bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid Composite Membrane of Phosphorylated Chitosan/Poly (Vinyl Alcohol)/Silica as a Proton Exchange Membrane
Authors: Rosli Nur Adiera Hanna , Loh Kee Shyuan , Wong Wai Yin , Lee Tian Khoon , Ahmad Azizan
Published: September 2021

Chitosan is one of the natural biopolymers that has been studied as an alternative material to replace Nafion membranes as proton change membranes. Nevertheless, unmodified chitosan membranes have limitations including low proton conductivity and mechanical stability. The aim of this work is to study the effect of modifying chitosan through polymer blending with different compositions and the addition of inorganic filler on the microstructure and physical properties of N-methylene phosphonic chitosan/poly (vinyl alcohol) (NMPC/PVA) composite membranes. In this work, the NMPC biopolymer and PVA polymer are used as host polymers to produce NMPC/PVA composite membranes with different compositions (30–70% NMPC content). Increasing NMPC content in the membranes increases their proton conductivity, and as NMPC/PVA-50 composite membrane demonstrates the highest conductivity (8.76 × 10−5 S cm−1 at room temperature), it is chosen to be the base membrane for modification by adding hygroscopic silicon dioxide (SiO2) filler into its membrane matrix. The loading of SiO2 filler is varied (0.5–10 wt.%) to study the influence of filler concentration on temperature-dependent proton conductivity of membranes. NMPC/PVA-SiO2 (4 wt.%) exhibits the highest proton conductivity of 5.08 × 10−4 S cm−1 at 100 °C. In conclusion, the study shows that chitosan can be modified to produce proton exchange membranes that demonstrate enhanced properties and performance with the addition of PVA and SiO2.
Impact of a Graphene Oxide Reducing Agent on a Semi-Permeable Graphene/Reduced Graphene Oxide Forward Osmosis Membrane Filtration Efficiency
Authors: Romaniak Grzegorz , Dybowski Konrad , Jędrzejczak Anna , Sobczyk-Guzenda Anna , Januszewicz Bartłomiej , Szymański Witold , Kowalczyk Paulina , Kaźmierczak Tomasz , Siniarski Jan , Kula Piotr
Published: September 2021

Graphene has been considered as a material that may overcome the limitations of polymer semi-permeable membranes in water treatment technology. However, monolayer graphene still suffers from defects that cause leakage. Here, we report a method of sealing defects in graphene transferred onto porous polymer substrate via reduced graphene oxide (rGO). The influence of various reducing agents (e.g., vitamin C, hydrazine) on the properties of rGO was investigated by SEM, Raman, FTIR, and XRD. Subsequently, membranes based on graphene/reduced graphene oxide were tested in a forward osmosis system using sodium chloride (NaCl). The effect of the effectiveness of the reduction of graphene oxide, the type and number of attached groups, the change in the distance between the rGO flakes, and the structure of this material were examined in terms of filtration efficiency. As a result, semi-permeable centimetre-scale membranes with ion blocking efficiency of up to 90% and water flux of 20 mL h−1 m−2 bar−1 were proposed.
Low-Hysteresis Shape Memory Alloy Scale-Up: DSC, XRD and Microstructure Analysis on Heat-Treated Vacuum Induction Melted Ni-Ti-Cu-Pd Alloys
Authors: Lemke Jannis Nicolas , Gallino Federico , Cresci Matteo , Zilio Stefano , Coda Alberto
Published: September 2021

Quaternary Ni-Ti-Cu-Pd formulations were cast by vacuum induction melting (VIM) with the aim of preparing low-hysteresis shape memory alloys and verifying the applicability of the Co-Factor theory in conventional industrial manufacturing processes. The cast alloys showed lower transformation hysteresis width in DSC measurements than binary Ni-Ti, but struggled to achieve a near zero hysteresis, as predicted by the theoretical framework, despite being close to satisfy the first Co-Factor condition (CC I) that foresees minimum hysteresis for formulations in which the middle eigenvalue of the martensitic transformation matrix λ2 approaches one. The microstructure of the annealed Ni-Ti-Cu-Pd alloys exhibited a considerable amount of mostly sub-micron-sized secondary phases, which distort the matrix composition and prevent it from reaching the optimum stoichiometry for satisfying the CC I. In addition, this class of materials is prone to aging effects, leading to the formation of semi-coherent tetragonal precipitates, which tend to also form at the grain boundaries after low-temperature annealing, further affecting the transformation hysteresis in DSC experiments depending on the thermal history. This work reveals the importance of considering typical casting effects that alter the theoretical λ2 of ideal materials in the compositional design for the development of high-performance low-hysteresis alloys.
Metabolic Profiling during Acute Myeloid Leukemia Progression Using Paired Clinical Bone Marrow Serum Samples
Authors: Kim Hyun Kyu , Son Su Young , Oh Jae Sang , Song Ye Na , Byun Ja Min , Koh Youngil , Hong Junshik , Yoon Sung-Soo , Lee Choong Hwan , Shin Dong-Yeop , Lee Man Ryul
Published: September 2021

