization of BRD7 was investigated. It was found that BRD7 was mainly localized in nucleus without distinct cell-specific difference between COS7 and HNE1. Furthermore, a functional nuclear localization signal (NLS) sequence ranging from amino acid 65 to 96 was identified and characterized. The NLS is composed of a cluster of four bipartite nuclear targeting sequences, which are tightly linked and extremely overlapped. We found that whether the entire NLS or the four bipartite nuclear targeting sequences could respectively determine the nuclear import of green fluorescent protein (GFP). The most important is that NLS-deleted BRD7 shifted the nuclear localization to be mostly in cytoplasm, and failed or reduced to negatively regulate the expression of cell cycle related molecules, cyclin D1 and E2F3, and cell cycle progression from G1 to S phase. In conclusion, NLS is an essential motif affecting BRD7 nuclear distribution, and the nuclear localization of BRD7 is critical for the expression of cell cycle related molecules and cell biological function.

Active Transport, Cell Nucleus↗
PubMed2006

Focal atrial tachycardia originating from the non-coronary aortic sinus: electrophysiological characteristics and catheter ablation.

OBJECTIVES: We sought to investigate electrophysiological characteristics and catheter ablation in patients with focal atrial tachycardia (AT) originating from the non-coronary aortic sinus (AS). BACKGROUND: In patients with failed ablation of focal AT near the His bundle (HB) region, an origin from the non-coronary AS should be considered because of the close anatomical relationship. METHODS: This study included 9 patients with focal AT, in 6 of whom attempted radiofrequency (RF) ablation had previously failed. Activation mapping was performed during tachycardia to identify an earliest activation in the atria and the AS. The aortic root angiography was performed to identify the origin in the AS before RF ablation. RESULTS: Focal AT was reproducibly induced by atrial pacing. Mapping in atria demonstrated that the earliest atrial activation was located at the HB region, whereas mapping in the non-coronary AS demonstrated that an earliest atrial activation preceded the atrial activation at the HB by 12.2 +/- 6.9 ms and was anatomically located superoposterior to the HB in all 9 patients. Also, His potentials were not found at the successful site in the non-coronary AS in all 9 patients. The focal AT was terminated in <8 s in all 9 patients. Junctional beats and PR prolongation did not occur during RF application in all 9 patients. No complications occurred in any of the nine patients. All 9 patients were free of arrhythmias without antiarrhythmic drugs during a follow-up of 9 +/- 3 months. CONCLUSIONS: In patients with focal AT near the HB region, mapping in the non-coronary AS can improve clinical outcome.

Adult↗
PubMed2006

Comparison of EMT and MST approaches in studying linear acoustics in bubbly liquid.

Two kinds of approaches have been used in literature to study the linear acoustics in a liquid-bubble mixture: The effective medium theory approach and the multiple scattering theory approach. Theoretical comparisons of mathematical formulations and intrinsic relations between these two approaches are given in this paper and show their consistency in dealing with the linear acoustics in bubbly liquids. Possible applications of these two methods are also generally discussed.

Journal Article↗
PubMed2006

Adeno-associated virus-mediated heme oxygenase-1 gene transfer suppresses the progression of micronodular cirrhosis in rats.

AIM: To test the hypothesis that enhancement of the activity of heme oxygenase can interfere with processes of fibrogenesis associated with recurrent liver injury, we investigated the therapeutic potential of over-expression of heme oxygense-1 in a CCl(4)-induced micronodular cirrhosis model. METHODS: Recombinant adeno-associated viruses carrying rat HO-1 or GFP gene were generated. 1x 10(12) vg of adeno-associated viruses were administered through portal injection at the time of the induction of liver fibrosis. RESULTS: Conditioning the rat liver with over-expression of HO-1 by rAAV/HO-1 significantly increased the HO enzymatic activities in a stable manner. The development of micronodular cirrhosis was significantly inhibited in rAAV/HO-1-transduced animals as compared to controls. Portal hypertension was markedly diminished in rAAV/HO-1-transduced animals as compared to controls, whereas there are no significant changes in systolic blood pressure. This finding was accompanied with improved liver biochemistry, less infiltrating macrophages and less activated hepatic stellate cells (HSCs) in rAAV/HO-1-transduced livers. CONCLUSION: Enhancement of HO activity in the livers suppresses the development of cirrhosis.

