bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Cytomegalovirus Infection and Genetic Background on the Frequencies of Peripheral Blood Suppressor Cells in Human Twins
Authors: Goldeck David , Larsen Lisbeth Aagaard , Christensen Kaare , Hamprecht Klaus , Öttinger Lilly , Hähnel Karin , Pawelec Graham
Published: August 2021

Frequencies and proportions of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in peripheral blood may be informative biomarkers for certain disease states. The influence of genetics and lifetime pathogen exposures on Treg and MDSC frequencies is largely unexplored. Cytomegalovirus (CMV) establishes a latent infection and causes an accumulation of late-differentiated CD8+ memory T cells, commonly associated with a lower frequency of naive cells. Here, analyzing peripheral blood mononuclear cells by multicolor flow cytometry, we found a tendency towards lower frequencies of CD4+CD25+FoxP3+ Tregs in CMV-seropositive than -seronegative middle-aged individuals (p = 0.054), whereas frequencies of lineage-negative CD14+HLA-DR-MDSCs were significantly lower in CMV-seropositive participants (p = 0.005). Assessing associations with the presence of antibodies against different CMV structural proteins, rather than merely assigning seropositivity or seronegativity, failed to yield any closer associations. Examining Treg subsets revealed at most a minor role of the individual’s genetic background, based on an analysis of monozygotic (MZ, n = 42) versus dizygotic (DZ, n = 39) twin pairs from the Danish Twin Registry. The same was true for MDSCs. These initial results suggest that an immunological history of exposures is more important than genetics in determining overall human suppressor cell levels.
Molecular Epidemiology of Sapovirus in Children Living in the Northwest Amazon Region
Authors: Moraes Marcia Terezinha Baroni de , Leitão Gabriel Azevedo Alves , Olivares Alberto Ignácio Olivares , Xavier Maria da Penha Trindade Pinheiro , Bispo Romanul de Souza , Sharma Sumit , Leite José Paulo Gagliardi , Svensson Lennart , Nordgren Johan
Published: August 2021

Sapovirus is an important etiological agent of acute gastroenteritis (AGE), mainly in children under 5 years old living in lower-income communities. Eighteen identified sapovirus genotypes have been observed to infect humans. The aim of this study was to identify sapovirus genotypes circulating in the Amazon region. Twenty-eight samples were successfully genotyped using partial sequencing of the capsid gene. The genotypes identified were GI.1 (n = 3), GI.2 (n = 7), GII.1 (n = 1), GII.2 (n = 1), GII.3 (n = 5), GII.5 (n = 1), and GIV.1 (n = 10). The GIV genotype was the most detected genotype (35.7%, 10/28). The phylogenetic analysis identified sapovirus genotypes that had no similarity with other strains reported from Brazil, indicating that these genotypes may have entered the Amazon region via intense tourism in the Amazon rainforest. No association between histo-blood group antigen expression and sapovirus infection was observed.
Three Immunocompetent Small Animal Models That Do Not Support Zika Virus Infection
Authors: Miller Megan R. , Fagre Anna C. , Clarkson Taylor C. , Markle Erin D. , Foy Brian D.
Published: August 2021

Zika virus (ZIKV) is a mosquito-borne flavivirus that is primarily transmitted to humans through the bite of an infected mosquito. ZIKV causes disease in infected humans with added complications of Guillain-Barré syndrome and birth defects in infants born to mothers infected during pregnancy. There are several large immunocompetent animal models for ZIKV including non-human primates (NHPs). NHP models closely reflect human infection; however, due to sample size restrictions, investigations into the effects of transmission route and the impacts on disease dynamics have been understudied. Mice have been widely used for modeling ZIKV infection, yet there are few ZIKV-susceptible immunocompetent mouse models and none of these have been used to investigate sexual transmission. In an effort to identify a small immunocompetent animal model to characterize sexual transmission of ZIKV, we attempt experimental infection of multimammate mice, New Zealand white rabbits, and Hartley guinea pigs. The multimammate mouse is the natural reservoir of Lassa fever virus and has been identified to harbor other human pathogens. Likewise, while NZW rabbits are susceptible to West Nile virus, they have not yet been examined for their susceptibility to infection with ZIKV. Guinea pigs have been successfully used as models for ZIKV infection, but only in immunocompromised life stages (young or pregnant). Here, it was found that the multimammate mouse and New Zealand White (NZW) rabbits are not susceptible ZIKV infection as determined by a lack viral RNA in tissues and fluids collected. Sexually mature male Hartley guinea pigs were inoculated subcutaneously and by mosquito bite, but found to be refractory to ZIKV infection, contrary to findings of other studies in young and pregnant guinea pigs. Interestingly, here it is shown that adult male guinea pigs are not susceptible to ZIKV infection, even when infected by natural route (e.g., mosquito bite). Although a new small animal model for the sexual transmission for ZIKV was not established through this study, these findings provide information on outbred animal species that are not permissive to infection (NZW rabbits and multimammate mice) and new information surrounding limitations of a previously established animal model (guinea pigs).
Does Methylphenidate Work in Children and Adolescents with Attention Deficit Hyperactivity Disorder?
Authors: Pereira Ribeiro Johanne , Arthur Emma Jasmine , Gluud Christian , Simonsen Erik , Storebø Ole Jakob
Published: August 2021

