bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolomic Profiling of Portal Blood and Bile Reveals Metabolic Signatures of Primary Sclerosing Cholangitis
Authors: Tietz-Bogert Pamela S. , Kim Minsuk , Cheung Angela , Tabibian James H. , Heimbach Julie K. , Rosen Charles B. , Nandakumar Madhumitha , Lazaridis Konstantinos N. , LaRusso Nicholas F. , Sung Jaeyun , O’Hara Steven P.
Published: October 2018

Primary sclerosing cholangitis (PSC) is a pathogenically complex, chronic, fibroinflammatory disorder of the bile ducts without known etiology or effective pharmacotherapy. Emerging in vitro and in vivo evidence support fundamental pathophysiologic mechanisms in PSC centered on enterohepatic circulation. To date, no studies have specifically interrogated the chemical footprint of enterohepatic circulation in PSC. Herein, we evaluated the metabolome and lipidome of portal venous blood and bile obtained at the time of liver transplantation in patients with PSC (n = 7) as compared to individuals with noncholestatic, end-stage liver disease (viral, metabolic, etc. (disease control, DC, n = 19)) and to nondisease controls (NC, living donors, n = 12). Global metabolomic and lipidomic profiling was performed on serum derived from portal venous blood (portal serum) and bile using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and differential mobility spectroscopy-mass spectroscopy (DMS-MS; complex lipid platform). The Mann–Whitney U test was used to identify metabolites that significantly differed between groups. Principal-component analysis (PCA) showed significant separation of both PSC and DC from NC for both portal serum and bile. Metabolite set enrichment analysis of portal serum and bile demonstrated that the liver-disease cohorts (PSC and DC) exhibited similar enrichment in several metabolite categories compared to NC. Interestingly, the bile in PSC was uniquely enriched for dipeptide and polyamine metabolites. Finally, analysis of patient-matched portal serum and biliary metabolome revealed that these biological fluids were more homogeneous in PSC than in DC or NC, suggesting aberrant bile formation and enterohepatic circulation. In summary, PSC and DC patients exhibited alterations in several metabolites in portal serum and bile, while PSC patients exhibited a unique bile metabolome. These specific alterations in PSC are amenable to hypothesis testing and, potentially, therapeutic pharmacologic manipulation.
Downregulation of C-Terminal Tensin-Like Protein (CTEN) Suppresses Prostate Cell Proliferation and Contributes to Acinar Morphogenesis
Authors: Wu Wei-Ming , Liao Yi-Chun
Published: October 2018

C-terminal tensin-like protein (CTEN) is a member of tensin family, which is crucial for the assembly of cell-matrix adhesome. Unlike other tensins, CTEN is selectively expressed only in a few tissues such as the prostate. However, the biological relevance of CTEN in normal prostate is poorly understood. In this study, we revealed that CTEN is selectively expressed in the prostate epithelial cells and enriched in the basal compartment. Knockdown of CTEN in RWPE-1 cells suppresses cell proliferation and results in G1/S cell cycle arrest as well as the accumulation of cyclin-dependent kinase (CDK) inhibitors, p21 and p27. Moreover, the expression of CTEN is decreased during acinar morphogenesis using Matrigel-based three-dimensional (3D) culture. In the course of acinar formation, induction of CTEN reactivates focal adhesion kinase (FAK) Y397 phosphorylation and disrupts the acini structure. This study, to our knowledge, is the first report demonstrating that downregulation of CTEN is required for luminal differentiation and acinar formation.
Thrombospondin-1 Is Necessary for the Development and Repair of Corneal Nerves
Authors: Tatematsu Yukako , Khan Qalbi , Blanco Tomas , Bair Jeffrey A. , Hodges Robin R. , Masli Sharmila , Dartt Darlene A.
Published: October 2018

Thrombospondin-1-deficient (TSP-1−/−) mice are used as an animal model of Sjögren’s Syndrome because they exhibit many of the symptoms associated with the autoimmune type of dry eye found in primary Sjögren’s Syndrome. This type of dry eye is linked to the inflammation of the lacrimal gland, conjunctiva, and cornea, and is thought to involve dysfunction of the complex neuronal reflex arc that mediates tear production in response to noxious stimuli on the ocular surface. This study characterizes the structural and functional changes to the corneal nerves that are the afferent arm of this arc in young and older TSP-1−/− and wild type (WT) mice. The structure and subtype of nerves were characterized by immunohistochemistry, in vivo confocal microscopy, and confocal microscopy. Cytokine expression analysis was determined by Q-PCR and the number of monocytes was measured by immunohistochemistry. We found that only the pro-inflammatory cytokine MIP-2 increased in young corneas of TSP-1−/− compared to WT mice, but tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2) all increased in older TSP-1−/− mouse corneas. In contrast, CD11b+ pro-inflammatory monocytes did not increase even in older mouse corneas. Calcitonin gene-related peptide (CGRP)-, but not Substance P (SubP)-containing corneal nerves decreased in older, but not younger TSP-1−/− compared to WT mouse corneas. We conclude that CGRP-containing corneal sensory nerves exhibit distinct structural deficiencies as disease progresses in TSP-1−/− mice, suggesting that: (1) TSP-1 is needed for the development or repair of these nerves and (2) impaired afferent corneal nerve structure and hence function may contribute to ocular surface dysfunction that develops as TSP-1−/− mice age.
Zinc Chloride Exposure Inhibits Brain Acetylcholine Levels, Produces Neurotoxic Signatures, and Diminishes Memory and Motor Activities in Adult Zebrafish
Authors: Sarasamma Sreeja , Audira Gilbert , Juniardi Stevhen , Sampurna Bonifasius Putera , Liang Sung-Tzu , Hao Erwei , Lai Yu-Heng , Hsiao Chung-Der
Published: October 2018

