bluuebunny/crossref_metadata_2025 huggingface dataset:
Dispersion Theory of Surface Plasmon Polaritons on Bilayer Graphene Metasurfaces
Authors: Liu Yong-Qiang , Ren Zhongru , Yin Hongcheng , Sun Jinhai , Li Liangsheng
Published: May 2022

Surface plasmon polaritons (SPPs) on the graphene metasurfaces (GSPs) are crucial to develop a series of novel functional devices that can merge the well-established plasmonics and novel nanomaterials. Dispersion theory on GSPs is an important aspect, which can provide a basic understanding of propagating waves and further guidance for potential applications based on graphene metamaterials. In this paper, the dispersion theory and its modal characteristics of GSPs on double-layer graphene metasurfaces consisting of the same upper and lower graphene micro-ribbon arrays deposited on the dielectric medium are presented. In order to obtain its dispersion expressions of GSP mode on the structure, an analytical approach is provided by directly solving the Maxwell’s equations in each region and then applying periodical conductivity boundary onto the double interfaces. The obtained dispersion expressions show that GSPs split into two newly symmetric and antisymmetric modes compared to that on the single graphene metasurface. Further, the resultant dispersion relation and its propagating properties as a function of some important physical parameters, such as spacer, ribbon width, and substrate, are treated and investigated in the Terahertz band, signifying great potentials in constructing various novel graphene-based plasmonic devices, such as deeply sub-wavelength waveguides, lenses, sensors, emitters, etc.
Raman, TEM, EELS, and Magnetic Studies of a Magnetically Reduced Graphene Oxide Nanohybrid following Exposure to Daphnia magna Biomarkers
Authors: Ramos-Guivar Juan A. , Zarria-Romero Jacquelyne Y. , Canchanya-Huaman Yamerson , Guerra Jorge Andres , Checca-Huaman Noemi-Raquel , Castro-Merino Isabel-Liz , Passamani Edson C.
Published: May 2022

A ternary nanocomposite made of nanomaghemite, nanoanatase, and graphene oxide has been successfully synthesized using an inorganic coprecipitation approach, and it has been systematically investigated by X-ray diffraction, transmission electron microscopy, and different spectrocopic techniques (electron energy loss, µ-Raman, and 57Fe Mössbauer) after interaction with an effluent containing Daphnia magna individuals. Specifically, the influence of the nanocomposite over the Daphnia magna carapace, administered in two doses (0.5 mg mL−1 and 1 mg mL−1), has been characterized using µ-Raman spectroscopy before and after laser burning protocols, producing information about the physicochemical interaction with the biomarker. The thermal stability of the nanocomposite was found to be equal to 500 °C, where the nanoanatase and the nanomaghemite phases have respectively conserved their structural identities. The magnetic properties of the nanomaghemite have also been kept unchanged even after the high-temperature experiments and exposure to Daphnia magna. In particular, the size, texture, and structural and morphological properties of the ternary nanocomposite have not shown any significant physicochemical modifications after magnetic decantation recuperation. A significant result is that the graphene oxide reduction was kept even after the ecotoxicological assays. These sets of observations are based on the fact that while the UV-Vis spectrum has confirmed the graphene oxide reduction with a localized peak at 260 nm, the 300-K and 15-K 57Fe Mössbauer spectra have only revealed the presence of stoichiometric maghemite, i.e., the two well-defined static magnetic sextets often found in the bulk ferrimagnetic counterpart phase. The Mössbauer results have also agreed with the trivalent-like valence state of Fe ions, as also suggested by electron energy loss spectroscopy data. Thus, the ternary nanocomposite does not substantially affect the Daphnia magna, and it can be easily recovered using an ordinary magnetic decantation protocol due to the ferrimagnetic-like character of the nanomaghemite phase. Consequently, it shows remarkable physicochemical properties for further reuse, such as cleaning by polluted effluents, at least where Daphnia magna species are present.
Diet Modification before or during Pregnancy on Maternal and Foetal Outcomes in Rodent Models of Maternal Obesity
Authors: Rodrigo Natassia , Saad Sonia , Pollock Carol , Glastras Sarah J.
Published: May 2022

