bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Analysis Reveals a Critical Point Mutation in the N-Terminal Region of the Signaling Lymphocytic Activation Molecule Responsible for the Cross-Species Infection with Canine Distemper Virus
Authors: Yamamoto Yuta , Nakano Shogo , Seki Fumio , Shigeta Yasuteru , Ito Sohei , Tokiwa Hiroaki , Takeda Makoto
Published: February 2021

Infection of hosts by morbilliviruses is facilitated by the interaction between viral hemagglutinin (H-protein) and the signaling lymphocytic activation molecule (SLAM). Recently, the functional importance of the n-terminal region of human SLAM as a measles virus receptor was demonstrated. However, the functional roles of this region in the infection process by other morbilliviruses and host range determination remain unknown, partly because this region is highly flexible, which has hampered accurate structure determination of this region by X-ray crystallography. In this study, we analyzed the interaction between the H-protein from canine distemper virus (CDV-H) and SLAMs by a computational chemistry approach. Molecular dynamics simulations and fragment molecular orbital analysis demonstrated that the unique His28 in the N-terminal region of SLAM from Macaca is a key determinant that enables the formation of a stable interaction with CDV-H, providing a basis for CDV infection in Macaca. The computational chemistry approach presented should enable the determination of molecular interactions involving regions of proteins that are difficult to predict from crystal structures because of their high flexibility.
Progresses in Food Packaging, Food Quality, and Safety—Controlled-Release Antioxidant and/or Antimicrobial Packaging
Authors: Vasile Cornelia , Baican Mihaela
Published: February 2021

Food packaging is designed to protect foods, to provide required information about the food, and to make food handling convenient for distribution to consumers. Packaging has a crucial role in the process of food quality, safety, and shelf-life extension. Possible interactions between food and packaging are important in what is concerning food quality and safety. This review tries to offer a picture of the most important types of active packaging emphasizing the controlled/target release antimicrobial and/or antioxidant packaging including system design, different methods of polymer matrix modification, and processing. The testing methods for the appreciation of the performance of active food packaging, as well as mechanisms and kinetics implied in active compounds release, are summarized. During the last years, many fast advancements in packaging technology appeared, including intelligent or smart packaging (IOSP), (i.e., time–temperature indicators (TTIs), gas indicators, radiofrequency identification (RFID), and others). Legislation is also discussed.
Protective Effects of Baicalin on Peritoneal Tight Junctions in Piglets Challenged with Glaesserella parasuis
Authors: Zhang Jiacheng , Zhang Zhaoran , Xu Jianfeng , Ye Chun , Fu Shulin , Hu Chien-An Andy , Qiu Yinsheng , Liu Yu
Published: February 2021

Glaesserella parasuis (G. parasuis) causes inflammation and damage to piglets. Whether polyserositis caused by G. parasuis is due to tight junctions damage and the protective effect of baicalin on it have not been examined. Therefore, this study aims to investigate the effects of baicalin on peritoneal tight junctions of piglets challenged with G. parasuis and its underlying molecular mechanisms. Piglets were challenged with G. parasuis and treated with or without baicalin. RT-PCR was performed to examine the expression of peritoneal tight junctions genes. Immunofluorescence was carried out to detect the distribution patterns of tight junctions proteins. Western blot assays were carried out to determine the involved signaling pathways. Our data showed that G. parasuis infection can down-regulate the tight junctions expression and disrupt the distribution of tight junctions proteins. Baicalin can alleviate the down-regulation of tight junctions mRNA in peritoneum, prevent the abnormalities and maintain the continuous organization of tight junctions. Our results provide novel evidence to support that baicalin has the capacity to protect peritoneal tight junctions from G. parasuis-induced inflammation. The protective mechanisms of baicalin could be associated with inhibition of the activation of PKC and MLCK/MLC signaling pathway. Taken together, these data demonstrated that baicalin is a promising natural agent for the prevention and treatment of G. parasuis infection.
3D Metal–Organic Frameworks Based on Co(II) and Bithiophendicarboxylate: Synthesis, Crystal Structures, Gas Adsorption, and Magnetic Properties
Authors: Dubskikh Vadim A. , Lysova Anna A. , Samsonenko Denis G. , Lavrov Alexander N. , Kovalenko Konstantin A. , Dybtsev Danil N. , Fedin Vladimir P.
Published: February 2021

Three new 3D metal-organic porous frameworks based on Co(II) and 2,2′-bithiophen-5,5′-dicarboxylate (btdc2−) [Co3(btdc)3(bpy)2]·4DMF, 1; [Co3(btdc)3(pz)(dmf)2]·4DMF·1.5H2O, 2; [Co3(btdc)3(dmf)4]∙2DMF∙2H2O, 3 (bpy = 2,2′-bipyridyl, pz = pyrazine, dmf = N,N-dimethylformamide) were synthesized and structurally characterized. All compounds share the same trinuclear carboxylate building units {Co3(RCOO)6}, connected either by btdc2– ligands (1, 3) or by both btdc2– and pz bridging ligands (2). The permanent porosity of 1 was confirmed by N2, O2, CO, CO2, CH4 adsorption measurements at various temperatures (77 K, 273 K, 298 K), resulted in BET surface area 667 m2⋅g−1 and promising gas separation performance with selectivity factors up to 35.7 for CO2/N2, 45.4 for CO2/O2, 20.8 for CO2/CO, and 4.8 for CO2/CH4. The molar magnetic susceptibilities χp(T) were measured for 1 and 2 in the temperature range 1.77–330 K at magnetic fields up to 10 kOe. The room-temperature values of the effective magnetic moments for compounds 1 and 2 are μeff (300 K) ≈ 4.93 μB. The obtained results confirm the mainly paramagnetic nature of both compounds with some antiferromagnetic interactions at low-temperatures T < 20 K in 2 between the Co(II) cations separated by short pz linkers. Similar conclusions were also derived from the field-depending magnetization data of 1 and 2.
Simulation of the In Vivo Fate of Polymeric Nanoparticles Traced by Environment-Responsive Near-Infrared Dye: A Physiologically Based Pharmacokinetic Modelling Approach
Authors: Li Lei , He Haisheng , Jiang Sifang , Qi Jianping , Lu Yi , Ding Ning , Lin Hai-Shu , Wu Wei , Xiang Xiaoqiang
Published: February 2021

