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  • Physiological and Transcriptome Profiling Analyses Reveal Important Roles of Coronatine in Improving Drought Tolerance of Tobacco
    J. Plant Growth. Regul. (IF 2.179) Pub Date : 2020-01-27
    Jiayang Xu, Yuyi Zhou, Zicheng Xu, Zheng Chen, Liusheng Duan

    Abstract Coronatine (COR) is a phytotoxin produced by Pseudomonas syringae and is a functional analogue of the bioactive hormone JA-Ile, which is widely involved in plant defence responses. In this study, we explored the effects of exogenous applications of COR on tobacco plants under polyethylene glycol-induced drought stress. Compared with control (CK), COR-treated tobacco plants exhibited higher leaf relative water content and better photosynthetic performance under drought exposure. Ultrastructural examination revealed that drought led to stomatal closure and disorganization of granum stacking in the chloroplasts (with obvious accumulation of plastoglobuli), and mitochondria in the CK samples presented injured cristae. In the leaf tissue of the COR-treated plants, regularly stacked granum thylakoids, few plastoglobuli and intact mitochondrial membranes and cristae were observed. Totals of 1803 and 6207 differentially expressed genes (DEGs) were identified between the samples from the COR-treated and CK plants under well-watered and drought conditions. Functional annotation analysis revealed that these DEGs were involved mainly in plant hormone signal transduction, cellular carbohydrate metabolic processes and photosynthesis processes. Six hundred forty transcription factor genes were also identified among the DEGs. This study provides a global view of COR-induced drought stress tolerance in tobacco from both physiological and transcriptional aspects.

    更新日期:2020-01-27
  • Enzymatic and Non-enzymatic Detoxification of Reactive Carbonyl Compounds Improves the Oxidative Stress Tolerance in Cucumber, Tobacco and Rice Seedlings
    J. Plant Growth. Regul. (IF 2.179) Pub Date : 2020-01-27
    Ambekar Nareshkumar, Sindhu Subbarao, Amarnatha Reddy Vennapusa, Vargheese Ashwin, Reema Banarjee, Mahesh J. Kulkarni, Vemanna S. Ramu, Makarla Udayakumar

    Abstract Detoxification of reactive carbonyl compounds (RCC) is crucial to sustain cellular activity to improve plant growth and development. Seedling growth is highly affected by accumulation of RCC under stress. We report non-enzymatic, enzymatic mechanisms of detoxification of RCC in the cucumber, tobacco and rice seedling systems exposed to glucose, NaCl, methyl viologen (MV) induced oxidative stress. The cucumber seedlings exposed to carbonyl stress had higher levels of malondialdehyde (MDA), protein carbonyls (PCs) and advanced glycation end-product N-carboxymethyl-lysine (AGE-CML) that negatively affected the seedling growth. The overexpression of enzyme encoding aldo-keto reductase-1 (AKR1) in tobacco and rice showed detoxification of RCC, MDA and methylglyoxal (MG) with improved seedling growth under glucose, NaCl and MV-induced oxidative stress. Further, small molecules like acetylsalicylic acid (ASA), aminoguanidine (AG), carnosine (Car), curcumin (Cur) and pyridoxamine (PM) showed detoxification of RCC non-enzymatically and rescued the cucumber seedling growth from glucose, NaCl and MV-stress. In autotrophically grown rice seedlings these molecules substantially improved seedling growth under MV-induced oxidative stress. Seedlings treated with the small molecules sustained higher guaiacol peroxidase (GPX) enzyme activity signifying the role of small molecules in reducing carbonyl stress-induced protein inactivation and AGE-CML protein modifications. The results showed that besides enzymatic detoxification of RCC, the small molecules also could reduce cytotoxic effect of RCC under stress. The study demonstrates that small molecules are attractive compounds to improve the seedling growth under stress conditions.

    更新日期:2020-01-27
  • WUSCHEL : a master regulator in plant growth signaling
    Plant Cell Rep. (IF 3.499) Pub Date : 2020-01-27
    Priyanka Jha, Sergio J. Ochatt, Vijay Kumar

    Abstract Key message This review summarizes recent knowledge on functions of WUS and WUS-related homeobox (WOX) transcription factors in diverse signaling pathways governing shoot meristem biology and several other aspects of plant dynamics. Abstract Transcription factors (TFs) are master regulators involved in controlling different cellular and biological functions as well as diverse signaling pathways in plant growth and development. WUSCHEL (WUS) is a homeodomain transcription factor necessary for the maintenance of the stem cell niche in the shoot apical meristem, the differentiation of lateral primordia, plant cell totipotency and other diverse cellular processes. Recent research about WUS has uncovered several unique features including the complex signaling pathways that further improve the understanding of vital network for meristem biology and crop productivity. In addition, several reports bridge the gap between WUS expression and plant signaling pathway by identifying different WUS and WUS-related homeobox (WOX) genes during the formation of shoot (apical and axillary) meristems, vegetative-to-embryo transition, genetic transformation, and other aspects of plant growth and development. In this respect, the WOX family of TFs comprises multiple members involved in diverse signaling pathways, but how these pathways are regulated remains to be elucidated. Here, we review the current status and recent discoveries on the functions of WUS and newly identified WOX family members in the regulatory network of various aspects of plant dynamics.

    更新日期:2020-01-27
  • Transplanckian censorship and the local swampland distance conjecture
    J. High Energy Phys. (IF 5.833) Pub Date : 2020-01-21
    Patrick Draper, Szilard Farkas

    Abstract The swampland distance conjecture (SDC) addresses the ability of effective field theory to describe distant points in moduli space. It is natural to ask whether there is a local version of the SDC: is it possible to construct local excitations in an EFT that sample extreme regions of moduli space? In many cases such excitations exhibit horizons or instabilities, suggesting that there are bounds on the size and structure of field excitations that can be achieved in EFT. Static bubbles in ordinary Kaluza-Klein theory provide a simple class of examples: the KK radius goes to zero on a smooth surface, locally probing an in- finite distance point, and the bubbles are classically unstable against radial perturbations. However, it is also possible to stabilize KK bubbles at the classical level by adding flux. We study the impact of imposing the Weak Gravity Conjecture (WGC) on these solutions, finding that a rapid pair production instability arises in the presence of charged matter with q/m ≳ 1. We also analyze 4d electrically charged dilatonic black holes. Small curvature at the horizon imposes a bound log (MBH) ,≳ |∆𝜙|, independent of the WGC, and the bound can be strengthened if the particle satisfying the WGC is sufficiently light. We conjecture that quantum gravity in asymptotically flat space requires a general bound on large localized moduli space excursions of the form |∆𝜙| ≲ | log(RΛ)|, where R is the size of the minimal region enclosing the excitation and Λ−1 is the short-distance cutoff on local EFT. The bound is qualitatively saturated by the dilatonic black holes and Kaluza-Klein monopoles.

    更新日期:2020-01-27
  • The dynamical diquark model: fine structure and isospin
    J. High Energy Phys. (IF 5.833) Pub Date : 2020-01-21
    Jesse F. Giron, Richard F. Lebed, Curtis T. Peterson

    Abstract We incorporate fine-structure corrections into the dynamical diquark model of multiquark exotic hadrons. These improvements include effects due to finite diquark size, spin-spin couplings within the diquarks, and most significantly, isospin-dependent couplings in the form of pionlike exchanges assumed to occur between the light quarks within the diquarks. Using a simplified two-parameter interaction Hamiltonian, we obtain fits in which the isoscalar JPC = 1++ state — identified as the X (3872) — appears naturally as the lightest exotic (including all states that are predicted by the model but have not yet been observed), while the closed-charm decays of Zc(3900) and Zc(4020) prefer J/𝜓 and hc modes, respectively, in accord with experiment. We explore implications of this model for the excited tetraquark multiplets and the pentaquarks.

    更新日期:2020-01-27
  • A Na + /H + antiporter, K2-NhaD, improves salt and drought tolerance in cotton ( Gossypium hirsutum L.)
    Plant Mol. Biol. (IF 3.928) Pub Date : 2020-01-27
    Wenfang Guo, Gangqiang Li, Nan Wang, Caifeng Yang, Yanan Zhao, Huakang Peng, Dehu Liu, Sanfeng Chen

    Key message Overexpression of K2-NhaD in transgenic cotton resulted in phenotypes with strong salinity and drought tolerance in greenhouse and field experiments, increased expression of stress-related genes, and improved regulation of metabolic pathways, such as the SOS pathway. Abstract Drought and salinity are major abiotic stressors which negatively impact cotton yield under field conditions. Here, a plasma membrane Na+/H+ antiporter gene, K2-NhaD, was introduced into upland cotton R15 using an Agrobacterium tumefaciens-mediated transformation system. Homozygous transgenic lines K9, K17, and K22 were identified by PCR and glyphosate-resistance. TAIL-PCR confirmed that T-DNA carrying the K2-NhaD gene in transgenic lines K9, K17 and K22 was inserted into chromosome 3, 19 and 12 of the cotton genome, respectively. Overexpression of K2-NhaD in transgenic cotton plants grown in greenhouse conditions and subjected to drought and salinity stress resulted in significantly higher relative water content, chlorophyll, soluble sugar, proline levels, and SOD, CAT, and POD activity, relative to non-transgenic plants. The expression of stress-related genes was significantly upregulated, and this resulted in improved regulation of metabolic pathways, such as the salt overly sensitive pathway. K2-NhaD transgenic plants growing under field conditions displayed strong salinity and drought tolerance, especially at high levels of soil salinity and drought. Seed cotton yields in transgenic line were significantly higher than in wild-type plants. In conclusion, the data indicate that K2-NhaD transgenic lines have great potential for the production of stress-tolerant cotton under field conditions.

    更新日期:2020-01-27
  • Deep Intact Proteoform Characterization in Human Cell Lysate Using High-pH and Low-pH Reversed-Phase Liquid Chromatography
    J. Am. Soc. Mass Spectrom. (IF 3.202) Pub Date : 2019-11-21
    Dahang Yu, Zhe Wang, Kellye A. Cupp-Sutton, Xiaowen Liu, Si Wu

    Abstract Post-translational modifications (PTMs) play critical roles in biological processes and have significant effects on the structures and dynamics of proteins. Top-down proteomics methods were developed for and applied to the study of intact proteins and their PTMs in human samples. However, the large dynamic range and complexity of human samples makes the study of human proteins challenging. To address these challenges, we developed a 2D pH RP/RPLC-MS/MS technique that fuses high-resolution separation and intact protein characterization to study the human proteins in HeLa cell lysate. Our results provide a deep coverage of soluble proteins in human cancer cells. Compared to 225 proteoforms from 124 proteins identified when 1D separation was used, 2778 proteoforms from 628 proteins were detected and characterized using our 2D separation method. Many proteoforms with critically functional PTMs including phosphorylation were characterized. Additionally, we present the first detection of intact human GcvH proteoforms with rare modifications such as octanoylation and lipoylation. Overall, the increase in the number of proteoforms identified using 2DLC separation is largely due to the reduction in sample complexity through improved separation resolution, which enables the detection of low-abundance PTM-modified proteoforms. We demonstrate here that 2D pH RP/RPLC is an effective technique to analyze complex protein samples using top-down proteomics.

