bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly Sensitive and Selective Fluorescence “Turn-On” Detection of Pb (II) Based on Fe3O4@Au–FITC Nanocomposite
Authors: Cai Yina , Ren Binxue , Peng Chifang , Zhang Cunzheng , Wei Xinlin
Published: May 2021

New nanocomposites, Fe3O4@Au–FITC, were prepared and explored to develop a fluorescent detection of Pb2+. The Fe3O4@AuNPs–FITC nanocomposites could be etched by Pb2+ in the presence of Na2S2O3, leading to fluorescence recovery of FITC quenched by Fe3O4@Au nanocomposites. With the increase of Pb2+ concentration, the fluorescence recovery of Fe3O4@AuNPs–FITC increased gradually. Under optimized conditions, a detection limit of 5.2 nmol/L of Pb2+ with a linear range of 0.02–2.0 µmol/L were obtained. The assay demonstrated negligible response to common metal ions. Recoveries of 98.2–106.4% were obtained when this fluorescent method was applied in detecting Pb2+ spiked in a lake-water sample. The above results demonstrated the high potential of ion-induced nanomaterial etching in developing robust fluorescent assays.
In Vitro Evaluation of Antiproliferative Properties of Novel Organotin(IV) Carboxylate Compounds with Propanoic Acid Derivatives on a Panel of Human Cancer Cell Lines
Authors: Pantelić Nebojša Đ. , Božić Bojan , Zmejkovski Bojana B. , Banjac Nebojša R. , Dojčinović Biljana , Wessjohann Ludger A. , Kaluđerović Goran N.
Published: May 2021

The synthesis of novel triphenyltin(IV) compounds, Ph3SnLn (n = 1–3), with oxaprozin (3-(4,5-diphenyloxazol-2-yl)propanoic acid), HL1, and the new propanoic acid derivatives 3-(4,5-bis(4-methoxylphenyl)oxazol-2-yl)propanoic acid, HL2, and 3-(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)propanoic acid, HL3, has been performed. The ligands represent commercial drugs or their derivatives and the tin complexes have been characterized by standard analytical methods. The in vitro antiproliferative activity of both ligands and organotin(IV) compounds has been evaluated on the following tumour cell lines: human prostate cancer (PC-3), human colorectal adenocarcinoma (HT-29), breast cancer (MCF-7), and hepatocellular cancer (HepG2), as well as on normal mouse embryonic fibroblast cells (NIH3T3) with the aid of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-12 diphenyltetrazolium bromide) and CV (crystal violet) assays. Contrary to the inactive ligand precursors, all organotin(IV) carboxylates showed very good activity with IC50 values ranging from 0.100 to 0.758 µM. According to the CV assay (IC50 = 0.218 ± 0.025 µM), complex Ph3SnL1 demonstrated the highest cytotoxicity against the caspase 3 deficient MCF-7 cell line. Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated a two-fold lower concentration of tin in MCF-7 cells in comparison to platinum. To investigate the mechanism of action of the compound Ph3SnL1 on MCF-7 cells, morphological, autophagy and cell cycle analysis, as well as the activation of caspase and ROS/RNS and NO production, has been performed. Results suggest that Ph3SnL1 induces caspase-independent apoptosis in MCF-7 cells.
Electrochemical Peptide-Based Sensors for Foodborne Pathogens Detection
Authors: Tertis Mihaela , Hosu Oana , Feier Bogdan , Cernat Andreea , Florea Anca , Cristea Cecilia
Published: May 2021

Food safety and quality control pose serious issues to food industry and public health domains, in general, with direct effects on consumers. Any physical, chemical, or biological unexpected or unidentified food constituent may exhibit harmful effects on people and animals from mild to severe reactions. According to the World Health Organization (WHO), unsafe foodstuffs are especially dangerous for infants, young children, elderly, and chronic patients. It is imperative to continuously develop new technologies to detect foodborne pathogens and contaminants in order to aid the strengthening of healthcare and economic systems. In recent years, peptide-based sensors gained much attention in the field of food research as an alternative to immuno-, apta-, or DNA-based sensors. This review presents an overview of the electrochemical biosensors using peptides as molecular bio-recognition elements published mainly in the last decade, highlighting their possible application for rapid, non-destructive, and in situ analysis of food samples. Comparison with peptide-based optical and piezoelectrical sensors in terms of analytical performance is presented. Methods of foodstuffs pretreatment are also discussed.
Asymmetric Synthesis of Tetrasubstituted α-Aminophosphonic Acid Derivatives
Authors: Maestro Aitor , del Corte Xabier , López-Francés Adrián , Martínez de Marigorta Edorta , Palacios Francisco , Vicario Javier
Published: May 2021

Due to their structural similarity with natural α-amino acids, α-aminophosphonic acid derivatives are known biologically active molecules. In view of the relevance of tetrasubstituted carbons in nature and medicine and the strong dependence of the biological activity of chiral molecules into their absolute configuration, the synthesis of α-aminophosphonates bearing tetrasubstituted carbons in an asymmetric fashion has grown in interest in the past few decades. In the following lines, the existing literatures for the synthesis of optically active tetrasubstituted α-aminophosphonates are summarized, comprising diastereoselective and enantioselective approaches.
Pineapple (Ananas comosus L.) By-Products Valorization: Novel Bio Ingredients for Functional Foods
Authors: Santos Diana I. , Martins Cátia F. , Amaral Renata A. , Brito Luísa , Saraiva Jorge A. , Vicente António A. , Moldão-Martins Margarida
Published: May 2021

