Fluorescence quenching and measurement of captopril in pharmaceuticals

The mechanism of fluorescence quenching of the product S in the presence of captopril was studied. The maximum emission wavelength of the product S was at 405 nm with the excitation wavelength at 316 nm. It was found that the fluorescence quenching of product S was of a static one and the binding constant (K) was 9.29 × 106 J mol-1. A linear relationship was found between the relative fluorescence intensity of the product S-captopril system and the concentration of captopril. Under optimum conditions, the linear range of the calibration curve for captopril was 2~160 μg L-1 with a correlation coefficient of 0.9926 and a detection limit of 0.1 μg L-1. The relative standard deviation (RSD) was 3.60%. The analytical results of the pharmaceuticals obtained by this novel method agreed quite well with those obtained by the KIO3 titrimetry

Fluorescence quenching and measurement of captopril in pharmaceuticals

270-276The mechanism of fluorescence quenching of the product S in the presence of captopril was studied. The maximum emission wavelength of the product S was at 405 nm with the excitation wavelength at 316 nm. It was found that the fluorescence quenching of product S was of a static one and the binding constant (K) was 9.29 × 106 J mol-1. A linear relationship was found between the relative fluorescence intensity of the product S-captopril system and the concentration of captopril. Under optimum conditions, the linear range of the calibration curve for captopril was 2~160 μg L-1 with a correlation coefficient of 0.9926 and a detection limit of 0.1 μg L-1. The relative standard deviation (RSD) was 3.60%. The analytical results of the pharmaceuticals obtained by this novel method agreed quite well with those obtained by the KIO3 titrimetry

MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor

Background: The Mitogen-activated protein kinase 1 (MAPK1) has both independent functions of phosphorylating histones as a kinase and directly binding the promoter regions of genes to regulate gene expression as a transcription factor. Previous studies have identified elevated expression of MAPK1 in human gastric cancer, which is associated with its role as a kinase, facilitating the migration and invasion of gastric cancer cells. However, how MAPK1 binds to its target genes as a transcription factor and whether it modulates related gene expressions in gastric cancer remains unclear. Results: Here, we integrated biochemical assays (protein interactions and chromatin immunoprecipitation (ChIP)), cellular analysis assays (cell proliferation and migration), RNA sequencing, ChIP sequencing, and clinical analysis to investigate the potential genomic recognition patterns of MAPK1 in a human gastric adenocarcinoma cell-line (AGS) and to uncover its regulatory effect on gastric cancer progression. We confirmed that MAPK1 promotes AGS cells invasion and migration by regulating the target genes in different directions, up-regulating seven target genes (KRT13, KRT6A, KRT81, MYH15, STARD4, SYTL4, and TMEM267) and down-regulating one gene (FGG). Among them, five genes (FGG, MYH15, STARD4, SYTL4, and TMEM267) were first associated with cancer procession, while the other three (KRT81, KRT6A, and KRT13) have previously been confirmed to be related to cancer metastasis and migration. Conclusion: Our data showed that MAPK1 can bind to the promoter regions of these target genes to control their transcription as a bidirectional transcription factor, promoting AGS cell motility and invasion. Our research has expanded the understanding of the regulatory roles of MAPK1, enriched our knowledge of transcription factors, and provided novel candidates for cancer therapeutics

