bluuebunny/crossref_metadata_2025 huggingface dataset:
Drosophila Interspecific Hybridization Causes a Deregulation of the piRNA Pathway Genes
Authors: Gámez-Visairas Víctor , Romero-Soriano Valèria , Martí-Carreras Joan , Segarra-Carrillo Eila , García Guerreiro Maria Pilar
Published: February 2020

Almost all eukaryotes have transposable elements (TEs) against which they have developed defense mechanisms. In the Drosophila germline, the main transposable element (TE) regulation pathway is mediated by specific Piwi-interacting small RNAs (piRNAs). Nonetheless, for unknown reasons, TEs sometimes escape cellular control during interspecific hybridization processes. Because the piRNA pathway genes are involved in piRNA biogenesis and TE control, we sequenced and characterized nine key genes from this pathway in Drosophila buzzatii and Drosophila koepferae species and studied their expression pattern in ovaries of both species and their F1 hybrids. We found that gene structure is, in general, maintained between both species and that two genes—armitage and aubergine—are under positive selection. Three genes—krimper, methyltransferase 2, and zucchini—displayed higher expression values in hybrids than both parental species, while others had RNA levels similar to the parental species with the highest expression. This suggests that the overexpression of some piRNA pathway genes can be a primary response to hybrid stress. Therefore, these results reinforce the hypothesis that TE deregulation may be due to the protein incompatibility caused by the rapid evolution of these genes, leading to a TE silencing failure, rather than to an underexpression of piRNA pathway genes.
Repetitive DNA Restructuring Across Multiple Nicotiana Allopolyploidisation Events Shows a Lack of Strong Cytoplasmic Bias in Influencing Repeat Turnover
Authors: Dodsworth Steven , Guignard Maïté S. , Pérez-Escobar Oscar A. , Struebig Monika , Chase Mark W. , Leitch Andrew R.
Published: February 2020

Allopolyploidy is acknowledged as an important force in plant evolution. Frequent allopolyploidy in Nicotiana across different timescales permits the evaluation of genome restructuring and repeat dynamics through time. Here we use a clustering approach on high-throughput sequence reads to identify the main classes of repetitive elements following three allotetraploid events, and how these are inherited from the closest extant relatives of the maternal and paternal subgenome donors. In all three cases, there was a lack of clear maternal, cytoplasmic bias in repeat evolution, i.e., lack of a predicted bias towards maternal subgenome-derived repeats, with roughly equal contributions from both parental subgenomes. Different overall repeat dynamics were found across timescales of <0.5 (N. rustica L.), 4 (N. repanda Willd.) and 6 (N. benthamiana Domin) Ma, with nearly additive, genome upsizing, and genome downsizing, respectively. Lower copy repeats were inherited in similar abundance to the parental subgenomes, whereas higher copy repeats contributed the most to genome size change in N. repanda and N. benthamiana. Genome downsizing post-polyploidisation may be a general long-term trend across angiosperms, but at more recent timescales there is species-specific variance as found in Nicotiana.
BTG4 is A Novel p53 Target Gene That Inhibits Cell Growth and Induces Apoptosis
Authors: Zhang Na , Jiang Tinghui , Wang Yitao , Hu Lanyue , Bu Youquan
Published: February 2020

BTG4 is the last cloned and poorly studied member of BTG/Tob family. Studies have suggested that BTG4 is critical for the degradation of maternal mRNAs in mice during the process of maternal-to-zygotic transition, and downregulated in cancers, such as gastric cancer. However, the regulatory mechanism of BTG4 and its function in cancers remain elusive. In this study, we have for the first time identified the promoter region of the human BTG4 gene. Serial luciferase reporter assay demonstrated that the core promoter of BTG4 is mainly located within the 388 bp region near its transcription initiation site. Transcription factor binding site analysis revealed that the BTG4 promoter contains binding sites for canonical transcription factors, such as Sp1, whereas its first intron contains two overlapped consensus p53 binding sites. However, overexpression of Sp1 has negligible effects on BTG4 promoter activity, and site-directed mutagenesis assay further suggested that Sp1 is not a critical transcription factor for the transcriptional regulation of BTG4. Of note, luciferase assay revealed that one of the intronic p53 binding sites is highly responsive to p53. Both exogenous p53 overexpression and adriamycin-mediated endogenous p53 activation result in the transcriptional upregulation of BTG4. In addition, BTG4 is downregulated in lung and colorectal cancers, and overexpression of BTG4 inhibits cell growth and induces apoptosis in cancer cells. Taken together, our results strongly suggest that BTG4 is a novel p53-regulated gene and probably functions as a tumor suppressor in lung and colorectal cancers.
Two Novel FAM20C Variants in a Family with Raine Syndrome
Authors: Hernández-Zavala Araceli , Cortés-Camacho Fernando , Palma-Lara Icela , Godínez-Aguilar Ricardo , Espinosa Ana María , Pérez-Durán Javier , Villanueva-Ocampo Patricia , Ugarte-Briones Carlos , Serrano-Bello Carlos Alberto , Sánchez-Santiago Paula Jesús , Bonilla-Delgado José , Yáñez-López Marco Antonio , Victoria-Acosta Georgina , López-Ornelas Adolfo , García Alonso-Themann Patricia , Moreno José , Palacios-Reyes Carmen
Published: February 2020

