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Biomedical subjects

Qi Zhou

Publications and source records attributed to Qi Zhou.

At least 19 recordsLinked to original sources

Occlusion site and outcomes in intra-arterial tenecteplase after successful endovascular therapy: a secondary analysis of the ANGEL-TNK trial.

BACKGROUND: Endovascular thrombectomy achieves macroreperfusion in large vessel occlusion (LVO) stroke, but only one-quarter of patients had excellent functional outcome. Adjunct intra-arterial (IA) tenecteplase could further improve the treatment effect, yet its efficacy across internal carotid artery (ICA) versus middle cerebral artery (MCA) M1/M2 occlusion remains unclear. OBJECTIVE: To evaluate whether IA tenecteplase improves 90-day functional outcomes in LVO patients stratified by occlusion site (ICA, MCA M1, MCA M2). METHODS: Prespecified secondary analysis of the ANGEL-TNK trial (multicenter, randomized, open-label, blinded endpoint) in 19 Chinese stroke centers. Participants were enrolled who had anterior circulation LVO, 4.5-24&#x2009;hours from symptom onset, and CT angiography (CTA)/magnetic resonance angiography (MRA)-proven ICA, M1, or M2 occlusion. INTERVENTION: Randomization (1:1) to IA tenecteplase (0.125&#x2009;mg/kg) or standard medical management after expanded Thrombolysis in Cerebral Infarction (eTICI) 2b50-3 reperfusion. MAIN OUTCOME MEASURE: The primary outcome was the rate of 90-day modified Rankin Scale (mRS) 0-1. RESULTS: There were 256 patients in the trial, including 71 (27.7%) ICA, 122 (47.6%) MCA M1, and 62 (24.2%) MCA M2. ICA occlusion patients treated with IA tenecteplase had higher rates of 90-day mRS 0-1 (39.4% vs 13.2%; relative risk (RR) 2.99; 95%&#x2009;CI 1.51 to 5.96; p=0.002) and mRS 0-3 (54.5% vs 42.1%; RR 1.30; p=0.048) versus controls, with a significant shift toward better mRS scores (median 3 (IQR 1-4) vs 4 (2-6); odds ratio (OR) 2.26; p<0.001). Post hoc analysis showed higher eTICI progression in ICA patients (51.5%) versus MCA M1 (37.9%) and M2 (25.7%). IA tenecteplase had a lower any intracranial hemorrhage within 48 hours in ICA patients (15.2% vs 39.5%; RR 0.38; p<0.001) compared with standard medical management. No significant benefits were observed in the MCA M1/M2 subgroups, and interaction effects were significant between ICA and MCA segments for functional outcomes and safety. CONCLUSIONS AND RELEVANCE: IA tenecteplase had a better functional outcome and lower hemorrhage risk in ICA occlusion compared with standard medical management but not in MCA M1/M2. Occlusion site is a critical determinant of response to IA tenecteplase. A pooled analysis of IA tenecteplase stratified by occlusion site strata is warranted.

Humans↗

L-glutamine supplementation improves porcine sperm quality and early embryo development during in vitro fertilization.

L-glutamine (Gln), as a key additive in porcine sperm capacitation medium and in vitro fertilization (IVF) systems, has been shown to significantly improve sperm motility and survival rates. However, its precise roles during porcine IVF and subsequent early embryonic development remain elusive. This study utilized an IVF model in pigs to investigate the effects of glutamine on sperm quality and embryonic development. We found that Gln supplementation during sperm treatment significantly improved sperm quality, as evidenced by reduced reactive oxygen species (ROS) production and early apoptosis, while enhancing calcium ion levels and endoplasmic reticulum activity. Supplementing glutamine during embryo culture reduced polyspermy rates, promoted zygotic genome activation (ZGA) and accumulation of 5-ethynyluridine (EU) and histone modifications (H3K4me3 and H3K27ac) at the two-cell and four-cell stages, increased blastocyst formation rates and total cell numbers, while simultaneously reducing DNA damage and early apoptosis during the blastocyst stage. In summary, these findings demonstrate that Gln enhances porcine IVF outcomes by improving sperm quality, reducing polyspermy, and facilitating early embryonic development, thereby providing a basis for optimizing culture systems.

