bluuebunny/crossref_metadata_2025 huggingface dataset:
The Combination of Liposomes and Metallic Nanoparticles as Multifunctional Nanostructures in the Therapy and Medical Imaging—A Review
Authors: Musielak Marika , Potoczny Jakub , Boś-Liedke Agnieszka , Kozak Maciej
Published: June 2021

Nanotechnology has introduced a new quality and has definitely developed the possibilities of treating and diagnosing various diseases. One of the scientists’ interests is liposomes and metallic nanoparticles (LipoMNPs)—the combination of which has introduced new properties and applications. However, the field of creating hybrid nanostructures consisting of liposomes and metallic nanoparticles is relatively little understood. The purpose of this review was to compile the latest reports in the field of treatment and medical imaging using of LipoMNPs. The authors focused on presenting this issue in the direction of improving the used conventional treatment and imaging methods. Most of all, the nature of bio-interactions between nanostructures and cells is not sufficiently taken into account. As a result, overcoming the existing limitations in the implementation of such solutions in the clinic is difficult. We concluded that hybrid nanostructures are used in a very wide range, especially in the treatment of cancer and magnetic resonance imaging. There were also solutions that combine treatments with simultaneous imaging, creating a theragnostic approach. In the future, researchers should focus on the description of the biological interactions and the long-term effects of the nanostructures to use LipoMNPs in the treatment of patients.
Superior Alignment of Human iPSC-Osteoblasts Associated with Focal Adhesion Formation Stimulated by Oriented Collagen Scaffold
Authors: Ozasa Ryosuke , Matsugaki Aira , Matsuzaka Tadaaki , Ishimoto Takuya , Yun Hui-Suk , Nakano Takayoshi
Published: June 2021

Human-induced pluripotent stem cells (hiPSCs) can be applied in patient-specific cell therapy to regenerate lost tissue or organ function. Anisotropic control of the structural organization in the newly generated bone matrix is pivotal for functional reconstruction during bone tissue regeneration. Recently, we revealed that hiPSC-derived osteoblasts (hiPSC-Obs) exhibit preferential alignment and organize in highly ordered bone matrices along a bone-mimetic collagen scaffold, indicating their critical role in regulating the unidirectional cellular arrangement, as well as the structural organization of regenerated bone tissue. However, it remains unclear how hiPSCs exhibit the cell properties required for oriented tissue construction. The present study aimed to characterize the properties of hiPSCs-Obs and those of their focal adhesions (FAs), which mediate the structural relationship between cells and the matrix. Our in vitro anisotropic cell culture system revealed the superior adhesion behavior of hiPSC-Obs, which exhibited accelerated cell proliferation and better cell alignment along the collagen axis compared to normal human osteoblasts. Notably, the oriented collagen scaffold stimulated FA formation along the scaffold collagen orientation. This is the first report of the superior cell adhesion behavior of hiPSC-Obs associated with the promotion of FA assembly along an anisotropic scaffold. These findings suggest a promising role for hiPSCs in enabling anisotropic bone microstructural regeneration.
Semi-Automated Cell Panning for Efficient Isolation of FGFR3-Targeting Antibody
Authors: Min Byeongkwi , Yoo Minyoung , Kim Hyeree , Cho Minjung , Nam Do-Hyun , Yoon Yeup
Published: June 2021

Phage display technology is a widely used practical tool for isolating binding molecules against the desired targets in phage libraries. In the case of targeting the membrane protein with its natural conformation, conventional bio-panning has limitations on the efficient screening of the functionally relevant antibodies. To enrich the single-chain variable fragment (scFv) pools for recognizing the natural conformation of the membrane targets, the conventional bio-panning and screening process was modified to include the semi-automated cell panning protocol. Using FGFR3-overexpressing patient-derived cancer cells, biotin-X-DHPE was introduced and coupled to Streptavidin-coated magnetic beads for use in the solution-phage bio-panning procedure. The resulting clones of scFv were compared to the diversity of the binding region, especially on CDR-H3. The clones enriched further by cell-based panning procedure possessed a similar binding site and the CDR-H3 loop structure. The resulting antibodies inhibited cell growth and induced target degradation. This process may be a useful tool for screening biologically related antibodies that recognize natural conformational structure on cell membrane protein. Furthermore, cell-based panning has the potential to further expand to a high-throughput screening (HTS) system and automation process.
3D Clumps/Extracellular Matrix Complexes of Periodontal Ligament Stem Cells Ameliorate the Attenuating Effects of LPS on Proliferation and Osteogenic Potential
Authors: Banavar Spoorthi Ravi , Rawal Swati Yeshwant , Pulikkotil Shaju Jacob , Daood Umer , Paterson Ian C. , Davamani Fabian Amalraj , Kajiya Mikihito , Kurihara Hidemi , Khoo Suan Phaik , Tan Eng Lai
Published: June 2021

