bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitrogen Removal Performance and Metabolic Pathways Analysis of a Novel Aerobic Denitrifying Halotolerant Pseudomonas balearica Strain RAD-17
Authors: Ruan Yunjie , Taherzadeh Mohammad J. , Kong Dedong , Lu Huifeng , Zhao Heping , Xu Xiangyang , Liu Yu , Cai Lei
Published: January 2020

An aerobic denitrification strain, Pseudomonas balearica RAD-17, was identified and showed efficient inorganic nitrogen removal ability. The average NO3−-N, NO2−-N, and total ammonium nitrogen (TAN) removal rate (>95% removal efficiency) in a batch test was 6.22 mg/(L∙h), 6.30 mg/(L∙h), and 1.56 mg/(L∙h), respectively. Meanwhile, optimal incubate conditions were obtained through single factor experiments. For nitrogen removal pathways, the transcriptional results proved that respiratory nitrate reductases encoded by napA, which was primarily performed in aerobic denitrification and cell assimilation, were conducted by gluS and gluD genes for ammonium metabolism. In addition, adding the strain RAD-17 into actual wastewater showed obvious higher denitrification performance than in the no inoculum group (84.22% vs. 22.54%), and the maximum cell abundance achieved 28.5 ± 4.5% in a ratio of total cell numbers. Overall, the efficient nitrogen removal performance plus strong environmental fitness makes the strain RAD-17 a potential alternative for RAS (recirculating aquaculture system) effluent treatment.
Occurrence and Co-Occurrence of Mycotoxins in Cereal-Based Feed and Food
Authors: Palumbo Roberta , Crisci Alfonso , Venâncio Armando , Cortiñas Abrahantes José , Dorne Jean-Lou , Battilani Paola , Toscano Piero
Published: January 2020

Dietary (co)-exposure to mycotoxins is associated with human and animal health concerns as well as economic losses. This study aims to give a data-based insight from the scientific literature on the (co-)occurrence of mycotoxins (i.e., parent and modified forms) in European core cereals, and to estimate potential patterns of co-exposure in humans and animals. Mycotoxins were mainly reported in wheat and maize showing the highest concentrations of fumonisins (FBs), deoxynivalenol (DON), aflatoxins (AFs), and zearalenone (ZEN). The maximum concentrations of FB1+FB2 were reported in maize both in feed and food and were above legal maximum levels (MLs). Similar results were observed in DON-food, whose max concentrations in wheat, barley, maize, and oat exceeded the MLs. Co-occurrence was reported in 54.9% of total records, meaning that they were co-contaminated with at least two mycotoxins. In the context of parental mycotoxins, co-occurrence of DON was frequently observed with FBs in maize and ZEN in wheat; DON + NIV and DON + T2/HT2 were frequently reported in barley and oat, respectively. Apart from the occurrence of ZEN and its phase I and phase II modified forms, only a limited number of quantified data were available for other modified forms; i.e., mainly the acetyl derivatives of DON. Data gaps are highlighted together with the need for monitoring studies on multiple mycotoxins to identify co-occurrence patterns for parent mycotoxins, metabolites, and their modified forms.
Identification of Differentially Expressed Proteins in Sugarcane in Response to Infection by Xanthomonas albilineans Using iTRAQ Quantitative Proteomics
Authors: Meng Jian-Yu , Ntambo Mbuya Sylvain , Rott Philippe C. , Fu Hua-Ying , Huang Mei-Ting , Zhang Hui-Li , Gao San-Ji
Published: January 2020

Sugarcane can suffer severe yield losses when affected by leaf scald, a disease caused by Xanthomonas albilineans. This bacterial pathogen colonizes the vascular system of sugarcane, which can result in reduced plant growth and plant death. In order to better understand the molecular mechanisms involved in the resistance of sugarcane to leaf scald, a comparative proteomic study was performed with two sugarcane cultivars inoculated with X. albilineans: one resistant (LCP 85-384) and one susceptible (ROC20) to leaf scald. The iTRAQ (isobaric tags for relative and absolute quantification) approach at 0 and 48 h post-inoculation (hpi) was used to identify and annotate differentially expressed proteins (DEPs). A total of 4295 proteins were associated with 1099 gene ontology (GO) terms by GO analysis. Among those, 285 were DEPs during X. albilineans infection in cultivars LCP 85-384 and ROC20. One hundred seventy-two DEPs were identified in resistant cultivar LCP 85-384, and 113 of these proteins were upregulated and 59 were downregulated. One hundred ninety-two DEPs were found in susceptible cultivar ROC20 and half of these (92) were upregulated, whereas the other half corresponded to downregulated proteins. The significantly upregulated DEPs in LCP 85-384 were involved in metabolic pathways, the biosynthesis of secondary metabolites, and the phenylpropanoid biosynthesis pathway. Additionally, the expression of seven candidate genes related to photosynthesis and glycolytic pathways, plant innate immune system, glycosylation process, plant cytochrome P450, and non-specific lipid transfer protein was verified based on transcription levels in sugarcane during infection by X. albilineans. Our findings shed new light on the differential expression of proteins in sugarcane cultivars in response to infection by X. albilineans. The identification of these genes provides important information for sugarcane variety improvement programs using molecular breeding strategies.
Identifying Ortholog Selective Fragment Molecules for Bacterial Glutaredoxins by NMR and Affinity Enhancement by Modification with an Acrylamide Warhead
Authors: Khattri Ram B. , Morris Daniel L. , Bilinovich Stephanie M. , Manandhar Erendra , Napper Kahlilah R. , Sweet Jacob W. , Modarelli David A. , Leeper Thomas C.
Published: January 2020