The obesity epidemic has serious implications for women of reproductive age; its rising incidence is associated not just with health implications for the mother but also has transgenerational ramifications for the offspring. Increased incidence of diabetes, cardiovascular disease, obesity, and kidney disease are seen in both the mothers and the offspring. Animal models, such as rodent studies, are fundamental to studying maternal obesity and its impact on maternal and offspring health, as human studies lack rigorous controlled experimental design. Furthermore, the short and prolific reproductive potential of rodents enables examination across multiple generations and facilitates the exploration of interventional strategies to mitigate the impact of maternal obesity, both before and during pregnancy. Given that obesity is a major public health concern, it is important to obtain a greater understanding of its pathophysiology and interaction with reproductive health, placental physiology, and foetal development. This narrative review focuses on the known effects of maternal obesity on the mother and the offspring, and the benefits of interventional strategies, including dietary intervention, before or during pregnancy on maternal and foetal outcomes. It further examines the contribution of rodent models of maternal obesity to elucidating pathophysiological pathways of disease development, as well as methods to reduce the impact of obesity on the mothers and the developing foetus. The translation of these findings into the human experience will also be discussed.
Trehalose Suppresses Lysosomal Anomalies in Supporting Cells of Oocytes and Maintains Female Fertility
Authors: Kang Woojin , Ishida Eri , Amita Mitsuyoshi , Tatsumi Kuniko , Yonezawa Hitomi , Yohtsu Miku , Katano Daiki , Onozawa Kae , Kaneko Erika , Iwasaki Wakako , Naito Natsuko , Yamada Mitsutoshi , Kawano Natsuko , Miyado Mami , Sato Ban , Saito Hidekazu , Saito Takakazu , Miyado Kenji
Published: May 2022

Supporting cells of oocytes, i.e., cumulus cells, control oocyte quality, which determines fertilization success. Therefore, the transformation of mature and immature cumulus cells (MCCs and ICCs, respectively) into dysmature cumulus cells (DCCs) with dead characteristics deteriorates oocyte quality. However, the molecular basis for this transformation remains unclear. Here, we explored the link between autophagic decline and cumulus transformation using cumulus cells from patients with infertility, female mice, and human granulosa cell-derived KGN cell lines. When human cumulus cells were labeled with LysoTracker probes, fluorescence corresponding to lysosomes was enhanced in DCCs compared to that in MCCs and ICCs. Similarly, treatment with the autophagy inhibitor chloroquine elevated LysoTracker fluorescence in both mouse cumulus cells and KGN cells, subsequently suppressing ovulation in female mice. Electron microscopy analysis revealed the proliferation of abnormal lysosomes in chloroquine-treated KGN cells. Conversely, the addition of an autophagy inducer, trehalose, suppressed chloroquine-driven problematic lysosomal anomalies and ameliorated ovulation problems. Our results suggest that autophagy maintains the healthy state of the supporting cells of human oocytes by suppressing the formation of lysosomes. Thus, our results provide insights into the therapeutic effects of trehalose on female fertility.
Vitamin D Status and Gestational Diabetes in Russian Pregnant Women in the Period between 2012 and 2021: A Nested Case–Control Study
Authors: Tkachuk Aleksandra S. , Vasukova Elena A. , Anopova Anna D. , Karonova Tatiana L. , Pustozerov Evgenii A. , Teplova Yana A. , Eriskovskaya Angelina I. , Isakov Artem O. , Vasilieva Elena Y. , Kokina Maria A. , Zazerskaya Irina Y. , Pervunina Tatiana M. , Grineva Elena N. , Popova Polina V.
Published: May 2022

