bluuebunny/crossref_metadata_2025 huggingface dataset:
Tunable Multilevel Data Storage Bioresistive Random Access Memory Device Based on Egg Albumen and Carbon Nanotubes
Authors: Wang Lu , Yang Tianyu , Wen Dianzhong
Published: August 2021

In this paper, a tuneable multilevel data storage bioresistive memory device is prepared from a composite of multiwalled carbon nanotubes (MWCNTs) and egg albumen (EA). By changing the concentration of MWCNTs incorporated into the egg albumen film, the switching current ratio of aluminium/egg albumen:multiwalled carbon nanotubes/indium tin oxide (Al/EA:MWCNT/ITO) for resistive random access memory increases as the concentration of MWCNTs decreases. The device can achieve continuous bipolar switching that is repeated 100 times per cell with stable resistance for 104 s and a clear storage window under 2.5 × 104 continuous pulses. Changing the current limit of the device to obtain low-state resistance values of different states achieves multivalue storage. The mechanism of conduction can be explained by the oxygen vacancies and the smaller number of iron atoms that are working together to form and fracture conductive filaments. The device is nonvolatile and stable for use in rewritable memory due to the adjustable switch ratio, adjustable voltage, and nanometre size, and it can be integrated into circuits with different power consumption requirements. Therefore, it has broad application prospects in the fields of data storage and neural networks.
TiO2 (Core)/Crumpled Graphene Oxide (Shell) Nanocomposites Show Enhanced Photodegradation of Carbamazepine
Authors: Fu Han , Gray Kimberly A.
Published: August 2021

The presence of pharmaceuticals and personal care products (PPCPs) in aquatic systems is a serious threat to human and ecological health. The photocatalytic degradation of PPCPs via titanium oxide (TiO2) is a well-researched potential solution, but its efficacy is limited by a variety of environmental conditions, such as the presence of natural organic macromolecules (NOM). In this study, we investigate the synthesis and performance of a novel photoreactive composite: a three-dimensional (3D) core (TiO2)-shell (crumpled graphene oxide) composite (TiGC) used as a powerful tool for PPCP removal and degradation in complex aqueous environments. TiGC exhibited a high adsorption capacity (maximum capacity 11.2 mg/g, 100 times larger than bare TiO2) and a 30% enhancement of photodegradation (compared to bare TiO2) in experiments with a persistent PPCP model, carbamazepine (CBZ). Furthermore, the TiGC performance was tested under various conditions of NOM concentration, light intensity, CBZ initial concentration, and multiple cycles of CBZ addition, in order to illustrate that TiGC performance is stable over a range of field conditions (including NOM). The enhanced and stable performance of TiCG to adsorb and degrade CBZ in water extends from its core-shell composite nanostructure: the crumpled graphene oxide shell provides an adsorptive surface that favors CBZ sorption over NOM, and optical and electronic interactions between TiO2 and graphene oxide result in higher hydroxyl radical (•OH) yields than bare TiO2.
Towards Red Emissive Systems Based on Carbon Dots
Authors: Gavalas Spyridon , Kelarakis Antonios
Published: August 2021

Carbon dots (C-dots) represent an emerging class of nontoxic nanoemitters that show excitation wavelength-dependent photoluminescence (PL) with high quantum yield (QY) and minimal photobleaching. The vast majority of studies focus on C-dots that exhibit the strongest PL emissions in the blue/green region of the spectrum, while longer wavelength emissions are ideal for applications such as bioimaging, photothermal and photodynamic therapy and light-emitting diodes. Effective strategies to modulate the PL emission of C-dot-based systems towards the red end of the spectrum rely on extensive conjugation of sp2 domains, heteroatom doping, solvatochromism, surface functionalization and passivation. Those approaches are systematically presented in this review, while emphasis is given on important applications of red-emissive suspensions, nanopowders and polymer nanocomposites.
Free Vibration of Thin-Walled Composite Shell Structures Reinforced with Uniform and Linear Carbon Nanotubes: Effect of the Elastic Foundation and Nonlinearity
Authors: Mahmure Avey , Tornabene Francesco , Dimitri Rossana , Kuruoglu Nuri
Published: August 2021

In this work, we discuss the free vibration behavior of thin-walled composite shell structures reinforced with carbon nanotubes (CNTs) in a nonlinear setting and resting on a Winkler–Pasternak Foundation (WPF). The theoretical model and the differential equations associated with the problem account for different distributions of CNTs (with uniform or nonuniform linear patterns), together with the presence of an elastic foundation, and von-Karman type nonlinearities. The basic equations of the problem are solved by using the Galerkin and Grigolyuk methods, in order to determine the frequencies associated with linear and nonlinear free vibrations. The reliability of the proposed methodology is verified against further predictions from the literature. Then, we examine the model for the sensitivity of the vibration response to different input parameters, such as the mechanical properties of the soil, or the nonlinearities and distributions of the reinforcing CNT phase, as useful for design purposes and benchmark solutions for more complicated computational studies on the topic.
Anion Dependent Particle Size Control of Platinum Nanoparticles Synthesized in Ethylene Glycol
Authors: Schröder Johanna , Neumann Sarah , Quinson Jonathan , Arenz Matthias , Kunz Sebastian
Published: August 2021