Illustrated here is the development of a new class of antibiotic lead molecules targeted at Pseudomonas aeruginosa glutaredoxin (PaGRX). This lead was produced to (a) circumvent efflux-mediated resistance mechanisms via covalent inhibition while (b) taking advantage of species selectivity to target a fundamental metabolic pathway. This work involved four components: a novel workflow for generating protein specific fragment hits via independent nuclear magnetic resonance (NMR) measurements, NMR-based modeling of the target protein structure, NMR guided docking of hits, and synthetic modification of the fragment hit with a vinyl cysteine trap moiety, i.e., acrylamide warhead, to generate the chimeric lead. Reactivity of the top warhead-fragment lead suggests that the ortholog selectivity observed for a fragment hit can translate into a substantial kinetic advantage in the mature warhead lead, which bodes well for future work to identify potent, species specific drug molecules targeted against proteins heretofore deemed undruggable.
Design of Iodonium Salts for UV or Near-UV LEDs for Photoacid Generator and Polymerization Purposes
Authors: Villotte Ségolène , Gigmes Didier , Dumur Frédéric , Lalevée Jacques
Published: January 2020

Iodonium salts are well established photoacid generators, cationic photoinitiators, as well as additives commonly used in photoredox catalytic cycles. However, as a strong limitation, iodonium salts are characterized by low light absorption properties for λ > 300 nm so that these latter cannot be activated with cheap, safe, and eco-friendly near UV or even visible light emitting diodes (LEDs). To overcome this drawback, the covalent linkage of an iodonium salt to a chromophore absorbing at longer wavelength is actively researched. With aim at red-shifting the absorption spectrum of the iodonium salt, the synthesis of new compounds combining within a unique chemical structure both the chromophore (here the naphthalimide scaffold) and the iodonium salt is presented. By mean of this strategy, a polymerization could be initiated at 365 nm with the modified iodonium salts whereas no polymerization could be induced with the benchmark iodonium salt i.e., Speedcure 938 at this specific wavelength. To examine the effect of the counter-anion on the photoinitiating ability of these different salts, five different counter-anions were used. Comparison between the different anions revealed the bis(trifluoromethane)sulfonimide salt to exhibit the best photoinitiating ability in both the free radical polymerization of acrylates and the cationic polymerization of epoxides. To support the experimental results, molecular orbital calculations have been carried out. By theoretical calculations, the initiating species resulting from the photocleavage of the iodonium salts could be determined. The cleavage selectivity and the photochemical reactivity of the new iodoniums are also discussed.
Photochromic and Photocatalytic Properties of Ultra-Small PVP-Stabilized WO3 Nanoparticles
Authors: Kozlov Daniil A. , Shcherbakov Alexander B. , Kozlova Taisiya O. , Angelov Borislav , Kopitsa Gennady P. , Garshev Alexey V. , Baranchikov Alexander E. , Ivanova Olga S. , Ivanov Vladimir K.
Published: January 2020

Tungsten oxide-based bulk and nanocrystalline materials are widely used as photocatalytic and photo- and electrochromic materials, as well as materials for biomedical applications. In our work, we focused our attention on the effect of sodium cations on the structure and photochromic properties of the WO3@PVP aqueous sols. To establish the effect, the sols were synthesized by either simple pH adjusting of sodium or ammonium tungstates’ solutions, or using an ion exchange technique to remove the cations from the materials to the greatest possible extent. We showed that the presence of sodium cations in WO3@PVP favors the formation of reduced tungsten species (W+5) upon UV irradiation of the materials, strongly affecting their photochromic and photocatalytic properties. The pronounced photoreductive properties of WO3@PVP sols in photocatalytic reactions were demonstrated. Due to photoreductive properties, photochromic sols of tungsten oxide can act as effective photoprotectors in photooxidation processes. We believe that our work provides a considerable contribution to the elucidation of photochromic and redox phenomena in WO3-based materials.
Promising Terpenes as Natural Antagonists of Cancer: An In-Silico Approach
Authors: Muhseen Ziyad Tariq , Li Guanglin
Published: January 2020

Overexpression of murine double minute 2 (MDM2) results in the inactivation of p53 and causes cancer which is a leading cause of death in recent era. In recent decades, much attention has been paid to discover potential inhibitors against MDM2 in order to cure cancer. Outcomes from studies proposes that the MDM2 is a hot target to screen potent antagonists. Thus, this study aims at discovering natural compounds using several computational approaches to inhibit the MDM2 and to eliminate p53-MDM2 interaction, which would result in the reactivation of p53 activity. A library of 500 terpenes was prepared and several virtual screening approaches were employed to find out the best hits which could serve as p53-MDM2 antagonists. On the basis of the designed protocol, three terpenes were selected. In the present study, for the stability and validation of selected three protein-ligand complexes 20 ns molecular dynamics simulations and principal component analyses (PCA) were performed. Results found that the selected terpenes hits (3-trans-p-coumaroyl maslinic acid, Silvestrol and Betulonic acid) are potential inhibitors of p53–MDM2 interaction and could serve as potent antagonists.
Meroterpenoids from the Fungus Ganoderma sinensis and First Absolute Configuration Clarification of Zizhine H
Authors: Yin Yan-Jiao , Huang Dan-Ling , Qiu Bin , Cai Dan , Zhang Jiao-Jiao , Wang Shao-Xiang , Qin Da-Peng , Cheng Yong-Xian
Published: January 2020