Several meta-analyses found an association between low maternal serum 25-hydroxyvitamin D (25(OH)D) level and gestational diabetes mellitus (GDM). However, some of them reported significant heterogeneity. We examined the association of serum 25(OH)D concentration measured in the first and in the second halves of pregnancy with the development of GDM in Russian women surveyed in the periods of 2012–2014 and 2018–2021. We conducted a case–control study (including 318 pregnant women) nested on two previous studies. In 2012–2014, a total of 214 women (83 GDM and 131 controls) were enrolled before 15 weeks of gestation and maternal serum 25(OH)D concentrations were measured twice: at 8th–14th week of gestation and simultaneously with two-hour 75 g oral glucose tolerance test (OGTT) at 24th–32nd week of gestation. In the period of 2018–2021, 104 women (56 GDM and 48 controls) were included after OGTT and 25(OH)D concentrations were measured at 24th–32nd week of gestation. Median 25(OH)D levels were 20.0 [15.1–25.7] vs. 20.5 [14.5–27.5] ng/mL (p = 0.565) in GDM and control group in the first half of pregnancy and 25.3 [19.8–33.0] vs. 26.7 [20.8–36.8] ng/mL (p = 0.471) in the second half of pregnancy, respectively. The prevalence rates for vitamin D deficiency (25(OH)D levels < 20 ng/mL) were 49.4% and 45.8% (p = 0.608) in the first half of pregnancy and 26.2% vs. 22.1% (p = 0.516) in the second half of pregnancy in women who developed GDM and in women without GDM, respectively. The frequency of vitamin D supplements intake during pregnancy increased in 2018–2021 compared to 2012–2014 (p = 0.001). However, the third trimester 25(OH)D levels and prevalence of vitamin D deficiency (25.5 vs. 23.1, p = 0.744) did not differ in women examined in the periods of 2012–2014 and 2018–2021. To conclude, there was no association between gestational diabetes risk and maternal 25(OH)D measured both in the first and in the second halves of pregnancy. The increased prevalence of vitamin D supplements intake during pregnancy by 2018–2021 did not lead to higher levels of 25(OH)D.
Role of Diet and Nutrients in SARS-CoV-2 Infection: Incidence on Oxidative Stress, Inflammatory Status and Viral Production
Authors: Brahmi Fatiha , Vejux Anne , Ghzaiel Imen , Ksila Mohamed , Zarrouk Amira , Ghrairi Taoufik , Essadek Soukena , Mandard Stéphane , Leoni Valerio , Poli Giuseppe , Vervandier-Fasseur Dominique , Kharoubi Omar , El Midaoui Adil , Atanasov Atanas G. , Meziane Smail , Latruffe Norbert , Nasser Boubker , Bouhaouala-Zahar Balkiss , Masmoudi-Kouki Olfa , Madani Khodir , Boulekbache-Makhlouf Lila , Lizard Gérard
Published: May 2022

Coronavirus illness (COVID-19) is an infectious pathology generated by intense severe respiratory syndrome coronavirus 2 (SARS-CoV-2). This infectious disease has emerged in 2019. The COVID-19-associated pandemic has considerably affected the way of life and the economy in the world. It is consequently crucial to find solutions allowing remedying or alleviating the effects of this infectious disease. Natural products have been in perpetual application from immemorial time given that they are attested to be efficient towards several illnesses without major side effects. Various studies have shown that plant extracts or purified molecules have a promising inhibiting impact towards coronavirus. In addition, it is substantial to understand the characteristics, susceptibility and impact of diet on patients infected with COVID-19. In this review, we recapitulate the influence of extracts or pure molecules from medicinal plants on COVID-19. We approach the possibilities of plant treatment/co-treatment and feeding applied to COVID-19. We also show coronavirus susceptibility and complications associated with nutrient deficiencies and then discuss the major food groups efficient on COVID-19 pathogenesis. Then, we covered emerging technologies using plant-based SARS-CoV-2 vaccine. We conclude by giving nutrient and plants curative therapy recommendations which are of potential interest in the COVID-19 infection and could pave the way for pharmacological treatments or co-treatments of COVID-19.
Acid Catalyzed N-Alkylation of Pyrazoles with Trichloroacetimidates
Authors: Meador Rowan I. L. , Mate Nilamber A. , Chisholm John D.
Published: May 2022

N-Alkyl pyrazoles are important heterocycles in organic and medicinal chemistry, demonstrating a wide range of biological activity. A new method for the N-alkylation of pyrazoles has been developed using trichloroacetimidate electrophiles and a Brønsted acid catalyst. These reactions provide ready access to N-alkyl pyrazoles which are present in a variety of medicinally relevant lead structures. Benzylic, phenethyl and benzhydryl trichloroacetimidates provide good yields of the N-alkyl pyrazole products. Unsymmetrical pyrazoles provide a mixture of the two possible regioisomers, with the major product being controlled by sterics. This methodology provides an alternative to other alkylation methods that require strong base or high temperature.
Solid and Liquid Oxygen under Ultrahigh Magnetic Fields
Authors: Nomura Toshihiro , Matsuda Yasuhiro H. , Kobayashi Tatsuo C.
Published: May 2022