Objective: Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder diagnosed in increasing proportions of children and adolescents. The psychostimulant methylphenidate has been considered the first-line pharmacological treatment for children and adolescents with ADHD for more than 60 years. Considering recent publications on methylphenidate for ADHD, we here give an overview of its effects in children and adolescents with ADHD, elicited by a well-disputed Cochrane review and narratively synthesise the evidence in the field. Method: We searched for systematic reviews and meta-analyses that investigated methylphenidate as an intervention for children and adolescence with ADHD compared with placebo or no treatment. We assessed the quality of the evidence using AMSTAR II. Results: We found 24 eligible systematic reviews and meta-analyses of which 11 were rated as high- quality evidence according to AMSTAR II. The evidence claiming that methylphenidate is beneficial in treating children and adolescents with ADHD was of very low certainty. The underreporting of adverse events in randomised clinical trials may impede an adequate depiction of the balance between benefits and harms. Conclusions: It appears that there is uncertain evidence on group-level to support the claim that methylphenidate is beneficial in treating children and adolescents with ADHD. Future randomised clinical trials and systematic reviews should include individual participant data, which would allow us to assess intervention effects across modifiers, like age, sex, ADHD subtypes, comorbidities, and dose.
Acquired Zinc Deficiency Mimicking Acrodermatitis Enteropathica in a Breast-Fed Premature Infant
Authors: D’Amico Giovanna , De Laet Corinne , Smits Guillaume , Salik Deborah , Deprez Guillaume , Vilain Catheline , Perlot Pascale , Vicinanza Alfredo
Published: August 2021

We present a case of a transient acquired zinc deficiency in a breast-fed, 4-month-old-male prematurely born infant, with acrodermatitis enteropathica-like symptoms such as crusted, eroded, erythemato-squamous eruption in periorificial and acral patterns. The laboratory investigations showed low zinc levels in the infant’s and the mother’s serum and in the mother’s milk; genetic analysis did not show any mutation in the SLC39A4 gene, involved in acrodermatitis enteropathica. Acquired zinc deficiency is often found in premature infants because of their increased requirement, the low serum and milk zinc levels in breastfeeding women being also an important risk factor, as in this case. A prompt zinc supplementation is essential for the good prognosis of the disease.
Nanoparticles in Dentistry: A Comprehensive Review
Authors: Moraes Gustavo , Zambom Carolina , Siqueira Walter L.
Published: August 2021

In recent years, nanoparticles (NPs) have been receiving more attention in dentistry. Their advantageous physicochemical and biological properties can improve the diagnosis, prevention, and treatment of numerous oral diseases, including dental caries, periodontal diseases, pulp and periapical lesions, oral candidiasis, denture stomatitis, hyposalivation, and head, neck, and oral cancer. NPs can also enhance the mechanical and microbiological properties of dental prostheses and implants and can be used to improve drug delivery through the oral mucosa. This paper reviewed studies from 2015 to 2020 and summarized the potential applications of different types of NPs in the many fields of dentistry.
The Pathogenic Role of Smooth Muscle Cell-Derived Wnt5a in a Murine Model of Lung Fibrosis
Authors: Carmo-Fernandes André , Puschkarow Michelle , Peters Karin , Gnipp Stefanie , Peters Marcus
Published: August 2021

Idiopathic pulmonary fibrosis (IPF) is a disease characterized by extensive fibrosis of the lung tissue. Wnt5a expression was observed to be upregulated in IPF and suggested to be involved in the progression of the disease. Interestingly, smooth muscle cells (SMC) are a major source of Wnt5a in IPF patients. However, no study has been conducted until now to investigate the precise role of smooth muscle-derived Wnt5a in IPF. Here, we used the bleomycin-induced lung fibrosis model in a conditional gene-deficient mouse, where the Wnt5a gene was excised from SMC. We show here that the excision of the Wnt5a gene in SMC led to significantly improved health conditions with minimized weight loss and improved lung function. This improvement was based on a significantly lower deposition of collagen in the lung with a reduced number of fibrotic foci in lung parenchyma. Furthermore, the bleomycin-induced cellular infiltration into the airways was not altered in the gene-deficient mice compared with wild-type mice. Thus, we demonstrate that the Wnt5a expression of SMC of the airways leads to aggravated fibrosis of the lung with poor clinical conditions. This aggravation was not an influence in the bleomycin-induced inflammatory processes but on the development of fibrotic foci in lung parenchyma and the deposition of collagen.
Prospective Evaluation of Local Sustained Release of Celecoxib in Dogs with Low Back Pain
Authors: Wiersema Tijn , Tellegen Anna , Beukers Martijn , van Stralen Marijn , Wouters Erik , van de Vooren Mandy , Woike Nina , Mihov George , Thies Jens , Creemers Laura , Tryfonidou Marianna , Meij Björn
Published: August 2021