The polyol synthesis is a well-established method to form so-called “surfactant-free” nanoparticles (NPs). In the present study, the NP size resulting from the thermal reduction of the precursors H2PtCl6, H2Pt(OH)6, or Pt(acac)2 in presence of the bases NaOH or Na(acac) at different concentrations is studied. It is shown that the size control depends more strongly on the nature of the precursor (metal salt) than on the anion present in the base. The latter is surprising as the concentration of the base anion is often an important factor to achieve a size control. The reduction of H2PtCl6 or H2Pt(OH)6 in presence of NaOH and Na(acac) confirm the observation that the NP size is determined by the OH−/Pt molar ratio and expands it to the base anion/Pt molar ratio. In contrast, the reduction of Pt(acac)2 in presence of the bases NaOH (previous reports) or Na(acac) (shown in the present work) leads to larger NPs of ca. 3 nm, independent of the concentration of the base anions. Hence, the anion effect observed here seems to originate predominantly from the nature of the precursor (precursor anion dependence) and only for certain precursors as H2PtCl6 or H2Pt(OH)6 the size control depends on the base anion/Pt molar ratio.
Graphene for the Building of Electroanalytical Enzyme-Based Biosensors. Application to the Inhibitory Detection of Emerging Pollutants
Authors: Bonet-San-Emeterio Marta , Felipe Montiel Noelia , del Valle Manel
Published: August 2021

Graphene and its derivates offer a wide range of possibilities in the electroanalysis field, mainly owing to their biocompatibility, low-cost, and easy tuning. This work reports the development of an enzymatic biosensor using reduced graphene oxide (RGO) as a key nanomaterial for the detection of contaminants of emerging concern (CECs). RGO was obtained from the electrochemical reduction of graphene oxide (GO), an intermediate previously synthesized in the laboratory by a wet chemistry top-down approach. The extensive characterization of this material was carried out to evaluate its proper inclusion in the biosensor arrangement. The results demonstrated the presence of GO or RGO and their correct integration on the sensor surface. The detection of CECs was carried out by modifying the graphene platform with a laccase enzyme, turning the sensor into a more selective and sensitive device. Laccase was linked covalently to RGO using the remaining carboxylic groups of the reduction step and the carbodiimide reaction. After the calibration and characterization of the biosensor versus catechol, a standard laccase substrate, EDTA and benzoic acid were detected satisfactorily as inhibiting agents of the enzyme catalysis obtaining inhibition constants for EDTA and benzoic acid of 25 and 17 mmol·L−1, respectively, and a maximum inhibition percentage of the 25% for the EDTA and 60% for the benzoic acid.
AgNPs Argovit™ Modulates Cyclophosphamide-Induced Genotoxicity on Peripheral Blood Erythrocytes In Vivo
Authors: Castañeda-Yslas Idalia Yazmin , Torres-Bugarín Olivia , García-Ramos Juan Carlos , Toledano-Magaña Yanis , Radilla-Chávez Patricia , Bogdanchikova Nina , Pestryakov Alexey , Ruiz-Ruiz Balam , Arellano-García María Evarista
Published: August 2021

Silver nanoparticles (AgNPs) have been studied worldwide for their potential biomedical applications. Specifically, they are proposed as a novel alternative for cancer treatment. However, the determination of their cytotoxic and genotoxic effects continues to limit their application. The commercially available silver nanoparticle Argovit™ has shown antineoplastic, antiviral, antibacterial, and tissue regenerative properties, activities triggered by its capacity to promote the overproduction of reactive oxygen species (ROS). Therefore, in this work, we evaluated the genotoxic and cytotoxic potential of the Argovit™ formulation (average size: 35 nm) on BALB/c mice using the micronucleus in a peripheral blood erythrocytes model. Besides, we evaluated the capability of AgNPs to modulate the genotoxic effect induced by cyclophosphamide (CP) after the administration of the oncologic agent. To achieve this, 5–6-week-old male mice with a mean weight of 20.11 ± 2.38 g were treated with water as negative control (Group 1), an single intraperitoneal dose of CP (50 mg/kg of body weight, Group 2), a daily oral dose of AgNPs (6 mg/kg of weight, Group 3) for three consecutive days, or a combination of these treatment schemes: one day of CP doses (50 mg/kg of body weight) followed by three doses of AgNPs (one dose per day, Group 4) and three alternate doses of CP and AgNPs (six days of exposure, Group 5). Blood samples were taken just before the first administration (0 h) and every 24 h for seven days. Our results show that Argovit™ AgNPs induced no significant cytotoxic or acute genotoxic damage. The observed cumulative genotoxic damage in this model could be caused by the accumulation of AgNPs due to administered consecutive doses. Furthermore, the administration of AgNPs after 24 h of CP seems to have a protective effect on bone marrow and reduces by up to 50% the acute genotoxic damage induced by CP. However, this protection is not enough to counteract several doses of CP. To our knowledge, this is the first time that the exceptional chemoprotective capacity produced by a non-cytotoxic silver nanoparticle formulation against CP genotoxic damage has been reported. These findings raise the possibility of using AgNPs as an adjuvant agent with current treatments, reducing adverse effects.
Optical Performance and Moisture Stability Enhancement of Flexible Luminescent Films Based on Quantum-Dot/Epoxy Composite Particles
Authors: Liang Guanwei , Tang Yong , Huang Jiarui , Li Jiasheng , Yuan Yikai , Yang Shu , Li Zongtao
Published: August 2021

