bluuebunny/crossref_metadata_2025 huggingface dataset:
The Amine Functionalized Sugarcane Bagasse Biocomposites as Magnetically Adsorbent for Contaminants Removal in Aqueous Solution
Authors: Irawan Chairul , Putra Meilana Dharma , Wijayanti Hesti , Juwita Rinna , Meliana Yenny , Nata Iryanti Fatyasari
Published: September 2021

The method of solvothermal by one-step operation has been performed to synthesize of magnetic amine-functionalized sugarcane bagasse biocomposites (SB-MH). The obtained SB-MH contains 62.34% of Fe, 17.8 mmol/g of amine, and a magnetic property of 19.46 emu/g. The biocomposite surface area increased significantly from 1.617 to 25.789 m2/g after amine functionalization. The optimum condition of SB-MH used for Pb(II) ion removal was achieved at pH 5 for 360 min with adsorption capacity of 203.522 mg/g. The pseudo 2nd order was well-fitted to the model of Pb(II) ion adsorption. Meanwhile, other contaminant parameters number of Chemical Oxygen Demand (COD), Total Suspended Solid (TSS), and dye in wastewater were also remarkably reduced by about 74.4%, 88.0%, and 96.7%, respectively. The reusability of SB-MH with 4th repetitions showed only a slight decrease in performance of 5%. Therefore, the proposed magnetic amine-functionalized sugarcane bagasse biocomposites lead to a very potential adsorbent implemented in high scale due to high surface area, easy separation, stable materials and capability to adsorb contaminants from aqueous solution.
A Non-Covalent Dimer Formation of Quaternary Ammonium Cation with Unusual Charge Neutralization in Electrospray-Ionization Mass Spectrometry
Authors: Grocholska Paulina , Kowalska Marta , Wieczorek Robert , Bąchor Remigiusz
Published: September 2021

Specific and nonspecific non-covalent molecular association of biomolecules is characteristic for electrospray-ionization mass spectrometry analysis of biomolecules. Understanding the interaction between two associated molecules is of significance not only from the biological point of view but also gas phase analysis by mass spectrometry. Here we reported a formation of non-covalent dimer of quaternary ammonium denatonium cation with +1 charge detected in the positive ion mode electrospray ionization mass spectrometry analysis of denatonium benzoate. Hydrogen deuterium exchange of amide and carbon-bonded hydrogens revealed that charge neutralization of one denatonium cation is the consequence of amide hydrogen dissociation. DFT (Density Functional Theory) calculations proved high thermodynamic stable of formed dimer stabilized by the short and strong N..H-N hydrogen bond. The signal intensity of the peak characterizing non-covalent dimer is low intensity and does not depend on the sample concentration. Additionally, dimer observation was found to be instrument-dependent. The current investigation is the first experimental and theoretical study on the quaternary ammonium ions dimer. Thus the present study has great significance for understanding the structures of the biomolecules as well as materials.
Imidazolium Based Ionic Liquids: Unbiased Recovering of Vaporization Enthalpies from Infinite-Dilution Activity Coefficients
Authors: Verevkin Sergey P.
Published: September 2021

We propose and test an efficient approach for the assessment of the enthalpies of vaporization of ionic liquids at the reference temperature 298.15 K. The approach is based on activity coefficients at infinite dilution of volatile organic solutes in ionic liquids bearing the imidazolium cation of the general formula [Cnmim][Anion].
Analysis of IV Drugs in the Hospital Workflow by Raman Spectroscopy: The Case of Piperacillin and Tazobactam
Authors: Chrisikou Ioanna , Orkoula Malvina , Kontoyannis Christos
Published: September 2021

Medical errors associated with IV preparation and administration procedures in a hospital workflow can even cost human lives due to the direct effect they have on patients. A large number of such incidents, which have been reported in bibliography up to date, indicate the urgent need for their prevention. This study aims at proposing an analytical methodology for identifying and quantifying IV drugs before their administration, which has the potential to be fully harmonized with clinical practices. More specifically, it reports on the analysis of a piperacillin (PIP) and tazobactam (TAZ) IV formulation, using Raman spectroscopy. The simultaneous analysis of the two APIs in the same formulation was performed in three stages: before reconstitution in the form of powder without removing the substance out of the commercial glass bottle (non-invasively), directly after reconstitution in the same way, and just before administration, either the liquid drug is placed in the infusion set (on-line analysis) or a minimal amount of it is transferred from the IV bag to a Raman optic cell (at-line analysis). Except for the successful identification of the APIs in all cases, their quantification was also achieved through calibration curves with correlation coefficients ranging from 0.953 to 0.999 for PIP and from 0.965 to 0.997 for TAZ. In any case, the whole procedure does not need more than 10 min to be completed. The current methodology, based on Raman spectroscopy, outweighs other spectroscopic (UV/Vis, FT-IR/ATR) or chromatographic (HPLC, UHPLC) protocols, already applied, which are invasive, costly, time-consuming, not environmentally friendly, and require specialized staff and more complex sample preparation procedures, thus exposing the staff to hazardous materials, especially in cases of cytotoxic drugs. Such an approach has the potential to bridge the gap between experimental setup and clinical implementation through exploitation of already developed handheld devices, along with the presence of digital spectral libraries.
Utilizing AgNPt-SALDI to Classify Edible Oils by Multivariate Statistics of Triacylglycerol Profile
Authors: Yang Tzu-Ling , Huang Cheng-Liang , Lee Chu-Ping
Published: September 2021