The application of physiologically based pharmacokinetic models to nanoparticles is still very restricted and challenging, owing to the complicated in vivo transport mechanisms involving nanoparticles, including phagocytosis, enhanced permeability and retention effects, cellular recognition, and internalisation, enzymatic degradation, lymphatic transport, and changes in physical properties. In our study, five nanoparticle formulations were synthesised using polycaprolactone as a framework material and methoxy poly (ethylene glycol)-poly(ε-caprolactone) as a long-circulating decorating material, as well as types of environmentally responsive near-infrared aza-boron-dipyrromethene dyes. According to quantification data and direct visualisation involving specific organs, a phagocytosis physiologically based pharmacokinetic model was developed to describe the dynamics of nanoparticles within and between organs in mice, considering cellular mechanisms involving phagocytosis and enhanced permeability and retention effects. Our results offer a better understanding of the in vivo fate of polymeric nanoparticles.
Synthesis of Highly Potent Anti-Inflammatory Compounds (ROS Inhibitors) from Isonicotinic Acid
Authors: Yaqoob Sana , Nasim Nourina , Khanam Rahila , Wang Yan , Jabeen Almas , Qureshi Urooj , Ul-Haq Zaheer , El-Seedi Hesham R. , Jiang Zi-Hua , Khan Farooq-Ahmad
Published: February 2021

In search of anti-inflammatory compounds, novel scaffolds containing isonicotinoyl motif were synthesized via an efficient strategy. The compounds were screened for their in vitro anti-inflammatory activity. Remarkably high activities were observed for isonicotinates 5–6 and 8a–8b. The compound 5 exhibits an exceptional IC50 value (1.42 ± 0.1 µg/mL) with 95.9% inhibition at 25 µg/mL, which is eight folds better than the standard drug ibuprofen (11.2 ± 1.9 µg/mL). To gain an insight into the mode of action of anti-inflammatory compounds, molecular docking studies were also performed. Decisively, further development and fine tuning of these isonicotinates based scaffolds for the treatment of various aberrations is still a wide-open field of research.
Conversion of Racemic Unnatural Amino Acids to Optically Pure Forms by a Coupled Enzymatic Reaction
Authors: Lee Hannae , Kim Dongchan , Kim Sooin , Lee Hyun Soo
Published: February 2021

Genetic code expansion (GCE) technology is a useful tool for the site-specific modification of proteins. An unnatural amino acid (UAA) is one of the essential components of this technique, typically required at high concentration (1 mM or higher) in growth medium. The supply of UAAs is an important limitation to the application of GCE technology, as many UAAs are either expansive or commercially unavailable. In this study, two UAAs in a racemic mixture were converted into optically pure forms using two enzymes, the d-amino acid oxidase (RgDAAO) from Rhodotorula gracilis and the aminotransferase (TtAT) from Thermus thermophilus. In the coupled enzyme system, RgDAAO oxidizes the d-form of UAAs in a stereospecific manner and produces the corresponding α-keto acids, which are then converted into the l-form of UAAs by TtAT, resulting in the quantitative and stereospecific conversion of racemic UAAs to optically pure forms. The genetic incorporation of the optically pure UAAs into a target protein produced a better protein yield than the same experiments using the racemic mixtures of the UAAs. This method could not only be used for the preparation of optically pure UAAs from racemic mixtures, but also the broad substrate specificity of both enzymes would allow for its expansion to structurally diverse UAAs.
Induction of Apoptosis and Regulation of MicroRNA Expression by (2E,6E)-2,6-bis-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone (BHMC) Treatment on MCF-7 Breast Cancer Cells
Authors: Yeap Swee Keong , Mohd Ali Norlaily , Akhtar Muhammad Nadeem , Razak Nursyamirah Abd , Chong Zhi Xiong , Ho Wan Yong , Boo Lily , Zareen Seema , Kurniawan Tonni Agustiono , Avtar Ram , Ng Stephanie Y. L. , Ong Alan Han Kiat , Alitheen Noorjahan Banu
Published: February 2021