Oxygen is a unique molecule that possesses a spin quantum number S=1. In the condensed phases of oxygen, the delicate balance between the antiferromagnetic interaction and van der Waals force results in the various phases with different crystal structures. By applying ultrahigh magnetic fields, the antiferromagnetic coupling between O2 molecules breaks, and novel high-field phases can appear. We have investigated the physical properties of condensed oxygen under ultrahigh magnetic fields and have found that the stable crystal structure of solid oxygen changes around 100 T. Even in liquid oxygen, we observed a strong acoustic attenuation, which indicates the fluctuation of local molecular arrangements. These results demonstrate that magnetic fields can modulate the packing structure of oxygen through spin-lattice coupling. Our study implies the possibility of controlling oxygen-related (bio-)chemical processes by using an external magnetic field.
Redirecting Imipramine against Bluetongue Virus Infection: Insights from a Genome-wide Haploid Screening Study
Authors: John Lijo , Vernersson Caroline , Kwon Hyesoo , Elling Ulrich , Penninger Josef M. , Mirazimi Ali
Published: May 2022

Bluetongue virus (BTV), an arbovirus of ruminants, is a causative agent of numerous epidemics around the world. Due to the emergence of novel reassortant BTV strains and new outbreaks, there is an unmet need for efficacious antivirals. In this study, we used an improved haploid screening platform to identify the relevant host factors for BTV infection. Our screening tool identified and validated the host factor Niemann–Pick C1 (NPC1), a lysosomal membrane protein that is involved in lysosomal cholesterol transport, as a critical factor in BTV infection. This finding prompted us to investigate the possibility of testing imipramine, an antidepressant drug known to inhibit NPC1 function by interfering with intracellular cholesterol trafficking. In this study, we evaluated the sensitivity of BTV to imipramine using in vitro assays. Our results demonstrate that imipramine pretreatment inhibited in vitro replication and progeny release of BTV-4, BTV-8, and BTV-16. Collectively, our findings highlight the importance of NPC1 for BTV infection and recommend the reprofiling of imipramine as a potential antiviral drug against BTV.
Comparison Study of Four Extraction Methods Combined with PCR and LAMP for Feline Tritrichomonas foetus Detection in Fecal Samples
Authors: Dąbrowska Joanna , Karamon Jacek , Kochanowski Maciej , Sroka Jacek , Zdybel Jolanta , Cencek Tomasz
Published: May 2022

Feline trichomonosis occurs worldwide, with gastrointestinal symptoms such as chronic large-bowel diarrhea and abdominal pain. The inclusion of molecular methods in diagnostic and epidemiological studies has necessitated an effective method for extracting DNA from feces. We tested four extraction commercial kits: ZR Fecal DNA MiniPrep (50 preps) (Zymo Research, Irvine, CA, USA), QIAamp® DNA Stool Mini Kit (Qiagen Inc., Valencia, CA, USA), UltraClean Fecal DNA Kit (50 preps) (MO BIO, San Diego, CA, USA), and Sherlock AX/100 isolations (A&A Biotechnology, Gdynia, Poland). We assessed the sensitivity of detection of Tritrichomonas foetus in spiked fecal samples for the four kits combined with two molecular assays: PCR and LAMP. The extraction efficacy was quantified using defined aliquots of fecal samples spiked with 5 μL of suspensions containing serial dilutions of trophozoites (0.1; 1; 10; 100; 1000; 10,000), with six replicates for each concentration. In our study, we proved that the ZR Fecal DNA MiniPrep (50 preps) kit combined with LAMP and PCR had the highest efficiency among all the compared methods for the detection of feline T. foetus from fecal samples.
Flavivirus NS1 Triggers Tissue-Specific Disassembly of Intercellular Junctions Leading to Barrier Dysfunction and Vascular Leak in a GSK-3β-Dependent Manner
Authors: Puerta-Guardo Henry , Biering Scott B. , de Sousa Francielle Tramontini Gomes , Shu Jeffrey , Glasner Dustin R. , Li Jeffrey , Blanc Sophie F. , Beatty P. Robert , Harris Eva
Published: May 2022