    更新日期:2020-01-27
  • Quantitation of Single and Combinatorial Histone Modifications by Integrated Chromatography of Bottom-up Peptides and Middle-down Polypeptide Tails
    J. Am. Soc. Mass Spectrom. (IF 3.202) Pub Date : 2019-09-11
    Kevin A. Janssen, Mariel Coradin, Congcong Lu, Simone Sidoli, Benjamin A. Garcia

    Abstract The analysis of histone post-translational modifications (PTMs) by mass spectrometry (MS) has been critical to the advancement of the field of epigenetics. The most sensitive and accurate workflow is similar to the canonical proteomics analysis workflow (bottom-up MS), where histones are digested into short peptides (4-20 aa) and quantitated in extracted ion chromatograms. However, this limits the ability to detect even very common co-occurrences of modifications on histone proteins, preventing biological interpretation of PTM crosstalk. By digesting with GluC rather than trypsin, it is possible to produce long polypeptides corresponding to intact histone N-terminal tails (50-60 aa), where most modifications reside. This middle-down MS approach is used to study distant PTM co-existence. However, the most sensitive middle-down workflow uses weak cation exchange-hydrophilic interaction chromatography (WCX-HILIC), which is less robust than conventional reversed-phase chromatography. Additionally, since the buffer systems for middle-down and bottom-up proteomics differ substantially, it is cumbersome to toggle back and forth between both experimental setups on the same LC system. Here, we present a new workflow using porous graphitic carbon (PGC) as a stationary phase for histone analysis where bottom-up and middle-down sized histone peptides can be analyzed simultaneously using the same reversed-phase buffer setup. By using this protocol for middle-down sized peptides, we identified 406 uniquely modified intact histone tails and achieved a correlation of 0.85 between PGC and WCX-HILIC LC methods. Together, our method facilitates the analysis of single and combinatorial histone PTMs with much simpler applicability for conventional proteomics labs than the state-of-the-art middle-down MS.

    更新日期:2020-01-27
  • Comprehensive Characterization of the Recombinant Catalytic Subunit of cAMP-Dependent Protein Kinase by Top-Down Mass Spectrometry
    J. Am. Soc. Mass Spectrom. (IF 3.202) Pub Date : 2019-12-02
    Zhijie Wu, Yutong Jin, Bifan Chen, Morgan K. Gugger, Chance L. Wilkinson-Johnson, Timothy N. Tiambeng, Song Jin, Ying Ge

    Abstract Reversible phosphorylation plays critical roles in cell growth, division, and signal transduction. Kinases which catalyze the transfer of γ-phosphate groups of nucleotide triphosphates to their substrates are central to the regulation of protein phosphorylation and are therefore important therapeutic targets. Top-down mass spectrometry (MS) presents unique opportunities to study protein kinases owing to its capabilities in comprehensive characterization of proteoforms that arise from alternative splicing, sequence variations, and post-translational modifications. Here, for the first time, we developed a top-down MS method to characterize the catalytic subunit (C-subunit) of an important kinase, cAMP-dependent protein kinase (PKA). The recombinant PKA C-subunit was expressed in Escherichia coli and successfully purified via his-tag affinity purification. By intact mass analysis with high resolution and high accuracy, four different proteoforms of the affinity-purified PKA C-subunit were detected, and the most abundant proteoform was found containing seven phosphorylations with the removal of N-terminal methionine. Subsequently, the seven phosphorylation sites of the most abundant PKA C-subunit proteoform were characterized simultaneously using tandem MS methods. Four sites were unambiguously identified as Ser10, Ser11, Ser18, and Ser30, and the remaining phosphorylation sites were localized to Ser2/Ser3, Ser358/Thr368, and Thr[215-224]Tyr in the PKA C-subunit sequence with a 20mer 6xHis-tag added at the N-terminus. Interestingly, four of these seven phosphorylation sites were located at the 6xHis-tag. Furthermore, we have performed dephosphorylation reaction by Lambda protein phosphatase and showed that all phosphorylations of the recombinant PKA C-subunit phosphoproteoforms were removed by this phosphatase.

    更新日期:2020-01-27
  • Discovery of Missing Methylation Sites on Endogenous Peptides of Human Cell Lines
    J. Am. Soc. Mass Spectrom. (IF 3.202) Pub Date : 2019-08-19
    Xin Yan, Lingjun Li, Chenxi Jia

    Abstract Methylation of proteins has considerable impacts on physiological processes including signal transduction, DNA damage repair, transcriptional regulation, gene activation, and inhibition of gene expression. However, the traditional proteomics-based approach suffers from limited identification rates of these critical methylation sites on endogenous peptides. In this work, a peptidomics-based workflow was established to discover and characterize the global methylome of endogenous peptides in human cells. The reliability of our strategy was validated by methyl-SILAC labeling, resulting in 83% true-positive identifications in the HeLa cell line. We applied this approach to seven human cell lines, and 700 methylated forms on 646 putative methylation sites were identified in total, with over 61% of the methylation sites being newly identified. This study provides a complementary strategy for a traditional proteomics-based approach that enables identification of missing methylation sites and creates a first methylome draft of endogenous peptides of human cell lines, offering a valuable resource for in-depth studies of biological functions of methylated endogenous peptides.

    更新日期:2020-01-27
  • One-Pot Quantitative Top- and Middle-Down Analysis of GluC-Digested Histone H4
    J. Am. Soc. Mass Spectrom. (IF 3.202) Pub Date : 2019-05-30
    Matthew V. Holt, Tao Wang, Nicolas L. Young

    Abstract Histone post-translational modifications (PTMs) have been intensively investigated due to their essential function in eukaryotic genome regulation. Histone modifications have been effectively studied using modified bottom-up proteomics approaches; however, the methods often do not capture single-molecule combinations of PTMs (proteoforms) that mediate known and expected biochemical mechanisms. Both middle-down mass spectrometry (MS) and top-down MS quantitation of H4 proteoforms present viable access to this important information. Histone H4 middle-down has previously avoided GluC digestion due to complex digestion products and interferences; however, the common AspN digestion cleaves at amino acid 23, disconnecting K31ac from other PTMs. Here, we demonstrate the effective use of GluC-based middle-down quantitation and compare it to top-down-based quantitation of proteoforms. Despite potential interferences in the m/z space, the proteoforms arising from all three GluC products (E52, E53, and E63) and intact H4 are chromatographically resolved and successfully analyzed in a single LC–MS analysis. Quantitative results and associated analytical metrics are compared between the different analytes of a single sample digested to different extents to reveal general concordance as well as the relative biases and complementarity of each approach. There is moderate proteoform discordance between digestion products (e.g., E52 and E53); however, each digestion product exhibits high concordance, regardless of digestion time. Under the conditions used, the GluC products are better chromatographically resolved yet show greater variance than the top-down quantitation that are more extensively sampled for MS2. GluC-based middle-down of H4 is thus viable. Both top-down and middle-down approaches have comparable quantitation capacity and are complementary.

    更新日期:2020-01-27
  • Finding the Sweet Spot in ERLIC Mobile Phase for Simultaneous Enrichment of N-Glyco and Phosphopeptides
    J. Am. Soc. Mass Spectrom. (IF 3.202) Pub Date : 2019-07-08
    Yusi Cui, Ka Yang, Dylan Nicholas Tabang, Junfeng Huang, Weiping Tang, Lingjun Li

    Abstract Simultaneous enrichment of glyco- and phosphopeptides will benefit the studies of biological processes regulated by these posttranslational modifications (PTMs). It will also reveal potential crosstalk between these two ubiquitous PTMs. Unlike custom-designed multifunctional solid phase extraction (SPE) materials, operating strong anion exchange (SAX) resin in electrostatic repulsion-hydrophilic interaction chromatography (ERLIC) mode provides a readily available strategy to analytical labs for enrichment of these PTMs for subsequent mass spectrometry (MS)-based characterization. However, the choice of mobile phase has largely relied on empirical rules from hydrophilic interaction chromatography (HILIC) or ion-exchange chromatography (IEX) without further optimization and adjustments. In this study, ten mobile phase compositions of ERLIC were systematically compared; the impact of multiple factors including organic phase proportion, ion pairing reagent, pH, and salt on the retention of glycosylated and phosphorylated peptides was evaluated. This study demonstrated good enrichment of glyco- and phosphopeptides from the nonmodified peptides in a complex tryptic digest. Moreover, the enriched glyco- and phosphopeptides elute in different fractions by orthogonal retention mechanisms of hydrophilic interaction and electrostatic interaction in ERLIC, maximizing the LC-MS identification of each PTM. The optimized mobile phase can be adapted to the ERLIC HPLC system, where the high resolution in separating multiple PTMs will benefit large-scale MS-based PTM profiling and in-depth characterization.

    更新日期:2020-01-27
  • Detection of E. coli labeled with metal-conjugated antibodies using lateral-flow assay and laser-induced breakdown spectroscopy
    Anal. Bioanal. Chem. (IF 3.286) Pub Date : 2020-01-27
    Carmen Gondhalekar, Eva Biela, Bartek Rajwa, Euiwon Bae, Valery Patsekin, Jennifer Sturgis, Cole Reynolds, Iyll-Joon Doh, Prasoon Diwakar, Larry Stanker, Vassilia Zorba, Xianglei Mao, Richard Russo, J. Paul Robinson

    Abstract This study explores the adoption of laser-induced breakdown spectroscopy (LIBS) for the analysis of lateral-flow immunoassays (LFIAs). Gold (Au) nanoparticles are standard biomolecular labels among LFIAs, typically detected via colorimetric means. A wide diversity of lanthanide-complexed polymers (LCPs) are also used as immunoassay labels but are inapt for LFIAs due to lab-bound detection instrumentation. This is the first study to show the capability of LIBS to transition LCPs into the realm of LFIAs, and one of the few to apply LIBS to biomolecular label detection in complete immunoassays. Initially, an in-house LIBS system was optimized to detect an Au standard through a process of line selection across acquisition delay times, followed by determining limit of detection (LOD). The optimized LIBS system was applied to Au-labeled Escherichia coli detection on a commercial LFIA; comparison with colorimetric detection yielded similar LODs (1.03E4 and 8.890E3 CFU/mL respectively). Optimization was repeated with lanthanide standards to determine if they were viable alternatives to Au labels. It was found that europium (Eu) and ytterbium (Yb) may be more favorable biomolecular labels than Au. To test whether Eu-complexed polymers conjugated to antibodies could be used as labels in LFIAs, the conjugates were successfully applied to E. coli detection in a modified commercial LFIA. The results suggest interesting opportunities for creating highly multiplexed LFIAs. Multiplexed, sensitive, portable, and rapid LIBS detection of biomolecules concentrated and labeled on LFIAs is highly relevant for applications like food safety, where in-field food contaminant detection is critical. Graphical abstract

    更新日期:2020-01-27
  • Optimization of in vitro trophoblast assay for real-time impedimetric sensing of trophoblast-erythrocyte interactions in Plasmodium falciparum malaria
    Anal. Bioanal. Chem. (IF 3.286) Pub Date : 2020-01-27
    Jia Liu, Olga Chesnokova, Irina Oleinikov, Yuhao Qiang, Andrew V. Oleinikov, E Du

    Abstract Sequestration of Plasmodium falciparum–infected erythrocytes (IEs) is responsible for the pathophysiology of placental malaria, leading to serious complications such as intrauterine growth restriction and low birth weight. However, it is an experimental challenge to study the biology of human placenta. Conventional cell culture–based in vitro placental models rely on immunostaining techniques and high-magnification microscopy is limited in providing real-time quantitative analysis. Impedimetric sensing in combination with cell culture may offer a useful tool. In this paper, we report that real-time label-free measurement of cellular electrical impedance using xCELLigence technology can be used to quantify the proliferation, syncytial fusion, and long-term response of BeWo cells to IEs cytoadhesion. Specifically, we optimized key experimental parameters of cell seeding density and concentration of forskolin, a compound used to promote cell syncitiation, based on electrical signals and immunostaining results. Prolonged time of infection with IEs that led to cell-cell junction vanishment in BeWo cells and release of inflammatory cytokines were monitored in real time by continuous change in electrical impedance. The results suggest that the impedimetric technique is sensitive and can offer new opportunities for the study of cellular responses of trophoblast cells to IEs. The developed system can provide potentially a high-throughput screening tool of anti-adhesion or anti-inflammatory drugs for placental malaria infections.