In this study, we evaluated the acute (24, 48, 72, and 96 h) and chronic (21 days) adverse effects induced by low doses (0.1, 0.5, 1, and 1.5 mg/L) of zinc chloride (ZnCl2) exposure in adult zebrafish by using behavioral endpoints like three-dimensional (3D) locomotion, passive avoidance, aggression, circadian rhythm, and predator avoidance tests. Also, brain tissues were dissected and subjected to analysis of multiple parameters related to oxidative stress, antioxidant responses, superoxide dismutase (SOD), neurotoxicity, and neurotransmitters. The results showed that ZnCl2-exposed fishes displayed decreased locomotor behavior and impaired short-term memory, which caused an Alzheimer’s Disease (AD)-like syndrome. In addition, low concentrations of ZnCl2 induced amyloid beta (amyloid β) and phosphorylated Tau (p-Tau) protein levels in brains. In addition, significant induction in oxidative stress indices (reactive oxygen species (ROS) and malondialdehyde (MDA)), reduction in antioxidant defense system (glutathione (GSH), GSH peroxidase (GSH-Px) and SOD) and changes in neurotransmitters were observed at low concentrations of ZnCl2. Neurotoxic effects of ZnCl2 were observed with significant inhibition of acetylcholine (ACh) activity when the exposure dose was higher than 1 ppm. Furthermore, we found that zinc, metallothionein (MT), and cortisol levels in brain were elevated compared to the control group. A significantly negative correlation was observed between memory and acetylcholinesterase (AChE) activity. In summary, these findings revealed that exposure to ZnCl2 affected the behavior profile of zebrafish, and induced neurotoxicity which may be associated with damaged brain areas related to memory. Moreover, our ZnCl2-induced zebrafish model may have potential for AD-associated research in the future.
Low-Dose Radiotherapy Has No Harmful Effects on Key Cells of Healthy Non-Inflamed Joints
Authors: Deloch Lisa , Rückert Michael , Fietkau Rainer , Frey Benjamin , Gaipl Udo S.
Published: October 2018

Low-dose radiotherapy (LD-RT) for benign inflammatory and/or bone destructive diseases has been used long. Therefore, mechanistic investigations on cells being present in joints are mostly made in an inflammatory setting. This raises the question whether similar effects of LD-RT are also seen in healthy tissue and thus might cause possible harmful effects. We performed examinations on the functionality and phenotype of key cells within the joint, namely on fibroblast-like synoviocytes (FLS), osteoclasts and osteoblasts, as well as on immune cells. Low doses of ionizing radiation showed only a minor impact on cytokine release by healthy FLS as well as on molecules involved in cartilage and bone destruction and had no significant impact on cell death and migration properties. The bone resorbing abilities of healthy osteoclasts was slightly reduced following LD-RT and a positive impact on bone formation of healthy osteoblasts was observed after in particular exposure to 0.5 Gray (Gy). Cell death rates of bone-marrow cells were only marginally increased and immune cell composition of the bone marrow showed a slight shift from CD8+ to CD4+ T cell subsets. Taken together, our results indicate that LD-RT with particularly a single dose of 0.5 Gy has no harmful effects on cells of healthy joints.
Targeting Oncogenic Signaling in Mutant FLT3 Acute Myeloid Leukemia: The Path to Least Resistance
Authors: Staudt Dilana , Murray Heather C. , McLachlan Tabitha , Alvaro Frank , Enjeti Anoop K. , Verrills Nicole M. , Dun Matthew D.
Published: October 2018

The identification of recurrent driver mutations in genes encoding tyrosine kinases has resulted in the development of molecularly-targeted treatment strategies designed to improve outcomes for patients diagnosed with acute myeloid leukemia (AML). The receptor tyrosine kinase FLT3 is the most commonly mutated gene in AML, with internal tandem duplications within the juxtamembrane domain (FLT3-ITD) or missense mutations in the tyrosine kinase domain (FLT3-TKD) present in 30–35% of AML patients at diagnosis. An established driver mutation and marker of poor prognosis, the FLT3 tyrosine kinase has emerged as an attractive therapeutic target, and thus, encouraged the development of FLT3 tyrosine kinase inhibitors (TKIs). However, the therapeutic benefit of FLT3 inhibition, particularly as a monotherapy, frequently results in the development of treatment resistance and disease relapse. Commonly, FLT3 inhibitor resistance occurs by the emergence of secondary lesions in the FLT3 gene, particularly in the second tyrosine kinase domain (TKD) at residue Asp835 (D835) to form a ‘dual mutation’ (ITD-D835). Individual FLT3-ITD and FLT3-TKD mutations influence independent signaling cascades; however, little is known about which divergent signaling pathways are controlled by each of the FLT3 specific mutations, particularly in the context of patients harboring dual ITD-D835 mutations. This review provides a comprehensive analysis of the known discrete and cooperative signaling pathways deregulated by each of the FLT3 specific mutations, as well as the therapeutic approaches that hold the most promise of more durable and personalized therapeutic approaches to improve treatments of FLT3 mutant AML.
Pharmacoepigenomic Interventions as Novel Potential Treatments for Alzheimer’s and Parkinson’s Diseases
Authors: Teijido Oscar , Cacabelos Ramón
Published: October 2018