The flavivirus nonstructural protein 1 (NS1) is secreted from infected cells and contributes to endothelial barrier dysfunction and vascular leak in a tissue-dependent manner. This phenomenon occurs in part via disruption of the endothelial glycocalyx layer (EGL) lining the endothelium. Additionally, we and others have shown that soluble DENV NS1 induces disassembly of intercellular junctions (IJCs), a group of cellular proteins critical for maintaining endothelial homeostasis and regulating vascular permeability; however, the specific mechanisms by which NS1 mediates IJC disruption remain unclear. Here, we investigated the relative contribution of five flavivirus NS1 proteins, from dengue (DENV), Zika (ZIKV), West Nile (WNV), Japanese encephalitis (JEV), and yellow fever (YFV) viruses, to the expression and localization of the intercellular junction proteins β-catenin and VE-cadherin in endothelial cells from human umbilical vein and brain tissues. We found that flavivirus NS1 induced the mislocalization of β-catenin and VE-cadherin in a tissue-dependent manner, reflecting flavivirus disease tropism. Mechanistically, we observed that NS1 treatment of cells triggered internalization of VE-cadherin, likely via clathrin-mediated endocytosis, and phosphorylation of β-catenin, part of a canonical IJC remodeling pathway during breakdown of endothelial barriers that activates glycogen synthase kinase-3β (GSK-3β). Supporting this model, we found that a chemical inhibitor of GSK-3β reduced both NS1-induced permeability of human umbilical vein and brain microvascular endothelial cell monolayers in vitro and vascular leakage in a mouse dorsal intradermal model. These findings provide insight into the molecular mechanisms regulating NS1-mediated endothelial dysfunction and identify GSK-3β as a potential therapeutic target for treatment of vascular leakage during severe dengue disease.
A Robust and Fast/Multiplex Pharmacogenetics Assay to Simultaneously Analyze 17 Clinically Relevant Genetic Polymorphisms in CYP3A4, CYP3A5, CYP1A2, CYP2C9, CYP2C19, CYP2D6, ABCB1, and VKORC1 Genes
Authors: Tron Camille , Bouvet Régis , Verdier Marie-Clémence , Lamoureux Fabien , Hennart Benjamin , Dubourg Christèle , Bellissant Eric , Galibert Marie-Dominique
Published: May 2022

In the field of pharmacogenetics, the trend is to analyze a panel of several actionable genetic polymorphisms. It may require the use of high-throughput sequencing which demands expensive reagents/instruments and specific skills to interpret results. As an alternative, the aim of this work was to validate an easy, fast, and inexpensive multiplex pharmacogenetics assay to simultaneously genotype a panel of 17 clinically actionable variants involved in drug pharmacokinetics/pharmacodynamics. We designed primers to perform a multiplex PCR assay using a single mix. Primers were labeled by two fluorescent dye markers to discriminate alleles, while the size of the PCR fragments analyzed by electrophoresis allowed identifying amplicon. Polymorphisms of interest were CYP3A4*22, CYP3A5*3, CYP1A2*1F, CYP2C9*2-*3, CYP2C19*2-*3-*17, VKORC1-1639G > A, ABCB1 rs1045642-rs1128503-rs2229109-rs2032582, and CYP2D6*3-*4-*6-*9. The assay was repeatable and a minimum quantity of 10 ng of DNA/ sample was needed to obtain accurate results. The method was applied to a validation cohort of 121 samples and genotyping results were consistent with those obtained with reference methods. The assay was fast and cost-effective with results being available within one working-day. This robust assay can easily be implemented in laboratories as an alternative to cumbersome simplex assays or expensive multiplex approaches. Together it should widespread access to pharmacogenetics in clinical routine practice.
Vascular Effects of Polyphenols from Agrimonia eupatoria L. and Role of Isoquercitrin in Its Vasorelaxant Potential in Human Arteries
Authors: Malheiros Jéssica , Simões Daniela M. , Antunes Pedro E. , Figueirinha Artur , Cotrim Maria Dulce , Fonseca Diogo A.
Published: May 2022

Agrimonia eupatoria L. has been traditionally used for the treatment of inflammatory diseases but also as a hypotensive. To our knowledge, only one study has previously suggested an improvement in vascular endothelial function in diabetic conditions, as the underlying mechanisms and responsible compounds are unknown. In this study, we aimed to assess the direct vascular effects of Agrimonia eupatoria L. in human arteries. The infusion elicited a mild increase in basal vascular tone and a significant potentiation of the adrenergic contraction of 49.18% at 0.02 mg/mL, suggesting the presence of compounds with mild vasoconstrictor activity. In contrast, the ethyl acetate fraction inhibited adrenergic contraction by 80.65% at 2 mg/mL and elicited no effect on basal vascular tone. A potent concentration-dependent vasorelaxation was observed for both the infusion and the ethyl acetate fraction (maximal relaxation above 76% and 47%, respectively). Inhibition of nitric oxide synthase and cyclooxygenase elicited significant decreases in the vasorelaxation to the infusion, as, for the ethyl acetate fraction, only the cyclooxygenase pathway appeared to be involved. Isoquercitrin elicited a vasoactivity consistent with the ethyl acetate fraction, suggesting this is a major component responsible for the vasorelaxant properties of A. eupatoria. Further research is warranted to fully evaluate its vasoprotective properties with therapeutic potential in several conditions, e.g., atherosclerosis.
Novel Effects of Statins on Cancer via Autophagy
Authors: Mengual Daniela , Medrano Luz Elena , Villamizar-Villamizar Wendy , Osorio-Llanes Estefanie , Mendoza-Torres Evelyn , Bolívar Samir
Published: May 2022