Five new meroterpenoids, zizhines P-S and U (1−4,7), together with two known meroterpenoids (5 and 6) were isolated from Ganoderma sinensis. Their structures including absolute configurations were assigned by using spectroscopic, computational, and chemical methods. Racemics zizhines P and Q were purified by HPLC on chiral phase. Biological evaluation found that 4, 5 and 6 are cytotoxic toward human cancer cells (A549, BGC-823, Kyse30) with IC50 values in the range of 63.43–80.83 μM towards A549, 59.2 ± 2.73 μM and 64.25 ± 0.37 μM towards BGC-823, 76.28 ± 1.93 μM and 85.42 ± 2.82 μM towards Kyse30.
Corrections of Molecular Morphology and Hydrogen Bond for Improved Crystal Density Prediction
Authors: Wang Linyuan , Zhang Miao , Chen Jie , Su Liang , Zhao Shicao , Zhang Chaoyang , Liu Jian , Chen Chunyan
Published: January 2020

Density prediction is of great significance for molecular design of energetic materials, since detonation velocity linearly with density and detonation pressure increases with the density squared. However, the accuracy and generalization of former reported prediction models need further improvement, because most of them are derived from small data sets and few molecular descriptors. As shown in this paper, for molecules presenting brick-like shape or containing more hydrogen-bond donors the predicted densities have large negative deviations from experimental values. Thus, a molecular morphology descriptor η and a hydrogen-bond descriptor Hb are introduced as correction items to build 3 new QSPR models. Besides, 3694 nitro compounds are adopted as data set by this work. The accuracies are obviously improved, and the generalizations are verified by an independent test set. At the level of B3PW91/6-31G(d,p), the effective ratios (ERs) of the 3 Equations, for Δρ < 5%, are 92.7%, 91.8%, and 93.3%; for Δρ < 2%, the values are 53.5%, 51.3%, and 54.7%. At the level of B3LYP/6-31G**, for Δρ < 5%, the values are 92.3%, 91.4% and 92.9%; for Δρ < 2%, the values are 53.7%, 51.4% and 53.2%.
L-Carnitine Is Involved in Hyperbaric Oxygen-Mediated Therapeutic Effects in High Fat Diet-Induced Lipid Metabolism Dysfunction
Authors: Yuan Junhua , Jiang Qixiao , Song Limin , Liu Yuan , Li Manwen , Lin Qian , Li Yanrun , Su Kaizhen , Ma Zhengye , Wang Yifei , Liu Defeng , Dong Jing
Published: January 2020

Lipid metabolism dysfunction and obesity are serious health issues to human beings. The current study investigated the effects of hyperbaric oxygen (HBO) against high fat diet (HFD)-induced lipid metabolism dysfunction and the roles of L-carnitine. C57/B6 mice were fed with HFD or normal chew diet, with or without HBO treatment. Histopathological methods were used to assess the adipose tissues, serum free fatty acid (FFA) levels were assessed with enzymatic methods, and the endogenous circulation and skeletal muscle L-carnitine levels were assessed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Additionally, western blotting was used to assess the expression levels of PPARα, CPT1b, pHSL/HSL, and UCP1. HFD treatment increased body/adipose tissue weight, serum FFA levels, circulation L-carnitines and decreased skeletal muscle L-carnitine levels, while HBO treatment alleviated such changes. Moreover, HFD treatment increased fatty acid deposition in adipose tissues and decreased the expression of HSL, while HBO treatment alleviated such changes. Additionally, HFD treatment decreased the expression levels of PPARα and increased those of CPT1b in skeletal muscle, while HBO treatment effectively reverted such changes as well. In brown adipose tissues, HFD increased the expression of UCP1 and the phosphorylation of HSL, which was abolished by HBO treatment as well. In summary, HBO treatment may alleviate HFD-induced fatty acid metabolism dysfunction in C57/B6 mice, which seems to be associated with circulation and skeletal muscle L-carnitine levels and PPARα expression.
Evaluation Procoagulant Activity and Mechanism of Astragalin
Authors: Li Changqin , Hu Miyun , Jiang Shengjun , Liang Zhenhua , Wang Jinmei , Liu Zhenhua , Wang Hui-Min David , Kang Wenyi
Published: January 2020

Astragalin, isolated from flowers of Rosa chinensis Jacq., is a kind of flavonoid, with anti-inflammatory, antioxidant, antiviral, analgesic, antibacterial, antiallergic, and antihepatotoxic effects. However, no studieson the procoagulant effect of astragalin have been reported. This study aimed to investigate the procoagulant activity of astragalin and its mechanism. Its procoagulant effect was investigated by activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), and fibrinogen (FIB) in vitro, and a rat model established by heparin sodium was used to evaluate the mechanism for the procoagulant effect in vivo. The results showed that astragalin had good procoagulant effects compared with the control group in vitro. Compared with the model group in vivo, astragalin could shorten the coagulation time and significantly increase the number of platelets. Meanwhile, astragalin could significantly reduce the effectual time of PT and APTT and increase the content of FIB. The contents of 6-keto-PGF1α and eNOS significantly decreased. Astragalin could increase whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte sedimentation rate (ESR) and packedcell volume (PCV). All of the above revealed that astragalin had good procoagulant effects by promoting the intrinsic and extrinsic coagulation system.
Phytochemical Profiles and Cellular Antioxidant Activities in Chestnut (Castanea mollissima BL.) Kernels of Five Different Cultivars
Authors: Chang Xiaoxiao , Liu Fengyuan , Lin Zhixiong , Qiu Jishui , Peng Cheng , Lu Yusheng , Guo Xinbo
Published: January 2020

