bluuebunny/crossref_metadata_2025 huggingface dataset:
CRANAD-28: A Robust Fluorescent Compound for Visualization of Amyloid Beta Plaques
Authors: Ran Kathleen , Yang Jing , Nair Anil V. , Zhu Biyue , Ran Chongzhao
Published: February 2020

CRANAD-28, a difluoroboron curcumin analogue, has been demonstrated in earlier reports to successfully label amyloid beta (Aβ) plaques for imaging both ex vivo and in vivo. CRANAD-28’s imaging brightness, ability to penetrate the blood brain barrier, and low toxicity make the compound a potentially potent imaging tool in Alzheimer’s research. In this study, the Aβ-labeling ability of CRANAD-28 was investigated in further detail using histological staining to assess different criteria, including stained Aβ plaque brightness, Aβ plaque size, and Aβ plaque number count. The results of this study demonstrated CRANAD-28 to be superior across all criteria assessed. Furthermore, CRANAD-28 and IBA-1 antibody were used to label Aβ-plaques and microglia respectively. Statistical analysis with Spearman regression revealed a statistically significant negative correlation between the size of labeled Aβ plaques and surrounding microglia density. This finding provides interesting insight into Aβ plaque and microglia dynamism in AD pathology and corroborates the findings of previous studies. In addition, we found that CRANAD-28 provided distinct spectral signatures for Aβs in the core and periphery of the plaques. Based on the study’s results, CRANAD-28 could be considered as an alternative standard for imaging Aβ-plaques in future research studies.
Functional MgO–Lignin Hybrids and Their Application as Fillers for Polypropylene Composites
Authors: Grząbka-Zasadzińska Aleksandra , Klapiszewski Łukasz , Jesionowski Teofil , Borysiak Sławomir
Published: February 2020

Inorganic–organic hybrids are a group of materials that have recently become the subject of intense scientific research. They exhibit some of the specific properties of both highly durable inorganic materials (e.g., titanium dioxide, zinc) and organic products with divergent physicochemical traits (e.g., lignin, chitin). This combination results in improved physicochemical, thermal or mechanical properties. Hybrids with defined characteristics can be used as fillers for polymer composites. In this study, three types of filler with different MgO/lignin ratio were used as fillers for polypropylene (PP). The effectiveness of MgO-lignin binding was confirmed using Fourier transform infrared spectroscopy. The fillers were also tested in terms of thermal stability, dispersive-morphological properties as well as porous structure. Polymer composites containing 3 wt.% of each filler were subjected to wide angle X-ray diffraction tests, differential scanning calorimetry and microscopic studies to define their structure, morphology and thermal properties. Additionally, tensile tests of the composites were performed. It was established that the composition of the filler has a significant influence on the crystallization of polypropylene—either spherulites or transcrystalline layers were formed. The value of Young’s modulus and tensile strength remained unaffected by filler type. However, composites with hybrid fillers exhibited lower elongation at break than unfilled polypropylene.
The Appearance of 4-Hydroxy-2-Nonenal (HNE) in Squamous Cell Carcinoma of the Oropharynx
Authors: Jakovčević Antonia , Žarković Kamelija , Jakovčević Danica , Rakušić Zoran , Prgomet Drago , Waeg Georg , Šunjić Suzana Borović , Žarković Neven
Published: February 2020

Tumor growth is associated with oxidative stress, which causes lipid peroxidation. The most intensively studied product of lipid peroxidation is 4-hydroxy-2-nonenal (HNE), which is considered as a “second messenger of free radicals” that binds to proteins and acts as a growth-regulating signaling factor. The incidence of squamous cell carcinoma of the oropharynx is associated with smoking, alcohol and infection of human papilloma virus (HPV), with increasing incidence world-wide. The aim of this retrospective study involving 102 patients was to determine the immunohistochemical appearance of HNE-protein adducts as a potential biomarker of lipid peroxidation in squamous cell carcinoma of the oropharynx. The HNE-protein adducts were detected in almost all tumor samples and in the surrounding non-tumorous tissue, while we found that HNE is differentially distributed in squamous cell carcinomas in dependence of clinical stage and histological grading of these tumors. Namely, the level of HNE-immunopositivity was increased in comparison to the normal oropharyngeal epithelium in well- and in moderately-differentiated squamous cell carcinoma, while it was decreasing in poorly differentiated carcinomas and in advanced stages of cancer. However, more malignant and advanced cancer was associated with the increase of HNE in surrounding, normal tissue. This study confirmed the onset of lipid peroxidation, generating HNE-protein adducts that can be used as a valuable bioactive marker of carcinogenesis in squamous cell carcinoma of the oropharynx, as well as indicating involvement of HNE in pathophysiological changes of the non-malignant tissue in the vicinity of cancer.
Synthesis and In Vitro Anticancer Evaluation of Novel Chrysin and 7-Aminochrysin Derivatives
Authors: Mayer Szabolcs , Keglevich Péter , Ábrányi-Balogh Péter , Szigetvári Áron , Dékány Miklós , Szántay Csaba , Hazai László
Published: February 2020

