Porous Organic Polymers-Supported Zeigler-Natta Catalysts for Preparing Highly Isotactic Polypropylene with Broad Molecular Weight Distribution.

Porous organic polymers (POPs) have attracted much attention in numerous areas, including catalysis, adsorption and separation. Herein, POP supported Ziegler-Natta catalysts were designed for preparation of isotactic polypropylene (iPP). The POPs-based Ziegler-Natta catalysts exhibited the characteristic of broad molecular weight distribution (MWD > 11) with or without adding an extra internal electron donor. The added internal electron donor 3-methyl-5-tert-butyl-1,2-phenylene dibenzoate (ID-2) used in cat-2 showed good propylene polymerization activity of 15.3 × 106 g·PP/mol·Ti·h, high stereoregularity with 98.2% of isotacticity index and broad molecular weight distribution (MWD) of 12.3. Compared to the MgCl2-supported Ziegler-Natta catalysts (cat-4) with the same ID-2, cat-2 showed higher chain stereoregularity for propylene polymerization. As seen in the TREF results, the elution peak of PP-2 (124.0 °C, 91.7%) is 1.5 °C higher than the isotactic fraction from PP-4 (122.5 °C, 87.2%), and even 1.2 °C higher than PP-5 prepared from ID-3 with the characteristics of high stereoregularity. Moreover, the pentad methyl sequence mmmm of PP-2 (93.0%) from cat-2 is 0.5% higher than that of PP-4 from cat-4. XPS analysis revealed that the minute difference in binding energy of Ti, Mg, C and O atoms exist between the inorganic MgCl2 and the organic polymer based Z-N catalysts. The plausible interaction mechanism of active sites of Mg and Ti with the functional groups in the POP support and the added ID was proposed, which could be explained by their high stereoregularity and the broad molecular weight distribution of the POP-based Z-N catalysts.

[Research advance in chemical compounds,pharmacological action and clinical application of Dengzhan Shengmai Capsules].

Dengzhan Shengmai Capsules( DZSMC),a well-known traditional Chinese medicine( TCM) formula,is comprised of the main drug of Erigeron breviscapus,and supplemented with Panax ginseng,Ophiopogon japonicus and Schisandra chinensis,with functions of supplementing Qi and nourishing Yin,promoting blood circulation and strengthening brain. DZSMC is the only Chinese patent drug with A-level evidence-based medicine in secondary prevention for stroke and ranks first among TCMs for neurological treatment. Modern studies indicate that the chemical constituents of DZSMC mainly include flavonoids,phenolic acids,lignans,saponins and so on. Pharmacological experimental studies have shown that DZSMC has such pharmacological effects as anti-oxidation,anti-inflammatory and anti-myocardial ischemia. DZSMC is mainly used in the convalescent care of ischemic cardiovascular and cerebrovascular diseases,and is often used in combination with various conventional therapeutic drugs to exert clinical efficacy through brain protection,neuroprotection,etc.,and improve clinical symptoms in patients. In this review,according to domestic and international related literature combined with research results obtained by our project,the research advances in the chemical constituents,pharmacological effects and clinical application of DZSMC have been systematically reviewed and summarized,providing reference and support for further study and secondary development of the formula.

Facile synthesis of carbon nanotube-supported NiO//Fe2O3 for all-solid-state supercapacitors.

We have successfully prepared iron oxide and nickel oxide on carbon nanotubes on carbon cloth for the use in supercapacitors via a simple aqueous reduction method. The obtained carbon cloth-carbon nanotube@metal oxide (CC-CNT@MO) three-dimensional structures combine the high specific capacitance and rich redox sites of metal oxides with the large specific area and high electrical conductivity of carbon nanotubes. The prepared CC-CNT@Fe2O3 anode reaches a high capacity of 226 mAh·g-1 at 2 A·g-1 with a capacitance retention of 40% at 40 A·g-1. The obtained CC-CNT@NiO cathode exhibits a high capacity of 527 mAh·g-1 at 2 A·g-1 and an excellent rate capability with a capacitance retention of 78% even at 40 A·g-1. The all-solid-state asymmetric supercapacitor fabricated with these two electrodes delivers a high energy density of 63.3 Wh·kg-1 at 1.6 kW·kg-1 and retains 83% of its initial capacitance after 5000 cycles. These results demonstrate that our simple aqueous reduction method to combine CNT and metal oxides reveals an exciting future in constructing high-performance supercapacitors.