Edible oils are valuable sources of nutrients, and their classification is necessary to ensure high quality, which is essential to food safety. This study reports the establishment of a rapid and straightforward SALDI-TOF MS platform used to detect triacylglycerol (TAG) in various edible oils. Silver nanoplates (AgNPts) were used to optimize the SALDI samples for high sensitivity and reproducibility of TAG signals. TAG fingerprints were combined with multivariate statistics to identify the critical features of edible oil discrimination. Eleven various edible oils were discriminated using principal component analysis (PCA). The results suggested the creation of a robust platform that can examine food adulteration and food fraud, potentially ensuring high-quality foods and agricultural products.
Enhancement of O-GlcNAcylation on Mitochondrial Proteins with 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside, Contributes to the Mitochondrial Network, Cellular Bioenergetics and Stress Response in Neuronal Cells under Ischemic-like Conditions
Authors: Xu Hui , Du Mingzhi , Shen Yuntian , Yang Yumin , Ding Fei , Yu Shu
Published: September 2021

O-GlcNAcylation is a nutrient-driven post-translational modification known as a metabolic sensor that links metabolism to cellular function. Recent evidences indicate that the activation of O-GlcNAc pathway is a potential pro-survival pathway and that acute enhancement of this response is conducive to the survival of cells and tissues. 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside (SalA-4g), is a salidroside analogue synthesized in our laboratory by chemical structure-modification, with a phenyl ring containing a para-methoxy group and a sugar ring consisting of N-acetylglucosamine. We have previously shown that SalA-4g elevates levels of protein O-GlcNAc and improves neuronal tolerance to ischemia. However, the specific target of SalA-4g regulating O-GlcNAcylation remains unknown. To address these questions, in this study, we have focused on mitochondrial network homeostasis mediated by O-GlcNAcylation in SalA-4g’s neuroprotection in primary cortical neurons under ischemic-like conditions. O-GlcNAc-modified mitochondria induced by SalA-4g demonstrated stronger neuroprotection under oxygen glucose deprivation and reoxygenation stress, including the improvement of mitochondrial homeostasis and bioenergy, and inhibition of mitochondrial apoptosis pathway. Blocking mitochondrial protein O-GlcNAcylation with OSMI-1 disrupted mitochondrial network homeostasis and antagonized the protective effects of SalA-4g. Collectively, these data demonstrate that mitochondrial homeostasis mediated by mitochondrial protein O-GlcNAcylation is critically involved in SalA-4g neuroprotection.
Preparation of Quaternary Amphiphilic Block Copolymer PMA-b-P (NVP/MAH/St) and Its Application in Surface Modification of Aluminum Nitride Powders
Authors: Wang Yu , Zhu Guangdong , Wang Shun , Xie Jianjun , Chen Zhan , Shi Ying
Published: September 2021

Poly(methyl acrylate)-b-poly(N-vinyl pyrrolidone/maleic anhydride/styrene) (PMA-b-P (NVP/MAH/St)) quaternary amphiphilic block copolymer prepared by reversible addition-fragmentation chain transfer (RAFT) was used to improve the anti-hydrolysis and dispersion properties of aluminum nitride (AIN) powders that were modified by copolymers. Its structure was characterized by Fourier transform infrared spectroscopy (FT-IR) and Hydrogen nuclear magnetic spectroscopy (1H-NMR). The results demonstrate that the molecular weight distribution of the quaternary amphiphilic block copolymers is 1.35–1.60, which is characteristic of controlled molecular weight and narrow molecular weight distribution. Through charge transfer complexes, NVP/MAH/St produces a regular alternating arrangement structure. After being treated with micro-crosslinking, AlN powder modified by copolymer PMA-b-P(NVP/MAH/St) exhibits outstanding resistance to hydrolysis and can be stabilized in hot water at 50 °C for more than 14 h, and the agglomeration of powder particles was improved remarkably.
A Systematic Review of the Biological Effects of Cordycepin
Authors: Radhi Masar , Ashraf Sadaf , Lawrence Steven , Tranholm Asta Arendt , Wellham Peter Arthur David , Hafeez Abdul , Khamis Ammar Sabah , Thomas Robert , McWilliams Daniel , de Moor Cornelia Huiberdina
Published: September 2021

We conducted a systematic review of the literature on the effects of cordycepin on cell survival and proliferation, inflammation, signal transduction and animal models. A total of 1204 publications on cordycepin were found by the cut-off date of 1 February 2021. After application of the exclusion criteria, 791 papers remained. These were read and data on the chosen subjects were extracted. We found 192 papers on the effects of cordycepin on cell survival and proliferation and calculated a median inhibitory concentration (IC50) of 135 µM. Cordycepin consistently repressed cell migration (26 papers) and cellular inflammation (53 papers). Evaluation of 76 papers on signal transduction indicated consistently reduced PI3K/mTOR/AKT and ERK signalling and activation of AMPK. In contrast, the effects of cordycepin on the p38 and Jun kinases were variable, as were the effects on cell cycle arrest (53 papers), suggesting these are cell-specific responses. The examination of 150 animal studies indicated that purified cordycepin has many potential therapeutic effects, including the reduction of tumour growth (37 papers), repression of pain and inflammation (9 papers), protecting brain function (11 papers), improvement of respiratory and cardiac conditions (8 and 19 papers) and amelioration of metabolic disorders (8 papers). Nearly all these data are consistent with cordycepin mediating its therapeutic effects through activating AMPK, inhibiting PI3K/mTOR/AKT and repressing the inflammatory response. We conclude that cordycepin has excellent potential as a lead for drug development, especially for age-related diseases. In addition, we discuss the remaining issues around the mechanism of action, toxicity and biodistribution of cordycepin.
In Vitro Multiplication and NMR Fingerprinting of Rare Veronica caucasica M. Bieb
Authors: Mantovska Desislava I. , Zhiponova Miroslava K. , Georgiev Milen I. , Grozdanova Tsvetinka , Gerginova Dessislava , Alipieva Kalina , Simova Svetlana , Popova Milena , Kapchina-Toteva Veneta M. , Yordanova Zhenya P.
Published: September 2021

