bluuebunny/crossref_metadata_2025 huggingface dataset:
Building Accurate Intracellular Polarity Maps through Multiparametric Microscopy
Authors: Gonzalez-Garcia M. Carmen , Herrero-Foncubierta Pilar , Garcia-Fernandez Emilio , Orte Angel
Published: November 2020

The precise knowledge of intracellular polarity, a physiological parameter that involves complex and intertwined intracellular mechanisms, may be relevant in the study of important diseases like cancer or Alzheimer’s. In this technical note, we illustrate our recently developed, accurate method for obtaining intracellular polarity maps employing potent fluorescence microscopy techniques. Our method is based on the selection of appropriate luminescent probes, in which several emission properties vary with microenvironment polarity, specifically spectral shifts and luminescence lifetime. A multilinear calibration is performed, correlating polarity vs. spectral shift vs. luminescence lifetime, to generate a powerful and error-free 3D space for reliable interpolation of microscopy data. Multidimensional luminescence microscopy is then used to obtain simultaneously spectral shift and luminescence lifetime images, which are then interpolated in the 3D calibration space, resulting in accurate, quantitative polarity maps.
Silver-Polystyrene (Ag/PS) Nanocomposites Doped with Polyvinyl Alcohol (PVA)—Fabrication and Bactericidal Activity
Authors: Krzywicka Anna , Megiel Elżbieta
Published: November 2020

In the present work, we report the studies on perfectly homogeneous nanocomposites composed of polystyrene-grafted silver nanoparticles (Ag@PS) as a bioactive fulfilment and a mixture of polystyrene (PS) and polyvinyl alcohol (PVA) as a matrix. The procedure developed by our group of the nanocomposites’ preparation consists of three steps: synthesis of narrow-dispersive AgNPs (5.96 ± 1.02 nm); grafting of narrowly dispersed polystyrene onto the surface of AgNPs; thermoforming with a mixture of PS/PVA. Kirby-Bauer (K-B) and Dynamic Shake Flask (DSF) assays revealed high antibacterial activity against a series of Gram(−) and Gram(+) bacteria strains of the fabricated nanocomposites at low silver content (0.5%). We showed that the doping of Ag/PS composites with PVA increases the antibacterial activity of composites. The hydrophilic component in the nanocomposites enables easier water migration inside the polymer matrix, which makes releasing silver nanoparticles and silver ions to the environment facile.
Dietary Supplements: Are Current Policies Adequate for Promoting Health?
Authors: Shi Zumin , Yan Alice
Published: November 2020

Globally, there has been a dramatic increase in the use of dietary supplements over recent decades [...]
Metabolomic and Metataxonomic Fingerprinting of Human Milk Suggests Compositional Stability over a Natural Term of Breastfeeding to 24 Months
Authors: Shenker Natalie S. , Perdones-Montero Alvaro , Burke Adam , Stickland Sarah , McDonald Julie A.K. , Alexander-Hardiman Kate , Flanagan James , Takats Zoltan , Cameron Simon J.S.
Published: November 2020

Sparse data exist regarding the normal range of composition of maternal milk beyond the first postnatal weeks. This single timepoint, observational study in collaboration with the ‘Parenting Science Gang’ citizen science group evaluated the metabolite and bacterial composition of human milk from 62 participants (infants aged 3–48 months), nearly 3 years longer than previous studies. We utilised rapid evaporative ionisation mass spectrometry (REIMS) for metabolic fingerprinting and 16S rRNA gene metataxonomics for microbiome composition analysis. Milk expression volumes were significantly lower beyond 24 months of lactation, but there were no corresponding changes in bacterial load, composition, or whole-scale metabolomic fingerprint. Some individual metabolite features (~14%) showed altered abundances in nursling age groups above 24 months. Neither milk expression method nor nursling sex affected metabolite and metataxonomic fingerprints. Self-reported lifestyle factors, including diet and physical traits, had minimal impact on metabolite and metataxonomic fingerprints. Our findings suggest remarkable consistency in human milk composition over natural-term lactation. The results add to previous studies suggesting that milk donation can continue up to 24 months postnatally. Future longitudinal studies will confirm the inter-individual and temporal nature of compositional variations and the use of donor milk as a personalised therapeutic.
Maternal Linoleic Acid Overconsumption Alters Offspring Gut and Adipose Tissue Homeostasis in Young but Not Older Adult Rats
Authors: Marchix Justine , Alain Charlène , David-Le Gall Sandrine , Acuña-Amador Luis Alberto , Druart Céline , Delzenne Nathalie M. , Barloy-Hubler Frédérique , Legrand Philippe , Boudry Gaëlle
Published: November 2020

Maternal n-6 polyunsaturated fatty acids (PUFA) consumption during gestation and lactation can predispose offspring to the development of metabolic diseases such as obesity later in life. However, the mechanisms underlying the potential programming effect of n-6 PUFA upon offspring physiology are not yet all established. Herein, we investigated the effects of maternal and weaning linoleic acid (LA)-rich diet interactions on gut intestinal and adipose tissue physiology in young (3-month-old) and older (6-month-old) adult offspring. Pregnant rats were fed a control diet (2% LA) or an LA-rich diet (12% LA) during gestation and lactation. At weaning, offspring were either maintained on the maternal diet or fed the other diet for 3 or 6 months. At 3 months of age, the maternal LA-diet favored low-grade inflammation and greater adiposity, while at 6 months of age, offspring intestinal barrier function, adipose tissue physiology and hepatic conjugated linoleic acids were strongly influenced by the weaning diet. The maternal LA-diet impacted offspring cecal microbiota diversity and composition at 3 months of age, but had only few remnant effects upon cecal microbiota composition at 6 months of age. Our study suggests that perinatal exposure to high LA levels induces a differential metabolic response to weaning diet exposure in adult life. This programming effect of a maternal LA-diet may be related to the alteration of offspring gut microbiota.
Effect of Zinc Supplementation on the Serum Metabolites Profile at the Early Stage of Breast Cancer in Rats
Authors: Bobrowska-Korczak Barbara , Gątarek Paulina , Skrajnowska Dorota , Bielecki Wojciech , Wyrebiak Rafal , Kovalczuk Tomas , Wrzesień Robert , Kałużna-Czaplińska Joanna
Published: November 2020