Cerebrovascular and neurodegenerative disorders affect one billion people around the world and result from a combination of genomic, epigenomic, metabolic, and environmental factors. Diagnosis at late stages of disease progression, limited knowledge of gene biomarkers and molecular mechanisms of the pathology, and conventional compounds based on symptomatic rather than mechanistic features, determine the lack of success of current treatments, including current FDA-approved conventional drugs. The epigenetic approach opens new avenues for the detection of early presymptomatic pathological events that would allow the implementation of novel strategies in order to stop or delay the pathological process. The reversibility and potential restoring of epigenetic aberrations along with their potential use as targets for pharmacological and dietary interventions sited the use of epidrugs as potential novel candidates for successful treatments of multifactorial disorders involving neurodegeneration. This manuscript includes a description of the most relevant epigenetic mechanisms involved in the most prevalent neurodegenerative disorders worldwide, as well as the main potential epigenetic-based compounds under investigation for treatment of those disorders and their limitations.
Oviposition Preferences and Behavior of Wild-Caught and Laboratory-Reared Coconut Rhinoceros Beetle, Oryctes rhinoceros (Coleoptera: Scarabaeidae), in Relation to Substrate Particle Size
Authors: Manley Megan , Melzer Michael J. , Spafford Helen
Published: October 2018

The coconut rhinoceros beetle (CRB), Oryctes rhinoceros (L.) (Coleoptera: Scarabaeidae), has become one of the most important coconut and oil palm pests. This species was detected attacking coconut palms on Oʻahu, Hawaiʻi in December 2013, and an eradication program was initiated. One of the major challenges for eradication has been the identification of new breeding sites. Information on the factors influencing oviposition is needed to aid in finding sites likely to host the immature stages of this insect. In this study, a series of choice tests were conducted to assess the oviposition preferences of both laboratory-reared and wild-caught CRB. Mated females, of both lab-reared and wild-caught beetles, were offered for oviposition a choice between sand and two mulch substrates, one with small and one with large particle sizes. Both types of CRB laid eggs preferentially in substrate of small particle size rather than large and none laid eggs in sand. Lab-reared and wild-caught CRB differed in their oviposition behavior and size. These results can be used to aid in the identification of breeding sites for management programs and eradication efforts.
Market-Based Conservation for Better Livelihoods? The Promises and Fallacies of REDD+ in Tanzania
Authors: Scheba Andreas
Published: October 2018

Governments, multilateral organisations, and international conservation NGOs increasingly frame nature conservation in terms that emphasise the importance of technically managing and economically valuing nature, and introducing markets for ecosystem services. New mechanisms, such as REDD+, have been incorporated in national-level policy reforms, and have been piloted and implemented in rural project settings across the Global South. By reflecting on my research on REDD+ implementation in two case study villages in Tanzania, the paper argues that the emergence and nature of market-based conservation are multi-faceted, complex, and more profoundly shaped by structural challenges than is commonly acknowledged. The paper identifies three particularly important challenges: the politics surrounding the establishment of community-based forest management; the mismatch between formal governance institutions and actual practices on the ground; and the fickleness of income from carbon sales and alternative livelihood opportunities. I argue that these challenges are not merely teething troubles, but they question fundamental assumptions of market-based conservation, more generally. I end with reference to better ideas for achieving sustainable development.
Constitutive Model Prediction and Flow Behavior Considering Strain Response in the Thermal Processing for the TA15 Titanium Alloy
Authors: Li Jiang , Li Fuguo , Cai Jun
Published: October 2018

To investigate the flow stress, microstructure, and usability of TA15 titanium alloy, isothermal compression was tested at 1073–1223 K and strain rates of 10, 1, 0.1, 0.01, and 0.001 s−1, and strain of 0.9. The impact of strain and temperature on thermal deformation was investigated through the exponent-type Zener–Hollomon equation. Based on the influence of various material constants (including α, n, Q, and lnA) on the TA15 titanium alloy, the strain effect was included in the constitutive equation considering strain compensation, which is presented in this paper. The validity of the proposed constitutive equation was verified through the correlation coefficient (R) and the average absolute relative error (AARE), the values of which were 0.9929% and 6.85%, respectively. Research results demonstrated that the strain-based constitutive equation realizes consistency between the calculated flow stress and the measured stress of TA15 titanium alloy at high temperatures.
Bound (“Glassy”) Rubber as a Free Radical Cross-linked Rubber Layer on a Carbon Black
Authors: Kondyurin Alexey V. , Eliseeva Anastasia Yu. , Svistkov Alexander L.
Published: October 2018

A model of rubber with a cross-linked rubber layer on a carbon black filler has been proposed. The cross-links are the result of free radical reactions generated by carbon atoms with unpaired electrons at the edge of graphitic sheets in a carbon black filler. The experimental study of the cross-linking reactions in polyisoprene was done on a flat carbonized surface after ion beam implantation. The cross-linking process in the polyisoprene macromolecules between two particles was simulated. The model with a cross-linked rubber layer on a carbon filler as a “glassy layer” explains the mechanical properties of the rubber materials.
Pyrolysis and Combustion of Polyvinyl Chloride (PVC) Sheath for New and Aged Cables via Thermogravimetric Analysis-Fourier Transform Infrared (TG-FTIR) and Calorimeter
Authors: Wang Zhi , Wei Ruichao , Wang Xuehui , He Junjiang , Wang Jian
Published: October 2018