Cancer is one of the main causes of death globally. Most of the molecular mechanisms underlying cancer are marked by complex aberrations that activate the critical cell-signaling pathways that play a pivotal role in cell metabolism, tumor development, cytoskeletal reorganization, and metastasis. The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of the rapamycin (PI3K/AKT/mTOR) pathway is one of the main signaling pathways involved in carcinogenesis and metastasis. Autophagy, a cellular pathway that delivers cytoplasmic components to lysosomes for degradation, plays a dual role in cancer, as either a tumor promoter or a tumor suppressor, depending on the stage of the carcinogenesis. Statins are the group of drugs of choice to lower the level of low-density lipoprotein (LDL) cholesterol in the blood. Experimental and clinical data suggest the potential of statins in the treatment of cancer. In vitro and in vivo studies have demonstrated the molecular mechanisms through which statins inhibit the proliferation and metastasis of cancer cells in different types of cancer. The anticancer properties of statins have been shown to result in the suppression of tumor growth, the induction of apoptosis, and autophagy. This literature review shows the dual role of the autophagic process in cancer and the latest scientific evidence related to the inducing effect exerted by statins on autophagy, which could explain their anticancer potential.
Downstream Signaling of Inflammasome Pathway Affects Patients’ Outcome in the Context of Distinct Molecular Breast Cancer Subtypes
Authors: Saponaro Concetta , Fanizzi Annarita , Sonnessa Margherita , Mondelli Paolo , Vergara Daniele , Loisi Donato , Massafra Raffaella , Latorre Agnese , Zito Francesco A. , Schirosi Laura
Published: May 2022

Inflammasomes are protein complexes involved in the regulation of different biological conditions. Over the past few years, the role of NLRP3 in different tumor types has gained interest. In breast cancer (BC), NLRP3 has been associated with multiple processes including epithelia mesenchymal transition, invasion and metastization. Little is known about molecular modifications of NLRP3 up-regulation. In this study, in a cohort of BCs, the expression levels of NLRP3 and PYCARD were analyzed in combination with CyclinD1 and MYC ones and their gene alterations. We described a correlation between the NLRP3/PYCARD axis and CyclinD1 (p < 0.0001). NLRP3, PYCARD and CyclinD1’s positive expression was observed in estrogen receptor (ER) and progesterone receptor (PgR) positive cases (p < 0.0001). Furthermore, a reduction of NLRP3 and PYCARD expression has been observed in triple negative breast cancers (TNBCs) with respect to the Luminal phenotypes (p = 0.017 and p = 0.0015, respectively). The association NLRP3+/CCND1+ or PYCARD+/CCND1+ was related to more aggressive clinicopathological characteristics and a worse clinical outcome, both for progression free survival (PFS) and overall survival (OS) with respect to NLRP3+/CCND1− or PYCARD+/CCND1− patients, both in the whole cohort and also in the subset of Luminal tumors. In conclusion, our study shows that the NLRP3 inflammasome complex is down-regulated in TNBC compared to the Luminal subgroup. Moreover, the expression levels of NLRP3 and PYCARD together with the alterations of CCND1 results in Luminal subtype BC’ss poor prognosis.
A Review of the Phytochemistry and Pharmacological Properties of the Genus Arrabidaea
Authors: do Nascimento Jessyane Rodrigues , de Jesus Alves Miranda Amanda , Vieira Felipe Costa , Rodrigues Carla Daniele Pinheiro , Vasconcelos Luna Nascimento , Filho José Lima Pereira , Lopes Auxiliadora Cristina Corrêa Barata , Tangerina Marcelo Marucci Pereira , Vilegas Wagner , da Rocha Cláudia Quintino
Published: May 2022