(2E,6E)-2,6-bis-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone (BHMC) is a synthetic curcumin analogue, which has been reported to possess anti-tumor, anti-metastatic, and anti-invasion properties on estrogen receptor (ER) negative breast cancer cells in vitro and in vivo. However, the cytotoxic effects of BHMC on ER positive breast cancer cells were not widely reported. This study was aimed to investigate the cytotoxic potential of BHMC on MCF-7 cells using cell viability, cell cycle, and apoptotic assays. Besides, microarray and quantitative polymerase chain reaction (qPCR) were performed to identify the list of miRNAs and genes, which could be dysregulated following BHMC treatment. The current study discovered that BHMC exhibits selective cytotoxic effects on ER positive MCF-7 cells as compared to ER negative MDA-MB-231 cells and normal breast cells, MCF-10A. BHMC was shown to promote G2/M cell cycle arrest and apoptosis in MCF-7 cells. Microarray and qPCR analysis demonstrated that BHMC treatment would upregulate several miRNAs like miR-3195 and miR-30a-3p and downregulate miRNAs such as miR-6813-5p and miR-6132 in MCF-7 cells. Besides, BHMC administration was also found to downregulate few tumor-promoting genes like VEGF and SNAIL in MCF-7. In conclusion, BHMC induced apoptosis in the MCF-7 cells by altering the expressions of apoptotic-regulating miRNAs and associated genes.
Structure Elucidation and Cholinesterase Inhibition Activity of Two New Minor Amaryllidaceae Alkaloids
Authors: Maříková Jana , Mamun Abdullah Al , Shammari Latifah Al , Korábečný Jan , Kučera Tomáš , Hulcová Daniela , Kuneš Jiří , Malaník Milan , Vašková Michaela , Kohelová Eliška , Nováková Lucie , Cahlíková Lucie , Pour Milan
Published: February 2021

Two new minor Amaryllidaceae alkaloids were isolated from Hippeastrum × hybridum cv. Ferrari and Narcissus pseudonarcissus cv. Carlton. The chemical structures were identified by various spectroscopic (one- and two-dimensional (1D and 2D) NMR, circular dichroism (CD), high-resolution mass spectrometry (HRMS) and by comparison with literature data of similar compounds. Both isolated alkaloids were screened for their human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBuChE) inhibition activity. One of the new compounds, a heterodimer alkaloid of narcikachnine-type, named narciabduliine (2), showed balanced inhibition potency for both studied enzymes, with IC50 values of 3.29 ± 0.73 µM for hAChE and 3.44 ± 0.02 µM for hBuChE. The accommodation of 2 into the active sites of respective enzymes was predicted using molecular modeling simulation.
Clinical Relevance of [18F]Florbetaben and [18F]FDG PET/CT Imaging on the Management of Patients with Dementia
Authors: Librizzi Damiano , Cabanel Nicole , Zavorotnyy Maxim , Riehl Elisabeth , Kircher Tilo , Luster Markus , Hooshyar Yousefi Behrooz
Published: February 2021

PET of β-Amyloid plaques (Aβ) using [18F]florbetaben ([18F]FBB) and [18F]fluorodeoxyglucose ([18F]FDG) increasingly aid clinicians in early diagnosis of dementia, including Alzheimer’s disease (AD), frontotemporal disease, dementia with Lewy bodies, and vascular dementia. The aim of this retrospective analysis was to evaluate clinical relevance of [18F]FBB, [18F]FDG PET and complimentary CSF measurements in patients with suspected dementia. In this study, 40 patients with clinically suspected or history of dementia underwent (1) measurement of Aβ peptides, total tau, and p-tau protein levels in the cerebrospinal fluid (CSF) compared with healthy controls (HC); (2) clinical and neuropsychological assessment, which included Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological assessment battery (CERAD-NAB); (3) [18F]FBB and [18F]FDG PET imaging within an average of 3 weeks. The subjects were within 15 days stratified using PET, CSF measurements as HC, mild cognitive impaired (MCI) and dementia including Alzheimer´s disease. The predictive dementia-related cognitive decline values were supporting the measurements. PET images were evaluated visually and quantitatively using standard uptake value ratios (SUVR). Twenty-one (52.5%) subjects were amyloid-positive (Aβ+), with a median neocortical SUVR of 1.80 for AD versus 1.20 relative to the respective 19 (47.5 %) amyloid-negative (Aβ-) subjects. Moreover, the [18F]FDG and [18F]FBB confirmed within a sub-group of 10 patients a good complimentary role by correlation between amyloid pathology and brain glucose metabolism in 8 out of 10 subjects. The results suggest the clinical relevance for [18F]FBB combined with [18F]FDG PET retention and CFS measurements serving the management of our patients with dementia. Therefore, [18F]FBB combined with [18F]FDG PET is a helpful tool for differential diagnosis, and supports the patients’ management as well as treatment.
Methionine-Functionalized Graphene Oxide/Sodium Alginate Bio-Polymer Nanocomposite Hydrogel Beads: Synthesis, Isotherm and Kinetic Studies for an Adsorptive Removal of Fluoroquinolone Antibiotics
Authors: Yadav Sushma , Asthana Anupama , Singh Ajaya Kumar , Chakraborty Rupa , Vidya S. , Singh Ambrish , Carabineiro Sónia A. C.
Published: February 2021