    更新日期:2020-01-27
  • A novel peptide-based electrochemical biosensor for the determination of a metastasis-linked protease in pancreatic cancer cells
    Anal. Bioanal. Chem. (IF 3.286) Pub Date : 2020-01-27
    Cristina Muñoz-San Martín, María Pedrero, Maria Gamella, Ana Montero-Calle, Rodrigo Barderas, Susana Campuzano, José M. Pingarrón

    Abstract Proteases are involved in cancer‚ taking part in immune (dis)regulation, malignant progression and tumour growth. Recently, it has been found that expression levels of one of the members of the serine protease family, trypsin, is upregulated in human cancer cells of several organs, being considered as a specific cancer biomarker. Considering the great attention that electrochemical peptide sensors have nowadays, in this work, we propose a novel electroanalytical strategy for the determination of this important biomolecule. It implies the immobilization of a short synthetic peptide sequence, dually labelled with fluorescein isothiocyanate (FITC) and biotin, onto neutravidin-modified magnetic beads (MBs), followed by the peptide digestion with trypsin. Upon peptide disruption, the modified MBs were incubated with a specific fluorescein Fab fragment antibody labelled with horseradish peroxidase (HRP-antiFITC) and magnetically captured on the surface of a screen-printed carbon electrode (SPCE), where amperometric detection was performed using the hydroquinone (HQ)/HRP/H2O2 system. The biosensor exhibited a good reproducibility of the measurements (RSD 3.4%, n = 10), and specificity against other proteins and proteases commonly found in biological samples. This work reports the first quantitative data so far on trypsin expression in human cell lysates. The developed bioplatform was used for the direct determination of this protease in lysates from pancreatic cancer, cervix carcinoma and kidney cells in only 3 h and 30 min using low amounts (~ 0.1 μg) of raw extracts. Graphical abstract

    更新日期:2020-01-27
  • Separation of subcellular fluorescent microspheres by capillary electrophoresis
    Anal. Bioanal. Chem. (IF 3.286) Pub Date : 2020-01-27
    Zhenqing Li, Xiaoxiao Wang, Jin Chen, Chunxian Tao, Dawei Zhang, Yoshinori Yamaguchi

    Abstract Fluorescent microspheres (FMs) are widely employed in diagnostics and life sciences research; here, we investigated the effect of capillary coating, polymer concentration, electric field strength, and sample concentration on the separation performance of 1.0 μm FMs in hydroxyethyl cellulose (HEC) by capillary electrophoresis (CE). Results showed that (1) capillary coating could enhance the fluorescence signal. (2) For HEC with the same molecular weight, the higher HEC concentration is, the later the first peak appears in the electropherogram. (3) When FMs are diluted, increasing the electric field strength can enhance the migration speed and reduce the aggregation of FMs. (4) The number of FMs calculated is close to the theoretical value when it is diluted 10,000 times. The optimum conditions for CE were as follows: 6 cm/8 cm of effective length and total length of the coated capillary, 0.3% HEC (1300 k), and 300 V/cm of electric field strength. Such a study is helpful for the development of a FM counting system. Graphical abstract

    更新日期:2020-01-27
  • One-pot microplate-based chemiluminescent assay coupled with catalytic hairpin assembly amplification for DNA detection
    Anal. Bioanal. Chem. (IF 3.286) Pub Date : 2020-01-27
    Oleg L. Bodulev, Konstantin M. Burkin, Eugene E. Efremov, Ivan Yu. Sakharov

    Abstract Nowadays, considerable efforts are focused on advancing DNA detection methods, which are extremely important in clinical diagnostics, pathogen determination, gene therapy, and forensic analysis. A one-pot sensitive microplate-based chemiluminescent assay coupled with catalytic hairpin assembly (CHA) amplification for detection of a 35-mer DNA oligonucleotide was developed. To improve the assay sensitivity, a triple amplification strategy based on the application of CHA (1), streptavidin-polyperoxidase conjugate (Stp-polyHRP) (2), and an enhanced chemiluminescent reaction (3) was used. The one-pot format of the assay, where all steps of the DNA determination are performed in the same well without transfer of samples from one test tube to another, increased its precision. The proposed assay detected the target DNA in the fM range and distinguished the target DNA from related DNAs, demonstrating its high sensitivity and high selectivity. Moreover, the assay was applied successfully for the quantitative determination of the target in spiked samples of human plasma. A microplate format of the assay was convenient for the analysis of a large number of samples. This study provides a prospective tool for DNA detection. Graphical abstract

    更新日期:2020-01-27
  • A Method to Stop Analyzing Random Error and Start Analyzing Differential Responders to Exercise
    Sports Med. (IF 7.583) Pub Date : 2019-06-28
    Scott J. Dankel, Jeremy P. Loenneke

    Abstract It is commonly stated that individuals respond differently to exercise even when the same exercise intervention is performed. This has led many researchers to conduct exercise interventions and subsequently categorize individuals into different responder categories to determine what causes individuals to respond differently. Some methods by which differential responders are categorized include percentile ranks, standard deviations from the mean, and cluster analyses. Notably, each of these methods will result in the presence of differential responders even in the absence of an exercise intervention, indicating that individuals may be categorized based on the presence of random error as opposed to true differences in the exercise response. Here we propose a method by which differential responders can be classified after accounting for the presence of random error that is quantified from a time-matched control group. Individuals who exceed random error from the mean response of the intervention group can be confidently labelled as high and low responders. Importantly, the number of differential responders will be proportional to the ratio of variance in the exercise and control groups. We provide easy-to-follow steps and examples to demonstrate how this technique can identify differential responders to exercise. We also detail the flaws in other classification methods by demonstrating the number of differential responders who would have been classified using the same data set. Our hope is that this method will help to avoid misclassifying individuals based on random error and, in turn, increase the replicability of differential responder studies.

    更新日期:2020-01-27
  • Effects of Small-Sided Soccer Games on Physical Fitness, Physiological Responses, and Health Indices in Untrained Individuals and Clinical Populations: A Systematic Review
    Sports Med. (IF 7.583) Pub Date : 2020-01-27
    Hassane Zouhal, Amri Hammami, Jed M. Tijani, Ayyappan Jayavel, Maysa de Sousa, Peter Krustrup, Zouita Sghaeir, Urs Granacher, Abderraouf Ben Abderrahman

    Abstract Background Small-sided soccer games (SSSG) are a specific exercise regime with two small teams playing against each other on a relatively small pitch. There is evidence from original research that SSSG exposure provides performance and health benefits for untrained adults. Objectives The aim of this systematic review was to summarize recent evidence on the acute and long-term effects of SSSG on physical fitness, physiological responses, and health indices in healthy untrained individuals and clinical populations. Methods This systematic literature search was conducted in four electronic databases (PubMed, Web of Science, SPORTDiscus) from inception until June 2019. The following key terms (and synonyms searched for by the MeSH database) were included and combined using the operators “AND”, “OR”, “NOT”: ((soccer OR football) AND (“soccer training” OR “football training” OR “soccer game*” OR “small-sided soccer game*”) AND (“physical fitness” OR “physiological adaptation*” OR “physiological response*” OR health OR “body weight” OR “body mass” OR “body fat” OR “bone composition” OR “blood pressure”)). The search syntax initially identified 1145 records. After screening for titles, abstracts, and full texts, 41 studies remained that examined the acute (7 studies) and long-term effects (34 studies) of SSSG-based training on physical fitness, physiological responses, and selected alth indices in healthy untrained individuals and clinical populations. Results No training-related injuries were reported in the 41 acute and long-term SSSG studies. Typically, a single session of SSSG lasted 12–20 min (e.g., 3 × 4 min with 3 min rest or 5 × 4 min with 4 min rest) involving 4–12 players (2 vs. 2 to 6 vs. 6) at an intensity ≥ 80% of HRmax. Following single SSSG session, high cardiovascular and metabolic demands were observed. Specifically, based on the outcomes, the seven acute studies reported average heart rates (HR) ≥ 80% of HRmax (165–175 bpm) and mean blood lactate concentrations exceeding 5 mmol/l (4.5–5.9 mmol/l) after single SSSG sessions. Based on the results of 34 studies (20 with healthy untrained, 10 with unhealthy individuals, and 4 with individuals with obesity), SSSG training lasted between 12 and 16 weeks and was performed 2–3 times per week. SSSG had positive long-term effects on physical fitness (e.g., Yo–Yo IR1 performance), physiological responses including maximal oxygen uptake (VO2max) [+ 7 to 16%], and many health-related markers such as blood pressure (reductions in systolic [− 7.5%] and diastolic [− 10.3%] blood pressure), body composition (decreased fat mass [− 2 to − 5%]), and improved indices of bone health (bone mineral density: [+ 5 to 13%]; bone mineral content: [+ 4 to 5%]), and metabolic (LDL-cholesterol [− 15%] as well as cardiac function (left-ventricular internal diastolic diameter [+ 8%], end diastolic volume [+ 21%], left-ventricular mass index [+ 18%], and left-ventricular ejection fraction [+ 8%]). Irrespective of age or sex, these health benefits were observed in both, untrained individuals and clinical populations. Conclusions In conclusion, findings from this systematic review suggest that acute SSSG may elicit high cardiovascular and metabolic demands in untrained healthy adults and clinical populations. Moreover, this type of exercise is safe with positive long-term effects on physical fitness and health indices. Future studies are needed examining the long-term effects on physical fitness and physiological adaptations of different types of SSSG training (e.g., 3 vs. 3; 6 vs. 6) in comparison to continuous or interval training in different cohorts.

    更新日期:2020-01-27
  • Particle Detector (PD) Experiment of the Korea Space Environment Monitor (KSEM) Aboard Geostationary Satellite GK2A
    Space Sci. Rev. (IF 8.142) Pub Date : 2020-01-27
    J. Seon, K.-S. Chae, G. W. Na, H.-K. Seo, Y.-C. Shin, J. Woo, C.-H. Lee, W.-H. Seol, C.-A. Lee, S. Pak, H. Lee, S.-H. Shin, D. E. Larson, K. Hatch, G. K. Parks, J. Sample, M. McCarthy, C. Tindall, Y.-J. Jeon, J.-K. Choi, J.-Y. Park

    Abstract The Particle Detector (PD) experiment aboard the geostationary satellite GEO-KOMPSAT-2A (GK2A) measures populations of electrons and positive ions in the Earth’s geostationary orbit at a geographic longitude of \(128.2^{\circ }\mbox{E}\), inclination of \(0^{\circ }\) and a mean orbital radius of 6.6 Earth radii (\(R_{E}\)). The PD experiment consists of three sensors with different viewing angles relative to the spacecraft. Each sensor consists of two telescopes that are mechanically configured back-to-back with a field-of-view of \(20^{\circ }\times 20^{\circ }\) and measures electrons and ions, using silicon detectors equipped with foils and magnets for the separation of ions and electrons. The energy ranges of the sensor for electrons and ions are 100–3800 keV and 148–22500 keV, respectively. A particular emphasis on electron measurement is given by allocating 48 energy bins in the measured energy range, whereas 22 energy bins are allocated for ion measurements. This unprecedented energy resolution of \(\Delta E/E\) in the range 5–25% for the electron and ion flux measurements is acquired every three seconds with cyclic polling of each sensor every second to provide an effective temporal resolution of one second. Together with the magnetometer aboard the spacecraft, the PD experiment will provide quantitative observations that will enable improved understanding of the adiabatic and nonadiabatic dynamics of the Earth’s magnetosphere for space weather studies at geostationary orbits from the vantage point of a far-east longitude.

    更新日期:2020-01-27
  • Correction to: Vendor boundary spanning in Indian Information Technology (IT) companies
    Asia Pac. J. Manag. (IF 2.737) Pub Date : 2020-01-27
    Smita Prashant Chattopadhyay, Madhuchhanda Das Aundhe

    The original version of this article unfortunately contained mistakes.

