PubMed Health⌕ Search

Biomedical subjects

Ya Li

Publications and source records attributed to Ya Li.

At least 19 recordsLinked to original sources

Multistrategy metabolic engineering of Talaromyces pinophilus for α-amylase production from lignocellulosic biomass.

Filamentous fungi are important hosts for industrial enzyme production. Growing demand for α-amylase has increased reliance on food-derived carbon substrates, necessitating fungal strains that efficiently utilize nongrain biomass. In this study, Talaromyces pinophilus Y117 was metabolically engineered to produce α-amylase from lignocellulosic biomass. A strong cellobiohydrolase I gene (cbh1) promoter (Pcbh1Tru) was identified to drive expression. Multiple rounds of multilocus integration of the α-amylase gene were performed using homologous multicopy genomic sequences as recombination arms with a Cre/loxP-based recyclable selection system, yielding the multicopy strain Tp4, which achieved 4124.5 U/mL α-amylase activity in shake-flask fermentation with corncob powder as the sole carbon source. To minimize enzyme degradation, the protease gene 8538 was deleted using the Cre/lox2272 system, generating Tp4Δp. This strain showed a 50% increase in shake-flask α-amylase activity (6208.4 U/mL). In 3-L bioreactor cultivation, Tp4Δp exhibited excellent production performance, achieving 26 712.2 U/mL α-amylase activity. When corncob powder was used as the sole substrate, the cellulose and hemicellulose degradation rates reached 90.00% and 70.01%, respectively, and the enzyme yield reached 213 697.5 U per gram of corncob powder. This engineered strain demonstrates strong potential for industrial applications. The synthesis-degradation synergistic optimization strategy provides a practical approach for engineering filamentous fungal cell factories to produce enzymes directly from lignocellulosic biomass. One sentence summary Metabolic engineering of Talaromyces pinophilus through promoter optimization, multicopy integration, and protease deletion enables efficient α-amylase production from lignocellulosic biomass, achieving 26 712 U/mL in bioreactor fermentation.

Talaromyces↗

Mimicry and antibody-mediated cell signaling in autoimmune myocarditis.

The mechanisms by which autoantibodies against cardiac myosin (CM) may lead to heart dysfunction is unknown. We show that autoantibodies to CM in anti-CM sera and mAbs derived from experimental autoimmune myocarditis targeted the heart cell surface and induced Ab-mediated cAMP-dependent protein kinase A activity. Ab-mediated cell signaling of protein kinase A was blocked by CM, anti-IgG, or by specific inhibitors of the beta-adrenergic receptor (beta-AR) pathway. mAbs confirmed mimicry between CM and the beta-AR. Passive transfer of purified Ab (IgG) from CM-immunized rats resulted in IgG deposition and apoptosis in the heart, leading to a cardiomyopathic heart disease phenotype in recipients. Our novel findings link anti-CM Ab with the beta-AR and subsequent Ab-mediated cell signaling in the heart.

Animals↗

Nucleophilic fluoroalkylation of epoxides with fluorinated sulfones.

The unprecedented nucleophilic fluoroalkylation of simple epoxides with fluorinated sulfones was achieved to give the beta-fluoroalkyl alcohols in one step. The negative "fluorine effect" in the nucleophilic fluoroalkylation of epoxides with fluorinated carbanions was probed by the reactivity comparison between carbanions PhSO2CF2- (3) and PhSO2CCl2- (4) and between carbanions PhSO2CHF- (7) and PhSO2CHCl- (13). The mediation of this fluorine effect by introducing another electron-withdrawing benzenesulfonyl group was found to be an effective way to significantly increase the nucleophilicity of the fluorinated carbanions, with the reactivity order [(PhSO2)2CF-] (16) > PhSO2CFH- (7) >> PhSO2CF2- (3).

Anions↗

Stereoselective nucleophilic monofluoromethylation of N-(tert-butanesulfinyl)imines with fluoromethyl phenyl sulfone.