Cellular metabolic changes reflect the characteristics of patients with acute myeloid leukemia (AML) caused by genetic variations, which are important in establishing AML treatment. However, little is known about the metabolic profile of patients with genetic variation-induced AML. Furthermore, the metabolites differ with disease progression. Here, metabolites in the bone marrow serum of ten patients with AML and healthy individuals were analyzed using gas chromatography–mass spectrometry. Compared with that in healthy individuals, expression of most metabolites decreased in patients with AML; hydroxylamine, 2-hydroxybutyric acid, monomethylphosphate, and ethylphosphate expression was unusually increased in the patients. We further examined serial metabolite changes across the initial diagnosis, postremission, and relapse phases. Patients with relapse showed increased metabolite expression compared with those in the diagnostic phase, confirming that patients with AML had aggressively modified leukemic cells. However, a clear difference in metabolite distribution was not observed between the diagnosis and complete remission phases, suggesting that the metabolic microenvironment did not change significantly despite complete remission. Interestingly, metabolite profiles differed with genetic variations in leukemic cells. Our results, which were obtained using paired samples collected during AML progression, provide valuable insights for identifying vulnerable targets in the AML metabolome and developing new treatment strategies.
Miniaturized Portable Total Phosphorus Analysis Device Based on Photocatalytic Reaction for the Prevention of Eutrophication
Authors: Jung Dong Geon , Han Maeum , Kim Seung Deok , Kwon Soon Yeol , Kwon Jin-Beom , Lee Junyeop , Kong Seong Ho , Jung Daewoong
Published: September 2021

Phosphorus (P) is one of the most important elements in the aquatic ecosystem, but its overuse causes eutrophication, which is a serious issue worldwide. In this study, we developed a miniaturized portable total phosphorus (TP) analysis device by integrating a TP sensor with a photocatalyst to pretreat analyte and optical components (LED and photodetector) to measure the absorbance of the blue-colored analyte for real-time TP monitoring and prevention of eutrophication. The size of the miniaturized portable TP analysis device is about 10.5 cm × 9.5 cm × 8 cm. Analyte-containing phosphorus was pretreated and colored blue by colorizing agent as a function of the phosphorus concentration. Absorbance of the blue-colored analyte was estimated by the LED and the photodetector such that the phosphorus concentration was quantitatively measured. This device can obtain a wide linear response range from 0.5 mg/L to 2.0 mg/L (R2 = 0.97381), and its performance can be improved by increasing the intensity of the UV light emitted from the LED array. Consequently, the performance of this miniaturized portable TP analysis device was found to be similar to that of a conventional TP analysis system; thus, it can be used in automated in situ TP analysis.
Cinnamon as a Useful Preventive Substance for the Care of Human and Plant Health
Authors: Kowalska Jolanta , Tyburski Józef , Matysiak Kinga , Jakubowska Magdalena , Łukaszyk Joanna , Krzymińska Joanna
Published: September 2021

Cinnamon is widely used as a food spice, but due to its antibacterial and pharmacological properties, it can also be used in processing, medicine and agriculture. The word “Cinnamon” can refer to the plant, processed material, or an extract. It is sometimes used as a substance, and sometimes used as a mixture or as compounds or a group. This article reviews research into the effectiveness of various forms of cinnamon for the control of plant diseases and pests in crops and during storage of fruit and vegetables. Cinnamon acts on pests mainly as a repellent, although in higher doses it has a biocidal effect and prevents egg-laying. Cinnamon and its compounds effectively hinder bacterial and fungal growth, and the phytotoxic effects of cinnamon make it a possible herbicide. This article presents the wide practical use of cinnamon for various purposes, mainly in agriculture. Cinnamon is a candidate for approval as a basic substance with protective potential. In particular, it can be used in organic farming as a promising alternative to chemical pesticides for use in plant protection, especially in preventive treatments. The use of natural products is in line with the restriction of the use of chemical pesticides and the principles of the EU’s Green Deal.
Short Overview of Some Assays for the Measurement of Antioxidant Activity of Natural Products and Their Relevance in Dermatology
Authors: Jaganjac Morana , Sredoja Tisma Vesna , Zarkovic Neven
Published: September 2021

Impaired systemic redox homeostasis is implicated in the onset and development of various diseases, including skin diseases. Therefore, continuous search for natural products with antioxidant bioactivities applicable in biomedicine is attractive topic of general interest. Research efforts aiming to validate antioxidant potentials of natural products has led to the development of several assays based on various test principles. Hence, understanding the advantages and limitations of various assays is important for selection of assays useful to study antioxidant and related bioactivities of natural products of biomedical interest. This review paper gives a short overview on some chemical and cellular bioassays used to estimate the antioxidant activity of chosen natural products together with a brief overview on the use of natural products with antioxidant activities as adjuvant medicinal remedies in dermatology.
Nutraceuticals in Immune Function
Authors: Ooi Soo-Liang , Pak Sok-Cheon
Published: September 2021

Nutraceutical, a term derived from ‘nutrition’ and ‘pharmaceutical’, refers to any product isolated from herbs, nutrients, specific diets, processed foods, and beverages used not only for nutritional but also for medicinal purposes [...]
Unraveling the Photodynamic Activity of Cationic Benzoporphyrin-Based Photosensitizers against Bladder Cancer Cells
Authors: Gomes Ana T. P. C. , Neves M. Graça P. M. S. , Fernandes Rosa , Ribeiro Carlos F. , Cavaleiro José A. S. , Moura Nuno M. M.
Published: September 2021