Background: The effects of lipopolysaccharide (LPS) on cell proliferation and osteogenic potential (OP) of MSCs have been frequently studied. Objective: to compare the effects of LPS on periodontal-ligament-derived mesenchymal stem cells (PDLSCs) in monolayer and 3D culture. Methods: The PDLSCs were colorimetrically assessed for proliferation and osteogenic potential (OP) after LPS treatment. The 3D cells were manually prepared by scratching and allowing them to clump up. The clumps (C-MSCs) were treated with LPS and assessed for Adenosine triphosphate (ATP) and OP. Raman spectroscopy was used to analyze calcium salts, DNA, and proline/hydroxyproline. Multiplexed ELISA was performed to assess LPS induced local inflammation. Results: The proliferation of PDLSCs decreased with LPS. On Day 28, LPS-treated cells showed a reduction in their OP. C-MSCs with LPS did not show a decrease in ATP production. Principal bands identified in Raman analysis were the P–O bond at 960 cm−1 of the mineral component, 785 cm−1, and 855 cm−1 showing qualitative changes in OP, proliferation, and proline/hydroxyproline content, respectively. ELISA confirmed increased levels of IL-6 and IL-8 but with the absence of TNF-α and IL-1β secretion. Conclusions: These observations demonstrate that C-MSCs are more resistant to the effects of LPS than cells in monolayer cell culture. Though LPS stimulation of C-MSCs creates an early pro-inflammatory milieu by secreting IL-6 and IL-8, PDLSCs possess inactivated TNF promoter and an ineffective caspase-1 activating process.
Obesity-Related Indices Are Associated with Peripheral Artery Occlusive Disease in Patients with Type 2 Diabetes Mellitus
Authors: Wung Chih-Hsuan , Lee Mei-Yueh , Wu Pei-Yu , Huang Jiun-Chi , Chen Szu-Chia
Published: June 2021

Type 2 diabetes mellitus (DM) is an increasing global health issue. Peripheral artery occlusive disease (PAOD) is a common complication of diabetes, and it is a complex and costly disease. The association between type 2 DM and obesity is well known, however, the relationship between obesity and PAOD in patients with type 2 DM has yet to be elucidated. Therefore, the aim of this study was to examine associations between obesity-related indices and PAOD in patients with type 2 DM. A total of 1872 outpatients with type 2 DM were recruited from two hospitals in southern Taiwan. An ankle–brachial index (ABI) < 0.9 in either leg was considered to indicate the presence of PAOD. The following obesity-related indices were investigated: conicity index (CI), waist–hip ratio (WHR), body roundness index (BRI), waist-to-height ratio (WHtR), abdominal volume index, a body shape index (ABSI), visceral adiposity index (VAI), lipid accumulation product (LAP), body adiposity index, body mass index and triglyceride–glucose index. Overall, 4.1% of the enrolled patients had an ABI < 0.9. High values of the following obesity-related indices were significantly associated with a low ABI: WHtR (p = 0.045), VAI (p = 0.003), CI (p = 0.042), BRI (p = 0.021) and ABSI (p = 0.043). Furthermore, WHR (area under the curve (AUC) = 0.661), CI (AUC = 0.660) and LAP (AUC = 0.642) had the best performance (all p < 0.001) to predict PAOD. In conclusion, high WHtR, BRI, CI, VAI and BAI values were associated with a low ABI in the enrolled patients, and WHR, CI and LAP were the most powerful predictors of PAOD.
3′-UTR Polymorphisms in Thymidylate Synthase with Colorectal Cancer Prevalence and Prognosis
Authors: Jeon Young-Joo , Cho Sung-Hwan , Kim Eo-Jin , Ryu Chang-Soo , Park Han-Sung , Kim Jong-Woo , Lee Jeong-Yong , An Hui-Jeong , Kim Nam-Keun
Published: June 2021

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related mortality in Western countries. Polymorphisms in one-carbon metabolism and angiogenesis-related genes have been shown to play important roles in tumor development, progression, and metastasis for many cancers, including CRC. Moreover, recent studies have reported that polymorphisms in specific microRNA (miRNA)-binding regions, which are located in the 3′-untranslated region (UTR) of miRNA-regulated genes, are present in a variety of cancers. Here, we investigated the association between two thymidylate synthase (TYMS or TS) 3′-UTR polymorphisms, 1100T>C [rs699517] and 1170A>G [rs2790], and CRC susceptibility and progression in Korean patients. A total of 450 CRC patients and 400 healthy controls were enrolled in this study, and genotyping at the TS locus was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) or TaqMan allelic discrimination assays. We found that TS 1170A>G genotypes, as well as the TS 1100T-1170G and 1100C-1170A haplotypes, are strongly associated with CRC. The TS 1100TC+CC type was associated with a poor survival (OS and RFS) rate. In addition, levels of the TS 1100C and TS 1170G allele were found to be significantly increased in CRC tissue. Our study provides the first evidence for 3′-UTR variants in TS genes as potential biomarkers of CRC prognosis and prevention.
A Mathematical Model of the Expansion Evolution of Magnesium Oxide in Mass Concrete Based on Hydration Characteristics
Authors: Feng Chuqiao , Zhao Cheng , Yu Xiaomin , Xiong Jie , Tang Longwen
Published: June 2021

The low swelling property of magnesium oxide concrete is a significant feature that can be used to control the cracking of mass concrete. Based on the characteristics of the chemical reaction, this work proposes a coupled hydro-thermo-mechanical model that can be implemented with the finite element method for predicting the autogenous volumetric deformation of magnesium concrete. By introducing the degree of the hydration reaction of magnesia and the degree of the hydration reaction of cementitious materials as intermediate variables of the chemical reaction system, a prediction model of the concrete temperature and chemical fields is established, and using this model, the effect of the temperature on the reaction rate can be considered in real time. In addition, by combining the relationship between the degree of the hydration reaction of magnesium oxide and the comprehensive expansion of concrete, a mathematical model for calculating the expansion stress of magnesia concrete was established. The algorithms were derived by mathematical equations, and the simulation results were compared to the experimental temperature and autogenous volumetric strain curves, which showed that the hydration model provides a relatively high accuracy. The model was also applied to an arch dam, and the coupled thermo-chemical-mechanical responses of mass concrete during construction were investigated. Simulation results show that the increase in temperature (hydration of cementitious material) and expansion volumetric deformation (hydration of MgO) of the concrete on the upstream and downstream surfaces lags obviously behind that of the inner regions. Quantitative analysis for differences of internal and external expansion is worthy of further attention and study on a basis of further experimental data as well as monitored data.
Neural Network-Based Prediction Model to Investigate the Influence of Temperature and Moisture on Vibration Characteristics of Skew Laminated Composite Sandwich Plates
Authors: Kallannavar Vinayak , Kattimani Subhaschandra , Soudagar Manzoore Elahi M. , Mujtaba M. A. , Alshahrani Saad , Imran Muhammad
Published: June 2021