Animals↗

Selection of GhTT2-A07 promoter enhances fiber quality in improved cotton varieties.

Modern cultivated cotton fibers are predominantly white with enhanced quality compared to their wild ancestors. However, the molecular mechanisms and evolutionary drivers linking fiber color to quality remain least focused. In this study, we identified FQC1 (Fiber Quality and Color 1), a major quantitative trait locus (QTL) on chromosome A07 that concurrently regulates both fiber quality and pigmentation. Through map-based cloning, we revealed that Gossypium hirsutum TRANSPARENT TESTA2-A07 (GhTT2-A07), an R2R3-MYB transcription factor, resides within this locus. GhTT2-A07 modulates fiber development by directly activating genes in the general phenylpropanoid pathway, thereby promoting the metabolic flux toward downstream secondary metabolites. Variations in the GhTT2-A07 promoter led to its reduced expression in modern white cotton cultivars. This down-regulation suppresses the accumulation of S/G/H-type lignin monomers and proanthocyanidins, resulting in altered secondary cell wall composition and ultimately enhancing the quality of mature white fibers. Population genetic analyses further indicate that the white-fiber allele GhTT2-A07W has been fixed in modern breeding genotypes, underscoring the impact of artificial selection during cotton domestication. Overall, our study elucidates the biochemical and molecular mechanisms underlying fiber quality and pigmentation in cotton, clarifies the selection criteria for high-quality white fibers in modern cultivars, and provides a theoretical basis for future targeted genetic improvement of cotton fibers.

Alleles↗

Adult bi-paternal offspring generated through direct modification of imprinted genes in mammals.

Imprinting abnormalities pose a significant challenge in applications involving embryonic stem cells, induced pluripotent stem cells, and animal cloning, with no universal correction method owing to their complexity and stochastic nature. In this study, we targeted these defects at their source-embryos from same-sex parents-aiming to establish a stable, maintainable imprinting pattern de novo in mammalian cells. Using bi-paternal mouse embryos, which exhibit severe imprinting defects and are typically non-viable, we introduced frameshift mutations, gene deletions, and regulatory edits at 20 key imprinted loci, ultimately achieving the development of fully adult animals, albeit with a relatively low survival rate. The findings provide strong evidence that imprinting abnormalities are a primary barrier to unisexual reproduction in mammals. Moreover, this approach can significantly improve developmental outcomes for embryonic stem cells and cloned animals, opening promising avenues for advancements in regenerative medicine.

Animals↗

Establishment of customized mouse stem cell lines by sequential nuclear transfer.

Therapeutic cloning, whereby embryonic stem cells (ESCs) are derived from nuclear transfer (NT) embryos, may play a major role in the new era of regenerative medicine. In this study we established forty nuclear transfer-ESC (NT-ESC) lines that were derived from NT embryos of different donor cell types or passages. We found that NT-ESCs were capable of forming embryoid bodies. In addition, NT-ESCs expressed pluripotency stem cell markers in vitro and could differentiate into embryonic tissues in vivo. NT embryos from early passage R1 donor cells were able to form full term developed pups, whereas those from late passage R1 ES donor cells lost the potential for reprogramming that is essential for live birth. We subsequently established sequential NT-R1-ESC lines that were developed from NT blastocyst of late passage R1 ESC donors. However, these NT-R1-ESC lines, when used as nuclear transfer donors at their early passages, failed to result in live pups. This indicates that the therapeutic cloning process using sequential NT-ESCs may not rescue the developmental deficiencies that resided in previous donor generations.

Animals↗

Isolation and characterization of thermotolerant bacterium utilizing ammonium and nitrate ions under aerobic conditions.

