bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantity–Quality Trade-Off and Early Childhood Development in Rural Family: Evidence from China’s Guizhou Province
Authors: Zhong Jingdong , Gao Jingjing , Liu Chengfang , Huang Jie , Luo Renfu
Published: April 2019

This paper empirically investigates the causal effect of having siblings on the cognitive, language, motor, and social-emotional skills of infants under the age of 2 in rural families in Guizhou Province in China. The results are based on data from a survey conducted in 2017. To effectively relieve the endogeneity induced by selection bias, we applied the matching-smoothing (MS) method to evaluate the effects of having siblings. The results show that, first, having siblings produces significant negative impacts on an infant’s cognitive, language, and social-emotional skills; second, intrahousehold resource allocation is the mechanism behind the Quantity–Quality (Q–Q) trade-off, and it exerts its effects through two key identified channels—the home environment and parental warmth. By spreading the parents’ investment among siblings in terms of both the home environment and parental warmth, having siblings hinders infants’ early development. Our findings provide new evidence for the relation between the Q–Q trade-off and early childhood development in rural families in western China.
Psychosocial Management Before, During, and After Emergencies and Disasters—Results from the Kobe Expert Meeting
Authors: Généreux Mélissa , Schluter Philip J. , Takahashi Sho , Usami Shiori , Mashino Sonoe , Kayano Ryoma , Kim Yoshiharu
Published: April 2019

Emergencies and disasters typically affect entire communities, cause substantial losses and disruption, and result in a significant and persistent mental health burden. There is currently a paucity of evidence on safe and effective individual- and community-level strategies for improving mental health before, during, and after such events. In October 2018, the World Health Organization (WHO) Centre for Health Development (WHO Kobe Centre) convened a meeting bringing together leading Asia Pacific and international disaster research experts. The expert meeting identified key research needs in five major areas, one being “Psychosocial management before, during, and after emergencies and disasters”. Experts for this research area identified critical gaps in observational research (i.e., the monitoring of long-term psychological consequences) and interventional research (i.e., the development and evaluation of individual- and community-level interventions). Three key research issues were identified. First, experts underscored the need for a standardized and psychometrically robust instrument that classified the mental health/psychosocial risk of people within both a clinical and community setting. Then, the need for a standardization of methods for prevention, screening, diagnosis, and treatment for affected people was highlighted. Finally, experts called for a better identification of before, during, and after emergency or disaster assets associated with greater community resilience.
Between Privilege and Oppression: An Intersectional Analysis of Active Transportation Experiences Among Washington D.C. Area Youth
Authors: Roberts Jennifer D. , Mandic Sandra , Fryer Craig S. , Brachman Micah L. , Ray Rashawn
Published: April 2019

The use of active transportation (AT), such as walking, cycling, or even public transit, as a means of transport offers an opportunity to increase youth physical activity and improve health. Despite the well-known benefits of AT, there are environmental and social variables that converge on the AT experiences of low-income youth and youth of color (YOC) that have yet to be fully uncovered. This study uses an intersectional framework, largely focusing on the race-gender-class trinity, to examine youth AT within a context of transportation inequity. Theoretically guided by the Ecological Model of Active Transportation, focus groups were completed with two groups of girls (15 participants) and two groups of boys (nine participants) ranging between the ages of 12–15 years who lived within the Washington D.C. area. This research found race, gender, and class to be inhibitors of AT for both boys and girls, but with more pronounced negative influences on girls.
Utilization and Safety of Percutaneous Lung Biopsy: A 10-Year Nationwide Population-Based Study
Authors: Chen Chun-Ku , Chang Hsiao-Ting , Chen Yu-Chun , Chiang Shu-Chiung , Chou Hsiao-Ping , Chen Tzeng-Ji
Published: April 2019

Percutaneous lung biopsy is a technique used for sampling peripherally located lung masses and has been gaining in popularity. However, its exact utilization is unknown, and its safety has not been well studied. The current study aimed to assess the trend of utilization and study the safety of this procedure. Using the National Health Insurance Research Database, we retrospectively determined the total number of procedures that were performed on subjects older than 20 years between 2001 and 2010. We also estimated the rates of major complications, such as pneumothorax, requiring intercostal drainage. A total of 630 percutaneous biopsies were performed in 2001, while 3814 were performed in 2010, representing a 6.1-fold increase. The compound annual growth rate was 22.1%. The number of hospitals that performed the procedure increased from 55 to 99. Pneumothorax requiring drainage occurred in 1.5% of the procedures. The factors associated with a higher complication rate included male gender, chronic obstructive pulmonary disease, rural hospital, and low-volume hospital. Percutaneous lung biopsies are a relatively safe procedure, and their performance has been rapidly increasing. The number of procedures performed by a hospital was associated with the complication rate.
Development, Characterization and In Vitro Biological Properties of Scaffolds Fabricated From Calcium Phosphate Nanoparticles
Authors: Morejón Lizette , Delgado José Angel , Antunes Ribeiro Alexandre , Varella de Oliveira Marize , Mendizábal Eduardo , García Ibrahim , Alfonso Adrián , Poh Patrina , van Griensven Martijn , Balmayor Elizabeth R.
Published: April 2019