In this study, we report the preparation of new mono-charged benzoporphyrin complexes by reaction of the appropriate neutral benzoporphyrin with (2,2′-bipyridine)dichloroplatinum(II) and of the analogs’ derivatives synthesized through alkylation of the neutral scaffold with iodomethane. All derivatives were incorporated into polyvinylpyrrolidone (PVP) micelles. The ability of the resultant formulations to generate reactive oxygen species was evaluated, mainly the singlet oxygen formation. Then, the capability of the PVP formulations to act as photosensitizers against bladder cancer cells was assessed. Some of the studied formulations were the most active photosensitizers causing a decrease in HT-1376 cells’ viability. This creates an avenue to further studies related to bladder cancer cells.
Synthesis, Crystal Structure and Bioactivity of Phenazine-1-carboxylic Acylhydrazone Derivatives
Authors: Wu Shouting , Liang Xi , Luo Fang , Liu Hua , Shen Lingyi , Yang Xianjiong , Huang Yali , Xu Hong , Wu Ning , Zhang Qilong , Redshaw Carl
Published: September 2021

A phenazine-1-carboxylic acid intermediate was synthesized from the reaction of aniline and 2-bromo-3-nitro-benzoic acid. It was then esterified and reacted with hydrazine hydrate to afford phenazine-1-carboxylic hydrazine. Finally, 10 new hydrazone compounds 3a–3j were obtained by the condensation reaction of phenazine-1-carboxylic acid hydrazide and the respective aldehyde-containing compound. The structures were characterized by 1H and 13C NMR spectroscopy, MS and single crystal X-ray diffraction. The antitumor activity of the target compounds in vitro (HeLa and A549) was determined by thiazolyl blue tetrazolium bromide. The results showed that compound (E)-N′-(2-hydroxy-4-(2-(piperidine-1-yl) ethoxy) benzyl) phenazine-1-carbonyl hydrazide 3d exhibited good cytotoxic activity.
Fluorescent Nanoparticles Synthesized from DNA, RNA, and Nucleotides
Authors: Wang Maofei , Tsukamoto Masaki , Sergeyev Vladimir G. , Zinchenko Anatoly
Published: September 2021

Ubiquitous on Earth, DNA and other nucleic acids are being increasingly considered as promising biomass resources. Due to their unique chemical structure, which is different from that of more common carbohydrate biomass polymers, materials based on nucleic acids may exhibit new, attractive characteristics. In this study, fluorescent nanoparticles (biodots) were prepared by a hydrothermal (HT) method from various nucleic acids (DNA, RNA, nucleotides, and nucleosides) to establish the relationship between the structure of precursors and fluorescent properties of biodots and to optimize conditions for preparation of the most fluorescent product. HT treatment of nucleic acids results in decomposition of sugar moieties and depurination/depyrimidation of nucleobases, while their consequent condensation and polymerization gives fluorescent nanoparticles. Fluorescent properties of DNA and RNA biodots are drastically different from biodots synthesized from individual nucleotides. In particular, biodots synthesized from purine-containing nucleotides or nucleosides show up to 50-fold higher fluorescence compared to analogous pyrimidine-derived biodots. The polymeric nature of a precursor disfavors formation of a bright fluorescent product. The reported effect of the structure of the nucleic acid precursor on the fluorescence properties of biodots should help designing and synthesizing brighter fluorescent nanomaterials with broader specification for bioimaging, sensing, and other applications.
Interaction of Reactive Gases with Platinum Aerosol Particles at Room Temperature: Effects on Morphology and Surface Properties
Authors: Olszok Vinzent , Bierwirth Malte , Weber Alfred P.
Published: September 2021

Nanoparticles produced in technical aerosol processes exhibit often dendritic structures, composed of primary particles. Surprisingly, a small but consistent discrepancy was observed between the results of common aggregation models and in situ measurements of structural parameters, such as fractal dimension or mass-mobility exponent. A phenomenon which has received little attention so far is the interaction of agglomerates with admixed gases, which might be responsible for this discrepancy. In this work, we present an analytical series, which underlines the agglomerate morphology depending on the reducing or oxidizing nature of a carrier gas for platinum particles. When hydrogen is added to openly structured particles, as investigated by tandem differential mobility analysis (DMA) and transmission electron microscopy (TEM) analysis, Pt particles compact already at room temperature, resulting in an increased fractal dimension. Aerosol Photoemission Spectroscopy (APES) was also able to demonstrate the interaction of a gas with a nanoscaled platinum surface, resulting in a changed sintering behavior for reducing and oxidizing atmospheres in comparison to nitrogen. The main message of this work is about the structural change of particles exposed to a new environment after complete particle formation. We suspect significant implications for the interpretation of agglomerate formation, as many aerosol processes involve reactive gases or slightly contaminated gases in terms of trace amounts of unintended species.
The Effect of Micro-Inertia and Flexoelectricity on Love Wave Propagation in Layered Piezoelectric Structures
Authors: Hrytsyna Olha , Sladek Jan , Sladek Vladimir
Published: September 2021

The non-classical linear governing equations of strain gradient piezoelectricity with micro-inertia effect are used to investigate Love wave propagation in a layered piezoelectric structure. The influence of flexoelectricity and micro-inertia effect on the phase wave velocity in a thin homogeneous flexoelectric layer deposited on a piezoelectric substrate is investigated. The dispersion relation for Love waves is obtained. The phase velocity is numerically calculated and graphically illustrated for the electric open-circuit and short-circuit conditions and for distinct material properties of the layer and substrate. The influence of direct flexoelectricity, micro-inertia effect, as well as the layer thickness on Love wave propagation is studied individually. It is found that flexoelectricity increases the Love-wave phase velocity, while the micro-inertia effect reduces its value. These effects become more significant for Love waves with shorter wavelengths and small guiding layer thicknesses.
Agility and Safety Performance among Nurses: The Mediating Role of Mindful Organizing
Authors: Saleem Muhammad Shoaib , Isha Ahmad Shahrul Nizam , Mohd Yusop Yuzana , Awan Maheen Iqbal , Naji Gehad Mohammed Ahmed
Published: September 2021