Micropropagation of rare Veronica caucasica M. Bieb. was achieved by successful in vitro cultivation of mono-nodal segments on MS medium supplemented with 1.0 mg L–1 6-benzylaminopurine (BA) and then transferring the regenerated plants on hormone free basal MS medium for root development. In vitro multiplicated plants were successively acclimated in a growth chamber and a greenhouse with 92% survival. The number of plastid pigments and the total phenolics content in in vitro cultivated and ex vitro adapted plants were unchanged, and no accumulation of reactive oxygen species (ROS) was detected by staining with 3-3′-diaminobenzidine (DAB) and 2′,7′-dichlorofluorescein diacetate (DCF-DA). Nuclear Magnetic Resonance (NMR) fingerprinting allowed for the identification of the major alterations in metabolome of V. caucasica plants during the process of ex situ conservation. Iridoid glucosides such as verproside, aucubin and catalpol were characteristic for in vitro cultivated plants, while in ex vitro acclimated plants phenolic acid–protocatechuic acid and caffeic acid appeared dominant. The successful initiation of in vitro and ex vitro cultures is an alternative biotechnological approach for the preservation of V. caucasica and would allow for further studies of the biosynthetic potential of the species and the selection of lines with a high content of pharmaceutically valuable molecules and nutraceuticals.
LC-MS/MS Determination of 21 Non-Steroidal Anti-Inflammatory Drugs Residues in Animal Milk and Muscles
Authors: Pietruk Marta , Jedziniak Piotr , Olejnik Małgorzata
Published: September 2021

The presented procedure combines experience from two LC-MS/MS methods previously developed by our team for NSAIDs determination in meat and milk. The novelty was a modification of sample preparation and combining LC-MS/MS method for milk and muscle. The clean-up procedure was investigated, leading to a change from SPE to dSPE with C18 bulk sorbent. Unlike most of the existing methods, chromatographic separation was achieved on a C8 chromatographic column. This method was developed and validated under European Commission Decision 2002/657/EC. Recovery for milk samples values between 86.3% to 108%, with the coefficient of variation, varied from 5.51% to 16.2%. The recovery for muscle was calculated to be between 85.0% and 109%, and the coefficient of variation was—4.73% to 16.6%. The validation results prove that the method is suitable for confirmatory purposes in milk and muscle. Of 452 samples tested in 2019 and 2020, two have been identified as non-compliant.
Catalytic Oxidation of CO and Benzene over Metal Nanoparticles Loaded on Hierarchical MFI Zeolite
Authors: Todorova Totka , Petrova Petya , Kalvachev Yuri
Published: September 2021

In order to obtain highly active catalytic materials for oxidation of carbon monoxide and volatile organic compounds (VOCs), monometallic platinum, copper, and palladium catalysts were prepared by using of two types of ZSM-5 zeolite as supports—parent ZSM-5 and the same one treated by HF and NH4F buffer solution. The catalyst samples, obtained by loading of platinum, palladium, and copper on ZSM-5 zeolite treated using HF and NH4F buffer solution, were more active in the reaction of CO and benzene oxidation compared with catalyst samples containing untreated zeolite. The presence of secondary mesoporosity played a positive role in increasing the catalytic activity due to improved reactant diffusion. The only exception was the copper catalysts in the reaction of CO oxidation, in which case the catalyst, based on untreated ZSM-5 zeolite, was more active. In this specific case, the key role is played by the oxidative state of copper species loaded on the ZSM-5 zeolites.
Evaporation of Methylammonium Iodide in Thermal Deposition of MAPbI3
Authors: Wang Ke , Ecker Benjamin , Huang Jinsong , Gao Yongli
Published: September 2021

Thermal evaporation is an important technique for fabricating methylammonium lead iodide (MAPbI3), but the process is complicated by the need to co-evaporate methylammonium iodide (MAI) and PbI2. In this work, the effect of water vapor during the thermal deposition of MAPbI3 was investigated under high vacuum. The evaporation process was monitored with a residual gas analyzer (RGA), and the film quality was examined with X-ray photoelectron spectroscopy (XPS). The investigations showed that during evaporation, MAI decomposed while PbI2 evaporated as a whole compound. It was found that the residual water vapor reacted with one of the MAI-dissociated products. The higher iodine ratio suggests that the real MAI flux was higher than the reading from the QCM. The XPS analysis demonstrated that the residual water vapor may alter the elemental ratios of C, N, and I in thermally deposited MAPbI3. Morphologic properties were investigated with atomic force microscopy (AFM), scanning electron microscopy (SEM), and X-ray diffraction (XRD). It was observed that a sample grown with high water vapor pressure had a roughened surface and poor film quality. Therefore, an evaporation environment with water vapor pressure below 10−8 Torr is needed to fabricate high quality perovskite films.
Grand Canonical Monte Carlo Simulations to Determine the Optimal Interlayer Distance of a Graphene Slit-Shaped Pore for Adsorption of Methane, Hydrogen and their Equimolar Mixture
Authors: Vekeman Jelle , Bahamon Daniel , García Cuesta Inmaculada , Faginas-Lago Noelia , Sánchez-Marín José , Sánchez de Merás Alfredo , Vega Lourdes F.
Published: September 2021