Animals↗
PubMed2006

Left posterior fascicular block: a new endpoint of ablation for verapamil-sensitive idiopathic ventricular tachycardia.

BACKGROUND: Verapamil-sensitive, idiopathic left ventricular tachycardia (ILVT) with right bundle branch block configuration and left-axis deviation is known to be due to re-entry mechanism but the exact nature of reentrant circuit in ILVT is not fully elucidated. Radiofrequency (RF) ablation was applied during ventricular tachycardia (VT) and termination of the VT or abolishing the inducibility of the tachycardia was used as an endpoint for successful RF. In this study, the left posterior fascicular block in surface electrocardiogram (ECG) was used as a new endpoint of ablation to cure ILVT. METHODS: Electrophysiological studies and radiofrequency ablation were performed in 39 consecutive patients [30 men, 9 women; age ranging from 10 to 64 years, mean (29 +/- 16) years] with verapamil-sensitive ILVT and structurally normal hearts. VT could be terminated by the intravenous administration of verapamil in all patients. The target site was the midseptum of LV where the earliest Purkinje potentials were recorded during VT. RF current was applied to the target site with or without late diastolic potential (LDP) during sinus rhythm in 37 patients and during VT in 2 patients to meet the ablation endpoint: the left posterior fascicular block in the surface ECG. RESULTS: Thirty-seven patients with ILVT had been treated by RF ablation during sinus rhythm and two had been treated during VT. All of them met the endpoint of the left posterior fascicular block. Thirty-eight cases were symptom-free without medications during the follow-up period (range from 3 to 95 months, median 17 months). One patient developed a clinical recurrence and the left posterior fascicular block in surface ECG disappeared. The patient received another treatment. The endpoint was met and the procedure was successful. CONCLUSIONS: The left posterior fascicular block in surface ECG used as an endpoint of RF ablation to treat ILVT is effective. It is important especially in those patients whose VT can not be induced or the inducible condition is unstable. The effective endpoint implied that the left posterior fascicle might be a critical part of the re-entrant circuit.

Adolescent↗
PubMed2006

Effect of docosahexaenoic acid on interleukin-2 receptor signaling pathway in lipid rafts.

Recent studies have shown that polyunsaturated fatty acids (PUFA) regulated the functions of membrane receptors in T cells and suppressed T cell -mediated immune responses. But the molecular mechanisms of immune regulation are not yet elucidated. Lipid rafts are plasma membrane microdomains, in which many receptors localized. The purpose of this study was to investigate the effect of DHA on IL-2R signaling pathway in lipid rafts. We isolated lipid rafts by discontinuous sucrose density gradient ultracentrifugation, and found that DHA could change the composition of lipid rafts and alter the distribution of key molecules of IL-2R signaling pathway, which transferred from lipid rafts to detergent-soluble membrane fractions. These results revealed that DHA treatment increased the proportion of polyunsaturated fatty acids especially n-3 polyunsaturated fatty acids in lipid rafts and changed the lipid environment of membrane microdomains in T cells. Compared with controls, DHA changed the localization of IL-2R, STAT5a and STAT5b in lipid rafts and suppressed the expression of JAK1, JAK3 and tyrosine phosphotyrosine in soluble membrane fractions. Summarily, this study concluded the effects of DHA on IL-2R signaling pathway in lipid rafts and explained the regulation of PUFAs in T cell-mediated immune responses.

Docosahexaenoic Acids↗
PubMed2006

Differential expression of Epstein-Barr virus-encoded RNA and several tumor-related genes in various types of nasopharyngeal epithelial lesions and nasopharyngeal carcinoma using tissue microarray analysis.