[reaction: see text] Highly stereoselective nucleophilic monofluoromethylation of (R)-(tert-butanesulfinyl)imines with fluoromethyl phenyl sulfone was achieved to afford alpha-monofluoromethylamines with a nonchelation-controlled stereoselectivity mode. By using the same chemistry, (R)-(tert-butanesulfinyl)imines bearing a terminal tosylate (OTs) group can be converted to alpha-monofluoromethylated cyclic secondary amines with high stereoselectivity.

Journal Article↗

[Transfection of recombinant bone morphogenetic protein-7 expressing plasmid into cultured human renal tubular epithelial cells attenuates the extracellular matrix accumulation induced by transforming growth factor-beta].

OBJECTIVE: To investigate the effects of bone morphogenetic protein (BMP)-7 on the extracellular matrix (ECM) accumulation induced by transforming growth factor (TGF)-beta. METHODS: Mouse full length BMP-7 cDNA was ligated into a eukaryotic expression vector pcDNA3.1. Restriction enzymatic analyses and DNA sequencing were used to confirm the accuracy of the BMP-7 expressing plasmid thus constructed. The recombinant expression plasmid pcDNA3.1-BMP-7 was transfected into cultured human renal tubular epithelial cells of the line HK-2 mediated by liposome. Positive clones were selected so as to obtain the human renal epithelial cells with stable transfection. These HK-2 cells were cultured and divided into 5 groups to be treated with 5 ng/ml TGF-beta, blank plasmid pcDNA3.1, blank plasmid pcDNA3.1 + 5 ng/ml TGF-beta, pcDNA3.1-BMP-7, pcDNA3.1-BMP-7 + 5 ng/ml TGF-beta, and an additional grin the cells and the supernatant of the cell culture fluid were collected. The expression level of BMP-7 protein was determined by Western blotting. RT-PCR and ELISA were used to determine the mRNA and protein expression of collagen (Col) I and III, and fibronectin (FN) in the human renal tubular epithelial cells and supernatant of different groups. RESULTS: The recombinant plasmid pcDNA3.1-BMP-7 was successfully constructed. The cell mRNA expression levels of Col I and III and FN of the 5 ng/ml TGF-beta group and blank plasmid pcDNA3.1 + 5 ng/ml TGF-beta group were all significantly higher than those of the blank plasmid pcDNA3.1 group, pcDNA3.1-BMP-7 group, and control group (all P < 0.05). The cell mRNA expression levels of Col I and FN of the pcDNA3.1-BMP-7 + 5 ng/ml TGF-beta were all significantly lower than those of the TGF-beta group (all P < 0.05). The cell mRNA expression level of Col III of the pcDNA3.1-BMP-7 + 5 ng/ml TGF-beta was lower, however, not significantly, than that of the TGF-beta group. The supernatant FN levels of the 5 ng/ml TGF-beta group and pcDNA3.1 + 5 ng/ml TGF-beta group were both significantly higher than that of the control group (both P < 0.05), and the supernatant FN level of the pcDNA3.1-BMP-7 + 5 ng/ml TGF-beta group was significantly lower that that of the 5 ng/ml TGF-beta group (P < 0.05). CONCLUSION: Over-expression of BMP-7 significantly inhibits the increased syntheses of collagen I and III, and fibronectin induced by TGF-beta. BMP-7 exerts its antifibrotic effect partially through blocking the TGF-beta-induced accumulation of extracellular matrix in human renal tubular epithelial cells.

Animals↗

T cell mimicry and epitope specificity of cross-reactive T cell clones from rheumatic heart disease.