Ceramic materials mimic the mineral composition of native bone and feature osteoconductive properties; they are therefore used to regenerate bone tissue. Much research focuses on increasing the porosity and pore interconnectivity of ceramic scaffolds to increase osteoconductivity, cell migration and cell-cell interaction. We aimed to fabricate biocompatible 3D-scaffolds featuring macro- and microporous calcium phosphates with high pore interconnection. Nanoparticles of hydroxyapatite (HA) and calcium deficient hydroxyapatite (CDHA) were synthesized by wet chemical precipitation. Scaffolds were produced from them by the replication polymeric foam technique. Solid content and sintering temperature were varied. Nanoparticles and scaffolds were characterized regarding morphology, chemical and mineral composition, porosity and mechanical properties. Biocompatibility, cell attachment and distribution were evaluated in vitro with human adipose mesenchymal stem cells. Scaffolds with total porosity of 71%–87%, pores in the range of 280–550 µm and connectivity density up to 43 mm−3 were obtained. Smaller pore sizes were obtained at higher sintering temperature. High solid content resulted in a decrease of total porosity but increased interconnectivity. Scaffolds 50HA/50β-TCP featured superior interconnectivity and mechanical properties. They were bioactive and biocompatible. High HA solid content (40 wt.%) in the HA pure scaffolds was negative for cell viability and proliferation, while in the 50HA/50β-TCP composite scaffolds it resulted more biocompatible.
Cerebrospinal Fluid (CSF) Exchange with Artificial CSF Enriched with Mesenchymal Stem Cell Secretions Ameliorates Experimental Autoimmune Encephalomyelitis
Authors: Valitsky Michael , Benhamron Sandrine , Nitzan Keren , Karussis Dimitrios , Ella Ezra , Abramsky Oded , Kassis Ibrahim , Rosenmann Hanna
Published: April 2019

The complexity of central nervous system (CNS) degenerative/inflammatory diseases and the lack of substantially effective treatments point to the need for a broader therapeutic approach to target multiple components involved in the disease pathogenesis. We suggest a novel approach directed for the elimination of pathogenic agents from the CNS and, in parallel, its enrichment with an array of neuroprotective substances, using a “cerebrospinal fluid (CSF) exchange” procedure, in which endogenous (pathogenic) CSF is removed and replaced by artificial CSF (aCSF) enriched with secretions of human mesenchymal stem cells (MSCs). MSCs produce a variety of neuroprotective agents and have shown beneficial effects when cells are transplanted in animals and patients with CNS diseases. Our data show that MSCs grown in aCSF secrete neurotrophic factors, anti-inflammatory cytokines, and anti-oxidant agents; moreover, MSC-secretions-enriched-aCSF exerts neuroprotective and immunomodulatory effects in neuronal cell lines and spleen lymphocytes. Treatment of experimental-autoimmune-encephalomyelitis (EAE) mice with this enriched-aCSF using an intracerebroventricular (ICV) CSF exchange procedure (“CSF exchange therapy”) caused a significant delay in the onset of EAE and amelioration of the clinical symptoms, paralleled by a reduction in axonal damage and demyelination. These findings point to the therapeutic potential of the CSF exchange therapy using MSC-secretions-enriched-aCSF in inflammatory/degenerative diseases of the CNS.
Molecular Cloning, Characterization, and Nutritional Regulation of Elovl6 in Large Yellow Croaker (Larimichthys crocea)
Authors: Li Yongnan , Pang Yuning , Xiang Xiaojun , Du Jianlong , Mai Kangsen , Ai Qinghui
Published: April 2019

Elongation of very long chain fatty acids protein 6 (Elovl6) is a key enzyme in fatty acid synthesis, which participates in converting palmitate (C16:0) to stearate (C18:0). Although studies of Elovl6 have been carried out in mammals, the nutritional regulation of elovl6 in fish remains poorly understood. In the present study, the cloning and nutritional regulation of elovl6 were determined in large yellow croaker. Sequence and phylogenetic analysis revealed that the full-length cDNA of elovl6 was 1360 bp, including an open reading frame of 810 bp encoding a putative protein of 269 amino acid that possesses the characteristic features of Elovl proteins. The transcript level of elovl6 was significantly increased in the liver of croaker fed the diets with soybean oil (enriched with 18: 2n-6, LA) or linseed oil (enriched with 18: 3n-3, ALA) than that in croaker fed the diet with fish oil (enriched with 20: 5n-3 and 22: 6n-3). Correspondingly, the elovl6 expression in croaker’s hepatocytes treated with ALA or LA was remarkably increased compared to the controls. Furthermore, the transcription factors including hepatocyte nuclear factor 1α (HNF1α), CCAAT-enhancer-binding protein β (CEBPβ), retinoid X receptor α (RXRα), and cAMP response element-binding protein 1 (CREB1) greatly enhanced promoter activity of elovl6 in large yellow croaker, and the expression of transcription factors is consistent with the changes of elovl6 expression in response to fatty acids in vivo and in vitro. In conclusion, this study revealed that elovl6 expression in large yellow croaker could be upregulated by dietary ALA or LA via the increased transcriptional expression of transcription factors including hnf1α, cebpβ, rxrα, and creb1.
Virus-Like Particle Facilitated Deposition of Hydroxyapatite Bone Mineral on Nanocellulose after Exposure to Phosphate and Calcium Precursors
Authors: Sinitsyna Olga V. , Makarov Valentine V. , McGeachy Kara , Bukharova Tatyana , Whale Eric , Hepworth David , Yaminsky Igor V. , Kalinina Natalia O. , Taliansky Michael E. , Love Andrew J.
Published: April 2019