Quantum dots (QDs) have been widely applied in luminescent sources due to their strong optical characteristics. However, a moisture environment causes their quenching, leading to an inferior optical performance in commercial applications. In this study, based on the high moisture resistance of epoxy resin, a novel epoxy/QDs composite particle structure was proposed to solve this issue. Flexible luminescent films could be obtained by packaging composite particles in silicone resin, combining the hydrophobicity of epoxy resin and the flexibility of PDMS simultaneously. The photoluminescence and light extraction were improved due to the scattering properties of the structure of composite particles, which was caused by the refractive index mismatch between the epoxy and silicone resin. Compared to the QD/silicone film under similar lighting conditions, the proposed flexible film demonstrated increased light efficiency as well as high moisture stability. The results revealed that a light-emitting diode (LED) device using the composite particle flexible (CPF) structure obtained a 34.2% performance enhancement in luminous efficiency as well as a 32% improvement in color conversion efficiency compared to those of devices with QD/silicone film (QSF) structure. Furthermore, the CPF structure exhibited strong thermal and moisture stability against extreme ambient conditions of 85 °C and 85% relative humidity simultaneously. The normalized luminous flux degradation of devices embedded in CPF and QSF structures after aging for 118 h were ~20.2% and ~43.8%, respectively. The satisfactory performance of the CPF structure in terms of optical and moisture stability shows its great potential value in flexible commercial QD-based LED displays and lighting applications.
A Systematic Review of Severe Neurological Manifestations in Pediatric Patients with Coexisting SARS-CoV-2 Infection
Authors: O’Loughlin Lauren , Alvarez Toledo Nilo , Budrie Leon , Waechter Randall , Rayner Joanna
Published: August 2021

SARS-CoV-2 infection in children produces mild respiratory symptoms or no symptoms at all in most cases. Some pediatric patients develop a severe complication associated with high mortality, the multisystem inflammatory syndrome in children (MIS-C). In both scenarios, there are reports of neurological manifestations. This article aims to review the cases of pediatric patients with severe neurological issues and a coexisting positive SARS-CoV-2 test. A literature search was performed between March 2020 and May 2021. The results included the data from 41 studies, with 159 children with severe neurological manifestations, within an age range from 24 h to 17 years. The neurological disorders included 38 cases with stroke, 32 with encephalitis, 22 with encephalopathy, and 10 with Guillain–Barre syndrome. Sixty-five out of 159 cases with severe neurological manifestations were diagnosed with MIS-C. Direct neuroinvasion and the exaggerated immune response in some patients seem to be the most critical factors triggering these manifestations. Further research in the ongoing pandemic is needed to elucidate the precise mechanism.
Effects of Milk Protein in Resistance Training-Induced Lean Mass Gains for Older Adults Aged ≥ 60 y: A Systematic Review and Meta-Analysis
Authors: Huang Ling-Pi , Condello Giancarlo , Kuo Chia-Hua
Published: August 2021

This review evaluated the effects of milk-based protein supplementation on resistance training (RT)-induced gains in lean body mass or fat free mass (LBM/FFM) and muscle strength for older adults. A systematic search of PubMed, Scopus and EBSCOhost/SPORTDiscus was conducted. Eligibility criteria: Randomized controlled trials comparing all types of milk-based protein supplements with control supplements for the training older adults at mean age ≥ 60 y. Twenty studies were included in the qualitative synthesis, whilst seventeen studies were included in the quantitative synthesis. A dose of 10–15 g of milk protein supplementation was sufficient to augment RT-induced LBM/FFM. Intriguingly, four out of five studies show negative effect of whey protein supplementation at the same dose range (or even higher) compared with control supplementation (−0.49 kg, 95% CI: −0.69, −0.29, I2 = 14%, Z = 4.82, p < 0.001). For milk-based protein supplementation, RT-induced improvements in muscle strength were observed only when the protein doses ≥22 g (+0.66 kg, 95% CI: 0.07, 1.25, I2 = 0%, Z = 2.18, p = 0.03). Conclusion: Milk protein is superior to whey protein in enhancing RT-induced LBM/FFM gains for older adults. Optimal daily protein intake can dilute the protein supplementation effect.
Increasing Fruit and Vegetable Variety over Time Is Associated with Lower 15-Year Healthcare Costs: Results from the Australian Longitudinal Study on Women’s Health
Authors: Baldwin Jennifer N. , Ashton Lee M. , Forder Peta M. , Haslam Rebecca L. , Hure Alexis J. , Loxton Deborah J. , Patterson Amanda J. , Collins Clare E.
Published: August 2021

Healthcare costs are lower for adults who consume more vegetables; however, the association between healthcare costs and fruit and vegetable varieties is unclear. Our aim was to investigate the association between (i) baseline fruit and vegetable (F&V) varieties, and (ii) changes in F&V varieties over time with 15-year healthcare costs in an Australian Longitudinal Study on Women’s Health. The data for Survey 3 (n = 8833 women, aged 50–55 years) and Survey 7 (n = 6955, aged 62–67 years) of the 1946–1951 cohort were used. The F&V variety was assessed using the Fruit and Vegetable Variety (FAVVA) index calculated from the Cancer Council of Victoria’s Dietary Questionnaire for Epidemiological Studies food frequency questionnaire. The baseline FAVVA and change in FAVVA were analysed as continuous predictors of Medicare claims/costs by using multiple regression analyses. Healthy weight women made, on average, 4.3 (95% confidence interval (CI) 1.7–6.8) fewer claims for every 10-point-higher FAVVA. Healthy weight women with higher fruit varieties incurred fewer charges; however, this was reversed for women overweight/obese. Across the sample, for every 10-point increase in FAVVA over time, women made 4.3 (95% CI 1.9–6.8) fewer claims and incurred $309.1 (95% CI $129.3–488.8) less in charges over 15 years. A higher F&V variety is associated with a small reduction in healthcare claims for healthy weight women only. An increasing F&V variety over time is associated with lower healthcare costs.
Trajectories of Dietary Patterns and Their Associations with Overweight/Obesity among Chinese Adults: China Health and Nutrition Survey 1991–2018
Authors: Zhang Jiguo , Wang Huijun , Wang Zhihong , Huang Feifei , Zhang Xiaofan , Du Wenwen , Su Chang , Ouyang Yifei , Li Li , Bai Jing , Zhang Bing , Du Shufa , Ding Gangqiang
Published: August 2021