The genus Arrabidaea, consisting of ~170 species, belongs to the family Bignoniaceae, distributed around the Neotropics and temperate zone. The center of diversity of the family is in Brazil, where 56 genera and about 340 species exist. Most species of the genus Arrabidaea are traditionally utilized as diuretics and antiseptics, as well as for treating intestinal colic, diarrhea, kidney stones, rheumatoid arthritis, wounds, and enterocolitis. The genus is chemically diverse with different substance classes; most of them are triterpenes, phenolic acids, and flavonoids, and they exhibit valuable pharmacological properties, such as antitumor, antioxidant, leishmanicidal, trypanocidal, anti-inflammatory, and healing properties. This review presents information on the chemical constituents isolated from seven Arrabidaea species, and the pharmacological activities of the extracts, fractions and pure substances isolated since 1994, obtained from electronic databases. The various constituents present in the different species of this genus demonstrate a wide pharmacological potential for the development of new therapeutic agents, however its potential has been underestimated.
Structural Elucidation of Rift Valley Fever Virus L Protein towards the Discovery of Its Potential Inhibitors
Authors: Alamri Mubarak A. , Mirza Muhammad Usman , Adeel Muhammad Muzammal , Ashfaq Usman Ali , Tahir ul Qamar Muhammad , Shahid Farah , Ahmad Sajjad , Alatawi Eid A. , Albalawi Ghadah M. , Allemailem Khaled S. , Almatroudi Ahmad
Published: May 2022

Rift valley fever virus (RVFV) is the causative agent of a viral zoonosis that causes a significant clinical burden in domestic and wild ruminants. Major outbreaks of the virus occur in livestock, and contaminated animal products or arthropod vectors can transmit the virus to humans. The viral RNA-dependent RNA polymerase (RdRp; L protein) of the RVFV is responsible for viral replication and is thus an appealing drug target because no effective and specific vaccine against this virus is available. The current study reported the structural elucidation of the RVFV-L protein by in-depth homology modeling since no crystal structure is available yet. The inhibitory binding modes of known potent L protein inhibitors were analyzed. Based on the results, further molecular docking-based virtual screening of Selleckchem Nucleoside Analogue Library (156 compounds) was performed to find potential new inhibitors against the RVFV L protein. ADME (Absorption, Distribution, Metabolism, and Excretion) and toxicity analysis of these compounds was also performed. Besides, the binding mechanism and stability of identified compounds were confirmed by a 50 ns molecular dynamic (MD) simulation followed by MM/PBSA binding free energy calculations. Homology modeling determined a stable multi-domain structure of L protein. An analysis of known L protein inhibitors, including Monensin, Mycophenolic acid, and Ribavirin, provide insights into the binding mechanism and reveals key residues of the L protein binding pocket. The screening results revealed that the top three compounds, A-317491, Khasianine, and VER155008, exhibited a high affinity at the L protein binding pocket. ADME analysis revealed good pharmacodynamics and pharmacokinetic profiles of these compounds. Furthermore, MD simulation and binding free energy analysis endorsed the binding stability of potential compounds with L protein. In a nutshell, the present study determined potential compounds that may aid in the rational design of novel inhibitors of the RVFV L protein as anti-RVFV drugs.
Evaluation of 3-Borono-l-Phenylalanine as a Water-Soluble Boron Neutron Capture Therapy Agent
Authors: Kondo Naoya , Hirano Fuko , Temma Takashi
Published: May 2022

Although 4-borono-l-phenylalanine (4-BPA) is currently the only marketed agent available for boron neutron capture therapy (BNCT), its low water solubility raises concerns. In this study, we synthesized 3-borono-l-phenylalanine (3-BPA), a positional isomer of 4-BPA, with improved water solubility. We further evaluated its physicochemical properties, tumor accumulation, and biodistribution. The water solubility of 3-BPA was 125 g/L, which is more than 100 times higher than that of 4-BPA. Due to the high water solubility, we prepared the administration solution of 3-BPA without a solubilizer sugar, which is inevitably added to 4-BPA preparation and has adverse effects. In in vitro and in vivo experiments, boron accumulation in cancers after administration was statistically equivalent in both sugar-complexed 3-BPA and 4-BPA. Furthermore, the biodistribution of 3-BPA was comparable with that of sugar-complexed 3-BPA. Since 3-BPA has high water solubility and tumor targetability equivalent to 4-BPA, 3-BPA can replace 4-BPA in future BNCT.
Assessment of Diverse Solid−State Accelerated Autoxidation Methods for Droperidol
Authors: Iyer Jayant , Saraf Isha , Ray Andrew , Brunsteiner Michael , Paudel Amrit
Published: May 2022