In spite of the growing demand for new antibiotics, in the recent years, the occurrence of fluoroquinolone antibiotics (as a curative agent for urinary tract disorders and respiratory problems) in wastewater have drawn immense attention. Traces of antibiotic left-overs are present in the water system, causing noxious impact on human health and ecological environments, being a global concern. Our present work aims at tackling the major challenge of toxicity caused by antibiotics. This study deals with the efficient adsorption of two commonly used fluoroquinolone (FQ) antibiotics, i.e., Ofloxacin (OFX) and Moxifloxacin (MOX) on spherical hydrogel beads generated from methionine‒functionalized graphene oxide/ sodium alginate polymer (abbreviated Met-GO/SA) from aqueous solutions. The composition, morphology and crystal phase of prepared adsorbents were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FTIR), high-resolution transmission electron microscopy (HR-TEM) and thermogravimetric analysis/differential thermogravimetry (TGA/DTG). Batch adsorption tests are followed to optimize the conditions required for adsorption process. Both functionalized and non-functionalized adsorbents were compared to understand the influence of several experimental parameters, such as, the solution pH, contact time, adsorbent dosage, temperature and initial concentration of OFX and MOX on adsorption. The obtained results indicated that the functionalized adsorbent (Met-GO/SA) showed a better adsorption efficiency when compared to non-functionalized (GO/SA) adsorbent. Further, the Langmuir isotherm was validated as the best fitting model to describe adsorption equilibrium and pseudo second-order-kinetic model fitted well for both types of adsorbate. The maximum adsorption capacities of Met-GO/SA were 4.11 mg/g for MOX and 3.43 mg/g for OFX. Thermodynamic parameters, i.e., ∆G°, ∆H° and ∆S° were also calculated. It was shown that the overall adsorption process was thermodynamically favorable, spontaneous and exothermic in nature. The adsorbents were successfully regenerated up to four cycles with 0.005 M NaCl solutions. Overall, our work showed that the novel Met-GO/SA nanocomposite could better contribute to the removal of MOX and OFX from the liquid media. The gel beads prepared have adequate features, such as simple handling, eco-friendliness and easy recovery. Hence, polymer gel beads are promising candidates as adsorbents for large-scale water remediation.
Artificial Cathode-Electrolyte Interphase towards High-Performance Lithium-Ion Batteries: A Case Study of β-AgVO3
Authors: Liu Liang , Dai Wei , Zhu Hongzheng , Gu Yanguang , Wang Kangkang , Li Chao , Pan Chaofeng , Zhou Min , Liu Jian
Published: February 2021

Silver vanadates (SVOs) have been widely investigated as cathode materials for high-performance lithium-ion batteries (LIBs). However, similar to most vanadium-based materials, SVOs suffer from structural collapse/amorphization and vanadium dissolution from the electrode into the electrolyte during the Li insertion and extraction process, causing poor electrochemical performance in LIBs. We employ ultrathin Al2O3 coatings to modify β-AgVO3 (as a typical example of SVOs) by an atomic layer deposition (ALD) technique. The galvanostatic charge-discharge test reveals that ALD Al2O3 coatings with different thicknesses greatly affected the cycling performance. Especially, the β-AgVO3 electrode with ~10 nm Al2O3 coating (100 ALD cycles) exhibits a high specific capacity of 271 mAh g−1, and capacity retention is 31%, much higher than the uncoated one of 10% after 100 cycles. The Coulombic efficiency is improved from 89.8% for the pristine β-AgVO3 to 98.2% for Al2O3-coated one. Postcycling analysis by cyclic voltammetry (CV), cyclic voltammetry (EIS), and scanning electron microscopy (SEM) disclose that 10-nm Al2O3 coating greatly reduces cathode-electrolyte interphase (CEI) resistance and the charge transfer resistance in the β-AgVO3 electrode. Al2O3 coating by the ALD method is a promising technique to construct artificial CEI and stabilize the structure of SVOs, providing new insights for vanadium-based electrodes and their energy storage devices.
Evaluation of Ni-Based Flexible Resistance Temperature Detectors Fabricated by Laser Digital Pattering
Authors: Nam Vu Binh , Lee Daeho
Published: February 2021

Temperature sensors are ubiquitous in every field of engineering application since temperature control is vital in operating, testing and monitoring various equipment systems. Herein, we introduce a facile and rapid laser digital patterning (LDP) process to fabricate low-cost, Ni-based flexible resistance temperature detectors (RTDs). Ni-based RTDs are directly generated on a thin flexible polyimide substrate (thickness: 50 µm) by laser-induced reductive sintering of a solution-processed nonstoichiometric nickel oxide (NiOx) nanoparticle thin film under ambient conditions. The shape of RTDs can be easily adjusted by controlling computer-aided design (CAD) data without using the physical patterning mask while the sensitivity (temperature coefficient of resistance (α) ~ 3.52 × 10−3 °C−1) of the sensors can be maintained regardless of shape and size of the sensor electrodes. The flexible Ni-based RTDs can operate over a wide temperature range up to 200 °C with excellent repeatability. Additionally, the Ni-based RTDs respond quickly to the temperature change and can operate in corrosive environments including water and seawater. Moreover, the Ni-based RTDs show a superior mechanical and electrical stability with a negligible resistance change up to a radius of curvature of 1.75 mm. Finally, a tape-pull test demonstrates the robust adhesion of Ni-based RTDs on the substrate.
Development of an Innovative and Green Method to Obtain Nanoparticles in Aqueous Solution from Carbon-Based Waste Ashes
Authors: Striani Raffaella , Stasi Enrica , Giuri Antonella , Seiti Miriam , Ferraris Eleonora , Esposito Corcione Carola
Published: February 2021

In this study, an original and green procedure to produce water-based solutions containing nanometric recycled carbon particles is proposed. The nanometric particles are obtained starting from carbon waste ashes, produced by the wooden biomass pyro-gasification plant CMD (Costruzioni motori diesel) ECO20. The latter is an integrated system combining a downdraft gasifier, a spark-ignition internal combustion engine, an electric generator and syngas cleaning devices, and it can produce electric and thermal power up to 20 kWe and 40 kWth. The carbon-based ashes (CA) produced by the CMD ECO20 plant were, first, characterized by using differential scanning calorimetry (DSC) and microcomputed tomography (microCT). Afterward, they were reduced in powder by using a milling mortar and analyzed by scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) spectrometry, thermogravimetric analysis (TGA), X-ray diffraction (WAXD) and Fourier-transform infrared (FTIR) spectroscopy. The optimization of an original procedure to reduce the dimensions of the ashes in an aqueous solution was then developed by using ball milling and sonication techniques, and the nanometric dimensions of the particles dispersed in water were estimated by dynamic light scattering (DLS) measurements in the order of 300 nm. Finally, possible industrial applications for the nanomaterials obtained from the waste ashes are suggested, including, for example, inks for Aerosol Jet® Printing (AJ® P).
Effect of the Anionic Counterpart: Molybdate vs. Tungstate in Energy Storage for Pseudo-Capacitor Applications
Authors: Sharma Pratigya , Minakshi Manickam , Whale Jonathan , Jean-Fulcrand Annelise , Garnweitner Georg
Published: February 2021