Chrysin is a naturally occurring flavonoid with mild anticancer activity. In this paper we report the synthesis of new chrysin derivatives alkylated with N-phenylchloroacetamides in position 7. A novel method was developed for the preparation of 7-aminochrysin derivatives via the Smiles rearrangement, resulting in diphenylamine-type compounds. In silico studies of the Smiles rearrangement were performed. We also present the in vitro antiproliferative activity of the synthesized compounds against 60 human tumor cell lines (NCI60). The most potent derivative exhibited nanomolar antitumor activity on the MCF7 cell line of breast cancer (GI50 = 30 nM) and on the HCT-15 cell line of colon cancer (GI50 = 60 nM).
Silk Particle Production Based on Silk/PVA Phase Separation Using a Microfabricated Co-flow Device
Authors: Vargas Montoya Natalia , Peterson Rachel , Ornell Kimberly J. , Albrecht Dirk R. , Coburn Jeannine M.
Published: February 2020

Polymeric particles are ideal drug delivery systems due to their cellular uptake-relevant size. Microparticles could be developed for direct injection of drug formulations into a diseased site, such as a tumor, allowing for drug retention and slow drug exposure over time through sustained release mechanisms. Bombyx mori silk fibroin has shown promise as a biocompatible biomaterial both in research and the clinic. Silk has been previously used to make particles using an emulsion-based method with poly(vinyl alcohol) (PVA). In this study, polydimethylsiloxane-based microfluidic devices were designed, fabricated, and characterized to produce silk particles through self-association of silk when exposed to PVA. Three main variables resulted in differences in particle size and size distribution, or polydispersity index (PDI). Utilizing a co-flow microfluidic device decreased the PDI of the silk particles as compared to an emulsion-based method (0.13 versus 0.65, respectively). With a flow-focusing microfluidics device, lowering the silk flow rate from 0.80 to 0.06 mL/h resulted in a decrease in the median particle size from 6.8 to 3.0 μm and the PDI from 0.12 to 0.05, respectively. Lastly, decreasing the silk concentration from 12% to 2% resulted in a decrease in the median particle size from 5.6 to 2.8 μm and the PDI from 0.81 to 0.25, respectively. Binding and release of doxorubicin, a cytotoxic drug commonly used for cancer treatment, with the fabricated silk particles was evaluated. Doxorubicin loading in the silk particles was approximately 41 µg/mg; sustained doxorubicin release occurred over 23 days. When the cytotoxicity of the released doxorubicin was tested on KELLY neuroblastoma cells, significant cell death was observed. To demonstrate the potential for internalization of the silk particles, both KELLY and THP-1-derived macrophages were exposed to fluorescently labelled silk particles for up to 24 h. With the macrophages, internalization of the silk particles was observed. Additionally, THP-1 derived macrophages exposure to silk particles increased TNF-α secretion. Overall, this microfluidics-based approach for fabricating silk particles utilizing PVA as a means to induce phase separation and silk self-assembly is a promising approach to control particle size and size distribution. These silk particles may be utilized for a variety of biomedical applications including drug delivery to multiple cell types within a tumor microenvironment.
NH2-MIL-53(Al) Polymer Monolithic Column for In-Tube Solid-Phase Microextraction Combined with UHPLC-MS/MS for Detection of Trace Sulfonamides in Food Samples
Authors: Zhang Qian-Chun , Xia Guang-Ping , Liang Jun-Yi , Zhang Xiao-Lan , Jiang Li , Zheng Yu-Guo , Wang Xing-Yi
Published: February 2020

In this study, a novel monolithic capillary column based on a NH2-MIL-53(Al) metal–organic framework (MOF) incorporated in poly (3-acrylamidophenylboronic acid/methacrylic acid-co-ethylene glycol dimethacrylate) (poly (AAPBA/MAA-co-EGDMA)) was prepared using an in situ polymerization method. The characteristics of the MOF-polymer monolithic column were investigated by scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, X-ray diffractometry, Brunauer-Emmett-Teller analysis, and thermogravimetric analysis. The prepared MOF-polymer monolithic column showed good permeability, high extraction efficiency, chemical stability, and good reproducibility. The MOF-polymer monolithic column was used for in-tube solid-phase microextraction (SPME) to efficiently adsorb trace sulfonamides from food samples. A novel method combining MOF-polymer-monolithic-column-based SPME with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was successfully developed. The linear range was from 0.015 to 25.0 µg/L, with low limits of detection of 1.3–4.7 ng/L and relative standard deviations (RSDs) of < 6.1%. Eight trace sulfonamides in fish and chicken samples were determined, with recoveries of the eight analytes ranging from 85.7% to 113% and acceptable RSDs of < 7.3%. These results demonstrate that the novel MOF-polymer-monolithic-column-based SPME coupled with UHPLC-MS/MS is a highly sensitive, practical, and convenient method for monitoring trace sulfonamides in food samples previously extracted with an adequate solvent.
New Hybrid Pyrazole and Imidazopyrazole Antinflammatory Agents Able to Reduce ROS Production in Different Biological Targets
Authors: Brullo Chiara , Massa Matteo , Rapetti Federica , Alfei Silvana , Bertolotto Maria B. , Montecucco Fabrizio , Signorello Maria Grazia , Bruno Olga
Published: February 2020