The cytotoxic properties of zinc nanoparticles have been evaluated in vitro against several types of cancer. However, there is a lack of significant evidence of their activity in vivo, and a potential therapeutic application remains limited. Herein we report the effective inhibition of tumor growth by zinc nanoparticles in vivo, as the effect of the dietary intervention, after the chemical induction in a rodent model of breast cancer. Biopsy images indicated grade 1 tumors with multiple inflammatory infiltrates in the group treated with zinc nanoparticles, whereas, in the other groups, a moderately differentiated grade 2 adenocarcinoma was identified. Moreover, after the supplementation with zinc nanoparticles, the levels of several metabolites associated with cancer metabolism, important to its survival, were found to have been altered. We also revealed that the biological activity of zinc in vivo depends on the size of applied particles, as the treatment with zinc microparticles has not had much effect on cancer progression.
Do Diet and Lifestyles Play a Role in the Pathogenesis of NMSCs?
Authors: Skroza Nevena , Proietti Ilaria , Marchesiello Anna , Volpe Salvatore , Balduzzi Veronica , Bernardini Nicoletta , Maddalena Patrizia , Mambrin Alessandra , Michelini Simone , Tolino Ersilia , La Torre Giuseppe , Potenza Concetta
Published: November 2020

Background and Aims: Literature highlights the role of risk factors like age, body mass index (BMI), tobacco smoking, alcohol intake and diet in the pathogenesis of several cancer types but little is known for non-melanoma skin cancers (NMSC). The aim of this epidemiological study was to evaluate the correlation between modifiable risk factors (BMI, metabolic panel, diet, lifestyle, medical history) and not modifiable risk factors (gender, age) and NMSC development. Methods: From February 2018 to September 2019, 162 patients affected by NMSC were compared to a group of 167 controls. A univariate and multivariate analysis was conducted to elaborate the data collected through face-to-face interviews. Results: While our evidence did not always reach statistical significance, NMSC study group patients exhibited high rates of analyzed risk factors (male gender aging over 55 years, high BMI, reduced physical activity) compared to the control group. Conclusions: Our study indicates that practicing more than 30 min of physical activity daily could be a protective factor against the NMSC onset. Other risk factors were not correlated with NMSC, but more evidence is needed to establish a possible link.
Effect of High-Oleic Peanut Intake on Aging and Its Hippocampal Markers in Senescence-Accelerated Mice (SAMP8)
Authors: Igarashi Kiharu , Kurata Daisuke
Published: November 2020

In many previous studies, the preventive effects of peanut against aging and cognitive impairment have often been unclear, so to clarify the effects we first investigated effective markers for evaluating its effects in the hippocampus of senescence-accelerated mouse prone/8 (SAMP8) mice, mainly using proteomics. The effects of dietary high-oleic peanuts on the hair appearance of SAMP8, the expression of effective markers in the hippocampus, and the TBARS and amino acid contents of the hippocampus were examined. Hippocampus solute carrier family 1 (glial high-affinity glutamate transporter), calcium/calmodulin-dependent protein kinase type II, and sodium- and chloride-dependent GABA transporter, which all are considered to be closely related to glutamic acid concentration were decreased by feeding of the samples, and the GABA/glutamic acid ratio in the hippocampus was increased by feeding with the samples. The formation of glial fibrillary acidic protein and synapsin-2, which showed higher levels in the SAMP8 than in SAMR1, and the protein expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein and dihydropteridine reductase, which are considered to be related to the formation of adrenergic neuron transmitters, were reduced by the feeding of peanuts and their germ-rich fraction. Ferulic acid, as an ester and minor component in peanuts, could be partly connected to the effect of peanuts. These results indicate that high-oleic peanuts and their germ-rich fraction can protect against aging and cognitive impairment by regulating protein expression, which could be measured by the proteomics of the above hippocampus proteins of SAMP8 and the hippocampal GABA/glutamic acid ratio.
Cross-Talk between Diet-Associated Dysbiosis and Hand Osteoarthritis
Authors: Silvestre Marta P. , Rodrigues Ana M. , Canhão Helena , Marques Cláudia , Teixeira Diana , Calhau Conceição , Branco Jaime
Published: November 2020