We produced and isolated tobacco mosaic virus-like particles (TMV VLPs) from bacteria, which are devoid of infectious genomes, and found that they have a net negative charge and can bind calcium ions. Moreover, we showed that the TMV VLPs could associate strongly with nanocellulose slurry after a simple mixing step. We sequentially exposed nanocellulose alone or slurries mixed with the TMV VLPs to calcium and phosphate salts and utilized physicochemical approaches to demonstrate that bone mineral (hydroxyapatite) was deposited only in nanocellulose mixed with the TMV VLPs. The TMV VLPs confer mineralization properties to the nanocellulose for the generation of new composite materials.
Conventional and Microwave Hydrothermal Synthesis and Application of Functional Materials: A Review
Authors: Yang Guijun , Park Soo-Jin
Published: April 2019

With the continuous development and progress of materials science, increasingly more attention has been paid to the new technology of powder synthesis and material preparation. The hydrothermal method is a promising liquid phase preparation technology that has developed rapidly during recent years. It is widely used in many fields, such as the piezoelectric, ferroelectric, ceramic powder, and oxide film fields. The hydrothermal method has resulted in many new methods during the long-term research process, such as adding other force fields to the hydrothermal condition reaction system. These force fields mainly include direct current, electric, magnetic (autoclaves composed of non-ferroelectric materials), and microwave fields. Among them, the microwave hydrothermal method, as an extension of the hydrothermal reaction, cleverly uses the microwave temperature to compensate for the lack of temperature in the hydrothermal method, allowing better practical application. This paper reviews the development of the hydrothermal and microwave hydrothermal methods, introduces their reaction mechanisms, and focuses on the practical application of the two methods.
Effect of Urchin-Like Mullite Whiskers on the High-Temperature Performance of Porous SiO2-Based Ceramic Molds
Authors: Chen Yi , Lu Zhongliang , Wan Weijian , Li Jian , Miao Kai , Li Dichen
Published: April 2019

Urchin-like mullite whiskers synthesized by the vapor–liquid–solid growth method were used to improve the high-temperature performance of porous gelcast SiO2-based ceramic molds. Aluminum was used to facilitate the synthesis of polycrystal urchin-like mullite whiskers which acted as bridges between particles. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) were used to investigate the microstructures and phase compositions of the sintered ceramic samples, respectively. Urchin-like mullite whiskers with diameters of 0.2~1.0 µm and lengths of 1.0~8.0 µm were successfully synthesized in SiO2-based ceramic. When 15 vol% Al was added, the high-temperature strength at 1200 °C was improved from 8.5 to 27.5 MPa, and the creep deformation was decreased to 0.56 mm. Meanwhile, a sintering shrinkage below 0.3% was obtained, and the de-coring rate was accelerated by 67% compared to that of the pure SiO2-based ceramic. This method showed excellent high-temperature strength and high precision, having remarkable potential in the fabrication of hollow turbine blades.
Effect of Aluminum Addition on the Microstructure and Properties of Non-Eutectic Sn-20Bi Solder Alloys
Authors: Yang Wenchao , Li Jidong , Li Yitai , Feng Junli , Wu Jingwu , Zhou Xiankun , Yu Aihua , Wang Jiahui , Liang Siyu , Wei Mei , Zhan Yongzhong
Published: April 2019

This study investigates the effect of aluminum (Al) on the microstructure, micro-hardness, and wettability of environmentally friendly Sn-20Bi-xAl (x = 0, 0.1, 0.3, 0.5 (wt.%)) solder alloys. Scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS) analysis, and X-ray diffraction (XRD), were used to identify the microstructure morphology and composition. The spreading area and contact angle of the Sn-20Bi-xAl alloys on Cu substrates were used to measure the wettability of solder alloys. The results indicate that Al increased the hardness to a maximum value of ~27.1 HV for x = 0.5. When the content of Al was more than 0.3 wt.%, the hardness change value gradually flattened. From the spreading test results, Al reduced the wettability of solder alloys. When the content of Al was 0.1 wt.%, the change was slight. When more than 0.3 wt.%, the wettability of Sn-20Bi-xAl solder alloys sharply dropped. The corrosion resistance of Sn-20Bi-0.1Al alloy was the best, and the corrosion rate was at the lowest value at 0.092 mm/a due to the dense corrosion products.
Experimental Study on Wet Skid Resistance of Asphalt Pavements in Icy Conditions
Authors: Yan Boxiang , Mao Huanhuan , Zhong Sai , Zhang Pengfei , Zhang Xiaoshan
Published: April 2019

In this research, the durability of skid resistance during the ice melting process with temperature increasing from −5 °C to 10 °C was characterized by means of a British Pendulum Skid Tester. Four types of pavement surfaces were prepared and tested. The difference between two antiskid layers prepared with bitumen emulsion was the aggregate. The detailed angularity and form 2D index of fine aggregates used for antiskid surfaces, characterized by means of the Aggregate Image Measure System (AIMS) with micro image analysis methods, were then correlated with British Pendulum Number (BPN) values. Results indicate that skid resistance has the lowest value during the ice-melting process. The investigated antiskid layers can increase the surface friction during icy seasons. In icy conditions, the skid resistance behavior first worsens until reaches the lowest value, and then increases gradually with increasing temperature. Results from ice-melting conditions on four investigated pavement surfaces give the same temperature range where there will be lowest skid resistance. That temperature range is from 3 °C to 5 °C. A thicker ice layer will result in a lower skid resistance property and smaller “lowest BPN”.
Marine-Derived Natural Compounds for the Treatment of Parkinson’s Disease
Authors: Huang Chunhui , Zhang Zaijun , Cui Wei
Published: April 2019