Several anti-inflammatory agents based on pyrazole and imidazopyrazole scaffolds and a large library of substituted catechol PDE4D inhibitors were reported by us in the recent past. To obtain new molecules potentially able to act on different targets involved in inflammation onset we designed and synthesized a series of hybrid compounds by linking pyrazole and imidazo-pyrazole scaffolds to differently decorated catechol moieties through an acylhydrazone chain. Some compounds showed antioxidant activity, inhibiting reactive oxygen species (ROS) elevation in neutrophils, and a good inhibition of phosphodiesterases type 4D and, particularly, type 4B, the isoform most involved in inflammation. In addition, most compounds inhibited ROS production also in platelets, confirming their ability to exert an antiinflammatory response by two independent mechanism. Structure–activity relationship (SAR) analyses evidenced that both heterocyclic scaffolds (pyrazole and imidazopyrazole) and the substituted catechol moiety were determinant for the pharmacodynamic properties, even if hybrid molecules bearing to the pyrazole series were more active than the imidazopyrazole ones. In addition, the pivotal role of the catechol substituents has been analyzed. In conclusion the hybridization approach gave a new serie of multitarget antiinflammatory compounds, characterized by a strong antioxidant activity in different biological targets.
Moscatilin Induces Apoptosis in Human Head and Neck Squamous Cell Carcinoma Cells via JNK Signaling Pathway
Authors: Lee Eunji , Han Ah-Reum , Nam Bomi , Kim Ye-Ram , Jin Chang Hyun , Kim Jin-Baek , Eun Young-Gyu , Jung Chan-Hun
Published: February 2020

Dendrobii Herba is an herbal medicine that uses the stems of Dendrobium species (Orchidacea). It has been traditionally used to treat fever, hydrodipsomania, stomach disorders, and amyotrophia. In our previous study, a bibenzyl compound, moscatilin, which is isolated from Dendrobii Herba, showed potent cytotoxicity against a FaDu human pharyngeal squamous carcinoma cell line. Prompted by this finding, we performed additional studies in FaDu cells to investigate the mechanism of action. Moscatilin induced FaDu cell death by using 5 μM of concentration and by mediating apoptosis, whereas cell proliferation following treatment with 1 μM of moscatilin was not suppressed to the same levels as by the anti-cancer agent, cisplatin. Apoptosis-related protein expression (cleaved caspase-8, cleaved caspase-7, cytochrome c, cleaved caspase-9, cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP) was increased by treating with 5 μM of moscatilin. This suggests that moscatilin-mediated apoptosis is associated with the extrinsic and intrinsic apoptotic signaling pathways. In addition, moscatilin-induced apoptosis was mediated by the c-Jun N-terminal kinase (JNK) signaling pathway. Overall, this study identified additional biological activity of moscatilin derived from natural products and suggested its potential application as a chemotherapeutic agent for the management of head and neck squamous cell carcinoma.
Supramolecular Sandwiches: Halogen-Bonded Coformers Direct [2+2] Photoreactivity in Two-Component Cocrystals
Authors: Quentin Jay , C. Swenson Dale , R. MacGillivray Leonard
Published: February 2020

The halogen-bond (X-bond) donors 1,3- and 1,4-diiodotetrafluorobenzene (1,3-di-I-tFb and 1,4-di-I-tFb, respectively) form cocrystals with trans-1,2-bis(2-pyridyl)ethylene (2,2′-bpe) assembled by N···I X-bonds. In each cocrystal, 2(1,3-di-I-tFb)·2(2,2′-bpe) and (1,4-di-I-tFb)·(2,2′-bpe), the donor molecules support the C=C bonds of 2,2′-bpe to undergo an intermolecular [2+2] photodimerization. UV irradiation of each cocrystal resulted in stereospecific and quantitative conversion of 2,2′-bpe to rctt-tetrakis(2-pyridyl)cyclobutane (2,2′-tpcb). In each case, the reactivity occurs via face-to-face π-stacked columns wherein nearest-neighbor pairs of 2,2′-bpe molecules lie sandwiched between X-bond donor molecules. Nearest-neighbor C=C bonds are stacked criss-crossed in both cocrystals. The reactivity was ascribed to the olefins undergoing pedal-like motion in the solid state. The stereochemistry of 2,2′-tpcb is confirmed in cocrystals 2(1,3-di-I-tFb)·(2,2′-tpcb) and (1,4-di-I-tFb)·(2,2′-tpcb).
Regioselective Monobromination of Phenols with KBr and ZnAl–BrO3−–Layered Double Hydroxides
Authors: Wang Ligeng , Feng Chun , Zhang Yan , Hu Jun
Published: February 2020

The regioselective mono-bromination of phenols has been successfully developed with KBr and ZnAl–BrO3−–layered double hydroxides (abbreviated as ZnAl–BrO3−–LDHs) as brominating reagents. The para site is much favorable and the ortho site takes the priority if para site is occupied. This reaction featured with excellent regioselectivity, cheap brominating reagents, mild reaction condition, high atom economy, broad substrate scope, and provided an efficient method to synthesize bromophenols.
The High Permeability of Nanocarriers Crossing the Enterocyte Layer by Regulation of the Surface Zonal Pattern
Authors: Chang Ya-Nan , Liang Yuelan , Xia Shibo , Bai Xue , Zhang Jiaxin , Kong Jianglong , Chen Kui , Li Juan , Xing Gengmei
Published: February 2020

The intestinal epithelium is a major barrier that limits the absorption of oral drugs. The integrity of the epithelial tissue is a very important factor for preventing intestinal diseases. However, destabilization of the epithelium can promote the transportation of nanocarriers and increase the absorption of oral drugs. In our research, three different gold nanoparticles (GNPs) of the same size but with differing negative surface charge were designed and constructed as a model to determine the surface properties crucial for promoting absorptivity and bioavailability of the nanocarriers. The higher the ratio of surface carboxyl groups on GNPs, the higher capacity to induce transepithelial electrical resistance change and cell monolayer tight junction opening with higher permeability. The half carboxyl and half methyl surfaced GNPs displayed unique zonal surface patterns exhibited the greater ability to pass through intestinal epithelial cell layer but had a relatively small influence on tight junction distribution.
A Synthetic Curcuminoid Analog, (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone, Ameliorates Impaired Wound Healing in Streptozotocin-Induced Diabetic Mice by Increasing miR-146a
Authors: Huang Jingjuan , Fu Jia , Liu Bing , Wang Rui , You Tianhui
Published: February 2020