Hand osteoarthritis (OA) is a degenerative joint disease which leads to pain and disability. Recent studies focus on the role of obesity and metabolic syndrome in inducing or worsening joint damage in hand OA patients, suggesting that chronic low-grade systemic inflammation may represent a possible linking factor. The gut microbiome has a crucial metabolic role which is fundamental for immune system development, among other important functions. Intestinal microbiota dysbiosis may favour metabolic syndrome and low-grade inflammation—two important components of hand OA onset and evolution. The aim of this narrative is to review the recent literature concerning the possible contribution of dysbiosis to hand OA onset and progression, and to discuss the importance of gut dysbiosis on general health and disease.
Associations between Pro- and Anti-Inflammatory Gastro-Intestinal Microbiota, Diet, and Cognitive Functioning in Dutch Healthy Older Adults: The NU-AGE Study
Authors: van Soest Annick P. M. , Hermes Gerben D. A. , Berendsen Agnes A. M. , van de Rest Ondine , Zoetendal Erwin G. , Fuentes Susana , Santoro Aurelia , Franceschi Claudio , de Groot Lisette C. P. G. M. , de Vos Willem M.
Published: November 2020

Dietary modulation of the gastro-intestinal microbiota is a potential target in improving healthy ageing and age-related functional outcomes, including cognitive decline. We explored the association between diet, gastro-intestinal microbiota and cognition in Dutch healthy older adults of the ‘New dietary strategies addressing the specific needs of the elderly population for healthy aging in Europe’ (NU-AGE) study. The microbiota profile of 452 fecal samples from 226 subjects was determined using a 16S ribosomal RNA gene-targeted microarray. Dietary intake was assessed by 7-day food records. Cognitive functioning was measured with an extensive cognitive test battery. We observed a dietary and microbial pro- to anti-inflammatory gradient associated with diets richer in animal- or plant-based foods. Fresh fruits, nuts, seeds and peanuts, red and processed meat and grain products were most strongly associated to microbiota composition. Plant-rich diets containing fresh fruits, nuts, seeds and peanuts were positively correlated with alpha-diversity, various taxa from the Bacteroidetes phylum and anti-inflammatory species, including those related to Faecalibacterium prausnitzii and Eubacterium rectale and E. biforme. Animal product-rich diets associated with pro-inflammatory species, including those related to Ruminococcus gnavus and Collinsella spp.. Cognition was neither associated with microbiota composition nor alpha-diversity. In conclusion, diets richer in animal- and plant-based foods were related to a pro- and anti-inflammatory microbial profile, while cognition was associated with neither.
What Should I Eat before Exercise? Pre-Exercise Nutrition and the Response to Endurance Exercise: Current Prospective and Future Directions
Authors: Rothschild Jeffrey A. , Kilding Andrew E. , Plews Daniel J.
Published: November 2020

The primary variables influencing the adaptive response to a bout of endurance training are exercise duration and exercise intensity. However, altering the availability of nutrients before and during exercise can also impact the training response by modulating the exercise stimulus and/or the physiological and molecular responses to the exercise-induced perturbations. The purpose of this review is to highlight the current knowledge of the influence of pre-exercise nutrition ingestion on the metabolic, physiological, and performance responses to endurance training and suggest directions for future research. Acutely, carbohydrate ingestion reduces fat oxidation, but there is little evidence showing enhanced fat burning capacity following long-term fasted-state training. Performance is improved following pre-exercise carbohydrate ingestion for longer but not shorter duration exercise, while training-induced performance improvements following nutrition strategies that modulate carbohydrate availability vary based on the type of nutrition protocol used. Contrasting findings related to the influence of acute carbohydrate ingestion on mitochondrial signaling may be related to the amount of carbohydrate consumed and the intensity of exercise. This review can help to guide athletes, coaches, and nutritionists in personalizing pre-exercise nutrition strategies, and for designing research studies to further elucidate the role of nutrition in endurance training adaptations.
Molecular Changes in Dengue Envelope Protein Domain III upon Interaction with Glycosaminoglycans
Authors: Hyatt James G. , Prévost Sylvain , Devos Juliette M. , Mycroft-West Courtney J. , Skidmore Mark A. , Winter Anja
Published: November 2020

Dengue fever is a rapidly emerging vector-borne viral disease with a growing global burden of approximately 390 million new infections per annum. The Dengue virus (DENV) is a flavivirus spread by female mosquitos of the aedes genus, but the mechanism of viral endocytosis is poorly understood at a molecular level, preventing the development of effective transmission blocking vaccines (TBVs). Recently, glycosaminoglycans (GAGs) have been identified as playing a role during initial viral attachment through interaction with the third domain of the viral envelope protein (EDIII). Here, we report a systematic study investigating the effect of a range of biologically relevant GAGs on the structure and oligomeric state of recombinantly generated EDIII. We provide novel in situ biophysical evidence that heparin and chondroitin sulphate C induce conformational changes in EDIII at the secondary structure level. Furthermore, we report the ability of chondroitin sulphate C to bind EDIII and induce higher-order dynamic molecular changes at the tertiary and quaternary structure levels which are dependent on pH, GAG species, and the GAG sulphation state. Lastly, we conducted ab initio modelling of Small Angle Neutron Scattering (SANS) data to visualise the induced oligomeric state of EDIII caused by interaction with chondroitin sulphate C, which may aid in TBV development.
Adhesins of Brucella: Their Roles in the Interaction with the Host
Authors: Bialer Magalí G. , Sycz Gabriela , Muñoz González Florencia , Ferrero Mariana C. , Baldi Pablo C. , Zorreguieta Angeles
Published: November 2020