In this study, the phytochemical profiles, total and cellular antioxidant activities of five different Chinese chestnut (Castanea mollissima BL.) cultivars were analyzed. Phenolics, flavonoids as well as phytochemical compounds in five cultivars of chestnut kernels were determined. Results showed that the free forms played a dominant role in total phenolics, flavonoids and antioxidant activities of all five cultivars of chestnut kernels. The cultivar ‘Fyou’ showed the highest total and free phenolic contents, ‘Heguoyihao’ showed the highest total and free flavonoids contents, and ‘Chushuhong’ showed the highest total and cellular antioxidant activities. Eight phenolic compounds were detected, and chlorogenic acid, gallic acid, and quercetin were shown as three predominant components in all five cultivars. These results provide valuable information which may be a guidance for selection of good chestnut variety to be used as functional food.
Mainly Dimers and Trimers of Chinese Bayberry Leaves Proanthocyanidins (BLPs) are Utilized by Gut Microbiota: In Vitro Digestion and Fermentation Coupled with Caco-2 Transportation
Authors: Tao Wenyang , Wei Chaoyang , Shen Shuyu , Wang Mengting , Chen Shiguo , Ye Xingqian , Cao Yanping
Published: January 2020

Chinese bayberry leaf proanthocyanidins (BLPs) are Epigallocatechin gallate (EGCG) oligomers or polymers, which have a lot of health-promoting activity. The activity is closely related to their behavior during in vitro digestion, which remains unknown and hinders further investigations. To clarify the changes of BLPs during gastrointestinal digestion, further research is required. For in vitro digestion, including gastric-intestinal digestion, colon fermentation was applied. Caco-2 monolayer transportation was also applied to investigate the behavior of different BLPs with different degrees of polymerization. The trimers and the tetramers were significantly decreased during in vitro gastric-intestinal digestion resulting in a significant increase in the content of dimers. The dimers and trimers were the main compounds utilized by gut microbiota and they were assumed not to degrade through cleavage of the inflavan bond. The monomers and dimers were able to transport through the Caco-2 monolayer at a rate of 10.45% and 6.4%, respectively.
Pterostilbene Enhances Endurance Capacity via Promoting Skeletal Muscle Adaptations to Exercise Training in Rats
Authors: Zheng Jiawei , Liu Wujian , Zhu Xiaohui , Ran Li , Lang Hedong , Yi Long , Mi Mantian , Zhu Jundong
Published: January 2020

It has been demonstrated that skeletal muscle adaptions, including muscle fibers transition, angiogenesis, and mitochondrial biogenesis are involved in the regular exercise-induced improvement of endurance capacity and metabolic status. Herein, we investigated the effects of pterostilbene (PST) supplementation on skeletal muscle adaptations to exercise training in rats. Six-week-old male Sprague Dawley rats were randomly divided into a sedentary control group (Sed), an exercise training group (Ex), and exercise training combined with 50 mg/kg PST (Ex + PST) treatment group. After 4 weeks of intervention, an exhaustive running test was performed, and muscle fiber type transformation, angiogenesis, and mitochondrial content in the soleus muscle were measured. Additionally, the effects of PST on muscle fiber transformation, paracrine regulation of angiogenesis, and mitochondrial function were tested in vitro using C2C12 myotubes. In vivo study showed that exercise training resulted in significant increases in time-to-exhaustion, the proportion of slow-twitch fibers, muscular angiogenesis, and mitochondrial biogenesis in rats, and these effects induced by exercise training could be augmented by PST supplementation. Moreover, the in vitro study showed that PST treatment remarkably promoted slow-twitch fibers formation, angiogenic factor expression, and mitochondrial function in C2C12 myotubes. Collectively, our results suggest that PST promotes skeletal muscle adaptations to exercise training thereby enhancing the endurance capacity.
Identification of Potential Dipeptidyl Peptidase (DPP)-IV Inhibitors among Moringa oleifera Phytochemicals by Virtual Screening, Molecular Docking Analysis, ADME/T-Based Prediction, and In Vitro Analyses
Authors: Yang Yang , Shi Chong-Yin , Xie Jing , Dai Jia-He , He Shui-Lian , Tian Yang
Published: January 2020

Moringa oleifera Lam. (MO) is called the “Miracle Tree” because of its extensive pharmacological activity. In addition to being an important food, it has also been used for a long time in traditional medicine in Asia for the treatment of chronic diseases such as diabetes and obesity. In this study, by constructing a library of MO phytochemical structures and using Discovery Studio software, compounds were subjected to virtual screening and molecular docking experiments related to their inhibition of dipeptidyl peptidase (DPP-IV), an important target for the treatment of type 2 diabetes. After the four-step screening process, involving screening for drug-like compounds, predicting the absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of pharmacokinetic properties, LibDock heatmap matching analysis, and CDOCKER molecular docking analysis, three MO components that were candidate DPP-IV inhibitors were identified and their docking modes were analyzed. In vitro activity verification showed that all three MO components had certain DPP-IV inhibitory activities, of which O-Ethyl-4-[(α-l-rhamnosyloxy)-benzyl] carbamate (compound 1) had the highest activity (half-maximal inhibitory concentration [IC50] = 798 nM). This study provides a reference for exploring the molecular mechanisms underlying the anti-diabetic activity of MO. The obtained DPP-IV inhibitors could be used for structural optimization and in-depth in vivo evaluation.
Metabolome and Transcriptome Analysis Reveals Putative Genes Involved in Anthocyanin Accumulation and Coloration in White and Pink Tea (Camellia sinensis) Flower
Authors: Zhou Caibi , Mei Xin , Rothenberg Dylan O’Neill , Yang Zaibo , Zhang Wenting , Wan Shihua , Yang Haijun , Zhang Lingyun
Published: January 2020