The impairment in diabetic wound healing represents a significant clinical problem, with no efficient targeted treatments for these wound disorders. Curcumin is well confirmed to improve diabetic wound healing, however, its low bioavailability and poor solubility severely limit its clinical application. This study aims to provide the pharmacological basis for the use of (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone (C66). The results showed that topically applied C66 improved cutaneous wound healing in vivo. Further studies showed that C66 treatment increased the level of microRNA-146a (miR-146a) in the wounds in streptozotocin (STZ)-induced diabetic mice, downregulated the expression of interleukin-1 receptor-associated kinase 1 (IRAK1) and phosphorylated nuclear factor-κB (NF-κB) p65 subunit (p-p65) (both p < 0.05), and suppressed the mRNA expression of inflammation-related cytokines, tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6). The in vitro data obtained in human umbilical vein endothelial cells (HUVECs) showed that C66 could reverse high glucose (HG)-induced NF-κB activation due to upregulation of miR-146a expression, which matched the in vivo findings. In conclusion, the present study indicates that C66 exerts anti-inflammation activity and accelerates skin wound healing of diabetic mice, probably via increasing miR-146a and inhibiting the NF-κB-mediated inflammation pathway. Therefore, C66 may be a promising alternative for the treatment of diabetic wounds.
Validation of an HPLC Method for the Simultaneous Quantification of Metabolic Reaction Products Catalysed by CYP2E1 Enzyme Activity: Inhibitory Effect of Cytochrome P450 Enzyme CYP2E1 by Salicylic Acid in Rat Liver Microsomes
Authors: Salhab Hassan , Naughton Declan P. , Barker James
Published: February 2020

Inhibition of cytochrome P450 (CYP) alters the pharmacokinetic parameters of the drug and causes drug–drug interactions. Salicylic acid been used for the treatment of colorectal cancer (CRC) and chemoprevention in recent decades. Thus, the aim of this study was to examine the in vitro inhibitory effect of salicylic acid on CYP2E1 activity in rat liver microsomes (RLMs) using high-performance liquid chromatography (HPLC). High-performance liquid chromatography analysis of a CYP2E1 assay was developed on a reversed phase C18 column (SUPELCO 25 cm × 4.6 mm × 5 µm) at 282 nm using 60% H2O, 25% acetonitrile, and 15% methanol as mobile phase. The CYP2E1 assay showed a good linearity (R2 > 0.999), good reproducibility, intra- and inter-day precision (<15%), acceptable recovery and accuracy (80–120%), and low detection (4.972 µM and 1.997 µM) and quantitation limit values (15.068 µM and 6.052 µM), for chlorzoxazone and 6-hydroxychlorzoxazone, respectively. Salicylic acid acts as a mixed inhibitor (competitive and non-competitive inhibition), with Ki (inhibition constant) = 83.56 ± 2.730 µM and concentration of inhibitor causing 50% inhibition of original enzyme activity (IC50) exceeding 100 µM (IC50 = 167.12 ± 5.460 µM) for CYP2E1 enzyme activity. Salicylic acid in rats would have both low and high potential to cause toxicity and drug interactions with other drugs that are substrates for CYP2E1.
The Effect of Formulation of Curcuminoids on Their Metabolism by Human Colonic Microbiota
Authors: Bresciani Letizia , Favari Claudia , Calani Luca , Francinelli Veronica , Riva Antonella , Petrangolini Giovanna , Allegrini Pietro , Mena Pedro , Del Rio Daniele
Published: February 2020

Turmeric (Curcuma longa L.) is the only edible plant recognized as a dietary source of curcuminoids, among which curcumin, demethoxycurcumin (DMC) and bis-demethoxycurcumin (Bis-DMC) are the most representative ones. Curcumin shows a very low systemic bioavailability and for this reason, several technologies have been adopted to improve it. These technologies generally improve curcuminoid absorption in the small intestine, however, no data are available about the effect of curcuminoid formulation on colonic biotransformation. The present study aims at investigating the human colonic metabolism of curcuminoids, prepared with two different technologies, using an in vitro model. Unformulated curcuminoid and lecithin-curcuminoid botanical extracts were fermented using an in vitro fecal model and colonic catabolites were identified and quantified by uHPLC-MSn. Native compounds, mainly curcumin, DMC and bis-DMC, were metabolized by colonic microbiota within the 24-h incubation. The degradation of curcuminoids led to the formation of specific curcuminoid metabolites, among which higher concentrations of bis(demethyl)-tetrahydrocurcumin and bis(demethyl)-hexahydrocurcumin were found after lecithin-extract fermentation compared to the concentration detected after unformulated extract. In conclusion, both curcumin-based botanical extracts can be considered important sources of curcuminoids, although the lecithin-formulated extract led to a higher production of curcuminoid catabolites. Moreover, a new curcuminoid catabolite, namely bis(demethyl)-hexahydrocurcumin, has been putatively identified, opening new perspectives in the investigation of curcuminoid bioavailability and their potential metabolite bioactivity.
Thermostable Tannase from Aspergillus Niger and Its Application in the Enzymatic Extraction of Green Tea
Authors: Shao Yuan , Zhang Yong-Hui , Zhang Feng , Yang Qiu-Ming , Weng Hui-Fen , Xiao Qiong , Xiao An-Feng
Published: February 2020