Two siblings from a Mexican family who carried lethal Raine syndrome are presented. A newborn term male (case 1) and his 21 gestational week brother (case 2), with a similar osteosclerotic pattern: generalized osteosclerosis, which is more evident in facial bones and cranial base. Prenatal findings at 21 weeks and histopathological features for case 2 are described. A novel combination of biallelic FAM20C pathogenic variants were detected, a maternal cytosine duplication at position 456 and a paternal deletion of a cytosine in position 474 in exon 1, which change the reading frame with a premature termination at codon 207 and 185 respectively. These changes are in concordance with a negative detection of the protein in liver and kidney as shown in case 2. Necropsy showed absence of pancreatic Langerhans Islets, which are reported here for the first time. Corpus callosum absence is added to the few reported cases of brain defects in Raine syndrome. This report shows two new FAM20C variants not described previously, and negative protein detection in the liver and the kidney. We highlight that lethal Raine syndrome is well defined as early as 21 weeks, including mineralization defects and craniofacial features. Pancreas and brain defects found here in FAM20C deficiency extend the functional spectrum of this protein to previously unknown organs.
Ubiquitin E3 Ligase AaBre1 Responsible for H2B Monoubiquitination Is Involved in Hyphal Growth, Conidiation and Pathogenicity in Alternaria alternata
Authors: Liu Ye , Xin Jingjing , Liu Lina , Song Aiping , Liao Yuan , Guan Zhiyong , Fang Weimin , Chen Fadi
Published: February 2020

Ubiquitination is one of several post-transcriptional modifications of histone 2B (H2B) which affect the chromatin structure and, hence, influence gene transcription. This study focuses on Alternaria alternata, a fungal pathogen responsible for leaf spot in many plant species. The experiments show that the product of AaBRE1, a gene which encodes H2B monoubiquitination E3 ligase, regulates hyphal growth, conidial formation and pathogenicity. Knockout of AaBRE1 by the homologous recombination strategy leads to the loss of H2B monoubiquitination (H2Bub1), as well as a remarkable decrease in the enrichment of trimethylated lysine 4 on histone 3 (H3K4me3). RNA sequencing assays elucidated that the transcription of genes encoding certain C2H2 zinc-finger family transcription factors, cell wall-degrading enzymes and chitin-binding proteins was suppressed in the AaBRE1 knockout cells. GO enrichment analysis showed that these proteins encoded by the set of genes differentially transcribed between the deletion mutant and wild type were enriched in the functional categories “macramolecular complex”, “cellular metabolic process”, etc. A major conclusion was that the AaBRE1 product, through its effect on histone 2B monoubiquitination and histone 3 lysine 4 trimethylation, makes an important contribution to the fungus’s hyphal growth, conidial formation and pathogenicity.
Anti-Aging Effects of Leontopodium alpinum (Edelweiss) Callus Culture Extract through Transcriptome Profiling
Authors: Cho Won Kyong , Kim Hye-In , Kim Soo-Yun , Seo Hyo Hyun , Song Jihyeok , Kim Jiyeon , Shin Dong Sun , Jo Yeonhwa , Choi Hoseong , Lee Jeong Hun , Moh Sang Hyun
Published: February 2020

Edelweiss (Leontopodium Alpinum) in the family Asteraceae is a wildflower that grows in rocky limestone places. Here, we investigated the efficacy of edelweiss callus culture extract (Leontopodium Alpinum callus culture extract; LACCE) using multiple assays from in vitro to in vivo as well as transcriptome profiling. Several in vitro assay results showed the strong antioxidant activity of LACCE in response to UVB treatment. Moreover, LACCE suppressed inflammation and wrinkling; however, moisturizing activity was increased by LACCE. The clinical test in vivo demonstrated that constant application of LACCE on the face and skin tissues improved anti-periorbital wrinkles, skin elasticity, dermal density, and skin thickness compared with the placebo. The RNA-Sequencing results showed at least 16.56% of human genes were expressed in keratinocyte cells. LACCE up-regulated genes encoding several KRT proteins; DDIT4, BNIP3, and IGFBP3 were involved in the positive regulation of the developmental process, programmed cell death, keratinization, and cornification forming skin barriers, which provide many advantages in the human skin. By contrast, down-regulated genes were stress-responsive genes, including metal, oxidation, wounding, hypoxia, and virus infection, suggesting LACCE did not cause any harmful stress on the skin. Our comprehensive study demonstrated LACCE is a promising agent for anti-aging cosmetics.
Serendipitous In Situ Conservation of Faba Bean Landraces in Tunisia: A Case Study
Authors: Babay Elyes , Khamassi Khalil , Sabetta Wilma , Miazzi Monica Marilena , Montemurro Cinzia , Pignone Domenico , Danzi Donatella , Finetti-Sialer Mariella Matilde , Mangini Giacomo
Published: February 2020

Cultivation of faba bean (Vicia faba L.) in Tunisia is largely based on improved varieties of the crop. However, a few farmers continue to produce local cultivars or landraces. The National Gene Bank of Tunisia (NGBT) recently launched a collection project for faba bean landraces, with special focus on the regions of the North West, traditionally devoted to cultivating grain legumes, and where around 80% of the total national faba bean cultivation area is located. The seed phenotypic features of the collected samples were studied, and the genetic diversity and population structure analyzed using simple sequence repeat markers. The genetic constitution of the present samples was compared to that of faba bean samples collected by teams of the International Center for Agricultural Research in the Dry Areas (ICARDA) in the 1970s in the same region, and stored at the ICARDA gene bank. The results of the diversity analysis demonstrate that the recently collected samples and those stored at ICARDA largely overlap, thus demonstrating that over the past 50 years, little genetic change has occurred to the local faba bean populations examined. These findings suggest that farmers serendipitously applied international best practices for in situ conservation of agricultural crops.
Universal Screening for CCHD in Saudi Arabia: The Road to a ‘State of the Art’ Program
Authors: AlAql Fahad , Khaleel Huda , Peter Vetha
Published: February 2020

