bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial Contamination of Photographic and Cinematographic Materials in Archival Funds in the Czech Republic
Authors: Purkrtova Sabina , Savicka Dana , Kadava Jana , Sykorova Hana , Kovacova Nikola , Kalisova Dominika , Nesporova Tereza , Novakova Martina , Masek Benetkova Barbora , Koukalova Lucie , Boryskova Stepanka , Hnulikova Blanka , Durovic Michal , Demnerova Katerina
Published: January 2022

In this study we investigated the microbial contamination of 126 samples of photographic and cinematographic materials from 10 archival funds in the Czech Republic. Microorganisms were isolated from the light-sensitive layer by swabbing it with a polyurethane sponge. Microbial isolates were identified by MALDI-TOF MS (bacteria) or by phenotype testing and microscopy (fungi). Bacterial contamination was more abundant and more diverse than fungal contamination, and both were significantly associated with archives. The most frequently isolated fungal genera were Cladosporium, Eurotium, Penicillium, Aspergillus and Alternaria. The most frequently isolated bacteria were Gram-positive genera such as Staphylococcus, Micrococcus, Kocuria, Streptococcus and Bacillus. This bacterial and fungal diversity suggests that air is the main vehicle of contamination. We also analysed the impact of the type of material used for the carrier (paper, baryta paper, cellulose acetate and nitrate or glass) or the light-sensitive layer (albumen, gelatine, collodion and other) on the level and diversity of microbial contamination. Carriers such as polyester and cellulose nitrate may have a negative impact on bacterial contamination, while paper and baryta paper may have a partially positive impact on both fungal and bacterial contamination.
Effects of Process and Formulation Parameters on Submicron Polymeric Particles Produced by a Rapid Emulsion-Diffusion Method
Authors: Domínguez-Delgado Clara Luisa , Akhtar Zubia , Awuah-Mensah Godfrey , Wu Braden , Smyth Hugh David Charles
Published: January 2022

Emulsification-diffusion method is often used to produce polymeric nanoparticles. However, their numerous and/or lengthy steps make it difficult to use widely. Thus, a modified method using solvent blends (miscible/partially miscible in water, 25–100%) as the organic phases to overcome these disadvantages and its design space were investigated. To further simplify the process, no organic/aqueous phase saturation and no water addition after the emulsification step were performed. Biodegradable (PLGA) or pH-sensitive (Eudragit® E100) nanoparticles were robustly produced using low/medium shear stirring adding dropwise the organic phase into the aqueous phase or vice versa. Several behaviors were also obtained: lowering the partially water-miscible solvent ratio relative to the organic phase or the poloxamer-407 concentration; or increasing the organic phase polarity or the polyvinyl alcohol concentration produced smaller particle sizes/polydispersity. Nanoparticle zeta potential increased as the water-miscible solvent ratio increased. Poloxamer-407 showed better performance to decrease the particle size (~50 nm) at low concentrations (≤1%, w/v) compared with polyvinyl alcohol at 1–5% (w/v), but higher concentrations produced bigger particles/polydispersity (≥600 nm). Most important, an inverse linear correlation to predict the particle size by determining the solubility parameter was found. A rapid method to broadly prepare nanoparticles using straightforward equipment is provided.
Photolysis of Fluorinated Graphites with Embedded Acetonitrile Using a White-Beam Synchrotron Radiation
Authors: Semushkina Galina I. , Fedoseeva Yuliya V. , Makarova Anna A. , Smirnov Dmitry A. , Asanov Igor P. , Pinakov Dmitry V. , Chekhova Galina N. , Okotrub Alexander V. , Bulusheva Lyubov G.
Published: January 2022

Fluorinated graphitic layers with good mechanical and chemical stability, polar C–F bonds, and tunable bandgap are attractive for a variety of applications. In this work, we investigated the photolysis of fluorinated graphites with interlayer embedded acetonitrile, which is the simplest representative of the acetonitrile-containing photosensitizing family. The samples were continuously illuminated in situ with high-brightness non-monochromatized synchrotron radiation. Changes in the compositions of the samples were monitored using X-ray photoelectron spectroscopy and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy. The NEXAFS N K-edge spectra showed that acetonitrile dissociates to form HCN and N2 molecules after exposure to the white beam for 2 s, and the latter molecules completely disappear after exposure for 200 s. The original composition of fluorinated matrices CF0.3 and CF0.5 is changed to CF0.10 and GF0.17, respectively. The highly fluorinated layers lose fluorine atoms together with carbon neighbors, creating atomic vacancies. The edges of vacancies are terminated with the nitrogen atoms and form pyridinic and pyrrolic units. Our in situ studies show that the photolysis products of acetonitrile depend on the photon irradiation duration and composition of the initial CFx matrix. The obtained results evaluate the radiation damage of the acetonitrile-intercalated fluorinated graphites and the opportunities to synthesize nitrogen-doped graphene materials.
Metal–Dielectric Polarization-Preserving Anisotropic Mirror for Chiral Optical Tamm State
Authors: Rudakova Natalya V. , Bikbaev Rashid G. , Pankin Pavel S. , Vetrov Stepan Ya. , Timofeev Ivan V. , Chen Kuo-Ping , Lee Wei
Published: January 2022