Parkinson’s disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic neurons, leading to the motor dysfunctions of patients. Although the etiology of PD is still unclear, the death of dopaminergic neurons during PD progress was revealed to be associated with the abnormal aggregation of α-synuclein, the elevation of oxidative stress, the dysfunction of mitochondrial functions, and the increase of neuroinflammation. However, current anti-PD therapies could only produce symptom-relieving effects, because they could not provide neuroprotective effects, stop or delay the degeneration of dopaminergic neurons. Marine-derived natural compounds, with their novel chemical structures and unique biological activities, may provide anti-PD neuroprotective effects. In this study, we have summarized anti-PD marine-derived natural products which have shown pharmacological activities by acting on various PD targets, such as α-synuclein, monoamine oxidase B, and reactive oxygen species. Moreover, marine-derived natural compounds currently evaluated in the clinical trials for the treatment of PD are also discussed.
Study of the Microstructure and Fracture Toughness of TC17 Titanium Alloy Linear Friction Welding Joint
Authors: Li Xiaohong , He Jianchao , Ji Yajuan , Zhang Tiancang , Zhang Yanhua
Published: April 2019

In this paper, the fracture toughness of the thermo-mechanically affected zone (TMAZ) and the weld zone (WZ) of the TC17 titanium alloy linear friction welding joint was studied. The relationship between microstructure and fracture toughness of the joint, as well as the morphologies of the joint microstructure and fracture were investigated. The results indicate that after heat treatment, there was no significant difference in hardness between the WZ and the TMAZ of the joint, which was about 420 HV. However, the microstructures of the different zones of the joint were significantly different. The TMAZ was composed of coarse grains having an internal basket-shaped α phase with an uneven grain size, while the WZ was composed of relatively uniform fine grains and contained a sheet-like α phase. The fracture toughness of the TMAZ was found to be higher than that of the WZ, indicating that the microstructure of the joint had a significant impact on the fracture toughness. In addition, the fracture resistance of the TMAZ with coarser grains and uneven microstructure was better than that of the WZ with fine grains and uniform microstructure.
Synthesis and Antiproliferative Activities of Conjugates of Paclitaxel and Camptothecin with a Cyclic Cell-Penetrating Peptide
Authors: El-Sayed Naglaa Salem , Shirazi Amir Nasrolahi , Sajid Muhammad Imran , Park Shang Eun , Parang Keykavous , Tiwari Rakesh Kumar
Published: April 2019

Cell-penetrating peptide [WR]5 has been previously shown to be an efficient molecular transporter for various hydrophilic and hydrophobic molecules. The peptide was synthesized using Fmoc/tBu solid-phase chemistry, and one arginine was replaced with one lysine to enable the conjugation with the anticancer drugs. Paclitaxel (PTX) was functionalized with an esterification reaction at the C2′ hydroxyl group of PTX with glutaric anhydride and conjugated with the cyclic peptide [W(WR)4K(βAla)] in DMF to obtain the peptide-drug conjugate PTX1. Furthermore, camptothecin (CPT) was modified at the C(20)-hydroxyl group through the reaction with triphosgene. Then, it was conjugated with two functionalized cyclic peptides through a formyl linker affording two different conjugates, namely CPT1 and CPT2. All the conjugates showed better water solubility as compared to the parent drug. The cytotoxicity assay of the drugs and their conjugates with the peptides were evaluated in the human breast cancer MCF-7 cell line. PTX inhibited cell proliferation by 39% while the PTX-peptide conjugate inhibited the proliferation by ~18% after 72 h incubation. On the other hand, CPT, CPT1, and CPT2 reduced the cell proliferation by 68%, 39%, and 62%, respectively, in the MCF-7 cell lines at 5 µM concentration after 72 h incubation.
Novel Anti-Aging Benzoquinone Derivatives from Onosma bracteatum Wall
Authors: Farooq Umer , Pan Yanjun , Disasa Dejene , Qi Jianhua
Published: April 2019

The aim of this study was to investigate anti-aging molecules from Onosma bracteatum Wall, a traditional medicinal plant used in the Unani and Ayurvedic systems of medicine. During bioassay-guided isolation, two known benzoquinones, allomicrophyllone (1) and ehretiquinone (2) along with three novel benzoquinones designated as ehretiquinones B–D (3−5) were isolated from O. bracteatum. Their structures were characterized by spectroscopic analysis through 1D and 2D NMR, by MS spectroscopic analysis and comparing with those reported in the literatures. The anti-aging potential of the isolated benzoquinones was evaluated through a yeast lifespan assay, and the results indicated that 1, 2, 4 and 5 significantly extended the replicative lifespan of K6001 yeast, indicating that these benzoquinones obtained from O. brateatum have the ability to be employed as a potential therapeutic agent against age-related diseases.
Potential Pharmacokinetic Drug–Drug Interaction Between Harmine, a Cholinesterase Inhibitor, and Memantine, a Non-Competitive N-Methyl-d-Aspartate Receptor Antagonist
Authors: Zhang Yunpeng , Li Shuping , Wang Youxu , Deng Gang , Cao Ning , Wu Chao , Ding Wenzheng , Wang Yuwen , Cheng Xuemei , Wang Changhong
Published: April 2019