Critical congenital heart disease (CCHD) has been defined as structural heart defects that are usually associated with hypoxia in the newborn period and have potential for significant morbidity and mortality early in life. CCHD has been estimated to be present in ∼3 in 1000 live births, including Saudi Arabia. Pulse Oximetry Screening (POS) is a highly specific and moderately sensitive test for detecting CCHD with very low false-positive rates. The Kingdom of Saudi Arabia is among high-income countries with a population of more than 33 million and more than 600,000 annual live births. In 2015, the Universal Screening Program for CCHD using Pulse Oximetry was approved in Saudi Arabia. It is expected that any new national program will undergo a learning curve and face many challenges. We believe that developing countries may face different challenges during implementation of such national projects, but the success achieved by Saudi Arabia in implementing the program was mainly due to good preparation before launching the project and advancements in the use of the technology involved in this project. Since starting the universal CCHD screening in 2016, more than 900,000 babies have been screened in Saudi Arabia and many lives have been saved using this safe, non-invasive, inexpensive, and reasonably sensitive test.
Intraoperative Oxygen Delivery and Acute Kidney Injury after Liver Transplantation
Authors: Kim Won Ho , Lee Ho-Jin , Yoon Hee-Chul , Lee Kook Hyun , Suh Kyung-Suk
Published: February 2020

Although intraoperative hemodynamic variables were reported to be associated with acute kidney injury (AKI) after liver transplantation, the time-dependent association between intraoperative oxygen delivery and AKI has not yet been evaluated. We reviewed 676 cases of liver transplantation. Oxygen delivery index (DO2I) was calculated at least ten times during surgery. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. The area under the curve (AUC) was calculated as below a DO2I of 300 (AUC < 300), 400 and 500 mL/min/m2 threshold. Also, the cumulative time below a DO2I of 300 (Time < 300), 400, and 500 mL/min/m2 were calculated. Multivariable logistic regression analysis was performed to evaluate whether AUC < 300 or time < 300 was independently associated with the risk of AKI. As a sensitivity analysis, propensity score matching analysis was performed between the two intraoperative mean DO2I groups using a cutoff of 500 ml/min/m2, and the incidence of AKI was compared between the groups. Multivariable analysis showed that AUC < 300 or time < 300 was an independent predictor of AKI (AUC < 300: odds ratio [OR] = 1.10, 95% confidence interval [CI] 1.06–1.13, time < 300: OR = 1.10, 95% CI 1.08–1.14). Propensity score matching yielded 192 pairs of low and high mean DO2I groups. The incidence of overall and stage 2 or 3 AKI was significantly higher in the lower DO2I group compared to the higher group (overall AKI: lower group, n = 64 (33.3%) vs. higher group, n = 106 (55.2%), P < 0.001). In conclusion, there was a significant time-dependent association between the intraoperative poor oxygen delivery <300 mL/min/m2 and the risk of AKI after liver transplantation. The intraoperative optimization of oxygen delivery may mitigate the risk of AKI.
Surgical Outcomes of Secondary Alveolar Bone Grafting and Extensive Gingivoperiosteoplasty Performed at Mixed Dentition Stage in Unilateral Complete Cleft Lip and Palate
Authors: Chu Yu-Ying , Chang Frank Chun-Shin , Lu Ting-Chen , Lee Che-Hsiung , Chen Philip Kuo-Ting
Published: February 2020

Secondary alveolar bone grafting (SABG) is associated with donor site morbidities. We aimed to compare the outcomes of SABG and extensive gingivoperiosteoplasty (EGPP) at the mixed dentition stage. This single-blinded, randomized, prospective trial enrolled 50 consecutive patients with unilateral complete cleft lip and palate who had residual alveolar bone cleft, of which 44 (19 SABG, 25 EGPP) completed the study. Bone volumes before surgery, 6 months postoperatively, and 1-year postoperatively were compared using computed tomography. The Bergland scale score was recorded at 6 months postoperatively. Both groups had the same preoperative alveolar cleft volume. On the Bergland scale, 21, 3, and 1 patient in the EGPP group and 16, 2, and 1 patient in the SABG group were classified as types I, II, and IV, respectively, which did not show significant difference. With perioperative orthodontic treatment, the 1-year residual bone defect volume in both groups did not show significant difference (SABG 0.12 cm3 vs. EGPP at 0.14 cm3, p > 0.05). The study was not able to reveal much difference between SABG and EGPP combined with perioperative orthodontic treatment.
A Note on the Topological Transversality Theorem for Weakly Upper Semicontinuous, Weakly Compact Maps on Locally Convex Topological Vector Spaces
Authors: O’Regan Donal
Published: February 2020

A simple theorem is presented that automatically generates the topological transversality theorem and Leray–Schauder alternatives for weakly upper semicontinuous, weakly compact maps. An application is given to illustrate our results.
Could the Age Difference of a Single Calendar Year between Patients Undergoing IVF at 34, 35 or at 36 Years Old Affect the IVF Outcome? A Retrospective Data Analysis
Authors: Pantos Konstantinos , Sfakianoudis Konstantinos , Grigoriadis Sokratis , Maziotis Evangelos , Tsioulou Petroula , Rapani Anna , Giannelou Polina , Atzampos Anastasios , Koulouraki Sevasti , Koutsilieris Michael , Vlahos Nikolaos , Mastorakos George , Simopoulou Mara
Published: February 2020