Back pain affects millions globally and in 40% of the cases is attributed to intervertebral disc degeneration. Oral analgesics are associated with adverse systemic side-effects and insufficient pain relief. Local drug delivery mitigates systemic effects and accomplishes higher local dosing. Clinical efficacy of intradiscally injected celecoxib (CXB)-loaded polyesteramide microspheres (PEAMs) was studied in a randomized prospective double-blinded placebo controlled veterinary study. Client-owned dog patients suffering from back pain were treated with CXB-loaded (n = 20) or unloaded PEAMs (“placebo”) (n = 10) and evaluated by clinical examination, gait analysis, owners’ questionnaires, and MRI at 6 and 12 weeks follow-up. At 6 and 12 weeks, CXB-treated dogs experienced significantly less pain interference with their daily life activities compared to placebo. The risk ratio for treatment success was 1.90 (95% C.I. 1.24–2.91, p = 0.023) at week 6 and 1.95 (95% C.I. 1.10–3.45, p = 0.036) at week 12. The beneficial effects of CXB-PEAMs were more pronounced for the subpopulation of male dogs and those with no Modic changes in MRI at inclusion in the study; disc protrusion did not affect the outcome. It remains to be determined whether intradiscal injection of CXB-PEAMs, in addition to analgesic properties, has the ability to halt the degenerative process in the long term or restore the disc.
Quantifying Delivered Dose with Jet and Mesh Nebulizers during Spontaneous Breathing, Noninvasive Ventilation, and Mechanical Ventilation in a Simulated Pediatric Lung Model with Exhaled Humidity
Authors: Ari Arzu , Fink James B.
Published: August 2021

Acutely ill children may transition between spontaneous breathing (SB), noninvasive ventilation (NIV), and mechanical ventilation (MV), and commonly receive the same drug dosage with each type of ventilatory support and interface. This study aims to determine the aerosol deposition with jet (JN) and mesh nebulizers (MN) during SB, NIV, and MV using a pediatric lung model. Drug delivery with JN (Mistymax10) and MN (Aerogen Solo) was compared during SB, NIV, and MV using three different lung models set to simulate the same breathing parameters (Vt 250 mL, RR 20 bpm, I:E ratio 1:3). A heated humidifier was placed between the filter and test lung to simulate exhaled humidity (35 ± 2 °C, 100% RH) with all lung models. Albuterol sulfate (2.5 mg/3 mL) was delivered, and the drug deposited on an absolute filter was eluted and analyzed with spectrophotometry. Aerosol delivery with JN was not significantly different during MV, NIV, and SB (p = 0.075), while inhaled dose obtained with MN during MV was greater than NIV and SB (p = 0.001). The delivery efficiency of MN was up to 3-fold more than JN during MV (p = 0.008), NIV (p = 0.005), and SB (p = 0.009). Delivered dose with JN was similar during MV, NIV, and SB, although the delivery efficiency of MN differs with different modes of ventilation.
Mathematical Modeling of Remdesivir to Treat COVID-19: Can Dosing Be Optimized?
Authors: Conway Jessica M. , Abel zur Wiesch Pia
Published: August 2021

The antiviral remdesivir has been approved by regulatory bodies such as the European Medicines Agency (EMA) and the US Food and Drug administration (FDA) for the treatment of COVID-19. However, its efficacy is debated and toxicity concerns might limit the therapeutic range of this drug. Computational models that aid in balancing efficacy and toxicity would be of great help. Parametrizing models is difficult because the prodrug remdesivir is metabolized to its active form (RDV-TP) upon cell entry, which complicates dose–activity relationships. Here, we employ a computational model that allows drug efficacy predictions based on the binding affinity of RDV-TP for its target polymerase in SARS-CoV-2. We identify an optimal infusion rate to maximize remdesivir efficacy. We also assess drug efficacy in suppressing both wild-type and resistant strains, and thereby describe a drug regimen that may select for resistance. Our results differ from predictions using prodrug dose–response curves (pseudo-EC50s). We expect that reaching 90% inhibition (EC90) is insufficient to suppress SARS-CoV-2 in the lungs. While standard dosing mildly inhibits viral polymerase and therefore likely reduces morbidity, we also expect selection for resistant mutants for most realistic parameter ranges. To increase efficacy and safeguard against resistance, we recommend more clinical trials with dosing regimens that substantially increase the levels of RDV-TP and/or pair remdesivir with companion antivirals.
Polyphenols Epigallocatechin Gallate and Resveratrol, and Polyphenol-Functionalized Nanoparticles Prevent Enterovirus Infection through Clustering and Stabilization of the Viruses
Authors: Reshamwala Dhanik , Shroff Sailee , Sheik Amamuddy Olivier , Laquintana Valentino , Denora Nunzio , Zacheo Antonella , Lampinen Vili , Hytonen Vesa , Tastan Bishop Özlem , Krol Silke , Marjomäki Varpu
Published: August 2021

To efficiently lower virus infectivity and combat virus epidemics or pandemics, it is important to discover broadly acting antivirals. Here, we investigated two naturally occurring polyphenols, Epigallocatechin gallate (EGCG) and Resveratrol (RES), and polyphenol-functionalized nanoparticles for their antiviral efficacy. Concentrations in the low micromolar range permanently inhibited the infectivity of high doses of enteroviruses (107 PFU/mL). Sucrose gradient separation of radiolabeled viruses, dynamic light scattering, transmission electron microscopic imaging and an in-house developed real-time fluorescence assay revealed that polyphenols prevented infection mainly through clustering of the virions into very stable assemblies. Clustering and stabilization were not compromised even in dilute virus solutions or after diluting the polyphenols-clustered virions by 50-fold. In addition, the polyphenols lowered virus binding on cells. In silico docking experiments of these molecules against 2- and 3-fold symmetry axes of the capsid, using an algorithm developed for this study, discovered five binding sites for polyphenols, out of which three were novel binding sites. Our results altogether suggest that polyphenols exert their antiviral effect through binding to multiple sites on the virion surface, leading to aggregation of the virions and preventing RNA release and reducing cell surface binding.
Solid Lipid Nanoparticles (SLNs): An Advanced Drug Delivery System Targeting Brain through BBB
Authors: Satapathy Mantosh Kumar , Yen Ting-Lin , Jan Jing-Shiun , Tang Ruei-Dun , Wang Jia-Yi , Taliyan Rajeev , Yang Chih-Hao
Published: August 2021