Layered coating of ultraflexible graphene-based electrodes for high-performance in-plane quasi-solid-state micro-supercapacitors.

To meet the demand of rapid development of portable and wearable electronic devices, in-plane quasi-solid-state micro-supercapacitors (QSS MSCs) have great potential as miniaturized energy storage devices. However, their ultralow areal capacitance and poor flexibility limit their practical applications. Here, we demonstrate a new strategy for the fabrication of ultraflexible MnO2@reduced graphene oxide (rGO) films (MGFs) for high-performance planar QSS MSCs through a facile layer-by-layer coating and a laser engraving method. Benefiting from conductive and flexible rGO films reduced by HI, the MGF based symmetrical QSS MSC exhibits a high areal capacitance (31.5 mF cm-2 at 0.2 mA cm-2), excellent flexibility (no capacity degradation at a bending radius from ∞ to 0 cm), and outstanding cycling stability (retaining 77.0% of its initial capacity after 6000 cycles). Most importantly, the electrochemical performance of QSS MSCs can be multiplied by simply adding more MGF layers. By adding up to 5 MGF layers, the MSC can deliver an ultrahigh areal capacitance of 144.3 mF cm-2 at 0.3 mA cm-2, and a superior energy density of 13.9 mW h cm-3 at 34.7 mW cm-3. Therefore, this work offers versatile quasi-solid-state MSCs and provides an impressive strategy to enhance electrochemical performance which will greatly enrich the design and fabrication of MSCs.

Comprehensive characterization of multiple components and metabolites of Xiaojin Capsule based on ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Xiaojin Capsule, a classic traditional Chinese medicine formula, has been used to treat mammary cancer, thyroid nodules, and hyperplasia of the mammary glands. However, its systematic chemical information remained unclear, which hindered the interpretation of the pharmacology and the mechanism of action of this drug. In this research, an ultra high performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometry method was developed to identify the complicated components and metabolites of Xiaojin Capsule. Two acquisition modes, including the MSEnergy mode and fast data directed acquisition mode, were utilized for chemical profiling. As a result, 156 compounds were unambiguously or tentatively identified by comparing their retention times and mass spectrometry data with those of reference standards or literature. After the oral administration of Xiaojin Capsule, 53 constituents, including 24 prototype compounds and 29 metabolites, were detected in rat plasma. The obtained results were beneficial for a better understanding of the therapeutic basis of Xiaojin Capsule. A high-resolution and efficient separation method was firstly established for systematically characterizing the compounds of Xiaojin Capsule and the associated metabolites in vivo, which could be helpful for quality control and pharmacokinetic studies of this medicine.

Identification and characterization of chemical constituents in Dengzhan Shengmai Capsule and their metabolites in rat plasma by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Dengzhan Shengmai Capsule (DZSMC) is a traditional Chinese medicine (TCM) formula with remarkable clinical effect in the treatment of stroke sequelae. Exploring the components of DZSMC and detecting the absorbed prototype constituents and metabolites in blood are of great significance to clarify the effective substances of this prescription. Here, a reliable method using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was established for the comprehensive analysis of chemical constituents of DZSMC and their metabolites in rat plasma after gastric perfusion. Two acquisition modes, including MSE mode and Fast DDA mode, were performed for acquiring more precursor ions and cleaner precursor-product ions background during the study of constituents of DZSMC. As a result, a total of 125 constituents were unambiguously characterized or tentatively identified. For the first time, a total of 92 components, including 44 prototype components and 48 metabolites were unambiguously or tentatively identified in rat plasma. The metabolic pathways included phase I reactions (hydration, hydrogenation, oxidation, demethylation and hydroxylation) and phase II reactions (conjugation with glucuronide, sulfate and methyl). Furthermore, the metabolites from caffeic acid and scutellarin were characterized and validated by phase II metabolic reactions in vitro, which could be established as a simulated in vivo environment of metabolites identification and verification of TCM formula. It is the first systematic study on metabolism of DZSMC in vivo and could also provide a valid analytical strategy for characterization of the chemical compounds and metabolites of TCM formula.