Background and Objectives: Clinicians are called to overcome age-related challenges in decision making during In Vitro Fertilization (IVF) treatment. The aim of this study was to investigate the possible impact of a single calendar year difference among patients aged 34, 35 and 36 on IVF outcomes. Materials and Methods: Medical records between 2008 and 2019 were analyzed retrospectively. The study group consisted of women diagnosed with tubal factor infertility. Sample size was divided in three categories at 34, 35 and 36 years of age. Embryo transfer including two blastocysts was performed for every patient. Comparisons were performed regarding hormonal profile, response to stimulation, quality of transferred embryos, positive hCG test and clinical pregnancy rate. Results: A total of 706 women were eligible to participate. Two-hundred and forty-eight women were 34, 226 were 35 while the remaining 232 were 36 years old. Regarding the hormonal profile, the number of accumulated oocytes and the quality of embryos transferred, no statistically significant difference was documented between the three age groups. Women aged 34 and 35 years old indicated a significantly increased positive hCG rate in comparison to women aged 36 years old (p-value = 0.009, p-value = 0.023, respectively). Women aged 34 and 35 years old presented with a higher clinical pregnancy rate in comparison to those aged 36 years old (p-value = 0.04, p-value = 0.05, respectively). Conclusion: A calendar year difference between patients undergoing IVF treatment at 34 or 35 years of age does not appear to exert any influence regarding outcome. When treatment involves patients above the age of 35, then a single calendar year may exert considerable impact on IVF outcome. This observation indicates that age 35 may serve as a valid cut-off point regarding IVF outcome.
Predictors of Hyperuricemia after Kidney Transplantation: Association with Graft Function
Authors: Folkmane Inese , Tzivian Lilian , Folkmane Elizabete , Valdmane Elina , Kuzema Viktorija , Petersons Aivars
Published: February 2020

Background and objectives: In kidney transplant recipients (KTR), hyperuricemia (HU) is a commonly-observed phenomenon, due to calcineurin inhibitors and reduced kidney graft function. Factors predicting HU, and its association with graft function, remains equivocal. Materials and Methods: We conducted a retrospective longitudinal study to assess factors associated with HU in KTR, and to determine risk factors associated with graft function, measured as glomerular filtration rate (GFR). Moreover, GFR > 60 mL/min/1.73 m2 was considered normal. HU was defined as a serum uric acid level of > 416 μmol/L (4.70 mg/dL) in men and >357 μmol/L (4.04 mg/dL) in women, or xanthine-oxidase inhibitor use. We built multiple logistic regression models to assess predictors of HU in KTR, as well as the association of demographic, clinical, and biochemical parameters of patients with normal GFR after a three-year follow-up. We investigated the effect modification of this association with HU. Results: There were 144 patients (mean age 46.6 ± 13.9), with 42.4% of them having HU. Predictors of HU in KTR were the presence of cystic diseases (OR = 9.68 (3.13; 29.9)), the use of diuretics (OR = 4.23 (1.51; 11.9)), and the male gender (OR = 2.45 (1.07; 5.56)). Being a younger age, of female gender, with a normal BMI, and the absence of diuretic medications increased the possibility of normal GFR. HU was the effect modifier of the association between demographic, clinical, and biochemical factors and a normal GFR. Conclusions: Factors associated with HU in KTR: Presence of cystic diseases, diuretic use, and male gender. HU was the effect modifier of the association of demographic, clinical, and biochemical factors to GFR.
Measurement of Heat Transfer from Anodic Oxide Film on Aluminum in High Knudsen Number Flows
Authors: Yamaguchi Hiroki , Kito Kenji
Published: February 2020

The heat transfer in vacuum depends on the gas–surface interaction. In this study, the heat flux from anodic oxide films on aluminum with different anodizing times through a gas confined between two surfaces with different temperatures was studied. We prepared a non-treated surface, a surface with a normal anodizing time of 30 min, and a surface with 90 min, where the formed film would partially dissolve by long time exposure to the solution. The formation of the films was checked by electrical resistance. Scanning electron microscope (SEM) images were obtained for the three sample surfaces. Even though it was difficult to observe the hexagonal cylindrical cell structures on anodic oxide films, the 30 min sample surface was shown to be rough, and it was relatively smooth and powdery for the 90 min sample surface. The heat fluxes from three sample surfaces were measured from the free-molecular to near free-molecular flow regimes, and analyzed to obtain the energy accommodation coefficients. The heat fluxes were well fitted by the fitting curves. The energy accommodation coefficients for both helium and argon increased by anodizing an aluminum sample surface, while they decreased with increasing the anodizing time up to 90 min indicating the dissolution of the film.
Evaluation of a Spatial Heterodyne Spectrometer for Raman Spectroscopy of Minerals
Authors: Zettner Alina , Gojani Ardian B. , Schmid Thomas , Gornushkin Igor B.
Published: February 2020

Spatial heterodyne spectroscopy (SHS) is a novel spectral analysis technique that is being applied for Raman spectroscopy of minerals. This paper presents the theoretical basis of SHS and its application for Raman measurements of calcite, quartz and forsterite in marble, copper ore and nickel ore, respectively. The SHS measurements are done using a broadband (518–686 nm) and resolving power R ≈ 3000 instrument. The spectra obtained using SHS are compared to those obtained by benchtop and modular dispersive spectrometers. It is found that SHRS performance in terms of resolution is comparable to that of the benchtop spectrometer and better than the modular dispersive spectrometer, while the sensitivity of SHRS is worse than that of a benchtop spectrometer, but better than that of a modular dispersive spectrometer. When considered that SHS components are small and can be packaged into a handheld device, there is interest in developing an SHS-based instrument for mobile Raman spectroscopy. This paper evaluates the possibility of such an application.
3D Nanoparticle Tracking Inside the Silver Nanofluid
Authors: Vafaei Saeid
Published: February 2020