To fill the shortages in the knowledge of the pyrolysis and combustion properties of new and aged polyvinyl chloride (PVC) sheaths, several experiments were performed by thermogravimetric analysis (TG), Fourier transform infrared (FTIR), microscale combustion calorimetry (MCC), and cone calorimetry. The results show that the onset temperature of pyrolysis for an aged sheath shifts to higher temperatures. The value of the main derivative thermogravimetric analysis (DTG) peak of an aged sheath is greater than that of a new one. The mass of the final remaining residue for an aged sheath is also greater than that of a new one. The gas that is released by an aged sheath is later but faster than that of a new one. The results also show that, when compared with a new sheath, the heat release rate (HRR) is lower for an aged one. The total heat release (THR) of aged sheath is reduced by 16.9–18.5% compared to a new one. In addition, the cone calorimetry experiments illustrate that the ignition occurrence of an aged sheath is later than that of a new one under different incident heat fluxes. This work indicates that an aged sheath generally pyrolyzes and it combusts more weakly and incompletely.
Application of Approximate Analytical Technique Using the Homotopy Perturbation Method to Study the Inclination Effect on the Thermal Behavior of Porous Fin Heat Sink
Authors: Oguntala George , Sobamowo Gbeminiyi , Ahmed Yinusa , Abd-Alhameed Raed
Published: October 2018

This article presents the homotopy perturbation method (HPM) employed to investigate the effects of inclination on the thermal behavior of a porous fin heat sink. The study aims to review the thermal characterization of heat sink with the inclined porous fin of rectangular geometry. The study establishes that heat sink of an inclined porous fin shows a higher thermal performance compared to a heat sink of equal dimension with a vertical porous fin. In addition, the study also shows that the performance of inclined or tilted fin increases with decrease in length–thickness aspect ratio. The study further reveals that increase in the internal heat generation variable decreases the fin temperature gradient, which invariably decreases the heat transfer of the fin. The obtained results using HPM highlights the accuracy of the present method for the analysis of nonlinear heat transfer problems, as it agrees well with the established results of Runge–Kutta.
Association between the Vicious Cycle of Diabetes-Associated Complications and Glycemic Control among the Elderly: A Systematic Review
Authors: Atif Muhammad , Saleem Quratulain , Babar Zaheer-Ud-Din , Scahill Shane
Published: October 2018

Background and objectives: Improved quality of life (QoL) and life expectancy of elderly diabetic patients revolves around optimal glycemic control. Inadequate glycemic control may lead to the development of diabetes-associated complications (DAC), which not only complicate the disease, but also affect morbidity and mortality. Based on the available literature, the aim was to elucidate the vicious cycle underpinning the relationship between diabetes complications and glycemic control. Materials and Methods: A comprehensive literature search was performed to find eligible studies published between 1 January 2000 and 22 September 2018 pertaining to diabetes complications and glycemic control. Results: Initially, 261 studies were retrieved. Out of these, 67 were duplicates and therefore were excluded. From the 194 remaining articles, 85 were removed based on irrelevant titles and/or abstracts. Subsequently, the texts of 109 articles were read in full and 71 studies were removed at this stage for failing to provide relevant information. Finally, 38 articles were selected for this review. Depression, impaired cognition, poor physical functioning, frailty, malnutrition, chronic pain, and poor self-care behavior were identified as the major diabetes-associated complications that were associated with poor glycemic control in elderly diabetic patients. Conclusions: This paper proposes that diabetes-associated complications are interrelated, and that impaired glycemic control aggravates diabetes complications; as a result, patient’s self-care abilities are compromised. A schema is generated to reflect a synthesis of the literature found through the systematic review process. This not only affects patients’ therapeutic goals, but may also hamper their health-related quality of life (HRQoL) and financial status.
Surface Modification of Q195 Structure Carbon Steel by Electrolytic Plasma Processing
Authors: Cheng Fang , Gui Wanyuan , Lin Junpin
Published: October 2018

In this study, we applied an emerging, environmentally friendly surface engineering technology, electrolytic plasma processing (EPP), for the surface modification of Q195 structure carbon steel surface pretreatment and further Zn coating. Treating the surfaces of Q195 structure carbon steel by EPP was a quite dynamic process, which was investigated using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD). The results shown that surface scale can be effectively remove after 40 s EPP treatment, and the EPP-treated Q195 structure carbon steel revealed a slight decrease in elastic modulus and hardness, but a substantial improvement in tensile (especially plastic) mechanical properties. Moreover, the further EPP modification conducted on the pretreated Q195 structure carbon steel sample for production of a layer of compact zinc coating with 15 μm thickness under an optimization EPP process. We also identified the modification mechanism of EPP to Q195 structure carbon steel, which may provide theoretical and practical guidance for future researchers and developers.
The Effect of High-Intensity Ultraviolet Light to Elicit Microalgal Cell Lysis and Enhance Lipid Extraction
Authors: Sydney Thomas , Marshall-Thompson Jo-Ann , Kapoore Rahul Vijay , Vaidyanathan Seetharaman , Pandhal Jagroop , Fairclough J. Patrick A.
Published: October 2018

Currently, the energy required to produce biofuel from algae is 1.38 times the energy available from the fuel. Current methods do not deliver scalable, commercially viable cell wall disruption, which creates a bottleneck on downstream processing. This is primarily due to the methods depositing energy within the water as opposed to within the algae. This study investigates ultraviolet B (UVB) as a disruption method for the green algae Chlamydomonas reinhardtii, Dunaliella salina and Micractinium inermum to enhance solvent lipid extraction. After 232 seconds of UVB exposure at 1.5 W/cm2, cultures of C. reinhardtii (culture density 0.7 mg/mL) showed 90% disruption, measured using cell counting, correlating to an energy consumption of 5.6 MJ/L algae. Small-scale laboratory tests on C. reinhardtii showed bead beating achieving 45.3 mg/L fatty acid methyl esters (FAME) and UV irradiation achieving 79.9 mg/L (lipids solvent extracted and converted to FAME for measurement). The alga M. inermum required a larger dosage of UVB due to its thicker cell wall, achieving a FAME yield of 226 mg/L, compared with 208 mg/L for bead beating. This indicates that UV disruption had a higher efficiency when used for solvent lipid extraction. This study serves as a proof of concept for UV irradiation as a method for algal cell disruption.
Carbonaceous Materials in the Longmenshan Fault Belt Zone: 3. Records of Seismic Slip from the Trench and Implications for Faulting Mechanisms
Authors: Si Jialiang , Li Haibing , Kuo Li-Wei , Huang Jyh-Rou , Song Sheng-Rong , Pei Junling , Wang Huan , Song Lei , Fang Jiann-Neng , Sheu Hwo-Shuenn
Published: October 2018