Tannase is widely used in tea beverage processing because of its ability to catalyze the hydrolysis of hydrolysable tannins or gallic acid esters and effectively improve the quality of tea extracts through enzymatic extraction. A new thermophilic tannase was cloned from Aspergillus niger FJ0118 and characterized. The tannase exhibited an optimal reaction temperature of 80 °C and retained 89.6% of the initial activity after incubation at 60 °C for 2 h. The enzymatic extraction of green tea at high temperature (70 °C) for a short time (40 min) was devised on the basis of the superior thermal stability of tannase. The enzymatic reaction significantly increased the total polyphenol content of green tea extract from 137 g·kg−1 to 291 g·kg−1. The enzymatic reaction effectively degraded the ester catechins into non-ester catechins compared with the water extraction method. Results suggested that the thermally stable tannase exhibited potential applications in the enzymatic extraction of green tea beverage.
Probing Reversible Guest Binding with Hyperpolarized 129Xe-NMR: Characteristics and Applications for Cucurbit[n]urils
Authors: Jayapaul Jabadurai , Schröder Leif
Published: February 2020

Cucurbit[n]urils (CB[n]s) are a family of macrocyclic host molecules that find various applications in drug delivery, molecular switching, and dye displacement assays. The CB[n]s with n = 5–7 have also been studied with 129Xe-NMR. They bind the noble gas with a large range of exchange rates. Starting with insights from conventional direct detection of bound Xe, this review summarizes recent achievements with chemical exchange saturation transfer (CEST) detection of efficiently exchanging Xe in various CB[n]-based supramolecular systems. Unprecedented sensitivity has been reached by combining the CEST method with hyperpolarized Xe, the production of which is also briefly described. Applications such as displacement assays for enzyme activity detection and rotaxanes as emerging types of Xe biosensors are likewise discussed in the context of biomedical applications and pinpoint future directions for translating this field to preclinical studies.
In Silico, Ex Vivo and In Vivo Studies of Roflumilast as a Potential Antidiarrheal and Antispasmodic agent: Inhibition of the PDE-4 Enzyme and Voltage-gated Ca++ ion Channels
Authors: Rehman Najeeb Ur , Ansari Mohd Nazam , Samad Abdul
Published: February 2020

The aim of the present study was to evaluate the possible gut inhibitory role of the phosphodiesterase (PDE) inhibitor roflumilast. Increasing doses of roflumilast were tested against castor oil-induced diarrhea in mice, whereas the pharmacodynamics of the same effect was determined in isolated rabbit jejunum tissues. For in silico analysis, the identified PDE protein was docked with roflumilast and papaverine using the Autodock vina program from the PyRx virtual screening tool. Roflumilast protected against diarrhea significantly at 0.5 and 1.5 mg/kg doses, with 40% and 80% protection. Ex vivo findings from jejunum tissues show that roflumilast possesses an antispasmodic effect by inhibiting spontaneous contractions in a concentration-dependent manner. Roflumilast reversed carbachol (CCh, 1 µM)-mediated and potassium (K+, 80 mM)-mediated contractile responses with comparable efficacies but different potencies. The observed potency against K+ was significantly higher in comparison to CCh, similar to verapamil. Experiments were extended to further confirm the inhibitory effect on Ca++ channels. Interestingly, roflumilast deflected Ca++ concentration–response curves (CRCs) to the right with suppression of the maximum peak at both tested doses (0.001-0.003 mg/mL), similar to verapamil. The PDE-inhibitory effect was authenticated when pre-incubation of jejunum tissues with roflumilast (0.03-0.1 mg/mL) produced a leftward deflection of isoprenaline-mediated inhibitory CRCs and increased the tissue level of cAMP, similar to papaverine. This idea was further strengthened by molecular docking studies, where roflumilast exhibited a better binding affinity (-9.4 kcal/mol) with the PDE protein than the standard papaverine (-8.3 kcal/mol). In conclusion, inhibition of Ca++ channels and the PDE-4 enzyme explains the pharmacodynamics of the gut inhibitory effect of roflumilast.
Free-standing Reduced Graphene Oxide/Carbon Nanotube Paper for Flexible Sodium-ion Battery Applications
Authors: Hao Yong , Wang Chunlei
Published: February 2020

We propose a flexible, binder-free and free-standing carbonaceous paper fabricated via electrostatic spray deposition using reduced graphene oxide/carbon nanotube (rGO/CNT) as a promising electrode material for flexible sodium-ion batteries (NIBs). The as-prepared rGO/CNT paper exhibits a three-dimensional (3D) layered structure by employing rGO as conductive frameworks to provide sodium-storage active sites and CNT as spacer to increase rGO interlayer distance and benefit the diffusion kinetics of sodium ions. Consequently, the rGO/CNT paper delivers an enhanced sodium ion storage capacity of 166.8 mAh g−1 at 50 mA g−1, retaining an average capacity of 101.4 mAh g−1 when current density sets back 100 mA g−1 after cycling at various current rates. An average capacity of 50 mAh g−1 at 200 mA g−1 was stabilized when cycling up to 300 cycles. The well-maintained electrochemical performance of free-standing rGO/CNT paper is due to the well-established hybrid 3D nanostructures, which demonstrates our carbon based material fabricated by a facile approach can be applied as one of the high-performance and low-cost electrode materials for applications in flexible energy storage devices.
Potential Therapeutic Anti-Inflammatory and Immunomodulatory Effects of Dihydroflavones, Flavones, and Flavonols
Authors: Zaragozá Cristina , Villaescusa Lucinda , Monserrat Jorge , Zaragozá Francisco , Álvarez-Mon Melchor
Published: February 2020

