Structural Analysis of Heparin-Derived 3- O -Sulfated Tetrasaccharides: Antithrombin Binding Site Variants

Heparin is a polysaccharide that is widely used as an anticoagulant drug. The mechanism for heparin’s anticoagulant activity is primarily through its interaction with a serine protease inhibitor, antithrombin III (AT), that enhances its ability to inactivate blood coagulation serine proteases, including thrombin (factor IIa) and factor Xa. The AT-binding site in the heparin is one of the most well-studied carbohydrate-protein binding sites and its structure is the basis for the synthesis of the heparin pentasaccharide drug, fondaparinux. Despite our understanding of the structural requirements for the heparin pentasaccharide AT-binding site, there is a lack of data on the natural variability of these binding sites in heparins extracted from animal tissues. The present work provides a detailed study on the structural variants of the tetrasaccharide fragments of this binding site afforded following treatment of a heparin with heparin lyase II. The 5 most commonly observed tetrasaccharide fragments of the AT-binding site are fully characterized, and a method for their quantification in heparin and low-molecular-weight heparin products is described

Metabolomics-based discovery of XHP as a CYP3A4 inhibitor against pancreatic cancer

Background: Xihuang Wan (XHW), a purgative and detoxifying agent, is commonly utilized in modern medicine as a treatment and adjuvant therapy for various malignancies, including breast cancer, liver cancer, and lung cancer. A clinical study demonstrated the potential usefulness of the combination of XHW and gemcitabine as a therapy for pancreatic cancer (PC), indicating that XHW’s broad-spectrum antitumor herbal combination could be beneficial in the treatment of PC. However, the precise therapeutic efficacy of XHW in treating pancreatic cancer remains uncertain.Aim: This study assessed the biological activity of XHW by optimizing the therapeutic concentration of XHW (Xihuang pills, XHP). We performed cell culture and developed an animal test model to determine whether XHP can inhibit pancreatic cancer (PC). We also applied the well-known widely targeted metabolomics analysis and conducted specific experiments to assess the feasibility of our method in PC therapy.Materials and Methods: We used UPLC/Q-TOF-MS to test XHP values to set up therapeutic concentrations for the in vivo test model. SW1990 pancreatic cancer cells were cultured to check the effect the anti-cancer effects of XHP by general in vitro cell analyses including CCK-8, Hoechst 33258, and flow cytometry. To develop the animal model, a solid tumor was subcutaneously formed on a mouse model of PC and assessed by immunohistochemistry and TUNEL apoptosis assay. We also applied the widely targeted metabolomics method following Western blot and RT-PCR to evaluate multiple metabolites to check the therapeutic effect of XHP in our cancer test model.Results: Quantified analysis from UPLC/Q-TOF-MS showed the presence of the following components of XHP: 11-carbonyl-β-acetyl-boswellic acid (AKBA), 11-carbonyl-β-boswellic acid (KBA), 4-methylene-2,8,8-trimethyl-2-vinyl-bicyclo [5.2.0]nonane, and (1S-endo)-2-methyl-3-methylene-2-(4-methyl-3-3-pentenyl)-bicyclo [2.2.1heptane]. The results of the cell culture experiments demonstrated that XHP suppressed the growth of SW1990 PC cells by enhancing apoptosis. The results of the animal model tests also indicated the suppression effect of XHP on tumor growth. Furthermore, the result of the widely targeted metabolomics analysis showed that the steroid hormone biosynthesis metabolic pathway was a critical factor in the anti-PC effect of XHP in the animal model. Moreover, Western blot and RT-PCR analyses revealed XHP downregulated CYP3A4 expression as an applicable targeted therapeutic approach.Conclusion: The results of this study demonstrated the potential of XHP in therapeutic applications in PC. Moreover, the widely targeted metabolomics method revealed CYP3A4 is a potential therapeutic target of XHP in PC control. These findings provide a high level of confidence that XHP significantly acts as a CYP3A4 inhibitor in anti-cancer therapeutic applications

A Multipopulation Dynamic Adaptive Coevolutionary Strategy for Large-Scale Complex Optimization Problems

In this paper, a multipopulation dynamic adaptive coevolutionary strategy is proposed for large-scale optimization problems, which can dynamically and adaptively adjust the connection between population particles according to the optimization problem characteristics. Based on analysis of the network evolution characteristics of collaborative search between particles, a dynamic adaptive evolutionary network (DAEN) model with multiple interconnection couplings is established in this algorithm. In the model, the swarm type is divided according to the judgment threshold of particle types, and the dynamic evolution of collaborative topology in the evolutionary process is adaptively completed according to the coupling connection strength between different particle types, which enhances the algorithm’s global and local searching capability and optimization accuracy. Based on that, the evolution rules of the particle swarm dynamic cooperative search network were established, the search algorithm was designed, and the adaptive coevolution between particles in different optimization environments was achieved. Simulation results revealed that the proposed algorithm exhibited a high optimization accuracy and converging rate for high-dimensional and large-scale complex optimization problems