The present study deals with the development of a prediction model to investigate the impact of temperature and moisture on the vibration response of a skew laminated composite sandwich (LCS) plate using the artificial neural network (ANN) technique. Firstly, a finite element model is generated to incorporate the hygro-elastic and thermo-elastic characteristics of the LCS plate using first-order shear deformation theory (FSDT). Graphite-epoxy composite laminates are used as the face sheets, and DYAD606 viscoelastic material is used as the core material. Non-linear strain-displacement relations are used to generate the initial stiffness matrix in order to represent the stiffness generated from the uniformly varying temperature and moisture concentrations. The mechanical stiffness matrix is derived using linear strain-displacement associations. Then the results obtained from the numerical model are used to train the ANN. About 11,520 data points were collected from the numerical analysis and were used to train the network using the Levenberg–Marquardt algorithm. The developed ANN model is used to study the influence of various process parameters on the frequency response of the system, and the outcomes are compared with the results obtained from the numerical model. Several numerical examples are presented and conferred to comprehend the influence of temperature and moisture on the LCS plates.
Adhesion and Growth of Neuralized Mouse Embryonic Stem Cells on Parylene-C/SiO2 Substrates
Authors: Murray Alan F. , Delivopoulos Evangelos
Published: June 2021

Neuronal patterning on microfabricated architectures has developed rapidly over the past few years, together with the emergence of soft biocompatible materials and tissue engineering scaffolds. Previously, we introduced a patterning technique based on serum and the biopolymer parylene-C, achieving highly compliant growth of primary neurons and astrocytes on different geometries. Here, we expanded this technique and illustrated that neuralized cells derived from mouse embryonic stem cells (mESCs) followed stripes of variable widths with conformity equal to or higher than that of primary neurons and astrocytes. Our results indicate the presence of undifferentiated mESCs, which also conformed to the underlying patterns to a high degree. This is an exciting and unexpected outcome, as molecular mechanisms governing cell and ECM protein interactions are different in stem cells and primary cells. Our study enables further investigations into the development and electrophysiology of differentiating patterned neural stem cells.
Preparation of Soluble POSS-Linking Polyamide and Its Application in Antifogging Films
Authors: Kozuma Tomoya , Mihata Aki , Kaneko Yoshiro
Published: June 2021

In this study, we prepared a polyhedral oligomeric silsesquioxane (POSS)-linking polyamide (POSS polyamide) by a polycondensation of ammonium-functionalized POSS (POSS-A) and carboxyl-functionalized POSS (POSS-C) in dehydrated dimethyl sulfoxide (DMSO) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) as condensing agents. The obtained POSS polyamide was soluble in various highly polar solvents, and it could form a self-standing film. FT-IR, 1H NMR, and 29Si NMR analyses showed that POSS polyamide is a polymer in which POSS-A and POSS-C are linked almost linearly by amide bonds. Furthermore, the cast film obtained by heat-treating the polymer at 150 °C for 30 min exhibited excellent transparency and hard-coating (pencil scratch test: 5H) and antifogging properties (evaluation by water vapor exposure).
Atomic Simulations for Packing Changes of Nano-Sized Cu Clusters Embedded in the Febulk on Heating
Authors: Yu Peng , Zhang Lin , Du Linxiu
Published: June 2021

Understanding of the defect evolution mechanism under irradiation is very important for the research of pressure vessel steel embrittlement. In this paper, the embedded atom method (EAM) based canonical ensemble molecular dynamics (MD) method was used to study the evolution of the stacking structure of different nano-sized Cun (n = 13, 43 and 87) clusters in an Febulk embedded with BCC lattice structure during continuous heating. The mean square displacement, pair distribution functions and atomic structures of Cu atom clusters at the nanometer scale were calculated at different temperatures. The structural changes present apparent differences, for the Febulks contain nano-sized Cu clusters with different atom numbers during heating. For the Febulk–Cu13 system, since the ability to accommodate the atomic Cu in the Fe substrate is lesser, a small number of Cu atoms in BCC lattice positions cannot influence the whole structure of the Fe-Cu system. For the Febulk–Cu43 system, with an increase in temperature, a Cu atomic pile structural change happened, and the strain areas decreased significantly in the Febulk, but a single strain area grew large. For the Febulk–Cu87 system, when the Cu atoms are constrained by the Fe atoms in bulk, only a few of the Cu atoms adjust their positions. With the increase in temperature, strain in the Fe eased.
Metabolite Profiling Reveals Distinct Modulation of Complex Metabolic Networks in Non-Pigmented, Black, and Red Rice (Oryza sativa L.) Cultivars
Authors: Kim Tae Jin , Kim So Yeon , Park Young Jin , Lim Sun-Hyung , Ha Sun-Hwa , Park Sang Un , Lee Bumkyu , Kim Jae Kwang
Published: June 2021