The adsorption—for separation, storage and transportation—of methane, hydrogen and their mixture is important for a sustainable energy consumption in present-day society. Graphene derivatives have proven to be very promising for such an application, yet for a good design a better understanding of the optimal pore size is needed. In this work, grand canonical Monte Carlo simulations, employing Improved Lennard–Jones potentials, are performed to determine the ideal interlayer distance for a slit-shaped graphene pore in a large pressure range. A detailed study of the adsorption behavior of methane, hydrogen and their equimolar mixture in different sizes of graphene pores is obtained through calculation of absolute and excess adsorption isotherms, isosteric heats and the selectivity. Moreover, a molecular picture is provided through z-density profiles at low and high pressure. It is found that an interlayer distance of about twice the van der Waals distance of the adsorbate is recommended to enhance the adsorbing ability. Furthermore, the graphene structures with slit-shaped pores were found to be very capable of adsorbing methane and separating methane from hydrogen in a mixture at reasonable working conditions (300 K and well below 15 atm).
Graphene-Based Films: Fabrication, Interfacial Modification, and Applications
Authors: Guo Sihua , Chen Jin , Zhang Yong , Liu Johan
Published: September 2021

Graphene-based film attracts tremendous interest in many potential applications due to its excellent thermal, electrical, and mechanical properties. This review focused on a critical analysis of fabrication, processing methodology, the interfacial modification approach, and the applications of this novel and new class material. Strong attention was paid to the preparation strategy and interfacial modification approach to improve its mechanical and thermal properties. The overview also discussed the challenges and opportunities regarding its industrial production and the current status of the commercialization. This review showed that blade coating technology is an effective method for industrial mass-produced graphene film with controllable thickness. The synergistic effect of different interface interactions can effectively improve the mechanical properties of graphene-based film. At present, the application of graphene-based film on mobile phones has become an interesting example of the use of graphene. Looking for more application cases is of great significance for the development of graphene-based technology.
Limitations of Thermal Stability Analysis via In-Situ TEM/Heating Experiments
Authors: El-Atwani Osman , Kim Hyosim , Harvey Cayla , Efe Mert , Maloy Stuart A.
Published: September 2021

This work highlights some limitations of thermal stability analysis via in-situ transmission electron microscopy (TEM)-annealing experiments on ultrafine and nanocrystalline materials. We provide two examples, one on nanocrystalline pure copper and one on nanocrystalline HT-9 steel, where in-situ TEM-annealing experiments are compared to bulk material annealing experiments. The in-situ TEM and bulk annealing experiments demonstrated different results on pure copper but similar output in the HT-9 steel. The work entails discussion of the results based on literature theoretical concepts, and expound on the inevitability of comparing in-situ TEM annealing experimental results to bulk annealing when used for material thermal stability assessment.
Antioxidants Supplementation Reduces Ceramide Synthesis Improving the Cardiac Insulin Transduction Pathway in a Rodent Model of Obesity
Authors: Hodun Katarzyna , Sztolsztener Klaudia , Chabowski Adrian
Published: September 2021

Obesity-related disruption in lipid metabolism contributes to cardiovascular dysfunction. Despite numerous studies on lipid metabolism in the left ventricle, there is no data describing the influence of n-acetylcysteine (NAC) and α-lipoic acid (ALA), as glutathione precursors, on sphingolipid metabolism, and insulin resistance (IR) occurrence. The aim of our experiment was to evaluate the influence of chronic antioxidants administration on myocardial sphingolipid state and intracellular insulin signaling as a potential therapeutic strategy for obesity-related cardiovascular IR. The experiment was conducted on male Wistar rats fed a standard rodent chow or a high-fat diet with intragastric administration of NAC or ALA for eight weeks. Cardiac and plasma sphingolipid species were assessed by high-performance liquid chromatography (HPLC). The proteins expressed from sphingolipid and insulin signaling pathways were determined by Western blot. Antioxidant supplementation markedly reduced ceramide accumulation by lowering the expression of selected proteins from the sphingolipid pathway and simultaneously increased the myocardial sphingosine-1-phosphate level. Moreover, NAC and ALA augmented the expression of GLUT4 and the phosphorylation state of Akt (Ser473) and GSK3β (Ser9), which improved the intracellular insulin transduction pathway. Based on our results, we may postulate that NAC and ALA have a beneficial influence on the cardiac ceramidose under IR conditions.
Is the Magnesium Content in Food Supplements Consistent with the Manufacturers’ Declarations?
Authors: Puścion-Jakubik Anna , Bartosiewicz Natalia , Socha Katarzyna
Published: September 2021

Food supplements (FS) are gaining more and more popularity because they are a quick way to compensate for deficiencies in the diet. Due to their affordable price and easy-to-take form, they are eaten by all age groups and by healthy and sick people. There are many categories of this type of preparations on the market, and FS with magnesium (Mg) are some of the most commonly used. Therefore, the aim of the study was to determine the Mg content in FS and to compare the estimated value with that declared by the manufacturer. The study included 116 FS containing Mg. In order to determine the Mg content, the atomic absorption spectrometry (AAS) method was used. The tested FS were divided in terms of the declared content, pharmaceutical form, chemical form of Mg, composition complexity, and price. It was shown that in the case of 58.7% of the samples, the Mg content was different than the permissible tolerance limits set by the Polish chief sanitary inspectorate, which range from −20% to +45%. It has been estimated that as a result of the differences in the content, the patient may take up to 304% more Mg per day or 98% less than it is stated in the declaration. The above results indicate that the quality and safety of FS should be more closely monitored.
Maternal Metformin Treatment during Gestation and Lactation Improves Skeletal Muscle Development in Offspring of Rat Dams Fed High-Fat Diet
Authors: Cui Jiaqi , Song Lin , Wang Rui , Hu Shuyuan , Yang Zhao , Zhang Zengtie , Sun Bo , Cui Wei
Published: September 2021