Harmine (HAR) is a beta-carboline alkaloid widely distributed in nature. It exhibits psychopharmacological effects of improving learning and memory. However, excessive dose of HAR can cause central tremor toxicity, which may be related to the glutamate system. Memantine (MEM) is a non-competitive N-methyl-d-aspartate receptor antagonist. It can be used for the treatment of Alzheimer’s disease and also can block the neurotoxicity caused by glutamate. Therefore, combination of HAR and MEM would be meaningful and the pharmacokinetics investigation of HAR and MEM in combination is necessary. A ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established and validated for the simultaneous quantitative determination of MEM, HAR and harmol (HOL), a main metabolite of HAR, in rat plasma after oral administration of HAR and MEM in combination (5.0 mg/kg of MEM combined with 20.0, 40.0, 80.0 mg/kg of HAR). The contents of HAR and HOL were determined after oral administration of HAR (20.0, 40.0 and 80.0 mg/kg), and the content of MEM was determined after oral administration of MEM (5.0 mg/kg). Blood samples were collected from each rat at 0 (pre-dose), 0.08, 0.17, 0.25, 0.33, 0.50, 0.75, 1.0, 2.0, 4.0, 8.0, 12.0 and 24.0 h after administration. The maximum peak concentration (Cmax) of MEM was obviously decreased, and the area under the plasma concentration versus time curve from zero to time t (AUC(0-t)) and mean residence time (MRT) were significantly increased after combination with HAR. The Cmax and AUC(0-t) of HAR and its metabolite HOL were increased after combination with MEM. These findings suggested that co-administration of HAR and MEM could extend their residence time in rats, and then might increase the efficacy for treatment of Alzheimer’s disease. Therefore, this study will provide a basis for the rational combined application of HAR and MEM.
Biological Activities of Euphorbia peplus Leaves Ethanolic Extract and the Extract Fabricated Gold Nanoparticles (AuNPs)
Authors: Ghramh Hamed A. , Khan Khalid Ali , Ibrahim Essam H.
Published: April 2019

Euphorbia peplus leaves extract (EpExt) and gold nanoparticles (AuNPs) phytofabricated with extract (EpExt-AuNPs) were investigated for biological activities. EpExt and EpExt-AuNPs were screened for: (i) anticancer activity against Hela and HepG2 cell lines; (ii) antimicrobial activity; (iii) hemolytic activity; (iv) cytotoxic or stimulatory effects; and (v) insecticidal activity. AuNPs (size 50 nm) were synthesized. (i) EpExt had a stimulatory effect (51.04%) on Hela cells and an inhibitory effect (−12.83%) on HepG2 cells while EpExt-AuNPs showed inhibitory effects (−54.25% and −59.64% on Hela and HepG2 cells respectively). (ii) Antimicrobial activity of EpExt-AuNPs was significantly higher (ranged from 11.67 mm to 14.33 mm) than that of EpExt (ranged from 5.33 mm to 6.33 mm). (iii) Both EpExt and EpExt-AuNPs displayed 100% hemolysis. (iv) A dose-dependent inhibitory effect of EpExt was observed (ranged from −48.5% to −92.1%), which was greater than that of EpExt-AuNPs (ranged from −32.1% to −69.1%) (v) EpExt-AuNPs was more lethal against mosquito larvae with lethal concentration (LC50) value (202.692 ppm) compared to EpExt (1430.590 ppm). In conclusion, EpExt-AuNPs were inhibitory against HepG2 and Hela cells, while EpExt inhibited HepG2 but stimulated Hela cells. EpExt-AuNPs had antimicrobial effects. EpExt showed dose-dependent inhibitory effects on splenic cells. EpExt-AuNPs were lethal against mosquito larvae.
Modulation of Endocannabinoid-Binding Receptors in Human Neuroblastoma Cells by Tunicamycin
Authors: Rapino Cinzia , Castellucci Annalisa , Lizzi Anna Rita , Sabatucci Annalaura , Angelucci Clotilde B. , Tortolani Daniel , Rossi Gianna , D’Andrea Gabriele , Maccarrone Mauro
Published: April 2019

Endocannabinoid (eCB)-binding receptors can be modulated by several ligands and membrane environment, yet the effect of glycosylation remains to be assessed. In this study, we used human neuroblastoma SH-SY5Y cells to interrogate whether expression, cellular localization, and activity of eCB-binding receptors may depend on N-linked glycosylation. Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively. In addition, the activity of type-1 and type-2 cannabinoid receptors (CB1 and CB2) was assessed by means of rapid binding assays. Significant changes in gene and protein expression were found upon tunicamycin treatment for CB1 and CB2, as well as for GPR55 receptors, but not for transient receptor potential vanilloid 1 (TRPV1). Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB1 (70 kDa), that was reduced by tunicamycin. Morphological studies demonstrated the co-localization of CB1 with GlcNAc residues, and showed that tunicamycin reduced CB1 membrane expression with a marked nuclear localization, as confirmed by immunoblotting. Cleavage of the carbohydrate side chain did not modify CB receptor binding affinity. Overall, these results support N-linked glycosylation as an unprecedented post-translational modification that may modulate eCB-binding receptors’ expression and localization, in particular for CB1.
Dereplication of Components Coupled with HPLC-qTOF-MS in the Active Fraction of Humulus japonicus and It’s Protective Effects against Parkinson’s Disease Mouse Model
Authors: Lee Hee Ju , Dhodary Basanta , Lee Ju Yong , An Jin-Pyo , Ryu Young-Kyoung , Kim Kyoung-Shim , Lee Chul-Ho , Oh Won Keun
Published: April 2019