In recent studies on the recognition of graphitized gouges within the principal slip zone (PSZ) of the Longmenshan fault in China, we proposed that the presence of graphite might be evidence of fault slip. Here, we characterized the clay- and carbonaceous-rich gouges of the active fault zone of the Longmenshan fault belt using samples collected from the trench at Jiulong, which was deformed during the 2008 MW-7.9 Wenchuan earthquake, to determine if graphite is present and study both the processes influencing fault behavior and the associated faulting mechanism. Mineralogical and geochemical analyses of the Jiulong trench sample show the presence of a hydrothermal mineral (i.e., dickite) integrated with dramatic relative chemical enrichment and relative depletion within a yellowish zone, suggesting the presence of vigorous high-temperature fluid–rock interactions, which are likely the fingerprint of thermal pressurization. This is further supported by the absence of carbonaceous materials (CMs) given the spectrometric data obtained. Interestingly, the Raman parameters measured near the carbonaceous-rich gouge fall within the recognized range of graphitization in the mature fault zone, implying the origin of a mature fault, as shown in the companion paper. According to both the sharp boundary within the very recent coseismic rupture zone of the 2008 MW-7.9 Wenchuan earthquake and the presence of kinetically unstable dickite, it is strongly implied that the yellow/altered gouge likely formed from a recent coseismic event as aconsequence of hydrothermal fluid penetration. We further surmise that the CM characteristics varied according to several driving reactions, e.g., transient hydrothermal heating versus long-term geological metamorphism and sedimentation.
Strong Tetrel Bonds: Theoretical Aspects and Experimental Evidence
Authors: Esrafili Mehdi D. , Mousavian Parisasadat
Published: October 2018

In recent years, noncovalent interactions involving group-14 elements of the periodic table acting as a Lewis acid center (or tetrel-bonding interactions) have attracted considerable attention due to their potential applications in supramolecular chemistry, material science and so on. The aim of the present study is to characterize the geometry, strength and bonding properties of strong tetrel-bond interactions in some charge-assisted tetrel-bonded complexes. Ab initio calculations are performed, and the results are supported by the quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) approaches. The interaction energies of the anionic tetrel-bonded complexes formed between XF3M molecule (X=F, CN; M=Si, Ge and Sn) and A− anions (A−=F−, Cl−, Br−, CN−, NC− and N3−) vary between −16.35 and −96.30 kcal/mol. The M atom in these complexes is generally characterized by pentavalency, i.e., is hypervalent. Moreover, the QTAIM analysis confirms that the anionic tetrel-bonding interaction in these systems could be classified as a strong interaction with some covalent character. On the other hand, it is found that the tetrel-bond interactions in cationic tetrel-bonded [p-NH3(C6H4)MH3]+···Z and [p-NH3(C6F4)MH3]+···Z complexes (M=Si, Ge, Sn and Z=NH3, NH2CH3, NH2OH and NH2NH2) are characterized by a strong orbital interaction between the filled lone-pair orbital of the Lewis base and empty BD*M-C orbital of the Lewis base. The substitution of the F atoms in the benzene ring provides a strong orbital interaction, and hence improved tetrel-bond interaction. For all charge-assisted tetrel-bonded complexes, it is seen that the formation of tetrel-bond interaction is accompanied bysignificant electron density redistribution over the interacting subunits. Finally, we provide some experimental evidence for the existence of such charge-assisted tetrel-bond interactions in crystalline phase.
A New Environmentally-Friendly Colorimetric Probe for Formaldehyde Gas Detection under Real Conditions
Authors: Martínez-Aquino Carlos , Costero Ana M. , Gil Salvador , Gaviña Pablo
Published: October 2018

A new environmentally-friendly, simple, selective and sensitive probe for detecting formaldehyde, based on naturally-occurring compounds, through either colorimetric or fluorescence changes, is described. The probe is able to detect formaldehyde in both solution and the gas phase with limits of detection of 0.24 mM and 0.7 ppm, respectively. The probe has been tested to study formaldehyde emission in contaminated real atmospheres. The supported probe is easy to use and to dispose, and is safe and suitable as an individual chemodosimeter.
Thermal Degradation Characteristic and Flame Retardancy of Polylactide-Based Nanobiocomposites
Authors: Malkappa Kuruma , Bandyopadhyay Jayita , Ray Suprakas Sinha
Published: October 2018