Metabolite profiling of traditional Chinese medicine formula Dan Zhi Tablet: An integrated strategy based on UPLC-QTOF/MS combined with multivariate statistical analysis.

Metabolites derived from traditional Chinese medicine (TCM) are becoming active substances of pharmacologically as well as promising sources for discovering new drugs. However, detection and identification of constituents in vivo remains a challenge for TCM, due to massive endogenous interference and low abundance of metabolites in biological matrix. Traditional Chinese medicine formula Dan Zhi Tablet (DZT), a well-established TCM formula developed based on years of clinical experiences, was widely used to treat cerebral infraction disease. In this study, an integrated strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was adopted to comprehensively identify the prototype and metabolite constituents of DZT. The potential constituents were screened by cross orthogonal partial least-squares discriminant analysis (OPLS-DA). Automatic matching analysis was performed on UNIFI platform based on the function of predicting metabolites. Using this strategy, a total of 170 compounds, including 51 prototype constituents and 119 metabolites were unambiguously or tentatively identified in rat plasma. Furthermore, 31 compounds have also been detected in rat cerebrospinal fluid. The metabolism reactions included phase I reactions (hydroxylation, hydrolysis, deglycosylation, hydrogenation, demethylation and dehydroxylation) and phase II reactions (conjugation with glutatione, cysteine, acetylcysteine, glucuronide, sulfate). It is the first systematic metabolic study of DZT in vivo and some metabolites were also reported for the first time, which could provide a scientific basis for explaining the multiple functions of DZT. More importantly, the integrated strategy also shows promising perspectives in the identification of the metabolites in TCM from a complicated biological matrix.

Rapid characterization and identification of the chemical constituents and rat metabolites of Deng-Zhan-Xi-Xin injection using ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Deng-Zhan-Xi-Xin injection is a well-known traditional Chinese medicine prescription for the treatment of cardiovascular and cerebral vessel diseases. However, there have been few reports on its chemical constituents and metabolic pathway, which has blocked its further quality control and studies on its pharmacology and mechanism of action. In this study, an integrative method was established to rapidly explore the chemical constituents and metabolites of Deng-Zhan-Xi-Xin injection using ultra high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and the UNIFI™ software combined with multiple data processing approaches. As a result, a total of 40 compounds, including 9 flavonoids and 31 phenolic acids were identified or tentatively characterized, and five compounds were first reported in Deng-Zhan-Xi-Xin injection. Under the same analysis conditions, 70 compounds have been detected in rats, including 25 prototypes and 45 metabolites. This was the first systematic research study on the metabolic profiling of Deng-Zhan-Xi-Xin injection. This study provides valuable chemical information for the quality control and research on pharmacology and mechanism of action of Deng-Zhan-Xi-Xin injection. Moreover, it provides a valuable strategy for analyzing the chemical components and metabolites of other traditional Chinese medicine prescriptions.

Genetic variability and lineage phylogeny of human papillomavirus type 45 based on E6 and E7 genes in Southwest China.

The current study investigated nucleotide variability and phylogeny in high-risk HPV45 collected from Chinese women. Fifty-one samples positive for single infections of HPV45 were collected for DNA extraction and HPV typing. The E6 and E7 genes of HPV45 were sequenced, and then the phylogenetic tree was reconstructed by the maximum likelihood method implemented in IQ-TREE under the HKY nucleotide substitution model. The selection pressures of the E6 and E7 genes were estimated using PAML software. Eleven nucleotide polymorphism sites were observed in the HPV45 E6 sequences, with 6 synonymous (C134T, T163C, A284C, T341C, T482C, A497G) and 5 non-synonymous (A124C, C157T, T162A, G259T, G487A) mutations. Six nucleotide polymorphism sites were observed in the E7 sequences, with 5 non-synonymous (G600A, A603C, A769C, G808T, G832T) and 1 synonymous (A718C) mutation. Our investigation suggests that B2 was the most frequent HPV45 sublineage in Southwest China, followed by A2; no A1 or A3 variants were detected. Selective pressure analysis showed that these mutations could reflect positive selection in HPV45 E6 and E7 genes.