Maternal high-fat (HF) diet is associated with offspring metabolic disorder. This study intended to determine whether maternal metformin (MT) administration during gestation and lactation prevents the effect of maternal HF diet on offspring’s skeletal muscle (SM) development and metabolism. Pregnant Sprague-Dawley rats were divided into four groups according to maternal diet {CHOW (11.8% fat) or HF (60% fat)} and MT administration {control (CT) or MT (300 mg/kg/day)} during gestation and lactation: CH-CT, CH-MT, HF-CT, HF-MT. All offspring were weaned on CHOW diet. SM was collected at weaning and 18 weeks in offspring. Maternal metformin reduced plasma insulin, leptin, triglyceride and cholesterol levels in male and female offspring. Maternal metformin increased MyoD expression but decreased Ppargc1a, Drp1 and Mfn2 expression in SM of adult male and female offspring. Decreased MRF4 expression in SM, muscle dysfunction and mitochondrial vacuolization were observed in weaned HF-CT males, while maternal metformin normalized them. Maternal metformin increased AMPK phosphorylation and decreased 4E-BP1 phosphorylation in SM of male and female offspring. Our data demonstrate that maternal metformin during gestation and lactation can potentially overcome the negative effects of perinatal exposure to HF diet in offspring, by altering their myogenesis, mitochondrial biogenesis and dynamics through AMPK/mTOR pathways in SM.
Fasting and Exercise in Oncology: Potential Synergism of Combined Interventions
Authors: Wilson Rebekah L. , Kang Dong-Woo , Christopher Cami N. , Crane Tracy E. , Dieli-Conwright Christina M.
Published: September 2021

Nutrition and exercise interventions are strongly recommended for most cancer patients; however, much debate exists about the best prescription. Combining fasting with exercise is relatively untouched within the oncology setting. Separately, fasting has demonstrated reductions in chemotherapy-related side effects and improved treatment tolerability and effectiveness. Emerging evidence suggests fasting may have a protective effect on healthy cells allowing chemotherapy to exclusively target cancer cells. Exercise is commonly recommended and attenuates treatment- and cancer-related adverse changes to body composition, quality of life, and physical function. Given their independent benefits, in combination, fasting and exercise may induce synergistic effects and further improve cancer-related outcomes. In this narrative review, we provide a critical appraisal of the current evidence of fasting and exercise as independent interventions in the cancer population and discuss the potential benefits and mechanisms of combined fasting and exercise on cardiometabolic, body composition, patient-reported outcomes, and cancer-related outcomes. Our findings suggest that within the non-cancer population combined fasting and exercise is a viable strategy to improve health-related outcomes, however, its safety and efficacy in the oncology setting remain unknown. Therefore, we also provide a discussion on potential safety issues and considerations for future research in the growing cancer population.
Association of Iron-Deficiency Anemia and Non-Iron-Deficiency Anemia with Neurobehavioral Development in Children Aged 6–24 Months
Authors: Zheng Juan , Liu Jie , Yang Wenhan
Published: September 2021

(1) Background: Anemia has comprehensive adverse effects on the growth and development of children. In this study, we analyzed the potential effects of different types of anemia on early-life neurobehavioral development. (2) Methods: A total of 2601 children aged 6–24 months, whose parents agreed to participate in this study, underwent routine blood tests and neurobehavioral development assessment. The children’s parents or other primary caregivers were interviewed with a face-to-face questionnaire at the time of enrollment in the study. Anemia was determined by hemoglobin < 110 g/L and classified into iron-deficiency and non-iron-deficiency anemia according to the levels of serum ferritin, C-reactive protein, and alpha-1-acid glycoprotein. Neurobehavioral development was assessed by the China Developmental Scale for Children and divided into five domains: gross motor, fine movement, adaptability, language, and social behavior. The development quotient (DQ) was used to measure the level of total neurobehavioral development and each domain of neurobehavioral development. (3) Results: The prevalence of anemia in children aged 6–24 months was 26.45%, of which iron-deficiency anemia only accounted for 27.33%. Compared with children without anemia, those with iron-deficiency anemia had a significantly lower developmental quotient (DQ) for total neurobehavioral development and gross motor and adaptability development. The partial regression coefficients were −1.33 (95% CI −2.36, −0.29; p = 0.012), −1.88 (95% CI −3.74, −0.03; p = 0.047), and 1.48 (95% CI −2.92, −0.05; p = 0.042), respectively. Children with non-iron-deficiency anemia had significantly lower DQ for total neurobehavioral development and gross motor and fine movement development than those without anemia. The partial regression coefficients were −0.94 (95% CI −1.64, −0.25; p = 0.008), −1.25 (95% CI −2.48, −0.03; p = 0.044), and −1.18 (95% CI −2.15, −0.21; p = 0.017), respectively. There were no statistically significant differences in total neurobehavioral development and the five domains of neurobehavioral development between children with non-iron-deficiency and iron-deficiency anemia. The partial β values were 0.40 (95% CI −1.53, 2.33; p = 0.684), 0.21 (95% CI −1.39, 1.81; p = 0.795), 0.63 (95% CI −1.03, 2.28; p = 0.457), 0.16 (95% CI −1.78, 2.10; p = 0.871), 0.35 (95% CI −1.32, 2.01; p = 0.684), and 0.34 (95% CI −0.77, 1.46; p = 0.545), respectively. (4) Conclusions: Both iron-deficiency anemia and non-iron-deficiency anemia were negatively correlated with the neurobehavioral development of children. Negative correlations were found between iron-deficiency anemia and gross motor and adaptability development and between non-iron-deficiency anemia and gross motor and fine movement development.
The Onset of Dental Erosion Caused by Food and Drinks and the Preventive Effect of Alkaline Ionized Water
Authors: Sato Tsutomu , Fukuzawa Yoshitaka , Kawakami Satoshi , Suzuki Megumi , Tanaka Yoshinori , Terayama Hayato , Sakabe Kou
Published: September 2021