Nickel-based bimetallic oxides (BMOs) have shown significant potential in battery-type electrodes for pseudo-capacitors given their ability to facilitate redox reactions. In this work, two bimetallic oxides, NiMoO4 and NiWO4, were synthesized using a wet chemical route. The structure and electrochemical properties of the pseudo-capacitor cathode materials were characterized. NiMoO4 showed superior charge storage performance in comparison to NiWO4, exhibiting a discharge capacitance of 124 and 77 F·g−1, respectively. NiMoO4, moreover, demonstrates better capacity retention after 1000 cycles with 87.14% compared to 82.22% for NiWO4. The lower electrochemical performance of the latter was identified to result from the redox behavior during cycling. NiWO4 reacts in the alkaline solution and forms a passivation layer composed of WO3 on the electrode, while in contrast, the redox behavior of NiMoO4 is fully reversible.
Metal–Insulator Transition of Ultrathin Sputtered Metals on Phenolic Resin Thin Films: Growth Morphology and Relations to Surface Free Energy and Reactivity
Authors: Schuster Christian , Rennhofer Harald , Amenitsch Heinz , Lichtenegger Helga C. , Jungbauer Alois , Tscheliessing Rupert
Published: February 2021

Nanostructured metal assemblies on thin and ultrathin polymeric films enable state of the art technologies and have further potential in diverse fields. Rational design of the structure–function relationship is of critical importance but aggravated by the scarcity of systematic studies. Here, we studied the influence of the interplay between metal and polymer surface free energy and reactivity on the evolution of electric conductivity and the resulting morphologies. In situ resistance measurements during sputter deposition of Ag, Au, Cu and Ni films on ultrathin reticulated polymer films collectively reveal metal–insulator transitions characteristic for Volmer–Weber growth. The different onsets of percolation correlate with interfacial energy and energy of adhesion weakly but as expected from ordinary wetting theory. A more pronounced trend of lower percolation thickness for more reactive metals falls in line with reported correlations. Ex situ grazing incidence small angle X-ray scattering experiments were performed at various thicknesses to gain an insight into cluster and film morphology evolution. A novel approach to interpret the scattering data is used where simulated pair distance distributions of arbitrary shapes and arrangements can be fitted to experiments. Detailed approximations of cluster structures could be inferred and are discussed in view of the established parameters describing film growth behavior.
Association of Time-of-Day Energy Intake Patterns with Nutrient Intakes, Diet Quality, and Insulin Resistance
Authors: Song Xiaoyun , Wang Huijun , Su Chang , Wang Zhihong , Huang Feifei , Zhang Jiguo , Du Wenwen , Jia Xiaofang , Jiang Hongru , Ouyang Yifei , Wang Yun , Li Li , Ding Gangqiang , Zhang Bing
Published: February 2021

Evidence shows time-of-day of energy intake are associated with health outcomes; however, studies of time-of-day energy patterns and their health implication are still lacking in the Asian population. This study aims to examine the time-of-day energy intake pattern of Chinese adults and to examine its associations with nutrient intakes, diet quality, and insulin resistance. Dietary data from three 24-h recalls collected during the 2015 China Health and Nutrition Survey (CHNS) were analyzed (n = 8726, aged ≥ 18 years). Time-of-day energy intake patterns were determined by latent class analysis (LCA). General Linear Models and Multilevel Mixed-effects Logistic Regression Models were applied to investigate the associations between latent time-of-day energy intake patterns, energy-adjusted nutrient intakes, diet quality score, and insulin resistance. Three time-of-day energy intake patterns were identified. Participants in the “Evening dominant pattern” were younger, had higher proportions of alcohol drinkers and current smokers. The “Evening dominant pattern” was associated with higher daily energy intake and a higher percentage of energy from fat (%) (p < 0.001), as well as higher insulin resistance risk (OR = 1.21; 95% CI: 1.05, 1.40), after adjusting for multivariate covariates. The highest diet quality score was observed in participants with “Noon dominant pattern” (p < 0.001). A higher proportion of energy in the later of the day was associated with insulin resistance in free-living individuals.
Safety Assessment of Bacillus subtilis MB40 for Use in Foods and Dietary Supplements
Authors: Spears Jessica L. , Kramer Richard , Nikiforov Andrey I. , Rihner Marisa O. , Lambert Elizabeth A.
Published: February 2021

With the growing popularity of probiotics in dietary supplements, foods, and beverages, it is important to substantiate not only the health benefits and efficacy of unique strains but also safety. In the interest of consumer safety and product transparency, strain identification should include whole-genome sequencing and safety assessment should include genotypic and phenotypic studies. Bacillus subtilis MB40, a unique strain marketed for use in dietary supplements, and food and beverage, was assessed for safety and tolerability across in silico, in vitro, and in vivo studies. MB40 was assessed for the absence of undesirable genetic elements encoding toxins and mobile antibiotic resistance. Tolerability was assessed in both rats and healthy human volunteers. In silico and in vitro testing confirmed the absence of enterotoxin and mobile antibiotic resistance genes of safety concern to humans. In rats, the no-observed-adverse-effect level (NOAEL) for MB40 after repeated oral administration for 14 days was determined to be 2000 mg/kg bw/day (equivalent to 3.7 × 1011 CFU/kg bw/day). In a 28 day human tolerability trial, 10 × 109 CFU/day of MB40 was well tolerated. Based on genome sequencing, strain characterization, screening for undesirable attributes and evidence of safety by appropriately designed safety evaluation studies in rats and humans, Bacillus subtilis MB40 does not pose any human health concerns under the conditions tested.
The Promotion of Sustainable Diets in the Healthcare System and Implications for Health Professionals: A Scoping Review
Authors: Alberdi Goiuri , Begiristain-Zubillaga Mirene
Published: February 2021