The blood–brain barrier (BBB) plays a vital role in the protection and maintenance of homeostasis in the brain. In this way, it is an interesting target as an interface for various types of drug delivery, specifically in the context of the treatment of several neuropathological conditions where the therapeutic agents cannot cross the BBB. Drug toxicity and on-target specificity are among some of the limitations associated with current neurotherapeutics. In recent years, advances in nanodrug delivery have enabled the carrier system containing the active therapeutic drug to target the signaling pathways and pathophysiology that are closely linked to central nervous system (CNS) disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), multiple sclerosis (MS), brain tumor, epilepsy, ischemic stroke, and neurodegeneration. At present, among the nano formulations, solid lipid nanoparticles (SLNs) have emerged as a putative drug carrier system that can deliver the active therapeutics (drug-loaded SLNs) across the BBB at the target site of the brain, offering a novel approach with controlled drug delivery, longer circulation time, target specificity, and higher efficacy, and more importantly, reducing toxicity in a biomimetic way. This paper highlights the synthesis and application of SLNs as a novel nontoxic formulation strategy to carry CNS drugs across the BBB to improve the use of therapeutics agents in treating major neurological disorders in future clinics.
Enhanced Bilosomal Properties Resulted in Optimum Pharmacological Effects by Increased Acidification Pathways
Authors: Mooranian Armin , Foster Thomas , Ionescu Corina M. , Walker Daniel , Jones Melissa , Wagle Susbin Raj , Kovacevic Bozica , Chester Jacqueline , Johnston Edan , Wong Elaine , Atlas Marcus D. , Mikov Momir , Al-Salami Hani
Published: August 2021

Introduction: Recent studies in our laboratory have shown that some bile acids, such as chenodeoxycholic acid (CDCA), can exert cellular protective effects when encapsulated with viable β-cells via anti-inflammatory and anti-oxidative stress mechanisms. However, to explore their full potential, formulating such bile acids (that are intrinsically lipophilic) can be challenging, particularly if larger doses are required for optimal pharmacological effects. One promising approach is the development of nano gels. Accordingly, this study aimed to examine biological effects of various concentrations of CDCA using various solubilising nano gel systems on encapsulated β-cells. Methods: Using our established cellular encapsulation system, the Ionic Gelation Vibrational Jet Flow technology, a wide range of CDCA β-cell capsules were produced and examined for morphological, biological, and inflammatory profiles. Results and Conclusion: Capsules’ morphology and topographic characteristics remained similar, regardless of CDCA or nano gel concentrations. The best pharmacological, anti-inflammatory, and cellular respiration, metabolism, and energy production effects were observed at high CDCA and nano gel concentrations, suggesting dose-dependent cellular protective and positive effects of CDCA when incorporated with high loading nano gel.
Overcoming the Low Oral Bioavailability of Deuterated Pyrazoloquinolinone Ligand DK-I-60-3 by Nanonization: A Knowledge-Based Approach
Authors: Mitrović Jelena R. , Divović-Matović Branka , Knutson Daniel E. , Đoković Jelena B. , Kremenović Aleksandar , Dobričić Vladimir D. , Randjelović Danijela V. , Pantelić Ivana , Cook James M. , Savić Miroslav M. , Savić Snežana D.
Published: August 2021

Poor water solubility of new chemical entities is considered as one of the main obstacles in drug development, as it usually leads to low bioavailability after administration. To overcome these problems, the selection of the appropriate formulation technology needs to be based on the physicochemical properties of the drug and introduced in the early stages of drug research. One example of the new potential drug substance with poor solubility is DK-I-60-3, deuterated pyrazoloquinolinone, designed for the treatment of various neuropsychiatric disorders. In this research, based on preformulation studies, nanocrystal technology was chosen to improve the oral bioavailability of DK-I-60-3. Nanocrystal dispersions stabilized by sodium lauryl sulfate and polyvinylpyrrolidone were prepared by modified wet media milling technique, with the selection of appropriate process and formulation parameters. The nanoparticles characterization included particle size and zeta potential measurements, differential scanning calorimetry, X-ray powder diffraction, dissolution and solubility study, and in vivo pharmacokinetic experiments. Developed formulations had small uniform particle sizes and were stable for three months. Nanonization caused decreased crystallite size and induced crystal defects formation, as well as a DK-I-60-3 solubility increase. Furthermore, after oral administration of the developed formulations in rats, two to three-fold bioavailability enhancement was observed in plasma and investigated organs, including the brain.
Cellulose Nanofiber-Based Hydrogels Embedding 5-FU Promote Pyroptosis Activation in Breast Cancer Cells and Support Human Adipose-Derived Stem Cell Proliferation, Opening New Perspectives for Breast Tissue Engineering
Authors: Balahura Liliana-Roxana , Dinescu Sorina , Balaș Mihaela , Cernencu Alexandra , Lungu Adriana , Vlăsceanu George Mihail , Iovu Horia , Costache Marieta
Published: August 2021