Movement of nanoparticle was investigated at the vicinity of silver nanofluid by using a microscope equipped with 100X lens. It was observed that silver nanoparticles were constantly moving inside the nanofluid for the first time. To explore the silver nanoparticle movement, the silver nanofluid was mixed with fluorescent nanoparticles. The coated nanoparticles were tracked three-dimensionally using a Delta Vision Elite inverted optical microscope. It was found that Marangoni flow was a possible reason of the nanoparticle movement which was generated by a gradient of the surface tension at the vicinity of the triple line. A gradient of the surface tension was formed by the segregation of the surfactant from the base liquid at the vicinity of the triple line. The surfactant was separated from the base liquid inside the triple region, since they have different affinities for the substrate. It was also shown that ring phenomenon took place when nanoparticle movement was weak or negligible.
Effects of Amorphous Silica Nanopowders on the Avoidance Behavior of Five Soil Species—A Screening Study
Authors: Santos Joana , Barreto Ângela , Nogueira João , Daniel-da-Silva Ana Luísa , Trindade Tito , Amorim Mónica J. B. , Maria Vera L.
Published: February 2020

Silica nanoparticles (SiO2NPs) are one of the most used in commercial products and biomedical tools, however, their environmental effects have not been fully described. Although negative effects of SiO2NPs on the behavior of freshwater invertebrates have been reported, the knowledge is limited, especially the effect of nanopowders in terrestrial organisms. Accordingly, the aim of the present study is to understand the effects of SiO2NPs on the avoidance behavior of five soil species, whose niche may differ thus contributing to differential harmful SiO2NPs effects. Hence, avoidance assays testing SiO2NPs concentrations of 0, 10, 100, 250, 500 and 1000 mg/kg were performed with Enchytraeus crypticus, Folsomia candida, Tenebrio molitor, Porcellionides pruinosus and Eisenia fetida. SiO2NPs induced different behavioral effects, depending on the invertebrate ecology/habitat, exposure route and physiology. T. molitor, P. pruinosus and F. candida did not avoid contaminated soil; however, E. crypticus and E. fetida significantly avoided SiO2NPs spiked soil. Since these terrestrial worms (oligochaetes) live mostly burrowed in the soil, this can provide greater opportunity for SiO2NPs’ uptake. On the other hand, the other tested organisms mainly living on the upper part of the soil did not avoid the SiO2NPs spiked soil. The avoidance data obtained here also highlight the need for further studies to understand whether (or not) the detected behavioral responses are linked to either neurotransmission processes or sensorial aspects of the biological models.
Study on the Mechanism of Nano-SiO2 for Improving the Properties of Cement-Based Soil Stabilizer
Authors: Zhang Xingchen , Gao Jianen , Fan Henghui , Li Xinghua , Gao Zhe , Xue Li , Sun Shengli
Published: February 2020

A new nano-soil stabilizer (N-MBER, Nanometer Material Becoming Earth into Rock) material was developed in this research by using the high activity and ultrafine properties of nano-SiO2 (NS), which were able to improve the properties of cement-based soil stabilizer and had broad application prospects. The results showed that (1) the strength of N-MBER obeyed a compound function relation with curing period and additive amount of NS. The relationship between strength and curing period obeyed an exponential function when the additive amount was constant. The strength and additive amount were a power function when the curing period was fixed. The compressive strength of N-MBER increased by more than 15% compared with MBER at day 28 of the curing period, and 50% compared with grade 32.5 cement. (2) The pozzolanic catalytic activity of NS significantly increased the amount of calcium silicate hydrate gel (C–S–H) in the N-MBER colloid. NS was also able to make the distribution of the network structure of colloidal space more uniform and improved the fractal dimension of particles by 0.05. The above results provide theoretical data for exploring the mechanism of soil stabilizer strength growth and for promoting the application of solid waste utilization.
The Nanofication and Functionalization of Bacterial Cellulose and Its Applications
Authors: Choi Soon Mo , Shin Eun Joo
Published: February 2020

Since economic and environmental issues have become critical in the last several years, the amount of sustainable bio-based production has increased. In this article, microbial polysaccharides, including bacterial cellulose (BC), are analyzed as promising resources with the potential for applications in biofields and non-biofields. Many scientists have established various methods of BC production, nanofication, and functionalization. In particular, this review will address the essential advances in recent years focusing on nanofication methods and nanoficated BC applications as well as functionalization methods and functionalized BC applications.
Erratum: Wu, B.; et al. Metal–Organic Framework-Based Chemo-Photothermal Combinational System for Precise, Rapid, and Efficient Antibacterial Therapeutics. Pharmaceutics 2019, 11, 463
Authors: Wu Biyuan , Fu Jintao , Zhou Yixian , Shi Yin , Wang Jing , Feng Xiaoqian , Zhao Yiting , Zhou Guiling , Lu Chao , Quan Guilan , Pan Xin , Wu Chuanbin
Published: February 2020

The authors wish to make the following corrections to this paper [...]
Transporter-Mediated Delivery of Small Molecule Drugs to the Brain: A Critical Mechanism That Can Advance Therapeutic Development for Ischemic Stroke
Authors: Williams Erica I. , Betterton Robert D. , Davis Thomas P. , Ronaldson Patrick T.
Published: February 2020