This numerical study demonstrates the possibility of exciting a chiral optical Tamm state localized at the interface between a cholesteric liquid crystal and a polarization-preserving anisotropic mirror conjugated to a metasurface. The difference of the proposed structure from a fully dielectric one is that the metasurface makes it possible to decrease the number of layers of a polarization-preserving anisotropic mirror by a factor of more than two at the retained Q-factor of the localized state. It is shown that the proposed structure can be used in a vertically emitting laser.
Encapsulating Metal-Organic-Framework Derived Nanocages into a Microcapsule for Shuttle Effect-Suppressive Lithium-Sulfur Batteries
Authors: Liu Jinyun , Zhu Yajun , Cai Junfei , Zhong Yan , Han Tianli , Chen Zhonghua , Li Jinjin
Published: January 2022

Long-term stable secondary batteries are highly required. Here, we report a unique microcapsule encapsulated with metal organic frameworks (MOFs)-derived Co3O4 nanocages for a Li-S battery, which displays good lithium-storage properties. ZIF-67 dodecahedra are prepared at room temperature then converted to porous Co3O4 nanocages, which are infilled into microcapsules through a microfluidic technique. After loading sulfur, the Co3O4/S-infilled microcapsules are obtained, which display a specific capacity of 935 mAh g−1 after 200 cycles at 0.5C in Li-S batteries. A Coulombic efficiency of about 100% is achieved. The constructed Li-S battery possesses a high rate-performance during three rounds of cycling. Moreover, stable performance is verified under both high and low temperatures of 50 °C and −10 °C. Density functional theory calculations show that the Co3O4 dodecahedra display large binding energies with polysulfides, which are able to suppress shuttle effect of polysulfides and enable a stable electrochemical performance.
LncRNAs Are Differentially Expressed between Wildtype and Cell Line Strains of African Trypanosomes
Authors: Kim Hyung Chul , Jolly Emmitt R.
Published: January 2022

Trypanosoma brucei is a parasitic protist that causes African sleeping sickness. The establishment of T. brucei cell lines has provided a significant advantage for the majority of T. brucei research. However, these cell lines were isolated and maintained in culture for decades, occasionally accumulating changes in gene expression. Since trypanosome strains have been maintained in culture for decades, it is possible that difference may have accumulated in fast-evolving non-coding RNAs between trypanosomes from the wild and those maintained extensively in cultures. To address this, we compared the lncRNA expression profile of trypanosomes maintained as cultured cell lines (CL) to those extracted from human patients, wildtype (WT). We identified lncRNAs from CL and WT from available transcriptomic data and demonstrate that CL and WT have unique sets of lncRNAs expressed. We further demonstrate that the unique and shared lncRNAs are differentially expressed between CL and WT parasites, and that these lncRNAs are more evenly up-regulated and down-regulated than protein-coding genes. We validated the expression of these lncRNAs using qPCR. Taken together, this study demonstrates that lncRNAs are differentially expressed between cell lines and wildtype T. brucei and provides evidence for potential evolution of lncRNAs, specifically in T. brucei maintained in culture.
Adherence to a Mediterranean Diet Is Associated with Lower Depressive Symptoms among U.S. Adults
Authors: Oddo Vanessa M. , Welke Lauren , McLeod Andrew , Pezley Lacey , Xia Yinglin , Maki Pauline , Koenig Mary Dawn , Kominiarek Michelle A. , Langenecker Scott , Tussing-Humphreys Lisa
Published: January 2022

Depression is a leading cause of disability, yet current prevention and treatment approaches have only had modest effects. It is important to better understand the role of dietary patterns on depressive symptoms, which may help prevent depression or complement current treatments. This study examined whether adherence to a Mediterranean diet (Med Diet), determined by the Alternate Med Diet score (aMED), was associated with depressive symptoms in a representative sample of U.S. adults. The aMED score (range 0–9) was calculated from a 24-h diet recall with gender-specific quartiles (Q) estimated. The Patient Health Questionnaire-9 (PHQ-9) was used to define depressive symptoms, which was dichotomized as no to mild (0–9) versus moderate to severe symptoms (10–27). Logistic regression was used to investigate the association between quartiles of aMED and depressive symptoms when controlling for sociodemographics, total calories, and the time of year of diet recall; 7.9% of the sample had moderate to severe depressive symptoms. Compared to individuals with the lowest aMED (Q1), individuals in Q3 and Q4 had 40% and 45% lower odds of moderate to severe depressive symptoms (odds ratio [OR] = 0.60, 95% confidence interval [CI]: 0.50, 0.74; OR = 0.55, 95% CI: 0.36, 0.84, respectively). This study provides modest support of Med Diet’s role in supporting positive mental health.
Early Life and Nutrition and Allergy Development
Authors: Vandenplas Yvan
Published: January 2022

Much evidence has been accumulated over recent years on the importance of the first 1000 days of a child’s life, starting from conception to the postnatal age of two years, with regard to the risk of developing allergic disease [...]
Selenium Deficiency in COVID-19—A Possible Long-Lasting Toxic Relationship
Authors: Schomburg Lutz
Published: January 2022

In the last two years, there has been a surge in the number of publications on the trace element selenium (Se) and selenocysteine-containing selenoproteins in human health, largely due to the pandemic and the multiple roles that this micronutrient and Se-dependent selenoproteins play in various aspects of the disease [...]
Emerging Roles of Vitamin D-Induced Antimicrobial Peptides in Antiviral Innate Immunity
Authors: White John H.
Published: January 2022