The structure and biocompatibility analysis of a hydrogel based on cellulose nanofibers (CNFs) combined with alginate/pectin (A.CNF or P.CNF) and enriched with 1% or 5% 5-FU revealed more favorable properties for the cellular component when pectin was dispersed within CNFs. 5-Fluorouracil (5-FU) is an antimetabolite fluoropyrimidine used as antineoplastic drug for the treatment of multiple solid tumors. 5-FU activity leads to caspase-1 activation, secretion and maturation of interleukins (IL)-1, IL-18 and reactive oxygen species (ROS) generation. Furthermore, the effects of embedding 5-FU in P.CNF were explored in order to suppress breast tumor cell growth and induce inflammasome complex activation together with extra- and intracellular ROS generation. Exposure of tumor cells to P.CNF/5-FU resulted in a strong cytotoxic effect, an increased level of caspase-1 released in the culture media and ROS production—the latter directly proportional to the concentration of anti-tumor agent embedded in the scaffolds. Simultaneously, 5-FU determined the increase of p53 and caspase-1 expressions, both at gene and protein levels. In conclusion, P.CNF/5-FU scaffolds proved to be efficient against breast tumor cells growth due to pyroptosis induction. Furthermore, biocompatibility and the potential to support human adipose-derived stem cell growth were demonstrated, suggesting that these 3D systems could be used in soft tissue reconstruction post-mastectomy.
The Antimicrobial Properties of Modified Pharmaceutical Bentonite with Zinc and Copper
Authors: Martsouka Fotini , Papagiannopoulos Konstantinos , Hatziantoniou Sophia , Barlog Martin , Lagiopoulos Giorgos , Tatoulis Triantafyllos , Tekerlekopoulou Athanasia G. , Lampropoulou Paraskevi , Papoulis Dimitrios
Published: August 2021

Pharmaceutical grade bentonite, containing a high amount of montmorillonite, enriched with zinc (Zn) or copper (Cu) (ZnBent and CuBent, respectively) was used as the main component for the creation of formulations for cutaneous use and tested for their antimicrobial capacity. Bentonite (Bent) with added phenoxyethanol (PH) as a preservative and unmodified bentonite were used as control groups. The mineralogical composition, structural state, and physical or chemical properties, before and after the modification of the samples, were characterized utilizing X-ray Diffraction Analysis (XRD), Fourier-Transform Infrared Spectroscopy (FTIR) and X-ray Fluorescence (XRF) techniques, and Scanning Electron Microscope-Energy Dispersive Spectroscopy (SEM, SEM-EDS) analyses. In addition, the profile of zinc and copper concentration from two types of surfaces ZnBent and CuBent, and into Phosphate-Buffered Saline (PBS) are discussed. Finally, the formulations in the form of basic pastes were challenged against bacteria, molds, and yeasts, and their performance was evaluated based on the European Pharmacopeia criteria. The Cu-modified bentonite performed excellently against bacteria and yeasts, while the Zn-modified bentonite only showed great results against yeasts. Therefore, Cu-modified bentonite formulations could offer antimicrobial protection without the use of preservatives.
Study of the Vernier Effect Based on the Fabry–Perot Interferometer: Methodology and Application
Authors: Gao Haitao , Wang Junxian , Shen Jian , Zhang Shubing , Xu Danping , Zhang Yanan , Li Chaoyang
Published: August 2021

The optical Vernier effect is a powerful tool for improving the sensitivity of an optical sensor, which relies on the use of two sensor units with slightly detuned frequencies. However, an improper amount of detuning can easily cause the Vernier effect to be unusable. In this work, the effective generation range of the Vernier effect and the corresponding interferometer configuration are suggested and experimentally demonstrated through a tunable cascaded Fabry–Perot interferometer structure. We further demonstrate a practical method to increase the magnification factor of the Vernier effect based on the device bandwidth. Only the optical path length of an interferometer probe and the sensitivity of the measurement parameters are needed to design this practical interferometer based on the Vernier effect. Our results provide potential insights for the sensing applications of the Vernier effect.
Uncertainty in the Phase Flicker Measurement for the Liquid Crystal on Silicon Devices
Authors: Yang Zhiyuan , Wu Shiyu , Nie Jiewen , Yang Haining
Published: August 2021

Phase flicker has become an important performance parameter for the liquid crystal on silicon (LCOS) devices. Since the phase response of the LCOS device cannot be measured directly, it is usually derived from the intensity response of the modulated light beam when the LCOS device was placed between a pair of crossed polarisers. However, the relationship between the intensity of the beam and the phase response of the LCOS device is periodic. This would lead to uncertainty in the phase flicker measurement. This paper analyses this measurement uncertainty through both simulation and experiments. It also proposed a strategy to minimise the uncertainty.
Medicinal Properties and In Vitro Biological Activities of Selected Helichrysum Species from South Africa: A Review
Authors: Akinyede Kolajo Adedamola , Cupido Christopher Nelson , Hughes Gail Denise , Oguntibeju Oluwafemi Omoniyi , Ekpo Okobi Eko
Published: August 2021