    更新日期:2020-01-27
  • Three-institution study on applicability of initial brain metastasis velocity for breast cancer brain metastasis patients undergoing stereotactic radiosurgery
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-27
    Masaaki Yamamoto, Toru Serizawa, Osamu Nagano, Kyoko Aoyagi, Yoshinori Higuchi, Yasunori Sato, Hidetoshi Kasuya, Bierta E. Barfod

    Abstract Purpose This study aimed to validate whether the recently-proposed prognostic grading system, initial brain metastasis velocity (iBMV), is applicable to breast cancer patients receiving stereotactic radiosurgery (SRS). We focused particularly on whether this grading system is useful for patients with all molecular types, i.e., positive versus negative for EsR, PgR and HER2. Methods and materials This was an institutional review board-approved, retrospective cohort study using our database, prospectively accumulated at three gamma knife institutes, during the 20-year-period since 1998. We excluded patients for whom the day of primary cancer diagnosis was not available, had synchronous presentation, lacked information regarding molecular types, and/or had received pre-SRS radiotherapy and/or surgery. We ultimately studied 511 patients categorized into two classes by iBMV scores, i.e., < 2.00 and ≥ 2.00. Results The median iBMV score for the entire cohort was 0.97 (IQR 0.39–2.84). Median survival time (MST) in patients with iBMV < 2.00, 15.9 (95% CI 13.0–18.6, IQR 7.5–35.5) months, was significantly longer than that in patients with iBMV ≥ 2.00, 8.2 (95% CI 6.8–9.9, IQR 3.9–19.4) months (HR 1.582, 95% CI: 1.308–1.915, p < 0.0001). The same results were obtained in patients with EsR (−), PgR (−), HER2 (+) and HER2 (−) cancers, while MSTs did not differ significantly between iBMV < 2.00 vs ≥ 2.00 in patients with EsR (+) and PgR (+) cancers. Conclusions This system was clearly shown to be applicable to breast cancer patients with SRS-treated BMs. However, this system is not applicable to patients with hormone receptor (+) breast cancer.

    更新日期:2020-01-27
  • Finite element analysis of Tumor Treating Fields in a patient with posterior fossa glioblastoma
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-27
    Edwin Lok, Pyay San, Olivia Liang, Victoria White, Eric T. Wong

    Abstract Introduction Tumor Treating Fields (TTFields) are alternating electric fields at 200 kHz that disrupt tumor cells as they undergo mitosis. Patient survival benefit has been demonstrated in randomized clinical trials but much of the data are available only for supratentorial glioblastomas. We investigated a series of alternative array configurations for the posterior fossa to determine the electric field coverage of a cerebellar glioblastoma. Methods Semi-automated segmentation of neuro-anatomical structures was performed while the gross tumor volume (GTV) was manually delineated. A three-dimensional finite-element mesh was generated and then solved for field distribution. Results Compared to the supratentorial array configuration, the alternative array configurations consist of posterior displacement the 2 lateral opposing arrays and inferior displacement of the posteroanterior array, resulting in an average increase of 46.6% electric field coverage of the GTV as measured by the area under the curve of the electric field-volume histogram (EAUC). Hotspots, or regions of interest with the highest 5% of TTFields intensity (E5%), had an average increase of 95.6%. Of the 6 posterior fossa configurations modeled, the PAHorizontal arrangement provided the greatest field coverage at the GTV when the posteroanterior array was placed centrally along the patient’s posterior neck and horizontally parallel, along the longer axis, to the coronal plane of the patient’s head. Varying the arrays also produced hotspots proportional to TTFields coverage. Conclusions Our finite element modeling showed that the alternative array configurations offer an improved TTFields coverage to the cerebellar tumor compared to the conventional supratentorial configuration.

    更新日期:2020-01-27
  • Correction to: Vascular endothelial growth factor is an autocrine growth factor, signaling through neuropilin-1 in non-small cell lung cancer
    Mol. Cancer (IF 10.679) Pub Date : 2020-01-27
    Martin P. Barr; Steven G. Gray; Kathy Gately; Emily Hams; Padraic G. Fallon; Anthony Mitchell Davies; Derek J. Richard; Graham P. Pidgeon; Kenneth J. O’Byrne

    Since the publication of this work [1] and in response to a recent query that was brought to our attention in relation to the Western Blot in Figure 1(C) for NP2, protein lysates prepared around the same time as those presented in the manuscript in question, were run by SDS-PAGE under similar experimental conditions and probed using the same primary antibodies to NP1 and NP2 that were used originally.

    更新日期:2020-01-27
  • Mitochondrial dysfunction mediated through dynamin-related protein 1 (Drp1) propagates impairment in blood brain barrier in septic encephalopathy
    J. Neuroinflammation (IF 5.7) Pub Date : 2020-01-27
    Bereketeab Haileselassie; Amit U. Joshi; Paras S. Minhas; Riddhita Mukherjee; Katrin I. Andreasson; Daria Mochly-Rosen

    Out of the myriad of complications associated with septic shock, septic-associated encephalopathy (SAE) carries a significant risk of morbidity and mortality. Blood-brain-barrier (BBB) impairment, which subsequently leads to increased vascular permeability, has been associated with neuronal injury in sepsis. Thus, preventing BBB damage is an attractive therapeutic target. Mitochondrial dysfunction is an important contributor of sepsis-induced multi-organ system failure. More recently, mitochondrial dysfunction in endothelial cells has been implicated in mediating BBB failure in stroke, multiple sclerosis and in other neuroinflammatory disorders. Here, we focused on Drp1-mediated mitochondrial dysfunction in endothelial cells as a potential target to prevent BBB failure in sepsis. We used lipopolysaccharide (LPS) to induce inflammation and BBB disruption in a cell culture as well as in murine model of sepsis. BBB disruption was assessed by measuring levels of key tight-junction proteins. Brain cytokines levels, oxidative stress markers, and activity of mitochondrial complexes were measured using biochemical assays. Astrocyte and microglial activation were measured using immunoblotting and qPCR. Transwell cultures of brain microvascular endothelial cells co-cultured with astrocytes were used to assess the effect of LPS on expression of tight-junction proteins, mitochondrial function, and permeability to fluorescein isothiocyanate (FITC) dextran. Finally, primary neuronal cultures exposed to LPS were assessed for mitochondrial dysfunction. LPS induced a strong brain inflammatory response and oxidative stress in mice which was associated with increased Drp1 activation and mitochondrial localization. Particularly, Drp1-(Fission 1) Fis1-mediated oxidative stress also led to an increase in expression of vascular permeability regulators in the septic mice. Similarly, mitochondrial defects mediated via Drp1-Fis1 interaction in primary microvascular endothelial cells were associated with increased BBB permeability and loss of tight-junctions after acute LPS injury. P110, an inhibitor of Drp1-Fis1 interaction, abrogated these defects, thus indicating a critical role for this interaction in mediating sepsis-induced brain dysfunction. Finally, LPS mediated a direct toxic effect on primary cortical neurons, which was abolished by P110 treatment. LPS-induced impairment of BBB appears to be dependent on Drp1-Fis1-mediated mitochondrial dysfunction. Inhibition of mitochondrial dysfunction with P110 may have potential therapeutic significance in septic encephalopathy.

    更新日期:2020-01-27
  • A patient with left-sided inferior vena cava who received oblique lumbar interbody fusion surgery: a case report
    J. Med. Case Rep. (IF 0) Pub Date : 2020-01-27
    Chen Liu; Jian Zhai; Quan Yuan; Yu Zhang; Hongguang Xu

    Oblique lateral interbody fusion surgery has become increasingly popular for lumbar degenerative diseases. The oblique corridor is between the psoas muscle and the retroperitoneal vessels, and its use could result in decreased tissue trauma, minimal blood loss, and short operation times. Patients who undergo oblique lateral interbody fusion surgery are always placed in the right lateral position to avoid damage to the inferior vena cava, which is typically a right-sided vessel. There is a substantial risk of vascular injury during the operation if there are anatomical variations in the vessels. A 77-year-old man, of the Han nationality, with lumbar spinal stenosis underwent stand-alone oblique lateral interbody fusion surgery. Transverse magnetic resonance imaging of the lumbar spine indicated that his inferior vena cava was left-sided. A three-dimensional reconstructed image of abdominal computed tomography angiography showed that the inferior vena cava was located on the left side. Finally, the surgeon decided to change the position of our patient from a right lateral position to a left lateral position before the surgery. To date, this is the first reported case where a patient underwent oblique lateral interbody fusion surgery in a left lateral decubitus position due to a left-sided inferior vena cava. This case demonstrates that carefully reading radiological results is important for operation planning and avoiding anatomical complications.

    更新日期:2020-01-27
  • Correction to: Genome-wide assessment of DNA methylation in mouse oocytes reveals effects associated with in vitro growth, superovulation, and sexual maturity
    Clin. Epigenet. (IF 5.496) Pub Date : 2020-01-27
    Maria Desemparats Saenz-de-Juano; Elena Ivanova; Katy Billooye; Anamaria-Cristina Herta; Johan Smitz; Gavin Kelsey; Ellen Anckaert

    After publication of the original article [1], we were notified that.

    更新日期:2020-01-27
  • Cell death induced by the ER stressor thapsigargin involves death receptor 5, a non-autophagic function of MAP1LC3B, and distinct contributions from unfolded protein response components
    Cell Commun. Signal. (IF 5.111) Pub Date : 2020-01-27
    Paula Lindner; Søren Brøgger Christensen; Poul Nissen; Jesper Vuust Møller; Nikolai Engedal

    Cell death triggered by unmitigated endoplasmic reticulum (ER) stress plays an important role in physiology and disease, but the death-inducing signaling mechanisms are incompletely understood. To gain more insight into these mechanisms, the ER stressor thapsigargin (Tg) is an instrumental experimental tool. Additionally, Tg forms the basis for analog prodrugs designed for cell killing in targeted cancer therapy. Tg induces apoptosis via the unfolded protein response (UPR), but how apoptosis is initiated, and how individual effects of the various UPR components are integrated, is unclear. Furthermore, the role of autophagy and autophagy-related (ATG) proteins remains elusive. To systematically address these key questions, we analyzed the effects of Tg and therapeutically relevant Tg analogs in two human cancer cell lines of different origin (LNCaP prostate- and HCT116 colon cancer cells), using RNAi and inhibitory drugs to target death receptors, UPR components and ATG proteins, in combination with measurements of cell death by fluorescence imaging and propidium iodide staining, as well as real-time RT-PCR and western blotting to monitor caspase activity, expression of ATG proteins, UPR components, and downstream ER stress signaling. In both cell lines, Tg-induced cell death depended on death receptor 5 and caspase-8. Optimal cytotoxicity involved a non-autophagic function of MAP1LC3B upstream of procaspase-8 cleavage. PERK, ATF4 and CHOP were required for Tg-induced cell death, but surprisingly acted in parallel rather than as a linear pathway; ATF4 and CHOP were independently required for Tg-mediated upregulation of death receptor 5 and MAP1LC3B proteins, whereas PERK acted via other pathways. Interestingly, IRE1 contributed to Tg-induced cell death in a cell type-specific manner. This was linked to an XBP1-dependent activation of c-Jun N-terminal kinase, which was pro-apoptotic in LNCaP but not HCT116 cells. Molecular requirements for cell death induction by therapy-relevant Tg analogs were identical to those observed with Tg. Together, our results provide a new, integrated understanding of UPR signaling mechanisms and downstream mediators that induce cell death upon Tg-triggered, unmitigated ER stress.