In recent years, the incidence of dental erosion caused by the ingestion of acidic foods and drinks, including sports drinks, has been increasing in Japan and elsewhere. Therefore, the problems associated with this injury can no longer be ignored in dental clinical practice. The ingestion of these foods and drinks is important from the viewpoint of overall health and disease prevention. For example, fermented foods, such as Japanese pickles, enhance the nutritional value of foodstuffs and promote the absorption of nutrients into the body, and sports drinks are useful for preventing heat stroke and dehydration. Therefore, eliminating these intakes is not a viable solution. In this paper, we outline the mechanism of dental erosion caused by acidic beverages and also describe the effectiveness of alkaline ionized water (AIW) at preventing acid erosion. Given the fact that the complete elimination of acidic beverage consumption is highly unlikely, remedies such as the use of alkaline ionized water (AIW) may be helpful.
Monitored Supplementation of Vitamin D in Preterm Infants: A Randomized Controlled Trial
Authors: Kołodziejczyk-Nowotarska Alicja , Bokiniec Renata , Seliga-Siwecka Joanna
Published: September 2021

Appropriate supplementation of vitamin D can affect infections, allergy, and mental and behavioral development. This study aimed to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants. 109 preterm infants (24 0/7–32 6/7 weeks of gestation) were randomized to receive 500 IU vitamin D standard therapy (n = 55; approximately 800–1000 IU from combined sources) or monitored therapy (n = 54; with an option of dose modification). 25-hydroxyvitamin D [25(OH)D] concentrations were measured at birth, 4 weeks of age, and 35, 40, and 52 ± 2 weeks of post-conceptional age (PCA). Vitamin D supplementation was discontinued in 23% of infants subjected to standard treatment due to increased potentially toxic 25(OH)D concentrations (>90 ng/mL) at 40 weeks of PCA. A significantly higher infants’ percentage in the monitored group had safe vitamin D levels (20–80 ng/mL) at 52 weeks of PCA (p = 0.017). We observed increased vitamin D levels and abnormal ultrasound findings in five infants. Biochemical markers of vitamin D toxicity were observed in two patients at 52 weeks of PCA in the control group. Inadequate and excessive amounts of vitamin D can lead to serious health problems. Supplementation with 800–1000 IU of vitamin D prevents deficiency and should be monitored to avoid overdose.
Spasmolytic Effects of Aphanizomenon Flos Aquae (AFA) Extract on the Human Colon Contractility
Authors: Amato Antonella , Terzo Simona , Marchesa Pierenrico , Maffongelli Angela , Martorana Martina , Scoglio Stefano , Mulè Flavia
Published: September 2021

The blue-green algae Aphanizomenon flos aquae (AFA), rich in beneficial nutrients, exerts various beneficial effects, acting in different organs including the gut. Klamin® is an AFA extract particularly rich in β-PEA, a trace-amine considered a neuromodulator in the central nervous system. To date, it is not clear if β-PEA exerts a role in the enteric nervous system. The aims of the present study were to investigate the effects induced by Klamin® on the human distal colon mechanical activity, to analyze the mechanism of action, and to verify a β-PEA involvement. The organ bath technique, RT-PCR, and immunohistochemistry (IHC) were used. Klamin® reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions. EPPTB, a trace-amine receptor (TAAR1) antagonist, significantly antagonized the inhibitory effects of both Klamin® and exogenous β-PEA, suggesting a trace-amine involvement in the Klamin® effects. Accordingly, AphaMax®, an AFA extract containing lesser amount of β-PEA, failed to modify colon contractility. Moreover, the Klamin® effects were abolished by tetrodotoxin, a neural blocker, but not by L-NAME, a nitric oxide-synthase inhibitor. On the contrary methysergide, a serotonin receptor antagonist, significantly antagonized the Klamin® effects, as well as the contractility reduction induced by 5-HT. The RT-PCR analysis revealed TAAR1 gene expression in the colon and the IHC experiments showed that 5-HT-positive neurons are co-expressed with TAAR1 positive neurons. In conclusion, the results of this study suggest that Klamin® exerts spasmolytic effects in human colon contractility through β-PEA, that, by activating neural TAAR1, induce serotonin release from serotoninergic neurons of the myenteric plexus.
The Specificity and Broad Multitarget Properties of Ligands for the Free Fatty Acid Receptors FFA3/GPR41 and FFA2/GPR43 and the Related Hydroxycarboxylic Acid Receptor HCA2/GPR109A
Authors: Bisenieks Egils , Vigante Brigita , Petrovska Ramona , Turovska Baiba , Muhamadejev Ruslan , Soloduns Vitalijs , Velena Astrida , Pajuste Karlis , Saso Luciano , Klovins Janis , Duburs Gunars , Mandrika Ilona
Published: September 2021