This study aimed to assess the impact of workforce agility on private hospital nursing staff’s safety behavior with the mediating role of mindful organizing. This study was cross-sectional. A self-administered questionnaire was used to collect data from 369 nursing staff. The structural equation modeling (SEM) technique was used to check the internal consistency, convergent validity, discriminant validity, and hypotheses testing. For mediation analysis, the bootstrapping technique was used. Our findings suggested that workforce agility is the possible predictor of mindful organizing, as all of these dimensions have a positive impact on mindful organizing. Reference to safety performance sub-dimensions, proactivity, adaptability, and resilience had a positive significant impact on (a) safety compliance, and proactivity had a positive impact on (b) safety participation. Further, mindful organizing was also found to be positively associated with safety performance. Evidence for mediation between workforce agility and safety performance was also observed. Proactivity, adaptability, and resilience can enhance safety performance for the nursing staff. Workforce agility can also help the organization to attain mindful organizing, which will help them to achieve operational excellence, whereas in the past, high-reliability organizations were mainly found practicing mindful organizing. This study demonstrated the key impact of workforce agility and mindful organizing on safety behaviors directly and indirectly.
A Retrospective Review of Patient Records and Factors Associated with Decisions Made by Community Nurse-Paramedics’ in Finland
Authors: Rasku Tuija , Helminen Mika , Kaunonen Marja , Thyer Elizabeth , Paavilainen Eija , Joronen Katja
Published: September 2021

Community paramedicine (CP) has extended the role of paramedics and the main goal is to provide non-emergency care, which reduces the visits to emergency departments. The aim of this study was to describe the Finnish CP and examine the factors that were involved in CNPs’ decision-making processes. The study was based on data from 450 consecutive CP patient records from three hospital districts. A more detailed analysis was carried out on 339 cases in patients’ homes and elderly care homes, and the data analysis included multivariate logistic regression to examine the impact of variables on the CNPs’ decisions. These patients’ most common health issues were general weakness (15.9%) and fever (10.6%), and over half (58.7%) could remain at home after the CP visit. There were five independent factors associated with the CNPs’ decisions of the patient’s care continuum: the hospital district, if the patient could walk, whether the troponin test was performed, a physician was consulted, and the nature of the task. CP units played a valuable role in non-emergency care. Understanding the factors associated with CNP decision-making can increase the safety and effectiveness of reducing hospital visits, by providing patient care at home, or in elderly care facilities.
Nasopharyngeal Carcinoma: The Role of the EGFR in Epstein–Barr Virus Infection
Authors: Peng Xintong , Zhou Yanling , Tao Yongguang , Liu Shuang
Published: September 2021

Epstein–Barr virus (EBV), a type 4 γ herpes virus, is recognized as a causative agent in nasopharyngeal carcinoma (NPC). Incidence of EBV-positive NPC have grown in recent decades along with worse outcomes compared with their EBV-negative counterparts. Latent membrane protein 1 (LMP1), encoded by EBV, induces NPC progression. The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases (RTK), is a driver of tumorigenesis, including for NPC. Little data exist on the relationship between EGFR and EBV-induced NPC. In our initial review, we found that LMP1 promoted the expression of EGFR in NPC in two main ways: the NF-κB pathway and STAT3 activation. On the other hand, EGFR also enhances EBV infection in NPC cells. Moreover, activation of EGFR signalling affects NPC cell proliferation, cell cycle progression, angiogenesis, invasion, and metastasis. Since EGFR promotes tumorigenesis and progression by downstream signalling pathways, causing poor outcomes in NPC patients, EGFR-targeted drugs could be considered a newly developed anti-tumor drug. Here, we summarize the major studies on EBV, EGFR, and LMP1-regulatory EGFR expression and nucleus location in NPC and discuss the clinical efficacy of EGFR-targeted agents in locally advanced NPC (LA NPC) and recurrent or metastatic NPC (R/M NPC) patients.
Protozoan and Microbial Pathogens of House Cats in the Province of Tekirdag in Western Turkey
Authors: Muz Mustafa Necati , Erat Serkan , Mumcuoglu Kosta Y.
Published: September 2021