Pineapple is consumed on a large scale around the world due to its appreciated sensorial characteristics. The industry of minimally processed pineapple produces enormous quantities of by-products (30–50%) which are generally undervalued. The end-of-life of pineapple by-products (PBP) can be replaced by reuse and renewal flows in an integrated process to promote economic growth by reducing consumption of natural resources and diminishing food waste. In our study, pineapple shell (PS) and pineapple core (PC), vacuum-packed separately, were subjected to moderate hydrostatic pressure (225 MPa, 8.5 min) (MHP) as abiotic stress to increase bromelain activity and antioxidant capacity. Pressurized and raw PBP were lyophilized to produce a stable powder. The dehydrated samples were characterized by the following methodologies: chemical and physical characterization, total phenolic compounds (TPC), antioxidant capacity, bromelain activity, microbiology, and mycotoxins. Results demonstrated that PBP are naturally rich in carbohydrates (66–88%), insoluble (16–28%) and soluble (2–4%) fiber, and minerals (4–5%). MHP was demonstrated to be beneficial in improving TPC (2–4%), antioxidant activity (2–6%), and bromelain activity (6–32%) without affecting the nutritional value. Furthermore, microbial and mycotoxical analysis demonstrated that powdered PC is a safe by-product. PS application is possible but requires previous decontamination to reduce the microbiological load.
Durability of Flame-Retarded, Co-Extruded Profiles Based on High-Density Polyethylene and Wheat Straw Residues
Authors: Schirp Arne , Dannenberg Jan
Published: May 2021

At present, little information is available in the scientific literature related to the durability (weathering resistance) of fire-retarded wood and natural fiber-reinforced thermoplastics. In this work, thermoplastic profiles for façade applications based on high-density polyethylene, wheat straw particles, and fire-retardants were extruded and their reaction-to-fire performance before and after artificial weathering evaluated. Profile geometries were either solid or hollow-core profiles, and fire-retardants (FR) were added either in the co-extruded layer or in the bulk. Various FR for inclusion in the co-extruded layer were screened based on UL-94 tests. For profile extrusion, two types of FR were chosen: a coated intumescent combination based on ammonium polyphosphate (APP) and an APP coated with melamine and without formaldehyde. Before weathering, the peak heat release rate (pHRR) and the total heat release (THR), which were determined using cone calorimeter measurements, were reduced by up to 64% and 67% due to the FR. However, even before weathering, pHRR of the profiles was relatively high, with best (lowest) values between 230 and 250 kW/m2 under the test conditions. After 28 days of artificial weathering, changes in reaction-to-fire performance and color were evaluated. Use of the APP in the co-extruded layer worsened color change compared to the formulation without APP but the pHRR was not significantly changed. The influence of weathering on the fire behavior was small compared to the difference between fire-retarded and non-fire-retarded materials. Results from the cone calorimeter were analyzed with regard to ETAG 028, which provides requirements related to the durability of fire performance of building products. In many formulations, increase in THR was less than 20% compared to before weathering, which would place some of the profiles in class C or better (EN 13501-1). However, due to the high pHRR, at best, class D was obtained under the conditions of this study. In addition to cone calorimeter measurements, results from the single flame source test, limiting oxygen index determination and thermogravimetric analysis, are shown and discussed. Strength properties, water uptake and swelling of the profiles, thermal conductivity, and energy dispersive X-ray data are also presented.
Xylochemical Synthesis and Biological Evaluation of Shancigusin C and Bletistrin G
Authors: Geske Leander , Kauhl Ulrich , Saeed Mohamed , Schüffler Anja , Thines Eckhard , Efferth Thomas , Opatz Till
Published: May 2021

The biological activities of shancigusin C (1) and bletistrin G (2), natural products isolated from orchids, are reported along with their first total syntheses. The total synthesis of shancigusin C (1) was conducted by employing the Perkin reaction to forge the central stilbene core, whereas the synthesis of bletistrin G (2) was achieved by the Wittig olefination followed by several regioselective aromatic substitution reactions. Both syntheses were completed by applying only renewable starting materials according to the principles of xylochemistry. The cytotoxic properties of shancigusin C (1) and bletistrin G (2) against tumor cells suggest suitability as a starting point for further structural variation.
Salvia officinalis L.: Antitrypanosomal Activity and Active Constituents against Trypanosoma brucei rhodesiense
Authors: Llurba Montesino Núria , Kaiser Marcel , Mäser Pascal , Schmidt Thomas J.
Published: May 2021

As part of our studies on antiprotozoal activity of approved herbal medicinal products, we previously found that a commercial tincture from Salvia officinalis L. (common Sage, Lamiaceae) possesses high activity against Trypanosoma brucei rhodesiense (Tbr), causative agent of East African Human Trypanosomiasis. We have now investigated in detail the antitrypanosomal constituents of this preparation. A variety of fractions were tested for antitrypanosomal activity and analyzed by UHPLC/+ESI QqTOF MS. The resulting data were used to generate a partial least squares (PLS) regression model that highlighted eight particular constituents that were likely to account for the major part of the bioactivity. These compounds were then purified and identified and their activity against the pathogen tested. All identified compounds (one flavonoid and eight diterpenes) displayed significant activity against Tbr, in some cases higher than that of the total tincture. From the overall results, it can be concluded that the antitrypanosomal activity of S. officinalis L. is, for the major part, caused by abietane-type diterpenes of the rosmanol/rosmaquinone group.
Investigating the Cycling Stability of Fe2WO6 Pseudocapacitive Electrode Materials
Authors: Espinosa-Angeles Julio César , Goubard-Bretesché Nicolas , Quarez Eric , Payen Christophe , Sougrati Moulay-Tahar , Crosnier Olivier , Brousse Thierry
Published: May 2021