A variant of tea tree (Camellia sinensis (L.)) with purple buds and leaves and pink flowers can be used as a unique ornamental plant. However, the mechanism of flower coloration remains unclear. To elucidate the molecular mechanism of coloration, as well as anthocyanin accumulation in white and pink tea flowers, metabolite profiling and transcriptome sequencing was analyzed in various tea flower developmental stages. Results of metabolomics analysis revealed that three specific anthocyanin substances could be identified, i.e., cyanidin O-syringic acid, petunidin 3-O-glucoside, and pelargonidin 3-O-β-d-glucoside, which only accumulated in pink tea flowers, and were not able to be detected in white flowers. RNA-seq and weighted gene co-expression network analysis revealed eight highly expressed structural genes involved in anthocyanin biosynthetic pathway, and particularly, different expression patterns of flavonol synthase and dihydroflavonol-4-reductase genes were observed. We deduced that the disequilibrium of expression levels in flavonol synthases and dihydroflavonol-4-reductases resulted in different levels of anthocyanin accumulation and coloration in white and pink tea flowers. Results of qRT-PCR performed for 9 key genes suggested that the expression profiles of differentially expressed genes were generally consistent with the results of high-throughput sequencing. These findings provide insight into anthocyanin accumulation and coloration mechanisms during tea flower development, which will contribute to the breeding of pink-flowered and anthocyanin-rich tea cultivars.
Hybrid Mesoporous Silica Nanoparticles Grafted with 2-(tert-butylamino)ethyl Methacrylate-b-poly(ethylene Glycol) Methyl Ether Methacrylate Diblock Brushes as Drug Nanocarrier
Authors: Alswieleh Abdullah M , Beagan Abeer M , Alsheheri Bayan M , Alotaibi Khalid M , Alharthi Mansour D , Almeataq Mohammed S
Published: January 2020

This paper introduces the synthesis of well-defined 2-(tert-butylamino)ethyl methacrylate-b-poly(ethylene glycol) methyl ether methacrylate diblock copolymer, which has been grafted onto mesoporous silica nanoparticles (PTBAEMA-b-PEGMEMA-MSNs) via atom transfer radical polymerization (ATRP). The ATRP initiators were first attached to the MSN surfaces, followed by the ATRP of 2-(tert-butylamino)ethyl methacrylate (PTBAEMA). CuBr2/bipy and ascorbic acid were employed as the catalyst and reducing agent, respectively, to grow a second polymer, poly(ethylene glycol) methyl ether methacrylate (PEGMEMA). The surface structures of these fabricated nanomaterials were then analyzed using Fourier Transform Infrared (FTIR) spectroscopy. The results of Thermogravimetric Analysis (TGA) show that ATRP could provide a high surface grafting density for polymers. Dynamic Light Scattering (DLS) was conducted to investigate the pH-responsive behavior of the diblock copolymer chains on the nanoparticle surface. In addition, multifunctional pH-sensitive PTBAEMA-b-PEGMEMA-MSNs were loaded with doxycycline (Doxy) to study their capacities and long-circulation time.
Gold Nanoparticles in Conjunction with Nucleic Acids as a Modern Molecular System for Cellular Delivery
Authors: Graczyk Anna , Pawlowska Roza , Jedrzejczyk Dominika , Chworos Arkadiusz
Published: January 2020

Development of nanotechnology has become prominent in many fields, such as medicine, electronics, production of materials, and modern drugs. Nanomaterials and nanoparticles have gained recognition owing to the unique biochemical and physical properties. Considering cellular application, it is speculated that nanoparticles can transfer through cell membranes following different routes exclusively owing to their size (up to 100 nm) and surface functionalities. Nanoparticles have capacity to enter cells by themselves but also to carry other molecules through the lipid bilayer. This quality has been utilized in cellular delivery of substances like small chemical drugs or nucleic acids. Different nanoparticles including lipids, silica, and metal nanoparticles have been exploited in conjugation with nucleic acids. However, the noble metal nanoparticles create an alternative, out of which gold nanoparticles (AuNP) are the most common. The hybrids of DNA or RNA and metal nanoparticles can be employed for functional assemblies for variety of applications in medicine, diagnostics or nano-electronics by means of biomarkers, specific imaging probes, or gene expression regulatory function. In this review, we focus on the conjugates of gold nanoparticles and nucleic acids in the view of their potential application for cellular delivery and biomedicine. This review covers the current advances in the nanotechnology of DNA and RNA-AuNP conjugates and their potential applications. We emphasize the crucial role of metal nanoparticles in the nanotechnology of nucleic acids and explore the role of such conjugates in the biological systems. Finally, mechanisms guiding the process of cellular intake, essential for delivery of modern therapeutics, will be discussed.
Isoflavones Isolated from the Seeds of Millettia ferruginea Induced Apoptotic Cell Death in Human Ovarian Cancer Cells
Authors: Wang Yi-Yue , Kwak Jun Hyeok , Lee Kyung-Tae , Deyou Tsegaye , Jang Young Pyo , Choi Jung-Hye
Published: January 2020