A central aspect of Brucella pathogenicity is its ability to invade, survive, and replicate in diverse phagocytic and non-phagocytic cell types, leading to chronic infections and chronic inflammatory phenomena. Adhesion to the target cell is a critical first step in the invasion process. Several Brucella adhesins have been shown to mediate adhesion to cells, extracellular matrix components (ECM), or both. These include the sialic acid-binding proteins SP29 and SP41 (binding to erythrocytes and epithelial cells, respectively), the BigA and BigB proteins that contain an Ig-like domain (binding to cell adhesion molecules in epithelial cells), the monomeric autotransporters BmaA, BmaB, and BmaC (binding to ECM components, epithelial cells, osteoblasts, synoviocytes, and trophoblasts), the trimeric autotransporters BtaE and BtaF (binding to ECM components and epithelial cells) and Bp26 (binding to ECM components). An in vivo role has also been shown for the trimeric autotransporters, as deletion mutants display decreased colonization after oral and/or respiratory infection in mice, and it has also been suggested for BigA and BigB. Several adhesins have shown unipolar localization, suggesting that Brucella would express an adhesive pole. Adhesin-based vaccines may be useful to prevent brucellosis, as intranasal immunization in mice with BtaF conferred high levels of protection against oral challenge with B. suis.
Enhancing Stability and Tooth Bleaching Activity of Carbamide Peroxide by Electrospun Nanofibrous Film
Authors: Okonogi Siriporn , Kaewpinta Adchareeya , Rades Thomas , Müllertz Anette , Yang Mingshi , Khongkhunthian Sakornrat , Chaijareenont Pisaisit
Published: November 2020

Carbamide peroxide (CP) possesses a strong tooth bleaching activity, however, its clinical application is limited because of its instability in aqueous formulations. This study explores the improvement of CP stability and bleaching activity by loading CP in electrospun nanofibrous film (ENF). Polyvinylalcohol, polyvinylpyrrolidone, and silica were used as components for core-based nanofibers of ENF. Electrospinning feed aqueous solutions (EFASs) were developed for preparing CP loaded ENF (CP-ENF). Stability of CP in EFASs is significantly higher than in pure water. The highest stability of CP is found in PPS-CP3, composed of 0.5% CP, 5.5% polyvinylalcohol, 3% polyvinylpyrrolidone, and 1% silica. The results from X-ray diffraction indicate that CP is dispersed as a non-crystalline form in CP-ENFs. CP and the compositions of EFASs play a major role on characteristics and bleaching efficiency of CP-ENFs. Drug release of CP-ENFs is the first order kinetics. CP-ENF obtained from PPS-CP3 shows the highest drug entrapment efficiency, high adhesion, and suitable sustained release. Drug release mechanism is along with anomalous transport according to Korsmeyer–Peppas model. In an ex vivo study using human teeth, it shows the highest bleaching efficiency among the others. Therefore, CP-ENF obtained from PPS-CP3 is a promising ENF for clinical use.
Atorvastatin Increases the Expression of Long Non-Coding RNAs ARSR and CHROME in Hypercholesterolemic Patients: A Pilot Study
Authors: Paez Isis , Prado Yalena , Ubilla Carmen G. , Zambrano Tomás , Salazar Luis A.
Published: November 2020

Atorvastatin is extensively used to treat hypercholesterolemia. However, the wide interindividual variability observed in response to this drug still needs further elucidation. Nowadays, the biology of long non-coding RNAs (lncRNAs) is better understood, and some of these molecules have been related to cholesterol metabolism. Therefore, they could provide additional information on variability in response to statins. The objective of this research was to evaluate the effect of atorvastatin on three lncRNAs (lncRNA ARSR: Activated in renal cell carcinoma (RCC) with sunitinib resistance, ENST00000424980; lncRNA LASER: lipid associated single nucleotide polymorphism locus, ENSG00000237937; and lncRNA CHROME: cholesterol homeostasis regulator of miRNA expression, ENSG00000223960) associated with genes involved in cholesterol metabolism as predictors of lipid-lowering therapy performance. Twenty hypercholesterolemic patients were treated for four weeks with atorvastatin (20 mg/day). The lipid profile was determined before and after drug administration using conventional assays. The expression of lncRNAs was assessed in peripheral blood samples by RT-qPCR. As expected, atorvastatin improved the lipid profile, decreasing total cholesterol, LDL-C, and the TC/HDL-C ratio (p < 0.0001) while increasing the expression of lncRNAs ARSR and CHROME (p < 0.0001) upon completion of treatment. LASER did not show significant differences among the groups (p = 0.50). Our results indicate that atorvastatin modulates the expression of cholesterol-related lncRNAs differentially, suggesting that these molecules play a role in the variability of response to this drug; however, additional studies are needed to disclose the implication of this differential regulation on statin response.
Encapsulation of Activated Carbon into a Hollow-Type Spherical Bacterial Cellulose Gel and Its Indole-Adsorption Ability Aimed at Kidney Failure Treatment
Authors: Hoshi Toru , Endo Masahito , Hirai Aya , Suzuki Masashige , Aoyagi Takao
Published: November 2020

For reducing side effects and improvement of swallowing, we studied the encapsulation of activated carbon formulations with a hollow-type spherical bacterial cellulose (HSBC) gel using two kinds of encapsulating methods: Methods A and B. In Method A, the BC gelatinous membrane was biosynthesized using Komagataeibacter xylinus (K. xylinus) at the interface between the silicone oil and cell suspension containing activated carbon. In Method B, the bacterial cellulose (BC) gelatinous membrane was formed at the interface between the cell suspension attached to the alginate gel containing activated carbon and the silicone oil. After the BC gelatinous membrane was biosynthesized by K. xylnus, alginate gel was removed by soaking in a phosphate buffer. The activated carbon encapsulated these methods could neither pass through the BC gelatinous membrane of the HSBC gel nor leak from the interior cavity of the HSBC gel. The adsorption ability was evaluated using indole, which is a precursor of the uremic causative agent. From curve-fitting, the adsorption process followed the pseudo-first-order and intra-particle diffusion models, and the diffusion of the indole molecules at the surface of the encapsulated activated carbon within the HSBC gel was dominant at the initial stage of adsorption. It was observed that the adsorption of the encapsulated activated carbon by the intraparticle diffusion process became dominant with longer adsorption times.
3D Printed Calcium Phosphate Cement (CPC) Scaffolds for Anti-Cancer Drug Delivery
Authors: Wu Yan , Woodbine Lisa , Carr Antony M. , Pillai Amit R. , Nokhodchi Ali , Maniruzzaman Mohammed
Published: November 2020