Vitamin D deficiency, characterized by low circulating levels of calcifediol (25-hydroxyvitamin D, 25D) has been linked to increased risk of infections of bacterial and viral origin. Innate immune cells produce hormonal calcitriol (1,25-dihydroxyvitamin D, 1,25D) locally from circulating calcifediol in response to pathogen threat and an immune-specific cytokine network. Calcitriol regulates gene expression through its binding to the vitamin D receptor (VDR), a ligand-regulated transcription factor. The hormone-bound VDR induces the transcription of genes integral to innate immunity including pattern recognition receptors, cytokines, and most importantly antimicrobial peptides (AMPs). Transcription of the human AMP genes β-defensin 2/defensin-β4 (HBD2/DEFB4) and cathelicidin antimicrobial peptide (CAMP) is stimulated by the VDR bound to promoter-proximal vitamin D response elements. HDB2/DEFB4 and the active form of CAMP, the peptide LL-37, which form amphipathic secondary structures, were initially characterized for their antibacterial actively. Notably, calcitriol signaling induces secretion of antibacterial activity in vitro and in vivo, and low circulating levels of calcifediol are associated with diverse indications characterized by impaired antibacterial immunity such as dental caries and urinary tract infections. However, recent work has also provided evidence that the same AMPs are components of 1,25D-induced antiviral responses, including those against the etiological agent of the COVID-19 pandemic, the SARS-CoV2 coronavirus. This review surveys the evidence for 1,25D-induced antimicrobial activity in vitro and in vivo in humans and presents our current understanding of the potential mechanisms by which CAMP and HBD2/DEFB4 contribute to antiviral immunity.
Young Adults with Higher Salt Intake Have Inferior Hydration Status: A Cross-Sectional Study
Authors: Zhang Jianfen , Zhang Na , Liu Shufang , Du Songming , Ma Guansheng
Published: January 2022

The body’s water and sodium balances are tightly regulated and monitored by the brain. Few studies have explored the relationship between water and salt intake, and whether sodium intake with different levels of fluid intake leads to changes in hydration status remains unknown. The aim of the present study was to determine the patterns of water intake and hydration status among young adults with different levels of daily salt intakes. Participants’ total drinking fluids and water from food were determined by a 7-day 24-h fluid intake questionnaire for 7 days (from Day 1 to Day 7) and duplicate portion method (Day 5, Day 6 and Day 7). Urine of 24 h for 3 days (Day 5, Day 6 and Day 7) was collected and tested for the osmolality, the urine-specific gravity (USG), the concentrations of electrolytes, pH, creatinine, uric acid and the urea. The fasting blood samples for 1 day (Day 6) were collected and measured for the osmolality and the concentrations of electrolytes. The salt intakes of the participants were evaluated from the concentrations of Na of 24 h urine of 3 days (Day 5, Day 6 and Day 7). Participants were divided into four groups according to the quartile of salt intake, including the low salt intake (LS1), LS2, high salt intake (HS1) and HS2 groups. In total, 156 participants (including 80 male and 76 female young adults) completed the study. The salt intakes were 7.6, 10.9, 14.7 and 22.4 g among participants in the four groups (LS1, LS2, HS1 and HS2 groups, respectively), which differed significantly in all groups (F = 252.020; all p < 0.05). Compared to the LS1 and LS2 groups, the HS2 group had 310–381, 250–358 and 382–655 mL more amounts of water from the total water intake (TWI), total drinking fluids and water from food (all p < 0.05), respectively. Participants in the HS2 group had 384–403, 129–228 and 81–114 mL more in the water, water from dishes and staple foods, respectively, than those in the groups of LS1 and LS2 (p < 0.05). The HS2 group excreted 386–793 mL more urine than those in the groups of LS1 and LS2 (p < 0.05). However, regarding urine osmolality, the percentage of participants with optimal hydration status decreased from 41.0% in LS1 and LS2 to 25.6% in the HS2 group (p < 0.05). Participants with higher salt intake had higher TWI, total drinking fluids and water from food. Nevertheless, they had inferior hydration status. A reduction in salt intake should be encouraged among young adults to maintain optimal hydration status.
Effects of 2-Methoxyestradiol, a Main Metabolite of Estradiol on Hepatic ABCA1 Expression in HepG2 Cells
Authors: Ibata Tomohiro , Lyu Jingya , Imachi Hitomi , Fukunaga Kensaku , Sato Seisuke , Kobayashi Toshihiro , Saheki Takanobu , Yoshimura Takafumi , Murao Koji
Published: January 2022

ATP-binding cassette transporter A1 (ABCA1) is a key regulator of lipid efflux, and the absence of ABCA1 induces hepatic lipid accumulation, which is one of the major causes of fatty liver. 2-Methoxyestradiol (2-ME2) has been demonstrated to protect against fatty liver. In this study, we investigated the effects of 2-ME2 on the hepatic lipid content and ABCA1 expression. We found that 2-ME2 dose-dependently increased ABCA1 expression, and therefore, the lipid content was significantly decreased in HepG2 cells. 2-ME2 enhanced the ABCA1 promoter activity; however, this effect was reduced after the inhibition of the PI3K pathway. The overexpression of Akt or p110 induced ABCA1 promoter activity, while dominant-negative Akt diminished the ability of 2-ME2 on ABCA1 promoter activity. Further, 2-ME2 stimulated the rapid phosphorylation of Akt and FoxO1 and reduced the nuclear accumulation of FoxO1. Chromatin immunoprecipitation confirmed that FoxO1 bonded to the ABCA1 promoter region. The binding was reduced by 2-ME2, which facilitated ABCA1 gene transcription. Furthermore, mutating FoxO1-binding sites in the ABCA1 promoter region or treatment with FoxO1-specific siRNA disrupted the effect of 2-ME2 on ABCA1 expression. All of our results demonstrated that 2-ME2 might upregulate ABCA1 expression via the PI3K/Akt/FoxO1 pathway, which thus reduces the lipid content in hepatocytes.
Association between Milk Intake and All-Cause Mortality among Chinese Adults: A Prospective Study
Authors: Na Xiaona , Lan Hanglian , Wang Yu , Tan Yuefeng , Zhang Jian , Zhao Ai
Published: January 2022