The genus Helichrysum Mill comprises hundreds of species that are mostly flowering perennial shrubs. Some of these plants that belong to the Helichrysum species are used in traditional medicine to treat cough, back pain, diabetes, asthma, digestive problems, menstrual pain, chest pain, kidney disorders, skin disorders, wounds, open sores, among other conditions, but, only a few scientific studies are reported in the literature with sufficient information that validates the acclaimed folkloric benefits of these plants. This review, therefore, provides a comprehensive update of the available information on the cytotoxicity, genotoxicity, anti-proliferative, anti-bacterial, anti-fungal, anti-viral, anti-HIV, anti-malarial, anti-ulcerogenic, anti-tyrosinase, anti-inflammatory, and anti-oxidant activities of selected Helichrysum species of interest: H. petiolare, H. cymocum, H. foetidum, and H. pandurifolium Schrank, using scientific databases as well as electronic and print sources. The ethnobotanical and morphological characteristics as well as the phytochemical composition and biological activities of these plants are elucidated. The scientific rationale for their current use is discussed based on the evidence in the literature. This review highlights the putative use of the Helichrysum species as a reliable source of bioactive compounds for the production of standard commercial drugs to treat many ailments, including those reported in folkloric uses. Further research on the many plants in the genus Helichrysum is recommended to explore their economic importance both as edible crops and medicinal botanicals.
Assessment of Antidepressant-like, Anxiolytic Effects and Impact on Memory of Pimpinella anisum L. Total Extract on Swiss Albino Mice
Authors: Es-safi Imane , Mechchate Hamza , Amaghnouje Amal , Elbouzidi Amine , Bouhrim Mohamed , Bencheikh Noureddine , Hano Christophe , Bousta Dalila
Published: August 2021

Mental disorders are psychological symptoms that impact multiple areas of an individual’s life. Depression and anxiety are chronic illnesses described as the most prevalent stress-related mood disorders that cause injury and early death. In Morocco, Anise “Pimpinella anisum L.” is one of the most traditionally used condiment plants, which has long been used to cure various illnesses and in phytotherapy. The present study was designed to investigate the antidepressant, anxiolytic, and memory impact of the total extract of Pimpinella anisum (PATE) at the doses of 100 and 200 mg/kg, using the Forced Swimming Test (FST), Tail Suspension Test (TST), Open Field Test (OFT), and Light–Dark Box Test (LDBT) as an experimental paradigm of anxiety and depression, and Novel Object Recognition Test (NORT) and the Morris Water Maze Test (MWMT) as memory tests on Swiss albino mice. The tests were carried out on the 1st, 7th, 14th, and the 21st days of the study, and the extract groups were compared with normal controls and positive controls (receiving bromazepam and paroxetine at the doses of 1 mg/kg and 11.5 mg/kg for anxiety and depression, respectively). The daily oral gavage of the mice by the PATE induced a significant anxiolytic and antidepressant-like effect by shortening immobility time and decreasing downtime in the different tests. PATE at both doses was shown to have no impact on memory following the NORT and MWM tests. Different compounds, such as gallic acid, catechin, chlorogenic acid, caffeic acid, oleuropein, p-coumaric acid, trans-4-hydroxy-3-methoxycinnamic acid, myricetin, and quercetin, were identified during the phytochemical analysis carried out using HPLC analysis. This research supports and promotes the extract’s traditional use, suggesting its use as a phytomedicine against depression and anxiety, and calls for further research to clarify its mode of action.
Agrobacterium-Mediated Genetic Transformation of Taiwanese Isolates of Lemna aequinoctialis
Authors: Wang Kuang-Teng , Hong Ming-Chang , Wu Yu-Sheng , Wu Tsung-Meng
Published: August 2021

Duckweed (Lemna aequinoctialis) is one of the smallest flowering plants in the world. Due to its high reproduction rate and biomass, duckweeds are used as biofactors and feedstuff additives for livestock. It is also an ideal system for basic biological research and various practical applications. In this study, we attempt to establish a micropropagation technique and Agrobacterium-mediated transformation in L. aequinoctialis. The plant-growth regulator type and concentration and Agrobacterium-mediated transformation were evaluated for their effects on duckweed callus induction, proliferation, regeneration, and gene transformation efficiency. Calli were successfully induced from 100% of explants on Murashige and Skoog (MS) medium containing 25.0 μM 2,4-dichlorophenoxyacetic acid (2,4-D) and 2.0 μM thidiazuron (TDZ). MS medium containing 4.5 μM 2,4-D and 2.0 μM TDZ supported the long-lasting growth of calli. Fronds regenerated from 100% of calli on Schenk and Hildebrandt (SH) medium containing 1.0 μM 6-benzyladenine (6-BA). We also determined that 200 μM acetosyringone in the cocultivation medium for 1 day in the dark was crucial for transformation efficiency (up to 3 ± 1%). Additionally, we propose that both techniques will facilitate efficient high-throughput genetic manipulation in Lemnaceae.
Molecular Evaluation of Kyoho Grape Leaf and Berry Characteristics Influenced by Different NPK Fertilizers
Authors: Fiaz Muhammad , Wang Chen , Zia Ul Haq Muhammad , Haider Muhammad Salman , Zheng Ting , Mengqing Ge , Jia Haifeng , Jiu Songtao , Fang Jinggui
Published: August 2021