Phylogeny and polymorphism in the long control regions E6, E7, and L1 of HPV Type 56 in women from southwest China.

Globally, human papillomavirus (HPV)­56 accounts for a small proportion of all high­risk HPV types; however, HPV­56 is detected at a higher rate in Asia, particularly in southwest China. The present study analyzed polymorphisms, intratypic variants, and genetic variability in the long control regions (LCR), E6, E7, and L1 of HPV­56 (n=75). The LCRs, E6, E7 and L1 were sequenced using a polymerase chain reaction and the sequences were submitted to GenBank. Maximum­likelihood trees were constructed using Kimura's two­parameter model, followed by secondary structure analysis and protein damaging prediction. Additionally, in order to assess the effect of variations in the LCR on putative binding sites for cellular proteins, MATCH server was used. Finally, the selection pressures of the E6­E7 and L1 genes were estimated. A total of 18 point substitutions, a 42­bp deletion and a 19­bp deletion of LCR were identified. Some of those mutations are embedded in the putative binding sites for transcription factors. 18 single nucleotide changes occurred in the E6­E7 sequence, 11/18 were non­synonymous substitutions and 7/18 were synonymous mutations. A total 24 single nucleotide changes were identified in the L1 sequence, 6/24 being non­synonymous mutations and 18/24 synonymous mutations. Selective pressure analysis predicted that the majority of mutations of HPV­56 E6, E7 and L1 were of positive selection. The phylogenetic tree demonstrated that the isolates distributed in two lineages. Data on the prevalence and genetic variation of HPV­56 types in southwest China may aid future studies on viral molecular mechanisms and contribute to future investigations of diagnostic probes and therapeutic vaccines.

Construction of Hierarchical CNT/rGO-Supported MnMoO4 Nanosheets on Ni Foam for High-Performance Aqueous Hybrid Supercapacitors.

Rationally designed conductive hierarchical nanostructures are highly desirable for supporting pseudocapacitive materials to achieve high-performance electrodes for supercapacitors. Herein, manganese molybdate nanosheets were hydrothermally grown with graphene oxide (GO) on three-dimensional nickel foam-supported carbon nanotube structures. Under the optimal graphene oxide concentration, the obtained carbon nanotubes/reduced graphene oxide/MnMoO4 composites (CNT/rGO/MnMoO4) as binder-free supercapacitor cathodes perform with a high specific capacitance of 2374.9 F g-1 at the scan rate of 2 mV s-1 and good long-term stability (97.1% of the initial specific capacitance can be maintained after 3000 charge/discharge cycles). The asymmetric device with CNT/rGO/MnMoO4 as the cathode electrode and the carbon nanotubes/activated carbon on nickel foam (CNT-AC) as the anode electrode can deliver an energy density of 59.4 Wh kg-1 at the power density of 1367.9 W kg-1. These superior performances can be attributed to the synergistic effects from each component of the composite electrodes: highly pseudocapacitive MnMoO4 nanosheets and three-dimensional conductive Ni foam/CNTs/rGO networks. These results suggest that the fabricated asymmetric supercapacitor can be a promising candidate for energy storage devices.

Correction: E6 and E7 Gene Polymorphisms in Human Papillomavirus Types-58 and 33 Identified in Southwest China.

[This corrects the article DOI: 10.1371/journal.pone.0171140.].

E6 and E7 Gene Polymorphisms in Human Papillomavirus Types-58 and 33 Identified in Southwest China.