    更新日期:2020-01-27
  • FGFR3 signaling and function in triple negative breast cancer
    Cell Commun. Signal. (IF 5.111) Pub Date : 2020-01-27
    Nicole J. Chew; Elizabeth V. Nguyen; Shih-Ping Su; Karel Novy; Howard C. Chan; Lan K. Nguyen; Jennii Luu; Kaylene J. Simpson; Rachel S. Lee; Roger J. Daly

    Triple negative breast cancer (TNBC) accounts for 16% of breast cancers and represents an aggressive subtype that lacks targeted therapeutic options. In this study, mass spectrometry (MS)-based tyrosine phosphorylation profiling identified aberrant FGFR3 activation in a subset of TNBC cell lines. This kinase was therefore evaluated as a potential therapeutic target. MS-based tyrosine phosphorylation profiling was undertaken across a panel of 24 TNBC cell lines. Immunoprecipitation and Western blot were used to further characterize FGFR3 phosphorylation. Indirect immunofluorescence and confocal microscopy were used to determine FGFR3 localization. The selective FGFR1–3 inhibitor, PD173074 and siRNA knockdowns were used to characterize the functional role of FGFR3 in vitro. The TCGA and Metabric breast cancer datasets were interrogated to identify FGFR3 alterations and how they relate to breast cancer subtype and overall patient survival. High FGFR3 expression and phosphorylation were detected in SUM185PE cells, which harbor a FGFR3-TACC3 gene fusion. Low FGFR3 phosphorylation was detected in CAL51, MFM-223 and MDA-MB-231 cells. In SUM185PE cells, the FGFR3-TACC3 fusion protein contributed the majority of phosphorylated FGFR3, and largely localized to the cytoplasm and plasma membrane, with staining at the mitotic spindle in a small subset of cells. Knockdown of the FGFR3-TACC3 fusion and wildtype FGFR3 in SUM185PE cells decreased FRS2, AKT and ERK phosphorylation, and induced cell death. Knockdown of wildtype FGFR3 resulted in only a trend for decreased proliferation. PD173074 significantly decreased FRS2, AKT and ERK activation, and reduced SUM185PE cell proliferation. Cyclin A and pRb were also decreased in the presence of PD173074, while cleaved PARP was increased, indicating cell cycle arrest in G1 phase and apoptosis. Knockdown of FGFR3 in CAL51, MFM-223 and MDA-MB-231 cells had no significant effect on cell proliferation. Interrogation of public datasets revealed that increased FGFR3 expression in breast cancer was significantly associated with reduced overall survival, and that potentially oncogenic FGFR3 alterations (eg mutation and amplification) occur in the TNBC/basal, luminal A and luminal B subtypes, but are rare. These results indicate that targeting FGFR3 may represent a therapeutic option for TNBC, but only for patients with oncogenic FGFR3 alterations, such as the FGFR3-TACC3 fusion.

    更新日期:2020-01-27
  • The role of CSDE1 in translational reprogramming and human diseases
    Cell Commun. Signal. (IF 5.111) Pub Date : 2020-01-27
    Ao-Xiang Guo; Jia-Jia Cui; Lei-Yun Wang; Ji-Ye Yin

    CSDE1 (cold shock domain containing E1) plays a key role in translational reprogramming, which determines the fate of a number of RNAs during biological processes. Interestingly, the role of CSDE1 is bidirectional. It not only promotes and represses the translation of RNAs but also increases and decreases the abundance of RNAs. However, the mechanisms underlying this phenomenon are still unknown. In this review, we propose a “protein-RNA connector” model to explain this bidirectional role and depict its three versions: sequential connection, mutual connection and facilitating connection. As described in this molecular model, CSDE1 binds to RNAs and cooperates with other protein regulators. CSDE1 connects with different RNAs and their regulators for different purposes. The triple complex of CSDE1, a regulator and an RNA reprograms translation in different directions for each transcript. Meanwhile, a number of recent studies have found important roles for CSDE1 in human diseases. This model will help us to understand the role of CSDE1 in translational reprogramming and human diseases.

    更新日期:2020-01-27
  • The role of the redox/miR-6855-3p/PRDX5A axis in reversing SLUG-mediated BRCA2 silencing in breast cancer cells
    Cell Commun. Signal. (IF 5.111) Pub Date : 2020-01-27
    Marshall Ellison; Mukul Mittal; Minu Chaudhuri; Gautam Chaudhuri; Smita Misra

    We have previously shown that the zinc finger transcription repressor SNAI2 (SLUG) represses tumor suppressor BRCA2-expression in non-dividing cells by binding to the E2-box upstream of the transcription start site. However, it is unclear how proliferating breast cancer (BC) cells that has higher oxidation state, overcome this repression. In this study, we provide insight into the mechanism of de-silencing of BRCA2 gene expression by PRDX5A, which is the longest member of the peroxiredoxin5 family, in proliferating breast cancer cells. We used cell synchronization and DNA affinity pulldown to analyze PRDX5A binding to the BRCA2 silencer. We used oxidative stress and microRNA (miRNA) treatments to study nuclear localization of PRDX5A and its impact on BRCA2-expression. We validated our findings using mutational, reporter assay, and immunofluorescence analyses. Under oxidative stress, proliferating BC cells express PRDX5 isoform A (PRDX5A). In the nucleus, PRDX5A binds to the BRCA2 silencer near the E2-box, displacing SLUG and enhancing BRCA2-expression. Nuclear PRDX5A is translated from the second AUG codon in frame to the first AUG codon in the PRDX5A transcript that retains all exons. Mutation of the first AUG increases nuclear localization of PRDX5A in MDA-MB-231 cells, but mutation of the second AUG decreases it. Increased mitronic hsa-miRNA-6855-3p levels under oxidative stress renders translation from the second AUG preferable. Mutational analysis using reporter assay uncovered a miR-6855-3p binding site between the first and second AUG codon in the PRDX5A transcript. miR-6855-3p mimic increases accumulation of nuclear PRDX5A and inhibits reporter gene translation. Oxidative stress increases miR-6855-3p expression and binding to the inter-AUG sequence of the PRDX5A transcript, promoting translation of nuclear PRDX5A. Nuclear PRDX5A relieves SLUG-mediated BRCA2 silencing, resulting in increased BRCA2-expression.

    更新日期:2020-01-27
  • Gastrointestinal hemorrhage before anticoagulant therapy in Kawasaki disease: a case report
    BMC Pediatr. (IF 1.983) Pub Date : 2020-01-27
    Chenmin Hu; Yanping Yu

    Kawasaki disease (KD) is an acute febrile multisystem vasculitis and has been recognized to be the most common cause of acquired heart disease in children. Owing to its propensity to involve vessels throughout the entire body, KD often mimics other disease processes. The diagnosis might be delayed if other prominent symptoms appear before the characteristic clinical features of KD. Although gastrointestinal symptoms including vomiting, diarrhea, and abdominal pain are not uncommon in KD patients, KD with gastrointestinal bleeding is quite rare. A previously healthy 4-year-old boy initially presented with abdominal pain, followed by fever, rash, and gastrointestinal hemorrhage, eventually diagnosed as complete KD. The patient recovered smoothly after appropriate management and no subsequent complications occurred in the following months. The diagnosis of KD should be considered in children presenting with abdominal symptoms and fever without definable cause. Pediatricians should be aware of the risk of gastrointestinal bleeding in patients with KD, especially in those with prominent abdominal symptoms.

    更新日期:2020-01-27
  • Neonatal survival and determinants of mortality in Aroresa district, Southern Ethiopia: a prospective cohort study
    BMC Pediatr. (IF 1.983) Pub Date : 2020-01-27
    Alaka Adiso Limaso; Mesay Hailu Dangisso; Desalegn Tsegaw Hibstu

    The first 28 days of aliveness are the biggest challenge mentioned for the continuity of life for children. In Ethiopia, despite a significant reduction in under-five mortality during the last 15 years, neonatal mortality remains a public health problem accounting for 47% of under-five mortality. Understanding neonatal survival and risk factors for neonatal mortality could help devising tailored interventions. The aim of this study was to determine the neonatal survival and risk factors for neonatal mortality in Aroresa district, Southern Ethiopia. A community based prospective follow up study was conducted among a cohort of term pregnant mothers and neonates delivered from January 1/2018 to March 30/2018. A total of 586 term pregnant mothers were selected with a multistage sampling technique and 584 neonates were followed-up for a total of 28 days, with 12 twin pairs. Data were coded, entered cleaned and analyzed using SPSS version 22. Kaplan–Meier survival curve was used to show pattern of neonatal death in 28 days. Independent and adjusted relationships of different predictors with neonates’ survival were assessed with Cox regression model. The risk of mortality was explored and presented with hazard ratio and 95% confidence interval and P-value less than 0.05 were considered as significant. The overall neonatal mortality was 41 per 1000 live births. Hazards of neonatal mortality was high for neonates with complications (AHR = 3.643; 95% CI, 1.36–9.77), male neonates (AHR = 2.71; 95% CI, 1.03–7.09), neonates that mothers perceived to be small (AHR = 3.46; 95% CI, 1.119–10.704), neonates who had initiated exclusive breast feeding (EBF) after 1 h (AHR = 3.572; 95% CI, 1.255–10.165) and mothers who had no postnatal care (AHR = 3.07; 95% CI, 1.16–8.12). Neonatal mortality in the study area was 4.1% which was high and immediate action should be taken towards achieving the Sustainable Development Goals. To improve neonatal survival, high impact interventions such as promotion of maternal service utilization, essential newborn care and early initiation of exclusive breast feeding were recommended.

    更新日期:2020-01-27
  • Analysis of the relationship between the mutation site of the SLC39A4 gene and acrodermatitis enteropathica by reporting a rare Chinese twin: a case report and review of the literature
    BMC Pediatr. (IF 1.983) Pub Date : 2020-01-27
    Wei Zhong; Chao Yang; Lei Zhu; Yu-Qi Huang; Yong-Feng Chen

    Acrodermatitis enteropathica (AE) is a rare autosomal recessive hereditary skin disease caused by mutations in the SLC39A4 gene and is characterized by periorificial dermatitis, alopecia and diarrhoea due to insufficient zinc absorption. Only one of the three known sets of twins with AE has genetic information. This case reports the discovery of new mutation sites in rare twin patients and draws some interesting conclusions by analysing the relationship between genetic information and clinical manifestations. Here, we report a pair of 16-month-old twin boys with AE exhibiting periorificial and acral erythema, scales and blisters, while subsequent laboratory examination showed normal plasma zinc and alkaline phosphatase levels. Further Sanger sequencing demonstrated that the patients were compound heterozygous for two unreported SLC39A4 mutations: a missense mutation in exon 5 (c.926G > T), which led to a substitution of the 309th amino acid residue cysteine with phenylalanine, a splice site mutation occurring in the consensus donor site of intron 5 (c.976 + 2 T > A). A family study revealed that the boys’ parents were heterozygous carriers of these two mutations. We identified a new compound heterozygous mutation in Chinese twins with AE, which consisted of two previous unreported variants in exon 5 and intron 5 of SLC39A4. We propose an up-to-date review that different mutations in SLC39A4 may exhibit different AE manifestations. In conjunction with future research, our work may shed light on genotype-phenotype correlations in AE patients and provide knowledge for genetic counselling and treatment for AE patients.

    更新日期:2020-01-27
  • Correction to: Assessment of burnout in veterinary medical students using the Maslach burnout inventory-educational survey: a survey during two semesters
    BMC Med. Educ. (IF 1.87) Pub Date : 2020-01-27
    Munashe Chigerwe; Karen A. Boudreaux; Jan E. Ilkiw

    Following publication of the original article [1], we’ve been notified by an author that they have published their manuscript without seeking permission for the survey that was included in one of their tables (Table 1).

    更新日期:2020-01-27
  • Correction to: Twenty-five years on: revisiting Bosnia and Herzegovina after implementation of a family medicine development program
    BMC Fam. Pract. (IF 2.431) Pub Date : 2020-01-27
    Geoffrey Hodgetts; Glenn Brown; Olivera Batić-Mujanović; Larisa Gavran; Zaim Jatić; Maja Račić; Gordana Tešanović; Amra Zalihić; Mary Martin; Richard Birtwhistle

    Following publication of the original article [1], the authors opted to correct the name of co-author Amra Zalihić from Zahilić to Zalihić. The original article has been corrected.

    更新日期:2020-01-27
  • The HICU PIE results of EU ceramic breeder pebbles: General characterization
    J. Nucl. Mater. (IF 2.547) Pub Date : 2020-01-27
    M.H.H. Kolb; J.M. Heuser; R. Rolli; H.-C. Schneider; R. Knitter; M. Zmitko

    The HICU (High neutron fluence Irradiation of pebble staCks for fUsion) experiment was performed in the High Flux Reactor (HFR) in Petten, NL, in order to irradiate candidate tritium breeder materials in a fusion relevant environment. The presented work focuses on the post-irradiation examination of the irradiated lithium orthosilicate based breeder pebbles. The pebble samples showed three different contents of Li-6 and were irradiated at two different temperatures and in mechanically constrained and unconstrained state. In this particular publication, the influences of the irradiation conditions on the pebble morphology, microstructure, porosity, and mechanical strength are addressed. The results indicate that in general a high irradiation temperature seems to be advantageous for maintaining the mechanical strength of the irradiated pebbles. A higher mechanical strength and a significantly lower closer porosity is observed for samples that were irradiated at high temperatures in comparison to pebbles that were irradiated at low temperatures. The effects on the pebble properties with respect to the Li-6 content are small in contrast to effects of the irradiation temperature. With an increased Li-6 content, no deterioration of the material properties was observed, especially for samples irradiated at high temperatures.