Humulus japonicus is an annual plant belonging to the Cannabacea family, and it has been traditionally used to treat pulmonary tuberculosis, dysentery, chronic colitis, and hypertension. We investigated the active components against Parkinson’s disease from H. japonicus fraction (HJF) using high performance liquid chromatography (HPLC) coupled with quadruple-time-of-flight mass spectroscopy (qTOF-MS) and NMR. Fourteen compounds were isolated from HJF, including one new compound, using HPLC-qTOF-MS and NMR. The major compounds of HJF were luteolin-7-O-glucoside and apigenin-7-O-glucoside, and there was approximately 12.57- and 9.68-folds increase in the contents of these flavonoids compared to those of the 70% EtOH extract. Apigenin and luteolin exhibited the strongest inhibitory effects on monoamine oxidase (MAO) B enzyme activity. In animal studies, limb-use behavior was significantly reduced by unilateral 6-OHDA lesion and ipsilateral rotations. These results indicated that oral administration of 300 mg/kg HJF resulted in the improvement of motor asymmetry and motor impairment in unilateral 6-OHDA-lesioned mice. HJF, including active components leads to an improvement of motor behavior in a Parkinson’s disease mouse model.
Profile of Bioactive Compounds in the Morphological Parts of Wild Fallopia japonica (Houtt) and Fallopia sachalinensis (F. Schmidt) and Their Antioxidative Activity
Authors: Lachowicz Sabina , Oszmiański Jan
Published: April 2019

The aim of this study was to determine the content of triterpenoids and polyphenols, and antioxidative activity in leaves, stalks, and roots of plants from the species Fallopia as well as to present the main relationship between them. Polyphenolic compounds and triterpenoids were identified with liquid chromatography-photodiode detector-mass spectrometry/quadrupole time of flight (LC-MS-Q/TOF; qualitatively) and quantified with an ultra-performance liquid chromatography-photodiode detector (UPLC-PDA (quantitatively), and their antioxidative activity was determined with radical scavenging capacity (ABTS) and oxygen radical absorbance capacity (ORAC) assays. Generally, the wild Fallopia japonica Houtt. species had 1.2 times higher content of bioactive compounds and antioxidative activity than Fallopia sachalinensis. Contents of polyphenolic compounds determined in leaves, stalks, and roots were on average 17.81, 10.60, and 9.02 g/100 g of dry weight (DW), whereas the average contents of triterpenoids reached 0.78, 0.70, and 0.50 g/100 g DW, respectively. The leaves were a better source of polymeric procyanidins, phenolic acids, flavones, and flavonols, as well as oleanolic and ursolic acids than the other morphological parts of the tested plants. However, the roots were an excellent source of flavan-3-ols (monomeric and oligomer) and stilbenes, such as resveratrol, and their derivatives. The results obtained showed significant differences between plants of the wild Fallopia species and their morphological parts, and enabled selecting the most valuable morphological part of the tested plants to be used for food enrichment and nutraceuticals production. Therefore, the leaves seem to be the best as potential food additives for health, due to the above-average content of polyphenolic compounds and triterpenoids. In turn, roots, with their high contents of stilbenes and polyphenolic compounds, represent a good material for the medical, pharmaceutical, and cosmetic industries. The principal component analysis of the plants of wild Fallopia species and their morphological parts confirmed significant differences in their chemical composition.
1,4-Naphthoquinone Analogues: Potent Antibacterial Agents and Mode of Action Evaluation
Authors: Ravichandiran Palanisamy , Sheet Sunirmal , Premnath Dhanraj , Kim Ae Rhan , Yoo Dong Jin
Published: April 2019

1,4-Naphthoquinones have antibacterial activity and are a promising new class of compound that can be used to treat bacterial infections. The goal was to improve effective antibacterial agents; therefore, we synthesized a new class of naphthoquinone hybrids, which contain phenylamino-phenylthio moieties as significant counterparts. Compound 4 was modified as a substituted aryl amide moiety, which enhanced the antibacterial activity of earlier compounds 3 and 4. In this study, five bacterial strains Staphylococcus aureus (S. aureus), Listeria monocytogenes (L. monocytogenes), Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa) and Klebsiella pneumoniae (K. pneumoniae) were used to evaluate the antibacterial potency of synthesized naphthoquinones using the minimal inhibitory concentration (MIC) method. Most of the studied naphthoquinones demonstrated major antibacterial activity with a MIC of 15.6 µg/mL–500 µg/mL. Selected compounds (5a, 5f and 5x) were studied for the mode of action, using intracellular ROS generation, determination of apoptosis by the Annexin V-FITC/PI assay, a bactericidal kinetic study and in silico molecular modelling. Additionally, the redox potentials of the specified compounds were confirmed by cyclic voltammetry (CV).
Size-Dependent Biological Effects of Quercetin Nanocrystals
Authors: Liu Qian , Yang Xi , Sun Jianxu , Yu Fanglin , Zhang Hui , Gao Jing , Zheng Aiping
Published: April 2019

Quercetin (QE) is an attractive natural compound for cancer prevention due to its beneficial anti-oxidative and anti-proliferative effects. However, QE is poorly soluble in water and slightly soluble in oil, which results in its low oral bioavailability and limits its application in the clinic. The aim of this study was to prepare QE nanocrystals (QE-NCs) with improved solubility and high drug loading, furthermore, the size-dependent anti-cancer effects of QE-NCs were studied. We prepared QE-NCs with three different particle sizes by wet milling, then, cell proliferation, migration and invasion were studied in A549 cells. The QE-NCs had antitumor effects in a dose- and size-dependent manner. Compared with the large particles, the small particles had a strong inhibitory impact on cell biological effects (p < 0.05 or p < 0.01). Moreover, Western blot assay indicated that QE-NCs may inhibit the migration and invasion of A549 cells by inhibiting the STAT3 signaling pathway, and the particle size may have an effect on this process. In this study, it was proven that NCs could dramatically enhance the anticancer efficacy of QE at the cellular level. In addition, particle size had a considerable influence on the dissolution behavior and antitumor effects of NCs.
Tissue-Specific Metabolite Profiling on the Different Parts of Bolting and Unbolting Peucedanum praeruptorum Dunn (Qianhu) by Laser Microdissection Combined with UPLC-Q/TOF–MS and HPLC–DAD
Authors: Chen Ling Li , Chu Shan Shan , Zhang Ling , Xie Jin , Dai Min , Wu Xin , Peng Hua Sheng
Published: April 2019