Domestic felines’ re-emerging infectious and neglected zoonotic diseases are a significant focus of global “One Health” efforts. This study aimed to rapidly diagnose 14 pathogens, including zoonoses by using PCR primers in 167 client-owned symptomatic cats, routinely accepted to the Veterinary Clinics of Tekirdag. The prevalence of pathogens investigated were as follows: Babesia canis canis (24%), Babesia microti (2.4%), Hepatozoon felis (10.8%), Cytauxzoon felis (6.6%), Bartonella henselae (40.1%), Anaplasma platys (30.5%), Anaplasma phagocytophilum (7.2%), Rickettsia felis (26.3%), Borrelia burgdorferi (21%), and hemotropic Mycoplasma sp. (11.4%). There was a significant difference between the prevalence of the pathogens (χ2 = 152.26, df = 9, p < 0.001). There was also a statistical difference between the gender of the cats in terms of the prevalence of all pathogens considered together (χ2 = 4.80, df = 1, p = 0.028), where the female cats showed a higher prevalence. This was not the case for the different age groups (χ2 = 2.92, df = 1, p = 0.088). The lowest infection was observed for B. microti (p < 0.001), while the highest infection was observed for B. henselae (p < 0.01). Leishmania donovani, Plasmodium spp., Ehrlichia chaffeensis, and Neoehrlichia mikurensis PCR test results were negative in all samples. In conclusion, house cats of Tekirdag are apparently highly susceptible to some neglected zoonoses important for “One Health”, and their prevalence in the region is most probably underestimated. Hence, applying PCR tests to assist fast clinic diagnosis in routine, may be an efficient option to protect the public as well as the cats from severe diseases.
Overcoming the Negligence in Laboratory Diagnosis of Mucosal Leishmaniasis
Authors: Cantanhêde Lilian Motta , Mattos Cristiane Batista , Cruz Ana Karoline , Ikenohuchi Yoda Janaina , Fernandes Flavia Gonçalves , Medeiros Enmanuella Helga Ratier Terceiro , da Silva-Júnior Cipriano Ferreira , Cupolillo Elisa , Ferreira Gabriel Eduardo Melim , Ferreira Ricardo de Godoi Mattos
Published: September 2021

The northern region of Brazil, which has the largest number of cases of tegumentary leishmaniasis (TL) in the country, is also the region that has the highest diversity of species of vectors and Leishmania parasites. In this region, cases of mucosal leishmaniasis (ML), a clinical form of TL, exceed the national average of cases, reaching up to 12% of the total annual TL notifications. ML is associated with multiple factors, such as the parasite species and the viral endosymbiont Leishmania RNA virus 1 (LRV1). Being a chronic parasitological disease, laboratory diagnosis of ML poses a challenge for health services. Here, we evaluated more than 700 clinical samples from patients with clinical suspicion of TL, including patients with cutaneous leishmaniasis (CL) and mucosal leishmaniasis, comparing the results of parasitological tests—direct parasitological examination by microscopy (DP) and conventional PCR (cPCR) targeting of both kDNA and hsp70. The DP was performed by collecting material from lesions through biopsies (mucosal lesions) or scarification (cutaneous lesions); for PCR, a cervical brush was used for sample collection. Blood samples were tested employing standardized real-time PCR (qPCR) protocol targeting the HSP70 gene. PCR tests showed higher sensitivity than DP for both CL and ML samples. Considering ML samples only (N = 89), DP showed a sensitivity of 49.4% (N = 44) against 98.8% (N = 88) for kDNA PCR. The qPCR hsp70 for blood samples from patients with ML (N = 14) resulted in superior sensitivity (50%; N = 7) compared to DP (21.4%; N = 3) for samples from the same patients. Our results reinforced the need to implement a molecular test for the diagnosis of ML, in addition to proposing methods less invasive for collecting material from TL patients. Sample collection using a cervical brush in lesions observed in CL and ML patients is easy to perform and less invasive, compared to scarification and biopsies. Blood samples could be a good source for qPCR diagnosis for ML patients. Thus, we propose here a standardized method for collection and for performing of molecular diagnosis of clinical samples from suspicious ML patients that can be applied in reference services for improving ML diagnosis.
Screening of Dietary Ingredients against the Honey Bee Parasite Nosema ceranae
Authors: Braglia Chiara , Alberoni Daniele , Porrini Martin Pablo , Garrido Paula Melisa , Baffoni Loredana , Di Gioia Diana
Published: September 2021

Nosema ceranae is a major pathogen in the beekeeping sector, responsible for nosemosis. This disease is hard to manage since its symptomatology is masked until a strong collapse of the colony population occurs. Conversely, no medicaments are available in the market to counteract nosemosis, and only a few feed additives, with claimed antifungal action, are available. New solutions are strongly required, especially based on natural methods alternative to veterinary drugs that might develop resistance or strongly pollute honey bees and the environment. This study aims at investigating the nosemosis antiparasitic potential of some plant extracts, microbial fermentation products, organic acids, food chain waste products, bacteriocins, and fungi. Honey bees were singularly infected with 5 × 104 freshly prepared N. ceranae spores, reared in cages and fed ad libitum with sugar syrup solution containing the active ingredient. N. ceranae in the gut of honey bees was estimated using qPCR. The results showed that some of the ingredients administered, such as acetic acid at high concentration, p-coumaric acid, and Saccharomyces sp. strain KIA1, were effective in the control of nosemosis. On the other hand, wine acetic acid strongly increased the N. ceranae amount. This study investigates the possibility of using compounds such as organic acids or biological agents including those at the base of the circular economy, i.e., wine waste production, in order to improve honeybee health.
Endoscopic Evaluation for Stricture Formation Post Button Battery Ingestion
Authors: Bulna Amber , Fifi Amanda C.
Published: September 2021

Every year, there are over 3300 ingestions of button batteries, mostly by young children. Initial presentation of button battery ingestion may be nonspecific, with a delay in diagnosis and removal resulting in increased risk of complications. We present the case of a five-year-old female who presented with vomiting following unwitnessed button battery ingestion. The battery was impacted in the middle esophagus for at least six hours. Endoscopy was performed for immediate removal and showed a Grade 2B erosion, warranting nasogastric tube placement. The patient remained asymptomatic following discharge and had a barium swallow that was read as normal. However, a repeat endoscopy one month later visualized stricture formation at the previous battery injury site. This case highlights the importance of both clinician and parent awareness of button battery ingestion and demonstrates that endoscopy provides the most accurate assessment of esophageal injury and complication development, even in asymptomatic patients.
COVID 19 Vaccine for Adolescents. Concern about Myocarditis and Pericarditis
Authors: Calcaterra Giuseppe , Mehta Jawahar Lal , de Gregorio Cesare , Butera Gianfranco , Neroni Paola , Fanos Vassilios , Bassareo Pier Paolo
Published: September 2021