    更新日期:2020-01-27
  • Cordyceps militaris induces apoptosis in ovarian cancer cells through TNF-α/TNFR1-mediated inhibition of NF-κB phosphorylation
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-13
    Eunbi Jo; Hyun-Jin Jang; Kyeong Eun Yang; Min Su Jang; Yang Hoon Huh; Hwa-Seung Yoo; Jun Soo Park; Ik-Soon Jang; Soo Jung Park

    Cordyceps militaris (L.) Fr. (C. militaris) exhibits pharmacological activities, including antitumor properties, through the regulation of the nuclear factor kappa B (NF-κB) signaling. Tumor Necrosis Factor (TNF) and TNF-α modulates cell survival and apoptosis through NF- κB signaling. However, the mechanism underlying its mode of action on the NF-κB pathway is unclear. Here, we analyzed the effect of C. militaris extract (CME) on the proliferation of ovarian cancer cells by confirming viability, morphological changes, migration assay. Additionally, CME induced apoptosis was determined by apoptosis assay and apoptotic body formation under TEM. The mechanisms of CME were determined through microarray, immunoblotting and immunocytochemistry. CME reduced the viability of cells in a dose-dependent manner and induced morphological changes. We confirmed the decrease in the migration activity of SKOV-3 cells after treatment with CME and the consequent induction of apoptosis. Immunoblotting results showed that the CME-mediated upregulation of tumor necrosis factor receptor 1 (TNFR1) expression induced apoptosis of SKOV-3 cells via the serial activation of caspases. Moreover, CME negatively modulated NF-κB activation via TNFR expression, suggestive of the activation of the extrinsic apoptotic pathway. The binding of TNF-α to TNFR results in the disassociation of IκB from NF-κB and the subsequent translocation of the active NF-κB to the nucleus. CME clearly suppressed NF-κB translocation induced by interleukin (IL-1β) from the cytosol into the nucleus. The decrease in the expression levels of B cell lymphoma (Bcl)-xL and Bcl-2 led to a marked increase in cell apoptosis. These results suggest that C. militaris inhibited ovarian cancer cell proliferation, survival, and migration, possibly through the coordination between TNF-α/TNFR1 signaling and NF-κB activation. Taken together, our findings provide a new insight into a novel treatment strategy for ovarian cancer using C. militaris.

    更新日期:2020-01-27
  • Acute and sub-acute toxicity of Echinops kebericho decoction in rats
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-13
    Serawit Deyno; Abiy Abebe; Mesfin Asefa Tola; Ariya Hymete; Joel Bazira; Eyasu Makonnen; Paul E. Alele

    Echinops kebericho is widely used for treatment of a variety of diseases including infectious, non-infectious disease and fumigation during child birth. Antibacterial, antimalarial, anti-leshimania, anti-diarrheal and insect repellent activities have been elucidated. Its toxicity profile is not yet investigated and thus this study was to investigate acute and sub-acute toxicity of E. kebericho decoctions. Acute toxicity study was performed in female Wistar albino rats with single oral dose and followed up to 14 days. The sub-acute oral dose toxicity studies were conducted in rats of both sexes in accordance with the repeated dose 28-day oral toxicity study in rodent OECD guidelines. Physical observations were made regularly during the study period while body weight was measured weekly. Organ weight, histopathology, clinical chemistry and hematology data were collected on the 29th day. Results were presented as mean ± standard deviation. One-way analysis of variance (ANOVA) was performed if assumptions were met; otherwise Kruskal-Wallis analysis was performed. Oral administration of E. kebericho decoction showed no treatment-related mortality in female rats up to the dose of 5000 mg/kg. In sub-acute toxicity studies, no significant treatment-related abnormalities were observed compared to negative controls. Food consumption, body weight, organ weight, hematology, clinical chemistry, and histopathology did not show significant variation between controls and treatment groups. However, creatinine, relative lung weight, triglycerides, and monocytes were lower in treated compared to control groups. Significant variations between male and female groups in food consumption, relative organ weight, hematology, clinical chemistry were observed. Histolo-pathology of high-dose treated groups showed fatty liver. Echinops kebericho showed LD50 of greater than 5000 mg/kg in acute toxicity study and is well tolerated up to the dose of 600 mg/kg body weight in sub-acute toxicity study.

    更新日期:2020-01-27
  • Xiao-ai-ping injection adjunct with platinum-based chemotherapy for advanced non-small-cell lung cancer: a systematic review and meta-analysis
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-13
    Fanchao Feng; Jingyi Huang; Zhichao Wang; Jiarui Zhang; Di Han; Qi Wu; Hailang He; Xianmei Zhou

    Xiao-ai-ping injection (XAPI), as patented Chinese medicine, has shown promising outcomes in non-small-cell lung cancer (NSCLC) patients. This meta-analysis investigated the efficacy and safety of XAPI in combination with platinum-based chemotherapy. A comprehensive literature search was conducted to identify relevant studies in Pubmed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure, Wangfang Database, VIP Database, and Chinese Biology Medical Database from the date of their inception to September 2018. The RevMan 5.3 software was applied to calculate the risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI). We included and analyzed 24 randomized controlled trials. The meta-analysis showed that XAPI adjunctive to platinum-based chemotherapy had better outcomes in objective tumor response rate (ORR) (RR: 1.27, 95% CI, 1.14–1.40); improved Karnofsky performance scores (KPS) (RR: 1.70, 95% CI, 1.48–1.95); reduction in occurrence of grade 3/4 leukopenia (RR: 0.49, 95% CI, 0.38–0.64), anemia (RR: 0.63, 95% CI, 0.46–0.87) and thrombocytopenia (RR: 0.53, 95% CI, 0.38–0.73), nausea and vomiting (RR: 0.57, 95% CI, 0.36–0.90); and enhanced immune function (CD8+ [MD: 4.96, 95% CI, 1.16–8.76] and CD4+/CD8+ [MD: 2.58, 95% CI, 1.69–3.47]). However, it did not increase dysregulated liver and kidney function, diarrhea, constipation, and fatigue. Subgroup analysis of ORR and KPS revealed that dosage, treatment duration, and methodological quality did not affect the outcome significantly. Our meta-analyses demonstrated that XAPI in combination with platinum-based chemotherapy had a better tumor response, improved the quality of life, attenuated adverse side effects, and enhanced immune function, which suggests that it might be used for advanced NSCLC. Moreover, low dosage (< 60 ml/d) and long-term treatment of XAPI might be a choice for advanced NSCLC patients.

    更新日期:2020-01-27
  • Parents’ experiences of information-seeking and decision-making regarding complementary medicine for children with autism spectrum disorder: a qualitative study
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-13
    Caroline A. Smith; Chloe Parton; Marlee King; Gisselle Gallego

    Complementary and alternative medicine and therapies (CAM) are widely used by parents of children with autism spectrum disorder (ASD). However, there is a gap in our understanding of how and why parents of children with ASD make decisions about CAM treatment, and how “evidence” influences their decision-making. The aim of this study was to explore views and perspectives on CAM decision-making among parents of children with ASD in Australia. Semi-structured interviews were conducted with parents of children with ASD (18 years and under) who were living in Australia. The interviews were digitally recorded, transcribed and then analysed using thematic analysis. Twenty-one parents were interviewed (20 women and one man). The mean age of participants was 43 years, (SD = 5.12 years), the majority of whom were born in Australia (71%), and almost half (43%) had a bachelor degree or higher. Three main themes were identifiedin the thematic analysis. First theme was ‘Parents’ experiences of researching CAM treatments, the second theme was, “Navigating CAM information and practices”, which comprises of the subthemes: Assessing information on CAM treatments’ What counts as ‘evidence’? and Assessing the impact of CAM treatments on the child - What counts as effective?, and the final theme was, “Creating a central and trustworthy source about CAM”. Across themes parents’ CAM decision-making was described as pragmatic, influenced by time, cost, and feasibility. Parents also reported that information on CAM was complex and often conflicting, and the creation of a centralised and reliable source of information on CAM was identified as a potential solution to these challenges. The development of evidence-based information resources for parents and supporting CAM health literacy may assist with navigating CAM decision-making for children’s with ASD.

    更新日期:2020-01-27
  • Antiproliferative and apoptotic effects of proteins from black seeds (Nigella sativa) on human breast MCF-7 cancer cell line
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-13
    Yamna Khurshid; Basir Syed; Shabana U. Simjee; Obaid Beg; Aftab Ahmed

    Nigella sativa (NS), a member of family Ranunculaceae is commonly known as black seed or kalonji. It has been well studied for its therapeutic role in various diseases, particularly cancer. Literature is full of bioactive compounds from NS seed. However, fewer studies have been reported on the pharmacological activity of proteins. The current study was designed to evaluate the anticancer property of NS seed proteins on the MCF-7 cell line. NS seed extract was prepared in phosphate-buffered saline (PBS), and proteins were precipitated using 80% ammonium sulfate. The crude seed proteins were partially purified using gel filtration chromatography, and peaks were resolved by SDS-PAGE. MTT assay was used to screen the crude proteins and peaks for their cytotoxic effects on MCF-7 cell line. Active Peaks (P1 and P4) were further studied for their role in modulating the expression of genes associated with apoptosis by real-time reverse transcription PCR. For protein identification, proteins were digested, separated, and analyzed with LC-MS/MS. Data analysis was performed using online Mascot, ExPASy ProtParam, and UniProt Knowledgebase (UniProtKB) gene ontology (GO) bioinformatics tools. Gel filtration chromatography separated seed proteins into seven peaks, and SDS-PAGE profile revealed the presence of multiple protein bands. Among all test samples, P1 and P4 depicted potent dose-dependent inhibitory effect on MCF-7 cells exhibiting IC50 values of 14.25 ± 0.84 and 8.05 ± 0.22 μg/ml, respectively. Gene expression analysis demonstrated apoptosis as a possible cell killing mechanism. A total of 11 and 24 proteins were identified in P1 and P4, respectively. The majority of the proteins identified are located in the cytosol, associate with biological metabolic processes, and their molecular functions are binding and catalysis. Hydropathicity values were mostly in the hydrophilic range. Our findings suggest NS seed proteins as a potential therapeutic agent for cancer. To our knowledge, it is the first study to report the anticancer property of NS seed proteins.

    更新日期:2020-01-27
  • Study on the mechanisms of compound Kushen injection for the treatment of gastric cancer based on network pharmacology
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-15
    Wei Zhou; Jiarui Wu; Yingli Zhu; Ziqi Meng; Xinkui Liu; Shuyu Liu; Mengwei Ni; Shanshan Jia; Jingyuan Zhang; Siyu Guo

    As an effective prescription for gastric cancer (GC), Compound Kushen Injection (CKI) has been widely used even though few molecular mechanism analyses have been carried out. In this study, we identified 16 active ingredients and 60 GC target proteins. Then, we established a compound-predicted target network and a GC target protein-protein interaction (PPI) network by Cytoscape 3.5.1 and systematically analyzed the potential targets of CKI for the treatment of GC. Finally, molecular docking was applied to verify the key targets. In addition, we analyzed the mechanism of action of the predicted targets by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The results showed that the potential targets, including CCND1, PIK3CA, AKT1, MAPK1, ERBB2, and MMP2, are the therapeutic targets of CKI for the treatment of GC. Functional enrichment analysis indicated that CKI has a therapeutic effect on GC by synergistically regulating some biological pathways, such as the cell cycle, pathways in cancer, the PI3K-AKT signaling pathway, the mTOR signaling pathway, and the FoxO signaling pathway. Moreover, molecular docking simulation indicated that the compounds had good binding activity to PIK3CA, AKT1, MAPK1, ERBB2, and MMP2 in vivo. This research partially highlighted the molecular mechanism of CKI for the treatment of GC, which has great potential in the identification of the effective compounds in CKI and biomarkers to treat GC.