Polylactide (PLA) is one of the most widely used organic bio-degradable polymers. However, it has poor flame retardancy characteristics. To address this disadvantage, we performed melt-blending of PLA with intumescent flame retardants (IFRs; melamine phosphate and pentaerythritol) in the presence of organically modified montmorillonite (OMMT), which resulted in nanobiocomposites with excellent intumescent char formation and improved flame retardant characteristics. Triphenyl benzyl phosphonium (OMMT-1)- and tributyl hexadecyl phosphonium (OMMT-2)-modified MMTs were used in this study. Thermogravimetric analysis in combination with Fourier transform infrared spectroscopy showed that these nanocomposites release a smaller amount of toxic gases during thermal degradation than unmodified PLA. Melt-rheological behaviors supported the conclusions drawn from the cone calorimeter data and char structure of the various nanobiocomposites. Moreover, the characteristic of the surfactant used for the modification of MMT played a crucial role in controlling the fire properties of the composites. For example, the nanocomposite containing 5 wt.% OMMT-1 showed significantly improved fire properties with a 47% and 68% decrease in peak heat and total heat release rates, respectively, as compared with those of unmodified PLA. In summary, melt-blending of PLA, IFR, and OMMT has potential in the development of high-performance PLA-based sustainable materials.
Enrichment and Purification of the Bioactive Flavonoids from Flower of Abelmoschus manihot (L.) Medic Using Macroporous Resins
Authors: Yang Zhenzhong , Tang Haitao , Shao Qing , Bilia Anna Rita , Wang Yi , Zhao Xiaoping
Published: October 2018

Flower of Abelmoschus manihot (FAM) is clinically effective to treat chronic kidney disease (CKD) with a relatively high dosage. To improve the efficacy and the compliance of patients, macroporous resins were adopted to enrich and purify flavonoids from FAM, which are thought to be the major renal protective constituents in FAM. After screening six different kinds of macroporous resins, HPD-100 was selected for its great adsorption and desorption capacity. Then, orthogonal design tests were used to optimize parameters in the processes of impurity removal and flavonoids of FAM desorption on column chromatogram. Moreover, process scale-up was performed, and purification effects maintained after amplification. After purification, the content of seven main flavonoids in the product increased from 8.29% to 51.43%. Protective and anti-inflammatory effects of crude extract and the flavonoid component of FAM after purification were investigated on the adriamycin-damaged HK-2 cells and lipopolysaccharide-stimulated Raw 264.7 cells models. Both bioactivities were improved greatly after purification for these two cell models. Therefore, the purification process had enriched the main bioactive constituents with potential alleviating kidney injury activities. The flavonoid component of FAM is worthy of being developed as an improved remedy for CKD with better patients’ compliance.
Application of HPCCC Combined with Polymeric Resins and HPLC for the Separation of Cyclic Lipopeptides Muscotoxins A–C and Their Antimicrobial Activity
Authors: Cheel José , Hájek Jan , Kuzma Marek , Saurav Kumar , Smýkalová Iva , Ondráčková Eliška , Urajová Petra , Vu Dai Long , Faure Karine , Kopecký Jiří , Hrouzek Pavel
Published: October 2018

Muscotoxins are cyanobacterial cyclic lipopeptides with potential applications in biomedicine and biotechnology. In this study, Desmonostoc muscorum CCALA125 strain extracts were enriched by polymeric resin treatment, and subjected to HPCCC affording three cyclic lipopeptides (1–3), which were further repurified by semi-preparative HPLC, affording 1, 2, and 3, with a purity of 86%, 92%, and 90%, respectively. The chemical identities of 2–3 were determined as muscotoxins A and B, respectively, by comparison with previously reported ESI-HRMS/MS data, whereas 1 was determined as a novel muscotoxin variant (muscotoxin C) using NMR and ESI-HRMS/MS data. Owing to the high yield (50 mg), compound 2 was broadly screened for its antimicrobial potential exhibiting a strong antifungal activity against Alternaria alternata, Monographella cucumerina, and Aspergillus fumigatus, with minimum inhibitory concentration (MIC) values of 0.58, 2.34, and 2.34 µg/mL; respectively, and weak antibacterial activity against Bacillus subtilis with a MIC value of 37.5 µg/mL. Compounds 1 and 3 were tested only against the plant pathogenic fungus Sclerotinia sclerotiorum due to their low yield, displaying a moderate antifungal activity. The developed chromatographic method proved to be an efficient tool for obtaining muscotoxins with potent antifungal properties.
Novel 5′-Norcarbocyclic Derivatives of Bicyclic Pyrrolo- and Furano[2,3-d]Pyrimidine Nucleosides
Authors: Klimenko Anna A. , Matyugina Elena S. , Logashenko Evgeniya B. , Solyev Pavel N. , Zenkova Marina A. , Kochetkov Sergey N. , Khandazhinskaya Anastasia L.
Published: October 2018

Here we report the synthesis and biological activity of new 5′-norcarbocyclic derivatives of bicyclic pyrrolo- and furano[2,3-d]pyrimidines with different substituents in the heterocyclic ring. Lead compound 3i, containing 6-pentylphenyl substituent, displays inhibitory activity with respect to a number of tumor cells with a moderate selectivity index value. Compound 3i induces cell death by the apoptosis pathway with the dissipation of mitochondrial potential.
1,4-β-d-Glucomannan from Dendrobium officinale Activates NF-кB via TLR4 to Regulate the Immune Response
Authors: Huang Yan-Ping , He Tao-Bin , Cuan Xian-Dan , Wang Xuan-Jun , Hu Jiang-Miao , Sheng Jun
Published: October 2018

