bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction with Soil Bacteria Affects the Growth and Amino Acid Content of Piriformospora indica
Authors: Leyva-Rojas Jorge A. , Coy-Barrera Ericsson , Hampp Rüdiger
Published: January 2020

Exploration of the effect of soil bacteria on growth and metabolism of beneficial root endophytic fungi is relevant to promote favorable associations between microorganisms of the plant rhizosphere. Hence, the interaction between the plant-growth-promoting fungus Piriformospora indica and different soil bacteria was investigated. The parameters studied were fungal growth and its amino acid composition during the interaction. Fungus and bacteria were confronted in dual cultures in Petri dishes, either through agar or separated by a Perspex wall that only allowed the bacterial volatiles to be effective. Fungal growth was stimulated by Azotobacter chroococcum, whereas Streptomyces anulatus AcH 1003 inhibited it and Streptomyces sp. Nov AcH 505 had no effect. To analyze amino acid concentration data, targeted metabolomics was implemented under supervised analysis according to fungal-bacteria interaction and time. Orthogonal partial least squares-discriminant analysis (OPLS-DA) model clearly discriminated P. indica–A. chroococcum and P. indica–S. anulatus interactions, according to the respective score plot in comparison to the control. The most observable responses were in the glutamine and alanine size groups: While Streptomyces AcH 1003 increased the amount of glutamine, A. chroococcum decreased it. The fungal growth and the increase of alanine content might be associated with the assimilation of nitrogen in the presence of glucose as a carbon source. The N-fixing bacterium A. chroococcum should stimulate fungal amino acid metabolism via glutamine synthetase-glutamate synthase (GS-GOGAT). The data pointed to a stimulated glycolytic activity in the fungus observed by the accumulation of alanine, possibly via alanine aminotransferase. The responses toward the growth-inhibiting Streptomyces AcH 1003 suggest an (oxidative) stress response of the fungus.
Deep Eutectic Solvents as Effective Reaction Media for the Synthesis of 2-Hydroxyphenylbenzimidazole-Based Scaffolds en Route to Donepezil-Like Compounds
Authors: Piemontese Luca , Sergio Roberta , Rinaldo Federica , Brunetti Leonardo , Perna Filippo M. , Santos M. Amélia , Capriati Vito
Published: January 2020

An unsubstituted 2-hydroxyphenylbenzimidazole has recently been included as a scaffold in a series of hybrids (including the hit compound PZ1) based on the framework of the acetylcholinesterase (AChE) inhibitor Donepezil, which is a new promising multi-target ligand in Alzheimer’s disease (AD) treatment. Building upon these findings, we have now designed and completed the whole synthesis of PZ1 in the so-called deep eutectic solvents (DESs), which have emerged as an unconventional class of bio-renewable reaction media in green synthesis. Under optimized reaction conditions, the preparation of a series of 2-hydroxyphenylbenzimidazole-based nuclei has also been perfected in DESs, and comparison with other routes which employ toxic and volatile organic solvents (VOCs) provided. The functionalization of the aromatic ring can have implications on some important biological properties of the described derivatives and will be the subject of future studies of structure-activity relationships (SARs).
Molecular Mechanisms of the Anti-Cancer Effects of Isothiocyanates from Cruciferous Vegetables in Bladder Cancer
Authors: Mastuo Tomhiro , Miyata Yasuyoshi , Yuno Tsutomu , Mukae Yuta , Otsubo Asato , Mitsunari Kensuke , Ohba Kojiro , Sakai Hideki
Published: January 2020

Bladder cancer (BC) is a representative of urological cancer with a high recurrence and metastasis potential. Currently, cisplatin-based chemotherapy and immune checkpoint inhibitors are used as standard therapy in patients with advanced/metastatic BC. However, these therapies often show severe adverse events, and prolongation of survival is unsatisfactory. Therefore, a treatment strategy using natural compounds is of great interest. In this review, we focused on the anti-cancer effects of isothiocyanates (ITCs) derived from cruciferous vegetables, which are widely cultivated and consumed in many regions worldwide. Specifically, we discuss the anti-cancer effects of four ITC compounds—allyl isothiocyanate, benzyl isothiocyanate, sulforaphane, and phenethyl isothiocyanate—in BC; the molecular mechanisms underlying their anti-cancer effects; current trends and future direction of ITC-based treatment strategies; and the carcinogenic potential of ITCs. We also discuss the advantages and limitations of each ITC in BC treatment, furthering the consideration of ITCs in treatment strategies and for improving the prognosis of patients with BC.
Naphthoquinone Derivatives with Anti-Inflammatory Activity from Mangrove-Derived Endophytic Fungus Talaromyces sp. SK-S009
Authors: Liu Hongju , Yan Chong , Li Changqun , You Tingting , She Zhigang
Published: January 2020

Twelve 1, 4-naphthoquinone derivatives, including two new (1 and 2) and 10 known (3–12), were obtained from endophytic fungus Talaromyces sp. SK-S009 isolated from the fruit of Kandelia obovata. All structures were identified through extensive analysis of the nuclear magnetic resonance (NMR), mass spectrometry (MS) and circular dichroism (CD), as well as by comparison with literature data. These compounds significantly inhibited the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in the murine macrophage cell line (RAW 264.7 cells). The half maximal inhibitory concentration (IC50) values, except for compound 2, were lower than that of indomethacin (26.3 μM). Compound 9 inhibited the LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expressions in RAW 264.7 macrophages. Additionally, compound 9 reduced the mRNA levels of pro-inflammatory factors interleukin (IL)1β, IL-6, and tumor necrosis factor (TNF)-α. The results of this study demonstrated that these 1, 4-naphthoquinone derivatives can inhibit LPS-induced inflammation.
Phytochemistry and Comprehensive Chemical Profiling Study of Flavonoids and Phenolic Acids in the Aerial Parts of Allium Mongolicum Regel and Their Intestinal Motility Evaluation
Authors: Dong Yongzhe , Ruan Jingya , Ding Zhijuan , Zhao Wei , Hao Mimi , Zhang Ying , Jiang Hongyu , Zhang Yi , Wang Tao
Published: January 2020