    更新日期:2020-01-27
  • Comparison of the acute toxicity, analgesic and anti-inflammatory activities and chemical composition changes in Rhizoma anemones Raddeanae caused by vinegar processing
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-15
    Sha-Sha Wang; Shao-Yan Zhou; Xiao-Yan Xie; Ling Zhao; Yao Fu; Guang-Zhi Cai; Ji-Yu Gong

    As the dry rhizome of Anemone raddeana Regel, Rhizoma Anemones Raddeanae (RAR), which belongs to Ranunculaceae, is usually used to treat wind and cold symptoms, hand-foot disease and spasms, joint pain and ulcer pain in China. It is well known that the efficacy of RAR can be distinctly enhanced by processing with vinegar due to the reduced toxicity and side effects. However, the entry of vinegar into liver channels can cause a series of problems. In this paper, the differences in the acute toxicity, anti-inflammatory and analgesic effects between RAR and vinegar-processed RAR were compared in detail. The changes in the chemical compositions between RAR and vinegar-processed RAR were investigated, and the mechanism of vinegar processing was also explored. Acute toxicity experiments were used to examine the toxicity of vinegar-processed RAR. A series of studies, such as the writhing reaction, ear swelling experiment, complete Freund’s adjuvant-induced rat foot swelling experiment and cotton granuloma, in experimental mice was conducted to observe the anti-inflammatory effect of vinegar-processed RAR. The inflammatory cytokines of model rats were determined by enzyme-linked immunosorbent assay (ELISA). Liquid Chromatography-Quadrupole-Time of Flight mass spectrometer Detector (LC-Q-TOF) was used to analyse the chemical compositions of the RARs before and after vinegar processing. Neither obvious changes in mice nor death phenomena were observed as the amount of vinegar-processed RAR in crude drug was set at 2.1 g/kg. Vinegar-processed RAR could significantly prolong the latency, reduce the writhing reaction time to reduce the severity of ear swelling and foot swelling, and remarkably inhibit the secretion of Interleukin-1β(IL-1β), Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) proinflammatory cytokines. The content of twelve saponins (e.g., Eleutheroside K) in RAR was decreased after vinegar processing, but six other types (e.g., RDA) were increased. These results revealed that vinegar processing could not only improve the analgesic and anti-inflammatory effects of RAR but also reduce its own toxicity. Not applicable.

    更新日期:2020-01-27
  • Cytotoxycity and antiplasmodial activity of phenolic derivatives from Albizia zygia (DC.) J.F. Macbr. (Mimosaceae)
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-15
    Romeol Romain Koagne; Frederick Annang; Bastien Cautain; Jesús Martín; Guiomar Pérez-Moreno; Gabin Thierry M. Bitchagno; Dolores González-Pacanowska; Francisca Vicente; Ingrid Konga Simo; Fernando Reyes; Pierre Tane

    The proliferation and resistance of microorganisms area serious threat against humankind and the search for new therapeutics is needed. The present report describes the antiplasmodial and anticancer activities of samples isolated from the methanol extract of Albizia zygia (Mimosaseae). The plant extract was prepared by maceration in methanol. Standard chromatographic, HPLC and spectroscopic methods were used to isolate and identify six compounds (1–6). The acetylated derivatives (7–10) were prepared by modifying 2-O-β-D-glucopyranosyl-4-hydroxyphenylacetic acid and quercetin 3-O-α-L-rhamnopyranoside, previously isolated from A. zygia (Mimosaceae). A two-fold serial micro-dilution method was used to determine the IC50s against five tumor cell lines and Plasmodium falciparum. In general, compounds showed moderate activity against the human pancreatic carcinoma cell line MiaPaca-2 (10 < IC50 < 20 μM) and weak activity against other tumor cell lines such as lung (A-549), hepatocarcinoma (HepG2) and human breast adenocarcinoma (MCF-7and A2058) (IC50 > 20 μM). Additionally, the two semi-synthetic derivatives of quercetin 3-O-α-L-rhamnopyranoside exhibited significant activity against P. falciparum with IC50 of 7.47 ± 0.25 μM for compound 9 and 6.77 ± 0.25 μM for compound 10, higher than that of their natural precursor (IC50 25.1 ± 0.25 μM). The results of this study clearly suggest that, the appropriate introduction of acetyl groups into some flavonoids could lead to more useful derivatives for the development of an antiplasmodial agent.

    更新日期:2020-01-27
  • Toxicology studies of aqueous-alcohol extracts of Harpagophytum procumbens subsp. procumbens (Burch.) DC.Ex Meisn. (Pedaliaceae) in female and male rats
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-15
    Kirtan Joshi; Alan Parrish; Elizabeth A. Grunz-Borgmann; Mary Gerkovich; William R. Folk

    A variety of medicinal products prepared from secondary tubers of Harpagophytum procumbens subsp. procumbens (Burch.) DC.ex Meisn. (Devil’s Claw) and H. zeyheri are marketed in Africa, Europe, the United States, South America and elsewhere, where they are used for inflammatory and musculoskeletal conditions such as arthritis, lower back pain, rheumatism and neuralgia, etc. While clinical studies conducted over the last twenty years support the general safety of such products, infrequent gastrointestinal disturbances (diarrhea, nausea, vomiting, abdominal pain), headache, vertigo and hypersensitivity (allergic) reactions (rash, hives and face swelling) have been documented. Sex-related differences occur in the health conditions for which Devil’s Claw products are used, so it is likely that usage is similarly sex-related and so might be side effects and potential toxicities. However toxicologic studies of Devil’s Claw products have been conducted primarily with male animals. To address this deficit, we report toxicological studies in female and male rats of several H. procumbens (HP) aqueous-alcohol extracts chemically analyzed by UPLC-MS. Female and male Sprague Dawley rats were studied for one and three months in groups differing by consumption of diets without and with HP extracts at a 7–10-fold human equivalent dose (HED). Sera were analyzed for blood chemistry, and heart, liver, lung, kidney, stomach, and small and large intestine tissues were examined for histopathology. Treatment group differences for blood chemistry were analyzed by ANOVA with Dunnett’s test and significant group differences for endpoints with marginal distributional properties were verified using the Kruskal-Wallis test. Group differences for histopathology were tested using Chi Square analysis. Significant group by sex-related differences in blood chemistry were detected in both studies. Additionally, several sex-related differences occurred between the studies. However, significant histopathology effects associated with the consumption of the extracts were not detected. Toxicologic analysis of Devil’s Claw extracts cause significant sex-related effects in blood chemistry. However, in our judgement, none of the observed effects suggest serious toxicity at these doses and durations. Subsequent toxicologic and clinical studies of H. procumbens and other medicines with similar properties should explore in greater detail the basis and consequences of potential sex-related effects.

    更新日期:2020-01-27
  • Two-step foaming process combined with hot-rolling in fabrication of an aluminium foam sandwich panel
    Mater. Lett. (IF 3.019) Pub Date : 2020-01-27
    Xiaotong Lu; Hongjie Luo; Shijie Yang; You Wei; Jianrong Xu; Zhi Yao
    更新日期:2020-01-27
  • A Carburizing-quenching Jominy Curve Hardness Model
    Mater. Lett. (IF 3.019) Pub Date : 2020-01-27
    Wang Xin; Li Baokui

    An improved Jominy curve hardness model was built for carburizing-quenching process. In contrast to the other hardness model, it avoids the computational heterogeneity of phase transformation and has strong operability. Finally the model was applied to the carburized Jominy and gear specimens of 17CrNiMo6 steel. Namely, the corresponding experiment results were utilized to verify the simulation results. Hardness distribution between the measured and simulated results shows good agreement. Especially the simulation accuracy on the low Jominy distance and the hardened layer was better than that on other positions.

    更新日期:2020-01-27
  • Expert consensus on the development of a health-related questionnaire for the pediatric field of Korean medicine: a Delphi study
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-15
    Jihong Lee; Sun Haeng Lee; Gyu Tae Chang

    Although a variety of patient-reported outcome measures (PROMs) for children have been developed, there is no pediatric PROM specific to Korean medicine (KM) that is validated by experts in the field. The aim of this study was to collate the opinions of specialists in KM pediatrics on the development of a generic PROM that can be used by Korean medical doctors to assess the health status of children. A three-round Delphi survey was conducted to determine the level of consensus on the development of a new PROM. Delphi questionnaires were sent by e-mail to 91 KM pediatricians on January 24, 2018. The Delphi questionnaire was composed of four sections: conceptualization, construction, items, and sources of content for a PROM. A nine-point Likert scale was used, and if more than two-thirds of the panels agreed or disagreed with a given sentence, they were considered to have reached a consensus. A draft of a PROM for the pediatric field of KM was developed in accordance with the preliminary conceptual framework. Out of 91 experts, 18 finished three rounds of the Delphi survey. The experts reached a consensus on the necessity of a KM pediatric PROM for measuring various areas including child health, and using Likert scales with a recall period of 3 months. They also agreed on specific items and sources of content. A new draft of a health questionnaire for KM pediatrics was developed based on the Delphi consensus. It contains 44 items covering 7 domains: i) functions of the digestive system, ii) functions of the respiratory system, iii) mental functions, iv) skin functions, v) pain, vi) functions of the metabolic and endocrine systems, and vii) demographic details. This research represents the first step in developing a health questionnaire for the pediatric field of KM. The questionnaire can be used in clinical and research settings after verifying several types of validity and reliability.

    更新日期:2020-01-27
  • X-ray analysis and Rietveld refinement of polyvinyl alcohol
    Mater. Lett. (IF 3.019) Pub Date : 2020-01-27
    A. Lobo-Guerrero

    The Rietveld method has been used to refine the polyvinyl alcohol (PVA) structure. The PVA is a polymeric material exhibiting a semicrystalline “head-to-tail” arrangement of repeating units. Experimental X-ray pattern of PVA was adjusted considering a model based on monoclinic symmetry, but using the P21/m and P21/c spatial groups. The lattice parameters and atomic positions were adjusted in each case. The P21/c based model showed a better Rietveld adjust than the P21/m. Then, the P21/c model was used to analyze the structural behavior of the PVA subjected to different pH environments. From refinement results, the PVA subjected to acid environment remained unchanged and suffered a regalement of its crystalline structure when it is subjected to a basic pH, causing a loss of its permanence and crystallinity. The results provide a powerful model to evaluate the crystallinity degree of the PVA and its structural variations using the Rietveld refinement method.

    更新日期:2020-01-27
  • Ginsenoside Rb1 can ameliorate the key inflammatory cytokines TNF-α and IL-6 in a cancer cachexia mouse model
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-15
    Shuai Lu; Yubo Zhang; Huajun Li; Jing Zhang; Yingqian Ci; Mei Han

    Cancer cachexia is a severe condition that leads to the death of advanced cancer patients, and approximately 50~80% of cancer patients have cancer cachexia. Ginseng extract has been reported to have substantial anticancer and immune-enhancing effects; however, no study has reported the use of ginseng alone to treat cancer cachexia. Our study’s purpose was to investigate the therapeutic effects of ginseng-related monomers or mixtures on a cancer cachexia mouse model. We selected BALB/c mice and injected the mice subcutaneously with C26 colon cancer cells to construct a cancer cachexia experimental animal model. The water extract of ginseng (WEG), two types of ginseng extracts (ginsenosides at doses of 5 mg/kg (GE5) and 50 mg/kg (GE50)) and ginsenoside Rb1 (Rb1) were used to treat cancer cachexia mice. Enzyme-linked immunosorbent assays (ELISAs) were used to analyze the inhibitory effects on two key inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Our experimental results show that GE5, GE50 and Rb1 significantly reduced the levels of TNF-α (P < 0.01) and IL-6 (P < 0.01), which are closely related to cancer cachexia; however, WEG, GE5, GE50 and Rb1 did not significantly improve the gastrocnemius muscle weight or the epididymal fat weight of mice with cancer cachexia. These results indicate that GE5, GE50 and Rb1 may be useful for reducing symptoms due to inflammation by reducing the TNF-α and IL-6 cytokine levels in cancer cachexia mice, thereby ameliorating the symptoms of cancer cachexia. Our results may be beneficial for future studies on the use of Chinese herbal medicines to treat cancer cachexia.