Background: Little is known about the effect of milk intake on all-cause mortality among Chinese adults. The present study aimed to explore the association between milk intake and all-cause mortality in the Chinese population. Methods: Data from 1997 to 2015 of the China Health and Nutrition Survey (CHNS) were used. A total of 14,738 participants enrolled in the study. Dietary data were obtained by three day 24-h dietary recall. All-cause mortality was assessed according to information reported. The association between milk intake and all-cause mortality were explored using Cox regression and further stratified with different levels of dietary diversity score (DDS) and energy intake. Results: 11,975 (81.25%) did not consume milk, 1341 (9.10%) and 1422 (9.65%) consumed 0.1–2 portions/week and >2 portions/week, respectively. Milk consumption of 0.1–2 portions/week was related to the decreased all-cause mortality (HR: 0.59, 95% CI: 0.41–0.85). In stratified analysis, consuming 0.1–2 portions/week was associated with decreased all-cause mortality among people with high DDS and energy intake. Conclusions: Milk intake is low among Chinese adults. Consuming 0.1–2 portions of milk/week might be associated with the reduced risk of death among Chinese adults by advocating health education. Further research is required to investigate the relationships between specific dairy products and cause-specific mortality.
Changes in Total Energy, Nutrients and Food Group Intake among Children and Adolescents during the COVID-19 Pandemic—Results of the DONALD Study
Authors: Perrar Ines , Alexy Ute , Jankovic Nicole
Published: January 2022

The COVID-19 pandemic may have changed the habitual lifestyles of children and adolescents, in particular, due to the closure of kindergartens and schools. To investigate the impact of the pandemic on nutrients and food intake of children and adolescents in Germany, we analyzed repeated 3-day weighed dietary records from 108 participants (3–18 years; females: n = 45, males: n = 63) of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study. Polynomial mixed-effects regression models were used to identify prospective changes in dietary intake (total energy (TEI), carbohydrates, fat, protein, free sugar, ultra-processed foods, fruits and vegetables, sugar sweetened beverages and juices) before and during the first months of the COVID-19 pandemic. For the current analysis, we have chosen the first months of the pandemic (March 2020–August 2020), as this was the period with the most restrictions in Germany so far (kindergarten, school and restaurant closures; contact and outdoor activity restrictions). No significant changes in either the selected nutrients or food groups were observed. However, children and adolescents recorded a significantly lower TEI during the pandemic (β = −109.65, p = 0.0062). Results remained significant after the exclusion of participants with under-reported records (β = −95.77, p = 0.0063). While macronutrient intake did not change, descriptive data indicate a non-significant decrease in sugar sweetened beverages and ultra-processed foods intake. We suggest that children and adolescents from high socioeconomic families may have adapted lifestyle changes during the pandemic.
Successful Treatment with Corticosteroids in an 11-Year-Old Patient with Crohn’s Disease and Myopericarditis—Case Report
Authors: Ryzko Joanna , Zdanowicz Katarzyna , Lebensztejn Dariusz Marek , Daniluk Urszula
Published: January 2022

Extraintestinal manifestations (EIMs) are observed in 15–20% of patients with inflammatory bowel disease (IBD). One of the rare EIMs is myocarditis, the incidence of which is estimated at around 1%. The main cause of myocarditis is a viral infection. Other causes include autoimmune diseases and drug complications (sulfasalazine, mesalazine). We present the case of an 11-year-old girl with Crohn’s disease (CD) with EIMs, manifested as hip joint inflammation and erythema nodosum. At the same time, the symptoms of myopericarditis appeared with changes in electrocardiogram (ECG), echocardiography and high troponin I concentration. Therapy with corticosteroids resulted in the resolution of skin lesions and cardiological symptoms. Systemic connective tissue diseases, viral and bacterial infections were excluded in the differential diagnosis. The suspicion of mesalazine-induced EIMs was also ruled out as the symptoms resolved despite continued therapy with mesalazine. No further recurrences of myopericarditis were observed.
In Silico-Based Discovery of Natural Anthraquinones with Potential against Multidrug-Resistant E. coli
Authors: Alhadrami Hani A. , Abdulaal Wesam H. , Hassan Hossam M. , Alhakamy Nabil A. , Sayed Ahmed M.
Published: January 2022