Systemic inflammation, circulating immune cell activation, and endothelial cell damage play a critical role in vascular pathogenesis. Flavonoids have shown anti-inflammatory effects. In this study, we investigated the effects of different flavonoids on the production of pro-inflammatory interleukin (IL) 1β, 6, and 8, and tumor necrosis factor α (TNF-α), in peripheral blood cells. Methods: We studied the whole blood from 36 healthy donors. Lipopolysaccharide (LPS)-stimulated (0.5 μg/mL) whole-blood aliquots were incubated in the presence or absence of different concentrations of quercetin, rutin, naringenin, naringin, diosmetin, and diosmin for 6 h. Cultures were centrifuged and the supernatant was collected in order to measure IL-1β, TNF-α, IL-6, and IL-8 production using specific immunoassay techniques. This production was significantly inhibited by quercetin, naringenin, naringin, and diosmetin, but in no case by rutin or diosmin. Flavonoids exert different effects, maybe due to the differences between aglycons and glucosides present in their chemical structures. However, these studies suggest that quercetin, naringenin, naringin, and diosmetin could have a potential therapeutic effect in the inflammatory process of cardiovascular disease.
Niosome-Based Approach for In Situ Gene Delivery to Retina and Brain Cortex as Immune-Privileged Tissues
Authors: AL Qtaish Nuseibah , Gallego Idoia , Villate-Beitia Ilia , Sainz-Ramos Myriam , López-Méndez Tania Belén , Grijalvo Santiago , Eritja Ramón , Soto-Sánchez Cristina , Martínez-Navarrete Gema , Fernández Eduardo , Puras Gustavo , Pedraz José Luis
Published: February 2020

Non-viral vectors have emerged as a promising alternative to viral gene delivery systems due to their safer profile. Among non-viral vectors, recently, niosomes have shown favorable properties for gene delivery, including low toxicity, high stability, and easy production. The three main components of niosome formulations include a cationic lipid that is responsible for the electrostatic interactions with the negatively charged genetic material, a non-ionic surfactant that enhances the long-term stability of the niosome, and a helper component that can be added to improve its physicochemical properties and biological performance. This review is aimed at providing recent information about niosome-based non-viral vectors for gene delivery purposes. Specially, we will discuss the composition, preparation methods, physicochemical properties, and biological evaluation of niosomes and corresponding nioplexes that result from the addition of the genetic material onto their cationic surface. Next, we will focus on the in situ application of such niosomes to deliver the genetic material into immune-privileged tissues such as the brain cortex and the retina. Finally, as future perspectives, non-invasive administration routes and different targeting strategies will be discussed.
A New Integrated Multi-Criteria Decision Making and Multi-Objective Programming Model for Sustainable Supplier Selection and Order Allocation
Authors: You Shan-Yong , Zhang Li-Jun , Xu Xue-Guo , Liu Hu-Chen
Published: February 2020

With the increasing pressure from global competition, manufacturers have realized that sustainable production is significant in supply chain management. Sustainable supplier selection and order allocation (SSS&OA) play a distinct and critical role for organizations to achieve sustainable development and build competitive advantage. In this paper, we aim to develop a novel SSS&OA model for selecting the most suitable sustainable suppliers and determining the optimal order sizes among them. First, double hierarchy hesitant linguistic term sets (DHHLTSs) are adopted to deal with uncertainty in evaluating the sustainable performance of alternative suppliers. Then, an extended decision field theory is proposed to choose efficient sustainable suppliers dynamically. Considering quantity discount, a multi-objective linear programming (MOLP) model is established to allocate reasonable order quantities among the selected suppliers. Finally, the applicability and effectiveness of the developed model are illustrated through its application in the electronic industry and through a comparative analysis with other methods.
Zearalenone Removal from Corn Oil by an Enzymatic Strategy
Authors: Chang Xiaojiao , Liu Hujun , Sun Jing , Wang Jun , Zhao Chengcheng , Zhang Wan , Zhang Jie , Sun Changpo
Published: February 2020

The estrogen-like mycotoxin zearalenone (ZEN) is one of the most widely distributed contaminants especially in maize and its commodities, such as corn oil. ZEN degrading enzymes possess the potential for counteracting the negative effect of ZEN and its associated high safety risk in corn oil. Herein, we targeted enhancing the secretion of ZEN degrading enzyme by Pichia pastoris through constructing an expression plasmid containing three optimized expression cassettes of zlhy-6 codon and signal peptides. Further, we explored various parameters of enzymatic detoxification in neutralized oil and analyzed tocopherols and sterols losses in the corn oil. In addition, the distribution of degraded products was demonstrated as well by Agilent 6510 Quadrupole Time-of-Flight mass spectrometry. P. pastoris GSZ with the glucoamylase signal was observed with the highest ZLHY-6 secretion yield of 0.39 mg/mL. During the refining of corn oil, ZEN in the crude oil was reduced from 1257.3 to 13 µg/kg (3.69% residual) after neutralization and enzymatic detoxification. Compared with the neutralized oil, no significant difference in the total tocopherols and sterols contents was detected after enzymatic detoxification. Finally, the degraded products were found to be entirely eliminated by washing. This study presents an enzymatic strategy for efficient and safe ZEN removal with relatively low nutrient loss, which provides an important basis for further application of enzymatic ZEN elimination in the industrial process of corn oil production.
CCD Based Detector for Detection of Abrin Toxin Activity
Authors: Rasooly Reuven , Do Paula , Hernlem Bradley
Published: February 2020