The stability upon cycling of Fe2WO6 used as a negative electrode material for electrochemical capacitors was investigated. The material was synthesized using low temperature conditions for the first time (220 °C). The electrochemical study of Fe2WO6 in a 5 M LiNO3 aqueous electrolyte led to a specific and volumetric capacitance of 38 F g−1 and 240 F cm−3 when cycled at 2 mV·s−1, respectively, associated with a minor capacitance loss after 10,000 cycles. In order to investigate this very good cycling stability, both surface and bulk characterization techniques (such as Transmission Electron Microscopy, Mössbauer spectroscopy, and magnetization measurements) were used. Only a slight disordering of the Fe3+ cations was observed in the structure, explaining the good stability of the Fe2WO6 upon cycling. This study adds another pseudocapacitive material to the short list of compounds that exhibit such a behavior up to now.
Molecular and Crystal Structure of a Chitosan−Zinc Chloride Complex
Authors: Yui Toshifumi , Uto Takuya , Ogawa Kozo
Published: May 2021

We determined the molecular and packing structure of a chitosan–ZnCl2 complex by X-ray diffraction and linked-atom least-squares. Eight D-glucosamine residues—composed of four chitosan chains with two-fold helical symmetry, and four ZnCl2 molecules—were packed in a rectangular unit cell with dimensions a = 1.1677 nm, b = 1.7991 nm, and c = 1.0307 nm (where c is the fiber axis). We performed exhaustive structure searches by examining all of the possible chain packing modes. We also comprehensively searched the positions and spatial orientations of the ZnCl2 molecules. Chitosan chains of antiparallel polarity formed zigzag-shaped chain sheets, where N2···O6, N2···N2, and O6···O6 intermolecular hydrogen bonds connected the neighboring chains. We further refined the packing positions of the ZnCl2 molecules by theoretical calculations of the crystal models, which suggested a possible coordination scheme of Zn(II) with an O6 atom.
Association between Fatigue and Hoehn-Yahr Staging in Parkinson’s Disease: Eight-Year Follow-Up Study
Authors: Kataoka Hiroshi , Sugie Kazuma
Published: May 2021

The severity of Parkinson’s disease (PD) is developed by multifactorial factors. Falls can worsen disease severity. We previously found that frontal assessment battery (FAB) score was associated with a higher risk of future falls. This eight-year follow-up study aimed to verify whether factors including low FAB score can be the risk of PD progression based on the Hoehn and Yahr scale. In total, 95 patients were initially enrolled in this research and 45 were included in the final follow-up. Then, the cohort was classified into patients with and without disease progression, defined by upgrade of Hoehn-Yahr stage. Differences in clinical characteristics between patients with disease progression and those without were evaluated using the Mann–Whitney U test. Eighteen independent variables were evaluated via a univariate logistic regression analysis. Of the 45 patients enrolled, 32 had disease progression and 13 had no progression. Age (p = 0.033), BFI score (p = 0.003), Zung self-rating depression (p = 0.011), and anxiety scale (p = 0.026) were significantly increased in patients who had disease progression than those with no disease progression. On multivariate logistic regression analysis, brief fatigue inventory (BFI) score (OR = 1.048, p = 0.045, 95% CI = 1.001–1.098) was significantly related to disease progression. All BFI subscores related to general fatigue. Fatigue could predict the progression of motor dysfunction severity over a longitudinal duration in patients with PD with disease progression, having declining physical and mental fatigue.
Micronutrient Deficiencies and Stunting Were Associated with Socioeconomic Status in Indonesian Children Aged 6–59 Months
Authors: Ernawati Fitrah , Syauqy Ahmad , Arifin Aya Yuriestia , Soekatri Moesijanti Y. E. , Sandjaja Sandjaja
Published: May 2021

Micronutrient deficiencies and stunting are known as a significant problem in most developing countries, including Indonesia. The objective of this study was to analyze the association between micronutrient deficiencies and stunting with socioeconomic status (SES) among Indonesian children aged 6–59 months. This cross-sectional study was part of the South East Asian Nutrition Surveys (SEANUTS). A total of 1008 Indonesian children were included in the study. Anemia, iron deficiency, vitamin A deficiency, vitamin D deficiency, and stunting were identified in this study. Structured questionnaires were used to measure SES. Differences between micronutrient parameters and anthropometric indicators with the SES groups were tested using one-way ANOVA with post-hoc test after adjusted for age, area resident (rural and urban), and sex. The highest prevalence of anemia, stunting, and severe stunting were found to be most significant in the lowest SES group at 45.6%, 29.3%, and 54.5%, respectively. Children from the lowest SES group had significantly lower means of Hb, ferritin, retinol, and HAZ. Severely stunted children had a significantly lower mean of Hb concentration compared to stunted and normal height children. Micronutrient deficiencies, except vitamin D, and stunting, were associated with low SES among Indonesian children aged 6–59 months.
Caregiver Status and Diet Quality in Community-Dwelling Adults
Authors: Hossain Sharmin , Beydoun May A. , Evans Michele K. , Zonderman Alan B. , Kuczmarski Marie F.
Published: May 2021