One of the main applications of bone graft materials is filling the gap after the surgical removal of bone cancer or tumors. Insufficient healing commonly leads to non-union fracture which could lead to cancer resurgence or infection. Emerging 3D printing of on-demand bone graft biomaterials can deliver personalized solutions with minimized risk of relapse and recurrence of cancer after bone removal surgery. This research aims to explore 3D printed calcium phosphate cement (CPC) based scaffolds as novel anti-cancer drug delivery systems to treat bone cancer. For the study, various 3D printed CPC based scaffolds (diameter 5 mm) with interconnected pores were utilized. Various optimized polymeric solutions containing a model anticancer drug 5-fluorouracil (5-FU) was used to homogenously coat the CPC scaffolds. Both hydrophilic Soluplus (SOL) and polyethylene glycol (PEG) and a combination of both were used to develop stable coating solutions. The surface morphology of the coated scaffolds, observed via SEM, revealed deposition of the polymeric solution represented by a semi-smooth surface as opposed to the blank scaffolds that showed a smoother surface. An advanced surface analysis conducted via confocal microscopy showed a homogenous distribution of the drug throughout the coated scaffolds. Solid-state analysis studied by applying differential scanning calorimetry (DSC) and X-ray diffraction (XRD) revealed semi-crystalline nature of the drug whereas mechanical analysis conducted via texture analysis showed no evidence in the change of the mechanical properties of the scaffolds after polymeric solutions were applied. The FTIR analysis revealed no major intermolecular interactions between 5-FU and the polymers used for coatings except for F2 where a potential nominal interaction was evidenced corresponding to higher Soluplus content in the formulation. In vitro dissolution studies showed that almost 100% of the drug released within 2 h for all scaffolds. Moreover, in vitro cell culture using two different cell lines (Hek293T-human kidney immortalized cell line and HeLa-human bone osteosarcoma epithelial cell line) showed significant inhibition of cell growth as a function of decreased numbers of cells after 5 days. It can be claimed that the developed 5-FU coated 3D printed scaffolds can successfully be used as bone graft materials to potentially treat bone cancer or bone neoplasm and for personalized medical solutions in the form of scaffolds for regenerative medicine or tissue engineering applications.
Dual-Targeted Extracellular Vesicles to Facilitate Combined Therapies for Neuroendocrine Cancer Treatment
Authors: Si Yingnan , Guan JiaShiung , Xu Yuanxin , Chen Kai , Kim Seulhee , Zhou Lufang , Jaskula-Sztul Renata , Liu X. Margaret
Published: November 2020

Neuroendocrine (NE) cancers arise from cells within the neuroendocrine system. Chemotherapies and endoradiotherapy have been developed, but their clinical efficacy is limited. The objective of this study was to develop a dual-targeted extracellular vesicles (EV)-delivered combined therapies to treat NE cancer. Specifically, we produced EV in stirred-tank bioreactors and surface tagged both anti-somatostatin receptor 2 (SSTR 2) monoclonal antibody (mAb) and anti-C-X-C motif chemokine receptor 4 (CXCR4) mAb to generate mAbs-EV. Both live-cell confocal microscopy imaging and In Vivo Imaging System (IVIS) imaging confirmed that mAbs-EV specifically targeted and accumulated in NE cancer cells and NE tumor xenografts. Then the highly potent natural cytotoxic marine compound verrucarin A (Ver-A) with IC50 of 2.2–2.8 nM and microtubule polymerization inhibitor mertansine (DM1) with IC50 of 3.1–4.2 nM were packed into mAbs-EV. The in vivo maximum tolerated dose study performed in non-tumor-bearing mice indicated minimal systemic toxicity of mAbs-EV-Ver-A/DM1. Finally, the in vivo anticancer efficacy study demonstrated that the SSTR2/CXCR4 dual-targeted EV-Ver-A/DM1 is more effective to inhibit NE tumor growth than the single targeting and single drug. The results from this study could expand the application of EV to targeting deliver the combined potent chemotherapies for cancer treatment.
Bi-Functional Alginate Oligosaccharide–Polymyxin Conjugates for Improved Treatment of Multidrug-Resistant Gram-Negative Bacterial Infections
Authors: Stokniene Joana , Powell Lydia C. , Aarstad Olav A. , Aachmann Finn L. , Rye Philip D. , Hill Katja E. , Thomas David W. , Ferguson Elaine L.
Published: November 2020