It is essential to understand the impact of different dietary pattern trajectories on health over time. Therefore, we aimed to explore the long-term trajectories of dietary patterns among Chinese adults and examine the prospective association between different trajectory groups and the risk of overweight/obesity. The sample was 9299 adults aged 18 years or older from the China Health and Nutrition Survey (CHNS) between 1991 and 2018. We used factor analysis to identify dietary patterns and group-based trajectory modeling to identify dietary pattern trajectories. Three trajectories of a southern pattern and a modern pattern and four trajectories of a meat pattern were identified. Participants who followed the highest initial score and a slight decrease trajectory (OR = 1.63; 95% CI: 1.04, 2.54) of the meat dietary pattern were positively associated with risk of overweight/obesity when compared with the lowest initial score trajectory. The southern dietary pattern and the modern dietary pattern trajectories of participants in Group 2 (OR = 0.64; 95% CI: 0.51, 0.81; OR = 0.76; 95% CI: 0.63, 0.91) and Group 3 (OR = 0.71; 95% CI: 0.54, 0.91; OR = 0.64; 95% CI: 0.44, 0.90) were associated with lower risk of overweight/obesity when compared with Group 1. We observed that dietary pattern trajectories have different associations with overweight/obesity among Chinese adults.
The Association between Milk Intake and Nutrient Intake Adequacy among Japanese Female Junior High School Students: A Cross-Sectional Study
Authors: Matsumoto Mai , Hatamoto Yoichi , Sakamoto Azusa , Masumoto Ayumi , Murayama Chiaki , Ikemoto Shinji
Published: August 2021

The consumption of dairy products, including milk, may be important for improving the overall quality of a diet. The aim of this study was to examine the relationship between milk intake and nutritional adequacy among Japanese female junior high school students. The participants of this study were Japanese female junior high school students aged between 12 and 15 years. Dietary habits over the past month were assessed by a brief self-administered diet history questionnaire. The adequacy of each nutrient intake was determined based on the Dietary Reference Intakes for Japanese 2020, with two goals: the estimated average requirement for fourteen nutrients and tentative dietary goals for preventing lifestyle-related diseases for six nutrients. The participants were classified into five groups according to milk intake (Q1 (lowest) to Q5 (highest)) by quintile. The adequacy of vitamin B2, calcium, magnesium, and potassium were higher among students with a higher milk consumption than among those with a lower milk consumption. However, the intake of saturated fatty acids was in excess among higher milk consumers. The present study suggests that milk intake was related to an adequate intake of some vitamins and minerals and an inadequate intake of saturated fatty acids among Japanese female junior high school students.
Changes in the Gut Bacteria Composition of Healthy Men with the Same Nutritional Profile Undergoing 10-Week Aerobic Exercise Training: A Randomized Controlled Trial
Authors: Resende Ayane S. , Leite Geovana S. F. , Lancha Junior Antonio H.
Published: August 2021

Nutrient consumption and body mass index (BMI) are closely related to the gut microbiota, and exercise effects on gut bacteria composition may be related to those variables. Thus, we aimed to investigate the effect of 10-week moderate aerobic exercise on the cardiorespiratory fitness and gut bacteria composition of non-obese men with the same nutritional profile. Twenty-four previously sedentary men (age 25.18 [SD 4.66] years, BMI 24.5 [SD 3.72] kg/m2) were randomly assigned into Control (CG; n = 12) or Exercise Groups (EG; n = 12). Body composition, cardiorespiratory parameters, blood markers, dietary habits and gut bacteria composition were evaluated. EG performed 150 min per week of supervised moderate (60–65% of VO2peak) aerobic exercise, while CG maintained their daily routine. The V4 16S rRNA gene was sequenced and treated using QIIME software. Only EG demonstrated marked improvements in cardiorespiratory fitness (VO2peak, p < 0.05; Effect Size = 0.971) without changes in other gut bacteria-affecting variables. Exercise did not promote clustering based on diversity indices (p > 0.05), although significant variations in an unclassified genus from Clostridiales order and in Streptococcus genus were observed (p < 0.05). Moreover, α-diversity was correlated with VO2peak (Pearson’s R: 0.47; R2 0.23: 95%CI: 0.09 to 0.74, p = 0.02) and BMI (Pearson’s R: −0.50; R2 0.25: 95%CI: −0.75 to −0.12, p = 0.01). Roseburia, Sutterella and Odoribacter genera were associated with VO2peak, while Desulfovibrio and Faecalibacterium genera were associated with body composition (p < 0.05). Our study indicates that aerobic exercise at moderate intensity improved VO2peak and affected gut bacteria composition of non-obese men who maintained a balanced consumption of nutrients.
The Effectiveness of Nutrition Interventions Combined with Exercise in Upper Gastrointestinal Cancers: A Systematic Review
Authors: Sadeghi Fatemeh , Mockler David , Guinan Emer M. , Hussey Juliette , Doyle Suzanne L.
Published: August 2021