Objective: We investigated cross-sectional and longitudinal associations of diet quality with middle-aged caregiver status. Methods: Caregiving in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (57.7% women, 62% African American (AA)) was measured at waves 3 (2009–2013) and 4 (2013–2017) (mean follow-up time 4.1 years). Diet quality was assessed by the Healthy Eating Index 2010 (HEI-2010) derived from two separate 24 h diet recalls. Multivariable ordinary least square regression was performed for cross-sectional analyses of the association of wave 4 caregiving with wave 4 HEI-2010. Wave 3 caregiving was examined both cross-sectionally and with annual rate of change in HEI using mixed-effects linear regression Models. Multivariable models were adjusted for age, sex, and poverty status. Results: Cross-sectional analyses at wave 4 demonstrate an inverse association of frequent caregiving (“Daily or Weekly” vs. “Never”) for grandchildren with HEI-2010 total score (i.e., lower diet quality) among Whites (β = −2.83 ± 1.19, p = 0.03, Model 2) and AAs (β = −1.84 ± 0.79, p = 0.02,). The “cross-sectional” analysis pertaining to grandchildren caregiving frequency suggested that frequent caregiving (i.e., “Daily or Weekly” vs. “Never” (β = −2.90 ± 1.17, p = 0.04)) only among Whites was inversely related to HEI-2010 total score. Total HEI-2010 score was also related to caring (Model 1), for the elderly over “5 years vs. Never” among Whites (−7.31 ± 3.54, p = 0.04, Model 2). Longitudinally, we found slight potential improvement in diet quality over time (“Daily or Weekly” vs. Never by TIME interaction: +0.88 ± 0.38, p = 0.02) with frequent caregiving among Whites, but not so among AAs. Conclusions: Frequent caring for grandchildren had an inverse relationship with the diet quality of White and AA urban middle-aged caregivers, while caring for elderly was inversely linked to diet quality among Whites only. Longitudinal studies should address the paucity of research on caregivers’ nutritional quality.
The Breast Milk Immunoglobulinome
Authors: Rio-Aige Karla , Azagra-Boronat Ignasi , Castell Margarida , Selma-Royo Marta , Collado María Carmen , Rodríguez-Lagunas María J. , Pérez-Cano Francisco J.
Published: May 2021

Breast milk components contribute to the infant’s immune development and protection, and among other immune factors, immunoglobulins (Igs) are the most studied. The presence of IgA in milk has been known for a long time; however, less information is available about the presence of other Igs such as IgM, IgG, and their subtypes (IgG1, IgG2, IgG3, and IgG4) or even IgE or IgD. The total Ig concentration and profile will change during the course of lactation; however, there is a great variability among studies due to several variables that limit establishing a clear pattern. In this context, the aim of this review was firstly to shed light on the Ig concentration in breast milk based on scientific evidence and secondly to study the main factors contributing to such variability. A search strategy provided only 75 studies with the prespecified eligibility criteria. The concentrations and proportions found have been established based on the intrinsic factors of the study—such as the sampling time and quantification technique—as well as participant-dependent factors, such as lifestyle and environment. All these factors contribute to the variability of the immunoglobulinome described in the literature and should be carefully addressed for further well-designed studies and data interpretation.
Efficacy of Vitamin D Supplementation in Addition to Aerobic Exercise Training in Obese Women with Perceived Myalgia: A Single-Blinded Randomized Controlled Clinical Trial
Authors: Abdeen Heba Ahmed Ali , Rodriguez-Sanz David , Ewidea Mahmoud , Al-Hamaky Dina Mohamed Ali , Mohamed Marwa Abd El-Rahman , Elerian Ahmed Ebrahim
Published: May 2021

Obese women were more susceptible to myalgia because of their significantly lower vitamin D concentrations; the present study investigated the efficacy of vitamin D in addition to an aerobic interval training in the management of obese women with myalgia. Forty-five obese women with vitamin D deficiency and myalgia (30 to 40 years old) were assigned randomly into three equal groups. Group A received an aerobic interval training with vitamin D supplementation, Group B received vitamin D supplementation only, and Group C received aerobic interval training only; participants in all groups were on calorie deficient diets. The study outcomes were the Visual Analog Scale (VAS) for Pain Evaluation, serum vitamin D level, and Cooper 12-Minute Walk Test for Functional Capacity Evaluation, while the Short-Form Health Survey (SF) was used for assessment of quality of life. We detected a significant improvement in pain intensity level, serum vitamin D level, and quality of life in all groups with significant difference between Group A and groups B and C. We also detected a significant improvement in functional capacity in groups A and C, with no significant change in Group B. Aerobic interval training with vitamin D supplementation was more effective for the management of obese women with perceived myalgia.
Increased COVID-19 Lockdown Burden in Italian Adults with Gastrointestinal Diseases
Authors: Ruotolo Monica , Gagliardi Mario , Ciacci Carolina , Zingone Fabiana , de Santis Ciacci Corina , Santonicola Antonella , D'Arcangelo Giovanna , Siniscalchi Monica
Published: May 2021

