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Biomedical subjects

Qingwu Yang

Publications and source records attributed to Qingwu Yang.

7 recordsLinked to original sources
PubMed2026

Effect of Baseline ASPECTS on Tenecteplase Efficacy Before Thrombectomy in Acute Large-Vessel Occlusion Stroke: A Post Hoc Analysis of the BRIDGE-TNK Randomized Trial.

BACKGROUND AND OBJECTIVES: The impact of ischemic extent on the efficacy and safety of intravenous thrombolysis before thrombectomy remains uncertain. The aim of this study was to evaluate whether the baseline ischemic extent, measured by the Alberta Stroke Program Early Computed Tomography Score (ASPECTS), modifies outcomes of intravenous tenecteplase administered before endovascular thrombectomy. METHODS: This was a post hoc analysis of the BRIDGE-TNK (thrombectomy with vs without rhTNK-tPA in stroke) trial, conducted across China from May 2022 to September 2024. We compared the efficacy and safety of intravenous tenecteplase plus thrombectomy vs thrombectomy alone in acute large-vessel occlusion stroke patients within 4.5 hours of last known well, stratified by baseline ASPECTS (<8 vs 8-10). The outcomes included 90-day functional independence (modified Rankin Scale score of 0-2), 48-hour symptomatic intracranial hemorrhage (sICH), and 90-day mortality. Regression models incorporating a treatment-by-ASPECTS interaction term were used for analysis. RESULTS: Among 550 patients, 241 (43.8%) had ASPECTS <8 (median [interquartile range, IQR] age, 69 [61-77] years; 56.4% male) and 309 had ASPECTS 8-10 (median [IQR] age, 70 [61-77] years; 59.5% male). The rate of functional independence was significantly higher in the tenecteplase plus thrombectomy group than in the thrombectomy-alone group in the ASPECTS <8 subgroup (adjusted risk ratio [aRR], 1.67; 95% CI 1.18-2.35), but not in the ASPECTS 8-10 subgroup (aRR, 0.99; 95% CI 0.84-1.17; pinteraction = 0.007). Rates of sICH did not differ significantly between treatment groups in either ASPECTS subgroups (ASPECTS <8: 10.0% vs 11.2%; ASPECTS 8-10: 7.5% vs 2.8%; pinteraction = 0.11). Ninety-day mortality was comparable between treatment groups in the ASPECTS <8 subgroup, but numerically higher with tenecteplase plus thrombectomy in the ASPECTS 8-10 subgroup (aRR = 1.89, 95% CI 0.99-3.61, pinteraction = 0.04). DISCUSSION: In this exploratory post hoc analysis, a signal of benefit was observed in patients with ASPECTS <8 who received intravenous tenecteplase before thrombectomy, whereas no functional improvement and possible safety concerns were seen in those with ASPECTS 8-10. Prospective confirmation in randomized trials is required before practice change. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov; Unique identifier: NCT04733742.

Humans↗
PubMed2006

A polynomial time solvable formulation of multiple sequence alignment.

Since traditional multiple alignment formulations are NP-hard, heuristics are commonly employed to find acceptable alignments with no guaranteed performance bound. This causes a substantial difficulty in understanding what the resulting alignment means and in assessing the quality of these alignments. We propose an alternative formulation of multiple alignment based on the idea of finding a multiple alignment of k sequences which preserves k - 1 pairwise alignments as specified by edges of a given tree. Although it is well known that such a preserving alignment always exists, it did not become a mainstream method for multiple alignment since it seems that a lot of information is lost from ignoring pairwise similarities outside the tree. In contrast, by using pairwise alignments that incorporate consistency information from other sequences, we show that it is possible to obtain very good accuracy with the preserving alignment formulation. We show that a reasonable objective function to use is to find the shortest preserving alignment, and, by a reduction to a graph-theoretic problem, that the problem of finding the shortest preserving multiple alignment can be solved in polynomial time. We demonstrate the success of this approach on three sets of benchmark multiple alignments by using consistency-based pairwise alignments from the first stage of two of the best performing progressive alignment algorithms TCoffee and ProbCons and replace the second heuristic progressive step of these algorithms by the exact preserving alignment step. We apply this strategy to TCoffee and show that our approach outperforms TCoffee on two of the three test sets. We apply the strategy to a variant of ProbCons with no iterative refinements and show that our approach achieves similar or better accuracy except on one test set. We also compare our performance to ProbCons with iterative refinements and show that our approach achieves similar or better accuracy on many subcategories even without further refinements. The most important advantage of the preserving alignment formulation is that we are certain that we can solve the problem in polynomial time without using a heuristic. A software program implementing this approach (PSAlign) is available at http://faculty.cs.tamu.edu/shsze/psalign.

Algorithms↗
PubMed2006

Identification of the syr-syp box in the promoter regions of genes dedicated to syringomycin and syringopeptin production by Pseudomonas syringae pv. syringae B301D.