E. coli is a Gram-negative bacterium that causes different human infections. Additionally, it resists common antibiotics due to its outer protective membrane. Natural products have been proven to be efficient antibiotics. However, plant natural products are far less explored in this regard. Accordingly, over 16,000 structures covering almost all African medicinal plants in AfroDb in a structural-based virtual screening were used to find efficient anti-E. coli candidates. These drug-like structures were docked into the active sites of two important molecular targets (i.e., E. coli’s Ddl-B and Gyr-B). The top-scoring hits (i.e., got docking scores < −10 kcal/mol) produced in the initial virtual screening (0.15% of the database structures for Ddl-B and 0.17% of the database structures for Gyr-B in the database) were further refined using molecular dynamic simulation-based binding free energy (ΔG) calculation. Anthraquinones were found to prevail among the retrieved hits. Accordingly, readily available anthraquinone derivatives (10 hits) were selected, prepared, and tested in vitro against Ddl-B, Gyr-B, multidrug-resistant (MDR) E. coli, MRSA, and VRSA. A number of the tested derivatives demonstrated strong micromolar enzyme inhibition and antibacterial activity against E. coli, MRSA, and VRSA, with MIC values ranging from 2 to 64 µg/mL. Moreover, both E. coli’s Ddl-B and Gyr-B were inhibited by emodin and chrysophanol with IC50 values comparable to the reference inhibitors (IC50 = 216 ± 5.6, 236 ± 8.9 and 0.81 ± 0.3, 1.5 ± 0.5 µM for Ddl-B and Gyr-B, respectively). All of the active antibacterial anthraquinone hits showed low to moderate cellular cytotoxicity (CC50 > 50 µM) against human normal fibroblasts (WI-38). Furthermore, molecular dynamic simulation (MDS) experiments were carried out to reveal the binding modes of these inhibitors inside the active site of each enzyme. The findings presented in this study are regarded as a significant step toward developing novel antibacterial agents against MDR strains.
Disrupting GPCR Complexes with Smart Drug-like Peptides
Authors: Gallo Maria , Defaus Sira , Andreu David
Published: January 2022

G protein-coupled receptors (GPCRs) are a superfamily of proteins classically described as monomeric transmembrane (TM) receptors. However, increasing evidence indicates that many GPCRs form higher-order assemblies made up of monomers pertaining to identical (homo) or to various (hetero) receptors. The formation and structure of these oligomers, their physiological role and possible therapeutic applications raise a variety of issues that are currently being actively explored. In this context, synthetic peptides derived from TM domains stand out as powerful tools that can be predictably targeted to disrupt GPCR oligomers, especially at the interface level, eventually impairing their action. However, despite such potential, TM-derived, GPCR-disrupting peptides often suffer from inadequate pharmacokinetic properties, such as low bioavailability, a short half-life or rapid clearance, which put into question their therapeutic relevance and promise. In this review, we provide a comprehensive overview of GPCR complexes, with an emphasis on current studies using GPCR-disrupting peptides mimicking TM domains involved in multimerization, and we also highlight recent strategies used to achieve drug-like versions of such TM peptide candidates for therapeutic application.
Design of Oral Sustained-Release Pellets by Modeling and Simulation Approach to Improve Compliance for Repurposing Sobrerol
Authors: Lu Chu-Hsun , Huang Yu-Feng , Chu I-Ming
Published: January 2022

Sobrerol, an oral mucolytic agent, in a recent study showed promise for treating multiple sclerosis. A human equivalent dose of 486 mg of sobrerol administered thrice daily (i.e., 1459 mg of daily dose) demonstrated the highest therapeutic efficacy for repurposing use, which also points out the poor compliance of administration. In this study, oral sustained-release pellets of sobrerol were successfully developed with evaluated manufacturing conditions and drug release kinetics. For design of the target drug product, we used a modeling and simulation approach to establish a predictive model of oral pharmacokinetic profile, by exploring the characteristics and correlations corresponding to the pharmacokinetics and pharmacodynamics of sobrerol, such as absorption lag time (0.18 h), time-scaling in vitro–in vivo correlation (tin-vitro = 0.494 tin-vivo − 0.0904), gastrointestinal transit time (8 h), minimum effective concentration (1.61 μg/mL), and duration of action (12.8 h). Results showed that the frequency of administration and the daily dose remarkably reduced by 33.3% (i.e., from thrice to twice daily) and 22.8%, respectively, which indicates that this prototype approach can be adopted for rapidly developing a modified-release dosage form of sobrerol, with improvement of compliance of administration and therapeutic efficacy.
Polyphosphazene-Based Nanocarriers for the Release of Camptothecin and Epirubicin
Authors: Quiñones Javier Pérez , Roschger Cornelia , Iturmendi Aitziber , Henke Helena , Zierer Andreas , Peniche-Covas Carlos , Brüggemann Oliver
Published: January 2022

The design and study of efficient polymer-based drug delivery systems for the controlled release of anticancer drugs is one of the pillars of nanomedicine. The fight against metastatic and invasive cancers demands therapeutic candidates with increased and selective toxicity towards malignant cells, long-term activity and reduced side effects. In this sense, polyphosphazene nanocarriers were synthesized for the sustained release of the anticancer drugs camptothecin (CPT) and epirubicin (EPI). Linear poly(dichloro)phosphazene was modified with lipophilic tocopherol or testosterone glycinate, with antioxidant and antitumor activity, and with hydrophilic Jeffamine M1000 to obtain different polyphosphazene nanocarriers. It allowed us to encapsulate the lipophilic CPT and the more hydrophilic EPI. The encapsulation process was carried out via solvent exchange/precipitation, attaining a 9.2–13.6 wt% of CPT and 0.3–2.4 wt% of EPI. CPT-loaded polyphosphazenes formed 140–200 nm aggregates in simulated body physiological conditions (PBS, pH 7.4), resulting in an 80–100-fold increase of CPT solubility. EPI-loaded polyphosphazenes formed 250 nm aggregates in an aqueous medium. CPT and EPI release (PBS, pH 7.4, 37 °C) was monitored for 202 h, being almost linear during the first 8 h. The slow release of testosterone and tocopherol was also sustained for 150 h in PBS (pH 7.4 and 6.0) at 37 °C. The co-delivery of testosterone or tocopherol and the anticancer drugs from the nanocarriers was expected. Cells of the human breast cancer cell line MCF-7 demonstrated good uptake of anticancer-drug-loaded nanocarriers after 6 h. Similarly, MCF-7 spheroids showed good uptake of the anticancer-drug-loaded aggregates after 72 h. Almost all anticancer-drug-loaded polyphosphazenes exhibited similar or superior toxicity against MCF-7 cells and spheroids when compared to raw anticancer drugs. Additionally, cell-cycle arrest in the G2/M phase was increased in response to the drug-loaded nanocarriers. Almost no toxicity of anticancer-drug-loaded aggregates against primary human lung fibroblasts was observed. Furthermore, the aggregates displayed no hemolytic activity, which is in contrast to the parent anticancer drugs. Consequently, synthesized polyphosphazene-based nanocarriers might be potential nanomedicines for chemotherapy.
Evaluation of the Mucoadhesive Properties of Chitosan-Based Microstructured Lipid Carrier (CH-MLC)
Authors: Guerini Marta , Condrò Giorgia , Perugini Paola
Published: January 2022