To clarify whether flavonoids and phenols in Allium mongolicum Regel have the effect of improving gastrointestinal function and analyze its quality, this study was designed to isolate and identify them from the aerial parts of A. mongolicum by using various chromatographic and spectrophotometric methods, a bioassay on motility of mouse isolated intestine tissue, as well as qualitative analysis using liquid chromatography/mass spectrometry (LC-MS) analysis. As a result, 31 flavonoids and phenolic acids were obtained and identified, including six new flavonoid glycosides, mongoflavonosides A1 (1), A2 (2), A3 (3), A4 (4), B1 (5), B2 (6), and four new phenolic acid glycosides, mongophenosides A1 (7), A2 (8), A3 (9), B (10). Among them, eleven flavonoids and three phenolic acids showed significant increase in the height of mouse small intestinal muscle. It was a first systematic bioactive constituents’ study for A. mongolicum on gastrointestinal tract. Furthermore, according to the retention time (tR) and the exact mass-to-charge ratio (m/z), thirty-one compounds were unambiguously identified by comparing to the standard references by using LC-MS. Then, on the basis of generalized rules of MS/MS fragmentation pattern, chromatographic behaviors, as well as biosynthetic laws of the 31 isolates, five flavonoid glycosides and one phenolic acid glycoside were tentatively speculated. On the basis of the study, a fast analysis method for flavonoids and phenolic acids in A. mongolicum was established.
Small Molecules Targeting the Specific Domains of Histone-Mark Readers in Cancer Therapy
Authors: Zhu Huihui , Wei Tao , Cai Yong , Jin Jingji
Published: January 2020

Epigenetic modifications (or epigenetic tags) on DNA and histones not only alter the chromatin structure, but also provide a recognition platform for subsequent protein recruitment and enable them to acquire executive instructions to carry out specific intracellular biological processes. In cells, different epigenetic-tags on DNA and histones are often recognized by the specific domains in proteins (readers), such as bromodomain (BRD), chromodomain (CHD), plant homeodomain (PHD), Tudor domain, Pro-Trp-Trp-Pro (PWWP) domain and malignant brain tumor (MBT) domain. Recent accumulating data reveal that abnormal intracellular histone modifications (histone marks) caused by tumors can be modulated by small molecule-mediated changes in the activity of the above domains, suggesting that small molecules targeting histone-mark reader domains may be the trend of new anticancer drug development. Here, we summarize the protein domains involved in histone-mark recognition, and introduce recent research findings about small molecules targeting histone-mark readers in cancer therapy.
Diagnostic Potential of FT-IR Fingerprinting in Botanical Origin Evaluation of Laurus nobilis L. Essential Oil is Supported by GC-FID-MS Data
Authors: Ordoudi Stella A. , Papapostolou Maria , Kokkini Stella , Tsimidou Maria Z.
Published: January 2020

The last years, non-targeted fingerprinting by Fourier-transform infrared (FT-IR) spectroscopy has gained popularity as an alternative to classical gas chromatography (GC)-based methods because it may allow fast, green, non-destructive and cost-effective assessment of quality of essential oils (EOs) from single plant species. As the relevant studies for Laurus nobilis L. (bay laurel) EO are limited, the present one aimed at exploring the diagnostic potential of FT-IR fingerprinting for the identification of its botanical integrity. A reference spectroscopic dataset of 97 bay laurel EOs containing meaningful information about the intra-species variation was developed via principal component analysis (PCA). This dataset was used to train a one-class model via soft independent modelling class analogy (SIMCA). The model was challenged against commercial bay laurel and non-bay laurel EOs of non-traceable production history. Overall, the diagnostic importance of spectral bands at 3060, 1380–1360, 1150 and 1138 cm−1 was assessed using GC-FID-MS data. The findings support the introduction of FT-IR as a green analytical technique in the quality control of these often mislabeled and/or adulterated precious products. Continuous evaluation of the model performance against newly acquired authentic EOs from all producing regions is needed to ensure validity over time.
Effective Biobased Phosphorus Flame Retardants from Starch-Derived bis-2,5-(Hydroxymethyl)Furan
Authors: Howell Bob A. , Han Xiaorui
Published: January 2020

A series of biobased phosphorus flame retardants has been prepared by converting starch-derived bis-2,5-(hydroxymethyl)furan to the corresponding diacrylate followed by Michael addition of phosphite to generate derivatives with phosphorus moieties attached via P–C bonds. All compounds behave as effective flame retardants in DGEBA epoxy resin. The most effective is the DOPO derivative, 2,5-di[(3-dopyl-propanoyl)methyl]furan. When incorporated into a DGEBA blend at a level to provide 2% phosphorus, a material displaying a LOI of 30, an UL 94 rating of V0 and a 40% reduction in combustion peak heat release rate compared to that for resin containing no additive is obtained. The analogous compounds generated from bisphenol A and tetrabromobisphenol A exhibit similar flame-retarding properties.
A Versatile Approach to Access Trimetallic Complexes Based on Trisphosphinite Ligands
Authors: Miranda-Pizarro Juan , Alférez Macarena G. , Fernández-Martínez M. Dolores , Álvarez Eleuterio , Maya Celia , Campos Jesús
Published: January 2020