Malnutrition and muscle wasting are associated with impaired physical functioning and quality of life in oncology patients. Patients diagnosed with upper gastrointestinal (GI) cancers are considered at high risk of malnutrition and impaired function. Due to continuous improvement in upper GI cancer survival rates, there has been an increased focus on multimodal interventions aimed at minimizing the adverse effects of cancer treatments and enhancing survivors’ quality of life. The present study aimed to evaluate the effectiveness of combined nutritional and exercise interventions in improving muscle wasting, physical functioning, and quality of life in patients with upper GI cancer. A comprehensive search was conducted in MEDLINE, EMBASE, Web of Science, Cochrane Library, and CINHAL. Of the 4780 identified articles, 148 were selected for full-text review, of which 5 studies met the inclusion criteria. Whilst reviewed studies showed promising effects of multimodal interventions on physical functioning, no significant differences in postoperative complications and hospital stay were observed. Limited available evidence showed conflicting results regarding the effectiveness of these interventions on preserving muscle mass and improving health-related quality of life. Further studies examining the impact of nutrition and exercise interventions on upper GI patient outcomes are required and would benefit from reporting a core outcome set.
Angiotensin-Converting Enzyme 2 (ACE2) in the Context of Respiratory Diseases and Its Importance in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection
Authors: Ambrocio-Ortiz Enrique , Pérez-Rubio Gloria , Del Ángel-Pablo Alma , Buendía-Roldán Ivette , Chávez-Galán Leslie , Hernández-Zenteno Rafael , Ramírez-Venegas Alejandra , Rojas-Serrano Jorge , Mejía Mayra , Pérez-Padilla Rogelio , Guadarrama-Pérez Cristóbal , Falfán-Valencia Ramcés
Published: August 2021

Angiotensin-Converting Enzyme 2 (ACE2) is an 805 amino acid protein encoded by the ACE2 gene expressed in various human cells, especially in those located in the epithelia. The primary function of ACE2 is to produce angiotensin (1–7) from angiotensin II (Ang II). The current research has described the importance of ACE2 and Ang (1–7) in alternative routes of the renin-angiotensin system (RAS) that promote the downregulation of fibrosis, inflammation, and oxidative stress processes in a great variety of diseases, such as hypertension, acute lung injury, liver cirrhosis, and kidney abnormalities. Investigations into the recent outbreak of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have revealed the importance of ACE2 during infection and its role in recognizing viral binding proteins through interactions with specific amino acids of this enzyme. Additionally, the ACE2 expression in several organs has allowed us to understand the clinical picture related to the infection caused by SARS-CoV-2. This review aims to provide context for the functions and importance of ACE2 with regards to SARS-CoV-2 in the general clinical aspect and its impact on other diseases, especially respiratory diseases.
Preclinical Evaluation of the Safety and Immunological Action of Allogeneic ADSC-Collagen Scaffolds in the Treatment of Chronic Ischemic Cardiomyopathy
Authors: López-Díaz de Cerio Ascensión , Perez-Estenaga Iñigo , Inoges Susana , Abizanda Gloria , Gavira Juan José , Larequi Eduardo , Andreu Enrique , Rodriguez Saray , Gil Ana Gloria , Crisostomo Verónica , Sanchez-Margallo Francisco Miguel , Bermejo Javier , Jauregui Blanca , Quintana Lluis , Fernández-Avilés Francisco , Pelacho Beatriz , Prósper Felipe
Published: August 2021

The use of allogeneic adipose-derived mesenchymal stromal cells (alloADSCs) represents an attractive approach for treating myocardial infarction (MI). Furthermore, adding a natural support improves alloADSCs engraftment and survival in heart tissues, leading to a greater therapeutic effect. We aimed to examine the safety and immunological reaction induced by epicardial implantation of a clinical-grade collagen scaffold (CS) seeded with alloADSCs for its future application in humans. Thus, cellularized scaffolds were myocardially or subcutaneously implanted in immunosuppressed rodent models. The toxicological parameters were not significantly altered, and tumor formation was not found over the short or long term. Furthermore, biodistribution analyses in the infarcted immunocompetent rats displayed cell engraftment in the myocardium but no migration to other organs. The immunogenicity of alloADSC-CS was also evaluated in a preclinical porcine model of chronic MI; no significant humoral or cellular alloreactive responses were found. Moreover, CS cellularized with human ADSCs cocultured with human allogeneic immune cells produced no alloreactive response. Interestingly, alloADSC-CS significantly inhibited lymphocyte responses, confirming its immunomodulatory action. Thus, alloADSC-CS is likely safe and does not elicit any alloreactive immunological response in the host. Moreover, it exerts an immunomodulatory action, which supports its translation to a clinical setting.
MAP Kinase Pathways in Brain Endothelial Cells and Crosstalk with Pericytes and Astrocytes Mediate Contrast-Induced Blood–Brain Barrier Disruption
Authors: Matsunaga Yuki , Nakagawa Shinsuke , Morofuji Yoichi , Dohgu Shinya , Watanabe Daisuke , Horie Nobutaka , Izumo Tsuyoshi , Niwa Masami , Walter Fruzsina R. , Santa-Maria Ana Raquel , Deli Maria A. , Matsuo Takayuki
Published: August 2021

Neurointervention with contrast media (CM) has rapidly increased, but the impact of CM extravasation and the related side effects remain controversial. This study investigated the effect of CM on blood–brain barrier (BBB) integrity. We established in vitro BBB models using primary cultures of rat BBB-related cells. To assess the effects of CM on BBB functions, we evaluated transendothelial electrical resistance, permeability, and tight junction (TJ) protein expression using immunohistochemistry (IHC) and Western blotting. To investigate the mechanism of iopamidol-induced barrier dysfunction, the role of mitogen-activated protein (MAP) kinases in brain endothelial cells was examined. We assessed the effect of conditioned medium derived from astrocytes and pericytes under iopamidol treatment. Short-term iopamidol exposure on the luminal side induced transient, while on the abluminal side caused persistent BBB dysfunction. IHC and immunoblotting revealed CM decreased the expression of TJ proteins. Iopamidol-induced barrier dysfunction was improved via the regulation of MAP kinase pathways. Conditioned medium from CM-exposed pericytes or astrocytes lacks the ability to enhance barrier function. CM may cause BBB dysfunction. MAP kinase pathways in brain endothelial cells and the interactions of astrocytes and pericytes mediate iopamidol-induced barrier dysfunction. CM extravasation may have negative effects on clinical outcomes in patients.
Prevalence of Mutations in the pfcoronin Gene and Association with Ex Vivo Susceptibility to Common Quinoline Drugs against Plasmodium falciparum
Authors: Delandre Océane , Gendrot Mathieu , Fonta Isabelle , Mosnier Joel , Benoit Nicolas , Amalvict Rémy , Gomez Nicolas , Madamet Marylin , Pradines Bruno
Published: August 2021