Comprehensive profiling of primary and secondary metabolites was performed to understand metabolic differences associated with color formation in pigmented rice (Oryza sativa L.). Overall, 110 metabolites from non-pigmented, black, and red rice cultivars were identified. Black and red rice contained high levels of flavonoids associated with plant color. Black rice also contained high levels of terpenoids (carotenoids, tocopherols, phytosterols, and monoterpenes). The non-pigmented rice contained relatively low levels of secondary metabolites. Multivariate and pathway analyses were performed to data-mine the metabolite profiles. Hierarchical clustering analysis of correlation coefficients revealed metabolite clusters based on nitrogen and carbon sources. These clusters suggested a negative correlation between nitrogen and carbon. Pathway analysis revealed that black rice was rich in carbon-based secondary metabolites, with relatively low levels of primary metabolites compared with other rice cultivars. These data highlight the complex interactions between nitrogen and carbon metabolism of primary and secondary metabolites in rice. For the first time, the relationships and metabolic differences in terpenoid content (monoterpenes, triterpenes, and tetraterpenes) of non-pigmented and pigmented rice cultivars were analyzed. These findings should greatly contribute to the understanding of pigmented rice metabolome and inform breeding programs for new rice cultivars.
Plant Transcriptome Reprograming and Bacterial Extracellular Metabolites Underlying Tomato Drought Resistance Triggered by a Beneficial Soil Bacteria
Authors: Morcillo Rafael , Vílchez Juan , Zhang Song , Kaushal Richa , He Danxia , Zi Hailing , Liu Renyi , Niehaus Karsten , Handa Avtar , Zhang Huiming
Published: June 2021

Water deficit is one of the major constraints to crop production and food security worldwide. Some plant growth-promoting rhizobacteria (PGPR) strains are capable of increasing plant drought resistance. Knowledge about the mechanisms underlying bacteria-induced plant drought resistance is important for PGPR applications in agriculture. In this study, we show the drought stress-mitigating effects on tomato plants by the Bacillus megaterium strain TG1-E1, followed by the profiling of plant transcriptomic responses to TG1-E1 and the profiling of bacterial extracellular metabolites. Comparison between the transcriptomes of drought-stressed plants with and without TG1-E1 inoculation revealed bacteria-induced transcriptome reprograming, with highlights on differentially expressed genes belonging to the functional categories including transcription factors, signal transduction, and cell wall biogenesis and organization. Mass spectrometry-based analysis identified over 40 bacterial extracellular metabolites, including several important regulators or osmoprotectant precursors for increasing plant drought resistance. These results demonstrate the importance of plant transcriptional regulation and bacterial metabolites in PGPR-induced plant drought resistance.
Recent Advances in Transition Metal Dichalcogenide Cathode Materials for Aqueous Rechargeable Multivalent Metal-Ion Batteries
Authors: Hoang Huy Vo , Ahn Yong , Hur Jaehyun
Published: June 2021

The generation of renewable energy is a promising solution to counter the rapid increase in energy consumption. Nevertheless, the availability of renewable resources (e.g., wind, solar, and tidal) is non-continuous and temporary in nature, posing new demands for the production of next-generation large-scale energy storage devices. Because of their low cost, highly abundant raw materials, high safety, and environmental friendliness, aqueous rechargeable multivalent metal-ion batteries (AMMIBs) have recently garnered immense attention. However, several challenges hamper the development of AMMIBs, including their narrow electrochemical stability, poor ion diffusion kinetics, and electrode instability. Transition metal dichalcogenides (TMDs) have been extensively investigated for applications in energy storage devices because of their distinct chemical and physical properties. The wide interlayer distance of layered TMDs is an appealing property for ion diffusion and intercalation. This review focuses on the most recent advances in TMDs as cathode materials for aqueous rechargeable batteries based on multivalent charge carriers (Zn2+, Mg2+, and Al3+). Through this review, the key aspects of TMD materials for high-performance AMMIBs are highlighted. Furthermore, additional suggestions and strategies for the development of improved TMDs are discussed to inspire new research directions.
Data Shepherding in Nanotechnology. The Initiation
Authors: Furxhi Irini , Arvanitis Athanasios , Murphy Finbarr , Costa Anna , Blosi Magda
Published: June 2021

In this paper we describe the pragmatic approach of initiating, designing and implementing the Data Management Plan (DMP) and the data FAIRification process in the multidisciplinary Horizon 2020 nanotechnology project, Anticipating Safety Issues at the Design Stage of NAno Product Development (ASINA). We briefly describe the general DMP requirements, emphasizing that the initial steps in the direction towards data FAIRification must be conceptualized and visualized in a systematic way. We demonstrate the use of a generic questionnaire to capture primary data and metadata description from our consortium (data creators/experimentalists and data analysts/modelers). We then display the interactive process with external FAIR data initiatives (data curators/quality assessors), regarding guidance for data and metadata capturing and future integration into repositories. After the preliminary data capturing and FAIRification template is formed, the inner-communication process begins between the partners, which leads to developing case-specific templates. This paper assists future data creators, data analysts, stewards and shepherds engaged in the multi-faceted data shepherding process, in any project, by providing a roadmap, demonstrated in the case of ASINA.
Strengthening Mechanism of Electrothermal Actuation in the Epoxy Composite with an Embedded Carbon Nanotube Nanopaper
Authors: Slobodian Petr , Riha Pavel , Olejnik Robert , Matyas Jiri
Published: June 2021