A straightforward method for the preparation of trisphosphinite ligands in one step, using only commercially available reagents (1,1,1-tris(4-hydroxyphenyl)ethane and chlorophosphines) is described. We have made use of this approach to prepare a small family of four trisphosphinite ligands of formula [CH3C{(C6H4OR2)3], where R stands for Ph (1a), Xyl (1b, Xyl = 2,6-Me2-C6H3), iPr (1c), and Cy (1d). These polyfunctional phosphinites allowed us to investigate their coordination chemistry towards a range of late transition metal precursors. As such, we report here the isolation and full characterization of a number of Au(I), Ag(I), Cu(I), Ir(III), Rh(III) and Ru(II) homotrimetallic complexes, including the structural characterization by X-ray diffraction studies of six of these compounds. We have observed that the flexibility of these trisphosphinites enables a variety of conformations for the different trimetallic species.
Systemically Administered, Target-Specific, Multi-Functional Therapeutic Recombinant Proteins in Regenerative Medicine
Authors: Järvinen Tero A.H. , Pemmari Toini
Published: January 2020

Growth factors, chemokines and cytokines guide tissue regeneration after injuries. However, their applications as recombinant proteins are almost non-existent due to the difficulty of maintaining their bioactivity in the protease-rich milieu of injured tissues in humans. Safety concerns have ruled out their systemic administration. The vascular system provides a natural platform for circumvent the limitations of the local delivery of protein-based therapeutics. Tissue selectivity in drug accumulation can be obtained as organ-specific molecular signatures exist in the blood vessels in each tissue, essentially forming a postal code system (“vascular zip codes”) within the vasculature. These target-specific “vascular zip codes” can be exploited in regenerative medicine as the angiogenic blood vessels in the regenerating tissues have a unique molecular signature. The identification of vascular homing peptides capable of finding these unique “vascular zip codes” after their systemic administration provides an appealing opportunity for the target-specific delivery of therapeutics to tissue injuries. Therapeutic proteins can be “packaged” together with homing peptides by expressing them as multi-functional recombinant proteins. These multi-functional recombinant proteins provide an example how molecular engineering gives to a compound an ability to home to regenerating tissue and enhance its therapeutic potential. Regenerative medicine has been dominated by the locally applied therapeutic approaches despite these therapies are not moving to clinical medicine with success. There might be a time to change the paradigm towards systemically administered, target organ-specific therapeutic molecules in future drug discovery and development for regenerative medicine.
Ecotoxicological Studies of ZnO and CdS Nanoparticles on Chlorella vulgaris Photosynthetic Microorganism in Seine River Water
Authors: da Rocha Alice , Menguy Nicolas , Yéprémian Claude , Couté Alain , Brayner Roberta
Published: January 2020

Seine river water was used as natural environmental medium to study the ecotoxicological impact of ZnO and CdS nanoparticles and Zn2+ and Cd2+ free ions using Chlorella vulgaris as a biological target. It was demonstrated by viability tests and photosynthetic activity measurements that free Zn2+ (IC50 = 2.7 × 10−4 M) is less toxic than free Cd2+ and ZnO nanoparticles (IC50 = 1.4 × 10−4 M). In the case of cadmium species, free Cd2+ (IC50 = 3.5 × 10−5 M) was similar to CdS nanoparticles (CdS-1: IC50 = 1.9 × 10−5 M and CdS-2: IC50 = 1.9 × 10−5 M), as follows: CdS > Cd2+ > ZnO > Zn2+. Adenosine-5’-triphosphate (ATP) assay and superoxide dismutase (SOD) enzymatic activity confirmed these results. Transmission electron microscopy (TEM), coupled with energy-dispersive X-ray spectroscopy (EDS), confirmed the internalization of CdS-1 nanoparticles after 48 h of contact with Chlorella vulgaris at 10−3 M. With a higher concentration of nanoparticles (10−2 M), ZnO and CdS-2 were also localized inside cells.
A New Approach to UV Protection by Direct Surface Functionalization of TiO2 with the Antioxidant Polyphenol Dihydroxyphenyl Benzimidazole Carboxylic Acid
Authors: Battistin Mattia , Dissette Valeria , Bonetto Alessandro , Durini Elisa , Manfredini Stefano , Marcomini Antonio , Casagrande Elisa , Brunetta Andrea , Ziosi Paola , Molesini Sonia , Gavioli Riccardo , Nicoli Francesco , Vertuani Silvia , Baldisserotto Anna
Published: January 2020

Skin cancer is the most common malignant cancer with an incidence of 1 million cases/year. It is well known that exposure to UV radiation from sunlight leads the most frequent risk factors for several skin disorders including skin cancer. Sunscreen filters represent a valid protection against dangerous effects derived from UV radiation, and they can be divided in organic and inorganic UV filters. Adding, at the product formulation, molecules with booster effect, or also substances that can increase the protecting effectiveness via synergic mechanisms, can further enhance their protection activity. Moreover, this approach leads to develop formulations with high SPF (Sun Protection Factor) with a reduced content of UV filters, this is in line with the recent decisions of yet a few countries (Palau, Thailand, Philippines, and Hawaii) to ban some sunscreen filters to preserve marine environments (i.e., reef). In this work, a new class of sunscreen UV filters has been synthesized, by means the combination of physical filter and Oxisol, an antioxidant molecule with booster effect. In this study, the synthesis of new physical multifunctional ingredients is reported, by means the direct surface functionalization of inorganic filters (in particular TiO2) with Oxisol. In this study, the full characterization of these multifunctional ingredients is also reported, in addition to the cytotoxicity tests, the photocatalytic activity and the rheological properties involved on skin application.
Numerical and Theoretical Study of Tunable Plasmonically Induced Transparency Effect Based on Bright–Dark Mode Coupling in Graphene Metasurface
Authors: Ma Qichang , Dai Jianan , Luo Aiping , Hong Weiyi
Published: January 2020