The seeds of Millettia ferruginea are used in fishing, pesticides, and folk medicine in Ethiopia. Here, the anti-cancer effects of isoflavones isolated from M. ferruginea were evaluated in human ovarian cancer cells. We found that isoflavone ferrugone and 6,7-dimethoxy-3’,4’-methylenedioxy-8-(3,3-dimethylallyl)isoflavone (DMI) had potent cytotoxic effects on human ovarian cancer cell A2780 and SKOV3. Ferrugone and DMI treatment increased the sub-G1 cell population in a dose-dependent manner in A2780 cells. The cytotoxic activity of ferrugone and DMI was associated with the induction of apoptosis, as shown by an increase in annexin V-positive cells. Z-VAD-fmk, a broad-spectrum caspase inhibitor, and z-DEVD-fmk, a caspase-3 inhibitor, significantly reversed both the ferrugone and DMI-induced apoptosis, suggesting that cell death stimulated by the isoflavones is mediated by caspase-3-dependent apoptosis. Additionally, ferrugone-induced apoptosis was found to be caspase-8-dependent, while DMI-induced apoptosis was caspase-9-dependent. Notably, DMI, but not ferrugone, increased the intracellular levels of reactive oxygen species (ROS), and antioxidant N-acetyl-L-cysteine (NAC) attenuated the pro-apoptotic activity of DMI. These data suggest that DMI induced apoptotic cell death through the intrinsic pathway via ROS production, while ferrugone stimulated the extrinsic pathway in human ovarian cancer cells.
Pharmacokinetic Comparison of Epinastine Using Developed Human Plasma Assays
Authors: Jeong Seung-Hyun , Jang Ji-Hun , Cho Hea-Young , Lee Yong-Bok
Published: January 2020

The purpose of the study was to develop two new methods, HPLC-UV and UPLC-MS/MS, for quantifying epinastine in human plasma and to compare pharmacokinetic (PK) parameters obtained using them. Even in the same sample, there may be a difference in the quantitative value of drug depending on the assay, so that minor changes in PK parameter values may affect drug dose and usage settings. Therefore, selection and establishment of analytical methods are very important in PK studies of drugs, and a comparison of PK parameters according to analytical methods will be vital. For this study of PK parameter change, we newly developed two methods, HPLC-UV and UPLC-MS/MS, which are most commonly used to quantify epinastine concentrations in human plasma. All developed methods satisfied the international guidelines and criteria for successful application to PK study of 20 mg epinastine hydrochloride tablets after oral administration to twenty-six humans. A comparison of these two methods for in vivo analysis of epinastine was performed for the first time. This comparison study confirmed that different dose and usage settings might be possible based on PK parameters calculated using other analyses. Such changes in calculated PK parameters according to analytical methods would be crucial in the clinic.
An Efficient Synthesis and Photoelectric Properties of Green Carbon Quantum Dots with High Fluorescent Quantum Yield
Authors: Zheng Jingxia , Xie Yanting , Wei Yingying , Yang Yongzhen , Liu Xuguang , Chen Yongkang , Xu Bingshe
Published: January 2020

To greatly improve the production quality and efficiency of carbon quantum dots (CQDs), and provide a new approach for the large-scale production of high-quality CQDs, green carbon quantum dots (g-CQDs) with high product yield (PY) and high fluorescent quantum yield (QY) were synthesized by an efficient one-step solvothermal method with 2,7-dihydroxynaphthalene as the carbon source and ethylenediamine as the nitrogen dopant in this study. The PY and QY of g-CQDs were optimised by adjusting reaction parameters such as an amount of added ethylenediamine, reaction temperature, and reaction duration. The results showed that the maximum PY and QY values of g-CQDs were achieved, which were 70.90% and 62.98%, respectively when the amount of added ethylenediamine, reaction temperature, and reaction duration were 4 mL, 180 °C, and 12 h, respectively. With the optimised QY value of g-CQDs, white light emitting diodes (white LEDs) were prepared by combining g-CQDs and blue chip. The colour rendering index of white LEDs reached 87, and the correlated colour temperature was 2520 K, which belongs to the warm white light area and is suitable for indoor lighting. These results indicate that g-CQDs have potential and wide application prospects in the field of white LEDs.
A Convenient Colorimetric Bacteria Detection Method Utilizing Chitosan-Coated Magnetic Nanoparticles
Authors: Le Thao Nguyen , Tran Tai Duc , Kim Moon Il
Published: January 2020

An effective novel strategy to detect bacteria is promising because it may improve human health by allowing early diagnosis and timely treatment of bacterial infections. Here, we report a simple, reliable, and economical colorimetric assay using the peroxidase-like activity of chitosan-coated iron oxide magnetic nanoparticles (CS-MNPs). When CS-MNPs are incubated with a sample containing bacterial cells such as the gram-negative Escherichia coli or the gram-positive Staphylococcus aureus, the negatively-charged bacterial membrane interacts with positively-charged chitosan on the surface of CS-MNPs, thus resulting in significant reduction of their peroxidase-like activity presumably by a hindrance in the accessibility of the negatively charged substrate, 2-2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) to the positively-charged CS-MNPs. This simple colorimetric strategy allowed the rapid detection of bacterial cells down to 104 CFU mL−1 by the naked eye and 102 CFU mL−1 by spectrophotometry within 10 min. Based on the results, we anticipate that the CS-MNPs-based assay has great potential for the on-site diagnosis of bacterial infections in facility-limited or point-of-care testing (POCT) environments.
Recent Developments and Prospects of M13- Bacteriophage Based Piezoelectric Energy Harvesting Devices
Authors: Park In Woo , Kim Kyung Won , Hong Yunhwa , Yoon Hyun Ji , Lee Yonghun , Gwak Dham , Heo Kwang
Published: January 2020