Mimicry between streptococcal M protein and cardiac myosin is important in the pathogenesis of rheumatic heart disease. M protein-specific human T cell clones derived from rheumatic carditis were cross-reactive with human cardiac myosin, and laminin, a valve protein. Among the 11 CD4(+) and CD8(+) cross-reactive T cell clones, at least 6 different reactivity patterns were distinguished, suggesting different degrees of cross-reactivity and a very diverse T cell repertoire. The latter was confirmed by a heterogeneous Vbeta gene and CDR3 usage. HLA restriction and Th1 cytokine production in response to rM6 protein were preserved when the T cell clones were stimulated by human cardiac myosin or other alpha-helical proteins, such as tropomyosin and laminin. The cross-reactive human T cell clones proliferated to B2 and B3A, dominant peptide epitopes in the B repeat region of streptococcal M protein. In human cardiac myosin, epitopes were demonstrated in the S2 and light meromyosin regions. In our study, T cell mimicry was defined as recognition of structurally related Ags involved in disease and recognized by the same T cell. Mimicry in our study was related to alpha-helical coiled coil proteins which have a repetitive seven-aa residue periodicity that maintains alpha-helical structure and thus creates a high number of degenerate possibilities for recognition by T cells. The study of human T cell clones from rheumatic heart disease revealed potential sites of T cell mimicry between streptococcal M protein and human cardiac myosin and represents some of the most well-defined T cell mimicry in human autoimmune disease.

Amino Acid Sequence↗

Protection against experimental autoimmune myocarditis is mediated by interleukin-10-producing T cells that are controlled by dendritic cells.

Experimental autoimmune myocarditis (EAM) can be induced in the Lewis rat by cardiac myosin or its cryptic S2-16 peptide epitope (amino acids 1052 to 1076). To investigate cellular mechanisms and the role of antigen-presenting cells in regulation of myocarditis, we induced protection against EAM in Lewis rats by administration of S2-16 peptide in incomplete Freund's adjuvant (IFA). Protection to EAM was associated with activation of S2-16-reactive splenocytes secreting high levels of interleukin (IL)-10 and reduced levels of interferon-gamma and IL-2. Adoptive transfer of S2-16:IFA-induced splenocytes producing IL-10 suppressed myocarditis induction in syngeneic recipients, suggesting their regulatory cell nature. However, exposure of S2-16:IFA-induced cells to inflammatory cytokine IL-12 converted them to Th1 effectors that transferred EAM. Differentiated function of S2-16-reactive T cells in protected rats resulted from increased IL-10 production by dendritic cells (DCs). Purified DCs from S2-16:IFA-treated rats promoted S2-16-reactive CD4+ T cells to produce increased IL-10 and reduced interferon-gamma. In addition, adoptive transfer of IL-10-producing DCs from S2-16:IFA-treated rats also induced protection to EAM in recipient rats. These studies demonstrated DCs and key cytokines, such as IL-10 and IL-12, regulated the fate of T cells in myocarditis development in the Lewis rat.

Adoptive Transfer↗

Screening for ZNF230 gene mutation and analysis of its correlation with azoospermia.

OBJECTIVE: To investigate the possible association between ZNF230 gene and azoospermia. METHODS: Screening for mutation of all 6 exons of ZNF230 gene was performed by denaturing high performance liquid chromatography(DHPLC) in 99 patients with azoospermia and in 115 healthy men as controls. RESULTS: An A-->G transition at nucleotide 316 in exon 6 was identified. There were significant differences in the distribution profiles of both allele and genotype frequencies between patient group and control group (P < 0.01 and P < 0.05, respectively). In addition,there was a statistically significant difference in the serum follicle stimulating hormone (FSH) level between the patients with GG/GA genotype and those with AA genotype (P < 0.05). CONCLUSION: ZNF230 gene may be associated with azoospermia, and the A316G mutation may be correlated with the serum FSH level.

Adult↗

[Relationship between the R219K polymorphism of ATP-binding cassette transporter 1 gene and coronary heart disease].