In this paper, we numerically and theoretically study the tunable plasmonically induced transparency (PIT) effect based on the graphene metasurface structure consisting of a graphene cut wire (CW) resonator and double split-ring resonators (SRRs) in the middle infrared region (MIR). Both the theoretical calculations according to the coupled harmonic oscillator model and simulation results indicate that the realization of the PIT effect significantly depends on the coupling distance and the coupling strength between the CW resonator and SRRs. In addition, the geometrical parameters of the CW resonator and the number of the graphene layers can alter the optical response of the graphene structure. Particularly, compared with the metal-based metamaterial, the PIT effect realized in the proposed metasurface can be flexibly modulated without adding other actively controlled materials and reconstructing the structure by taking advantage of the tunable complex surface conductivity of the graphene. These results could find significant applications in ultrafast variable optical attenuators, sensors and slow light devices.
Rapid Microwave Polymerization of Porous Nanocomposites with Piezoresistive Sensing Function
Authors: Herren Blake , Charara Mohammad , Saha Mrinal C. , Altan M. Cengiz , Liu Yingtao
Published: January 2020

In this paper, polydimethylsiloxane (PDMS) and multi-walled carbon nanotube (MWCNT) nanocomposites with piezoresistive sensing function were fabricated using microwave irradiation. The effects of precuring time on the mechanical and electrical properties of nanocomposites were investigated. The increased viscosity and possible nanofiller re-agglomeration during the precuring process caused decreased microwave absorption, resulting in extended curing times, and decreased porosity and electrical conductivity in the cured nanocomposites. The porosity generated during the microwave-curing process was investigated with a scanning electron microscope (SEM) and density measurements. Increased loadings of MWCNTs resulted in shortened curing times and an increased number of small well-dispersed closed-cell pores. The mechanical properties of the synthesized nanocomposites including stress–strain behaviors and Young’s Modulus were examined. Experimental results demonstrated that the synthesized nanocomposites with 2.5 wt. % MWCNTs achieved the highest piezoresistive sensitivity with an average gauge factor of 7.9 at 10% applied strain. The piezoresistive responses of these nanocomposites were characterized under compressive loads at various maximum strains, loading rates, and under viscoelastic stress relaxation conditions. The 2.5 wt. % nanocomposite was successfully used in an application as a skin-attachable compression sensor for human motion detection including squeezing a golf ball.
Ultra-Uniform and Very Thin Ag Nanowires Synthesized via the Synergy of Cl−, Br− and Fe3+ for Transparent Conductive Films
Authors: Wang Xiao-Ming , Chen Long , Sowade Enrico , Rodriguez Raul D. , Sheremet Evgeniya , Yu Chun-Mei , Baumann Reinhard R. , Chen Jin-Ju
Published: January 2020

The properties and applications of Ag nanowires (AgNWs) are closely related to their morphology and composition. Therefore, controlling the growth process of AgNWs is of great significance for technological applications and fundamental research. Here, silver nanowires (AgNWs) were synthesized via a typical polyol method with the synergistic effect of Cl−, Br−, and Fe3+ mediated agents. The synergistic impact of these mediated agents was investigated intensively, revealing that trace Fe3+ ions provided selective etching and hindered the strong etching effect from Cl− and Br− ions. Controlling this synergy allowed the obtainment of highly uniform AgNWs with sub-30 nm diameter and an aspect ratio of over 3000. Transparent conductive films (TCFs) based on these AgNWs without any post-treatment showed a very low sheet resistance of 4.7 Ω sq−1, a low haze of 1.08% at a high optical transmittance of 95.2% (at 550 nm), and a high figure of merit (FOM) of 1210. TCFs exhibited a robust electrical performance with almost unchanged resistance after 2500 bending cycles. These excellent high-performance characteristics demonstrate the enormous potential of our AgNWs in the field of flexible and transparent materials.
Synthesis of Cerium Oxide Nanoparticles Using Various Methods: Implications for Biomedical Applications
Authors: Nyoka Mpumelelo , Choonara Yahya E. , Kumar Pradeep , Kondiah Pierre P. D. , Pillay Viness
Published: January 2020

Cerium oxide nanoparticles have been used in a number of non-medical products over the years. The therapeutic application of these nanoparticles has mainly been due to their oxidative stress ameliorating abilities. Their enzyme-mimetic catalytic ability to change between the Ce3+ and Ce4+ species makes them ideal for a role as free-radical scavengers for systemic diseases as well as neurodegenerative diseases. In this review, we look at various methods of synthesis (including the use of stabilizing/capping agents and precursors), and how the synthesis method affects the physicochemical properties, their behavior in biological environments, their catalytic abilities as well as their reported toxicity.
Vascular Wall–Mesenchymal Stem Cells Differentiation on 3D Biodegradable Highly Porous CaSi-DCPD Doped Poly (α-hydroxy) Acids Scaffolds for Bone Regeneration
Authors: Forni Monica , Bernardini Chiara , Zamparini Fausto , Zannoni Augusta , Salaroli Roberta , Ventrella Domenico , Parchi Greta , Degli Esposti Micaela , Polimeni Antonella , Fabbri Paola , Fava Fabio , Prati Carlo , Gandolfi Maria Giovanna
Published: January 2020