Studies have revealed that Epstein-Barr virus (EBV) infection, genetic aberration, and environmental factors are of importance in the development of nasopharyngeal carcinoma (NPC), although the definite mechanism remains to be fully elucidated. The aim of our study is to investigate using tissue microarray analysis whether differential expression of EBV-encoded small RNA-1 (EBER-1) and several tumor-related genes were associated with NPC carcinogenesis. Immunohistochemistry and in situ hybridization were performed on tissue microarrays containing 148 NPCs and 164 noncancerous nasopharyngeal epithelia (NPE) with different morphologic features. We found that overexpressions of EBER-1 hybridization signals, p53, p21ras, and bcl-2 proteins and loss expressions of p16 and p27 proteins were significantly increased in NPC tissues compared with normal NPE and hyperplastic NPE (P </= .001). The overexpressions of EBER-1 and p53 (P < .001) and the loss expressions of P16 (P < .001) and P27 (P = .005) were also significantly higher and more frequently observed in NPC than in dysplastic NPE. The positive expression of EBER-1 hybridization signals in NPC had significant associations with overexpressions of p53 (P < .001), p21ras (P = .041), and bcl-2 proteins (P < .001) and loss expression of p16 protein (P = .001). Further analysis confirmed that the abnormal expression of p53, p16, and p27 proteins occurred in the earliest stage of nasopharyngeal epithelial carcinogenesis. In the final logistic regression analysis model, the positive hybridization signals of EBER-1 and the abnormal expression of p53, p16, and p27 proteins were independent contributions for nasopharyngeal carcinogenesis, and EBER-1 was the most significant, independent predictor of nasopharyngeal carcinogenesis (hazard ratio = 13.412, 95% confidence interval 6.179-29.111, P < .001). In conclusion, EBV infection, together with overexpressions of p53, and loss expressions of p16 and p27 proteins are involved in the multistep process of human nasopharyngeal epithelial carcinogenesis.

Adenocarcinoma↗
PubMed2006

[Endoscopic transseptal transsphenoidal pituitary adenoma microsurgery].

OBJECTIVE: To introduce the approach and technique of endoscopic transseptal transsphenoidal pituitary adenoma microsurgery. METHOD: Endoscopic transseptal transsphenoidal pituitary adenoma microsurgery were performed in 23 patients. RESULT: Tumors were total resected in all of the patients. The mean volume of bleeding was 50 ml and there were not any severe complications. CONCLUSION: Compared with transsphenoidal pituitary adenoma microsurgery and endoscopic transsphenoidal pituitary adenoma surgery, endoscopic transseptal transsphenoidal pituitary adenoma microsurgery could combine the benefits of the two approaches. The approach has the benefit of microtrauma, convenience and could resect the tumor thoroughly. We could do best in treating suitable patients with good endoscopic technique.

Adolescent↗
PubMed2005

Bilirubin derived from heme degradation suppresses MHC class II expression in endothelial cells.

The enzymatic action of heme oxygenase (HO) is mediated by the cleavage of heme into carbon monoxide, ferrous iron, and biliverdin/bilirubin. Here, we show that induction of HO-1 expression, an inducible form of HO, down-regulates IFN-gamma-induced MHC class II expression in endothelial cells. Among three catalytic products of HO, bilirubin, but not carbon monoxide or ferrous iron, mediated the suppressive effects of HO through the reduction of mRNA levels of Stat-1-dependent class II transactivator. Expression of HO-1 could suppress the levels of IFN-gamma-induced Stat-1 phosphorylation. This effect could be mimicked by exposing the cells to one of its catalytic products, bilirubin. In addition, HO-1 or bilirubin could modulate the transcript activities of Stat-1-driven gene expression in luciferase reporter assays. These findings suggest an important role of HO-1 in the modulation of immune responses through suppression of MHC-II expression in antigen presenting cells. Our data provide a new line of evidence supporting HO-1-targeted therapy for immune modulation.

Animals↗