To study the distribution of R219K polymorphism in ATP-Binding Cassette Transporter 1 (ABCA1) gene in Chinese Han population and the association of this polymorphism with coronary heart disease (CHD) . Genotypes were determined by PCR-RFLP approach in 417 unrelated healthy controls and 396 CHD patients. The frequencies of K allele and KK genotype for controls (0.465, 0.228) were significantly higher than those (0.381, 0.162) for patients (P<0.05). When the patients were divided into two subgroups by onset-age, the frequencies of K allele and KK genotype for early-onset patients (0.34, 0.111) were lower than those (0.419, 0.205) for late-onset patients and those for controls (P<0.05) , while there were no such differences between late-onset patients and controls. Patients with RR genotype had a higher plasma concentration of triglycerides (TG) when compared with that of KK genotype (P<0.05) . No significant differences of plasma high-density lipoprotein cholesterol (HDL-C) level were observed among patients with different genotypes. These data suggest that the R219K polymorphism in ABCA1 gene is correlated with CHD, and the ABCA1 gene KK genotype may has a function against atherosclerosis without detectable change of plasma HDL-C level in Chinese Han population.

ATP Binding Cassette Transporter 1↗

Neurochemical and behavioral effects of the intrahippocampal co-injection of beta-amyloid protein1-40 and ibotenic acid in rats.

The present study was designed to investigate the effects of the intrahippocampal co-injection of beta-amyloid protein1-40 (Abeta(1-40)) with ibotenic acid (Ibo) on learning and memory in normal and aging model rats, and to explore the mechanism underlying the effects of the co-injection. The normal and aging rats were bilaterally injected Abeta(1-40) (4 microg for each side) with Ibo (2 microg for each side) into the hippocampus. Two weeks after the intrahippocampal injection, the exploratory behavior and learning-memory ability of the rats were tested by using open field, Y-maze and passive avoidance task. And the changes of membrane fluidity in hippocampal mitochondria, the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in hippocampus were also examined. The co-injection of Abeta(1-40) with Ibo induced tested rats a remarkable decrease in the explorative behaviors and a significant decline in learning-memory ability (P < 0.01). The neurochemical changes induced by the co-injection included a significant decrease in membrane fluidity of hippocampal mitochondria (P < 0.01), a significant decrease in the activity of SOD (P < 0.01), as well as a remarkable increase in the content of MDA (P < 0.01). The results suggest that co-injection of Abeta(1-40) with Ibo may induce an increase of hippocampal damage by peroxidation and a serious deficit in the learning and memory of the rats. The results also suggest that the co-injection of Abeta(1-40) with Ibo may provide a useful animal model for the Alzheimer's disease (AD) research.

Aging↗

Zaprinast stimulates extracellular adenosine accumulation in rat pontine slices.

Adenosine appears to be an endogenous somnogen. The lateral dorsal tegmental/pedunculopontine nucleus (LDT/PPT) located in the mesopontine tegmentum is important in the regulation of arousal. Neurons in this nucleus are strongly hyperpolarized by adenosine and express neuronal nitric oxide synthase. Zaprinast is a cyclic nucleotide phosphodiesterase inhibitor, and has been shown in the hippocampal slice to inhibit the field excitatory postsynaptic potential. This action could be blocked by an adenosine receptor antagonist, and therefore is presumably due to adenosine release stimulated by zaprinast. In the present study we tested the effect of zaprinast on extracellular adenosine accumulation in pontine slices containing the LDT. Zaprinast at 10 microM evoked an increase in extracellular adenosine concentration. This effect was blocked by impermeant inhibitors of 5'-nucleotidase, indicating that the extracellular adenosine was derived from extracellular AMP. However, inhibitors of cAMP degradation had little or no effect on zaprinast-evoked adenosine accumulation, suggesting that extracellular cAMP was not the source. Removal of extracellular calcium inhibited the effect of zaprinast. These results demonstrate that a pathway exists by which zaprinast stimulates extracellular adenosine accumulation, and the presence of this pathway in the pontine slice suggests the possibility that it may be relevant for the regulation of behavioral state.

Adenosine↗

[The experimental study on the oval cells participating in hepatocarcinogenesis].