Different mucoadhesive systems have been studied in recent years to increase the residence time of the delivery systems and to prolong the release of the drug. The aim of this work was to evaluate the mucoadhesive properties of chitosan-based Microstructured Lipid Carrier (CH-MLC) with a new approach which requires chitosan and mucin to be compacted into a tablet and mucoadhesion to be assessed on a non-mucoadhesive substrate. This type of test showed that chitosan maintains a close bond with mucin even in the presence of a fluid and even encapsulated in microparticles. After this, using a bioreactor, the release of N-acetylcysteine (NAC) from the microparticles (NA-CH-MLC) through a layer of mucus mimicking the pathological conditions of a patient with cystic fibrosis was tested. The release of the active from NAC-CH-MLC demonstrated how the chitosan inside the microparticles acts as a penetration enhancer and how the microparticles can impart a prolonged release over time.
Development and Evaluation of an In Silico Dermal Absorption Model Relevant for Children
Authors: Yun Yejin Esther , Calderon-Nieva Daniella , Hamadeh Abdullah , Edginton Andrea N.
Published: January 2022

The higher skin surface area to body weight ratio in children and the prematurity of skin in neonates may lead to higher chemical exposure as compared to adults. The objectives of this study were: (i) to provide a comprehensive review of the age-dependent anatomical and physiological changes in pediatric skin, and (ii) to construct and evaluate an age-dependent pediatric dermal absorption model. A comprehensive review was conducted to gather data quantifying the differences in the anatomy and physiology of child and adult skin. Maturation functions were developed for model parameters that were found to be age-dependent. A pediatric dermal absorption model was constructed by updating a MoBi implementation of the Dancik et al. 2013 skin permeation model with these maturation functions. Using a workflow for adult-to-child model extrapolation, the predictive performance of the model was evaluated by comparing its predicted rates of flux of diamorphine, phenobarbital and buprenorphine against experimental observations using neonatal skin. For diamorphine and phenobarbital, the model provided reasonable predictions. The ratios of predicted:observed flux in neonates for diamorphine ranged from 0.55 to 1.40. For phenobarbital, the ratios ranged from 0.93 to 1.26. For buprenorphine, the model showed acceptable predictive performance. Overall, the physiologically based pediatric dermal absorption model demonstrated satisfactory prediction accuracy. The prediction of dermal absorption in neonates using a model-based approach will be useful for both drug development and human health risk assessment.
Drug Repurposing for the Identification of Compounds with Anti-SARS-CoV-2 Capability via Multiple Targets
Authors: Yu Pei-Chen , Huang Chen-Hao , Kuo Chih-Jung , Liang Po-Huang , Wang Lily Hui-Ching , Pan Max Yu-Chen , Chang Sui-Yuan , Chao Tai-Ling , Ieong Si-Man , Fang Jun-Tung , Huang Hsuan-Cheng , Juan Hsueh-Fen
Published: January 2022

Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spreading worldwide, causing hundreds of millions of infections. Despite the development of vaccines, insufficient protection remains a concern. Therefore, the screening of drugs for the treatment of coronavirus disease 2019 (COVID-19) is reasonable and necessary. This study utilized bioinformatics for the selection of compounds approved by the U.S. Food and Drug Administration with therapeutic potential in this setting. In addition, the inhibitory effect of these compounds on the enzyme activity of transmembrane protease serine 2 (TMPRSS2), papain-like protease (PLpro), and 3C-like protease (3CLpro) was evaluated. Furthermore, the capability of compounds to attach to the spike-receptor-binding domain (RBD) was considered an important factor in the present assessment. Finally, the antiviral potency of compounds was validated using a plaque reduction assay. Our funnel strategy revealed that tamoxifen possesses an anti-SARS-CoV-2 property owing to its inhibitory performance in multiple assays. The proposed time-saving and feasible strategy may accelerate drug screening for COVID-19 and other diseases.
Theoretical Comparison of Optothermal Absorption in Transmissive Metalenses Composed of Nanobricks and Nanoholes
Authors: Tang Feng , Li Qingzhi , Yu Haichao , Yi Zao , Ye Xin
Published: January 2022