Ischemic stroke is the 5th leading cause of death in the United States. Despite significant improvements in reperfusion therapies, stroke patients still suffer from debilitating neurocognitive deficits. This indicates an essential need to develop novel stroke treatment paradigms. Endogenous uptake transporters expressed at the blood-brain barrier (BBB) provide an excellent opportunity to advance stroke therapy via optimization of small molecule neuroprotective drug delivery to the brain. Examples of such uptake transporters include organic anion transporting polypeptides (OATPs in humans; Oatps in rodents) and organic cation transporters (OCTs in humans; Octs in rodents). Of particular note, small molecule drugs that have neuroprotective properties are known substrates for these transporters and include 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (i.e., statins) for OATPs/Oatps and 1-amino-3,5-dimethyladamantane (i.e., memantine) for OCTs/Octs. Here, we review current knowledge on specific BBB transporters that can be targeted for improvement of ischemic stroke treatment and provide state-of-the-art perspectives on the rationale for considering BBB transport properties during discovery/development of stroke therapeutics.
Long-Lasting Exendin-4 Fusion Protein Improves Memory Deficits in High-Fat Diet/Streptozotocin-Induced Diabetic Mice
Authors: Park Kyung-Ah , Jin Zhen , Lee Jong Youl , An Hyeong Seok , Choi Eun Bee , Kim Kyung Eun , Shin Hyun Joo , Jeong Eun Ae , Min Kyoung Ah , Shin Meong Cheol , Roh Gu Seob
Published: February 2020

Glucagon-like peptide 1 (GLP-1) mimetics have been approved as an adjunct therapy for glycemic control in type 2 diabetic patients for the increased insulin secretion under hyperglycemic conditions. Recently, it is reported that such agents elicit neuroprotective effects against diabetes-associated cognitive decline. However, there is an issue of poor compliance by multiple daily subcutaneous injections for sufficient glycemic control due to their short duration, and neuroprotective actions were not fully studied, yet. In this study, using the prepared exendin-4 fusion protein agent, we investigated the pharmacokinetic profile and the role of this GLP-1 mimetics on memory deficits in a high-fat diet (HFD)/streptozotocin (STZ) mouse model of type 2 diabetic mellitus. After induction of diabetes, mice were administered weekly by intraperitoneal injection of GLP-1 mimetics for 6 weeks. This treatment reversed HFD/STZ-induced metabolic symptoms of increased body weight, hyperglycemia, and hepatic steatosis. Furthermore, the impaired cognitive performance of diabetic mice was significantly reversed by GLP-1 mimetics. GLP-1 mimetic treatment also reversed decreases in GLP-1/GLP-1 receptor expression levels in both the pancreas and hippocampus of diabetic mice; increases in hippocampal inflammation, mitochondrial fission, and calcium-binding protein levels were also reversed. These findings suggest that GLP-1 mimetics are promising agents for both diabetes and neurodegenerative diseases that are associated with increased GLP-1 expression in the brain.
Long-Acting Paliperidone Parenteral Formulations Based on Polycaprolactone Nanoparticles; the Influence of Stabilizer and Chitosan on In Vitro Release, Protein Adsorption, and Cytotoxicity
Authors: Elmowafy Mohammed , Alruwaili Nabil K. , Shalaby Khaled , Alharbi Khalid S. , Altowayan Waleed M. , Ahmad Naveed , Zafar Ameeduzzafar , Elkomy Mohammed
Published: February 2020

Long-acting preparations containing the antipsychotic paliperidone for intramuscular injection has drawn considerable attention to achieve harmless long-term treatment. This study aimed to develop paliperidone loaded polycaprolactone (PCL) nanoparticles and investigate the influence of PCL/drug ratio, stabilizer type, and chitosan coating on physicochemical properties, protein adsorption, and cellular toxicity. Results showed that chitosan coating produced enlarged particle sizes, shifted the surface charges from negative into positive and did not influence encapsulation efficiencies. Chitosan coating relatively sustained the drug release especially in pluronic stabilized formulations. Pluronic F127 based formulations exhibited the least protein adsorption (384.3 μg/mL). Chitosan coating of Tween 80 and polyvinyl alcohol stabilized formulations significantly (p < 0.05) increased protein adsorption. Cellular viability was concentration-dependent and negatively affected by stabilizers. All formulations did not show cellular death at 1.56 μg/mL. Inflammatory responses and oxidative stress were less affected by Tween 80 compared with other stabilizers. Chitosan minimized all aspects of cellular toxicity. Collectively, stabilizer type and chitosan coating play critical roles in developing safe and effective long-acting PCL nanoparticles intended for parenteral drug delivery. The coated formulations containing Tween 80 and Pluronic F127 as stabilizers are warranted a future in vivo study to delineate its safety and efficacy profiles.
A 3D Bioprinted Pseudo-Bone Drug Delivery Scaffold for Bone Tissue Engineering
Authors: Kondiah Pariksha Jolene , Kondiah Pierre P. D. , Choonara Yahya E. , Marimuthu Thashree , Pillay Viness
Published: February 2020