Background: Coronavirus disease 2019 (COVID-19) causes not only severe illness but also detrimental effects associated with the lockdown measures. The present study aimed to evaluate reported lifestyle changes in a cohort of adults in Italy, including physical exercise, food choices, and psychological wellbeing, after two months of lockdown. Methods: A web survey on social media (Facebook and LinkedIn) of 32 multiple-choice questions aiming to evaluate the impact of the national COVID-19 lockdown in a sample of Italian adults. Results: We received 1378 complete responses (women 68.3%, mean age 39.5 ± 12.5 years). The percentage of participants reporting regular exercise decreased during lockdown (52 vs. 56.5%). The vast majority of people continued to consume the three traditional meals per day, but the consumption of meat, fish, and eggs significantly decreased. Women reported more frequent anxiety, sadness, fear, and feelings of insecurity than men. The factors predicting the worst outcome during the lockdown were being a woman, low education and income, gastrointestinal diseases. Conclusion: The lockdown has had a limited impact on food choices and physical exercise in Italian adults of our series, since most of them made an effort to improve their lifestyle. However, women with gastrointestinal diseases reported more frequent negative feelings and poor adaptation to the lockdown.
Need and Importance of Nutrition Informatics in India: A Perspective
Authors: Joshi Ashish , Gaba Ann , Thakur Shyamli , Grover Ashoo
Published: May 2021

Nutrition informatics (NI) is the effective retrieval, organization, storage, and optimum use of information, data and knowledge for food-and-nutrition-related problem-solving and decision-making. There is a growing opportunity to facilitate technology-enabled behavioral change interventions to support NI research and practice. This paper highlights the changing landscape of food and nutrition practices in India to prepare a NI workforce that could provide some valuable tools to address the double burden of nutrition. Management and interpretation of data could help clarify the relationships and interrelationships of diet and disease in India on both national and regional levels. Individuals with expertise in food and nutrition may receive training in informatics to develop national informatics systems. NI professionals develop tools and techniques, manage various projects and conduct informatics research. These professionals should be well prepared to work in technological settings and communicate data and information effectively. Opportunities for training in NI are very limited in developing countries. Given the current progress in developing platforms and informatics infrastructure, India could serve as an example to other countries to promote NI to support achieving SDGs and other public health initiatives.
Applying Machine Learning to Predict the Exportome of Bovine and Canine Babesia Species That Cause Babesiosis
Authors: Goodswen Stephen J. , Kennedy Paul J. , Ellis John T.
Published: May 2021

Babesia infection of red blood cells can cause a severe disease called babesiosis in susceptible hosts. Bovine babesiosis causes global economic loss to the beef and dairy cattle industries, and canine babesiosis is considered a clinically significant disease. Potential therapeutic targets against bovine and canine babesiosis include members of the exportome, i.e., those proteins exported from the parasite into the host red blood cell. We developed three machine learning-derived methods (two novel and one adapted) to predict for every known Babesia bovis, Babesia bigemina, and Babesia canis protein the probability of being an exportome member. Two well-studied apicomplexan-related species, Plasmodium falciparum and Toxoplasma gondii, with extensive experimental evidence on their exportome or excreted/secreted proteins were used as important benchmarks for the three methods. Based on 10-fold cross validation and multiple train–validation–test splits of training data, we expect that over 90% of the predicted probabilities accurately provide a secretory or non-secretory indicator. Only laboratory testing can verify that predicted high exportome membership probabilities are creditable exportome indicators. However, the presented methods at least provide those proteins most worthy of laboratory validation and will ultimately save time and money.
Action of Carvacrol on Parascaris sp. and Antagonistic Effect on Nicotinic Acetylcholine Receptors
Authors: Trailovic Sasa M. , Rajkovic Milan , Marjanovic Djordje S. , Neveu Cédric , Charvet Claude L.
Published: May 2021

Parascaris sp. is the only ascarid parasitic nematode in equids and one of the most threatening infectious organisms in horses. Only a limited number of compounds are available for treatment of horse helminthiasis, and Parascaris sp. worms have developed resistance to the three major anthelmintic families. In order to overcome the appearance of resistance, there is an urgent need for new therapeutic strategies. The active ingredients of herbal essential oils are potentially effective antiparasitic drugs. Carvacrol is one of the principal chemicals of essential oil from Origanum, Thymus, Coridothymus, Thymbra, Satureja and Lippia herbs. However, the antiparasitic mode of action of carvacrol is poorly understood. Here, the objective of the work was to characterize the activity of carvacrol on Parascaris sp. nicotinic acetylcholine receptor (nAChR) function both in vivo with the use of worm neuromuscular flap preparations and in vitro with two-electrode voltage-clamp electrophysiology on nAChRs expressed in Xenopus oocytes. We developed a neuromuscular contraction assay for Parascaris body flaps and obtained acetylcholine concentration-dependent contraction responses. Strikingly, we observed that 300 µM carvacrol fully and irreversibly abolished Parascaris sp. muscle contractions elicited by acetylcholine. Similarly, carvacrol antagonized acetylcholine-induced currents from both the nicotine-sensitive AChR and the morantel-sensitive AChR subtypes. Thus, we show for the first time that body muscle flap preparation is a tractable approach to investigating the pharmacology of Parascaris sp. neuromuscular system. Our results suggest an intriguing mode of action for carvacrol, being a potent antagonist of muscle nAChRs of Parascaris sp. worms, which may account for its antiparasitic potency.
Synthesis of Multifunctional Nanoparticles for the Combination of Photodynamic Therapy and Immunotherapy
Authors: Lee Mei-Hwa , Thomas James , Li Jin-An , Chen Jyun-Ren , Wang Tzong-Liu , Lin Hung-Yin
Published: May 2021