A thermotolerant bacterium, identified as Bacillus licheniformis, completely utilized 0.1% (w/v) NH(4)NO(3) at 30 and 50 degrees C under aerobic condition. The addition of 0.5 mM Fe(2+) to the NH(4)NO(3 )medium markedly promoted the utilization of NH (4) (+) and NO (3) (-). At 50 degrees C, of total nitrogen originally provided, 24% was taken up into the cells and 20% remained in the culture supernatant. Residual nitrogen (56%) was probably removed into the atmosphere. The cell extracts contained enzymes involved in denitrification. GC-MS demonstrated that NH (4 ) (15) NO(3) had been converted to (15)N(2)O. These results indicate that the strain has denitrification ability under aerobic condition.

Aerobiosis↗

Molecular authentication of Alisma orientale by PCR-RFLP and ARMS.

As a widely used medicinal plant, Alisma orientale is always a possible target for fraudulent labeling. The internal transcribed spacer (ITS) regions of nuclear ribosomal DNA (nrDNA) of the six species of genus Alisma were sequenced, and two variant sites were found to be specific for A. orientale. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis and amplification refractory mutation system (ARMS) analysis were applied to the ITS region for the identification of A. orientale. A restriction site for PSTI useful for PCR-RFLP analysis was detected and a pair of diagnostic primers DFZX-JB02S and DFZX-JB02X were designed for ARMS.

Alisma↗

Generation and characterization of rabbit embryonic stem cells.

We described the derivation of four stable pluripotent rabbit embryonic stem cell (ESC) lines, one (RF) from blastocysts fertilized in vivo and cultured in vitro and three (RP01, RP02, and RP03) from parthenogenetic blastocysts. These ESC lines have been cultivated for extended periods (RF >1 year, RP01 >8 months, RP02 >8 months, and RP03 >6 months) in vitro while maintaining expression of pluripotent ESC markers and a normal XY or XX karyotype. The ESCs from all lines expressed alkaline phosphatase, transcription factor Oct-4, stage-specific embryonic antigens (SSEA-1, SSEA-3, and SSEA-4), and the tumor-related antigens (TRA-1-60 and TRA-1-81). Similar to human and mouse ESCs, rabbit ESCs expressed pluripotency (Oct-4, Nanog, SOX2, and UTF-1) and signaling pathway genes (fibroblast growth factor, WNT, and transforming growth factor pathway). Morphologically, rabbit ESCs resembled primate ESCs, whereas their proliferation characteristics were more like those seen in mouse ESCs. Rabbit ESCs were induced to differentiate into many cell types in vitro and formed teratomas with derivatives of the three major germ layers in vivo when injected into severe combined immunodeficient mice. Our results showed that pluripotent, stable ESC lines could be derived from fertilized and parthenote-derived rabbit embryos.

Animals↗

Epigenetic marks in cloned rhesus monkey embryos: comparison with counterparts produced in vitro.

Until now, no primate animals have been successfully cloned to birth with somatic cell nuclear transfer (SCNT) procedures, and little is known about the molecular events that occurred in the reconstructed embryos during preimplantation development. In many SCNT cases, epigenetic reprogramming of the donor nuclei after transfer into enucleated oocytes was hypothesized to be crucial to the reestablishment of embryonic totipotency. In the present study, we focused on two major epigenetic marks, DNA methylation and histone H3 lysine 9 (H3K9) acetylation, which we examined by indirect immunofluorescence and confocal laser scanning microscopy. During preimplantation development, 67% of two-cell- and 50% of eight-cell-cloned embryos showed higher DNA methylation levels than their in vitro fertilization (IVF) counterparts, which undergo gradual demethylation until the early morula stage. Moreover, whereas an asymmetric distribution of DNA methylation was established in an IVF blastocysts with a lower methylation level in the inner cell mass (ICM) than in the trophectoderm, in most cloned blastocysts, ICM cells maintained a high degree of methylation. Finally, two donor cell lines (S11 and S1-04) that showed a higher level of H3K9 acetylation supported more blastocyst formation after nuclear transfer than the other cell line (S1-03), with a relatively low level of acetylation staining. In conclusion, we propose that abnormal DNA methylation patterns contribute to the poor quality of cloned preimplantation embryos and may be one of the obstacles to successful cloning in primates.