Background: Qianhu is a traditional Chinese medicine. It is thought that Qianhu roots will harden after bolting and not be suitable for medicinal purposes. Bolting Qianhu and unbolting Qianhu are referred to as “Xiong Qianhu” and “Ci Qianhu,” respectively. In this study, the properties, microscopic and chemical characteristics of Ci Qianhu and Xiong Qianhu roots were compared using fluorescence microscopy, laser microdissection coupled with ultra-high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry, and high-performance liquid chromatography with diode-array detection. Results: Microscopy results showed that the area of secondary xylem in the root increased after bolting, with the cork and secretory canals showing strong fluorescence intensity. A total of 34 peaks, mostly pyranocoumarins, were identified in the tissues of Ci Qianhu and Xiong Qianhu. The secretory canals contained the highest variability of coumarins, whereas the secondary xylem contained the least coumarins. Moreover, seven coumarins, especially the pyran- coumarin, decreased after bolting. Generally, both before and after bolting, coumarin level was the highest in the bark, followed by the middle part, and the lowest in the inner part. Conclusion: Thus, it was indicated that the area of secondary xylem increased after bolting, however the coumarin variant and content decreased in the secondary xylem of Qianhu. The result shows that the quality of Qianhu decreases after bolting, which supports the viewpoint that Xiong Qianhu is not suitable for medicinal use.
Antioxidative and Potentially Anti-inflammatory Activity of Phenolics from Lovage Leaves Levisticum officinale Koch Elicited with Jasmonic Acid and Yeast Extract
Authors: Złotek Urszula , Szymanowska Urszula , Pecio Łukasz , Kozachok Solomiia , Jakubczyk Anna
Published: April 2019

The effect of elicitation with jasmonic acids (JA) and yeast extract (YE) on the production of phenolic compounds as well as the antioxidant and anti-inflammatory properties of phenolic extracts of lovage was evaluated. The analysis of phenolic compounds carried out with the UPLC-MS technique indicated that rutin was the dominant flavonoid, while 5-caffeoylquinic acid was the main component in the phenolic acid fraction in the lovage leaves. The application of 10 µM JA increased the content of most of the identified phenolic compounds. The highest antioxidant activities estimated as free radical scavenging activity against ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and reducing power were determined for the sample elicited with 10 µM JA, while this value determined as iron chelating ability was the highest for the 0.1% YE-elicited lovage. The 0.1% and 1% YE elicitation also caused significant elevation of the lipoxygenase (LOX) inhibition ability, while all the concentrations of the tested elicitors significantly improved the ability to inhibit cyclooxygenase 2 (COX2) (best results were detected for the 10 µM JA and 0.1% YE2 sample). Thus, 0.1% yeast extract and 10 µM jasmonic acid proved to be most effective in elevation of the biological activity of lovage.
Natural Ingredients-Based Gummy Bear Composition Designed According to Texture Analysis and Sensory Evaluation In Vivo
Authors: Čižauskaitė Ugnė , Jakubaitytė Greta , Žitkevičius Virgilijus , Kasparavičienė Giedrė
Published: April 2019

The increased interest in functional materials of natural origin has resulted in a higher market demand for preservative-free, “clean label”, or natural ingredients-based products. The gummy bear food supplements are more acceptable to consumers and have fewer limitations compared to other dosage forms. The aim of our study was to produce natural ingredients-based gummy bear composition, and evaluate the influence of the selected ingredients on the product’s textural properties, its acceptance in vivo, and the gummy bear’s quality. The optimal base composition was determined using a surface response design: gelatin 4.3 g and agave syrup 6.3 g. The investigated sweeteners did not affect the textural properties (p > 0.05). However, further studies demonstrated that a 100% increase of agave results in up to 27% higher flexibility (p < 0.05). The addition of calcium and cholecalciferol reduced firmness by 59.59 ± 1.45% (p < 0.05). On the other hand, acai berry extract had no significant effect. The presence of calcium resulted in a decreased smell and taste; however, the data indicated that experimental texture analysis is a more accurate technique than in vivo evaluation. The acai berry extract did not improve all of the tested sensory properties. We can conclude that the suggested gummy bear base can be supplemented with various active ingredients and commercialized, though further studies are needed to investigate the other natural sources to mask the unpleasant taste of active ingredients and avoid water loss.
MoleGear: A Java-Based Platform for Evolutionary De Novo Molecular Design
Authors: Chu Yunhan , He Xuezhong
Published: April 2019

A Java-based platform, MoleGear, is developed for de novo molecular design based on the chemistry development kit (CDK) and other Java packages. MoleGear uses evolutionary algorithm (EA) to explore chemical space, and a suite of fragment-based operators of growing, crossover, and mutation for assembling novel molecules that can be scored by prediction of binding free energy or a weighted-sum multi-objective fitness function. The EA can be conducted in parallel over multiple nodes to support large-scale molecular optimizations. Some complementary utilities such as fragment library design, chemical space analysis, and graphical user interface are also integrated into MoleGear. The candidate molecules as inhibitors for the human immunodeficiency virus 1 (HIV-1) protease were designed by MoleGear, which validates the potential capability for de novo molecular design.
In Silico Investigation of the Anti-Tumor Mechanisms of Epigallocatechin-3-Gallate
Authors: Wang Wang , Xiong Xiuhong , Li Xue , Zhang Qinyang , Yang Wentao , Du Linfang
Published: April 2019