Programmed death-ligand 1 protein (PD-L1) has been posited to have a major role in suppressing the immune system during pregnancy, tissue allografts, autoimmune disease and other diseases, such as hepatitis. Photodynamic therapy uses light and a photosensitizer to generate singlet oxygen, which causes cell death (phototoxicity). In this work, photosensitizers (such as merocyanine) were immobilized on the surface of magnetic nanoparticles. One peptide sequence from PD-L1 was used as the template and imprinted onto poly(ethylene-co-vinyl alcohol) to generate magnetic composite nanoparticles for the targeting of PD-L1 on tumor cells. These nanoparticles were characterized using dynamic light scattering, high-performance liquid chromatography, Brunauer-Emmett-Teller analysis and superconducting quantum interference magnetometry. Natural killer-92 cells were added to these composite nanoparticles, which were then incubated with human hepatoma (HepG2) cells and illuminated with visible light for various periods. The viability and apoptosis pathway of HepG2 were examined using a cell counting kit-8 and quantitative real-time polymerase chain reaction. Finally, treatment with composite nanoparticles and irradiation of light was performed using an animal xenograft model.
Immunotherapeutic Efficacy of IgY Antibodies Targeting the Full-Length Spike Protein in an Animal Model of Middle East Respiratory Syndrome Coronavirus Infection
Authors: El-Kafrawy Sherif A. , Abbas Aymn T. , Sohrab Sayed S. , Tabll Ashraf A. , Hassan Ahmed M. , Iwata-Yoshikawa Naoko , Nagata Noriyo , Azhar Esam I.
Published: May 2021

Identified in 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and often fatal acute respiratory illness in humans. No approved prophylactic or therapeutic interventions are currently available. In this study, we developed chicken egg yolk antibodies (IgY Abs) specific to the MERS-CoV spike (S) protein and evaluated their neutralizing efficiency against MERS-CoV infection. S-specific IgY Abs were produced by injecting chickens with the purified recombinant S protein of MERS-CoV at a high titer (4.4 mg/mL per egg yolk) at week 7 post immunization. Western blotting and immune-dot blot assays demonstrated specific binding to the MERS-CoV S protein. In vitro neutralization of the generated IgY Abs against MERS-CoV was evaluated and showed a 50% neutralizing concentration of 51.42 μg/mL. In vivo testing using a human-transgenic mouse model showed a reduction of viral antigen positive cells in treated mice, compared to the adjuvant-only controls. Moreover, the lung cells of the treated mice showed significantly reduced inflammation, compared to the controls. Our results show efficient neutralization of MERS-CoV infection both in vitro and in vivo using S-specific IgY Abs. Clinical trials are needed to evaluate the efficiency of the IgY Abs in camels and humans.
Therapeutic Drug Monitoring of Second- and Third-Generation Antipsychotic Drugs—Influence of Smoking Behavior and Inflammation on Pharmacokinetics
Authors: Moschny Nicole , Hefner Gudrun , Grohmann Renate , Eckermann Gabriel , Maier Hannah B , Seifert Johanna , Heck Johannes , Francis Flverly , Bleich Stefan , Toto Sermin , Meissner Catharina
Published: May 2021

Both inflammation and smoking can influence a drug’s pharmacokinetic properties, i.e., its liberation, absorption, distribution, metabolism, and elimination. Depending on, e.g., pharmacogenetics, these changes may alter treatment response or cause serious adverse drug reactions and are thus of clinical relevance. Antipsychotic drugs, used in the treatment of psychosis and schizophrenia, should be closely monitored due to multiple factors (e.g., the narrow therapeutic window of certain psychotropic drugs, the chronicity of most mental illnesses, and the common occurrence of polypharmacotherapy in psychiatry). Therapeutic drug monitoring (TDM) aids with drug titration by enabling the quantification of patients’ drug levels. Recommendations on the use of TDM during treatment with psychotropic drugs are presented in the Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology; however, data on antipsychotic drug levels during inflammation or after changes in smoking behavior—both clinically relevant in psychiatry—that can aid clinical decision making are sparse. The following narrative review provides an overview of relevant literature regarding TDM in psychiatry, particularly in the context of second- and third-generation antipsychotic drugs, inflammation, and smoking behavior. It aims to spread awareness regarding TDM (most pronouncedly of clozapine and olanzapine) as a tool to optimize drug safety and provide patient-tailored treatment.
Genomic Markers for Essential Tremor
Authors: Jiménez-Jiménez Félix Javier , Alonso-Navarro Hortensia , García-Martín Elena , Álvarez Ignacio , Pastor Pau , Agúndez José A. G.
Published: May 2021

There are many reports suggesting an important role of genetic factors in the etiopathogenesis of essential tremor (ET), encouraging continuing the research for possible genetic markers. Linkage studies in families with ET have identified 4 genes/loci for familial ET, although the responsible gene(s) have not been identified. Genome-wide association studies (GWAS) described several variants in LINGO1, SLC1A2, STK32B, PPARGC1A, and CTNNA3, related with ET, but none of them have been confirmed in replication studies. In addition, the case-control association studies performed for candidate variants have not convincingly linked any gene with the risk for ET. Exome studies described the association of several genes with familial ET (FUS, HTRA2, TENM4, SORT1, SCN11A, NOTCH2NLC, NOS3, KCNS2, HAPLN4, USP46, CACNA1G, SLIT3, CCDC183, MMP10, and GPR151), but they were found only in singular families and, again, not found in other families or other populations, suggesting that some can be private polymorphisms. The search for responsible genes for ET is still ongoing.
In Vitro Time-Kill of Common Ocular Pathogens with Besifloxacin Alone and in Combination with Benzalkonium Chloride
Authors: Blondeau Joseph , DeCory Heleen
Published: May 2021