Heritability enrichment of immunoglobulin G N-glycosylation in specific tissues

Genome-wide association studies (GWAS) have identified over 60 genetic loci associated with immunoglobulin G (IgG) N-glycosylation; however, the causal genes and their abundance in relevant tissues are uncertain. Leveraging data from GWAS summary statistics for 8,090 Europeans, and large-scale expression quantitative trait loci (eQTL) data from the genotype-tissue expression of 53 types of tissues (GTEx v7), we derived a linkage disequilibrium score for the specific expression of genes (LDSC-SEG) and conducted a transcriptome-wide association study (TWAS). We identified 55 gene associations whose predicted levels of expression were significantly associated with IgG N-glycosylation in 14 tissues. Three working scenarios, i.e., tissue-specific, pleiotropic, and coassociated, were observed for candidate genetic predisposition affecting IgG N-glycosylation traits. Furthermore, pathway enrichment showed several IgG N-glycosylation-related pathways, such as asparagine N-linked glycosylation, N-glycan biosynthesis and transport to the Golgi and subsequent modification. Through phenome-wide association studies (PheWAS), most genetic variants underlying TWAS hits were found to be correlated with health measures (height, waist-hip ratio, systolic blood pressure) and diseases, such as systemic lupus erythematosus, inflammatory bowel disease, and Parkinson’s disease, which are related to IgG N-glycosylation. Our study provides an atlas of genetic regulatory loci and their target genes within functionally relevant tissues, for further studies on the mechanisms of IgG N-glycosylation and its related diseases

Characterization of genome-wide H3K27ac profiles reveals a distinct PM2.5-associated histone modification signature

Complete list of differentially modified H3K27ac loci. (XLSX 69 kb

Ferroelectricity, Piezoelectricity, and Dielectricity of 0.06PMnN-0.94PZT(45/55) Thin Film on Silicon Substrate

The high piezoelectricity and high quality factor ferroelectric thin films are important for electromechanical applications especially the micro electromechanical system (MEMS). The ternary compound ferroelectric thin films 0.06Pb(Mn1/3, Nb2/3)O3 + 0.94Pb(Zr0.45, Ti0.55)O3 (0.06PMnN-0.94PZT(45/55)) were deposited on silicon(100) substrates by RF magnetron sputtering method considering that Mn and Nb doping will improve PZT properties in this research. For comparison, nondoped PZT(45/55) films were also deposited. The results show that both of thin films show polycrystal structures with the main (111) and (101) orientations. The transverse piezoelectric coefficients are e31,eff=−4.03 C/m2 and e31,eff=-3.5 C/m2, respectively. These thin films exhibit classical ferroelectricity, in which the coercive electric field intensities are 2Ec=147.31 kV/cm and 2Ec=135.44 kV/cm, and the saturation polarization Ps=30.86 μC/cm2 and Ps=17.74 μC/cm2, and the remnant polarization Pr=20.44 μC/cm2 and Pr=9.87 μC/cm2, respectively. Moreover, the dielectric constants and loss are εr=681 and D=5% and εr=537 and D=4.3%, respectively. In conclusion, 0.06PMnN-0.94PZT(45/55) thin films act better than nondoped films, even though their dielectric constants are higher. Their excellent ferroelectricity, piezoelectricity, and high power and energy storage property, especially the easy fabrication, integration realizable, and potentially high quality factor, make this kind of thin films available for the realistic applications

Methylation-state-specific recognition of histones by the MBT repeat protein L3MBTL2.

The MBT repeat has been recently identified as a key domain capable of methyl-lysine histone recognition. Functional work has pointed to a role for MBT domain-containing proteins in transcriptional repression of developmental control genes such as Hox genes. In this study, L3MBTL2, a human homolog of Drosophila Sfmbt critical for Hox gene silencing, is demonstrated to preferentially recognize lower methylation states of several histone-derived peptides through its fourth MBT repeat. High-resolution crystallographic analysis of the four MBT repeats of this protein reveals its unique asymmetric rhomboid architecture, as well as binding mechanism, which preclude the interaction of the first three MBT repeats with methylated peptides. Structural elucidation of an L3MBTL2-H4K20me1 complex and comparison with other MBT-histone peptide complexes also suggests that an absence of distinct surface contours surrounding the methyl-lysine-binding pocket may underlie the lack of sequence specificity observed for members of this protein family

DNA-directed nanofabrication of high-performance carbon nanotube field-effect transistors