The impacts of the current global food system are already visible in the environment and in the health of the population. The promotion of sustainable diets is key to counter the negative consequences. The healthcare system could be a powerful tool to educate patients by guiding their diets towards sustainability. This study aimed to assess the size and scope of the available literature regarding the promotion of sustainable diets in the healthcare system and to obtain a reliable approximation of the processes and roles related to sustainable diet promotion within healthcare systems. A scoping review where online databases were used to identify English written scientific and grey literature published between 2000–2019 was carried out. The analytical–synthetic approach was used for data charting. Twelve studies were included that were published between 2007–2020. The data highlight education, community and clinical health services, community engagement and policy advocacy, and governance as main action areas along with two transversal aspects, social support, and gender. A systemic approach to the food system is emphasized. Evidence suggests that health professionals have the potential to drive a paradigm shift in food–health environments. Currently, however, their role and potential impact is underestimated within healthcare systems. This review has identified a framework with key areas where processes need to be developed to guarantee sustainable diet promotion in healthcare services.
Type 2 Diabetes Prevention Focused on Normalization of Glycemia: A Two-Year Pilot Study
Authors: McKenzie Amy L , Athinarayanan Shaminie J , McCue Jackson J , Adams Rebecca N , Keyes Monica , McCarter James P , Volek Jeff S , Phinney Stephen D , Hallberg Sarah J
Published: February 2021

The purpose of this study is to assess the effects of an alternative approach to type 2 diabetes prevention. Ninety-six patients with prediabetes (age 52 (10) years; 80% female; BMI 39.2 (7.1) kg/m2) received a continuous remote care intervention focused on reducing hyperglycemia through carbohydrate restricted nutrition therapy for two years in a single arm, prospective, longitudinal pilot study. Two-year retention was 75% (72 of 96 participants). Fifty-one percent of participants (49 of 96) met carbohydrate restriction goals as assessed by blood beta-hydroxybutyrate concentrations for more than one-third of reported measurements. Estimated cumulative incidence of normoglycemia (HbA1c < 5.7% without medication) and type 2 diabetes (HbA1c ≥ 6.5% or <6.5% with medication other than metformin) at two years were 52.3% and 3%, respectively. Prevalence of metabolic syndrome, class II or greater obesity, and suspected hepatic steatosis significantly decreased at two years. These results demonstrate the potential utility of an alternate approach to type 2 diabetes prevention, carbohydrate restricted nutrition therapy delivered through a continuous remote care model, for normalization of glycemia and improvement in related comorbidities.
The Role of Creatine in the Development and Activation of Immune Responses
Authors: Bredahl Eric C. , Eckerson Joan M. , Tracy Steven M. , McDonald Thomas L. , Drescher Kristen M.
Published: February 2021

The use of dietary supplements has become increasingly common over the past 20 years. Whereas supplements were formerly used mainly by elite athletes, age and fitness status no longer dictates who uses these substances. Indeed, many nutritional supplements are recommended by health care professionals to their patients. Creatine (CR) is a widely used dietary supplement that has been well-studied for its effects on performance and health. CR also aids in recovery from strenuous bouts of exercise by reducing inflammation. Although CR is considered to be very safe in recommended doses, a caveat is that a preponderance of the studies have focused upon young athletic individuals; thus there is limited knowledge regarding the effects of CR on children or the elderly. In this review, we examine the potential of CR to impact the host outside of the musculoskeletal system, specifically, the immune system, and discuss the available data demonstrating that CR can impact both innate and adaptive immune responses, together with how the effects on the immune system might be exploited to enhance human health.
Sarcopenia, Malnutrition, and Cachexia: Adapting Definitions and Terminology of Nutritional Disorders in Older People with Cancer
Authors: Meza-Valderrama Delky , Marco Ester , Dávalos-Yerovi Vanesa , Muns Maria Dolors , Tejero-Sánchez Marta , Duarte Esther , Sánchez-Rodríguez Dolores
Published: February 2021

The recent publication of the revised Consensus on definition and diagnosis of sarcopenia (EWGSOP2) and the Global Leadership Initiative on Malnutrition (GLIM) criteria changed the approach to research on sarcopenia and malnutrition. Whilst sarcopenia is a nutrition-related disease, malnutrition and cachexia are nutritional disorders sharing the common feature of low fat-free mass. However, they have differential characteristics and etiologies, as well as specific therapeutic approaches. Applying the current definitions in clinical practice is still a challenge for health professionals and the potential for misdiagnosis is high. This is of special concern in the subgroup of older people with cancer, in which sarcopenia, malnutrition, and cancer cachexia are highly prevalent and can overlap or occur separately. The purpose of this review is to provide an updated overview of the latest research and consensus definitions of sarcopenia, malnutrition, and cachexia and to discuss their implications for clinical practice in older patients with cancer. The overall aim is to improve the quality of nutritional care in light of the latest findings.
Do Gut Hormones Contribute to Weight Loss and Glycaemic Outcomes after Bariatric Surgery?
Authors: Papamargaritis Dimitris , le Roux Carel W.
Published: February 2021