2,3-O-acetylated-1,4-β-d-glucomannan (DOP-1-1) is a polysaccharide isolated from the stem of Dendrobium officinale. DOP-1-1 has been demonstrated to have remarkable immunomodulatory properties, but little is known about the influence of its structural diversity on bioactivity (and even less about the exact mechanism underlying its immune responses). First, DOP-1-1 was stabilized at different temperatures and pH conditions based on differential scanning calorimetry and size exclusion-chromatography–high-performance liquid chromatography. Then, a detailed study on the effects of DOP-1-1 on a human leukemia monocytic cell line (THP-1) under normal conditions was undertaken. DOP-1-1 promoted the translocation of nuclear factor-kappa B (NF-κB) and degradation of IκB proteins. The expression of genes and proteins closely associated with the immune, survival and apoptotic functions of NF-κB were analyzed by quantitative real-time RT-PCR. Furthermore, CCL4 and IP10 were confirmed to be the novel targets of the immune response stimulated by DOP-1-1. The phosphorylation of NF-кB was inhibited by treatment with a toll-like receptor 4 (TLR4) antagonist (TAK-242) and myeloid differentiation factor 88 (MyD88) inhibitor (ST2825). These data suggested: (i) the O-acetylated glucomannan DOP-1-1 is present in the steady state in low-pH solutions; (ii) DOP-1-1 can induce an immune response through NF-кB mediated by a TLR4 signaling pathway; and (iii) CCL4 and IP10 could be the novel targets of the immune response stimulated by O-acetylated glucomannan.
Biochemical Characterization of the Rice Cinnamyl Alcohol Dehydrogenase Gene Family
Authors: Park Hye Lin , Kim Tae Lim , Bhoo Seong Hee , Lee Tae Hoon , Lee Sang-Won , Cho Man-Ho
Published: October 2018

Cinnamyl alcohol dehydrogenase (CAD) is involved in the final step of the phenylpropanod pathway, catalyzing the NADPH-dependent reduction of hydroxy-cinnamaldehydes into the corresponding alcohols. The rice genome contains twelve CAD and CAD-like genes, collectively called OsCADs. To elucidate the biochemical function of the OsCADs, OsCAD1, 2, 6, and 7, which are highly expressed in rice, were cloned from rice tissues. The cloned OsCADs were heterologously expressed in Escherichia coli as His-tag fusion proteins. The activity assay of the recombinant OsCADs showed that OsCAD2, 6, and 7 have CAD activity toward hydroxycinnamaldehydes, but OsCAD1 has no detectable catalytic activity. The kinetic parameters of the enzyme reactions demonstrated that OsCAD2 has the highest catalytic activity among the examined enzymes. This result agrees well with the finding that the Zn binding and NADPH binding motifs and the residues constituting the substrate binding pocket in bona fide plant CADs were fully conserved in OsCAD2. Although they have large variations in the residue for the substrate binding pocket, OsCAD6 and 7 catalyzed the reduction of hydroxycinnamaldehydes with a similar efficiency. Alignment of amino acid sequences showed that OsCAD1 lacks the GxxxxP motif for NADPH binding and has mismatches in residues important in the reduction process, which could be responsible for the loss of catalytic activity. OsCAD2 belongs to CAD Class I with bona fide CADs from other plant species and is constitutively expressed throughout the developmental stages of rice, with preferential expression in actively lignifying tissues such as the root, stem, and panicle, suggesting that it is mainly involved in developmental lignification in rice. The expression of OsCAD2 was also induced by biotic and abiotic stresses such as Xanthomonas oryzae pv. oryzae (Xoo) infection and UV-irradiation, suggesting that it plays a role in the defense response of rice, in addition to a bona fide role in developmental lignification. OsCAD6 and 7 belong in CAD Class II. Their expression is relatively lower than that of OsCAD2 and is confined to certain tissues, such as the leaf sheath, stem, and panicle. The expression of OsCAD6 was stimulated by Xoo infection and UV-irradiation. Thus OsCAD6 appears to be an inducible OsCAD that is likely involved in the defense response of rice against biotic and abiotic stresses.
Design, Synthesis of N-phenethyl Cinnamide Derivatives and Their Biological Activities for the Treatment of Alzheimer’s Disease: Antioxidant, Beta-amyloid Disaggregating and Rescue Effects on Memory Loss
Authors: Chai Tian , Zhao Xiao-Bo , Wang Wei-Feng , Qiang Yin , Zhang Xiao-Yun , Yang Jun-Li
Published: October 2018

Gx-50 is a bioactive compound for the treatment of Alzheimer’s disease (AD) found in Sichuan pepper (Zanthoxylum bungeanum). In order to find a stronger anti-AD lead compound, 20 gx-50 (1–20) analogs have been designed and synthesized, and their molecular structures were determined based on nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis, as well as comparison with literature data. Compounds 1–20 were evaluated for their anti-AD potential by using DPPH radical scavenging assay for considering their anti-oxidant activity, thioflavin T (ThT) fluorescence assay for considering the inhibitory or disaggregate potency of Aβ, and transgenic Drosophila model assay for evaluating their rescue effect on memory loss. Finally, compound 13 was determined as a promising anti-AD candidate.
Effect of Consumption of Cocoa-Derived Products on Uric Acid Crystallization in Urine of Healthy Volunteers
Authors: Costa-Bauza Antonia , Grases Felix , Calvó Paula , Rodriguez Adrian , Prieto Rafael M.
Published: October 2018