The paradigm of ligand-receptor interactions postulated as “one compound—one target” has been evolving; a multi-target, pleiotropic approach is now considered to be realistic. Novel series of 1,4,5,6,7,8-hexahydro-5-oxoquinolines, pyranopyrimidines and S-alkyl derivatives of pyranopyrimidines have been synthesized in order to characterise their pleiotropic, multitarget activity on the FFA3/GPR41, FFA2/GPR43, and HCA2/GPR109A receptors. Hexahydroquinoline derivatives have been known to exhibit characteristic activity as FFA3/GPR41 ligands, but during this study we observed their impact on FFA2/GPR43 and HCA2/GPR109A receptors as well as their electron-donating activity. Oxopyranopyrimidine and thioxopyranopyrimidine type compounds have been studied as ligands of the HCA2/GPR109A receptor; nevertheless, they exhibited equal or higher activity towards FFA3/GPR41 and FFA2/GPR43 receptors. S-Alkyl derivatives of pyranopyrimidines that have not yet been studied as ligands of GPCRs were more active towards HCA2/GPR109A and FFA3/GPR41 receptors than towards FFA2/GPR43. Representative compounds from each synthesized series were able to decrease the lipopolysaccharide-induced gene expression and secretion of proinflammatory cytokines (IL-6, TNF-α) and of a chemokine (MCP-1) in THP-1 macrophages, resembling the effect of HCA2/GPR109A ligand niacin and the endogenous ligand propionate. This study revealed groups of compounds possessing multitarget activity towards several receptors. The obtained data could be useful for further development of multitarget ligands.
Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Phase II/III Trials
Authors: Bhagavathula Akshaya Srikanth , Vidyasagar Kota , Tesfaye Wubshet
Published: September 2021

Tirzepatide is a novel once-a-week dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, currently under trial to assess glycemic efficacy and safety in people with type 2 diabetes. A systematic review and meta-analysis were conducted to investigate the efficacy of tirzepatide on glycated hemoglobin (HbA1c, %), fasting serum glucose (mg/dL), and body weight (kg) in patients with uncontrolled type 2 diabetes (HbA1c > 7.0%). Mean changes for efficacy and proportions (safety) with corresponding 95% confidence intervals (CIs) were used to provide pooled estimates. A total of four randomized controlled trials, comprising 2783 patients of whom 69.4% (n = 1934) were treated with 5 mg (n = 646), 10 mg (n = 641), or 15 mg (n = 647) of tirzepatide, were compared to the placebo (n = 192) or the selective GLP-1 receptor agonist (n = 523). The pooled analysis showed that tirzepatide treatment resulted in a greater lowering of the HbA1c (−1.94%, 95% CI: −2.02 to −1.87), fasting serum glucose (−54.72 mg/dL, 95% CI: −62.05 to −47.39), and body weight (−8.47, 95% CI: −9.66 to −7.27). We also found that improvement in the HbA1c levels was still maintained at weeks 26 and 40 from the long-term trials. As for safety, only 3% experienced hypoglycemia, and 4% (95% CI: 2 to 6) experienced serious adverse events, while the discontinuation of therapy percentage was 7% (95% CI: 5 to 8). Tirzepatide significantly improved glycemic control and body weight and had an acceptable safety profile, indicating that it is an effective therapeutic option for glucose-lowering in patients with type 2 diabetes mellitus.
Porous Nanomaterials Targeting Autophagy in Bone Regeneration
Authors: Zhang Qing , Xiao Lan , Xiao Yin
Published: September 2021

Porous nanomaterials (PNMs) are nanosized materials with specially designed porous structures that have been widely used in the bone tissue engineering field due to the fact of their excellent physical and chemical properties such as high porosity, high specific surface area, and ideal biodegradability. Currently, PNMs are mainly used in the following four aspects: (1) as an excellent cargo to deliver bone regenerative growth factors/drugs; (2) as a fluorescent material to trace cell differentiation and bone formation; (3) as a raw material to synthesize or modify tissue engineering scaffolds; (4) as a bio-active substance to regulate cell behavior. Recent advances in the interaction between nanomaterials and cells have revealed that autophagy, a cellular survival mechanism that regulates intracellular activity by degrading/recycling intracellular metabolites, providing energy/nutrients, clearing protein aggregates, destroying organelles, and destroying intracellular pathogens, is associated with the phagocytosis and clearance of nanomaterials as well as material-induced cell differentiation and stress. Autophagy regulates bone remodeling balance via directly participating in the differentiation of osteoclasts and osteoblasts. Moreover, autophagy can regulate bone regeneration by modulating immune cell response, thereby modulating the osteogenic microenvironment. Therefore, autophagy may serve as an effective target for nanomaterials to facilitate the bone regeneration process. Increasingly, studies have shown that PNMs can modulate autophagy to regulate bone regeneration in recent years. This paper summarizes the current advances on the main application of PNMs in bone regeneration, the critical role of autophagy in bone regeneration, and the mechanism of PNMs regulating bone regeneration by targeting autophagy.
Variants in COMT, CYP3A5, CYP2B6, and ABCG2 Alter Quetiapine Pharmacokinetics
Authors: Zubiaur Pablo , Fernández-Campos Paula , Navares-Gómez Marcos , Soria-Chacartegui Paula , Villapalos-García Gonzalo , Román Manuel , Mejía-Abril Gina , Ochoa Dolores , Abad-Santos Francisco
Published: September 2021