The alarming onset of some cases of myocarditis and pericarditis following the administration of Pfizer–BioNTech and Moderna COVID-19 mRNA-based vaccines in adolescent males has recently been highlighted. All occurred after the second dose of the vaccine. Fortunately, none of patients were critically ill and each was discharged home. Owing to the possible link between these cases and vaccine administration, the US and European health regulators decided to continue to investigate the potential causal relationship between COVID-19 mRNA vaccines and myocarditis. In any case, none of the patients fulfilled the criteria for multi-system inflammatory syndrome or Kawasaki-like disease and there was no evidence of acute SARS-CoV-2 infection.
Research and Clinical Landscape of Bispecific Antibodies for the Treatment of Solid Malignancies
Authors: Antonarelli Gabriele , Giugliano Federica , Corti Chiara , Repetto Matteo , Tarantino Paolo , Curigliano Giuseppe
Published: September 2021

Solid tumors adopt multiple mechanisms to grow, evade immune responses, and to withstand therapeutic approaches. A major breakthrough in the armamentarium of anti-cancer agents has been the introduction of monoclonal antibodies (mAbs), able to inhibit aberrantly activated pathways and/or to unleash antigen (Ag)-specific immune responses. Nonetheless, mAb-mediated targeted pressure often fails due to escape mechanisms, mainly Ag loss/downregulation, ultimately providing therapy resistance. Hence, in order to target multiple Ag at the same time, and to facilitate cancer-immune cells interactions, bispecific antibodies (bsAbs) have been developed and are being tested in clinical trials, yielding variable safety/efficacy results based on target selection and their structure. While in hematologic cancers the bsAb blinatumomab recently reached the Food and Drug Administration (FDA)-approval for B Cell Acute Lymphoblastic Leukemia, bsAbs use in solid tumors faces considerable challenges, such as target Ag selection, biodistribution, and the presence of an immune-suppressive tumor microenvironment (TME). This review will focus on the state-of-the art, the design, and the exploitation of bsAbs against solid malignancies, delineating their mechanisms of action, major pitfalls, and future directions.
Synthesis and Biological Evaluation of Honokiol Derivatives Bearing 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3H)-ones as Potential Viral Entry Inhibitors against SARS-CoV-2
Authors: Guo Yong , Meng Jie-Ru , Liu Jia-Zheng , Xu Ting , Zheng Zhi-Yuan , Jiang Zhi-Hong , Bai Li-Ping
Published: September 2021

The 2019 coronavirus disease (COVID-19) caused by SARS-CoV-2 virus infection has posed a serious danger to global health and the economy. However, SARS-CoV-2 medications that are specific and effective are still being developed. Honokiol is a bioactive component from Magnoliae officinalis Cortex with damp-drying effect. To develop new potent antiviral molecules, a series of novel honokiol analogues were synthesized by introducing various 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3H)-ones to its molecule. In a SARS-CoV-2 pseudovirus model, all honokiol derivatives were examined for their antiviral entry activities. As a result, 6a and 6p demonstrated antiviral entry effect with IC50 values of 29.23 and 9.82 µM, respectively. However, the parental honokiol had a very weak antiviral activity with an IC50 value more than 50 µM. A biolayer interfero-metry (BLI) binding assay and molecular docking study revealed that 6p binds to human ACE2 protein with higher binding affinity and lower binding energy than the parental honokiol. A competitive ELISA assay confirmed the inhibitory effect of 6p on SARS-CoV-2 spike RBD’s binding with ACE2. Importantly, 6a and 6p (TC50 > 100 μM) also had higher biological safety for host cells than honokiol (TC50 of 48.23 μM). This research may contribute to the discovery of potential viral entrance inhibitors for the SARS-CoV-2 virus, although 6p’s antiviral efficacy needs to be validated on SARS-CoV-2 viral strains in a biosafety level 3 facility.
In Silico Screening and In Vivo Evaluation of Potential CACNA2D1 Antagonists as Intraocular Pressure-Reducing Agents in Glaucoma Therapy
Authors: Li Hanxuan , Ibrahim Mohamed Moustafa , Chen Hao , Li Wei , Jablonski Monica M.
Published: September 2021

Glaucoma is a leading cause of permanent vision loss and current drugs do not halt disease progression. Thus, new therapies targeting different drug targets with novel mechanisms of action are urgently needed. Previously, we identified CACNA2D1 as a novel modulator of intraocular pressure (IOP) and demonstrated that a topically applied CACNA2D1 antagonist—pregabalin (PRG)—lowered IOP in a dose-dependent manner. To further validate this novel IOP modulator as a drug target for IOP-lowering pharmaceutics, a homology model of CACNA2D1 was built and docked against the NCI library, which is one of the world’s largest and most diverse compound libraries of natural products. Acivicin and zoledronic acid were identified using this method and together with PRG were tested for their plausible IOP-lowering effect on Dutch belted rabbits. Although they have inferior potency to PRG, both of the other compounds lower IOP, which in turn validates CACNA2D1 as a valuable drug target in treating glaucoma.
Improvement of Resveratrol Permeation through Sublingual Mucosa: Chemical Permeation Enhancers versus Spray Drying Technique to Obtain Fast-Disintegrating Sublingual Mini-Tablets
Authors: Di Prima Giulia , Angellotti Giuseppe , Scarpaci Amalia Giulia , Murgia Denise , D’agostino Fabio , Campisi Giuseppina , De Caro Viviana
Published: September 2021