The purpose of this study was to determine the effects of consumption of different cocoa-derived products on uric acid crystallization in urine of 20 healthy volunteers. Participants were requested to select the specific diet that they wished to follow during the 12 h prior to collection of urine. The only restriction was that the diet could not include any product with cocoa, coffee, or caffeine. On the first day, each volunteer followed their selected diet, and an overnight 12 h urine sample was collected as the baseline urine. After seven days on an unrestricted diet, each volunteer repeated the same diet with 20 g of milk chocolate, chocolate powder, or dark chocolate during breakfast and another 20 g during dinner. Overnight 12 h urine samples were then collected. Urine volume, pH, oxalate, creatinine, uric acid, theobromine, and a uric acid crystallization test were determined for each sample. The results for all 20 patients show that uric acid crystallization was significantly lower following the consumption of chocolate powder or dark chocolate relative to baseline or following the consumption of milk chocolate. The results indicated that increased concentrations of urinary theobromine reduced the risk of uric acid crystallization.
Evidence for Transient Receptor Potential (TRP) Channel Contribution to Arthritis Pain and Pathogenesis
Authors: Galindo Tabitha , Reyna Jose , Weyer Andy
Published: October 2018

Based on clinical and preclinical evidence, Transient Receptor Potential (TRP) channels have emerged as potential drug targets for the treatment of osteoarthritis, rheumatoid arthritis, and gout. This review summarizes the relevant data supporting a role for various TRP channels in arthritis pain and pathogenesis, as well as the current state of pharmacological efforts to ameliorate arthritis symptoms in patient populations.
The Role of Pharmacists in General Practice in Asthma Management: A Pilot Study
Authors: Deeks Louise S. , Kosari Sam , Boom Katja , Peterson Gregory M. , Maina Aaron , Sharma Ravi , Naunton Mark
Published: October 2018

Background: Asthma is principally managed in general practice. Appropriate prescribing and medication use are essential, so general practice pharmacists appear suitable to conduct asthma management consultations. This pilot study aimed to evaluate the asthma management role of a pharmacist in general practice. Methods: Analysis of an activity diary and stakeholder interviews were conducted to identify interventions in asthma management; determine whether asthma control changed following pharmacist input; and determine acceptability of asthma management review by a pharmacist in one general practice in Canberra, Australia. Results: Over 13 months, the pharmacist saw 136 individual patients. The most common activities were asthma control assessment; recommendations to adjust medication or device; counselling on correct device use; asthma action plan development and trigger avoidance. For patients with multiple consultations, the mean Asthma Control Test score improved from the initial to last visit (14.4 ± 5.2 vs. 19.3 ± 4.7, n = 23, p < 0.0001). Eight of the 19 (42%) patients moved from having poor to well-controlled asthma. Case studies and qualitative data indicated probable hospital admission avoidance and stakeholder acceptability of asthma management by a practice pharmacist. Conclusions: This pilot study demonstrated it is feasible, acceptable and potentially beneficial to have a general practice pharmacist involved in asthma management. Fuller evaluation is warranted.
ESR Dating Ungulate Teeth and Molluscs from the Paleolithic Site Marathousa 1, Megalopolis Basin, Greece
Authors: Blackwell Bonnie A. B. , Sakhrani Neeraj , Singh Impreet K. , Gopalkrishna Kalyani K. , Tourloukis Vangelis , Panagopoulou Eleni , Karkanas Panagiotis , Blickstein Joel I. B. , Skinner Anne R. , Florentin Jonathan A. , Harvati Katerina
Published: October 2018

At 37°24′ N 22°8′ E, the Megalopolis Basin lies in the central Peloponnese Peninsula, southwestern Greece. In the Megalopolis Basin at ~350 m amsl, the Paleolithic site, Marathousa 1, sits within a palustrine/lacustrine clastic package between Lignite Seams III and II, that both likely correlate with interglacial periods. At Marathousa 1, immediately below Lignite Seam III, lies a clayey-silty sand layer with a horizon rich in molluscs ranging from ~20–40 cm thick. About 0.8–1.3 m below the shell-rich horizon (SRH), lacustrine silty to muddy sands rich in organic matter yielded Paleolithic lithic artefacts associated with Middle Pleistocene fauna, some with cut marks and possible bone knapping, found within palustrine/lacustrine clastic deposits. Since ESR (electron spin resonance) can date teeth and molluscs aged >2 Ma, two bivalve samples, AM66 and AM65, five subsamples from a cervid molar, AT39, and one subsample from another cervid molar, AT68, were independently dated by ESR from Marathousa 1. To calculate the ages, time-averaged cosmic and time- and volumetrically-averaged sedimentary dose rates were calculated using past water depths and sedimentation rates as determined from paleontological and geological criteria. Found in the SRH in Layer UA2, AM66 and AM65 averaged 488 ± 37 ka, which correlates with MIS 13a. Because the bivalves sat stratigraphically above the artefacts and mammalian fossils, their ages constrain the ESR ages for the teeth deposited below. Lying on the unconformity at the base of Layer UA3c with UA4, and its correlative unconformity at the Layer UB4c/UB5 boundary, sat the dated teeth from large mammals. Because the bones in the Palaeoloxodon antiquus skeleton lay in quasi-anatomical association, the likelihood for fossil reworking on the Layer UB3c/UB4 surface is low. Isochron analysis suggests that using a U uptake model with p = 2 provides the most accurate ages for AT39. With p = 2, AT39 dates to 503 ± 13 ka, while AT68 dates to 512 ± 34 ka. Nonetheless, two to three more teeth and molluscs should be dated to confirm these ages, when more samples suitable for ESR dating are found. Both tooth ages correlate well with early MIS 13, an interglacial period with cooler mean global temperatures compared to MIS 11 or 9. Assuming that the archaeological site formed in one event, rather than as a palimpsest, the data suggest that hominins processed elephant and other faunal carcasses along the shores of a shallow lake or marsh in the Megalopolis Basin at 503 ± 12 ka. Between the two horizons dated here, their sedimentation rate averaged 4.8 ± 1.8 to 7.8 ± 2.9 cm/ka.