Background: Besifloxacin ophthalmic suspension 0.6% (w/v%) contains benzalkonium chloride (BAK) as a preservative. We evaluated the in vitro time-kill activity of besifloxacin, alone and in combination with BAK, against common bacteria implicated in ophthalmic infections. Methods: The activity of besifloxacin (100 µg/mL), BAK (10, 15, 20, and 100 µg/mL), and combinations of besifloxacin and BAK were evaluated against isolates of Staphylococcus epidermidis (n = 4), Staphylococcus aureus (n = 3), Haemophilus influenzae (n = 2), and Pseudomonas aeruginosa (n = 2) in time-kill experiments of 180 min duration. With the exception of one S. aureus isolate, all of the staphylococcal isolates were methicillin- and/or ciprofloxacin-resistant; one P. aeruginosa isolate was ciprofloxacin-resistant. The reductions in the viable colony counts (log10 CFU/mL) were plotted against time, and the differences among the time–kill curves were evaluated using an analysis of variance. Areas-under-the-killing-curve (AUKCs) were also computed. Results: Besifloxacin alone demonstrated ≥3-log killing of P. aeruginosa (<5 min) and H. influenzae (<120 min), and approached 3-log kills of S. aureus. BAK alone demonstrated concentration-dependent killing of S. epidermidis, S. aureus and H. influenzae, and at 100 µg/mL produced ≥3-log kills in <5 min against these species. The addition of BAK (10, 15, and 20 µg/mL) to besifloxacin increased the rate of killing compared to besifloxacin alone, with earlier 3-log kills of all species except P. aeruginosa and a variable impact on S. aureus. The greatest reductions in AUKC were observed among H. influenzae (8-fold) and S. epidermidis (≥5-fold). Similar results were found when the isolates were evaluated individually by their resistance phenotype. Conclusions: In addition to confirming the activity of 100 µg/mL BAK as a preservative in the bottle, these data suggest that BAK may help besifloxacin to achieve faster time-kills on-eye in the immediate timeframe post-instillation before extensive dilution against bacterial species implicated in ophthalmic infections, including drug-resistant S. epidermidis. Greater killing activity may help prevent resistance development and/or help treat resistant organisms.
A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition Studies
Authors: Nižić Nodilo Laura , Ugrina Ivo , Špoljarić Drago , Amidžić Klarić Daniela , Jakobušić Brala Cvijeta , Perkušić Mirna , Pepić Ivan , Lovrić Jasmina , Saršon Vesna , Safundžić Kučuk Maša , Zadravec Dijana , Kalogjera Livije , Hafner Anita
Published: May 2021

Nasal route of administration offers a unique opportunity of brain targeted drug delivery via olfactory and trigeminal pathway, providing effective CNS concentrations at lower doses and lower risk for adverse reactions compared to systemic drug administration. Therefore, it has been recently proposed as a route of choice for glucocorticoids to control neuroinflammation processes in patients with severe Covid-19. However, appropriate delivery systems tailored to enhance their efficacy yet need to emerge. In this work we present the development of sprayable brain targeting powder delivery platform of dexamethasone sodium phosphate (DSP). DSP-loaded microspheres, optimised employing Quality-by-Design approach, were blended with soluble inert carriers (mannitol or lactose monohydrate). Powder blends were characterized in terms of homogeneity, flow properties, sprayability, in vitro biocompatibility, permeability and mucoadhesion. Nasal deposition studies were performed using 3D printed nasal cavity model. Mannitol provided better powder blend flow properties compared to lactose. Microspheres blended with mannitol retained or enlarged their mucoadhesive properties and enhanced DSP permeability across epithelial model barrier. DSP dose fraction deposited in the olfactory region reached 17.0% revealing the potential of developed powder platform for targeted olfactory delivery. The observed impact of nasal cavity asymmetry highlighted the importance of individual approach when aiming olfactory region.
Resistance to Cucumber Green Mottle Mosaic Virus in Cucumis melo
Authors: Ruiz Leticia , López Carmelo , Picó Belén , Janssen Dirk
Published: May 2021

Cucumber green mottle mosaic virus (CGMMV) is a severe threat to melon production worldwide. At present, there are no cultivars available on the market which show an effective resistance or tolerance to CGMMV infection; only wild Cucumis species were reported as resistant. Germplasm accessions of Cucumis melo, as well as C. anguria, C. ficifolius, C. myriocarpus and C. metuliferus, were mechanically infected with isolates belonging to the European and Asian strain of CGMMV and screened for resistance by scoring symptom severity and comparing the accumulation of virus by qRT-PCR. The wild species C. anguria and C. ficifolius showed no symptoms and did not accumulate CGGMV following inoculation, while C. metuliferus was highly susceptible to the isolates of both strains of CGMMV. The virus accumulated also in C. myriocarpus and the European isolate produced symptoms, but the Asian isolate did not. Thirty C. melo accessions were susceptible to CGMMV. An isolate-dependent expression of symptoms was observed in 16 melon accessions: they showed mild and severe symptoms at 14 and 21 days after inoculation with the European and Asian isolate, respectively. Freeman’s Cucumber showed few or no symptoms following inoculation with the isolate of either CGMMV strain. This particular accession also showed reduced virus accumulation, whereas most other tested germplasm accessions showed significantly higher viral loads and, therefore, may well be a candidate for breeding programs aiming to reduce the losses produced by CGMMV with resistant commercial melon cultivars.
Two Fascinating Polysaccharides: Chitosan and Starch. Some Prominent Characterizations for Applying as Eco-Friendly Food Packaging and Pollutant Remover in Aqueous Medium. Progress in Recent Years: A Review
Authors: Alvarado Nancy , Abarca Romina L. , Linares-Flores Cristian
Published: May 2021