Background: Artemisinin-based combination therapy (ACT) was recommended to treat uncomplicated falciparum malaria. Unlike the situation in Asia where resistance to ACT has been reported, artemisinin resistance has not yet emerged in Africa. However, some rare failures with ACT or patients continuing to be parasitaemic on day 3 after ACT treatment have been reported in Africa or in travellers returning from Africa. Three mutations (G50E, R100K, and E107V) in the pfcoronin gene could be responsible for artemisinin resistance in Africa. Methods: The aims of this study were first to determine the prevalence of mutations in the pfcoronin gene in African P. falciparum isolates by Sanger sequencing, by targeting the 874 samples collected from patients hospitalised in France after returning from endemic areas in Africa between 2018 and 2019, and secondly to evaluate their association with in vitro reduced susceptibility to standard quinoline antimalarial drugs, including chloroquine, quinine, mefloquine, desethylamodiaquine, lumefantrine, piperaquine, and pyronaridine. Results: The three mutations in the pfcoronin gene (50E, 100K, and 107V) were not detected in the 874 P. falciparum isolates. Current data show that another polymorphism (P76S) is present in many countries of West Africa (mean prevalence of 20.7%) and Central Africa (11.9%) and, rarely, in East Africa (4.2%). This mutation does not appear to be predictive of in vitro reduced susceptibility to quinolines, including artemisinin derivative partners in ACT such as amodiaquine, lumefantrine, piperaquine, pyronaridine, and mefloquine. Another mutation (V62M) was identified at low prevalence (overall prevalence of 1%). Conclusions: The 76S mutation is present in many African countries with a prevalence above 10%. It is reassuring that this mutation does not confer in vitro resistance to ACT partners.
The Influence of Omeprazole on the Dissolution Processes of pH-Dependent Magnetic Tablets Assessed by Pharmacomagnetography
Authors: Soares Guilherme A. , Pires Deivid W. , Pinto Leonardo A. , Rodrigues Gustavo S. , Prospero André G. , Biasotti Gabriel G. A. , Bittencourt Gabriela N. , Stoppa Erick G. , Corá Luciana A. , Oliveira Ricardo B. , Miranda José R. A.
Published: August 2021

Pharmacomagnetography involves the simultaneous assessment of solid dosage forms (SDFs) in the human gastrointestinal (GI) tract and the drug plasmatic concentration, using a biomagnetic technique and pharmacokinetics analysis. This multi-instrumental approach helps the evaluation, as GI variables can interfere with the drug delivery processes. This study aimed to employ pharmacomagnetography to evaluate the influence of omeprazole on the drug release and absorption of metronidazole administered orally in magnetic-coated tablets. Magnetic-coated tablets, coated with Eudragit® E-100 (E100) and containing 100 mg of metronidazole, were produced. For the in vivo experiments, 12 volunteers participated in the two phases of the study (placebo and omeprazole) on different days to assess the bioavailability of metronidazole. The results indicated a shift as the pH of the solution increased and a delay in the dissolution of metronidazole, showing that the pH increase interferes with the release processes of tablets coated with E100. Our study reinforced the advantages of pharmacomagnetography as a tool to perform a multi-instrumental correlation analysis of the disintegration process and the bioavailability of drugs.
The Anti-Arthritic Efficacy of Khellin Loaded in Ascorbyl Decanoate Nanovesicles after an Intra-Articular Administration
Authors: Vanti Giulia , Di Cesare Mannelli Lorenzo , Micheli Laura , Cinci Lorenzo , Grifoni Lucia , Bergonzi Maria Camilla , Ghelardini Carla , Bilia Anna Rita
Published: August 2021

Osteoarthritis is the most widespread joint-affecting disease. The management of persistent pain remains inadequate and demands new therapeutic strategies. In this study, we explored the pain relieving and protective properties of a single intra-articular (i.a.) injection of khellin loaded in nanovesicles (K-Ves) based on ascorbyl decanoate plus phosphatidylcholine in a rat model of osteoarthritis (OA) induced by monosodium iodoacetate (MIA) treatment. The developed nanovesicles (approximately 136 nm) had a narrow size distribution (PdI 0.26), a good recovery (about 80%) and a worthy encapsulation efficiency (about 70%) with a ζ-potential of about −40 mV. The stability of K-Ves was assessed in simulated synovial fluid. Seven days after the articular damage with MIA, both K-Ves and a suspension of khellin (K, 50 μL) were i.a. injected. K-Ves significantly counteracted MIA-induced hypersensitivity to mechanical noxious (paw pressure test) and non-noxious stimuli (von Frey test) and significantly reduced the postural unbalance related to spontaneous pain (incapacitance test) and the motor alterations (beam balance test) 7 and 14 days after the i.a. injection. K was partially active only on day 7 after the treatment. The histology emphasized the improvement of several morphological factors in MIA plus K-Ves-treated animals. In conclusion, K-Ves could be successfully used for the local treatment of osteoarthritis.
In Vitro Investigations on Optimizing and Nebulization of IVT-mRNA Formulations for Potential Pulmonary-Based Alpha-1-Antitrypsin Deficiency Treatment
Authors: Guan Shan , Darmstädter Max , Xu Chuanfei , Rosenecker Joseph
Published: August 2021