We assessed an effect of an embedded electro-conductive multiwalled carbon nanotube nanopaper in an epoxy matrix on the release of the frozen actuation force and the actuation torque in the carbon nanotube nanopaper/epoxy composite after heating above its glass transition temperature. The presence of the nanopaper augmented the recovery of the actuation stress by the factor of two in comparison with the pure epoxy strips. We proposed a procedure that allowed us to assess this composite strengthening mechanism. The strengthening of the composite was attributed to the interlocking of the carbon nanotubes with the epoxy. When reheated, the composite samples, which contained stretched mutually intertwined nanotubes and epoxy segments, released a greater actuation stress then the epoxy samples, which comprised of less elastic networks of crosslinked segments of pure epoxy.
The Effects of High-Protein Diet and Resistance Training on Glucose Control and Inflammatory Profile of Visceral Adipose Tissue in Rats
Authors: Medeiros Claudia Stela , de Sousa Neto Ivo Vieira , Silva Keemilyn Karla Santos , Cantuária Ana Paula Castro , Rezende Taia Maria Berto , Franco Octávio Luiz , de Cassia Marqueti Rita , Freitas-Lima Leandro Ceotto , Araujo Ronaldo Carvalho , Yildirim Azize , Mackenzie Richard , Alves Almeida Jeeser
Published: June 2021

High-protein diets (HPDs) are widely accepted as a way to stimulate muscle protein synthesis when combined with resistance training (RT). However, the effects of HPDs on adipose tissue plasticity and local inflammation are yet to be determined. This study investigated the impact of HPDs on glucose control, adipocyte size, and epididymal adipose inflammatory biomarkers in resistance-trained rats. Eighteen Wistar rats were randomly assigned to four groups: normal-protein (NPD; 17% protein total dietary intake) and HPD (26.1% protein) without RT and NPD and HPD with RT. Trained groups received RT for 12 weeks with weights secured to their tails. Glucose and insulin tolerance tests, adipocyte size, and an array of cytokines were determined. While HPD without RT induced glucose intolerance, enlarged adipocytes, and increased TNF-α, MCP-1, and IL1-β levels in epididymal adipose tissue (p < 0.05), RT diminished these deleterious effects, with the HPD + RT group displaying improved blood glucose control without inflammatory cytokine increases in epididymal adipose tissue (p < 0.05). Furthermore, RT increased glutathione expression independent of diet (p < 0.05). RT may offer protection against adipocyte hypertrophy, pro-inflammatory states, and glucose intolerance during HPDs. The results highlight the potential protective effects of RT to mitigate the maladaptive effects of HPDs.
Resting Energy Expenditure and Related Factors in 6- to 9-Year-Old Southern African Children of Diverse Population Groups
Authors: Pretorius Adeline , Wood Paola , Becker Piet , Wenhold Friedeburg
Published: June 2021

Lower resting energy expenditure (REE) may partially explain the disproportionate prevalence of overweight/obesity among black African women. As no previous studies have investigated the REE of Southern African (South. Afr.) children, we aimed to determine, by sex and population group, the REE of 6- to 9-year-old urban school children. In a cross-sectional study with quota sampling, REE was measured with indirect calorimetry (IC). Confounders considered were: body composition (BC) (fat-free mass (FFM), FFM index, fat mass (FM), FM index), assessed using multifrequency bioelectrical impedance analysis, and physical activity (PA) measured with a pedometer. Multivariate regression was used to calculate REE adjusted for phenotypes (BC, z-scores of weight-for-age, height-for-age, body mass index-for-age) and PA. Sex and population differences in REE were determined with two-way ANOVA. Ninety-four healthy children (59.6% girls; 52.1% black) with similar socioeconomic status and PA opportunities participated. Despite BC variations, sex differences in REE were not significant (41 kcal/day; P = 0.375). The REE of black participants was lower than of white (146 kcal/day; P = 0.002). When adjusted for FFM and HFA z-score, the differences in REE declined but remained clinically meaningful at 91 kcal/day (P = 0.039) and 82 kcal/day (P = 0.108), respectively. We recommend the development of population-specific REE prediction equations for South. Afr. children.
Vitamin D Supplementation Regulates Postoperative Serum Levels of PD-L1 in Patients with Digestive Tract Cancer and Improves Survivals in the Highest Quintile of PD-L1: A Post Hoc Analysis of the AMATERASU Randomized Controlled Trial
Authors: Morita Makoto , Okuyama Mai , Akutsu Taisuke , Ohdaira Hironori , Suzuki Yutaka , Urashima Mitsuyoshi
Published: June 2021

Because vitamin D responsive elements have been found to be located in the PD-L1 gene, vitamin D supplementation was hypothesized to regulate serum PD-L1 levels and thus alter survival time of cancer patients. A post hoc analysis of the AMATERASU randomized, double-blind, placebo-controlled trial of postoperative vitamin D3 supplementation (2000 IU/day) in 417 patients with stage I to stage III digestive tract cancer from the esophagus to the rectum was conducted. Postoperative serum PD-L1 levels were measured by ELISA and divided into quintiles (Q1–Q5). Serum samples were available for 396 (95.0%) of the original trial. Vitamin D supplementation significantly (p = 0.0008) up-regulated serum PD-L1 levels in the lowest quintile (Q1), whereas it significantly (p = 0.0001) down-regulated them in the highest quintile (Q5), and it did not either up- or down-regulate them in the middle quintiles (Q2–Q4). Significant effects of vitamin D supplementation, compared with placebo on death (HR, 0.34; 95% CI, 0.12–0.92) and relapse/death (HR, 0.37; 95% CI, 0.15–0.89) were observed in the highest quintile (Q5) of serum PD-L1, whereas significant effects were not observed in other quintiles (Pinteraction = 0.02 for death, Pinteraction = 0.04 for relapse/death). Vitamin D supplementation significantly reduced the risk of relapse/death to approximately one-third in the highest quintile of serum PD-L1.
Bad Prognosis in Critical Ill Patients with COVID-19 during Short-Term ICU Stay regarding Vitamin D Levels
Authors: Herrera-Quintana Lourdes , Gamarra-Morales Yenifer , Vázquez-Lorente Héctor , Molina-López Jorge , Castaño-Pérez José , Machado-Casas Juan Francisco , Coca-Zúñiga Ramón , Pérez-Villares José Miguel , Planells Elena
Published: June 2021

Background and aims: Vitamin D inadequacy may be involved in the mechanisms of SARS-CoV-2 infection and in potential risk factors for disease propagation or control of coronavirus disease 2019 (COVID-19). This study assessed a short-term evolution of vitamin D status and its influence upon different clinical parameters in critically ill patients with COVID-19. Methods: A prospective analytical study in which 37 critically ill volunteers between 41 and 71 years of age with COVID-19 were evaluated at baseline and three days of intensive care unit (ICU) stay. 25-OH-D3 and 25-OH-D2 were analyzed by liquid chromatography–tandem mass spectrometry and total 25-OH-D levels were calculated as the sum of both. Results: All patients presented low 25-OH-D levels at baseline, decreasing total 25-OH-D (p = 0.011) mainly through 25-OH-D2 (p = 0.006) levels during ICU stay. 25-OH-D2 levels decreased a mean of 41.6% ± 89.6% versus 7.0% ± 23.4% for the 25-OH-D3 form during the ICU stay. Patients who did not need invasive mechanical ventilation presented higher levels of 25-OH-D2 at baseline and follow-up. Lower 25-OH-D and 25-OH-D3 levels were associated with higher D-dimer at baseline (p = 0.003; p = 0.001) and at follow up (p = 0.029), higher procalcitonin levels (p = 0.002; p = 0.018) at follow up, and lower percentage lymphocyte counts (p = 0.044; p = 0.040) during ICU stay. Conclusions: Deficient vitamin D status in critical patients was established at the admission and further worsened after three days of stay. Lower vitamin D levels were related to key altered clinical and biochemical parameters on patients with SARS-CoV-2 infection. Given the different response of the 25-OH-D3 and 25-OH-D2 forms, it would be useful to monitor them on the evolution of the critically ill patient.
The Impact of COVID-19 Pandemic during 2020–2021 on the Vitamin D Serum Levels in the Paediatric Population in Warsaw, Poland
Authors: Rustecka Agnieszka , Maret Justyna , Drab Ada , Leszczyńska Michalina , Tomaszewska Agata , Lipińska-Opałka Agnieszka , Będzichowska Agata , Kalicki Bolesław , Kubiak Jacek Z.
Published: June 2021

Background: The main source of vitamin D is skin synthesis, which depends on sunlight exposure. During the pandemic, COVID-19 children were obliged to home confinement, which potentially limiting sunlight exposure. The aim of this study was to evaluate whether home confinement led to decreased vitamin D serum levels in children in Warsaw, Poland. Methods: The study included 1472 children who were divided into two groups, based on the date of 25(OH)D level blood sampling: before and during the pandemic. Children under 1 year of age (infants) were analysed separately. Results: A statistically significant decrease in the average level of vitamin D was observed between groups of children over 1 year of age (35 ng/mL ± 18 vs. 31 ng/mL ± 14). In infants from both groups, the mean vitamin D levels were within the normal range (Group 1 inf 54 ng/mL ± 21 vs. Group 2 inf 47 ng/mL ± 15). The characteristic seasonal variability was observed before the pandemic, with maximal vitamin D levels in summer (40 ng/mL ± 17) and minimal levels in winter (30 ng/mL ± 14). During the pandemic, no seasonal variability was observed (summer 30 ng/mL ± 11 vs. winter 30 ng/mL ± 19). Conclusions: The COVID-19 pandemic restrictions led to a significant decrease in vitamin D serum levels in children.
Neisseria meningitidis Factor H Binding Protein Surface Exposure on Salmonella Typhimurium GMMA Is Critical to Induce an Effective Immune Response against Both Diseases
Authors: Necchi Francesca , Stefanetti Giuseppe , Alfini Renzo , Palmieri Elena , Carducci Martina , Di Benedetto Roberta , Schiavo Fabiola , Aruta Maria Grazia , Giusti Fabiola , Ferlenghi Ilaria , Goh Yun Shan , Rondini Simona , Micoli Francesca
Published: June 2021

GMMA, outer membrane vesicles resulting from hyperblebbing mutated bacterial strains, are a versatile vaccine platform for displaying both homologous and heterologous antigens. Periplasmic expression is a popular technique for protein expression in the lumen of the blebs. However, the ability of internalized antigens to induce antibody responses has not been extensively investigated. Herein, the Neisseria meningitidis factor H binding protein (fHbp) was heterologously expressed in the lumen of O-antigen positive (OAg+) and O-antigen negative (OAg−) Salmonella Typhimurium GMMA. Only the OAg− GMMA induced an anti-fHbp IgG response in mice if formulated on Alum, although it was weak and much lower compared to the recombinant fHbp. The OAg− GMMA on Alum showed partial instability, with possible exposure of fHbp to the immune system. When we chemically conjugated fHbp to the surface of both OAg+ and OAg− GMMA, these constructs induced a stronger functional response compared to the fHbp immunization alone. Moreover, the OAg+ GMMA construct elicited a strong response against both the target antigens (fHbp and OAg), with no immune interference observed. This result suggests that antigen localization on GMMA surface can play a critical role in the induction of an effective immune response and can encourage the development of GMMA based vaccines delivering key protective antigens on their surface.
Diagnosis and Staging of Pediatric Non-Alcoholic Fatty Liver Disease: Is Classical Ultrasound the Answer?
Authors: Papachristodoulou Angeliki , Kavvadas Dimitrios , Karamitsos Athanasios , Papamitsou Theodora , Chatzidimitriou Maria , Sioga Antonia
Published: June 2021

The increased prevalence of non-alcoholic fatty liver disease (NAFLD) requires special attention in pediatric patients, as it manifests in them in a more severe and progressive way compared to adults. The implementation of the appropriate therapeutic interventions is determinant of the attempts to treat it. For that purpose, early diagnosis and staging of the disease is essential. The purpose of this review was to find and reveal the most appropriate diagnostic strategies and tools for diagnosis and staging of pediatric NAFLD/NASH based on their accuracy, safety and effectiveness. The methodology followed was that of the literature review. Particular emphasis was put on the recent bibliography. A comparative study of published articles about the diagnosis and management of pediatric NAFLD/NASH was also performed. In terms of diagnosis, the findings converged on the use of classical ultrasound. Ultrasound presented average sensitivity and specificity for diagnosing the disease in children, while in the adult population, sensitivity and specificity were significantly higher. Proton density fat fraction magnetic resonance imaging has been increasingly used for the diagnosis of steatosis in pediatric patients. Elastography is an effective tool for staging liver fibrosis and discriminating NASH from NAFLD in children. Even though liver biopsy is the gold standard, especially for NASH, it should be avoided for pediatric patients. Biochemical tests are less specific and less sensitive for the diagnosis of NAFLD, and some of them are of high cost. It seems that diagnostic imaging should be a first-line tool for the staging and monitoring pediatric NAFLD/NASH in order for appropriate interventions to be implanted in a timely way.
Site-Specific Radiolabeling of a Human PD-L1 Nanobody via Maleimide–Cysteine Chemistry
Authors: Chigoho Dora Mugoli , Lecocq Quentin , Awad Robin Maximilian , Breckpot Karine , Devoogdt Nick , Keyaerts Marleen , Caveliers Vicky , Xavier Catarina , Bridoux Jessica
Published: June 2021

Immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1) and its ligand PD-L1 have proven to be efficient cancer therapies in a subset of patients. From all the patients with various cancer types, only 20% have a positive response. Being able to distinguish patients that do express PD-1/PD-L1 from patients that do not allows patients to benefit from a more personalized and efficient treatment of tumor lesion(s). Expression of PD-1 and PD-L1 is typically assessed via immunohistochemical detection in a tumor biopsy. However, this method does not take in account the expression heterogeneity within the lesion, nor the possible metastasis. To visualize whole-body PD-L1 expression by PET imaging, we developed a nanobody-based radio-immunotracer targeting PD-L1 site-specifically labeled with gallium-68. The cysteine-tagged nanobody was site-specifically conjugated with a maleimide (mal)-NOTA chelator and radiolabeling was tested at different nanobody concentrations and temperatures. Affinity and specificity of the tracer, referred to as [68Ga]Ga-NOTA-mal-hPD-L1 Nb, were assayed by surface plasmon resonance and on PD-L1POS or PD-L1NEG 624-MEL cells. Xenografted athymic nude mice bearing 624-MEL PD-L1POS or PD-L1NEG tumors were injected with the tracer and ex vivo biodistribution was performed 1 h 20 min post-injection. Ideal 68Ga-labeling conditions were found at 50 °C for 15 min. [68Ga]Ga-NOTA-mal-hPD-L1 Nb was obtained in 80 ± 5% DC-RCY with a RCP > 99%, and was stable in injection buffer and human serum up to 3 h (>99% RCP). The in vitro characterization showed that the NOTA-functionalized Nb retained its affinity and specificity. Ex vivo biodistribution revealed a tracer uptake of 1.86 ± 0.67% IA/g in the positive tumors compared with 0.42 ± 0.04% IA/g in the negative tumors. Low background uptake was measured in the other organs and tissues, except for the kidneys and bladder, due to the expected excretion route of Nbs. The data obtained show that the site-specific 68Ga-labeled NOTA-mal-hPD-L1 Nb is a promising PET radio-immunotracer due to its ease of production, stability and specificity for PD-L1.
Design and In Vitro Study of a Dual Drug-Loaded Delivery System Produced by Electrospinning for the Treatment of Acute Injuries of the Central Nervous System
Authors: Dolci Luisa Stella , Perone Rosaria Carmela , Di Gesù Roberto , Kurakula Mallesh , Gualandi Chiara , Zironi Elisa , Gazzotti Teresa , Tondo Maria Teresa , Pagliuca Giampiero , Gostynska Natalia , Baldassarro Vito Antonio , Cescatti Maura , Giardino Luciana , Focarete Maria Letizia , Calzà Laura , Passerini Nadia , Bolognesi Maria Laura
Published: June 2021

Vascular and traumatic injuries of the central nervous system are recognized as global health priorities. A polypharmacology approach that is able to simultaneously target several injury factors by the combination of agents having synergistic effects appears to be promising. Herein, we designed a polymeric delivery system loaded with two drugs, ibuprofen (Ibu) and thyroid hormone triiodothyronine (T3) to in vitro release the suitable amount of the anti-inflammation and the remyelination drug. As a production method, electrospinning technology was used. First, Ibu-loaded micro (diameter circa 0.95–1.20 µm) and nano (diameter circa 0.70 µm) fibers were produced using poly(l-lactide) PLLA and PLGA with different lactide/glycolide ratios (50:50, 75:25, and 85:15) to select the most suitable polymer and fiber diameter. Based on the in vitro release results and in-house knowledge, PLLA nanofibers (mean diameter = 580 ± 120 nm) loaded with both Ibu and T3 were then successfully produced by a co-axial electrospinning technique. The in vitro release studies demonstrated that the final Ibu/T3 PLLA system extended the release of both drugs for 14 days, providing the target sustained release. Finally, studies in cell cultures (RAW macrophages and neural stem cell-derived oligodendrocyte precursor cells—OPCs) demonstrated the anti-inflammatory and promyelinating efficacy of the dual drug-loaded delivery platform.
Multi-Walled Carbon Nanotubes Decorated with Guanidinylated Dendritic Molecular Transporters: An Efficient Platform for the Selective Anticancer Activity of Doxorubicin
Authors: Lyra Kyriaki-Marina , Kaminari Archontia , Panagiotaki Katerina N. , Spyrou Konstantinos , Papageorgiou Sergios , Sakellis Elias , Katsaros Fotios K. , Sideratou Zili
Published: June 2021