Cancer of the cervix is associated with infection by certain types of human papillomavirus (HPV). The gene variants differ in immune responses and oncogenic potential. The E6 and E7 proteins encoded by high-risk HPV play a key role in cellular transformation. HPV-33 and HPV-58 types are highly prevalent among Chinese women. To study the gene intratypic variations, polymorphisms and positive selections of HPV-33 and HPV-58 E6/E7 in southwest China, HPV-33 (E6, E7: n = 216) and HPV-58 (E6, E7: n = 405) E6 and E7 genes were sequenced and compared to others submitted to GenBank. Phylogenetic trees were constructed by Maximum-likelihood and the Kimura 2-parameters methods by MEGA 6 (Molecular Evolutionary Genetics Analysis version 6.0). The diversity of secondary structure was analyzed by PSIPred software. The selection pressures acting on the E6/E7 genes were estimated by PAML 4.8 (Phylogenetic Analyses by Maximun Likelihood version4.8) software. The positive sites of HPV-33 and HPV-58 E6/E7 were contrasted by ClustalX 2.1. Among 216 HPV-33 E6 sequences, 8 single nucleotide mutations were observed with 6/8 non-synonymous and 2/8 synonymous mutations. The 216 HPV-33 E7 sequences showed 3 single nucleotide mutations that were non-synonymous. The 405 HPV-58 E6 sequences revealed 8 single nucleotide mutations with 4/8 non-synonymous and 4/8 synonymous mutations. Among 405 HPV-58 E7 sequences, 13 single nucleotide mutations were observed with 10/13 non-synonymous mutations and 3/13 synonymous mutations. The selective pressure analysis showed that all HPV-33 and 4/6 HPV-58 E6/E7 major non-synonymous mutations were sites of positive selection. All variations were observed in sites belonging to major histocompatibility complex and/or B-cell predicted epitopes. K93N and R145 (I/N) were observed in both HPV-33 and HPV-58 E6.

[Idiopathic teratozoospermia is not correlated with c.144delC polymorphism in the AURKC gene in Sichuan].

OBJECTIVE: To investigate the association of a very common mutation of c.144delC in the aurora kinase C (AURKC) gene with idiopathic teratozoospermia in Chinese infertile men in Sichuan. METHODS: Using polymerase chain reaction (PCR) and next-generation sequencing, we analyzed the correlation between c.144delC polymorphism of the AURKC gene and male infertility in 98 idiopathic teratozoospermia patients in comparison with 162 normal fertile men. RESULTS: Neither c.144delC mutation nor other meaningful mutations were detected in the AURKC gene in the 98 idiopathic teratozoospermia patients or the 162 normal controls. CONCLUSIONS: Teratozoospermia is not correlated with c.144delC mutation in the AURKC gene in the men of the Sichuan area. Therefore, large-scale genotyping of the AURKC gene may not be necessary clinically among Chinese patients with idiopathic teratozoospermia.

Identification of the impact on T- and B- cell epitopes of human papillomavirus type-16 E6 and E7 variant in Southwest China.

Cervical cancers almost are infected by human papillmavirus (HPV), encoding E6 and E7 oncoproteins which are regard as ideal targets on the mechanism of this disease and development of vaccines. HLA (human leukocyte antigen) participates in the local immune response to prevent tumor invasion and progression. But due to highly polymorphism of HLA, prediction shows its importance in this study. More effective immunoinformatics was used for predicting epitopes from HPV-16 E6 and E7, including T- and B-cell epitopes. Eight substitutions are detected. Specifically speaking, for HLA-I, HLA-A*33:03 (26), HLA-B*13:01 (14), HLA-C*03:02 (5) for E6 and HLA-A*02:01 (6), HLA-B*40:01 (5), HLA-C*03:04 (4) for E7 are most frequency. Epitope 41-48EVYDFAFR for HLA-A*33:03 (0.1) for E6 has best binding affinity, as well as HLA*02:01 and HLA-B*40:01 (0.2) for E7. The mutations of D25E and L83V of E6 and N29S of E7 produce new epitopes, and the percentile values change with them. For HLA-II, seventeen epitopes in the reference at percentile value from 0.22 to 4.76, while in variant from 0.22 to 4.96. For the B-cell epitopes, three most potent epitopes for E6 were listed, and N29S lead the growth of score from 0.81 to 0.83. In summary, E640-55REVYDFAFRDLCIVYR and E711-22YMLDLQPETTDL are the important regions, containing the majority of predicted epitopes. E6 72-83 for HLA-A*02:01 and E6 74-84 for HLA-B*15:02 maybe are the new direct for therapeutic vaccine aimed at L83V variants. HLA-DRB1*15:02 is better binder with T cell in our HLA class II. It is a systematic, detail recognition for T- and B-cell epitopes of HPV-16 E6 and E7 from Southwest China, which may be helpful to design vaccines specifically for women in Southwest China and testing methods specifically for this region. The results of our study may contribute to future researches on vaccines improvement, or screening methods for a particular population.