The recent emergence of resistance to colistin, an antibiotic of last resort with dose-limiting toxicity, has highlighted the need for alternative approaches to combat infection. This study aimed to generate and characterise alginate oligosaccharide (“OligoG”)–polymyxin (polymyxin B and E (colistin)) conjugates to improve the effectiveness of these antibiotics. OligoG–polymyxin conjugates (amide- or ester-linked), with molecular weights of 5200–12,800 g/mol and antibiotic loading of 6.1–12.9% w/w, were reproducibly synthesised. In vitro inflammatory cytokine production (tumour necrosis factor alpha (TNFα) ELISA) and cytotoxicity (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) of colistin (2.2–9.3-fold) and polymyxin B (2.9–27.2-fold) were significantly decreased by OligoG conjugation. Antimicrobial susceptibility tests (minimum inhibitory concentration (MIC), growth curves) demonstrated similar antimicrobial efficacy of ester- and amide-linked conjugates to that of the parent antibiotic but with more sustained inhibition of bacterial growth. OligoG–polymyxin conjugates exhibited improved selectivity for Gram-negative bacteria in comparison to mammalian cells (approximately 2–4-fold). Both OligoG–colistin conjugates caused significant disruption of Pseudomonas aeruginosa biofilm formation and induced bacterial death (confocal laser scanning microscopy). When conjugates were tested in an in vitro “time-to-kill” (TTK) model using Acinetobacter baumannii, only ester-linked conjugates reduced viable bacterial counts (~2-fold) after 4 h. Bi-functional OligoG–polymyxin conjugates have potential therapeutic benefits in the treatment of multidrug-resistant (MDR) Gram-negative bacterial infections, directly reducing toxicity whilst retaining antimicrobial and antibiofilm activities.
An Observational Cohort Study Evaluating Antimicrobial Use in Peripartum Sepsis: A Tendency towards Overdiagnosis?
Authors: Abutheraa Nouf , Grant June , Mullen Alexander B.
Published: November 2020

(1) Background: Sepsis is the leading cause of maternal death in 11–15% of women worldwide. This emphasises the importance of administrating timely and appropriate antibiotic therapy to women with sepsis. We aimed to evaluate the appropriateness of antimicrobial prescribing in women diagnosed with peripartum sepsis. (2) Method: A prospective observational cohort study in a single Scottish health region with 12,233 annual live births. Data were collected on women diagnosed with sepsis in the peripartum period using physical and electronic medical records, drug Kardex® (medication administration) and ward handover records. (3) Results: A sepsis diagnosis was concluded in 89 of the 2690 pregnancy cases reviewed, with a median hospital stay of four days. Good overall adherence to the local guidelines for the empiric antimicrobial treatment of sepsis was observed. Group B Streptococcus was associated with 20.8% of maternal sepsis cases, whilst in 60% of clinical specimens tested no causative pathogen was isolated. (4) Conclusion: The lack of specific and sensitive clinical markers for sepsis, coupled with their inconsistent clinical application to inform diagnosis, hindered effective antimicrobial stewardship. This was further exacerbated by the lack of positive culture isolates from clinical specimens, which meant that patients were often continued on broader-spectrum empiric treatment.
Antibacterial Activity of Arbutus pavarii Pamp against Methicillin-Resistant Staphylococcus aureus (MRSA) and UHPLC-MS/MS Profile of the Bioactive Fraction
Authors: Buzgaia Nawal , Awin Tahani , Elabbar Fakhri , Abdusalam Khaled , Lee Soo Yee , Rukayadi Yaya , Abas Faridah , Shaari Khozirah
Published: November 2020

Arbutus pavarii Pamp is a medicinal plant commonly used by local tribes in East Libya for the treatment of many diseases, such as gastritis, renal infections, cancer and kidney diseases. In this study, the antibacterial activity of the leaf and stem bark extracts of the plant against methicillin-resistant Staphylococcus aureus (MRSA), as well as the metabolite profiles of the bioactive fractions, was investigated. The antibacterial activity was determined by disc diffusion method, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), while the microbial reduction by the bioactive fraction was evaluated using time–kill test. The bioactive fraction was further subjected to ultrahigh-performance liquid chromatography–mass spectrometry (UHPLC-ESI-MS/MS) analysis to putatively identify the chemical constituents contained therein. All the extracts and fractions showed different levels of antibacterial activity on the tested MRSA strains. The highest total antibacterial activity, i.e., 4007.6 mL/g, was exhibited by the crude leaf methanolic extract. However, the ethyl acetate fraction of the leaf showed moderate to significant antibacterial activity against MRSA at low MIC (0.08–1.25 mg/mL). Metabolite profiling of this fraction using UHPLC-ESI-MS/MS resulted in the putative identification of 28 compounds, which included phenolic acids, flavan-3-ols and flavonols. The results of this study showed that the ethyl acetate fraction of Arbutus pavarii leaf possessed potential antibacterial activity against MRSA and hence can be further explored for pharmaceutical applications as a natural antibacterial agent.
Modelling the Stiffness-Temperature Dependence of Resin-Rubber Blends Cured by High-Energy Electron Beam Radiation Using Global Search Genetic Algorithm
Authors: Kopal Ivan , Vršková Juliána , Bakošová Alžbeta , Harničárová Marta , Labaj Ivan , Ondrušová Darina , Valíček Jan , Krmela Jan
Published: November 2020