Vascularization is a crucial factor when approaching any engineered tissue. Vascular wall–mesenchymal stem cells are an excellent in vitro model to study vascular remodeling due to their strong angiogenic attitude. This study aimed to demonstrate the angiogenic potential of experimental highly porous scaffolds based on polylactic acid (PLA) or poly-e-caprolactone (PCL) doped with calcium silicates (CaSi) and dicalcium phosphate dihydrate (DCPD), namely PLA-10CaSi-10DCPD and PCL-10CaSi-10DCPD, designed for the regeneration of bone defects. Vascular wall–mesenchymal stem cells (VW-MSCs) derived from pig thoracic aorta were seeded on the scaffolds and the expression of angiogenic markers, i.e. CD90 (mesenchymal stem/stromal cell surface marker), pericyte genes α-SMA (alpha smooth muscle actin), PDGFR-β (platelet-derived growth factor receptor-β), and NG2 (neuron-glial antigen 2) was evaluated. Pure PLA and pure PCL scaffolds and cell culture plastic were used as controls (3D in vitro model vs. 2D in vitro model). The results clearly demonstrated that the vascular wall mesenchymal cells colonized the scaffolds and were metabolically active. Cells, grown in these 3D systems, showed the typical gene expression profile they have in control 2D culture, although with some main quantitative differences. DNA staining and immunofluorescence assay for alpha-tubulin confirmed a cellular presence on both scaffolds. However, VW-MSCs cultured on PLA-10CaSi-10DCPD showed an individual cells growth, whilst on PCL-10CaSi-10DCPD scaffolds VW-MSCs grew in spherical clusters. In conclusion, vascular wall mesenchymal stem cells demonstrated the ability to colonize PLA and PCL scaffolds doped with CaSi-DCPD for new vessels formation and a potential for tissue regeneration.
The Unfinished Agenda for Food Fortification in Low- and Middle-Income Countries: Quantifying Progress, Gaps and Potential Opportunities
Authors: Mkambula Penjani , Mbuya Mduduzi N. N. , Rowe Laura A. , Sablah Mawuli , Friesen Valerie M. , Chadha Manpreet , Osei Akoto K. , Ringholz Corinne , Vasta Florencia C. , Gorstein Jonathan
Published: January 2020

Large-scale food fortification (LSFF) is a cost-effective intervention that is widely implemented, but there is scope to further increase its potential. To identify gaps and opportunities, we first accessed the Global Fortification Data Exchange (GFDx) to identify countries that could benefit from new fortification programs. Second, we aggregated Fortification Assessment Coverage Toolkit (FACT) survey data from 16 countries to ascertain LSFF coverage and gaps therein. Third, we extended our narrative review to assess current innovations. We identified 84 countries as good candidates for new LSFF programs. FACT data revealed that the potential of oil/ghee and salt fortification is not being met due mainly to low coverage of adequately fortified foods (quality). Wheat, rice and maize flour fortification have similar quality issues combined with lower coverage of the fortifiable food at population-level (<50%). A four-pronged strategy is needed to meet the unfinished agenda: first, establish new LSFF programs where warranted; second, systems innovations informed by implementation research to address coverage and quality gaps; third, advocacy to form new partnerships and resources, particularly with the private sector; and finally, exploration of new fortificants and vehicles (e.g. bouillon cubes; salt fortified with multiple nutrients) and other innovations that can address existing challenges.
Antifungal and Antivirulence Activities of Hydroalcoholic Extract and Fractions of Platonia insignis Leaves against Vaginal Isolates of Candida Species
Authors: da Silva Anderson França , da Rocha Cláudia Quintino , da Silva Luís Cláudio Nascimento , Carvalho Júnior Alexsander Rodrigues , Mendes Iven Neylla Farias Vale , de Araruna Andrea Borges , Motta Elizangela Pestana , Silva Rayssa de Sousa , Campos Carmem Duarte Lima , Farias Josivan Regis , Oliveira Aluísio da Silva , Silva Douglas Henrique dos Santos , Nascimento Flávia Raquel F , Guerra Rosane Nassar Meireles , Monteiro Cristina Andrade
Published: January 2020

Vulvovaginal candidiasis is a common fungal infection in women. In this study, Platonia insignis hydroalcoholic extract (PiHE) and its fractions were evaluated for antifungal and antivirulence activities against vaginal Candida species. Dichloromethane (DCMF) and ethyl acetate fractions (EAF) obtained from PiHE effectively inhibited the pathogen. Electrospray ionization mass spectrometry was used for identifying the main compounds in extracts. Minimal inhibitory and fungicidal concentrations (MIC and MFC, respectively) were determined by a broth microdilution assay. Furthermore, we evaluated the effect of the extract and fractions on the virulence properties of Candida albicans, and their cytotoxicity effect was determined on RAW 264.7 cells. Compounds found in extracts were flavonoid glycosides, mainly derivatives of quercetin and myricetin. Extracts showed antifungal potential, with the lowest MIC value for EAF (1.3 mg/mL) and inhibited Candida adherence and biofilm formation. EAF disrupted 48 h biofilms with an inhibition rate of more than 90%. The extract and its fractions exhibited no cytotoxicity. The antifungal effects were attributed to the ability of these extracts to alter the mitochondrial membrane potential for the release of pro-apoptotic factors in the cytosol. In conclusion, our data suggest that PiHE and EAF could act as novel candidates for the development of new therapeutic treatments against fungal infections.
Human Metapneumovirus: Etiological Agent of Severe Acute Respiratory Infections in Hospitalized and Deceased Patients with a Negative Diagnosis of Influenza
Authors: Barrera-Badillo Gisela , Olivares-Flores Beatriz , Ruiz-López Adriana , Fierro-Valdez Miguel Ángel , Gutiérrez-Vargas Rosaura Idania , López-Martínez Irma
Published: January 2020