In vitro-transcribed (IVT) mRNA has come into focus in recent years as a potential therapeutic approach for the treatment of genetic diseases. The nebulized formulations of IVT-mRNA-encoding alpha-1-antitrypsin (A1AT-mRNA) would be a highly acceptable and tolerable remedy for the protein replacement therapy for alpha-1-antitrypsin deficiency in the future. Here we show that lipoplexes containing A1AT-mRNA prepared in optimum conditions could successfully transfect human bronchial epithelial cells without significant toxicity. A reduction in transfection efficiency was observed for aerosolized lipoplexes that can be partially overcome by increasing the initial number of components. A1AT produced from cells transfected by nebulized A1AT-mRNA lipoplexes is functional and could successfully inhibit the enzyme activity of trypsin as well as elastase. Our data indicate that aerosolization of A1AT-mRNA therapy constitutes a potentially powerful means to transfect airway epithelial cells with the purpose of producing functional A1AT, while bringing along the unique advantages of IVT-mRNA.
Assessing the Functional Redundancy between P-gp and BCRP in Controlling the Brain Distribution and Biliary Excretion of Dual Substrates with PET Imaging in Mice
Authors: Hernández-Lozano Irene , Mairinger Severin , Traxl Alexander , Sauberer Michael , Filip Thomas , Stanek Johann , Kuntner Claudia , Wanek Thomas , Langer Oliver
Published: August 2021

P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are co-localized at the blood–brain barrier, where they display functional redundancy to restrict the brain distribution of dual P-gp/BCRP substrate drugs. We used positron emission tomography (PET) with the metabolically stable P-gp/BCRP substrates [11C]tariquidar, [11C]erlotinib, and [11C]elacridar to assess whether a similar functional redundancy as at the BBB exists in the liver, where both transporters mediate the biliary excretion of drugs. Wild-type, Abcb1a/b(−/−), Abcg2(−/−), and Abcb1a/b(−/−)Abcg2(−/−) mice underwent dynamic whole-body PET scans after i.v. injection of either [11C]tariquidar, [11C]erlotinib, or [11C]elacridar. Brain uptake of all three radiotracers was markedly higher in Abcb1a/b(−/−)Abcg2(−/−) mice than in wild-type mice, while only moderately changed in Abcb1a/b(−/−) and Abcg2(−/−) mice. The transfer of radioactivity from liver to excreted bile was significantly lower in Abcb1a/b(−/−)Abcg2(−/−) mice and almost unchanged in Abcb1a/b(−/−) and Abcg2(−/−) mice (with the exception of [11C]erlotinib, for which biliary excretion was also significantly reduced in Abcg2(−/−) mice). Our data provide evidence for redundancy between P-gp and BCRP in controlling both the brain distribution and biliary excretion of dual P-gp/BCRP substrates and highlight the utility of PET as an upcoming tool to assess the effect of transporters on drug disposition at a whole-body level.
The Effect of Ozone Treatment on the Physicochemical Properties and Biocompatibility of Electrospun Poly(ε)caprolactone Scaffolds
Authors: Dabasinskaite Lauryna , Krugly Edvinas , Baniukaitiene Odeta , Martuzevicius Dainius , Ciuzas Darius , Jankauskaite Lina , Aukstikalne Lauryna , Usas Arvydas
Published: August 2021

Ozonation has been proved as a viable surface modification technique providing certain properties to the scaffolds that are essential in tissue engineering. However, the ozone (O3) treatment of PCL scaffolds in aqueous environments has not yet been presented. O3 treatment performed in aqueous environments is more effective compared with traditional, executed in ambient air treatment due to more abundant production of hydroxyl radicals (•OH) within the O3 reaction with water molecules. During interaction with •OH, the scaffold acquires functional groups which improve wettability properties and encapsulate growth factors. In this study, a poly(ε)caprolactone (PCL) scaffold was fabricated using solution electrospinning and was subsequently ozonated in a water reactor. The O3 treatment resulted in the expected occurrence of oxygen-containing functional groups, which improved scaffold wettability by almost 27% and enhanced cell proliferation for up to 14 days. The PCL scaffold was able to withhold 120 min of O3 treatment, maintaining fibrous morphology and mechanical properties.
Evaluation of a Novel Pharmacist-Delivered Adherence Improvement Service via Telehealth
Authors: Marupuru Srujitha , Dhatt Harman , Bingham Jennifer M. , Warholak Terri
Published: August 2021

Nearly half of all patients prescribed a chronic medication do not adhere to their regimen. Conversion from a 30- to 90-day medication refill is associated with improved adherence. The objective of the study was to assess the change in proportion of days covered (PDC) in those who converted to a 90-day fill and those who did not after a telehealth pharmacist-delivered, medication adherence intervention. This retrospective review involved data collected between May and December 2018. Patients with ≤85% baseline PDC rates were targeted. One group included patients who converted to a 90-day fill after the pharmacist intervention. The comparator group did not convert to a 90-day fill. Differences in median end-of-year (EOY) PDC rates for each medication class were compared between groups. An alpha level of 0.05 was set a priori. Overall, 237 patients converted to a 90-day fill and 501 did not. There was no significant difference in age, sex, and total number of drugs per patient. A Mann–Whitney U test revealed statistically significant improvements in median EOY PDC in the group that converted to a 90-day fill (+9% vs. −3%, p < 0.001). Pharmacist-delivered telehealth interventions were associated with improved PDC rates in those who converted to a 90-day fill.
Mixed Micellization and Spectroscopic Studies of Anti-Allergic Drug and Non-Ionic Surfactant in the Presence of Ionic Liquid
Authors: Azum Naved , Rub Malik Abdul , Asiri Abdullah M.
Published: August 2021