Abrin is a highly potent and naturally occurring toxin produced in the seeds of Abrus precatorius (Rosary Pea) and is of concern as a potential bioterrorism weapon. There are many rapid and specific assay methods to detect this toxic plant protein, but few are based on detection of toxin activity, critical to discern biologically active toxin that disables ribosomes and thereby inhibits protein synthesis, producing cytotoxic effects in multiple organ systems, from degraded or inactivated toxin which is not a threat. A simple and low-cost CCD detector system was evaluated with colorimetric and fluorometric cell-based assays for abrin activity; in the first instance measuring the abrin suppression of mitochondrial dehydrogenase in Vero cells by the MTT-formazan method and in the second instance measuring the abrin suppression of green fluorescent protein (GFP) expression in transduced Vero and HeLa cells. The limit of detection using the colorimetric assay was 10 pg/mL which was comparable to the fluorometric assay using HeLa cells. However, with GFP transduced Vero cells a hundred-fold improvement in sensitivity was achieved. Results were comparable to those using a more expensive commercial plate reader. Thermal inactivation of abrin was studied in PBS and in milk using the GFP-Vero cell assay. Inactivation at 100 °C for 5 min in both media was complete only at the lowest concentration studied (0.1 ng/mL) while treatment at 63 °C for 30 min was effective in PBS but not milk.
Whole Genome Analysis Revealed the Genes Responsible for Citreoviridin Biosynthesis in Penicillium citreonigrum
Authors: Okano Takumi , Kobayashi Naoki , Izawa Kazuki , Yoshinari Tomoya , Sugita-Konishi Yoshiko
Published: February 2020

Citreoviridin (CTV) is a mycotoxin that is produced by Aspergillus terreus, Eupenicillium ochrosalmoneum and Penicillium citreonigrum, and CTV has been detected in a wide range of cereal grains throughout the world. Furthermore, it is especially a serious problem in regions where rice is consumed as a staple food. Moreover, CTV is a well-known yellow rice toxin, and outbreaks of beriberi have occurred due to consumption of rice that is contaminated by CTV even in the recent years. Although CTV biosynthetic genes of A. terreus have been described, those of P. citreonigrum remain unclear, which is concerning since P. citreonigrum is the main cause of CTV contamination in rice. In the present study, we determined the draft genome of the P. citreonigrum strain IMI92228 and revealed the presence of all four genes that form a gene cluster and that are homologous to the CTV biosynthesis genes of A. terreus. The expression of these four homologous genes were highly correlated with CTV production, suggesting that they may play an important role in CTV biosynthesis in P. citreonigrum. We concluded that the gene cluster is a CTV biosynthesis cluster of P. citreonigrum. The findings will contribute to the understanding of the biosynthetic pathway of CTV and will ultimately lead to improvements in the CTV management of agricultural products.
Spatial Differences in the Chemical Composition of Surface Water in the Hornsund Fjord Area: A Statistical Analysis with A Focus on Local Pollution Sources
Authors: Koziol Krystyna , Ruman Marek , Pawlak Filip , Chmiel Stanisław , Polkowska Żaneta
Published: February 2020

Surface catchments in Svalbard are sensitive to external pollution, and yet what is frequently considered external contamination may originate from local sources and natural processes. In this work, we analyze the chemical composition of surface waters in the catchments surrounding the Polish Polar Station in Svalbard, Hornsund fjord area. We have pooled unpublished and already published data describing surface water composition in 2010, related to its pH, electrical conductivity (EC), metals and metalloids, total organic carbon (TOC) and selected organic compound concentrations, including persistent organic pollutants (POPs) and surfactants. These data were statistically analyzed for spatial differences, using Kruskal–Wallis ANOVA and principal component analysis (PCA), with distance from the station in the PCA approximating local human activity impact. The geological composition of the substratum was found to be a strong determinant of metal and metalloid concentrations, sufficient to explain significant differences between the studied water bodies, except for the concentration of Cr. The past and present human activity in the area may have contributed also to some of the polycyclic aromatic hydrocarbons (PAHs), although only in the case of naphthalene can such an effect be confirmed by an inverse correlation with distance from the station. Other likely factors contributing to the chemical concentrations in the local waters are marine influence, long-range pollution transport and release from past deposition in the environment.
Numerical Approaches for Estimating Daily River Leakage from Arid Ephemeral Streams
Authors: Min Leilei , Vasilevskiy Peter Yu. , Wang Ping , Pozdniakov Sergey P. , Yu Jingjie
Published: February 2020