Recently, biocompatible energy harvesting devices have received a great deal of attention for biomedical applications. Among various biomaterials, viruses are expected to be very promising biomaterials for the fabrication of functional devices due to their unique characteristics. While other natural biomaterials have limitations in mass-production, low piezoelectric properties, and surface modification, M13 bacteriophages (phages), which is one type of virus, are likely to overcome these issues with their mass-amplification, self-assembled structure, and genetic modification. Based on these advantages, many researchers have started to develop virus-based energy harvesting devices exhibiting superior properties to previous biomaterial-based devices. To enhance the power of these devices, researchers have tried to modify the surface properties of M13 phages, form biomimetic hierarchical structures, control the dipole alignments, and more. These methods for fabricating virus-based energy harvesting devices can form a powerful strategy to develop high-performance biocompatible energy devices for a wide range of practical applications in the future. In this review, we discuss all these issues in detail.
Substitution of Ag for Cu in Cu2ZnSn(S,Se)4: Toward Wide Band Gap Absorbers with Low Antisite Defects for Thin Film Solar Cells
Authors: Wu Yanjie , Sui Yingrui , He Wenjie , Zeng Fancong , Wang Zhanwu , Wang Fengyou , Yao Bin , Yang Lili
Published: January 2020

Cation substitution is a promising approach to reduce the antisite defects and further improve the efficiency of Cu2ZnSn(S,Se)4 (CZTSSe) cells. In this paper, silver (Ag) has been introduced into Cu2ZnSn(S,Se)4 (CZTSSe) thin film to replace Cu partially and form (Cu1-xAgx)2ZnSn(S,Se)4 (0 ≤ x ≤ 1) (CAZTSSe) alloy films by combination of solution method and a rapid annealing technique. The fundamental properties of the mixed Ag-Cu kesterite compound are systematically reported as a function of the Ag/(Ag+Cu) ratio. The results show that band gap of kesterite CAZTSSe is incessantly increased by adjusting the Ag doping content, indicating that the CAZTSSe alloy film is a potentially applicable bandgap grading absorption layers material to obtain higher CZTSSe device. Furthermore, CAZTSSe alloy films with better electrical performance were also obtained by adjusting the Ag content during film fabrication. Finally, we also observed an increment in open circuit voltage (Voc) by 160 mV and an accompanying rise in device efficiency from 4.24 to 5.95%. The improvement is correlated to the improved grain size and decreased antisite defects of Cu instead of Zn site (CuZn) in the lattice. The Voc enhancement evidences that the solution method is facile and viable to achieve proper cation substitution toward higher efficiency kesterite solar cells. In addition, the CAZTSSe cell also displays better charge collection performance because of the higher fill factor (FF) and power conversion efficiency (PCE). Therefore, it can be concluded that the doping of Ag is a potentially appropriate method to reduce the Cuzn antisite defects of CZTSSe and improve efficiency of CZTSSe device.
Microstructure and Mechanical Performance of Graphene Nanosheets Reinforced Nickel-Based Superalloy FGH95 Composite
Authors: Gao Yuxi , Zou Jinwen , Wang Xuqing , Wang Xiaofeng , Yang Jie , Wang Huaming
Published: January 2020

Graphene nanosheet (GNS)-reinforced nickel-based superalloy FGH95 (GNSs/FGH95) matrix composites are prepared via the powder metallurgy approach. Scanning electron microscopy, transmission electron microscope and static tensile tests are used to investigate the microstructure and mechanical properties of GNS-reinforced nickel-based superalloy FGH95. Mechanical properties and failure behavior at room temperature and high temperature are studied. Static tensile tests at room temperature and high temperature confirm that the strength and plasticity of GNS-reinforced FGH95 have been improved, compared to the unreinforced superalloy. The results show that with the increase of temperature, the failure behavior of GNSs/FGH95 composite changes from the interface debonding of the GNSs/matrix to the failure of the FGH95 matrix. This work suggests that GNSs/FGH95 composite has great potential to be a structural material in aero-engine fields.
MicroRNAs as Appropriate Discriminators in Non-Specific Alpha-Fetoprotein (AFP) Elevation in Testicular Germ Cell Tumor Patients
Authors: Lembeck Anna L. , Puchas Philip , Hutterer Georg , Barth Dominik A. , Terbuch Angelika , Bauernhofer Thomas , Pichler Martin
Published: January 2020

Testicular germ cell tumors (TGCTs) are the most commonly diagnosed malignancies in younger men. The monitoring of disease course and recurrence is supported by traditional tumor markers, including α-fetoprotein (AFP). AFP is physiologically synthesized in the liver and can be detected at increased levels in testicular cancer patients as well as under other benign liver diseases, which have been reported as a misleading cause of interpretation of TGCTs clinical course. A cluster of stem cell-associated microRNAs has been reported to outperform traditional tumor markers in newly diagnosed TGCTs, but the value of these microRNAs to differentiate between specific and unspecific AFP elevations, has never been reported. We report here a patient with chronic hepatitis B and normal liver related blood values presenting with a surgically removed primary TGCT and elevated AFP levels. Clinical staging revealed a suspect retroperitoneal metastatic lymph node together with other risk factors and first line treatment with PEB chemotherapy was administered. During curative treatment significantly rising AFP levels led to the assumption of chemo-resistant disease, mandating the initiation of salvage chemotherapy and surgical removal of the putative lymph node metastases. The AFP levels continuously decreased with the interruption of chemotherapeutic agents, indicating a chemotherapy-induced liver toxicity on the basis of pre-existing liver disease. MiR-371a-3p serum levels were not detectable in serum samples with elevated AFP levels. In conclusion, miR-371a-3p may be a reliable biomarker to differentiate between non-specific AFP elevations in TGCTs patients.
A Calorie-Restricted DASH Diet Reduces Body Fat and Maintains Muscle Strength in Obese Older Adults
Authors: Perry Cydne A. , Van Guilder Gary P. , Kauffman Alyssa , Hossain Mosharraf
Published: January 2020