Background: Optical components with high damage thresholds are very desirable in intense-light systems. Metalenses, being composed of phase-control nanostructures with peculiar properties, are one of the important component candidates in future optical systems. However, the optothermal mechanism in metalenses is still not investigated adequately. Methods: In this study, the optothermal absorption in transmissive metalenses made of silicon nanobricks and nanoholes is investigated comparatively to address this issue. Results: The geometrical dependencies of nanostructures’ transmittance, phase difference, and field distribution are calculated numerically via simulations. To demonstrate the optothermal mechanism in metalenses, the mean absorption efficiencies of the selected unit-cells, which would constitute metalenses, are analyzed. The results show that the electric field in the silicon zone would lead to an obvious thermal effect, and the enhancement of the localized electric field also results in the strong absorption of optical energy. Then, two typical metalenses are designed based on these nanobricks and nanoholes. The optothermal simulations show that the nanobrick-based metalens can handle a power density of 0.15 W/µm2, and the density of the nanohole-based design is 0.12 W/µm2. Conclusions: The study analyzes and compares the optothermal absorption in nanobricks and nanoholes, which shows that the electric-field distribution in absorbent materials and the localized-field enhancement are the two key effects that lead to optothermal absorption. This study provides an approach to improve the anti-damage potentials of transmissive metalenses for intense-light systems.
Comparative Investigation of Cellular Effects of Polyethylene Glycol (PEG) Derivatives
Authors: Pham Le Khanh Ha , Nemes Dániel , Rusznyák Ágnes , Ujhelyi Zoltán , Fehér Pálma , Fenyvesi Ferenc , Váradi Judit , Vecsernyés Miklós , Bácskay Ildikó
Published: January 2022

Nowadays, polyethylene glycols referred to as PEGs are widely used in cosmetics, consumer care products, and the pharmaceutical industry. Their advantageous properties such as chemical stability, low immunogenicity, and high tolerability explain why PEGs are applied in many fields of pharmaceutical formulations including parenteral, topical, ophthalmic, oral, and rectal preparations and also in modern drug delivery systems. Given their extensive use, they are considered a well-known group of chemicals. However, the number of large-scale comparative studies involving multiple PEGs of wide molecular weight range is low, as in most cases biological effects are estimated upon molecular weight. The aim of this publication was to study the action of PEGs on Caco-2 cells and G. mellonella larvae and to calculate the correlation of these effects with molecular weight and osmolality. Eleven PEGs of different molecular weight were used in our experiments: PEG 200, PEG 300, PEG 400, PEG 600, PEG 1000, PEG 1500, PEG 4000, PEG 8000, PEG 10,000, 12,000, and PEG 20,000. The investigated cellular effects included cytotoxicity (MTT and Neutral Red assays, flow cytometry with propidium iodide and annexin V) and autophagy. The osmolality of different molecular weight PEGs with various concentrations was measured by a vapor pressure osmometer OSMOMAT 070 and G. mellonella larvae were injected with the solutions of PEGs. Sorbitol was used as controls of the same osmolality. Statistical correlation was calculated to describe the average molecular weight dependence of the different measured effects. Osmolality, the cytotoxicity assays, flow cytometry data, and larvae mortality had significant correlation with the structure of the PEGs, while autophagosome formation and the proportion of early apoptotic cells showed no statistical correlation. Overall, it must be noted that PEGs must be tested individually for biological effects as not all effects can be estimated by the average molecular weight.
Effects of Different Mold Materials and Coolant Media on the Cooling Performance of Epoxy-Based Injection Molds
Authors: Kuo Chil-Chyuan , Xu Jing-Yan , Zhu Yi-Jun , Lee Chong-Hao
Published: January 2022

Metal additive manufacturing techniques are frequently applied to the manufacturing of injection molds with a conformal cooling channel (CCC) in order to shorten the cooling time in the injection molding process. Reducing the cooling time in the cooling stage is essential to reducing the energy consumption in mass production. However, the distinct disadvantages include higher manufacturing costs and longer processing time in the fabrication of injection mold with CCC. Rapid tooling technology (RTT) is a widely utilized technology to shorten mold development time in the mold industry. In principle, the cooling time of injection molded products is affected by both injection mold material and coolant medium. However, little work has been carried out to investigate the effects of different mold materials and coolant media on the cooling performance of epoxy-based injection molds quantitatively. In this study, the effects of four different coolant media on the cooling performance of ten sets of injection molds fabricated with different mixtures were investigated experimentally. It was found that cooling water with ultrafine bubble is the best cooling medium based on the cooling efficiency of the injection molded parts (since the cooling efficiency is increased further by about 12.4% compared to the conventional cooling water). Mold material has a greater influence on the cooling efficiency than the cooling medium, since cooling time range of different mold materials is 99 s while the cooling time range for different cooling media is 92 s. Based on the total production cost of injection mold and cooling efficiency, the epoxy resin filled with 41 vol.% aluminum powder is the optimal formula for making an injection mold since saving in the total production cost about 24% is obtained compared to injection mold made with commercially available materials.
The Influence of Synthesis Method on Characteristics of Buffer and Organic Solutions of Thermo- and pH-Responsive Poly(N-[3-(diethylamino)propyl]methacrylamide)s
Authors: Simonova Maria , Kamorin Denis , Sadikov Anton , Filippov Alexander , Kazantsev Oleg
Published: January 2022