Bariatric surgery is an effective intervention for management of obesity through treating dysregulated appetite and achieving long-term weight loss maintenance. Moreover, significant changes in glucose homeostasis are observed after bariatric surgery including, in some cases, type 2 diabetes remission from the early postoperative period and postprandial hypoglycaemia. Levels of a number of gut hormones are dramatically increased from the early period after Roux-en-Y gastric bypass and sleeve gastrectomy—the two most commonly performed bariatric procedures—and they have been suggested as important mediators of the observed changes in eating behaviour and glucose homeostasis postoperatively. In this review, we summarise the current evidence from human studies on the alterations of gut hormones after bariatric surgery and their impact on clinical outcomes postoperatively. Studies which assess the role of gut hormones after bariatric surgery on food intake, hunger, satiety and glucose homeostasis through octreotide use (a non-specific inhibitor of gut hormone secretion) as well as with exendin 9–39 (a specific glucagon-like peptide-1 receptor antagonist) are reviewed. The potential use of gut hormones as biomarkers of successful outcomes of bariatric surgery is also evaluated.
Acute Pancreatitis as a Complication of Antiepileptic Treatment: Case Series and Review of the Literature
Authors: Pawłowska-Kamieniak Agnieszka , Krawiec Paulina , Pac-Kożuchowska Elżbieta
Published: February 2021

Acute pancreatitis (AP) appears to be rare disease in childhood. In children, it has a different aetiology and course, and requires different management than in adult patients. The diagnosis of AP is based on at least two of the three criteria, which include typical clinical symptoms, abnormalities in laboratory tests and/or imaging studies of the pancreas. There are many known causes leading to AP in children including infections, blunt abdominal trauma, genetic factors, gallstone disease, metabolic disorders, anatomical defects of the pancreas, systemic diseases, as well as drugs, including antiepileptic drugs, and especially preparations of valproic acid. In our study, we present four cases of young patients diagnosed with acute pancreatitis as a complication of valproic acid therapy and we present a review of the literature. We believe that the activity of pancreatic enzymes should be monitored in children treated with valproate preparations in the case of clinical symptoms suggesting AP.
Evaluation of the Synergistic Antibacterial Effects of Fosfomycin in Combination with Selected Antibiotics against Carbapenem–Resistant Acinetobacter baumannii
Authors: Nwabor Ozioma F. , Terbtothakun Pawarisa , Voravuthikunchai Supayang P. , Chusri Sarunyou
Published: February 2021

The spread of multi-drug resistant (MDR) pathogens and the lagging pace in the development of novel chemotherapeutic agents warrant the use of combination therapy as a reliable, cost-effective interim option. In this study, the synergistic effects of fosfomycin in combination with other antibiotics were assessed. Of the 193 isolates, 90.6% were non-susceptible to fosfomycin, with minimum inhibitory concentrations (MICs) of ≥128 µg/mL. Antibacterial evaluation of fosfomycin-resistant isolates indicated multi-drug resistance to various antibiotic classes. Combinations of fosfomycin with 12 commonly used antibiotics synergistically inhibited most fosfomycin-resistant isolates. The fractional inhibitory concentration index indicated that combining fosfomycin with either aminoglycosides, glycylcyclines, fluoroquinolones, or colistin resulted in 2- to 16-fold reduction in the MIC of fosfomycin. Time-kill kinetics further confirmed the synergistic bactericidal effects of fosfomycin in combination with either amikacin, gentamicin, tobramycin, minocycline, tigecycline, or colistin, with more than 99.9% reduction in bacterial cells. Fosfomycin-based combination therapy might serve as an alternative option for the treatment of MDR A. baumannii. Further steps including in vivo efficacy and toxicity in experimental models of infection are required prior to clinical applications.
Prevalence of Drug-Related Problems and Complementary and Alternative Medicine Use in Malaysia: A Systematic Review and Meta-Analysis of 37,249 Older Adults
Authors: Chang Chee-Tao , Ang Ju-Ying , Islam Md Asiful , Chan Huan-Keat , Cheah Wee-Kooi , Gan Siew Hua
Published: February 2021

Drug-related problems (DRPs) in the elderly include polypharmacy, potentially inappropriate medications, nonadherence, and drug-related falls. In this systematic review and meta-analysis, the prevalence of DRPs and complementary and alternative medicine (CAM) use among the Malaysian elderly was estimated. PubMed, Scopus, Web of Science, and Google Scholar databases were searched to identify studies published since their inception up to 24 August 2020. A random-effects model was used to generate the pooled prevalence of DRPs along with its corresponding 95% confidence interval (CI). The heterogeneity of the results was estimated using the I2 statistics, and Cochran’s Q test and sensitivity analyses were performed to confirm the robustness of the results. We identified 526 studies, 23 of which were included in the meta-analysis. (n = 29,342). The pooled prevalence of DRPs among Malaysian elderly was as follows: (1) polypharmacy: 49.5% [95% CI: 20.5–78.6], (2) potentially inappropriate medications: 28.9% [95% CI: 25.4–32.3], (3) nonadherence to medications: 60.6% [95% CI: 50.2–70.9], and (4) medication-related falls 39.3% [95% CI: 0.0–80.8]. Approximately one in two Malaysian elderly used CAM. The prevalence of polypharmacy and potentially inappropriate medications among the Malaysian elderly population was high, calling for measures and evidence-based guidelines to ensure the safe medication use.
Metformin Increases Survival in Hypopharyngeal Cancer Patients with Diabetes Mellitus: Retrospective Cohort Study and Cell-Based Analysis
Authors: Tsou Yung-An , Chang Wei-Chao , Lin Chia-Der , Chang Ro-Lin , Tsai Ming-Hsui , Shih Liang-Chun , Staniczek Theresa , Wu Tsu-Fang , Hsu Hui-Ying , Chang Wen-Dien , Lai Chih-Ho , Chen Chuan-Mu
Published: February 2021