Human metapneumovirus (HMPV) is one of the four major viral pathogens associated with acute respiratory tract infections (ARI) and creates a substantial burden of disease, particularly in young children (<5 years) and older individuals (≥65 years). The objective of this study was to determine the epidemiological behavior of HMPV in Mexico. This retrospective study was conducted over a nine-year period and used 7283 influenza-negative respiratory samples from hospitalized and deceased patients who presented Severe Acute Respiratory Infection (SARI). The samples were processed with the help of qualitative multiplex RT-PCR for simultaneous detection of 14 respiratory viruses (xTAG® RVP FAST v2). 40.8% of the samples were positive for respiratory viruses, mainly rhinovirus/enterovirus (47.6%), respiratory syncytial virus (15.9%), HMPV (11.1%) and parainfluenza virus (8.9%). Other respiratory viruses and co-infections accounted for 16.5%. HMPV infects all age groups, but the most affected group was infants between 29 days and 9 years of age (65.6%) and adults who are 40 years and older (25.7%). HMPV circulates every year from November to April, and the highest circulation was observed in late winter. The results of this study aim to raise awareness among clinicians about the high epidemiological impact of HMPV in young children and older individuals in order to reduce the economic burden in terms of health care costs.
Plant-Produced Recombinant Influenza A Virus Candidate Vaccine Based on Flagellin Linked to Conservative Fragments of M2 Protein and Hemagglutintin
Authors: Blokhina Elena A. , Mardanova Eugenia S. , Stepanova Liudmila A. , Tsybalova Liudmila M. , Ravin Nikolai V.
Published: January 2020

The development of recombinant influenza vaccines with broad spectrum protection is an important task. The combination of conservative viral antigens, such as M2e, the extracellular domain of the transmembrane protein M2, and conserved regions of the second subunit of hemagglutinin (HA), provides an opportunity for the development of universal influenza vaccines. Immunogenicity of the antigens could be enhanced by fusion to bacterial flagellin, the ligand for Toll-like receptor 5, acting as a powerful mucosal adjuvant. In this study, we report the transient expression in plants of a recombinant protein comprising flagellin of Salmonella typhimurium fused to the conserved region of the second subunit of HA (76–130 a.a.) of the first phylogenetic group of influenza A viruses and four tandem copies of the M2e peptide. The hybrid protein was expressed in Nicotiana benthamiana plants using the self-replicating potato virus X-based vector pEff up to 300 µg/g of fresh leaf tissue. The intranasal immunization of mice with purified fusion protein induced high levels of M2e-specific serum antibodies and provided protection against lethal challenge with influenza A virus strain A/Aichi/2/68(H3N2). Our results show that M2e and hemagglutinin-derived peptide can be used as important targets for the development of a plant-produced vaccine against influenza.
SLIM1 Transcription Factor Promotes Sulfate Uptake and Distribution to Shoot, Along with Phytochelatin Accumulation, Under Cadmium Stress in Arabidopsis thaliana
Authors: Yamaguchi Chisato , Khamsalath Soudthedlath , Takimoto Yuki , Suyama Akiko , Mori Yuki , Ohkama-Ohtsu Naoko , Maruyama-Nakashita Akiko
Published: January 2020

Sulfur (S) assimilation, which is initiated by sulfate uptake, generates cysteine, the substrate for glutathione (GSH) and phytochelatin (PC) synthesis. GSH and PC contribute to cadmium (Cd) detoxification by capturing it for sequestration. Although Cd exposure is known to induce the expression of S-assimilating enzyme genes, including sulfate transporters (SULTRs), mechanisms of their transcriptional regulation are not well understood. Transcription factor SLIM1 controls transcriptional changes during S deficiency (−S) in Arabidopsis thaliana. We examined the potential involvement of SLIM1 in inducing the S assimilation pathway and PC accumulation. Cd treatment reduced the shoot fresh weight in the sulfur limitation1 (slim1) mutant but not in the parental line (1;2PGN). Cd-induced increases of sulfate uptake and SULTR1;2 expressions were diminished in the slim1 mutant, suggesting that SLIM1 is involved in inducing sulfate uptake during Cd exposure. The GSH and PC levels were lower in slim1 than in the parental line, indicating that SLIM1 was required for increasing PC during Cd treatment. Hence, SLIM1 indirectly contributes to Cd tolerance of plants by inducing −S responses in the cell caused by depleting the GSH pool, which is consumed by enhanced PC synthesis and sequestration to the vacuole.
Overview of Earth Observation Satellite Platform Microvibration Detection Methods
Authors: Tang Xinming , Xie Junfeng , Zhu Hong , Mo Fan
Published: January 2020

Satellite platform microvibration is a common phenomenon in earth observation satellite orbits that directly affects the imaging quality and accuracy of surveying and mapping. With the continuous improvement in the spatial resolution, the influence of satellite platform microvibration on image geometric accuracy is becoming increasingly significant. High-precision microvibration detection and compensation are key technologies for eliminating image distortion and location deviation caused by satellite platform microvibration. In this paper, the microvibration detection methods of different satellite platforms are summarized, and the verification and analysis are performed on the data downloaded from the Resource-3 satellite (ZY-3) platform, to provide technical support for subsequent refined processing of satellite attitude.
Determining Extremes for Future Precipitation in South Korea Based on RCP Scenarios Using Non-Parametric SPI
Authors: Butu Hemen Mark , Seo Yongwon , Huh Jeung Soo
Published: January 2020