Modelling the influence of high-energy ionising radiation on the properties of materials with polymeric matrix using advanced artificial intelligence tools plays an important role in the research and development of new materials for various industrial applications. It also applies to effective modification of existing materials based on polymer matrices to achieve the desired properties. In the presented work, the effects of high-energy electron beam radiation with various doses on the dynamic mechanical properties of melamine resin, phenol-formaldehyde resin, and nitrile rubber blend have been studied over a wide temperature range. A new stiffness-temperature model based on Weibull statistics of the secondary bonds breaking during the relaxation transitions has been developed to quantitatively describe changes in the storage modulus with temperature and applied radiation dose until the onset of the temperature of the additional, thermally-induced polymerisation reactions. A global search real-coded genetic algorithm has been successfully applied to optimise the parameters of the developed model by minimising the sum-squared error. An excellent agreement between the modelled and experimental data has been found.
Chain Entanglement of 2-Ethylhexyl Hydrogen-2-Ethylhexylphosphonate into Methacrylate-Grafted Nonwoven Fabrics for Applications in Separation and Recovery of Dy (III) and Nd (III) from Aqueous Solution
Authors: Hoshina Hiroyuki , Chen Jinhua , Amada Haruyo , Seko Noriaki
Published: November 2020

A nonwoven fabric adsorbent loaded with 2-ethylhexyl hydrogen-2-ethylhexylphosphonate (EHEP) was developed for the separation and recovery of dysprosium (Dy) and neodymium (Nd) from an aqueous solution. The adsorbent was prepared by the radiation-induced graft polymerization of a methacrylate monomer with a long alkyl chain onto a nonwoven fabric and the subsequent loading of EHEP by hydrophobic interaction and chain entanglement between the alkyl chains. The adsorbent was evaluated by batch and column tests with a Dy (III) and Nd (III) aqueous solution. In the batch tests, the adsorbent showed high Dy (III) adsorptivity close to 25.0 mg/g but low Nd (III) adsorptivity below 1.0 mg/g, indicating that the adsorbent had high selective adsorption. In particular, the octadecyl methacrylate (OMA)-adsorbent showed adsorption stability in repeated tests. In the column tests, the OMA-adsorbent was also stable and showed high Dy (III) adsorptivity and high selectivity in repeated adsorption–elution circle tests. This result suggested that the OMA-adsorbent may be a promising adsorbent for the separation and recovery of Dy (III) and Nd (III) ions.
Electrical Double Percolation of Polybutadiene/Polyethylene Glycol Blends Loaded with Conducting Polymer Nanofibers
Authors: Morita Jun , Goto Takanori , Kanehashi Shinji , Shimomura Takeshi
Published: November 2020

The critical phenomena of double percolation on polybutadiene (PB)/polyethylene glycol (PEG) blends loaded with poly-3-hexylthiophene (P3HT) nanofibers is investigated. P3HT nanofibers are selectively localized in the PB phase of the PB/PEG blend, as observed by scanning force microscopy (SFM). Moreover, double percolation is observed, i.e., the percolation of the PB phase in PB/PEG blends and that of the P3HT nanofibers in the PB phase. The percolation threshold (φcI) and critical exponent (tI) of the percolation of the PB phase in PB/PEG blends are estimated to be 0.57 and 1.3, respectively, indicating that the percolation exhibits two-dimensional properties. For the percolation of P3HT nanofibers in the PB phase, the percolation threshold (φcII) and critical exponent (tII) are estimated to be 0.02 and 1.7, respectively. In this case, the percolation exhibits properties in between two and three dimensions. In addition, we investigated the dimensionality with respect to the carrier transport in the P3HT nanofiber network. From the temperature dependence of the field-effect mobility estimated by field-effect transistor (FET) measurements, the carrier transport was explained by a three-dimensional variable range hopping (VRH) model.
Dielectric Elastomers UV-Cured from Poly(dimethylsiloxane) Solution in Vinyl Acetate
Authors: Park Seung Koo , Choi Meejeong , Kim Dong Wook , Park Bong Je , Shin Eun Jin , Park Suntak , Yun Sungryul
Published: November 2020

Poly(dimethylsiloxane) (PDMS) has been extensively used as an electroactive polymer material because it exhibits not only excellent moldability but also mechanical properties sufficient enough for electroactive performance despite low dielectric permittivity. Its low dielectric property is due to its molecular non-polarity. Here, we introduce a polar group into a PDMS elastomer by using vinyl acetate (VAc) as a crosslinker to improve the dielectric permittivity. We synthesized a high-molecular weight PDMS copolymer containing vinyl groups, namely poly(dimethylsiloxane-co-methylvinylsiloxane) (VPDMS), and prepared several of the VPDMS solutions in VAc. We obtained transparent PDMS films by UV curing of the solution layers. Electromechanical actuation-related physical properties of one of the UV-cured films were almost equivalent to or superior to those of platinum-catalyzed hydrosilylation-cured PDMS films. In addition, saponification of the UV-cured film significantly improved the electrical and mechanical properties (ɛ′ ~ 44.1 pF/m at 10 kHz, E ~ 350 kPa, ɛ ~ 320%). The chemical introduction of VAc into PDMS main chains followed by saponification would offer an efficacious method of enhancing the electroactive properties of PDMS elastomers.
Nitride-Coated and Anodic-Oxidized Titanium Promote a Higher Fibroblast and Reduced Streptococcus gordonii Proliferation Compared to the Uncoated Titanium
Authors: Zhurakivska Khrystyna , Ciacci Nagaia , Troiano Giuseppe , Caponio Vito , Scrascia Roberto , Pallecchi Lucia , Lo Muzio Lorenzo , Arena Fabio
Published: November 2020