A 3D bioprinted pseudo-bone drug delivery scaffold was fabricated to display matrix strength, matrix resilience, as well as porous morphology of healthy human bone. Computer-aided design (CAD) software was employed for developing the 3D bioprinted scaffold. Further optimization of the scaffold was undertaken using MATLAB® software and artificial neural networks (ANN). Polymers employed for formulating the 3D scaffold comprised of polypropylene fumarate (PPF), free radical polymerized polyethylene glycol- polycaprolactone (PEG-PCL-PEG), and pluronic (PF127). Simvastatin was incorporated into the 3D bioprinted scaffolds to further promote bone healing and repair properties. The 3D bioprinted scaffold was characterized for its chemical, morphological, mechanical, and in vitro release kinetics for evaluation of its behavior for application as an implantable scaffold at the site of bone fracture. The ANN-optimized 3D bioprinted scaffold displayed significant properties as a controlled release platform, demonstrating drug release over 20 days. The 3D bioprinted scaffold further displayed formation as a pseudo-bone matrix, using a human clavicle bone model, induced with a butterfly fracture. The strength of the pseudo-bone matrix, evaluated for its matrix hardness (MH) and matrix resilience (MR), was evaluated to be as strong as original bone, having a 99% MH and 98% MR property, to healthy human clavicle bones.
Controlled Release of Highly Hydrophilic Drugs from Novel Poly(Magnesium Acrylate) Matrix Tablets
Authors: Simancas-Herbada Rebeca , Fernández-Carballido Ana , Aparicio-Blanco Juan , Slowing Karla , Rubio-Retama Jorge , López-Cabarcos Enrique , Torres-Suárez Ana-Isabel
Published: February 2020

The potential of a new poly(magnesium acrylate) hydrogel (PAMgA) as a pharmaceutical excipient for the elaboration of matrix tablets for the extended release of highly hydrophilic drugs was evaluated. The polymer was synthetized with two different crosslinking degrees that were characterized by FTIR and DSC. Their acute oral toxicity was determined in a mouse model, showing no toxicity at doses up to 10 g/kg. Matrix tablets were prepared using metformin hydrochloride as a model drug and the mechanisms involved in drug release (swelling and/or erosion) were investigated using biorrelevant media. This new hydrogel effectively controlled the release of small and highly hydrophilic molecules as metformin, when formulated in matrix tablets for oral administration. The rate of metformin release from PAMgA matrices was mainly controlled by its diffusion through the gel layer (Fickian diffusion). The swelling capacity and the erosion of the matrix tablets influenced the metformin release rate, that was slower at pH 6.8, where polymer swelling is more intensive, than in gastric medium, where matrix erosion is slightly more rapid. The crosslinking degree of the polymer significantly influenced its swelling capacity in acid pH, where swelling is moderate, but not in intestinal fluid, where swelling is more intense.
RETRACTED: Drug Flux across RPE Cell Models: The Hunt for an Appropriate Outer Blood–Retinal Barrier Model for Use in Early Drug Discovery
Authors: Hellinen Laura , Hongisto Heidi , Ramsay Eva , Kaarniranta Kai , Vellonen Kati-Sisko , Skottman Heli , Ruponen Marika
Published: February 2020

The retinal pigment epithelial (RPE) cell monolayer forms the outer blood–retinal barrier and has a crucial role in ocular pharmacokinetics. Although several RPE cell models are available, there have been no systematic comparisons of their barrier properties with respect to drug permeability. We compared the barrier properties of several RPE secondary cell lines (ARPE19, ARPE19mel, and LEPI) and both primary (hfRPE) and stem-cell derived RPE (hESC-RPE) cells by investigating the permeability of nine drugs (aztreonam, ciprofloxacin, dexamethasone, fluconazole, ganciclovir, ketorolac, methotrexate, voriconazole, and quinidine) across cell monolayers. ARPE19, ARPE19mel, and hfRPE cells displayed a narrow Papp value range, with relatively high permeation rates (5.2–26 × 10−6 cm/s. In contrast, hESC-RPE and LEPI cells efficiently restricted the drug flux, and displayed even lower Papp values than those reported for bovine RPE-choroid, with the range of 0.4–32 cm−6/s (hESC-RPE cells) and 0.4–29 × 10−6 cm/s, (LEPI cells). Therefore, ARPE19, ARPE19mel, and hfRPE cells failed to form a tight barrier, whereas hESC-RPE and LEPI cells restricted the drug flux to a similar extent as bovine RPE-choroid. Therefore, LEPI and hESC-RPE cells are valuable tools in ocular drug discovery.
Halloysite- and Montmorillonite-Loaded Scaffolds as Enhancers of Chronic Wound Healing
Authors: Sandri Giuseppina , Faccendini Angela , Longo Marysol , Ruggeri Marco , Rossi Silvia , Bonferoni Maria Cristina , Miele Dalila , Prina-Mello Adriele , Aguzzi Carola , Viseras Cesar , Ferrari Franca
Published: February 2020

The increase in life expectancy and the increasing prevalence of diabetic disease and venous insufficiency lead to the increase of chronic wounds. The prevalence of ulcers ranges from 1% in the adult population to 3–5% in the over 65 years population, with 3–5.5% of the total healthcare expenditure, as recently estimated. The aim of this work was the design and the development of electrospun scaffolds, entirely based on biopolymers, loaded with montmorillonite (MMT) or halloysite (HNT) and intended for skin reparation and regeneration, as a 3D substrate mimicking the dermal ECM. The scaffolds were manufactured by means of electrospinning and were characterized for their chemico-physical and preclinical properties. The scaffolds proved to possess the capability to enhance fibroblast cells attachment and proliferation with negligible proinflammatory activity. The capability to facilitate the cell adhesion is probably due to their unique 3D structure which are assisting cell homing and would facilitate wound healing in vivo.
Development of Amphotericin B Micellar Formulations Based on Copolymers of Poly(ethylene glycol) and Poly(ε-caprolactone) Conjugated with Retinol
Authors: Rodriguez Yeimy J. , Quejada Luis F. , Villamil Jean C. , Baena Yolima , Parra-Giraldo Claudia M. , Perez Leon D.
Published: February 2020