Historical, downscaled and projected data for six cities in South Korea were collected and analyzed using non-parametric Standardized Precipitation Index (SPI) across the Representative Concentration Pathways (RCPs) RCP4.5 and RCP8.5. SPI results were utilized in further analyses: intensity, decadal frequency, and temporal shifts. Non-parametric SPI was used as it produces more reliable results in terms of their statistical, spatial and temporal characteristics. RCP4.5 was taken to represent concentrations under the current emissions trajectory, while RCP8.5 represents the high-end scenario. Findings suggest that extreme precipitation events are more likely to increase in number than extreme drought across all timescales and RCPs. Variability was observed to increase when comparing SPI obtained from actual, measured and gridded precipitation. More extreme droughts are expected under RCP8.5 forcing as are the occurrence of multiyear droughts and extreme wet events relative to RCP4.5. A seasonal shift in extreme precipitation of up to 3 months earlier was observed. Generally, the period between 2080 and 2100 holds the highest probability to host extremely rare and persistent events.
Participation and Goal Achievement of Multiparty Collaborative Systems Dealing with Complex Problems: A Natural Experiment
Authors: Curșeu Petru Lucian , Schruijer Sandra G.L.
Published: January 2020

Multiparty collaborative systems often deal with wicked sustainability challenges. Previous research has emphasized the important role of stakeholder representation and participation in comprehensive sustainability decisions. We report the results of an empirical test of the effect of stakeholder participation on systemic goal achievement and on multiparty dynamics in a natural experiment, using the results obtained through two simulations in which 44 professionals participated. In one of the simulations a ‘party exclusion dynamic’ evolved. As the two simulations had a similar baseline, the same number of participants distributed in a similar manner among seven stakeholder parties in each simulation, we could test the effect of stakeholder participation on goal achievement and systemic dynamics, using the other simulation as a comparison. Our results show that stakeholder exclusion prevents systemic goal achievement, disrupts collaboration and induces systemic powerlessness.
Immunization Status against Measles, Mumps, Rubella and Varicella in a Large Population of Internationally Adopted Children Referred to Meyer Children’s University Hospital from 2009 to 2018
Authors: Bechini Angela , Boccalini Sara , Alimenti Cecilia Maria , Bonanni Paolo , Galli Luisa , Chiappini Elena
Published: January 2020

Control of vaccine preventable diseases (VPDs) is a challenge for healthcare systems. Different studies highlighted the suboptimal immunization of internationally adopted children (IAC). To evaluate the immunization status against measles, mumps, rubella (MMR), and varicella (V) in a large cohort of IAC, data at first screening visit of all IAC (<18 years) consecutively referred to Meyer Children’s University Hospital (Florence, Italy) from 2009 to 2018 were collected and analyzed. In total, 1927 children (median age: 5.99 years, interquartile range: 3.33–8.21) were enrolled. More than half of IAC were unprotected against MMR-V. The reliability of the vaccination documentation of the country of origin was poor, since more than a quarter of the IAC serologically tested were not protected against MMR-V, despite the vaccination documentation attesting previous vaccination. This was significantly more pronounced in children aged 15–18 years and in those originating from Africa. High rate of discordant serological results/documentation brings up questions regarding the optimal management of IACs, and suggests a rapid, careful, and complete assessment of immunization status timely after IAC’s arrival. Serological testing of IAC of all ages followed by vaccination of seronegative children should be provided.
Exploring Influenza Vaccine Uptake and Its Determinants among University Students: A Cross-Sectional Study
Authors: Kawahara Yukako , Nishiura Hiroshi
Published: January 2020

While vaccination is the only established option to prevent a susceptible host from influenza, we have yet to clarify the decision-making mechanisms of vaccine uptake among Japanese university and college students. We aimed to explore vaccination coverage and the related demographic, sociocultural, and socioeconomic factors among university students. We performed a cross-sectional survey involving 604 students at Hokkaido University. Participants were asked if they received influenza vaccination in advance of the 2018/19 season, and subsequently, their demographic and sociocultural/socioeconomic characteristics were surveyed. We also explored the mechanisms underlying students’ vaccination decisions. Vaccination coverage was estimated at 27.3% (95% confidence interval: 23.7–30.9). Freshmen (p < 0.0001) were significantly associated with choosing vaccination, and their odds ratio of vaccination was 11.3 (95% confidence interval: 6.2–20.7) times greater than students in other years. Among students other than freshmen, students belonging to medicine- and healthcare-related faculties were vaccinated three times more frequently than other students, and the coverage in students from Hokkaido was twice as large as that for students from other prefectures. Moreover, extracurricular activity was a positive predictor of vaccination. Although the coverage was as small as 27.3% among university students, freshmen in Japan have high vaccination coverage, which we believe is associated with the entrance examination during high influenza activity. In addition to exposing students to proper education regarding their risk self-assessment, consciousness raising via appropriate understanding of influenza and its severity and offering vaccination at university health centers at a reasonable cost may promote vaccine acceptance.
Immune Therapy Targeting E6/E7 Oncogenes of Human Papillomavirus Type 6 (HPV-6) Reduces or Eliminates the Need for Surgical Intervention in the Treatment of HPV-6 Associated Recurrent Respiratory Papillomatosis
Authors: Aggarwal Charu , Cohen Roger B. , Morrow Matthew P. , Kraynyak Kimberly A. , Sylvester Albert J. , Cheung Jocelyn , Dickerson Kelsie , Schulten Veronique , Knoblock Dawson , Gillespie Elisabeth , Bauml Joshua M. , Yan Jian , Diehl Malissa , Boyer Jean , Dallas Michael , Kim J. Joseph , Weiner David B. , Skolnik Jeffrey M.
Published: January 2020