生物自组装结构具有精细的三维形貌，其关键结构参数小于光刻等传统纳米加工手段的分辨率极限。利用自组装的生物分子为加工模板，已经实现了金属、碳基、氧化物等材料的形貌可控合成。然而，基于生物模板的电学器件，其性能往往远落后于通过蚀刻或薄膜方法制备的同类器件，并且缺乏长程取向规整性，制约了生物模板在高性能器件中的应用。针对上述挑战，我校化学化工学院朱志教授课题组与北京大学孙伟研究员课题组、清华大学唐建石研究员课题组、美国国家标准与技术研究院郑明博士合作，探索了生物-碳纳米管复合界面及大面积取向排列的调控新方法。北京大学孙伟研究员团队长期从事核酸引导的精准纳米组装研究，厦门大学朱志教授团队长期从事微纳加工及微流控研究，双方紧密合作，优势互补，联合清华大学和美国国家标准与技术研究院等多团队联合攻关完成该工作。共同第一作者厦门大学化学化工学院2011协同创新中心博士研究生陈雅鸿负责了碳纳米管组装及大面积阵列化工作，孙伟研究员和朱志教授为论文的共同通讯作者。Biofabricated semiconductor arrays exhibit smaller channel pitches than existing lithographic feasibility. However, the metal ions within biolattices and the submicrometer dimensions of typical biotemplates result in both poor transport performance and small array uniformity. Using DNA-templated parallel carbon nanotube (CNT) arrays as model systems, we developed a rinsing-after-fixing approach to improve the key transport performance metrics by more than a factor of 10 folds over previous biotemplated field-effect transistors. We also used spatially confined placement of assembled CNT arrays within polymethyl methacrylate cavities to demonstrate centimeter-scale alignment. At the interface of high-performance electronics and biomolecular self-assembly, current approaches may enable scalable biotemplated electronics sensitive to local biological environments.W.S.,M.Z., Y.C., K.W., and Z.Z. acknowledge the National Science Foundation of China (Grant No. 21875003, 21991134, and 61621061) and PKU for financial support. Y.C., C.Y., and Z.Z. acknowledge the National Science Foundation of China (Grant No. 21775128, 21435004, and 21974113) for financial support. J.K.S., J.A.F., and M.Z. acknowledge NIST internal fund. 该研究工作得到国家自然科学基金等资助

Triptolide Inhibits the Proliferation of Prostate Cancer Cells and Down-Regulates SUMO-Specific Protease 1 Expression

Recently, traditional Chinese medicine and medicinal herbs have attracted more attentions worldwide for its anti-tumor efficacy. Celastrol and Triptolide, two active components extracted from the Chinese herb Tripterygium wilfordii Hook F (known as Lei Gong Teng or Thunder of God Vine), have shown anti-tumor effects. Celastrol was identified as a natural 26 s proteasome inhibitor which promotes cell apoptosis and inhibits tumor growth. The effect and mechanism of Triptolide on prostate cancer (PCa) is not well studied. Here we demonstrated that Triptolide, more potent than Celastrol, inhibited cell growth and induced cell death in LNCaP and PC-3 cell lines. Triptolide also significantly inhibited the xenografted PC-3 tumor growth in nude mice. Moreover, Triptolide induced PCa cell apoptosis through caspases activation and PARP cleavage. Unbalance between SUMOylation and deSUMOylation was reported to play an important role in PCa progression. SUMO-specific protease 1 (SENP1) was thought to be a potential marker and therapeutical target of PCa. Importantly, we observed that Triptolide down-regulated SENP1 expression in both mRNA and protein levels in dose-dependent and time-dependent manners, resulting in an enhanced cellular SUMOylation in PCa cells. Meanwhile, Triptolide decreased AR and c-Jun expression at similar manners, and suppressed AR and c-Jun transcription activity. Furthermore, knockdown or ectopic SENP1, c-Jun and AR expression in PCa cells inhibited the Triptolide anti-PCa effects. Taken together, our data suggest that Triptolide is a natural compound with potential therapeutic value for PCa. Its anti-tumor activity may be attributed to mechanisms involving down-regulation of SENP1 that restores SUMOylation and deSUMOyaltion balance and negative regulation of AR and c-Jun expression that inhibits the AR and c-Jun mediated transcription in PCa

Single cell atlas for 11 non-model mammals, reptiles and birds.

The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs