bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of the Nonlocal Thermoelastic Model in a Thermoelastic Nanoscale Material
Authors: Saeed Tareq , Abbas Ibrahim
Published: January 2022

In this work, a novel nonlocal model without energy dissipations is presented to investigate the impacts of the nonlocal thermoelastic parameters in a nanoscale material by the eigenvalue approach. The basic equations are applied under the Green and Naghdi model without energy dissipations. To obtain this model, the theory of the non-local continuum suggested by Eringen is applied. The Laplace transformation technique is used for the basic formulations to obtain the analytical solutions of the thermal stress, the displacement, and the temperature during the nanoscale thermo-electric medium. The inverse of the Laplace transformation is used with the numerical technique to obtain the complete solutions of the studying fields in the time–space domains. The main physical fields are displayed graphically and theoretically discussed under the influence of nonlocal parameters.
A Direct Method for Solving Singular Integrals in Three-Dimensional Time-Domain Boundary Element Method for Elastodynamics
Authors: Qin Xiaofei , Fan Youhua , Li Hongjun , Lei Weidong
Published: January 2022

The analytically time integrable time-space domain (ATI-TSD) is discovered based on which the minimum time-space domain is identified for treatment on singularities in the three-dimensional time-domain boundary element method (3D TD-BEM) formulation. A direct method to solve singular integrals in the 3D TD-BEM formulation for elastodynamic problems is proposed. The wavefront singularity can be analytically eliminated in ATI-TSD, while the dual singularity can be treated by the direct method using Kutt’s quadrature in the identified minimum time-space domain. Three benchmark examples are presented to verify the correctness and the applicability of the direct method for solving the singular integrals in 3D TD-BEM.
Estimation of the Instantaneous Reproduction Number and Its Confidence Interval for Modeling the COVID-19 Pandemic
Authors: Cortés-Carvajal Publio Darío , Cubilla-Montilla Mitzi , González-Cortés David Ricardo
Published: January 2022

In this paper, we derive an optimal model for calculating the instantaneous reproduction number, which is an important metric to help in controlling the evolution of epidemics. Our approach, within a frequentist framework, gave us the opportunity to calculate a more realistic confidence interval, a fundamental tool for a safe interpretation of the instantaneous reproduction number value, so that health and governmental people pay more attention to it. Our reasoning begins by decoupling the incidence data in mean and Gaussian noise by using practical series analysis techniques; then, we continue with a likely relationship between the present and past incidence data. Monte Carlo simulations and numerical integrations were conducted to complement the analytical proofs, and illustrations are provided for each stage of analysis to validate the analytical results. Finally, a real case study is discussed with the incidence data of the Republic of Panama regarding the COVID-19 pandemic. We have shown that, for the calculation of the confidence interval of the instantaneous reproduction number, it is essential to include all sources of variability, not only the Poissonian processes of the incidences. This proposal is delivered with analysis tools developed with Microsoft Excel.
New Trichothecenes Isolated from the Marine Algicolous Fungus Trichoderma brevicompactum
Authors: Safwan Safwan , Wang Shih-Wei , Hsiao George , Hsiao Sui-Wen , Hsu Su-Jung , Lee Tzong-Huei , Lee Ching-Kuo
Published: January 2022

Eight trichothecenes, including four new compounds 1–4 and four known entities 5–8, together with one known cyclonerane (9) were isolated from the solid-state fermentation of Trichoderma brevicompactum NTU439 isolated from the marine alga Mastophora rosea. The structures of 1–9 were determined by 1D/2D NMR (nuclear magnetic resonance), MS (mass spectrometry), and IR (infrared spectroscopy) spectroscopic data. All of the compounds were evaluated for cytotoxic activity against HCT-116, PC-3, and SK-Hep-1 cancer cells by the SRB assay, and compound 8 showed promising cytotoxic activity against all three cancer cell lines with the IC50 values of 3.3 ± 0.3, 5.3 ± 0.3, and 1.8 ± 0.8 μM, respectively. Compounds 1–2, 4–6, and 7–8 potently inhibited LPS-induced NO production, and compounds 5 and 8 showed markedly inhibited gelatinolysis of MMP-9 in S1 protein-stimulated THP-1 monocytes.
Ecotoxicological Impact of the Marine Toxin Palytoxin on the Micro-Crustacean Artemia franciscana
Authors: Cavion Federica , Pelin Marco , Ponti Cristina , Della Loggia Roberto , Tubaro Aurelia , Sosa Silvio
Published: January 2022

Palytoxin (PLTX) is a highly toxic polyether identified in various marine organisms, such as Palythoa soft corals, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria. In addition to adverse effects in humans, negative impacts on different marine organisms have been often described during Ostreopsis blooms and the concomitant presence of PLTX and its analogues. Considering the increasing frequency of Ostreopsis blooms due to global warming, PLTX was investigated for its effects on Artemia franciscana, a crustacean commonly used as a model organism for ecotoxicological studies. At concentrations comparable to those detected in culture media of O. cf. ovata (1.0–10.0 nM), PLTX significantly reduced cysts hatching and induced significant mortality of the organisms, both at larval and adult stages. Adults appeared to be the most sensitive developmental stage to PLTX: significant mortality was recorded after only 12 h of exposure to PLTX concentrations > 1.0 nM, with a 50% lethal concentration (LC50) of 2.3 nM (95% confidence interval = 1.2–4.7 nM). The toxic effects of PLTX toward A. franciscana adults seem to involve oxidative stress induction. Indeed, the toxin significantly increased ROS levels and altered the activity of the major antioxidant enzymes, in particular catalase and peroxidase, and marginally glutathione-S-transferase and superoxide dismutase. On the whole, these results indicate that environmentally relevant concentrations of PLTX could have a negative effect on Artemia franciscana population, suggesting its potential ecotoxicological impact at the marine level.
Analysis of Influencing Factors on the Gas Separation Performance of Carbon Molecular Sieve Membrane Using Machine Learning Technique
Authors: Pan Yanqiu , He Liu , Ren Yisu , Wang Wei , Wang Tonghua
Published: January 2022

Gas separation performance of the carbon molecular sieve (CMS) membrane is influenced by multiple factors including the microstructural characteristics of carbon and gas properties. In this work, the support vector regression (SVR) method as a machine learning technique was applied to the correlation between the gas separation performance, the multiple membrane structure, and gas characteristic factors of the self-manufactured CMS membrane. A simple quantitative index based on the Robeson’s upper bound line, which indicated the gas permeability and selectivity simultaneously, was proposed to measure the gas separation performance of CMS membrane. Based on the calculation results, the inferred key factors affecting the gas permeability of CMS membrane were the fractional free volume (FFV) of the precursor, the average interlayer spacing of graphite-like carbon sheet, and the final carbonization temperature. Moreover, the most influential factors for the gas separation performance were supposed to be the two structural factors of precursor influencing the porosity of CMS membrane, the carbon residue and the FFV, and the ratio of the gas kinetic diameters. The results would be helpful to the structural optimization and the separation performance improvement of CMS membrane.
A Review on Thermophysical Property Assessment of Metal Oxide-Based Nanofluids: Industrial Perspectives
Authors: Sujith Surendran V. , Kim Hansoo , Lee Joonho
Published: January 2022

Energy consumption in the industrial sector can be significantly reduced by improving heat transfer rates in heat exchanger circuits, pool boiling, metal cutting industries, etc. Numerous energy-related issues can be overcome to a large extent by improving heat flow properties by utilizing nanofluids. The present contribution reviews the improvement in thermophysical properties of metal oxide-based nanofluids. Key parameters affecting the thermophysical properties of nanofluids, such as particle volume fraction, temperature, particle size and various stabilizers, were reviewed. The importance of DLVO theory and zeta potential to control the electrostatic repulsion and pH values of nanofluids for stable nanofluid formulations were discussed. It has been observed that classical theories of thermal conductivity and viscosity cannot predict exact values for a wide range of variables. Therefore, various extensive correlations have been introduced to predict the thermophysical properties of nanofluids. In these correlations, individual dependent variables such as particle size, temperature, nanofluid layer thickness, and Brownian velocity of nanoparticles, etc. were considered for more accurate prediction. The heat transfer efficiencies of nanofluids to base fluids in the laminar and turbulent regimes have been discussed using various figures of merits. Finally, the scope of industrial applications of metal oxide-based nanofluids and future research opportunities have been discussed.
Metabolism of Imidazole Dipeptides, Taurine, Branched-Chain Amino Acids, and Polyamines of the Breast Muscle Are Affected by Post-Hatch Development in Chickens
Authors: Tomonaga Shozo , Kawase Takahiro , Tsukahara Takamitsu , Ohta Yoshiyuki , Shiraishi Jun-ichi
Published: January 2022

To explore metabolic characteristics during the post-hatch developmental period, metabolomic analyses of breast muscle and plasma were performed in chickens. The most significant growth-related changes in metabolite levels were observed between seven and 28 days of age. Some of these metabolites are essential nutrients or reported as growth-promoting metabolites. In the muscle, two imidazole dipeptides—carnosine and its methylated metabolite, anserine—increased with the development. These dipeptide levels may be, in part, regulated transcriptionally because in the muscle mRNA levels of carnosine synthase and carnosine methylation enzyme increased. In contrast, taurine levels in the muscle decreased. This would be substrate availability-dependent because some upstream metabolites decreased in the muscle or plasma. In branched-chain amino acid metabolism, valine, leucine, and isoleucine decreased in the muscle, while some of their downstream metabolites decreased in the plasma. The polyamines, putrescine and spermidine, decreased in the muscle. Furthermore, mRNA levels associated with insulin/insulin-like growth factor 1 signaling, which play important roles in muscle growth, increased in the muscle. These results indicate that some metabolic pathways would be important to clarify metabolic characteristics and/or growth of breast muscle during the post-hatch developmental period in chickens.
In Vitro Metabolism of Helenalin Acetate and 11α,13-Dihydrohelenalin Acetate: Natural Sesquiterpene Lactones from Arnica
Authors: Jürgens Franziska M. , Behrens Matthias , Humpf Hans-Ulrich , Robledo Sara M. , Schmidt Thomas J.
Published: January 2022

Arnica tincture is a herbal medicinal preparation with anti-inflammatory activity which is used traditionally for the topical treatment of blunt injuries as well as rheumatic muscle and joint complaints. Its main bioactive constituents are sesquiterpene lactones (STLs) of the helenalin and 11α,13-dihydrohelenalin types. Besides the mentioned activity, the tincture and its isolated STLs have antileishmanial activity. In a recent in vivo study, a treatment with Arnica tincture cured cutaneous Leishmaniasis (CL) in a golden hamster model. CL is a neglected tropical disease affecting more than two million people every year, for which new treatments are urgently needed. In order to use Arnica tincture on open CL lesions of human patients, it is important to know how the constituents are metabolized. Therefore, in vitro metabolism experiments with liver microsomes of different species (rat, pig and human) were performed with the Arnica STLs helenalin acetate and 11α,13-dihydrohelenalin acetate. Phase I and phase II metabolism experiments were performed, as well as a combination of both. Glutathione conjugation plays a major role in the metabolism of these STLs, as could be expected based on previous reports on their reactivity. Besides glutathione conjugates, several other metabolites were formed, e.g., water conjugates and hydroxides. Our results show for the first time a detailed picture of the metabolism of Arnica STLs. The fast and extensive formation of glutathione conjugates makes it unlikely that low absorbed levels of these compounds, as expected after dermal absorption from Arnica tincture, could be of toxicological concern.
Effects of Physical Properties and Processing Methods on Astragaloside IV and Flavonoids Content in Astragali radix
Authors: Chien Mei-Yin , Yang Chih-Min , Chen Chao-Hsiang
Published: January 2022

The aim of this study was to investigate the effects of the physical properties (diameter size, powder particle size, composition of bark- and wood-tissue, and turnover rate) and processing methods on the content of active ingredients in Astragali radix (AR), a popular Chinese herbal medicine. The astragaloside IV and flavonoid contents increased with decreasing diameter size. Bark-tissue had significantly higher astragaloside IV and formononetin content than that in the wood-tissue. As a higher proportion of bark-tissue is associated with decreasing diameter, a strong correlation was also shown between bark- to wood-tissue ratio and active ingredients’ content. Furthermore, an increase in astragaloside IV content was observed in thin powder as compared to coarse powder ground from the whole root. However, this association between active ingredients’ content and powder particle size was abolished when isolating bark- and wood-tissue individually. Moreover, AR stir-frying with refined honey, a typical processing method of AR, increased formononetin content. The turnover rate of active constituents upon decoction ranged from 61.9–81.4%. Assessing the active constituent contents using its physical properties and processing methods allows for a more comprehensive understanding of optimizing and strengthening the therapeutic potentials of AR used in food and herbal supplements.
Evaluation of Antibacterial and Antifungal Properties of Low Molecular Weight Chitosan Extracted from Hermetia illucens Relative to Crab Chitosan
Authors: Khayrova Adelya , Lopatin Sergey , Shagdarova Balzhima , Sinitsyna Olga , Sinitsyn Arkady , Varlamov Valery
Published: January 2022

This study shows the research on the depolymerisation of insect and crab chitosans using novel enzymes. Enzyme preparations containing recombinant chitinase Chi 418 from Trichoderma harzianum, chitinase Chi 403, and chitosanase Chi 402 from Myceliophthora thermophila, all belonging to the family GH18 of glycosyl hydrolases, were used to depolymerise a biopolymer, resulting in a range of chitosans with average molecular weights (Mw) of 6–21 kDa. The depolymerised chitosans obtained from crustaceans and insects were studied, and their antibacterial and antifungal properties were evaluated. The results proved the significance of the chitosan’s origin, showing the potential of Hermetia illucens as a new source of low molecular weight chitosan with an improved biological activity.
A Surfactant Enables Efficient Membrane Spanning by Non-Aggregating DNA-Based Ion Channels
Authors: Morzy Diana , Schaich Michael , Keyser Ulrich F.
Published: January 2022

DNA nanotechnology makes use of hydrophobically modified constructs to create synthetic membrane protein mimics. However, nucleic acid structures exhibit poor insertion efficiency, leading to a low activity of membrane-spanning DNA protein mimics. It is suggested that non-ionic surfactants improve insertion efficiency, partly by disrupting hydrophobicity-mediated clusters. Here, we employed confocal microscopy and single-molecule transmembrane current measurements to assess the effects of the non-ionic surfactant octylpolyoxyethylene (oPOE) on the clustering behavior and membrane activity of cholesterol-modified DNA nanostructures. Our findings uncover the role of aggregation in preventing bilayer interactions of hydrophobically decorated constructs, and we highlight that premixing DNA structures with the surfactant does not disrupt the cholesterol-mediated aggregates. However, we observed the surfactant’s strong insertion-facilitating effect, particularly when introduced to the sample separately from DNA. Critically, we report a highly efficient membrane-spanning DNA construct from combining a non-aggregating design with the addition of the oPOE surfactant.
A Systematic Review of Cementation Techniques to Minimize Cement Excess in Cement-Retained Implant Restorations
Authors: Reda Rodolfo , Zanza Alessio , Cicconetti Andrea , Bhandi Shilpa , Guarnieri Renzo , Testarelli Luca , Di Nardo Dario
Published: January 2022

Background: The most used types of retention of implant-supported prostheses are screw-retained or cement-retained restorations. The advantages and disadvantages of both have been identified by various authors over the years. However, cement-retained implant crowns and fixed partial dentures are among the most used types of restorations in implant prostheses, due to their aesthetic and clinical advantages. When cemented prostheses are made on implants, the problem of cement residues is important and often associated with biological implant pathologies. The objective of this research was to establish to what extent the techniques to reduce excess cement really affect the volume of cement residues. Materials and Methods: This review was written following the PRISMA statement; a detailed search was carried out in three different electronic databases—PubMed, Scopus, and Cochrane Library. The inclusion criteria were prospective clinical studies, with at least 10 participants per group, and with at least 6 months of the follow-up period. Results: There have been many proposals for techniques supposed to reduce the amount of excess cement in the peri-implant sulcus and on the prosthetic components, but of these, which are exceptional in their in vitro capabilities, very few have been clinically validated, and this represents the real limitation and a great lack of knowledge regarding this topic. Three articles met the inclusion criteria, which were analyzed and compared, to obtain the information necessary for the purposes of the systematic review. Discussion: Extraoral cementation can reduce the excess cement, which, after a normal excess removal procedure, is, nevertheless, of such size that it does not affect the possibility of peri-implant pathologies developing. All these studies concluded that a small amount of cement residue is found in the gingival sulcus, and using eugenol-free oxide cements, the residues were only deposited on the metal surfaces, with a better peri-implant tissues health. Conclusion: Despite the limitations of this study, it was possible to carefully analyze these characteristics and obtain valuable suggestions for daily clinical practice. Resinous cements are considered, due to the free monomers present in them, toxic for the soft tissues. The provisional zinc-oxide cements, also eugenol-free, represent the ideal choice. The different grades of retentive forces provided by these cements do not seem to have clinical effects on the decementation of restorations.
Contrast Enhanced Ultrasound Molecular Imaging of Spontaneous Chronic Inflammatory Bowel Disease in an Interleukin-2 Receptor α−/− Transgenic Mouse Model Using Targeted Microbubbles
Authors: Wang Huaijun , Vilches-Moure Jose G. , Bettinger Thierry , Cherkaoui Samir , Lutz Amelie , Paulmurugan Ramasamy
Published: January 2022

Inflammatory bowel disease (IBD) is a lifelong inflammatory disorder with relapsing–remission cycles, which is currently diagnosed by clinical symptoms and signs, along with laboratory and imaging findings. However, such clinical findings are not parallel to the disease activity of IBD and are difficult to use in treatment monitoring. Therefore, non-invasive quantitative imaging tools are required for the multiple follow-up exams of IBD patients in order to monitor the disease activity and determine treatment regimens. In this study, we evaluated a dual P- and E-selectin-targeted microbubble (MBSelectin) in an interleukin-2 receptor α deficient (IL-2Rα−/−) spontaneous chronic IBD mouse model for assessing long-term anti-inflammatory effects with ultrasound molecular imaging (USMI). We used IL-2Rα−/− (male and female on a C57BL/6 genetic background; n = 39) and C57BL/6 wild-type (negative control; n = 6) mice for the study. USMI of the proximal, middle, and distal colon was performed with MBSelectin using a small animal scanner (Vevo 2100) up to six times in each IL-2Rα−/− mouse between 6–30 weeks of age. USMI signals were compared between IL-2Rα−/− vs. wild-type mice, and sexes in three colonic locations. Imaged colon segments were analyzed ex vivo for inflammatory changes on H&E-stained sections and for selectin expression by immunofluorescence staining. We successfully detected spontaneous chronic colitis in IL-2Rα−/− mice between 6–30 weeks (onset at 6–14 weeks) compared to wild-type mice. Both male and female IL-2Rα−/− mice were equally (p = 0.996) affected with the disease, and there was no significant (p > 0.05) difference in USMI signals of colitis between the proximal, middle, and distal colon. We observed the fluctuating USMI signals in IL-2Rα−/− mice between 6–30 weeks, which might suggest a resemblance of the remission-flare pattern of human IBD. The ex vivo H&E and immunostaining further confirmed the inflammatory changes, and the high expression of P- and E-selectin in the colon. The results of this study highlight the IL-2Rα−/− mice as a chronic colitis model and are suitable for the long-term assessment of treatment response using a dual P- and E-selectin-targeted USMI.
Movable Layer Device for Rapid Detection of Influenza a H1N1 Virus Using Highly Bright Multi-Quantum Dot-Embedded Particles and Magnetic Beads
Authors: Seder Islam , Jo Ahla , Jun Bong-Hyun , Kim Sung-Jin
Published: January 2022

Preventing the rapid spread of viral infectious diseases has become a major concern for global health. In this study, we present a microfluidic platform that performs an immunoassay of viral antigens in a simple, automated, yet highly sensitive manner. The device uses silica particles embedded with highly bright quantum dots (QD2) and performs the immunoassay with a vertically movable top layer and a rotating bottom layer. Through the motion of the layers and the surface tension in the liquids, reagents move from top chambers to bottom chambers and mix homogeneously. A tip in the top layer with a mobile permanent magnet moves the immune complexes comprising the magnetic beads, virus particles, and QD2 between the bottom chambers. In this way, our automated device achieves a highly sensitive magnetic bead-based sandwich immunoassay for the influenza A H1N1 virus within 32.5 min. The detection limit of our method is 5.1 × 10−4 hemagglutination units, which is 2 × 103 times more sensitive than that of the conventional hemagglutination method and is comparable to PCR. Our device is useful for the rapid and sensitive detection of infectious diseases in point-of-care applications and resource-limited environments.
The Effect of Silane Coupling Agent on the Texture and Properties of In Situ Synthesized PI/SiO2 Nanocomposite Film
Authors: Huang Jindong , Chen Hong , Zhang Guanglu , Fan Xiaowei , Liu Juncheng
Published: January 2022

PI/SiO2 composite films have been prepared by using in situ polymerization. The influences of the dosage of silane coupling agent (KH-560) on the structure and performance of PI/SiO2 composite film have been investigated. The results show that in the components without KH-560, the addition of SiO2 decreases the transmittance of the sample. Compared to the same SiO2 doping amount, the transmittance in the visible light range of the sample using KH-560 is higher than that of the sample without KH-560. After adding KH-560, the tensile strength, the elastic modulus the elongation at break of the sample have largely changed. The thermal stability and the ability to resist ultraviolet radiation of the composite film first increases and then decreases. Furthermore, the optimal dosage of KH-560 is 3%. Moreover, the addition of KH-560 has little effect on the transmittance of the PI/SiO2 composite films before and after UV irradiation.
Single Nano-Sized Metal–Organic Framework for Bio-Nanoarchitectonics with In Vivo Fluorescence Imaging and Chemo-Photodynamic Therapy
Authors: Wang Yong-Mei , Xu Ying , Zhang Xinxin , Cui Yifan , Liang Qingquan , Liu Cunshun , Wang Xinan , Wu Shuqi , Yang Rusen
Published: January 2022

Theranostics is an emerging technique for cancer treatments due to its safety and high efficiency. However, the stability, efficiency, and convenience of preparation are the main challenges for developing theranostics. Here we describe a one-pot process for biocompatible metal–organic framework (MOF)-based theranostics. The ligand H2L designed for the MOF enables both red fluorescence emission and photodynamic therapy (PDT). The frame and regular channel structure of H2L-MOF empower the theranostics with good drug delivery performance, and the uniform and nano-sized particles facilitate the in vivo imaging/therapy applications. In vivo fluorescence imaging and in vitro chemo-photodynamic therapy were achieved with the MOF without any further modification. Our results reveal an effective strategy to achieve multifunctional theranostics by the synergistic action of the organic ligand, metal node, and channel structure of MOF nanoparticles.
Bacteria-Assisted Transport of Nanomaterials to Improve Drug Delivery in Cancer Therapy
Authors: Jiménez-Jiménez Carla , Moreno Víctor M. , Vallet-Regí María
Published: January 2022

Currently, the design of nanomaterials for the treatment of different pathologies is presenting a major impact on biomedical research. Thanks to this, nanoparticles represent a successful strategy for the delivery of high amounts of drugs for the treatment of cancer. Different nanosystems have been designed to combat this pathology. However, the poor penetration of these nanomaterials into the tumor tissue prevents the drug from entering the inner regions of the tumor. Some bacterial strains have self-propulsion and guiding capacity thanks to their flagella. They also have a preference to accumulate in certain tumor regions due to the presence of different chemo-attractants factors. Bioconjugation reactions allow the binding of nanoparticles in living systems, such as cells or bacteria, in a simple way. Therefore, bacteria are being used as a transport vehicle for nanoparticles, facilitating their penetration and the subsequent release of the drug inside the tumor. This review would summarize the literature on the anchoring methods of diverse nanosystems in bacteria and, interestingly, their advantages and possible applications in cancer therapy.
Simultaneous Influence of Gradients in Natural Organic Matter and Abiotic Parameters on the Behavior of Silver Nanoparticles in the Transition Zone from Freshwater to Saltwater Environments
Authors: Čarapar Ivana , Jurković Lara , Pavičić-Hamer Dijana , Hamer Bojan , Lyons Daniel Mark
Published: January 2022

As nanoparticles have been found to cause a range of harmful impacts in biota, understanding processes and transformations which may stabilize and increase their persistence time in the environment are of great importance. As nanoparticles carried in riverine or wastewaters will eventually reach estuaries, understanding their behavior and transport potential in this transition zone from fresh to marine waters is essential, particularly as estuaries are sensitive ecological zones, oftentimes encompassing ornithologically important areas. In this direction, we report on the influence of combined gradients of riverine and marine natural organic matter (NOM) on the temporal stability of biocorona-encapsulated silver nanoparticles in terms of ion release kinetics. In parallel, salinity, pH and oxygen saturation were simultaneously varied to create a model to mimic the complex estuarine environment. While humic acid (HA) and alginate (Alg) disrupted the stabilizing ability of the nanoparticle protein corona to a greater and lesser degree, respectively, they slowed the rate of ion release in freshwater at pH 6.6 and in saltwater at pH 8, respectively, while oxygen saturation was also found to be an important factor. Thus, as the type of NOM changes with pH along a salinity gradient in an estuary, conditions required to increase the persistence time of nanoparticles are serendipitously met, with greater colloidal stability achieved in cases where there is more rapid replacement of HA with Alg. Despite the strong gradients in ionic strength, pH and oxygen saturation, the protein corona was not sufficiently disrupted at the nanoparticle surface to be substituted by NOM indicating the greater adsorption energy of the protein’s hydrophobic domains. Ultimately, it is the specific NOM profile of individual estuaries that may provide the best indicator for predicting the stability and persistence of silver nanoparticles as they transition from fresh to salt water environments.
The Rise and Fall of the Mediterranean Diet and Related Nutrients in Preventing Diabetes
Authors: Mirabelli Maria , Brunetti Antonio
Published: January 2022

Four years after the successful narrative review of Alkhatib et al [...]
Modeling the Predictive Value of Evidence-Based Referral Criteria to Support Healthy Gestational Weight Gain among an Australian Pregnancy Cohort
Authors: Fealy Shanna , Hollis Jenna , Martin Julia , Leigh Lucy , Oldmeadow Christopher , Collins Clare E. , Smith Roger , Wilkinson Shelley , Hure Alexis
Published: January 2022

Globally, there has been a renewed focus on addressing gestational weight gain (GWG). In Australia, the Department of Health pregnancy care guidelines recommend women be offered routine weighing and receive brief nutritional and physical activity support during antenatal care visits. Women gaining weight outside the Institute of Medicine (IOM)’s weight gain reference values are further recommended to be referred to a dietitian. However, professional and organizational barriers, including an absence of weight gain referral pathways and limited workforce resources, exist with the translation and scaling of these recommendations into practice. This study aimed to explore patterns of GWG among a cohort of Australian pregnant women and to determine if pregnancy weight gains of above or below 2 kg or 5 kg in the second and third trimester can be used to predict total GWG outside recommendations. Sensitivity, specificity, negative, and positive likelihood ratios were calculated. The most predictive time point was 24 weeks’ gestation using the minimum weight change parameter of +/−2 kg, demonstrating reasonable sensitivity (0.81, 95% CI 0.61–0.83) and specificity (0.72, 95% CI 0.61–0.83), resulting in 55% (n = 72/131) of the cohort qualifying for dietetic referral. Given the current health service constraints, a review of dietetic services within maternity care is warranted.
Effect of Type 2 Diabetes and Impaired Glucose Tolerance on Digestive Enzymes and Glucose Absorption in the Small Intestine of Young Rats
Authors: Gromova Lyudmila V. , Polozov Alexandr S. , Savochkina Elizaveta V. , Alekseeva Anna S. , Dmitrieva Yulia V. , Kornyushin Oleg V. , Gruzdkov Andrey A.
Published: January 2022

The reactions of intestinal functional parameters to type 2 diabetes at a young age remain unclear. The study aimed to assess changes in the activity of intestinal enzymes, glucose absorption, transporter content (SGLT1, GLUT2) and intestinal structure in young Wistar rats with type 2 diabetes (T2D) and impaired glucose tolerance (IGT). To induce these conditions in the T2D (n = 4) and IGT (n = 6) rats, we used a high-fat diet and a low dose of streptozotocin. Rats fed a high-fat diet (HFD) (n = 6) or a standard diet (SCD) (n = 6) were used as controls. The results showed that in T2D rats, the ability of the small intestine to absorb glucose was higher in comparison to HFD rats (p < 0.05). This was accompanied by a tendency towards an increase in the number of enterocytes on the villi of the small intestine in the absence of changes in the content of SGLT1 and GLUT2 in the brush border membrane of the enterocytes. T2D rats also showed lower maltase and alkaline phosphatase (AP) activity in the jejunal mucosa compared to the IGT rats (p < 0.05) and lower AP activity in the colon contents compared to the HFD (p < 0.05) and IGT (p < 0.05) rats. Thus, this study provides insights into the adaptation of the functional and structural parameters of the small intestine in the development of type 2 diabetes and impaired glucose tolerance in young representatives.
Additive Effects of Exercise or Nutrition Intervention in a 24-Month Multidisciplinary Treatment with a Booster Intervention for Children and Adolescents with Overweight or Obesity: The ICAAN Study
Authors: Woo Sarah , Ju Young-Su , Seo Young-Gyun , Kim Yoon-Myung , Lim Hyunjung , Park Kyung-Hee
Published: January 2022

This study compared the effects of a real-world multidisciplinary intervention with additional exercise or nutritional elements and investigated the effectiveness of a booster intervention after weight regain. A total of 242 children and adolescents (age- and sex-specific body mass index [BMI] ≥ 85th percentile, mean age: 10.82 years, 60% male) were allocated to three groups: usual care, exercise, or nutrition. Six-month active treatment with 1:1 session and a maintenance stage with group activities were repeated twice to comprise a 24-month intervention. The primary outcome was change % of the BMI z-score (zBMI). A total of 110 (45.4%) participants completed the 24-month intervention. A mixed-effects model analysis indicated no significant interaction effect of the intervention group and treatment phase on the zBMI change % (p = 0.976). However, there was a significant main effect of the treatment phase on zBMI change % at 6 months (β = −2.98, [95% CI, −5.69–0.27]), 18 months (β = −3.99, [95% CI, −6.76–1.22]), and 24 months (β = −3.23, [95% CI, −5.94–0.52]; p = 0.042). The improvements in zBMI, body fat %, and cardiometabolic markers were observed only among males. Whereas the additive effect of intensive exercise or nutritional feedback was not detected in the long term, a booster intervention with 1:1 counseling was effective even after weight regain during the maintenance period. It may be useful to combine individualized counseling with a less intensive form of group care for long-term maintenance in a real-world setting.
Antibacterial Activity and Epigenetic Remodeling of Essential Oils from Calabrian Aromatic Plants
Authors: D’Aquila Patrizia , Paparazzo Ersilia , Crudo Michele , Bonacci Sonia , Procopio Antonio , Passarino Giuseppe , Bellizzi Dina
Published: January 2022

Natural compounds have historically had a wide application in nutrition. Recently, a fundamental role has been identified for essential oils extracted from aromatic plants for their nutritional, antimicrobial, and antioxidant properties, and as food preservatives. In the present study, essential oils (EOs) from ten aromatic plants grown in Calabria (Italy), used routinely to impart aroma and taste to food, were evaluated for their antibacterial activity. This activity was investigated against Escherichia coli strain JM109, and its derived antibiotic-resistant cells selected by growing the strain at low concentrations of ampicillin, ciprofloxacin, and gentamicin by measuring the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). Although all the essential oils showed bactericidal activity, those from Clinopodium nepeta, Origanum vulgare, and Foeniculum vulgare displayed the greatest inhibitory effects on the bacterial growth of all cell lines. It is plausible that the antibacterial activity is mediated by epigenetic modifications since the tested essential oils induce methylation both at adenine and cytosine residues in the genomes of most cell lines. This study contributes to a further characterization of the properties of essential oils by shedding new light on the molecular mechanisms that mediate these properties.
Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) II: Growth
Authors: Lin Luling , Gamble Greg D. , Crowther Caroline A. , Bloomfield Frank H. , Agosti Massimo , Atkinson Stephanie A. , Biasini Augusto , Embleton Nicholas D. , Lamy Filho Fernando , Fusch Christoph , Gianni Maria L. , Kutman Hayriye Gözde Kanmaz , Koo Winston , Litmanovitz Ita , Morgan Colin , Mukhopadhyay Kanya , Neri Erica , Picaud Jean-Charles , Rochow Niels , Roggero Paola , Stroemmen Kenneth , Tan Maw J. , Tandoi Francesco M. , Wood Claire L. , Zachariassen Gitte , Harding Jane E.
Published: January 2022

Neonatal nutritional supplements may improve early growth for infants born small, but effects on long-term growth are unclear and may differ by sex. We assessed the effects of early macronutrient supplements on later growth. We searched databases and clinical trials registers from inception to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter BMI in childhood (kg/m2: adjusted mean difference (aMD) −0.11[95% CI −0.47, 0.25], p = 0.54; 3 trials, n = 333). Supplementation increased length (cm: aMD 0.37[0.01, 0.72], p = 0.04; 18 trials, n = 2008) and bone mineral content (g: aMD 10.22[0.52, 19.92], p = 0.04; 6 trials, n = 313) in infancy, but not at older ages. There were no differences between supplemented and unsupplemented groups for other outcomes. In subgroup analysis, supplementation increased the height z-score in male toddlers (aMD 0.20[0.02, 0.37], p = 0.03; 10 trials, n = 595) but not in females, and no significant sex interaction was observed (p = 0.21). Macronutrient supplementation for infants born small may not alter BMI in childhood. Supplementation increased growth in infancy, but these effects did not persist in later life. The effects did not differ between boys and girls.
Plinia trunciflora Extract Administration Prevents HI-Induced Oxidative Stress, Inflammatory Response, Behavioral Impairments, and Tissue Damage in Rats
Authors: Carvalho Andrey Vinicios S. , Ribeiro Rafael T. , Durán-Carabali Luz Elena , Martini Ana Paula R. , Hoeper Eduarda , Sanches Eduardo F. , Konrath Eduardo Luis , Dalmaz Carla , Wajner Moacir , Netto Carlos Alexandre
Published: January 2022

The disruption of redox homeostasis and neuroinflammation are key mechanisms in the pathogenesis of brain hypoxia–ischemia (HI); medicinal plants have been studied as a therapeutic strategy, generally associated with the prevention of oxidative stress and inflammatory response. This study evaluates the neuroprotective role of the Plinia trunciflora fruit extract (PTE) in neonatal rats submitted to experimental HI. The HI insult provoked a marked increase in the lipoperoxidation levels and glutathione peroxidase (GPx) activity, accompanied by a decrease in the brain concentration of glutathione (GSH). Interestingly, PTE was able to prevent most of the HI-induced pro-oxidant effects. It was also observed that HI increased the levels of interleukin-1β in the hippocampus, and that PTE-treatment prevented this effect. Furthermore, PTE was able to prevent neuronal loss and astrocyte reactivity induced by HI, as demonstrated by NeuN and GFAP staining, respectively. PTE also attenuated the anxiety-like behavior and prevented the spatial memory impairment caused by HI. Finally, PTE prevented neural tissue loss in the brain hemisphere, the hippocampus, cerebral cortex, and the striatum ipsilateral to the HI. Taken together our results provide good evidence that the PTE extract has the potential to be investigated as an adjunctive therapy in the treatment of brain insult caused by neonatal hypoxia–ischemia.
West Nile Virus in Common Wild Avian Species in Israel
Authors: Schvartz Gili , Tirosh-Levy Sharon , Bider Shahar , Lublin Avishai , Farnoushi Yigal , Erster Oran , Steinman Amir
Published: January 2022

In order to evaluate the contribution of different wild bird species to West Nile virus (WNV) circulation in Israel, during the months preceding the 2018 outbreak that occurred in Israel, we randomly sampled 136 frozen carcasses of a variety of avian species. Visceral and central nervous system (CNS) tissue pools were tested using WNV NS2A RT qPCR assay; of those, 15 (11.03%, 95% CI: 6.31–17.54%) tissue pools were positive. A total of 13 out of 15 WNV RT qPCR positive samples were successfully sequenced. Phylogenetic analysis indicated that all WNV isolates were identified as lineage 1 and all categorized as cluster 2 eastern European. Our results indicated that WNV isolates that circulated within the surveyed wild birds in spring 2018 were closely related to several of the isolates of the previously reported 2018 outbreak in birds in Israel and that the majority of infected birds were of local species.
Prevalence of Toxoplasma gondii Measured by Western Blot, ELISA and DNA Analysis, by PCR, in Cats of Western Mexico
Authors: Galván-Ramírez María de la Luz , Charles-Niño Claudia , Pedroza-Roldán César , Salazar-Reveles Carolina , Ocampo-Figueroa Karen Lissete , Rodríguez-Pérez Laura Roció , Paez-Magallán Varinia Margarita
Published: January 2022

Toxoplasma gondii is the causative agent of toxoplasmosis in humans and animals. The sexual reproductive cycle of Toxoplasma takes place in the small intestine of felines, the definitive hosts. In the final part of the sexual cycle, T. gondii forms oocysts in infected cats. Oocysts transferred via the faeces to the environment are highly infectious to both animals and humans. This study aimed to determine the prevalence and risk factors associated with T. gondii infection in cats from the metropolitan region of Guadalajara in western Mexico. Western blotting and ELISA for anti-Toxoplasma IgG antibodies was performed, and Toxoplasma DNA was identified using polymerase chain reaction. Prevalence of anti-T. gondii antibodies was 14.8% (44/297), and only 2/297 cases were positive for PCR. Cats older than one year were at an increased risk of infection (OR = 3.9, 95% CI 1.844–8.362). Sex, raw meat feeding, hunting habits, vaccination status, and body condition were not associated with positivity. The prevalence of T. gondii infection determined with Western blot in cats in the metropolitan area of Guadalajara, Jalisco, Mexico, was lower than that reported in previous studies.
CD44-Targeted Carriers: The Role of Molecular Weight of Hyaluronic Acid in the Uptake of Hyaluronic Acid-Based Nanoparticles
Authors: Chiesa Enrica , Greco Antonietta , Riva Federica , Dorati Rossella , Conti Bice , Modena Tiziana , Genta Ida
Published: January 2022

Nanotechnology offers advanced biomedical tools for diagnosis and drug delivery, stressing the value of investigating the mechanisms by which nanocarriers interact with the biological environment. Herein, the cellular response to CD44-targeted nanoparticles (NPs) was investigated. CD44, the main hyaluronic acid (HA) receptor, is widely exploited as a target for therapeutic purposes. HA NPs were produced by microfluidic platform starting from HA with different molecular weights (Mw, 280, 540, 820 kDa) by polyelectrolyte complexation with chitosan (CS). Thanks to microfluidic technology, HA/CS NPs with the same physical features were produced, and only the effects of HA Mw on CD44-overexpressing cells (human mesenchymal stem cells, hMSCs) were studied. This work provides evidence of the HA/CS NPs biocompatibility regardless the HA Mw and reveals the effect of low Mw HA in improving the cell proliferation. Special attention was paid to the endocytic mechanisms used by HA/CS NPs to enter hMSCs. The results show the notable role of CD44 and the pronounced effect of HA Mw in the NPs’ internalization. HA/CS NPs uptake occurs via different endocytic pathways simultaneously, and most notably, NPs with 280 kDa HA were internalized by clathrin-mediated endocytosis. Instead, NPs with 820 kDa HA revealed a greater contribution of caveolae and cytoskeleton components.
Impact of Formulation Conditions on Lipid Nanoparticle Characteristics and Functional Delivery of CRISPR RNP for Gene Knock-Out and Correction
Authors: Walther Johanna , Wilbie Danny , Tissingh Vincent S. J. , Öktem Mert , van der Veen Heleen , Lou Bo , Mastrobattista Enrico
Published: January 2022

The CRISPR-Cas9 system is an emerging therapeutic tool with the potential to correct diverse genetic disorders. However, for gene therapy applications, an efficient delivery vehicle is required, capable of delivering the CRISPR-Cas9 components into the cytosol of the intended target cell population. In this study, we optimized the formulation conditions of lipid nanoparticles (LNP) for delivery of ready-made CRISPR-Cas9 ribonucleic protein (RNP). The buffer composition during complexation and relative DOTAP concentrations were varied for LNP encapsulating in-house produced Cas9 RNP alone or Cas9 RNP with additional template DNA for gene correction. The LNP were characterized for size, surface charge, and plasma interaction through asymmetric flow field flow fractionation (AF4). Particles were functionally screened on fluorescent reporter cell lines for gene knock-out and gene correction. This revealed incompatibility of RNP with citrate buffer and PBS. We demonstrated that LNP for gene knock-out did not necessarily require DOTAP, while LNP for gene correction were only active with a low concentration of DOTAP. The AF4 studies additionally revealed that LNP interact with plasma, however, remain stable, whereby HDR template seems to favor stability of LNP. Under optimal formulation conditions, we achieved gene knock-out and gene correction efficiencies as high as 80% and 20%, respectively, at nanomolar concentrations of the CRISPR-Cas9 RNP.