OBJECTIVE: To explore the genesis of the oval cells in hepatic tissue and relationship between the hepatic oval cells and the primary hepatocarcinoma. METHODS: Sixty SD rats were divided into normal group (20 cases) and experimental group (40 cases). C-kit and PCNA were continuously detected by immunohistochemistry and the liver pathologic changes were observed by optical microscope in the different period. RESULTS: The hepatical surface was lubricous and the histological morpha was normal in the normal group, and the positive cells of C-kit and PCNA were found on occasion. In the experimental group, the oval cells which express C-kit and PCNA were firstly discovered in the periportal regions in the second weeks, and these cells proliferate in turn and rangely in the bile duct epithelium. With the hepatic injury becoming more serious, the oval cells extended into the centrilobular regions from periportal regions. When HCC occurred, the oval cells were found in the cancer nodule and in the margin. In this period, the most of positive cells of C-kit still located in the periportal regions, while the PCNA cells were found in and out of the cancer nodule. CONCLUSIONS: The oval cells originate from bile duct of the periportal regions. The oval cells play an important role in the process of hepatocarcinogenesis.

Animals↗

Cryptic epitope identified in rat and human cardiac myosin S2 region induces myocarditis in the Lewis rat.

Myocarditis is a common cause of dilated cardiomyopathy leading to heart failure. Chronic stages of myocarditis may be initiated by autoimmune responses to exposed cardiac Ags after myocyte damage. Cardiac myosin, a heart autoantigen, induced experimental autoimmune myocarditis (EAM) in susceptible animals. Although cardiac myosin-induced myocarditis has been reported in Lewis rats, the main pathogenic epitope has not been identified. Using overlapping synthetic peptides of the S2 region of human cardiac myosin, we identified an amino acid sequence, S2-16 (residues 1052-1076), that induced severe myocarditis in Lewis rats. The myocarditic epitope was localized to a truncated S2-16 peptide (residues 1052-1073), which contained a sequence identical in human and rat cardiac myosin. The S2-16 peptide was not myocarditic for three other strains of rats, in which the lack of myocarditis was accompanied by the absence of strong S2-16-specific lymphocyte responses in vitro. For Lewis rats, S2-16 was characterized as a cryptic epitope of cardiac myosin because it did not recall lymphocyte and Ab responses after immunization with cardiac myosin. Lymphocytes from S2-16 immunized rats recognized not only S2-16, but also peptides in the S2-28 region. Furthermore, peptide S2-28 was the dominant epitope recognized by T cells from cardiac myosin immunized rats. S2-16 was presented by Lewis rat MHC class II molecules, and myocarditis induction was associated with an up-regulation of inflammatory cytokine production. S2-16-induced EAM provides a defined animal model to investigate mechanisms of EAM and modulation of immune responses to prevent autoimmune myocarditis.

Adjuvants, Immunologic↗

Association of estrogen receptor alpha polymorphisms with susceptibility to chronic hepatitis B virus infection.

Several studies have demonstrated that estrogen receptor alpha (ESR1) participates in the pathogenesis of persistent hepatitis B virus (HBV) infection. To examine whether polymorphisms at the ESR1 gene locus are associated with persistent HBV infection, we resequenced ESR1 genomic region for single nucleotide polymorphisms (SNPs) in 27 unrelated Chinese. Two haplotype-tagged SNPs (htSNP), T29C and A252966G, were selected for genotyping in 1,277 persistent HBV-infected cases, 748 spontaneously recovered controls, and 293 nuclear families using polymerase chain reaction (PCR)-restriction fragment length polymorphism (PCR-RFLP) analysis. We observed that the subjects bearing ESR1 29T/T genotype had an increased susceptibility to persistent HBV infection compared to those bearing at least one 29C allele (odds ratio 1.41; 95% CI, 1.17-1.71, P < .001). Consistent with the results of population-based association study, a significantly greater than expected transmission of the 29T allele (56.4%) from heterozygous parents to offspring with persistent HBV infection was observed (chi2 = 4.60, P = .033) using the transmission-disequilibrium test (TDT) in 293 nuclear families. Linkage disequilibrium (LD) mapping analysis indicated that the T29C polymorphism contained within a LD block located from promoter region to intron 3 of ESR1, suggesting that the strong association detected with T29C in ESR1 originated from ESR1 itself. In conclusion, our results suggest that the genetic variation at the ESR1 locus influences susceptibility to persistent HBV infection in a Chinese population.