Background: Recurrent respiratory papillomatosis (RRP) is a rare disorder characterized by the generation of papillomas of the aerodigestive tract, usually associated with human papilloma virus (HPV) subtypes 6, 11. INO-3106 is a DNA plasmid-based immunotherapy targeting E6 and E7 proteins of HPV6, in order to create a robust immune T cell response. Methods: Testing of INO-3016 in animal models confirmed immunogenicity of the DNA-based therapy. A single-site open-label Phase 1 study was initiated for patients with HPV6-positive RRP. Patients were dosed with INO-3106 with or without INO-9012, a DNA plasmid immunotherapy that encodes IL-12, delivered intramuscularly (IM) in combination with electroporation (EP) with the CELLECTRA® device. Patients received an escalating dose of INO-3106, 3 mg once and then 6 mg for three additional doses, each dose three weeks apart, with the third and fourth doses co-administered with INO-9012. The primary objective of the study was to evaluate the safety and tolerability of INO-3106 with and without INO-9012. The secondary objective was to determine cellular immune responses to INO-3106 with and without INO-9012. Exploratory objectives included preliminary clinical efficacy to the therapy. Results: Three patients were enrolled in this study, of which two had RRP. Study therapy was well-tolerated, with no related serious adverse events and all related adverse events (AEs) were low-grade. Injection site pain was the most common related AE reported. Immunogenicity was evidenced by multiple immune assays showing engagement and expansion of an HPV6-specific cellular response, including cytotoxic T cells. Preliminary efficacy was demonstrated in patients with RRP in the form of reduction in need for surgical intervention for papilloma growth. Prior to intervention, both patients required surgical intervention approximately every 180 days. One patient demonstrated a greater than three-fold increase in surgery avoidance (584 days) and the other patient remains completely surgery-free as of the last contact at 915 days, a greater than 5-fold increase in surgery interval. Conclusion: INO-3106 with and without INO-9012 was well tolerated, immunogenic and demonstrated preliminary efficacy in patients with HPV6-associated RRP aerodigestive lesions. Further clinical study is indicated.
METODOLOGIAS ATIVAS  ESTUDO DE CASO: RETENÇÃO E AVALIAÇÃO DE RESULTADOS
Authors: Santos Jadir Perpetuo dos , Junger Alex Paubel , Amaral Luiz Henrique , Andrade Alexandre Acácio de
Published: January 2020

Essa pesquisa tem como objetivo identificar fatores estimulantes de conhecimento na perspectiva do aluno e retenção de alunos nas Faculdades de Tecnologias, aplicar esses fatores em metodologias ativas e fazer um comparativo de aprendizado entre a metodologia tradicional, para isso o trabalho apresenta um framework descrevendo que a metodologia aplicada, iniciou-se com a leitura de referenciais teóricos em fontes primárias sobre metodologias ativas, criando-se um questionário semiestruturado aplicado aos alunos de diversos cursos de tecnologia, com esses resultados desenvolveu-se através da abordagem dedutiva uma aula (estudo de caso) com metodologias ativas, os resultados foram: a metodologia ativa não possui resultado inferior ao presencial, evidencia-se que 69,2% dos alunos preferem metodologia ativa a tradicional, considerando-as: dinâmicas motivadoras é de fácil entendimento entre teoria e prática. Entre os fatores estimulantes tem-se: Aulas dinâmicas mesclando metodologias ativas e aulas tradicionais; Aulas objetivas, dando oportunidade de expressão dos alunos; Redução de atividades extras, para ajudar o aluno a se organizar, quando possível. A qualidade dos professores está entre os fatores de retenção.
A IMPORTÂNCIA DA DISCUSSÃO DA MORAL NA EDUCAÇÃO PÚBLICA: ENSAIOS SOBRE AQUISIÇÃO DOS VALORES MORAIS NA SOCIEDADE CONTEMPORÂNEA
Authors: Martins Marcos Antonio Madeira de Mattos , Martins Karla Cristina da Costa e Silva de MAttos , Rosini Alessandro Marco , Palmisano Angelo , Conceição Marcio Magera
Published: January 2020

Este artigo trata do processo de transmissão da moralidade e a aprendizagem dos valores no mundo pós-moderno. A partir do aprofundamento dos conceitos de moralidade, educação e aquisição de moralidade, entende-se que é na interação e relação interpessoal que a moral se forma e se estabelece. O desenvolvimento moral ocorre quando a criança aprende como agir perante o outro, respeitando regras e promovendo a dignidade humana. O artigo indica um paradoxo da pós-modernidade: o imenso desenvolvimento tecnológico em detrimento de imaturidade política e crise da ética e moral. Por fim, apresenta o método construtivista como uma possível solução para resolução do problema de aquisição dos valores morais.
O COMPORTAMENTO AUTOLESIVO NA ADOLESCÊNCIA: UMA REVISÃO INTEGRATIVA DA LITERATURA.
Authors: Chaves Gislaine , Tardivo Leila Salomão de La Plata Cury , Pinto Júnior Antônio Augusto , Rosa Helena Rinaldi
Published: January 2020

RESUMO

Objetivo: Realizar uma revisão integrativa da literatura sobre o comportamento autolesivo na adolescência. Método: Foram consultadas as bases de dados do Portal de Periódicos da Capes, Biblioteca Virtual da Saúde, SciELO e bancos de teses da Universidade de São Paulo, da Pontifícia Universidade Católica de São Paulo e Universidade Estadual de Campinas, bem como o Google Acadêmico, no período de 2006 a 31 de maio de 2017. Foram considerados os estudos clínicos ou teóricos, originais ou revisões, completos e gratuitos sobre o comportamento autolesivo na adolescência publicados, nas bases investigadas. Resultados: Localizou-se um total de 502 estudos, sendo 24 selecionados. Conclusão: Observou-se, nas bases investigadas, a predominância de estudos qualitativos, em especial, os estudos de caso embasados na abordagem psicanalítica, demonstrando um crescente interesse nos sentidos e significados do comportamento autolesivo pela comunidade científica.

Descritores: Comportamentos autodestrutivo; Conduta autolesiva; Adolescente.