An efficient doxorubicin (DOX) drug delivery system with specificity against tumor cells was developed, based on multi-walled carbon nanotubes (MWCNTs) functionalized with guanidinylated dendritic molecular transporters. Acid-treated MWCNTs (oxCNTs) interacted both electrostatically and through hydrogen bonding and van der Waals attraction forces with guanidinylated derivatives of 5000 and 25,000 Da molecular weight hyperbranched polyethyleneimine (GPEI5K and GPEI25K). Chemical characterization of these GPEI-functionalized oxCNTs revealed successful decoration with GPEIs all over the oxCNTs sidewalls, which, due to the presence of guanidinium groups, gave them aqueous compatibility and, thus, exceptional colloidal stability. These GPEI-functionalized CNTs were subsequently loaded with DOX for selective anticancer activity, yielding systems of high DOX loading, up to 99.5% encapsulation efficiency, while the DOX-loaded systems exhibited pH-triggered release and higher therapeutic efficacy compared to that of free DOX. Most importantly, the oxCNTs@GPEI5K-DOX system caused high and selective toxicity against cancer cells in a non-apoptotic, fast and catastrophic manner that cancer cells cannot recover from. Therefore, the oxCNTs@GPEI5K nanocarrier was found to be a potent and efficient nanoscale DOX delivery system, exhibiting high selectivity against cancerous cells, thus constituting a promising candidate for cancer therapy.
Preparation of High Molecular Weight Poly(urethane-urea)s Bearing Deactivated Diamines
Authors: Rubio Hernández-Sampelayo Alejandra , Navarro Rodrigo , Marcos-Fernández Ángel
Published: June 2021

The synthesis of poly(urethane-urea) (PUUs) bearing deactivated diamines within the backbone polymer chain is presented. Several deactivated diamines present interesting properties for several applications in the biomaterial field due to their attractive biocompatibility. Through an activation with Chloro-(trimethyl)silane (Cl-TMS) during the polymerization reaction, the reactivity of these diamines against diisocyanates was triggered, leading to PUUs with high performance. Indeed, through this activation protocol, the obtained molecular weights and mechanical features increased considerably respect to PUUs prepared following the standard conditions. In addition, to demonstrate the feasibility and versatility of this synthetic approach, diisocyanate with different reactivity were also addressed. The experimental work is supported by calculations of the electronic parameters of diisocyanate and diamines, using quantum mechanical methods.
Hybrid Microporous Polymeric Materials with Outstanding Permeability and Increased Gas Transport Stability: PTMSP Aging Prevention by Sorption of the Polymerization Catalyst on HCPS
Authors: Golubev Georgy , Bakhtin Danila , Makaev Sergey , Borisov Ilya , Volkov Alexey
Published: June 2021

The influence of hyper-crosslinked polystyrene (HCPS) MacronetTM MN200 on the gas transport properties and aging of the highly permeable glassy polymer poly(1-trimethylsilyl-1-propyne) (PTMSP) was studied and analyzed in detail. The gas transport characteristics of dense PTMSP membranes containing 0–10.0 wt % HCPS were studied. It was shown that the introduction of a small amount of HCPS into the PTMSP matrix led to a 50–60% increase of the permeability coefficients of the material for light gases (N2, O2, CO2) and slowed down the deterioration of polymer transport properties over time. The lowest reduction in gas permeability coefficients (50–57%) was found for PTMSP containing HCPS 5.0 wt % after annealing at 100 °C for 300 h. It was found that HCPS sorbed residues of tantalum-based polymerization catalyst from PTMSP. In order to investigate the influence of catalysts on transport and physical properties of PTMSP, we purified the latter from the polymerization catalyst by addition of 5 wt % HCPS into polymer/chloroform solution. It was shown that sorption on HCPS allowed for almost complete removal of tantalum compounds from PTMSP. The membrane made of PTMSP purified by HCPS demonstrated more stable transport characteristics compared to the membrane made of the initial polymer. HCPS has a complex effect on the aging process of PTMSP. The introduction of HCPS into the polymer matrix not only slowed down the physical aging of PTMSP, but also reduced chemical aging due to removal of active reagents.
Synthesizing Religions: Vasily Rozanov’s “Phallic Christianity”
Authors: Mondry Henrietta
Published: June 2021

Vasily Rozanov was one of the first Russian writers of the fin de siècle to create a nexus between the study of the history of world religions and the history of sexuality. He viewed Christianity’s asceticism as a source of the disintegration of the contemporary family. This article examines Rozanov’s strategy to synthesize religions and to use pre-Christian religions of the Middle East as proof of common physical and metaphysical essence in celestial, human, animal, and mythological human/animal/divine bodies. I argue that while his rehabilitation of the physical life by endowing it with religious value was socially positive, his self-proclaimed “mission of sexuality”, when politically motivated, was manipulative and incorporated the notion of the atavistic ‘survivals’. In conclusion, I explain that Rozanov’s monistic search for the divine in the physical body as well as his strategy to synthesize religions were additionally driven by his personal doubts in the preeminence of Christian eschatology.