Acetylation↗

Hydrolysis and acidification of waste activated sludge at different pHs.

The effect of pH from 4.0 to 11.0 on the hydrolysis and acidification of waste activated sludge (WAS) was investigated. Experimental results showed that at room temperature the sludge hydrolysis was in the following order: alkaline>acidic>(neutral and blank test), and between pH 6.0 and 11.0 the sludge hydrolysis increased with pH. The three main components, soluble protein, carbohydrate and volatile fatty acids (VFAs) in the hydrolytic product were analyzed. It was observed that both the soluble protein and carbohydrate increased with pH in the pH range 7.0-11.0, but also increased to a smaller extent with pH from 7.0 to 4.0. The VFAs concentration was also affected by pH. Under alkaline conditions, the VFAs production was significantly higher than under other conditions. The concentration of VFAs on the 8th day of fermentation at pH 4.0, 7.0 and 10.0 was, respectively, 354.49, 842.00 and 2708.02 mg/L, while VFAs in the blank test was only 633.59 mg/L. The VFAs consisted of acetic, propionic, iso-butyric, n-butyric, iso-valeric and n-valeric acids, but acetic, propionic and iso-valeric were the three main products. Also, the release of soluble phosphorus and ammonia and the production of methane was studied during WAS fermentation at different pHs.

Anaerobiosis↗

Engineered xyloglucan specificity in a carbohydrate-binding module.

The field of plant cell wall biology is constantly growing and consequently so is the need for more sensitive and specific probes for individual wall components. Xyloglucan is a key polysaccharide widely distributed in the plant kingdom in both structural and storage tissues that exist in both fucosylated and non-fucosylated variants. Presently, the only xyloglucan marker available is the monoclonal antibody CCRC-M1 that is specific to terminal alpha-1,2-linked fucosyl residues on xyloglucan oligo- and polysaccharides. As a viable alternative to searches for natural binding proteins or creation of new monoclonal antibodies, an approach to select xyloglucan-specific binding proteins from a combinatorial library of the carbohydrate-binding module, CBM4-2, from xylanase Xyn10A of Rhodothermus marinus is described. Using phage display technology in combination with a chemoenzymatic method to anchor xyloglucan to solid supports, the selection of xyloglucan-binding modules with no detectable residual wild-type xylan and beta-glucan-binding ability was achieved.

Amino Acid Sequence↗

Comparative genomic analysis links karyotypic evolution with genomic evolution in the Indian muntjac (Muntiacus muntjak vaginalis).

The karyotype of Indian muntjacs (Muntiacus muntjak vaginalis) has been greatly shaped by chromosomal fusion, which leads to its lowest diploid number among the extant known mammals. We present, here, comparative results based on draft sequences of 37 bacterial artificial clones (BAC) clones selected by chromosome painting for this special muntjac species. Sequence comparison on these BAC clones uncovered sequence syntenic relationships between the muntjac genome and those of other mammals. We found that the muntjac genome has peculiar features with respect to intron size and evolutionary rates of genes. Inspection of more than 80 pairs of orthologous introns from 15 genes reveals a significant reduction in intron size in the Indian muntjac compared to that of human, mouse, and dog. Evolutionary analysis using 19 genes indicates that the muntjac genes have evolved rapidly compared to other mammals. In addition, we identified and characterized sequence composition of the first BAC clone containing a chromosomal fusion site. Our results shed new light on the genome architecture of the Indian muntjac and suggest that chromosomal rearrangements have been accompanied by other salient genomic changes.

Animals↗

Effect of initial pH control on enhanced biological phosphorus removal from wastewater containing acetic and propionic acids.