Hypopharyngeal squamous cell carcinoma (HSCC) is usually diagnosed at an advanced stage, leading to a poor prognosis. Even after improvement of surgical techniques, chemotherapy, and radiation technology, the survival rate of HSCC remains poor. Metformin, which is commonly used for type 2 diabetes mellitus (DM), has been suggested to reduce the risk of various cancer types. However, only a few clinical studies mentioned the relationship between metformin use and HSCC. Hence, the aim of this study was to elucidate the specific effect and mechanism of action of metformin in hypopharyngeal cancer. We first assessed whether metformin use has an effect on hypopharyngeal cancer patients with DM by conducting a retrospective cohort study. Our results showed that DM hypopharyngeal cancer patients who used metformin exhibited significantly better overall survival rates than that without metformin treatment. The cell-based analysis further indicated that metformin treatment regulated p38/JNK pathway to reduce Cyclin D1 and Bcl-2 expressions. In addition, metformin activated the pathways of AMPKα and MEK/ERK to phosphorylate p27(Thr198) and reduce mTOR phosphorylation in cells. These actions direct cells toward G1 cell cycle arrest, apoptosis, and autophagy. Our results, through combining a clinical cohort analysis with an in vitro study, demonstrate that metformin can be used for drug repositioning in the treatment of DM patients with hypopharyngeal cancer.
Decoding the Neuroprotective Potential of Methyl Gallate-Loaded Starch Nanoparticles against Beta Amyloid-Induced Oxidative Stress-Mediated Apoptosis: An In Vitro Study
Authors: Prakashkumar Nallasamy , Sivamaruthi Bhagavathi Sundaram , Chaiyasut Chaiyavat , Suganthy Natarajan
Published: February 2021

Alzheimer’s disease (AD) is a multifaceted neuronal disorder and a challenge to medical practitioners, as the blood–brain barrier (BBB) acts as a major obstacle for drug delivery to the brain. Development of a nanomaterial-based drug delivery system (DDS) paved a way to penetrate the BBB. Starch, a ubiquitous natural biopolymer, has received much attention as a DDS due to its biocompatibility, biodegradability and eco-friendly nature. The present study focuses on encapsulating methyl gallate (MG) within starch nanoparticles (starch-encapsulated MG (SEMG)) and assesses its neuroprotective potential against β-amyloid (Aβ)-induced toxicity, the key factor for AD pathogenesis in Neuro2A cells. SEMG showed potent acetylcholinesterase inhibitory, antioxidant activity and anti-amyloidogenic activity by attenuating the fibrillation of Aβ and destabilizing the preformed mature fibrils. Furthermore, SEMG also attenuated the cytotoxic effect induced by Aβ in Neuro2A cells (50% inhibitory concentration 18.25 ± 0.025 μg/mL) by mitigating reactive oxygen species (ROS)-mediated macromolecular damage, restoring mitochondrial membrane potential and attenuating apoptosis. Characterization of SEMG revealed amorphous rock-shaped structure with average particle size of 264.6 nm, exhibiting 83% loading efficiency and sustained release of drug, with 73% release within 24 h at physiological pH. Overall, the outcome of the present study signifies starch as a promising nanocarrier for the delivery of drugs for the treatment of AD.
Development of an In Vitro Blink Model for Ophthalmic Drug Delivery
Authors: Phan Chau-Minh , Shukla Manish , Walther Hendrik , Heynen Miriam , Suh David , Jones Lyndon
Published: February 2021

Purpose: The purpose of this study was to develop an advanced in vitro blink model that can be used to examine the release of a wide variety of components (for example, topical ophthalmic drugs, comfort-inducing agents) from soft contact lenses. Methods: The model was designed using computer-aided design software and printed using a stereolithography 3D printer. The eyelid and eyeball were synthesized from polyvinyl alcohol and silicone material, respectively. Simulated tear fluid was infused through tubing attached to the eyelid using a syringe pump. With each blink cycle, the eyelid slides and flexes across the eyeball to create an artificial tear film layer. The flow-through fluid was collected using a specialized trough. Two contact lenses, etafilcon A and senofilcon A, were incubated in 2 mL of a water-soluble red dye for 24 h and then placed on the eye model (n = 3). The release of the dye was measured over 24 h using a tear flow rate of 5 µL/min. Results: Approximately 25% of the fluid that flowed over the eye model was lost due to evaporation, nonspecific absorption, and residual dead volume. Senofilcon A absorbed more dye (47.6 ± 2.7 µL) than etafilcon A (22.3 ± 2.0 µL). For etafilcon A, the release of the dye followed a burst-plateau profile in the vial but was sustained in the eye model. For senofilcon A, the release of the dye was sustained in both the vial and the eye model, though more dye was released in the vial (p < 0.05). Overall, the release of the dye from the contact lenses was higher in the vial compared with the eye model (p < 0.05). Conclusion: The blink model developed in this study could be used to measure the release of topical ophthalmic drugs or comfort agents from contact lenses. Simulation of a blink mechanism, an artificial tear film, and nonspecific absorption in an eye model may provide better results than a simple, static vial incubation model.