Despite the significance of river leakage to riparian ecosystems in arid/semi-arid regions, a true understanding and the accurate quantification of the leakage processes of ephemeral rivers in these regions remain elusive. In this study, the patterns of river infiltration and the associated controlling factors in an approximately 150-km section of the Donghe River (lower Heihe River, China) were revealed using a combination of field investigations and modelling techniques. The results showed that from 21 April 2010 to 7 September 2012, river water leakage accounted for 33% of the total river runoff in the simulated segments. A sensitivity analysis showed that the simulated infiltration rates were most sensitive to the aquifer hydraulic conductivity and the maximum evapotranspiration (ET) rate. However, the river leakage rate, i.e., the ratio of the leakage volume to the total runoff volume, of a single runoff event relies heavily on the total runoff volume and river flow rate. In addition to the hydraulic parameters of riverbeds, the characteristics of ET parameters are equally important for quantifying the flux exchange between arid ephemeral streams and underlying aquifers. Coupled surface/groundwater models, which aim to estimate river leakage, should consider riparian zones because these areas play a dominant role in the formation of leakage from the river for recharging via ET. The results of this paper can be used as a reference for water resource planning and management in regulated river basins to help maintain riparian ecosystems in arid regions.
Utilizing the Internet of Things (IoT) to Develop a Remotely Monitored Autonomous Floodgate for Water Management and Control
Authors: Hussen Hajjaj Sami Salama , Hameed Sultan Mohamed Thariq , Moktar Muhammad Hafizuddin , Lee Seng Hua
Published: February 2020

In recent years, floods have increased in frequency and intensity, causing tremendous hardship. In badly affected regions, mostly the rural areas, Weir-type floodgates are the only measure against floods. However, these manually operated gates are numerous and scattered over vast areas. This makes flood mitigation efforts very challenging, which causes severe devastation. Current solutions to automate the floodgates are expensive, black-boxed, and focused on individual gates. In this paper, we present a Centralized Flood Monitoring and Coordination System developed through the Internet of Things (IoT) and other open-source technologies. For this work, we developed a working prototype of an autonomous floodgate that opens/closes according to the level of water. We also developed the required program to allow the gate controller to publish its data through the IoT gateway to the cloud. The data was then captured and viewed on a number of IoT clients, both for individuals and groups of floodgates, in real time. The developed system proved successful as the autonomous gates were monitored remotely through the established IoT framework, with room for future development and improvement. This paper serves as a proof of concept and a preparation for real, on-site implementation of the IoT-floodgates.
An Improved Ecological Footprint Method for Water Resources Utilization Assessment in the Cities
Authors: Li Hui , Zhao Fen , Li Chunhui , Yi Yujun , Bu Jiuhe , Wang Xuan , Liu Qiang , Shu Anping
Published: February 2020

Economic development and increasing population density along the lower reaches of the Yellow river have challenged the river’s ability to meet human and ecological demand. The evaluation of the sustainability of water resources in the lower reaches of the Yellow River is of great significance for the achievement of high-quality development in the region. Based on an improved ecological footprint method considering soil water, the spatial and temporal evolution of the water resources ecological footprint and water resources carrying capacity and evaluates the utilization of water resources in the lower Yellow River are comprehensively evaluated. The results show that agricultural water consumption in the urban agglomerations in the lower reaches of the Yellow River occupies a major position in water consumption, accounting for more than 70%. In 2013–2017, the per capita water resources ecological footprint of the cities along the lower reaches of the Yellow River decreases every year, while the water resources carrying capacity is slightly fluctuating, but remains in a relatively stable state. The deficit situation has eased, falling by 54.52% in the past five years. The water use efficiency of the lower reaches of the Yellow River has increased every year, and the water resources conflict improved significantly, after the implementation of the new environmental policy in 2015. In terms of space, the cities with the smallest per capita ecological deficits include Zibo, Zhengzhou, and Laiwu City, and Dezhou, and Kaifeng and Binzhou City have the largest. Strict water resources management measures and water pollution prevention and control regulations should be formulated to improve the water use efficiency in these areas in order to solve the problem of water shortage.
Parameterization and Application of Stanghellini Model for Estimating Greenhouse Cucumber Transpiration
Authors: Yan Haofang , Huang Song , Zhang Chuan , Gerrits Miriam Coenders , Wang Guoqing , Zhang Jianyun , Zhao Baoshan , Acquah Samuel Joe , Wu Haimei , Fu Hanwen
Published: February 2020

Accurate estimation of transpiration (Tr) is important in the development of precise irrigation scheduling and to enhance water-use efficiency in agricultural production. In this study, the air temperature (Ta) and relative humidity (RH) were measured at three different heights (0.5, 1.0, and 1.8 m above the ground near the plant canopy) parameterize aerodynamic resistance (ra) based on the heat transfer coefficient method and to estimate Tr using the Stanghellini model (SM) during two growing seasons of cucumber in a greenhouse. The canopy resistance (rc) was parameterized by an exponential relationship of stomata resistance and solar radiation, and the estimated Tr was compared to the values measured with lysimeters. After parameterization of ra and rc, the efficiency (EF) and the Root Mean Square Error (RMSE) of the estimated Tr by the SM based on micrometeorological data at a height of 0.5 m were 95% and 18 W m−2, respectively, while the corresponding values were 86% and 29 W m−2 at a height of 1.8 m for the autumn planting season. For the spring planting season, the EF and RMSE were 92% and 34 W m−2 at a height of 0.5 m, while the corresponding values were 81% and 56 W m−2 at a height of 1.8 m, respectively. This work demonstrated that when micrometeorological data within the canopy was applied alongside the data measured above the canopy, the SM led to better agreement with the lysimeter measurements.