Adult↗

Variants in TNFRSF5 locus and association analysis with Hepatitis B virus (HBV) infection.

Human TNFRSF5, a key signaling molecule expressed by antigen-presenting cells of the immune system, might have associations with autoimmune diseases and various infectious diseases. In the present study, we screened single-nucleotide polymorphisms (SNPs) in TNFRSF5 and examined whether they are risk factors for persistent HBV infection or disease severity. We resequenced all 9 exons, the promoter and splicing regions of all introns for 186 Chinese individuals, and identified 11 SNPs. Haplotypes and their frequencies were estimated. The linkage disequilibrium (LD) pattern was also evaluated. Neutrality tests indicated that the variation pattern at TNFRSF5 locus departs from neutrality and may be maintained by positive selection or demography factors such as population growth. Three SNPs (g.53031T>C, g.54068T>C and g.64493A>G) were determined as haplotype-tag SNPs (htSNPs). Furthermore, computer analyses indicated that sequences surrounding g.53031T>C and g.53824T>C were potential binding sites for transcription factors Sp1 and H4TF-2, respectively. We then genotyped these four SNPs for 603 persistent HBV infection patients and 384 spontaneously recovered subjects by PCR direct sequencing. No statistically significant associations were observed between any of the SNPs or haplotypes and persistent HBV infection or disease severity. The information from this study of the TNFRSF5 would be useful for genetic studies of other common diseases.

Adult↗

Determination of six major flavonoid glycosides in Saussurea mongolica by capillary electrophoresis.

A new capillary electrophoresis (CE) method was established for simultaneous assay of six flavonoid O-glycosides, asebotin (AS), kaempferol 3- O-beta- D-glucopyranoside (KG), kaempferol 3- O-alpha- L-rhamnopyranoside (KR), 7-methoxykaempferol 3- O-alpha- L-rhamnopyranoside (KMR), quercetin 3- O-beta- D-glucopyranoside (QG) and quercetin 3- O-alpha- L-rhamnopyranoside (QR) obtained from Chinese herbal plant extract of Saussurea mongolica. The optimum buffer system was 30 mmol/L borate buffer (Na2B4O7/HCl, pH 9.00) with 40 % (v/v) methanol. Voltage was 15 kV and detection at 270 nm. The application of this method for the separation and determination of the six flavonoid O-glycosides in S. mongolica is reported. The relative standard deviations of migration times and peak areas were < 2.61 and 4.41%, respectively. The contents of six natural products ranged from 0.043 to 0.60 mg/g and recoveries ranged from 92.4 to 104.4%. The effects of pH value, buffer concentration, surfactant, beta -cyclodextrin and organic modifier on the separation were investigated.

Electrophoresis, Capillary↗

Behavioral and neurochemical effects of the intrahippocampal co-injection of beta-amyloid protein 1-40 and ibotenic acid in rats.

The authors investigated the effects of bilateral intrahippocampal co-injection of Abeta1-40 (4 microg for each side) with ibotenic acid (Ibo, 2 microg for each side) on rats' performance in the open field behavior, Y-maze, and passive avoidance task, and also examined some neurochemical changes in hippocampus two weeks after the co-injection. The results showed that the co-injection of Abeta1-40 with Ibo induced a decrease in exploratory activity and a significant decline in learning-memory ability of the tested rats (p < .01). The neurochemistry changes induced by the co-injection included a significant decreased in membrane fluidity of hippocampal mitochondria (p < .01), a significant decrease in the activity of SOD (p < .01), and a remarkable increase in the content of MDA (p < .01). These results suggest that the co-injection of Abeta1-40 with Ibo may induce an increase of hippocampal damage by peroxidation, and a serious learning and memory impairment of the rats. The results also suggest that the co-injection of Abeta1-40 with Ibo may provide a useful animal model for Alzheimer's disease (AD) research.

Amyloid beta-Peptides↗