In the literature most of the studies on the effect of pH on enhanced biological phosphorous removal were conducted with the acetate wastewater, and the pH was controlled during the entire anaerobic and aerobic stages. This paper investigated the influence of anaerobic initial pH control, which will be more practical than the entire process pH control strategy, on enhanced biological phosphorus removal from wastewater containing acetic and propionic acids. Typical pH profile showed that both the initial alkaline and acidic pH tended to neutralize due to the consumption of short-chain fatty acid (SCFA) and intracellular pH regulation by polyphosphate accumulating organisms (PAOs). It was observed that the glycogen degradation and polyhydroxyalkanoates (PHA) accumulation decreased with increasing initial pH, which disagreed with previous reports. In the literature the metabolisms of both glycogen and PHA by PAOs in the acetate wastewater were independent of pH. An anaerobic mechanism model was proposed to explain the intra- and extra-cellular pH buffer nature of PAOs, and to address the reasons for increased polyphosphate degradation and decreased PHA synthesis and glycogen degradation at higher pH. The optimal initial pH for higher soluble ortho-phosphorus (SOP) removal efficiency should be controlled between 6.4 and 7.2. This pH control strategy will be easier to use in practice of wastewater treatment plant.

Acetates↗

Origination and evolution of a human-specific transmembrane protein gene, c1orf37-dup.

A transmembrane protein gene, c1orf37-dup, was identified as a young gene specific to humans. It was derived from the conserved c1orf37 gene through retroposition after the divergence of human and chimpanzee. This gene has evolved rapidly driven by positive Darwinian selection as evident from a significantly high ratio of non-synonymous substitution rate to synonymous substitution rate (K(a)/K(s)=2.08) between the new c1orf37-dup and the parental c1orf37 genes. Population genetics analysis disclosed a very low level of polymorphism in the c1orf37-dup gene and its neighboring regions, thus providing support for the occurrence of a recent selective sweep. The GFP experiments revealed that it encodes a transmembrane protein associated with cell membranes. Non-random distribution of amino acid changes indicates the C1ORF37-DUP protein may have evolved diverged functions in the presumably functionally important N-terminal region in the cytoplasm and the extracellular loop. These lines of evidence support that the functional adaptation of c1orf37-dup has occurred in humans. Unlike its ubiquitously expressed parental gene, c1orf37-dup expresses selectively in several human tissues including brain. It is suggested that c1orf37-dup encodes a novel transmembrane protein in humans which potentially endows new properties to cell surface interactions.

Animals↗

Detection of outliers and establishment of targets in external quality assessment programs.

BACKGROUND: The establishment of target values is important in external quality assessment (EQA) programs since most of the programs use the target as the assessment criterion. Results submitted to EQA programs usually are not Gaussian-distributed due to the contamination with outliers. The traditional or robust statistical method can be chosen for the truncation of outliers. We investigated the two methods when setting targets for glucose in an EQA program. METHODS: The results of glucose were analyzed as an all-methods group and divided into four subgroups according to the analytical methods prior to testing of each data distribution. Based on the distribution, the traditional or robust statistical method was used to detect outliers. After removal of outliers, the data distributions were retested and if Gaussian distributions were obtained, the mean values were used as the target. RESULTS: Original data sets were not Gaussian-distributed for all tested groups. Therefore, the robust statistical method was employed to detect outliers. After truncation of outliers, the data sets showed Gaussian distributions and the means were used to set target values. CONCLUSIONS: The targets of glucose were determined for all-methods and individual methods from the mean values following removal of outliers using the robust statistical method. This led to comparable targets among the tested groups.

Enzymes, Immobilized↗

Cloned ferrets produced by somatic cell nuclear transfer.

Somatic cell nuclear transfer (SCNT) offers great potential for developing better animal models of human disease. The domestic ferret (Mustela putorius furo) is an ideal animal model for influenza infections and potentially other human respiratory diseases such as cystic fibrosis, where mouse models have failed to reproduce the human disease phenotype. Here, we report the successful production of live cloned, reproductively competent, ferrets using species-specific SCNT methodologies. Critical to developing a successful SCNT protocol for the ferret was the finding that hormonal treatment, normally used for superovulation, adversely affected the developmental potential of recipient oocytes. The onset of Oct4 expression was delayed and incomplete in parthenogenetically activated oocytes collected from hormone-treated females relative to oocytes collected from females naturally mated with vasectomized males. Stimulation induced by mating and in vitro oocyte maturation produced the optimal oocyte recipient for SCNT. Although nuclear injection and cell fusion produced mid-term fetuses at equivalent rates (approximately 3-4%), only cell fusion gave rise to healthy surviving clones. Single cell fusion rates and the efficiency of SCNT were also enhanced by placing two somatic cells into the perivitelline space. These species-specific modifications facilitated the birth of live, healthy, and fertile cloned ferrets. The development of microsatellite genotyping for domestic ferrets confirmed that ferret clones were genetically derived from their respective somatic cells and unrelated to their surrogate mother. With this technology, it is now feasible to begin generating genetically defined ferrets for studying transmissible and inherited human lung diseases. Cloning of the domestic ferret may also aid in recovery and conservation of the endangered black-footed ferret and European mink.