The phytotoxins syringopeptin and syringomycin are synthesized by nonribosomal peptide synthetases which are encoded by the syringomycin (syr) and syringopeptin (syp) genomic island of Pseudomonas syringae pv. syringae. Previous studies demonstrated that expression of the syr-syp genes was controlled by the salA-syrF regulatory pathway, which in turn was induced by plant signal molecules. In this study, the 132-kb syr-syp genomic island was found to be organized into five polycistronic operons along with eight individual genes based on reverse transcriptional PCR and bioinformatic analysis. The transcriptional start sites of the salA gene and operons III and IV were located 63, 75, and 104 bp upstream of the start codons of salA, syrP, and syrB1, respectively, using primer extension analysis. The predicted -10/-35 promoter region of operon IV was confirmed based on deletion and site-directed mutagenesis analyses of the syrB1::uidA reporter with beta-glucuronidase assays. A 20-bp conserved sequence (TGtCccgN(6)cggGaCA, termed the syr-syp box) with dyad symmetry around the -35 region was identified via computer analysis for the syr-syp genes/operons responsible for biosynthesis and secretion of syringomycin and syringopeptin. Expression of the syrB1::uidA fusion was decreased 59% when 6 bp was deleted from the 5' end of the syr-syp box in the promoter region of operon IV. These results demonstrate that the conserved promoter sequences of the syr-syp genes contribute to the coregulation of syringomycin and syringopeptin production.

Bacterial Proteins↗
PubMed2003

Dynamic responses of protein homeostatic regulatory mechanisms to perturbations from steady state.

Nineteen hypothetical protein homeostatic regulatory mechanisms were constructed and analysed in terms of the rate at which they recovered from a perturbation in the steady-state concentration of any component. Systems were constructed to symbolize transcription/translation processes of the average protein from Escherichia coli (1000 copies of protein P along with 1 gene G per cell). In some model systems, G catalysed the synthesis of P directly, while in others G catalysed the synthesis of mRNA (called M), and M catalysed the synthesis of P in a subsequent step. Recovery rates for each regulatory mechanism were obtained by generating the corresponding system of differential equations, linearizing the system about the steady state, and determining eigenvalues of the associated coefficient matrix. The optimal rate of recovery for a given mechanism, R(D), was determined by combining random and gradient search approaches to find rate constants for which the system recovered fastest. Regulatory elements that improved dynamic regulation were identified. These consisted of negative feedback relationships that involved P binding to either G (to shut off the synthesis of P) or M (to stimulate its degradation). Regulation improved as increasing numbers of P's bound to either G or M; however, the binding to M was more effective. In other mechanisms PP dimers bound G. Dimer-binding mechanisms were roughly twice as effective in terms of regulation as those that bound P monomers. The effect of linking two regulatory "modules" was also investigated. Linking had no effect on R(D), but optimal rate constants for the linked system were similar to those of the unlinked modules, suggesting that it may be feasible to construct regulatory networks by linking individual modules of this type.

Animals↗
PubMed2003

Reduction and methyl transfer kinetics of the alpha subunit from acetyl coenzyme a synthase.

Stopped-flow was used to evaluate the methylation and reduction kinetics of the isolated alpha subunit of acetyl-Coenzyme A synthase from Moorella thermoacetica. This catalytically active subunit contains a novel Ni-X-Fe4S4 cluster and a putative unidentified n = 2 redox site called D. The D-site must be reduced for a methyl group to transfer from a corrinoid-iron-sulfur protein, a key step in the catalytic synthesis of acetyl-CoA. The Fe4S4 component of this cluster is also redox active, raising the possibility that it is the D-site or a portion thereof. Results presented demonstrate that the D-site reduces far faster than the Fe4S4 component, effectively eliminating this possibility. Rather, this component may alter catalytically important properties of the Ni center. The D-site is reduced through a pathway that probably does not involve the Fe4S4 component of this active-site cluster.

Acetate-CoA Ligase↗
PubMed2002

Lipopolysaccharide upregulates the expression of Toll-like receptor 4 in human vascular endothelial cells.

OBJECTIVE: To investigate the expression of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) and the effect of lipopolysaccharide (LPS) on their expression in cultured endothelial cells. METHODS: Total RNA was extracted from ECV304 cells and isolated human umbilical vein endothelial cells (HUVECs) exposed to LPS, respectively. The quantification of TLR2 and TLR4 mRNA in HUVECs and EVC304 cells was carried out by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: ECV304 cells and HUVECs were able to express TLR2 and TLR4 mRNA, but the expression levels of TLR4 appeared to be stronger than those of TLR2. LPS could upregulate the expression levels of TLR4 obviously, whereas it had no effect on the expression level of TLR2. CONCLUSIONS: Our data indicate that TLR4 may be the LPS signal transducer in endothelial cells and plays important roles in the cell activation of LPS. The ECV304 cell line is a better experimental model than isolated HUVECs in the research of endothelial cells.

Cell Line↗