Fertilization, a fundamental aspect of a plant’s life, has been of great concern for agricultural specialists to minimize the yield gap between actual and potential yield. Around the globe, fertilizers with different NPK ratios are being used to attain a better yield of grape. To find the suitable commercially available fertilizer for quality grape production, a 2 years (2017–2018) study was conducted for the evaluation of 10 fertilizers with different NPK ratios. Commercial fertilizers included were Zhanlan (16:16:16), Garsoni (15:15:15), Acron (16:16:16), Norway (21:7:12), Peters 1 (30:10:10), Nutrivant (14:14:30), Peters 2 (20:20:20), UMAX (15:15:15), G2 (20:20:20), and Yara (15:15:15). The fertilizer application rate was 20 g plant−1, and each was applied at L-29, L-33, and L-36 phenological stages. Chlorophylls, carotenoids, macro/micronutrients in leaf, and anthocyanin derivatives in grape peel were evaluated. Expression levels of 24 genes, including nitrogen, phosphorous, potassium, and anthocyanin pathways in leaf, peel, and pulp were validated by qPCR at L-29, L-33, and L-36 stages. Results indicated that Norway (21:7:12) and Peters 1 (30:10:10) increased carotenoids, chlorophylls, and anthocyanins in leaves, while Zhanlan (16:16:16) improved fruit biochemical attributes, and anthocyanin (cyanidin, delphinidin, petunidin, malvidin, peonidin, and pelargonidin contents). However, a better grape yield was obtained by the application of Peters 1 (30:10:10). Potassium pathway genes were upregulated by Nutrivant (14:14:30), phosphorous pathway genes by Peters 2 (20:20:20), and nitrogen pathway genes by Peters 1 (30:10:10), while Nutrivant (14:14:30) upregulated anthocyanin pathway genes and simultaneously enhanced anthocyanin biosynthesis in berry peels. Results of two years’ study concluded that Peters 1 (30:10:10) was proved better to increase yield, while Zhanlan (14:14:30) was superior in improving anthocyanin biosynthesis.
Quinoa for the Brazilian Cerrado: Agronomic Characteristics of Elite Genotypes under Different Water Regimes
Authors: da Silva Patrícia Carvalho , Ribeiro Junior Walter Quadros , Ramos Maria Lucrecia Gerosa , Celestino Sonia Maria Costa , Silva Alberto do Nascimento , Casari Raphael Augusto das Chagas Noqueli , Santana Charles Cardoso , de Lima Cristiane Andrea , Williams Thomas Christopher Rhys , Vinson Christina Cleo
Published: August 2021

Quinoa stands out as an excellent crop in the Cerrado region for cultivation in the off-season or irrigated winter season. Here, we tested the effects of different water regimes on the agronomic characteristics, physiology, and grain quality of different elite quinoa genotypes under field conditions. The experiment was conducted under field conditions at Embrapa Cerrados (Planaltina, DF, Brazil). The experimental design was in randomized blocks, in a split-plot scheme, with four replications. The plots were composed of 18 quinoa genotypes and modified BRS Piabiru (the currently used genotype), and the split-plots were divided into 4 different water regimes. The following variables were evaluated: productivity and productivity per unit of applied water (PUAA), plant height, flavonoids, anthocyanins, gas exchange, chlorophyll, leaf proline, and relative water content. Our results showed that water regimes between 309 and 389 mm can be recommended for quinoa in the Cerrado region. CPAC6 and CPAC13 presented the highest yield and PUAA under high and intermediate WRs, and hence were the most suitable for winter growth under irrigation. CPAC17 is most suitable for off-season growth under rainfed conditions, as it presented the highest PUAA under the low WRs (247 and 150). CPAC9 stood out in terms of accumulation of flavonoids and anthocyanins in all WRs. Physiological analyses revealed different responses of the genotypes to water restriction, together with symptoms of stress under lower water regimes. Our study reinforces the importance of detailed analyses of the relationship between productivity, physiology, and water use when choosing genotypes for planting and harvest in different seasons.
Effect of Glycero-(9,10-trioxolane)-trialeate on the Physicochemical Properties of Non-Woven Polylactic Acid Fiber Materials
Authors: Olkhov Anatoliy , Alexeeva Olga , Konstantinova Marina , Podmasterev Vyacheslav , Tyubaeva Polina , Borunova Anna , Siracusa Valentina , Iordanskii Alex L.
Published: August 2021

Biocompatible glycero (9,10-trioxolane) trioleate (ozonide of oleic acid triglyceride, OTOA) was incorporated into polylactic acid (PLA) fibers by electrospinning and nonwoven PLA mats with 1%, 3% and 5% OTOA content. The morphological, mechanical, thermal and water sorption properties of electrospun PLA mats after the addition of OTOA were studied. A morphological analysis showed that the addition of OTOA increased the average fiber diameter and induced the formation of pores on the fiber surface, leading to an increase in the specific surface area for OTOA-modified PLA fibrous mats. PLA fiber mats with 3% OTOA content were characterized by a highly porous surface morphology, an increased specific surface area and high-water sorption. Differential scanning calorimetry (DSC) was used to analyze the thermal properties of the fibrous PLA mats. The glass transition temperatures of the fibers from the PLA–OTOA composites decreased as the OTOA content increased, which was attributed to the plasticizing effect of OTOA. DSC results showed that OTOA aided the PLA amorphization process, thus reducing the crystallinity of the obtained nonwoven PLA–OTOA materials. An analysis of the mechanical properties showed that the tensile strength of electrospun PLA mats was improved by the addition of OTOA. Additionally, fibrous PLA mats with 3% OTOA content showed increased elasticity compared to the pristine PLA material. The obtained porous PLA electrospun fibers with the optimal 3% OTOA content have the potential for various biomedical applications such as drug delivery and in tissue engineering.
The Influence of the Furan and Maleimide Stoichiometry on the Thermoreversible Diels–Alder Network Polymerization
Authors: Safaei Ali , Terryn Seppe , Vanderborght Bram , Van Assche Guy , Brancart Joost
Published: August 2021