The call to use biodegradable, eco-friendly materials is urgent. The use of biopolymers as a replacement for the classic petroleum-based materials is increasing. Chitosan and starch have been widely studied with this purpose: to be part of this replacement. The importance of proper physical characterization of these biopolymers is essential for the intended application. This review focuses on characterizations of chitosan and starch, approximately from 2017 to date, in one of their most-used applications: food packaging for chitosan and as an adsorbent agent of pollutants in aqueous medium for starch.
Application of Electrospun Nanofibers for Fabrication of Versatile and Highly Efficient Electrochemical Devices: A Review
Authors: Banitaba Seyedeh Nooshin , Ehrmann Andrea
Published: May 2021

Electrochemical devices convert chemical reactions into electrical energy or, vice versa, electricity into a chemical reaction. While batteries, fuel cells, supercapacitors, solar cells, and sensors belong to the galvanic cells based on the first reaction, electrolytic cells are based on the reversed process and used to decompose chemical compounds by electrolysis. Especially fuel cells, using an electrochemical reaction of hydrogen with an oxidizing agent to produce electricity, and electrolytic cells, e.g., used to split water into hydrogen and oxygen, are of high interest in the ongoing search for production and storage of renewable energies. This review sheds light on recent developments in the area of electrospun electrochemical devices, new materials, techniques, and applications. Starting with a brief introduction into electrospinning, recent research dealing with electrolytic cells, batteries, fuel cells, supercapacitors, electrochemical solar cells, and electrochemical sensors is presented. The paper concentrates on the advantages of electrospun nanofiber mats for these applications which are mostly based on their high specific surface area and the possibility to tailor morphology and material properties during the spinning and post-treatment processes. It is shown that several research areas dealing with electrospun parts of electrochemical devices have already reached a broad state-of-the-art, while other research areas have large space for future investigations.
Phospholipid-Conjugated PEG-b-PCL Copolymers as Precursors of Micellar Vehicles for Amphotericin B
Authors: Arias Elsa R. , Angarita-Villamizar Vivian , Baena Yolima , Parra-Giraldo Claudia , Perez Leon D.
Published: May 2021

Amphotericin B (AmB) is a widely used antifungal that presents a broad action spectrum and few reports on the development of resistance. However, AmB is highly toxic, causing renal failure in a considerable number of treated patients. Although when AmB is transported via polymer micelles (PMs) as delivery vehicles its nephrotoxicity has been successfully attenuated, this type of nanoparticle has limitations, such as low encapsulation capacity and poor stability in aqueous media. In this research, the effect of modifying polyethyleglicol-block-poly(ε-caprolactone) (PEG-b-PCL) with 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine (DSPE) on the performance of PMs as vehicles for AmB was studied. PEG-b-PCL with two different lengths of a PCL segment was prepared via ring opening polymerisation and modified with DSPE at a post-synthesis stage through amidation. Upon modification with DSPE, a copolymer was self-assembled, thereby producing particles with hydrodynamic diameters below 100 nm and a lower critical micelle concentration than that of the raw copolymers. Likewise, in the presence of DSPE, the loading capacity of AmB increased because of the formed intermolecular interactions, such as hydrogen bonds, which also caused a lower aggregation of this drug. The assessment of in vitro toxicity against red blood cells indicated that the toxicity of AmB decreased upon encapsulation; however, its antifungal action against clinical yeasts was maintained and enhanced, as indicated by a decrease in its minimum inhibitory concentration.
Smart Hydrogel Bilayers Prepared by Irradiation
Authors: Huo Weixian , An Heng , Chang Shuquan , Yang Shengsheng , Huang Yin , Zhang Xiaohong , Hu Xiaodan , Zhang Haiqian
Published: May 2021

Environment-responsive hydrogel actuators have attracted tremendous attention due to their intriguing properties. Gamma radiation has been considered as a green cross-linking process for hydrogel synthesis, as toxic cross-linking agents and initiators were not required. In this work, chitosan/agar/P(N-isopropyl acrylamide-co-acrylamide) (CS/agar/P(NIPAM-co-AM)) and CS/agar/Montmorillonite (MMT)/PNIPAM temperature-sensitive hydrogel bilayers were synthesized via gamma radiation at room temperature. The mechanical properties and temperature sensitivity of hydrogels under different agar content and irradiation doses were explored. The enhancement of the mechanical properties of the composite hydrogel can be attributed to the presence of agar and MMT. Due to the different temperature sensitivities provided by the two layers of hydrogel, they can move autonomously and act as a flexible gripper as the temperature changes. Thanks to the antibacterial properties of the hydrogel, their storage time and service life may be improved. The as prepared hydrogel bilayers have potential applications in control devices, soft robots, artificial muscles and other fields.