Titanium shows optimal biocompatibility properties; however, its gray color may be a limit for aesthetic results of dental rehabilitations. Some surface treatments that change the color of the material have been proposed. The aim of this study is to, in vitro, investigate the biocompatibility of the surfaces subjected to titanium nitride (NiT) coating and anodic-oxidized (AO) treatment and their propensity to impair bacterial proliferation. The viability of primary human gingival fibroblasts (HGFs) has been evaluated through a methyl thiazolyl tetrazolium (MTT) assay in three experimental groups: uncoated titanium (UNCOATED), titanium nitride (NiT)-coated surface, and anodic-oxidized (AO) titanium. Bacterial proliferation experiments were performed using a Streptococcus gordonii clinical isolate in contact with the three different above-mentioned materials. The treated surfaces (NiT and AO) showed a significantly higher fibroblast proliferation than the uncoated titanium alloy (p < 0.05). In contrast, Streptococcus gordonii growth was significantly higher on the untreated titanium (p < 0.05).
The Spatial–Spectral–Environmental Extraction Endmember Algorithm and Application in the MODIS Fractional Snow Cover Retrieval
Authors: Zhao Hongyu , Hao Xiaohua , Wang Jian , Li Hongyi , Huang Guanghui , Shao Donghang , Su Bo , Lei Huajin , Hu Xiaojing
Published: November 2020

Endmember extraction is a primary and indispensable component of the spectral mixing analysis model applicated to quantitatively retrieve fractional snow cover (FSC) from satellite observation. In this study, a new endmember extraction algorithm, the spatial–spectral–environmental (SSE) endmember extraction algorithm, is developed, in which spatial, spectral and environmental information are integrated together to automatically extract different types of endmembers from moderate resolution imaging spectroradiometer (MODIS) images. Then, combining the linear spectral mixture analysis model (LSMA), the SSE endmember extraction algorithm is practically applied to retrieve FSC from standard MODIS surface reflectance products in China. The new algorithm of MODIS FSC retrieval is named as SSEmod. The accuracy of SSEmod is quantitatively validated with 16 higher spatial-resolution FSC maps derived from Landsat 8 binary snow cover maps. Averaged over all regions, the average root-mean-square-error (RMSE) and mean absolute error (MAE) are 0.136 and 0.092, respectively. Simultaneously, we also compared the SSEmod with MODImLAB, MODSCAG and MOD10A1. In all regions, the average RMSE of SSEmod is improved by 2.3%, 2.6% and 5.3% compared to MODImLAB for 0.157, MODSCAG for 0.157 and MOD10A1 for 0.189. Therefore, our SSE endmember extraction algorithm is reliable for the MODIS FSC retrieval and may be also promising to apply other similar satellites in view of its accuracy and efficiency.
Detecting Change at Archaeological Sites in North Africa Using Open-Source Satellite Imagery
Authors: Rayne Louise , Gatto Maria , Abdulaati Lamin , Al-Haddad Muftah , Sterry Martin , Sheldrick Nichole , Mattingly David
Published: November 2020

Our paper presents a remote sensing workflow for identifying modern activities that threaten archaeological sites, developed as part of the work of the Endangered Archaeology of the Middle East and North Africa (EAMENA) project. We use open-source Sentinel-2 satellite imagery and the free tool Google Earth Engine to run a per-pixel change detection to make the methods and data as accessible as possible for heritage professionals. We apply this and perform validation at two case studies, the Aswan and Kom-Ombo area in Egypt, and the Jufra oases in Libya, with an overall accuracy of the results ranging from 85–91%. Human activities, such as construction, agriculture, rubbish dumping and natural processes were successfully detected at archaeological sites by the algorithm, allowing these sites to be prioritised for recording. A few instances of change too small to be detected by Sentinel-2 were missed, and false positives were caused by registration errors, shadow and movements of sand. This paper shows that the expansion of agricultural and urban areas particularly threatens the survival of archaeological sites, but our extensive online database of archaeological sites and programme of training courses places us in a unique position to make our methods widely available.
Developing an Atlas of Harmful Algal Blooms in the Red Sea: Linkages to Local Aquaculture
Authors: Gokul Elamurugu Alias , Raitsos Dionysios E. , Gittings John A. , Hoteit Ibrahim
Published: November 2020

Harmful algal blooms (HABs) are one of the leading causes of biodiversity loss and alterations to ecosystem services. The Red Sea is one of the least studied large marine ecosystems (LMEs), and knowledge on the large-scale spatiotemporal distribution of HABs remains limited. We implemented the recently developed remote sensing algorithm of Gokul et al. (2019) to produce a high-resolution atlas of HAB events in the Red Sea and investigated their spatiotemporal variability between 2003 and 2017. The atlas revealed that (i) the southern part of the Red Sea is subject to a higher occurrence of HABs, as well as long-lasting and large-scale events, in comparison to the northern part of the basin, and (ii) the Red Sea HABs exhibited a notable seasonality, with most events occurring during summer. We further investigated the potential interactions between identified HAB events and the National Aquaculture Group (NAQUA), Al-Lith (Saudi Arabia)—the largest aquaculture facility on the Red Sea coast. The results suggest that the spatial coverage of HABs and the elevated chlorophyll-a concentration (Chl-a) (> 1 mg m−3; a proxy for high nutrient concentration), in the coastal waters of Al-Lith during summer, increased concurrently with the local aquaculture annual production over a nine-year period (2002–2010). This could be attributed to excessive nutrient loading from the NAQUA facility’s outfall, which enables the proliferation of HABs in an otherwise oligotrophic region during summer. Aquaculture is an expanding, high-value industry in the Kingdom of Saudi Arabia. Thus, a wastewater management plan should ideally be implemented at a national level, in order to prevent excessive nutrient loading. Our results may assist policy-makers’ efforts to ensure the sustainable development of the Red Sea’s coastal economic zone.