A Multipopulation Dynamic Adaptive Coevolutionary Strategy for Large-Scale Complex Optimization Problems

In this paper, a multipopulation dynamic adaptive coevolutionary strategy is proposed for large-scale optimization problems, which can dynamically and adaptively adjust the connection between population particles according to the optimization problem characteristics. Based on analysis of the network evolution characteristics of collaborative search between particles, a dynamic adaptive evolutionary network (DAEN) model with multiple interconnection couplings is established in this algorithm. In the model, the swarm type is divided according to the judgment threshold of particle types, and the dynamic evolution of collaborative topology in the evolutionary process is adaptively completed according to the coupling connection strength between different particle types, which enhances the algorithm’s global and local searching capability and optimization accuracy. Based on that, the evolution rules of the particle swarm dynamic cooperative search network were established, the search algorithm was designed, and the adaptive coevolution between particles in different optimization environments was achieved. Simulation results revealed that the proposed algorithm exhibited a high optimization accuracy and converging rate for high-dimensional and large-scale complex optimization problems

The complete chloroplast genome of Quercus robur ‘Fastigiata’

The Quercus robur ‘Fastigiata’ is an important ornamental plant, in which the complete chloroplast genome (accession no. MN562095) was identified and sequenced. The genome size is 161,172 bp, with a large single-copy (LSC, 90,505 bp) region, a small single-copy (SSC, 18,997 bp) region, and two inverted repeat regions (IRs, 25,835 bp each). A total of 134 genes are successfully annotated, including 89 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The phylogenetic relationships inferred that Q. robur ‘Fastigiata’ is closely related to Quercus mongolica, Quercus wutaishanica, and Quercus dentata

Complete chloroplast genome sequences of the ornamental plant Prunus cistena and comparative and phylogenetic analyses with its closely related species

Abstract Background Prunus cistena is an excellent color leaf configuration tree for urban landscaping in the world, which has purplish red leaves, light pink flowers, plant shape and high ornamental value. Genomic resources for P. cistena are scarce, and a clear phylogenetic and evolutionary history for this species has yet to be elucidated. Here, we sequenced and analyzed the complete chloroplast genome of P. cistena and compared it with related species of the genus Prunus based on the chloroplast genome. Results The complete chloroplast genome of P. cistena is a 157,935 bp long typical tetrad structure, with an overall GC content of 36.72% and higher GC content in the in the inverted repeats (IR) regions than in the large single-copy (LSC) and small single-copy (SSC) regions. It contains 130 genes, including 85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The ycf3 and clpP genes have two introns, with the longest intron in the trnK-UUU gene in the LSC region. Moreover, the genome has a total of 253SSRs, with the mononucleotide SSRs being the most abundant. The chloroplast sequences and gene arrangements of P. cistena are highly conserved, with the overall structure and gene order similar to other Prunus species. The atpE, ccsA, petA, rps8, and matK genes have undergone significant positive selection in Prunus species. P. cistena has a close evolutionary relationship with P. jamasakura. The coding and IR regions are more conserved than the noncoding regions, and the chloroplast DNA sequences are highly conserved throughout the genus Prunus. Conclusions The current genomic datasets provide valuable information for further species identification, evolution, and phylogenetic research of the genus Prunus

Characterization of the complete chloroplast genome of Malus spectabilis ‘Guanghui’

Malus spectabilis ‘Guanghui’ is an important ornamental plant, which complete chloroplast genome (Accession: MT501657) was sequenced, assembled and annotated. The genome size is 1601,230 bp and the overall GC content is 36.50%, with large single-copy (LSC, 89,310bp) regions, small single-copy (SSC, 19,196 bp) regions, and two inverted repeat regions (IRs, 23,632bp each). A total of 129 genes are successfully annotated, including 84 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The phylogenetic relationships showed that Malus spectabilis ‘Guanghui’ is closely related to the species of Malus sieversii

The first complete chloroplast genome of Quercus coccinea (Scarlet Oak) and its phylogenetic position within Fagaceae

Quercus coccinea is a native to North America, which grows well in acidic soil and resists cold to extreme low temperature –40 °C. The chloroplast (cp) genome of Q. coccinea, sequenced based on next-generation platform (NEOSAT), is 161,298 bp in size. The cp genome encodes 133 genes, including 88 protein-coding genes (PCGs), 8 rRNA genes, and 37 tRNA genes. Phylogenetic relationship analysis based on complete cp genome sequences exhibited that both of Q. coccinea and Q. rubra were phylogenetically closer to Q. aliena var. Acutiserrata