In drug delivery, surfactants are used to reduce side effects and to increase drug efficiency. The present work aimed to study the interaction of diphenhydramine hydrochloride (anti-allergic drug) with TX–45 (non-ionic surfactant) in the absence and presence of ionic liquid (1-hexyl-3-methylimidazolium chloride). The physicochemical parameters were estimated by the surface tension measurement. Various theoretical models (Clint, Rubingh, Motomura, and Maeda) were applied to determine the attractive behavior between drug and surfactant mixtures at the surface and in bulk. The drug and surfactant mixtures exhibit synergistic behavior in the absence and presence of ionic liquid. Several energetic parameters were also estimated with the assistance of regular solution approximation and pseudo phase separation model that indicate micelle formation and adsorption of surfactant at the surface is thermodynamically advantageous. The morphology of pure and mixture of amphiphiles has been estimated by the Tanford and Israelachvili theories. UV-visible spectroscopy was used to quantify the attractive behavior of the drug with surfactant with the help of a binding constant (K).
Analytical Review on Eccentric Axial Compression Behavior of Short and Slender Circular RC Columns Strengthened Using CFRP
Authors: Abid Muhammad , Isleem Haytham F. , Kamal Shah Muhammad Kamal , Zeb Shayan
Published: August 2021

Although reinforced concrete (RC) columns subjected to combined axial compression and flexural loads (i.e., eccentric load) are the most common structural members used in practice, research on FRP-confined circular RC columns subjected to eccentric axial compression has been very limited. More specifically, the available eccentric-loading models were mainly based on existing concentric stress–strain models of FRP-confined unreinforced concrete columns of small scale. The strength and ductility of FRP-strengthened slender circular RC columns predicted using these models showed significant errors. In light of such demand to date, this paper presents a stress–strain model for FRP-confined circular reinforced concrete (RC) columns under eccentric axial compression. The model is mainly based on observations of tests and results reported in the technical literature, in which 207 results of FRP-confined circular unreinforced and reinforced concrete columns were carefully studied and analyzed. A model for the axial-flexural interaction of FRP-confined concrete is also provided. Based on a full parametric analysis, a simple formula of the slenderness limit for FRP-strengthened RC columns is further provided. The proposed model considers the effects of key parameters such as longitudinal and hoop steel reinforcement, level of FRP hoop confinement, slenderness ratio, presence of longitudinal FRP wraps, and varying eccentricity ratio. The accuracy of the proposed model is finally validated through comparisons made between the predictions and the compiled test results.
Construction of Mechanically Reinforced Thermoplastic Polyurethane from Carbon Dioxide-Based Poly(ether carbonate) Polyols via Coordination Cross-Linking
Authors: Gu Gaosheng , Dong Jincheng , Duan Zhongyu , Liu Binyuan
Published: August 2021

Using carbon dioxide-based poly(propylene ether carbonate) diol (PPCD), isophorone diisocyanate (IPDI), dimethylolbutyric acid (DMBA), ferric chloride (FeCl3), and ethylene glycol (EG) as the main raw materials, a novel thermoplastic polyurethane (TPU) is prepared through coordination of FeCl3 and DMBA to obtain TPU containing coordination enhancement directly. The Fourier transform infrared spectroscopy, 1H NMR, gel permeation chromatography, UV−Vis spectroscopy, tensile testing, dynamic mechanical analysis, X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis were explored to characterize chemical structures and mechanical properties of as-prepared TPU. With the increasing addition of FeCl3, the tensile strength and modulus of TPU increase. Although the elongation at break decreases, it still maintains a high level. Dynamic mechanical analysis shows that the glass-transition temperature moves to a high temperature gradually along with the increasing addition of FeCl3. X-ray diffraction results indicate that TPUs reinforced with FeCl3 or not are amorphous polymers. That FeCl3 coordinates with DMBA first is an effective strategy of getting TPU, which is effective and convenient in the industry without the separation of intermediate products. This work confirms that such Lewis acids as FeCl3 can improve and adjust the properties of TPU contenting coordination structures with an in-situ reaction in a low addition amount, which expands their applications in industry and engineering areas.
Modification of Branched Polyethyleneimine Using Mesquite Gum for Its Improved Hemocompatibility
Authors: Pinilla-Torres Ana M. , Carrión-García Paola Y. , Sánchez-Domínguez Celia N. , Gallardo-Blanco Hugo , Sánchez-Domínguez Margarita
Published: August 2021

In the present study, the modification of branched polyethyleneimine (b-PEI) was carried out using mesquite gum (MG) to improve its hemocompatibility to be used in biomedical applications. In the copolymer synthesis process (carboxymethylated mesquite gum grafted polyethyleneimine copolymer (CBX-MG-PEI), an MG carboxymethylation reaction was initially carried out (carboxymethylated mesquite gum (CBX-MG). Subsequently, the functionalization between CBX-MG and b-PEI was carried out using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) as crosslinking agents. The synthesis products were characterized using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). Thermogravimetric analysis showed that CBX-MG and CBX-MG-PEI presented a lower decomposition temperature than MG. The CBX-MG-PEI has a high buffer capacity in the pH range of 4 to 7, similar to the b-PEI. In addition, the CBX-MG-PEI showed an improvement in hemocompatibility in comparison with the b-PEI. The results showed a non-hemolytic property at doses lower than 0.1 µg/mL (CBX-MG-PEI). These results allow us to propose that this copolymer be used in transfection, polymeric nanoparticles, and biomaterials due to its physicochemical and hemocompatibility properties.