Resveratrol (RSV) is a natural polyphenol with several interesting broad-spectrum pharmacological properties. However, it is characterized by poor oral bioavailability, extensive first-pass effect metabolism and low stability. Indeed, RSV could benefit from the advantage of the sublingual route of administration. In this view, RSV attitudes to crossing the porcine sublingual mucosa were evaluated and promoted both by six different chemical permeation enhancers (CPEs) as well as by preparing four innovative fast-disintegrating sublingual mini-tablets by spray drying followed by direct compression. Since RSV by itself exhibits a low permeation aptitude, this could be significantly enhanced by the use of CPEs as well as by embedding RSV in a spray-dried powder to be compressed in order to prepare fast-disintegrating mini-tablets. The most promising observed CPEs (menthol, lysine and urea) were then inserted into the most promising spray-dried excipients’ compositions (RSV-B and RSV-C), thus preparing CPE-loaded mini-tablets. However, this procedure leads to unsatisfactory results which preclude the possibility of merging the two proposed approaches. Finally, the best spray-dried composition (RSV-B) was further evaluated by SEM, FTIR, XRD and disintegration as well as dissolution behavior to prove its effectiveness as a sublingual fast-disintegrating formulation.
Drug Release Profiles of Mitomycin C Encapsulated Quantum Dots–Chitosan Nanocarrier System for the Possible Treatment of Non-Muscle Invasive Bladder Cancer
Authors: Manan Fariza Aina Abd , Yusof Nor Azah , Abdullah Jaafar , Mohammad Faruq , Nurdin Armania , Yazan Latifah Saiful , Khiste Sachin K. , Al-Lohedan Hamad A.
Published: September 2021

Nanotechnology-based drug delivery systems are an emerging technology for the targeted delivery of chemotherapeutic agents in cancer therapy with low/no toxicity to the non-cancer cells. With that view, the present work reports the synthesis, characterization, and testing of Mn:ZnS quantum dots (QDs) conjugated chitosan (CS)-based nanocarrier system encapsulated with Mitomycin C (MMC) drug. This fabricated nanocarrier, MMC@CS-Mn:ZnS, has been tested thoroughly for the drug loading capacity, drug encapsulation efficiency, and release properties at a fixed wavelength (358 nm) using a UV–Vis spectrophotometer. Followed by the physicochemical characterization, the cumulative drug release profiling data of MMC@CS-Mn:ZnS nanocarrier (at pH of 6.5, 6.8, 7.2, and 7.5) were investigated to have the highest release of 56.48% at pH 6.8, followed by 50.22%, 30.88%, and 10.75% at pH 7.2, 6.5, and 7.5, respectively. Additionally, the drug release studies were fitted to five different pharmacokinetic models including pesudo-first-order, pseudo-second-order, Higuchi, Hixson–Crowell, and Korsmeyers–Peppas models. From the analysis, the cumulative MMC release suits the Higuchi model well, revealing the diffusion-controlled mechanism involving the correlation of cumulative drug release proportional to the function square root of time at equilibrium, with the correlation coefficient values (R2) of 0.9849, 0.9604, 0.9783, and 0.7989 for drug release at pH 6.5, 6.8, 7.2, and 7.5, respectively. Based on the overall results analysis, the formulated nanocarrier system of MMC synergistically envisages the efficient delivery of chemotherapeutic agents to the target cancerous sites, able to sustain it for a longer time, etc. Consequently, the developed nanocarrier system has the capacity to improve the drug loading efficacy in combating the reoccurrence and progression of cancer in non-muscle invasive bladder diseases.
Comparing the Ability of Various Resin-Based Composites and Techniques to Seal Margins in Class-II Cavities
Authors: Aljamhan Abdullah Saleh , Alhazzaa Sultan Ali , Albakr Abdulrahman Hamoud , Habib Syed Rashid , Zafar Muhammad Sohail
Published: September 2021

Background: Resin-based composites (RBCs) provide excellent esthetics but the marginal micro-leakage in the proximal cavities remains a major concern. The aim of the present study was to assess the ability of various dental RBCs and techniques utilized for sealing deep dentin margin in class-II cavities. Methods: Box-cavities (class-II) on the distal and mesial surfaces of extracted (premolar) teeth were prepared with a gingival margin placed 1mm apical to the cemento-enamel junction. Teeth with prepared class II cavities were randomly divided into four study groups according to the type of restorative materials (conventional RBC; bulk-fill RBC; conventional RBC lined with flowable RBC and conventional RBC lined with resin-modified glass-ionomer-cement (GIC) as open sandwich-technique). Each group was further subdivided into a total-etch subgroup in which a separate etching step was performed before applying the bonding agent and a self-etch subgroup in which a self-etch adhesive system was used (n = 10). For each group, cavities were restored using the respective restorative materials and techniques, subjected to 1000 thermocycles, and placed in the methylene-blue dye. The specimen teeth were sectioned for further microscopic examination for micro-leakage. Results: The least dye penetration values were reported for group 4 (GIC) followed by the group Bulk-fill using the self-etch adhesive system (group 2b). The highest dye penetration was reported for the group Bulk-fill using the total-etch adhesive system (2a), followed by the group conventional RBC using the total-etch adhesive system). The total-etch adhesive system had significantly greater micro-leakage compared to the self-etch adhesive system (1a) (p = 0.026). Conclusions: The self-etch adhesive system significantly reduced the micro-leakage compared to the total-etch system. Bulk-fill RBC when bonded with the self-etch adhesive provided good marginal sealing ability comparable to open sandwich-technique using GIC.
Drug Amorphous Solid Dispersions Based on Poly(vinyl Alcohol): Evaluating the Effect of Poly(propylene Succinate) as Plasticizer
Authors: Kapourani Afroditi , Palamidi Artemis , Kontogiannopoulos Konstantinos N. , Bikiaris Nikolaos D. , Barmpalexis Panagiotis
Published: September 2021