Quetiapine is an atypical antipsychotic widely used for the treatment of schizophrenia and the depressive episodes of bipolar disorder. The aim of this work was to investigate the effect of variants in relevant pharmacogenes in the pharmacokinetics of quetiapine and to exploratorily evaluate adverse drug reaction (ADR) incidence based on genetic polymorphism. Specifically, 49 healthy volunteers enrolled in two bioequivalence clinical trials were included in this study. In addition, 80 variants in 19 relevant pharmacogenes were genotyped, including cytochrome P450 (CYP) genes, catechol-O-methyl transferase (COMT), other enzymes (e.g., UGT1A1 or UGT1A4), and transporters (e.g., SLCO1B1, ABCB1, or ABCG2). The COMT rs13306278 T allele was significantly related to quetiapine-increased exposure. We demonstrated the existence of quetiapine derivatives with a catechol-like structure (7,8-dihydroxi-quetiapine and 7,8-dihydroxi-N-desalkyl-quetiapine), which would be COMT metabolites and would explain quetiapine accumulation through CYP2D6 and CYP3A4 negative feedback. Moreover, CYP3A5 and CYP2B6 phenotypes were related to quetiapine exposure variability, which confirms (for CYP3A5) and suggests (for CYP2B6) that these enzymes play an important role in quetiapine’s metabolism. Finally, the ABCG2 rs2231142 T allele was related to quetiapine accumulation. Further studies are required to confirm the clinical relevance of our findings.
Population Pharmacokinetic Modelling of the Complex Release Kinetics of Octreotide LAR: Defining Sub-Populations by Cluster Analysis
Authors: Kapralos Iasonas , Dokoumetzidis Aristides
Published: September 2021

The aim of the study is to develop a population pharmacokinetic (PPK) model, of Octreotide long acting repeatable (LAR) formulation in healthy volunteers, which describes the highly variable, multiple peak absorption pattern of the pharmacokinetics of the drug, in individual and population levels. An empirical absorption model, coupled with a one-compartment distribution model with linear elimination was found to describe the data well. Absorption was modelled as a weighted sum of a first order and three transit compartment absorption processes, with delays and appropriately constrained model parameters. Identifiability analysis verified that all twelve parameters of the structural model are identifiable. A machine learning method, i.e., cluster analysis, was performed as pre-processing of the PK profiles, to define subpopulations, before PPK modelling. It revealed that 13% of the patients deviated considerably from the typical absorption pattern and allowed better characterization of the observed heterogeneity and variability of the study, while the approach may have wider applicability in building PPK models. The final model was evaluated by goodness of fit plots, Visual Predictive Check plots and bootstrap. The present model is the first to describe the multiple-peak absorption pattern observed after octreotide LAR administration and may be useful to provide insights and validate hypotheses regarding release from PLGA-based formulations.
Sandwich Structures Reflecting Thermal Radiation Produced by the Human Body
Authors: Militký Jiří , Křemenáková Dana , Venkataraman Mohanapriya , Večerník Josef , Martínková Lenka , Marek Jan
Published: September 2021

Far infrared (FIR) textiles are a new category of functional textiles that have presumptive health and well-being functionality and are closely related to human thermo-physiological comfort. FIR exerts strong rotational and vibrational effects at the molecular level, with the potential to be biologically beneficial. In general, after absorbing either sunlight or heat from the human body, FIR textiles are designed to transform the energy into FIR radiation with a wavelength of 4–14 μm and pass it back to the human body. FIR textiles can meet increased demand for light, warm, comfortable, and healthy clothing. The main aim of this research is to describe the procedure for creating the FIR reflective textile layer as part of multilayer textile structures that have enhanced thermal protection. To develop the active FIR reflecting surface, the deposition of copper nanolayer on lightweight polyester nonwoven structure Milife, which has beneficial properties of low fiber diameters, good shape stability and comfort, was used. This FIR reflective layer was used as an active component of sandwiches composed of the outer layer, insulation layer, active layer, and inner layer. The suitable types of individual layers were based on their morphology, air permeability, spectral characteristics in the infra-red region, and thermal properties. Reflectivity, transmittance, and emissivity were evaluated from IR measurements. Human skin thermal behavior and the prediction of radiation from the human body dependent on ambient conditions and metabolic rate are also mentioned. The FIR reflective textile layer created, as part of multilayer textile structures, was observed to have enhanced thermal protection.
Unravelling Constant pH Molecular Dynamics in Oligopeptides with Explicit Solvation Model
Authors: Privat Cristian , Madurga Sergio , Mas Francesc , Rubio-Martinez Jaime
Published: September 2021

An accurate description of the protonation state of amino acids is essential to correctly simulate the conformational space and the mechanisms of action of proteins or other biochemical systems. The pH and the electrochemical environments are decisive factors to define the effective pKa of amino acids and, therefore, the protonation state. However, they are poorly considered in Molecular Dynamics (MD) simulations. To deal with this problem, constant pH Molecular Dynamics (cpHMD) methods have been developed in recent decades, demonstrating a great ability to consider the effective pKa of amino acids within complex structures. Nonetheless, there are very few studies that assess the effect of these approaches in the conformational sampling. In a previous work of our research group, we detected strengths and weaknesses of the discrete cpHMD method implemented in AMBER when simulating capped tripeptides in implicit solvent. Now, we progressed this assessment by including explicit solvation in these peptides. To analyze more in depth the scope of the reported limitations, we also carried out simulations of oligopeptides with distinct positions of the titratable amino acids. Our study showed that the explicit solvation model does not improve the previously noted weaknesses and, furthermore, the separation of the titratable amino acids in oligopeptides can minimize them, thus providing guidelines to improve the conformational sampling in the cpHMD simulations.