Amphotericin B (AmB) is a broad spectrum of antifungal drug used to treat antifungal diseases. However, due to the high toxicity of AmB, treated patients may suffer the risk of side effects, such as renal failure. Nanoencapsulation strategies have been reported to elicit low toxicity, albeit most of them possess low encapsulation efficiency. The aim of this research is to develop micellar delivery systems for AmB with reduced toxicity while maintaining its affectivity by employing retinol (RET)-conjugated amphiphilic block copolymers (ABCs) as precursors. Copolymers composed of poly(ε-caprolactone) (A) and polyethylenglycol (B) of types AB and ABA were synthesized by ring opening polymerization and subsequently conjugated with RET by Steglich esterification. 1H-NMR spectroscopy was used to corroborate the structure of copolymers and their conjugates and determine their molecular weights. Analysis by gel permeation chromatography also found that the materials have narrow distributions. The resulting copolymers were used as precursors for delivery systems of AmB, thus reducing its aggregation and consequently causing a low haemolytic effect. Upon conjugation with RET, the encapsulation capacity was enhanced from approximately 2 wt % for AB and ABA copolymers to 10 wt %. AmB encapsulated in polymer micelles presented improved antifungal efficiency against Candida albicans and Candida auris strains compared with Fungizone®, as deduced from the low minimum inhibitory concentration.
Silver Can Induce Oxidative Stress in Parallel to Other Chemical Elicitors to Modulate the Ripening of Chili Cultivars
Authors: Ghosh Arijit , Saha Indraneel , Dolui Debabrata , De Arnab Kumar , Sarkar Bipul , Adak Malay Kumar
Published: February 2020

Two chili cultivars, i.e., cv. Bullet and cv. Tejaswini, were evaluated on postharvest related ripening characteristics with varying durations under hydrogen peroxide, putrescine and silver treatments. The reducing sugar was inversely related to the maximum values at 7 days of ripening. Silver and putrescine were the most regulatory in terms of changing of the total carbohydrate content as compared to hydrolysis of the total reducing sugar. Regarding pectin methylesterase activity, both chilies were consistent, regardless of the number of days of incubation. Still, putrescine and silver were significant contributors to variations in cv. Bullet and cv. Tejaswani. For the pigment content, lycopene and chlorophyll increased in a linear manner, although these treatments significantly varied over time. Hydrogen peroxide and putrescine were responsible for the maximum accumulation of lycopene for both the cultivars, whereas, only cv. Tejaswani displayed maximum carotenoid for putrescine. Silver for both chili varieties was the most inhibitory for lycopene and carotenoid content. Superoxide had a good impact on the accumulation of lipid peroxides, irrespective of the chili variety. The maximum accumulation of lipid peroxide was recorded at seven days of treatment. Phenolics and flavonoids were in decreasing order for both the chili varieties, progressing through the days of the study period in a similar manner. Silver was the main contributor to variations in the phenolics and flavonoid contents in cv. Tejaswani. The solubilization of total carbohydrate into reducing sugar was in an inverse relationship, with the maximum values being reached at 7 days of ripening.
Synthesis and Properties of Water-Based Acrylic Adhesives with a Variable Ratio of 2-Ethylhexyl Acrylate and n-Butyl Acrylate for Application in Glass Bottle Labels
Authors: Márquez Irene , Alarcia Felipe , Velasco José Ignacio
Published: February 2020

A series of Pressure-Sensitive Adhesives (PSAs) with different soft monomer compositions were prepared by using emulsion polymerization. The monomers used were acrylic acid (AA), n-butyl acrylate (n-BA) and 2-ethylhexyl acrylate (2-EHA). Maintaining the same acrylic acid fraction in all polymerizations, the n-BA/2-EHA weight ratio varied from 0 to 1. These polymers were characterized by using Fourier Transformed Infrared Spectroscopy (FTIR), and the Glass Transition Temperature (Tg) was determined both theoretically from the Fox equation and experimentally by means of differential scanning calorimetry (DSC). The tetrahydrofuran (THF) insoluble polymer fraction was used to calculate the gel content, and the soluble part was used to determine the average molecular weight by means of Gas Permeation Chromatography (GPC). The adhesive performance was assessed by measuring tack, peel and shear resistance. The results showed that with the 2-EHA rate, the elastic modulus slightly decreased and the shear yield strength slightly increased. Consequently, the loop tack and peel resistances decreased. This behavior was attributed to the increase of the gel content with the ratio of comonomers studied. The adhesives were tested in paper labels on glass bottles immersed in a cold-water bath, the so-called ice bucket test, and all of them showed that they could withstand wet and cold environment conditions.
Fabrication of Colorimetric Textile Sensor Based on Rhodamine Dye for Acidic Gas Detection
Authors: Park Young Ki , Oh Byeong M. , Jo A Ra , Han Ji Hyeon , Lim Jee Young , Oh Hyun Ju , Lim Seung Ju , Kim Jong H. , Lee Woo Sung
Published: February 2020

For the immediate detection of gaseous strong acids, it is advantageous to employ colorimetric textile sensors based on halochromic dyes. Thus, a rhodamine dye with superior pH sensitivity and high thermal stability was synthesized and incorporated in nylon 6 and polyester fabrics to fabricate textile sensors through dyeing and printing methods. The spectral properties and solubility of the dye were examined; sensitivity to acidic gas as well as durability and reversibility of the fabricated textile sensors were investigated. Both dyed and printed sensors exhibited a high reaction rate and distinctive color change under the acidic condition owing to the high pH sensitivity of the dye. In addition, both sensors have outstanding durability and reversibility after washing and drying.