Although significant actions have been taken towards the utilization of poly(vinyl alcohol) (PVA) in the preparation of drug amorphous solid dispersions (ASDs) using fusion-based techniques (such as melt-quench cooling and hot-melt extrusion), several drawbacks regarding its rather high melting temperature and its thermal degradation profile make the use of the polymer extremely challenging. This is especially important when the active pharmaceutical ingredient (API) has a lower melting temperature (than PVA) or when it is thermally labile. In this vein, a previous study showed that newly synthesized polyester-based plasticizers may improve the processability and the thermal properties of PVA. However, the effects of such polyester-based plasticizers on the drug’s physicochemical and pharmaco-technical properties are yet unknown. Hence, the aim of the present study is to extend our previous findings and evaluate the use of poly(propylene succinate) (PPSu, i.e., the most promising plasticizer in regard to PVA) in the preparation of drug-loaded PVA-based ASDs. Dronedarone (DRN), a poorly water-soluble API, was selected as a model drug, and drug ASDs (using either neat PVA or PVA-PPSu) were prepared using the melt-mixing/quench cooling approach at low melting temperatures (i.e., 170 °C). DSC and pXRD analysis showed that a portion of the API remained crystalline in the ASDs prepared only with the use of neat PVA, while the samples having PPSu as a plasticizer were completely amorphous. Further evaluation with ATR-FTIR spectroscopy revealed the formation of significant intermolecular interactions between the API and the PVA-PPSu matrix, which could explain the system’s physical stability during storage. Finally, dissolution studies, conducted under nonsink conditions, revealed that the use of PVA-PPSu is able to maintain DRN’s sustained supersaturation for up to 8 h.
Characterization of Sodium Alginate Hydrogels Reinforced with Nanoparticles of Hydroxyapatite for Biomedical Applications
Authors: Sánchez-Fernández José Antonio , Presbítero-Espinosa Gerardo , Peña-Parás Laura , Pizaña Edgar Iván Rodríguez , Galván Katya Patricia Villarreal , Vopálenský Michal , Kumpová Ivana , Elizalde-Herrera Luis Ernesto
Published: September 2021

In recent years, researchers working in biomedical science and technology have investigated alternatives for enhancing the mechanical properties of biomedical materials. In this work, sodium alginate (SA) hydrogel-reinforced nanoparticles (NPs) of hydroxyapatite (HA) were prepared to enhance the mechanical properties of this polymer. Compression tests showed an increase of 354.54% in ultimate compressive strength (UCS), and 154.36% in Young’s modulus with the addition of these NPs compared with pure SA. Thermogravimetric analysis (TGA) revealed that the amount of residual water is not negligible and covered a range from 20 to 35 wt%, and the decomposition degree of the alginate depends on the hydroxyapatite content, possibly due to the displacement of sodium ions by the hydroxyapatite and not by calcium chloride. Further, there is an important effect possibly due to the existence of an interaction of hydrogen bonds between the hydroxyl of the alginate and the oxygen atoms of the hydroxyapatite, so signals appear upfield in nuclear magnetic resonance (NMR) data. An increase in the accumulation of HA particles was observed with the use of X-ray microtomography, in which the quantified volume of particles per reconstructed volume corresponded accordingly to the increase in the mechanical properties of the hydrogel.
Chitosan-Based Glycolipid Conjugated siRNA Delivery System for Improving Radiosensitivity of Laryngocarcinoma
Authors: Miao Jing , Zhang Liwen , Gao Peng , Zhao Huawei , Xie Xianji , Wang Junyan
Published: September 2021

Glucose Transporter-1 (GLUT-1) is considered to be a possible intrinsic marker of hypoxia in malignant tumors, which is an important factor in radioresistance of laryngocarcinoma. We speculated that the inhibition of GLUT-1 expression might improve the radiosensitivity of laryngocarcinoma. GLUT-1 siRNA was designed to inhibit the GLUT-1 expression, but the high molecular weight and difficult drug delivery limited the application. Herein, we constructed a glycolipid polymer chitosan oligosaccharide grafted stearic acid (CSSA) to conjugate siRNA via electrostatic interaction. The characteristics of CSSA and CSSA/siRNA were studied, as well as the radiosensitization effect of siRNA on human laryngocarcinoma epithelial (Hep-2) cells. Compared with the traditional commercial vector LipofectamineTM2000 (Lipo), CSSA exhibited lower cytotoxicity, more efficiently cellular uptake. Incubating with CSSA/siRNA, the survival rates of Hep-2 cells were significantly decreased comparing with either the group before transfection or Lipo/siRNA. CSSA is a promising carrier for efficient siRNA delivery and radiosensitization of laryngocarcinoma.