The EGCG, an important component of polyphenol in green tea, is well known due to its numerous health benefits. We employed the reverse docking method for the identification of the putative targets of EGCG in the anti-tumor target protein database and these targets were further uploaded to public databases in order to understand the underlying pharmacological mechanisms and search for novel EGCG-associated targets. Similarly, the pharmacological linkage between tumor-related proteins and EGCG was manually constructed in order to provide greater insight into the molecular mechanisms through a systematic integration with applicable bioinformatics. The results indicated that the anti-tumor mechanisms of EGCG may involve 12 signaling transduction pathways and 33 vital target proteins. Moreover, we also discovered four novel putative target proteins of EGCG, including IKBKB, KRAS, WEE1 and NTRK1, which are significantly related to tumorigenesis. In conclusion, this work may provide a useful perspective that will improve our understanding of the pharmacological mechanism of EGCG and identify novel potential therapeutic targets.
Fused Heterocyclic Systems with an s-Triazine Ring. 34. Development of a Practical Approach for the Synthesis of 5-Aza-isoguanines
Authors: Junaid Ahmad , Lim Felicia Phei Lin , Zhou Yvonne Peijun , Chui Wai Keung , Dolzhenko Anton V.
Published: April 2019

Purine isosteres present excellent opportunities in drug design and development. Using isosteres of natural purines as scaffolds for the construction of new therapeutic agents has been a valid strategy of medicinal chemistry. Inspired by the similarity to isoguanine, we attempted to develop a practical method for the preparation of 5-aza-isoguanines. Several synthetic approaches were explored to establish a robust general protocol for the preparation of these compounds. The significant difference in the reactivity of the C-5 and C-7 electrophilic centers of 1,2,4-triazolo[1,5-a][1,3,5]triazines (5-azapurines) towards nucleophiles was demonstrated. The most practical and general method for the preparation of 5-aza-isoguanines involved a regioselective reaction of ethoxycarbonyl isothiocyanate with a 5-aminotriazole. The intramolecular ring closure of the resulted product followed by the S-methylation afforded 7-methylthio-2-phenyl-1,2,4-triazolo[1,5-a][1,3,5]triazin-5-one, which could be effectively aminated with various amines. The resulted 5-aza-isoguanines resemble a known purine nucleoside phosphorylase inhibitor and could be interesting for further investigations as potential anticancer agents.
Ameliorative Effect and Mechanism of the Purified Anthraquinone-Glycoside Preparation from Rheum Palmatum L. on Type 2 Diabetes Mellitus
Authors: Cheng Fang-Rong , Cui Hong-Xin , Fang Ji-Li , Yuan Ke , Guo Ying
Published: April 2019

Rheum palmatum L. is a traditional Chinese medicine with various pharmacological properties, including anti-inflammatory, antibacterial, and detoxification effects. In this study, the mechanism of the hypoglycemic effect of purified anthraquinone-Glycoside from Rheum palmatum L. (PAGR) in streptozotocin (STZ) and high-fat diet induced type 2 diabetes mellitus (T2DM) in rats was investigated. The rats were randomly divided into normal (NC), T2DM, metformin (Met), low, middle (Mid), and high (Hig) does of PAGR groups. After six weeks of continuous administration of PAGR, the serum indices and tissue protein expression were determined, and the pathological changes in liver, kidney, and pancreas tissues were observed. The results showed that compared with the type 2 diabetes mellitus group, the fasting blood glucose (FBG), total cholesterol (TC), and triglyceride (TG) levels in the serum of rats in the PAGR treatment groups were significantly decreased, while superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) levels were noticeably increased. The expression of Fas ligand (FasL), cytochrome C (Cyt-c), and caspase-3 in pancreatic tissue was obviously decreased, and the pathological damage to the liver, kidney, and pancreas was improved. These indicate that PAGR can reduce oxidative stress in rats with diabetes mellitus by improving blood lipid metabolism and enhancing their antioxidant capacity, thereby regulating the mitochondrial apoptotic pathway to inhibitβ-cell apoptosis and improve β-cell function. Furthermore, it can regulate Fas/FasL-mediated apoptosis signaling pathway to inhibit β-cell apoptosis, thereby lowering blood glucose levels and improving T2DM.
Template-Assisted Synthesis of Luminescent Carbon Nanofibers from Beverage-Related Precursors by Microwave Heating
Authors: Deeney Clara , McKiernan Eoin P. , Belhout Samir A. , Rodriguez Brian J. , Redmond Gareth , Quinn Susan J.
Published: April 2019

Luminescent carbon nanomaterials are important materials for sensing, imaging, and display technologies. This work describes the use of microwave heating for the template-assisted preparation of luminescent carbon nanofibers (CNFs) from the reaction of a range of beverage-related precursors with the nitrogen-rich polyethyleneimine. Highly luminescent robust carbon fibers that were 10 to 30 μm in length and had a diameter of 200 nm were obtained under moderate conditions of temperature (250–260 °C) and a short reaction time (6 min). The high aspect ratio fibers showed wavelength-dependent emission that can be readily imaged using epifluorescence. The development of these multi-emissive one-dimensional (1D) carbon nanomaterials offers potential for a range of applications.