Thermo- and pH-responsive poly(N-[3-(diethylamino)propyl]methacrylamide)s were synthesized by free radical polymerization and RAFT polymerization. The molar masses of the samples were 33,000–35,000 g∙mol−1. Investigations of the dilute solutions showed that the prepared samples were flexible chain polymers. The behavior of the synthesized polymers in the buffer solutions was analyzed by turbidity and light scattering at a pH range of 7–13 and a concentration range of 0.0002–0.008 g·cm−3. When the concentrated solutions were at a low temperature, there were macromolecules and aggregates, which were formed due to the interaction of hydrophobic units. For the investigated samples, the lower critical solution temperatures were equal. The phase separation temperatures decreased as pH increased. The influence of polydispersity index on the characteristics of the samples in the solutions was analyzed. The radii of molecules of poly(N-[3-(diethylamino)propyl]methacrylamide) obtained by RAFT polymerization at this temperature at the onset and end of the phase separation interval were lower than ones for samples synthesized by conventional free radical polymerization.
Iodine Immobilized UiO-66-NH2 Metal-Organic Framework as an Effective Antibacterial Additive for Poly(ε-caprolactone)
Authors: Chen Wei , Zhu Ping , Chen Yating , Liu Yage , Du Liping , Wu Chunsheng
Published: January 2022

Iodine has been widely used as an effective disinfectant with broad-spectrum antimicrobial potency. However, the application of iodine in an antibacterial polymer remains challenging due to its volatile nature and poor solubility. Herein, iodine immobilized UiO-66-NH2 metal-organic framework (MOF) (UiO66@I2) with a high loading capacity was synthesized and used as an effective antibacterial additive for poly(ε-caprolactone) (PCL). An orthogonal design approach was used to achieve the optimal experiments’ conditions in iodine adsorption. UiO66@I2 nanoparticles were added to the PCL matrix under ultrasonic vibration and evaporated the solvent to get a polymer membrane. The composites were characterized by SEM, XRD, FTIR, and static contact angle analysis. UiO-66-NH2 nanoparticles have a high iodine loading capacity, up to 18 wt.%. The concentration of iodine is the most important factor in iodine adsorption. Adding 0.5 wt.% or 1.0 wt.% (equivalent iodine content) of UiO66@I2 to the PCL matrix had no influence on the structure of PCL but reduces the static water angle. The PCL composites showed strong antibacterial activities against Staphylococcus aureus and Escherichia coli. In contrast, the same content of free iodine/PCL composites had no antibacterial activity. The difference in the antibacterial performance was due to the different iodine contents in the polymer composites. It was found that MOF nanoparticles could retain most of the iodine during the sample preparation and storage, while there was few iodine left in the free iodine/PCL composites. This study offers a common and simple way to immobilize iodine and prepare antibacterial polymers with low antiseptic content that would reduce the influence of an additive on polymers’ physical properties.
Cellulose-Based Nanofibers Processing Techniques and Methods Based on Bottom-Up Approach—A Review
Authors: Kramar Ana , González-Benito Francisco Javier
Published: January 2022

In the past decades, cellulose (one of the most important natural polymers), in the form of nanofibers, has received special attention. The nanofibrous morphology may provide exceptional properties to materials due to the high aspect ratio and dimensions in the nanometer range of the nanofibers. The first feature may lead to important consequences in mechanical behavior if there exists a particular orientation of fibers. On the other hand, nano-sizes provide a high surface-to-volume ratio, which can have important consequences on many properties, such as the wettability. There are two basic approaches for cellulose nanofibers preparation. The top-down approach implies the isolation/extraction of cellulose nanofibrils (CNFs) and nanocrystals (CNCs) from a variety of natural resources, whereby dimensions of isolates are limited by the source of cellulose and extraction procedures. The bottom-up approach can be considered in this context as the production of nanofibers using various spinning techniques, resulting in nonwoven mats or filaments. During the spinning, depending on the method and processing conditions, good control of the resulting nanofibers dimensions and, consequently, the properties of the produced materials, is possible. Pulp, cotton, and already isolated CNFs/CNCs may be used as precursors for spinning, alongside cellulose derivatives, namely esters and ethers. This review focuses on various spinning techniques to produce submicrometric fibers comprised of cellulose and cellulose derivatives. The spinning of cellulose requires the preparation of spinning solutions; therefore, an overview of various solvents is presented showing their influence on spinnability and resulting properties of nanofibers. In addition, it is shown how bottom-up spinning techniques can be used for recycling cellulose waste into new materials with added value. The application of produced cellulose fibers in various fields is also highlighted, ranging from drug delivery systems, high-strength nonwovens and filaments, filtration membranes, to biomedical scaffolds.
NIR and Reduction Dual-Sensitive Polymeric Prodrug Nanoparticles for Bioimaging and Combined Chemo-Phototherapy
Authors: Li Shuying , Wu Yanjuan , Xue Xiukun , Liu Siyuan
Published: January 2022

The combination of chemotherapy, photothermal therapy (PTT) and photodynamic therapy (PDT) based on a single nanosystem is highly desirable for cancer treatment. In this study, we developed a versatile Pt(IV) prodrug-based nanodrug, PVPt@Cy NPs, to realize synchronous chemotherapy, PDT and PTT and integrate cancer treatment with bioimaging. To construct PVPt@Cy NPs, the amphiphilic Pt(IV)-based polymeric prodrug PVPt was synthesized by a facile one-pot coupling reaction, and then it was used to encapsulate an optotheranostic agent (HOCyOH, Cy) via hydrophobic interaction-induced self-assembly. These NPs would disaggregate under acidic, reductive conditions and NIR irradiation, which are accompanied by photothermal conversion and reactive oxygen species (ROS) generation. Moreover, the PVPt@Cy NPs exhibited an enhanced in vitro anticancer efficiency with 808-nm light irradiation. Furthermore, the PVPt@Cy NPs showed strong NIR fluorescence and photothermal imaging in H22 tumor-bearing mice, allowing the detection of the tumor site and monitoring of the drug biodistribution. Therefore, PVPt@Cy NPs displayed an enormous potential in combined chemo-phototherapy.