In recent work, the thermoreversible Diels–Alder reaction between furan and maleimide functional groups has been studied extensively in the context of self-healing elastomers and thermosets. To elaborate the influence of the stoichiometric ratio between the maleimide and furan reactive groups on the thermomechanical properties and viscoelastic behavior of formed reversible covalent polymer networks, a series of Diels–Alder-based networks with different stoichiometric ratios was synthesized. Differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA) and dynamic rheology measurements were performed on the reversible polymer networks, to relate the reversible network structure to the material properties and reactivity. Such knowledge allows the design and optimization of the thermomechanical behavior of the reversible networks for intended applications. Lowering the maleimide-to-furan ratio creates a deficit of maleimide functional groups, resulting in a decrease in the crosslink density of the system, and a consequent decrease in the glass transition temperature, Young’s modulus, and gel transition temperature. The excess of unreacted furan in the system results in faster reaction and healing kinetics and a shift of the reaction equilibrium.
Functional Nanocellulose, Alginate and Chitosan Nanocomposites Designed as Active Film Packaging Materials
Authors: Lavrič Gregor , Oberlintner Ana , Filipova Inese , Novak Uroš , Likozar Blaž , Vrabič-Brodnjak Urška
Published: August 2021

The aim of the study was to characterize and compare films made of cellulose nanocrystals (CNC), nano-fibrils (CNF), and bacterial nanocellulose (BNC) in combination with chitosan and alginate in terms of applicability for potential food packaging applications. In total, 25 different formulations were made and evaluated, and seven biopolymer films with the best mechanical performance (tensile strength, strain)—alginate, alginate with 5% CNC, chitosan, chitosan with 3% CNC, BNC with and without glycerol, and CNF with glycerol—were selected and investigated regarding morphology (SEM), density, contact angle, surface energy, water absorption, and oxygen and water barrier properties. Studies revealed that polysaccharide-based films with added CNC are the most suitable for packaging purposes, and better dispersing of nanocellulose in chitosan than in alginate was observed. Results showed an increase in hydrophobicity (increase of contact angle and reduced moisture absorption) of chitosan and alginate films with the addition of CNC, and chitosan with 3% CNC had the highest contact angle, 108 ± 2, and 15% lower moisture absorption compared to pure chitosan. Overall, the ability of nanocellulose additives to preserve the structure and function of chitosan and alginate materials in a humid environment was convincingly demonstrated. Barrier properties were improved by combining the biopolymers, and water vapor transmission rate (WVTR) was reduced by 15–45% and oxygen permeability (OTR) up to 45% by adding nanocellulose compared to single biopolymer formulations. It was concluded that with a good oxygen barrier, a water barrier that is comparable to PLA, and good mechanical properties, biopolymer films would be a good alternative to conventional plastic packaging used for ready-to-eat foods with short storage time.
Development of a 3D Printed Double-Acting Linear Pneumatic Actuator for the Tendon Gripping
Authors: Grgić Ivan , Wertheimer Vjekoslav , Karakašić Mirko , Ivandić Željko
Published: August 2021

The lack of standardization in tissue testing procedures results in a variety of custom-made devices. In the case of the determination of the mechanical properties of tendons, it is sometimes necessary to adapt the existing laboratory equipment for conducting experiments when specific commercial equipment is not applicable to solve issues such as proper gripping to prevent tendon slipping and rupturing, gripping control and manoeuvrability in case of tendon submerging and without contamination of the testing liquid. This paper presents the systematic development, design, and fabrication using 3D printing technology and the application of the double-acting linear pneumatic actuator to overcome such issues. It is designed to do its work submerged in the Ringers’ solution while gripping the tendon along with the clamps. The pneumatic foot valve unit of the Shimadzu AGS-X tensile testing machine controls the actuator thus preventing Ringers’ solution to be contaminated by the machine operator during specimen set-up. The actuator has a length of 60 mm, a bore of 50 mm, and a stroke length of 20 mm. It is designed to operate with an inlet pressure of up to 0.8 MPa. It comprises the cylinder body with the integrated thread, the piston, the piston head, and the gripper jaw. Fused deposition modeling (FDM) has been used as the 3D printing technique, along with polylactic acid (PLA) as the material for 3D printing. The 3D printed double-acting linear pneumatic actuator was developed into an operating prototype. This study could open new frontiers in the field of tissue testing and the development of similar specialized devices for medical purposes.
HPMA-Based Polymer Conjugates for Repurposed Drug Mebendazole and Other Imidazole-Based Therapeutics
Authors: Studenovský Martin , Rumlerová Anna , Kostka Libor , Etrych Tomáš
Published: August 2021

Recently, the antitumor potential of benzimidazole anthelmintics, such as mebendazole and its analogues, have been reported to have minimal side effects, in addition to their well-known anti-parasitic abilities. However, their administration is strongly limited owing to their extremely poor solubility, which highly depletes their overall bioavailability. This study describes the design, synthesis, and physico-chemical properties of polymer-mebendazole nanomedicines for drug repurposing in cancer therapy. The conjugation of mebendazole to water-soluble and biocompatible polymer carrier was carried out via biodegradable bond, relying on the hydrolytic action of lysosomal hydrolases for mebendazole release inside the tumor cells. Five low-molecular-weight mebendazole derivatives, differing in their inner structure, and two polymer conjugates differing in their linker structure, were synthesized. The overall synthetic strategy was designed to enable the modification and polymer conjugation of most benzimidazole-based anthelmintics, such as albendazole, fenbendazole or albendazole, besides the mebendazole. Furthermore, the described methodology may be suitable for conjugation of other biologically active compounds with a heterocyclic N-H group in their molecules.