    更新日期:2020-01-27
  • Therapeutic use of cannabis and cannabinoids: an evidence mapping and appraisal of systematic reviews
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-15
    Nadia Montero-Oleas; Ingrid Arevalo-Rodriguez; Solange Nuñez-González; Andrés Viteri-García; Daniel Simancas-Racines

    Although cannabis and cannabinoids are widely used with therapeutic purposes, their claimed efficacy is highly controversial. For this reason, medical cannabis use is a broad field of research that is rapidly expanding. Our objectives are to identify, characterize, appraise, and organize the current available evidence surrounding therapeutic use of cannabis and cannabinoids, using evidence maps. We searched PubMed, EMBASE, The Cochrane Library and CINAHL, to identify systematic reviews (SRs) published from their inception up to December 2017. Two authors assessed eligibility and extracted data independently. We assessed methodological quality of the included SRs using the AMSTAR tool. To illustrate the extent of use of medical cannabis, we organized the results according to identified PICO questions using bubble plots corresponding to different clinical scenarios. A total of 44 SRs published between 2001 and 2017 were included in this evidence mapping with data from 158 individual studies. We extracted 96 PICO questions in the following medical conditions: multiple sclerosis, movement disorders (e.g. Tourette Syndrome, Parkinson Disease), psychiatry conditions, Alzheimer disease, epilepsy, acute and chronic pain, cancer, neuropathic pain, symptoms related to cancer (e.g. emesis and anorexia related with chemotherapy), rheumatic disorders, HIV-related symptoms, glaucoma, and COPD. The evidence about these conditions is heterogeneous regarding the conclusions and the quality of the individual primary studies. The quality of the SRs was moderate to high according to AMSTAR scores. Evidence on medical uses of cannabis is broad. However, due to methodological limitations, conclusions were weak in most of the assessed comparisons. Evidence mapping methodology is useful to perform an overview of available research, since it is possible to systematically describe the extent and distribution of evidence, and to organize scattered data.

    更新日期:2020-01-27
  • Fabrication of superhydrophobicity on foamed concrete surface by GO/Silane coating
    Mater. Lett. (IF 3.019) Pub Date : 2020-01-27
    Geng Yongjuan; Li Shaochun; Hou Dongshuai; Zhang Weifeng; Jin Zuquan; Li Qiuyi; Luo Jianlin

    Foamed concrete is a lightweight building material, but its high water absorption is one of its main disadvantages. The objective of this study was to fabricate, characterize and evaluate a GO/Silane superhydrophobic coatings on foamed concrete surface. The results showed that the water contact angle of the foamed concrete was 165.5° and water can roll off from the surface easily. Superhydrophobic modification improves waterproof properties of the foamed concrete obviously, the water sorptivity was reduced about 97.2%. SEM results showed that the superhydrophobic surface was mainly due to the rough structure brought by GO and the low surface energy brought by silane.

    更新日期:2020-01-27
  • Hydrogen-bond induced nucleation and growth of β-poly(vinylidene fluoride)
    Mater. Lett. (IF 3.019) Pub Date : 2020-01-27
    Biao Li; Siyuan Dong; Yingqi Jia; Kaiqiang Shi; Yanjun Lin; Jingbin Han

    A series of polyvinylidene fluoride (PVDF)/layered double hydroxide (LDH) composite membranes were prepared via phase inversion method, in which the presence of LDH promotes the formation of β-phase PVDF. This work reveals the key role of hydrogen-bonds on the nucleation mechanism and crystallization behavior of PVDF. The composite membranes exhibit improved porosity and hydrophilicity, leading to an enhanced antifouling property against proteins.

    更新日期:2020-01-27
  • Buyang Huanwu Tang inhibits cellular epithelial-to-mesenchymal transition by inhibiting TGF-β1 activation of PI3K/Akt signaling pathway in pulmonary fibrosis model in vitro
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-15
    Zi-fei Yin; Yang-lin Wei; Xuan Wang; Li-na Wang; Xia Li

    Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease. Buyang Huanwu Tang (BYHWT), a classical traditional Chinese medicine formula, has been widely utilized for the treatment of PF in China. This present study aimed to explore the mechanism of BYHWT in the treatment of PF in vitro. TGF-β1 stimulated human alveolar epithelial A549 cells were used as in vitro model for PF. Post the treatment of BYHWT, cell viability was measured by MTT assay, and cell morphology was observed under microscope. The epithelial-to-mesenchymal transition (EMT) markers (E-cadherin, Vimentin) and collagen I (Col I) were detected by western blot, immunofluorescence staining and real-time quantitative polymerase chain reaction. With the co-administration of activators (IGF-1, SC79) and inhibitors (LY294002, MK2206), the effect of BYHWT on PI3K/Akt pathway was analyzed by western blot. BYHWT inhibited cell growth, and prevented cell morphology changed from epithelial to fibroblasts in TGF-β1 induced A549 cells. BYHWT decreased Vimentin and Col I, while increased E-cadherin at both protein and mRNA levels. Moreover, phosphorylation of PI3K (p-PI3K) and phosphorylation of Akt (p-Akt) were significantly down-regulated by BYHWT in TGF-β1 stimulated A549 cells. These results indicate that BYHWT suppressed TGF-β1-induced collagen accumulation and EMT of A549 cells by inhibiting the PI3K/Akt signaling pathway. These findings suggest that BYHWT may have potential for the treatment of PF.

    更新日期:2020-01-27
  • Laser-synthesized Ce3+ and Pr3+ doped Y2O3 nanoparticles and their characteristics
    Mater. Lett. (IF 3.019) Pub Date : 2020-01-27
    I. Krutikova; M. Ivanov; A. Murzakaev; K. Nefedova

    Ce3+:Y2O3, Pr3+:Y2O3, Ce3+:(LaxY1-x)2O3, Pr3+:(LaxY1-x)2O3 nanoparticles were fabricated by laser ablation. The nanopowders consisted of spherical particles with average size of 14÷17 nm. Ytterbium fiber laser operated in pulse mode at 5 kHz repetition rate and average radiation power of 255 W. The intensity of the laser radiation in focal spot was about 106 W/cm2 with close-to-Gaussian profile. The structural and morphological properties of the nanoparticles were investigated employing TEM, BET, FT-IR, XRD analysis.

    更新日期:2020-01-27
  • A Nanograins-attached and Ultrathin Cu Flake Powder Fabricated by High Energy Mechanical Milling and Dealloying
    Mater. Lett. (IF 3.019) Pub Date : 2020-01-27
    Chenguang Li; Mingwei Zhang; Mianmian Ruan; Jun Wang; Jiamiao Liang; Deliang Zhang

    Metal powders with hierarchical nanostructures are generally designed and fabricated by dealloying with or without assistance of other processes. However, they are mainly nanoporous metal powders and their derivatives which have limited applications, so metal powders with novel nanostructures should be explored further for various applications. Herein, high energy mechanical milling and dealloying were combined for fabricating metal powders with controllable nanostructures. As an example, a nanograins-attached and ultrathin Cu flake powder was fabricated by partial mechanical alloying of a Cu-42wt.%Al powder mixture and subsequent dealloying. The dealloyed Cu powder particles had ultrathin flaky shapes with numerous Cu nanograins being attached to their surfaces, and the microstructure of the as-milled Cu-42wt.%Al powder particles and the dealloyed Cu particles were studied to elucidate the formation mechanism of the unique morphology of the dealloyed Cu powder.

    更新日期:2020-01-27
  • The use of Euphorbia hirta L. (Euphorbiaceae) in diarrhea and constipation involves calcium antagonism and cholinergic mechanisms
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-16
    Muhammad Zeeshan Ali; Malik Hassan Mehmood; Muhammad Saleem; Anwarul-Hassan Gilani

    Euphorbia hirta (Linn) family Euphorbiaceae has been used in indigenous system of medicine for the treatment of gastrointestinal disorders. This study was designed to determine the pharmacological basis for the medicinal use of E. hirta in diarrhea and constipation. The aqueous-methanol extract of whole herb of E. hirta (EH.Cr) and its petroleum ether (Pet.EH), chloroform (CHCl3.EH), ethyl acetate (Et.Ac.EH) and aqueous (Aq.EH) fractions were tested in the in-vivo experiments using Balb/c mice, while the in-vitro studies were performed on isolated jejunum and ileum preparations of locally bred rabbit and Sprague Dawley rats, respectively, using PowerLab data system. Qualitative phytochemical analysis showed the presence of alkaloids, saponins, flavonoids, tannins, phenols, cardiac glycosides, while HPLC of EH.Cr showed quercetin in high proportion. In mice, EH.Cr at the dose of 500 and 1000 mg/kg showed 41 and 70% protection from castor oil-induced diarrhea, respectively, similar to the effect of quercetin and loperamide, while at lower doses (50 and 100 mg/kg), it caused an increase in the fecal output. In loperamide-induced constipated mice, EH.Cr also displayed laxative effect with respective values of 28.6 and 35.3% at 50 and 100 mg/kg. In rabbit jejunum, EH.Cr showed atropine-sensitive inhibitory effect in a concentration-dependent manner, while quercetin and nifedipine exhibited atropine-insensitive effects. Fractions of E. hirta also produced atropine-sensitive inhibitory effects except Pet.EH and CHCl3.EH. On high (80 mM) and low (20 mM) K+ − induced contractions, the crude extract and fractions exhibited a concentration-dependent non-specific inhibition of both spasmogens and displaced concentration-response curves of Ca++ to the right with suppression of the maximum effect similar to the effect quercetin and nifedipine. Fractions showed wide distribution of spasmolytic and Ca++ antagonist like effects. In rat ileum, EH.Cr and its fractions exhibited atropine-sensitive gut stimulant effects except Pet.EH. The crude extract of E. hirta possesses antidiarrheal effect possibly mediated through Ca++ antagonist like gut inhibitory constituents, while its laxative effect was mediated primarily through muscarinic receptor agonist like gut stimulant constituents. Thus, these findings provide an evidence to the folkloric use of E. hirta in diarrhea and constipation.

    更新日期:2020-01-27
  • 更新日期:2020-01-27
  • The effects of add-on self-care education on quality of life and fatigue in gastrointestinal cancer patients undergoing chemotherapy
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-16
    Jun Xie; Tingli Zhu; Qun Lu; Xiaomin Xu; Yinghua Cai; Zhenghong Xu

    Gastrointestinal cancer is one of the most common malignancies and imposes heavy burdens on both individual health and social economy. We sought to survey the effect of a self-care education program on quality of life and fatigue in gastrointestinal cancer patients who received chemotherapy. Ninety-one eligible gastrointestinal cancer patients were enrolled in this study and 86 valid samples were analyzed. Data were acquired with a demographics questionnaire, endpoint multidimensional questionnaire and the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire QLQ-C30. The collected data were analyzed using SPSS software. The self-care education intervention significantly improved the quality of life with respect to emotional function (p = 0.018), role function (p = 0.041), cognitive function (p = 0.038) and alleviated side effects such as nausea/vomiting (p = 0.028) and fatigue (p = 0.029). Further analysis demonstrated that the self-care education benefited total fatigue, affective fatigue and cognitive fatigue in gastrointestinal cancer patients regardless of baseline depression. Our results suggested the beneficial effects of the self-care education in both quality of life and anti-fatigue in gastrointestinal cancer patients under chemotherapy. The self-care education could be considered as a complementary approach during combination chemotherapy in gastrointestinal cancer patients.

    更新日期:2020-01-27
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