Animals↗

Improved bioproduction of short-chain fatty acids (SCFAs) from excess sludge under alkaline conditions.

The production of short-chain fatty acids (SCFAs) from excess sludge was conducted in batch fermentation tests at different pH values ranging from 4.0 to 11.0. Experimental results of the impacts of different pHs on SCFAs production showed that during the first 8-day fermentation time the total SCFAs production at either pH 9.0 or pH 10.0 was much greater than that at acidic or neutral pH, and the maximal yield of 256.2 mg SCFAs-COD per gram of volatile suspended solids (VSS) was at pH 10.0, which was, respectively, over3 and 4times that at pH 5.0 and uncontrolled pH. Clearly, SCFAs production from excess sludge could be significantly improved and maintained stable by controlling the fermentation pH at 10.0. The composition of SCFAs and the percent distribution of individual SCFAs accounting for total SCFAs at pH 10.0 were analyzed. The SCFAs consisted of acetic, propionic, iso-butyric, n-butyric, iso-valeric, and n-valeric acids, and acetic acid was the most prevalent product with a fraction of 40-55%. Because the results of this study were differentfrom those of previous studies of SCFAs production, the mechanism of increased SCFAs production under alkaline conditions was investigated. Results showed that as soluble COD increased, more soluble protein was provided as the substrate for producing SCFAs. In addition, less or even no SCFAs were consumed by methanogens at alkaline pH, so the SCFAs production was therefore remarkably improved. Further investigation revealed thatthe formation of SCFA at pH 10.0 was dominated by biological effects rather than by chemical hydrolysis.

Biodegradation, Environmental↗

Depletion of intracellular glutathione mediates butenolide-induced cytotoxicity in HepG2 cells.

Butenolide, 4-acetamido-4-hydroxy-2-butenoic acid gamma-lactone is one of the mycotoxins produced by Fusarium species which are often found on cereal grains and animal feeds throughout the world. It has been implicated as the etiology of some diseases both in animals and in humans. Though butenolide represents a potential threat to animal and human heath, there are few studies on its toxicity so far, especially on the toxic mechanisms. In this study, we investigated the cytotoxicity of butenolide on HepG2 cells and its possible mechanism from the viewpoint of oxidative stress. Butenolide reduced cell viability in a concentration- and time-dependent manner. A rapid depletion of intracellular glutathione (GSH) was observed after exposure cells to butenolide, concomitantly an increase in intracellular reactive oxygen species (ROS) production prior to cell death, indicating that oxidative stress was involved in butenolide cytotoxicity. To elucidate the role of GSH in the cytotoxicity of butenolide, intracellular GSH content was modulated before exposure to butenolide. l-buthionine-[S,R]-sulfoximine (BSO), a well-known inhibitor of GSH synthesis, aggravated butenolide-induced GSH depletion, ROS production and the loss in cell viability; in contrast, GSH depletion and ROS production was strongly inhibited, and the loss in cell viability was completely abrogated by thiol-containing compounds GSH, N-acetylcysteine (NAC) and dithiothreitol (DTT). Furthermore, a ROS scavenger catalase obviously abated ROS production and cytotoxicity induced by butenolide. Together, these results clearly demonstrate that oxidative stress plays an important role in butenolide cytotoxicity, and intracellular GSH depletion may be an original trigger of the onset of butenolide cytotoxicity.

Acetamides↗