Association of polymorphisms in PATE1 gene with idiopathic asthenozoospermia in Sichuan, China.

PURPOSE: Idiopathic Asthenozoospermia (AZS) is a common symptom of male infertility described as reduced forward motility or absence of sperm motility. The PATE1 is generally expressed in male genital tract and related to sperm development, maturation and fertilization. However, the single nucleotide polymorphisms (SNPs) of the PATE1 gene which contribute to AZS were still unknown. For this reason, the possible association between the single nucleotide polymorphisms of the PATE1 gene and idiopathic asthenozoospermia was investigated in this research. METHODS: 108 idiopathic asthenozoospermia were screened by karyotype analysis, detection of Y microdeletions and mutations in 5 other genes from 140 clinical AZS. The sequence analyses of the PATE1 gene were conducted in 108 idiopathic asthenozoospermia and 106 fertile men with normospermic parameters in Sichuan, China. RESULTS: In this study, a total 108 patients without chromosomal abnormalities, Y microdeletions and selected genes mutation were confirmed. The 1423G (odds ratio [OR] 1.939, 95% confidence interval [CI] 1.320-2.848, P=0.001) was found to be increased significantly in idiopathic asthenozoospermic patients compared with their fertile counterparts. This mutation substitutes a highly conserved glutamic to arginine at the position of the 47th amino acid which was shown to be located on the flank of the pleated sheet domain in PATE1 protein by the 3D model given by the Protein Model Portal (PMP). Moreover, PolyPhen-2 analysis predicted that this variant was "probably damaging". CONCLUSIONS: These results suggested that PATE1 variant (A1423G) was probably one of the high risk genetic factors for idiopathic asthenozoospermia among males in Sichuan, China.

Importance of polypyrrole in constructing 3D hierarchical carbon nanotube@MnO2 perfect core-shell nanostructures for high-performance flexible supercapacitors.

This study reports the preparation of 3D hierarchical carbon nanotube (CNT) @MnO2 core-shell nanostructures under the assistance of polypyrrole (PPy). The as-prepared CNT@PPy@MnO2 core-shell structures show a perfect coating of MnO2 on each CNT and, more importantly, a robust bush-like pseudocapacitive shell to effectively increase the specific surface area and enhance the ion accessibility. As expected, a high specific capacity of 490-530 F g(-1) has been achieved from CNT@PPy@MnO2 single electrodes. And about 98.5% of the capacity is retained after 1000 charge/discharge cycles at a current density of 5 A g(-1). Furthermore, the assembled asymmetric CNT@PPy@MnO2//AC capacitors show the maximum energy density of 38.42 W h kg(-1) (2.24 mW h cm(-3)) at a power density of 100 W kg(-1) (5.83 mW cm(-3)), and they maintain 59.52% of the initial value at 10,000 W kg(-1) (0.583 W cm(-3)). In addition, the assembled devices show high cycling stabilities (89.7% after 2000 cycles for asymmetric and 87.2% for symmetric), and a high bending stability (64.74% after 200 bending tests). This ability to obtain high energy densities at high power rates while maintaining high cycling stability demonstrates that this well-designed structure could be a promising electrode material for high-performance supercapacitors.