This study examined the effect of the Dietary Approaches to Stop Hypertension (DASH) diet containing lean red meat on measures of body composition and muscle strength in a cohort of obese adults 65 and older; 36 males (n = 15) and females (n = 21) consumed 1800 kcal/day for 12 weeks under controlled feeding conditions. The study diet included daily intakes of 126 g of meat. Measures of body composition and muscle strength were obtained at weeks 0, 3, 6, 9, and 12. Breakfast, lunch, and dinner were provided every day for 12 weeks, and equal portions of meat were distributed at each meal. Significant effects of the study diet were detected across time for total body weight, body mass index (BMI), waist circumference, hip circumference, body fat percentage, absolute fat mass (AFM), and blood pressure such that a decrease (p < 0.001) was observed over 12 weeks. Significant effects of the study diet were detected across time for sit/stand (p < 0.001) such that an increase was observed. From baseline to study end, total body weight decreased by 6.3% (p < 0.001), body fat percentage decreased by 2.5% (p < 0.001), and absolute fat mass (AFM) decreased by 4.4 kg (p < 0.001). By the study end, skeletal muscle mass (SMM) was positively correlated with handgrip strength (R2 = 0.75; p = 0.001) and resting energy expenditure (REE) (R2 = 0.29; p = 0.001). Handgrip strength, gait, balance, and resting energy expenditure (REE) were well maintained (p > 0.05) throughout the study. These findings suggest that the DASH diet has the potential to be a tool to preserve muscle strength while reducing fat mass in obese older adults.
Beneficial Effect of a Multistrain Synbiotic Prodefen® Plus on the Systemic and Vascular Alterations Associated with Metabolic Syndrome in Rats: The Role of the Neuronal Nitric Oxide Synthase and Protein Kinase A
Authors: Llévenes Pablo , Rodrigues-Díez Raquel , Cros-Brunsó Laia , Prieto Mᵃ Isabel , Casaní Laura , Balfagón Gloria , Blanco-Rivero Javier
Published: January 2020

A high fat diet (HFD) intake is crucial for the development and progression of metabolic syndrome (MtS). Increasing evidence links gut dysbiosis with the metabolic and vascular alterations associated with MtS. Here we studied the use of a combination of various probiotic strains together with a prebiotic (synbiotic) in a commercially available Prodefen® Plus. MtS was induced by HFD (45%) in male Wistar rats. Half of the MtS animals received Prodefen® Plus for 4 weeks. At 12 weeks, we observed an increase in body weight, together with the presence of insulin resistance, liver steatosis, hypertriglyceridemia and hypertension in MtS rats. Prodefen® Plus supplementation did not affect the body weight gain but ameliorated all the MtS-related symptoms. Moreover, the hypertension induced by HFD is caused by a diminished both nitric oxide (NO) functional role and release probably due to a diminished neuronal nitric oxide synthase (nNOS) activation by protein kinase A (PKA) pathway. Prodefen® Plus supplementation for 4 weeks recovered the NO function and release and the systolic blood pressure was returned to normotensive values as a result. Overall, supplementation with Prodefen® Plus could be considered an interesting non-pharmacological approach in MtS.
The Polymorphism of Drugs: New Approaches to the Synthesis of Nanostructured Polymorphs
Authors: Chistyakov Dmitry , Sergeev Gleb
Published: January 2020

Among the significant problems of modern pharmacology are the low solubility and bioavailability of drugs. One way to resolve this problem is to obtain new polymorphic forms of drugs with improved physicochemical properties. Various approaches have been developed with this aim, including the preparation of co-crystals, the use of nanoparticles, or the use of compounds in the form of a salt. A promising direction in pharmacology concerns the production of new stable polymorphic structures. In this mini-review, we consider certain aspects of drug polymorphism, methods for the synthesis of polymorphs, and the stability, size, and transformation of crystalline polymorphs. Moreover, we summarize our results from several studies demonstrating the problems associated with the synthesis of new polymorphous modifications based on inert gases and cryotemperatures. The results indicate that the problems specific to drug polymorphisms have only been partly resolved, are of current interest, and require further development.
Docetaxel-Loaded Disulfide Cross-Linked Nanoparticles Derived from Thiolated Sodium Alginate for Colon Cancer Drug Delivery
Authors: Chiu Hock Ing , Ayub Asila Dinie , Mat Yusuf Siti Nur Aishah , Yahaya Noorfatimah , Abd Kadir Erazuliana , Lim Vuanghao
Published: January 2020

In this study, fluorescein-labelled wheat germ agglutinin (fWGA)-conjugated disulfide cross-linked sodium alginate nanoparticles were developed to specifically target docetaxel (DTX) to colon cancer cells. Different amounts of 3-mercaptopropionic acid (MPA) were covalently attached to sodium alginate to form thiolated sodium alginate (MPA1–5). These polymers were then self-assembled and air-oxidised to form disulfide cross-linked nanoparticles (MP1–5) under sonication. DTX was successfully loaded into the resulting MP1–5 to form DTX-loaded nanoparticles (DMP1–5). DMP2 had the highest loading efficiency (17.8%), thus was chosen for fWGA surface conjugation to form fWGA-conjugated nanoparticles (fDMP2) with a conjugation efficiency of 14.1%. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses showed spherical nanoparticles, and an in vitro drug release study recorded a cumulative drug release of 48.6%. Dynamic light scattering (DLS) analysis revealed a mean diameter (MD) of 289 nm with a polydispersity index (PDI) of 0.3 and a zeta potential of −2.2 mV for fDMP2. HT-29 human colon cancer cells treated with fDMP2 showed lower viability than that of L929 mouse fibroblast cells. These results indicate that fDMP2 was efficiently taken up by HT-29 cells (29.9%). Fluorescence and confocal imaging analyses also showed possible internalisation of nanoparticles by HT-29 cells. In conclusion, fDMP2 shows promise as a DTX carrier for colon cancer drug delivery.