The present study aimed to investigate methods for accelerating autoxidation of crystalline drugs in the solid-state that can potentially predict real−time stability. Solid droperidol (DPD) was selected as the model drug. A common free−radical initiator, 2,2′−azobisisobutyronitrile (AIBN), was used to induce autoxidation in solutions. AIBN decomposes at elevated temperatures to yield carbon−centred cyano−isopropyl free radicals that can auto−oxidize neighboring drug molecules. Although the reaction of AIBN is relatively straightforward in solution, it is less so in solids. In this study, we used solid AIBN mixed with DPD powder in the presence and absence of pressurized oxygen headspace. Samples were prepared directly in the form of binary mixtures with DPD and additionally in the form of powder compact/pellet with DPD. The main challenge in carrying out the reaction was related to the preservation of AIBN at elevated temperatures due to the disintegration of the pellet containing the latter. A commercially available free−radical coated silica particle (i.e., 2,2,6,6−tetramethyl−1−piperinyloxy (TEMPO) or (SiliaCATTM TEMPO)) was tested as a potential stressor, but with limited success to induce autoxidation. The most valuable results were obtained when a physical mixture of pre−milled PVP K−60 containing free radicals and DPD was exposed to elevated oxygen−temperature conditions, which yielded significant degradation of DPD. The study highlights the practical challenges for conducting accelerated solid−state stress studies to assess the autoxidation susceptibility of drugs using traditional free−radical initiators and presents a proof of application of milled PVP with free−radical as a potential alternative.
Engineering and Evaluation of Forcespun Gelatin Nanofibers as an Isorhamnetin Glycosides Delivery System
Authors: García-Valderrama Elsy J. , Mamidi Narsimha , Antunes-Ricardo Marilena , Gutiérrez-Uribe Janet A. , Del Angel-Sanchez Karina , Elías-Zúñiga Alex
Published: May 2022

Opuntia ficus-indica (L.) Mill (OFI) is considered a natural source of bioactive phytochemicals, mainly isorhamnetin glycosides (IRGs). These compounds have demonstrated antioxidant, anti-inflammatory, and anticancer activities, among others. The development of a suitable delivery system for these compounds is needed to improve their chemical and biological stability. This study aimed to evaluate the feasibility of fabrication and characterization of IRG-loaded gelatin (GL) forcespun fibers and crosslinking with glutaraldehyde (GTA). Two different percentages (25% and 30% w/v) of GL were evaluated with 12% (w/v) OFI flour to obtain nanofibers GL/OFI1 and GL/OFI2, respectively. The morphology and physicochemical properties of the fibers were investigated. The results indicated that the diameters of the fibers were on the nanoscale. The amount of IRGs was determined using high-performance liquid chromatography (HPLC). The IRGs release and the cytocompatibility of the nanofibers were also evaluated. GL concentration significantly affected the IRG release. Among both nanofibers, the GL/OFI2 nanofiber achieved a cumulative IRGs release of 63% after 72 h. Both fibers were shown to be biocompatible with human skin/fibroblast cells. Specifically, GL/OFI1 nanofibers exhibited favorable features for their application as an extract-coupled release system. The IRGs-embedded GL nanofiber mats may become a good alternative for the delivery of phytochemicals for the health sector and biomedical applications.
Evaluation of the Cytotoxic Activity and Anti-Migratory Effect of Berberine–Phytantriol Liquid Crystalline Nanoparticle Formulation on Non-Small-Cell Lung Cancer In Vitro
Authors: Alnuqaydan Abdullah , Almutary Abdulmajeed , Azam Mohd , Manandhar Bikash , Yin Geena , Yen Lee , Madheswaran Thiagarajan , Paudel Keshav , Hansbro Philip , Chellappan Dinesh , Dua Kamal
Published: May 2022

Non-small-cell lung cancer (NSCLC) is the most common form of lung cancer, which is a leading cause of cancer-related deaths worldwide. Berberine is an isoquinoline alkaloid that is commercially available for use as a supplement for the treatment of diabetes and cardiovascular diseases. However, the therapeutic benefits of berberine are limited by its extremely low bioavailability and toxicity at higher doses. Increasing evidence suggests that the incorporation of drug compounds in liquid crystal nanoparticles provides a new platform for the safe, effective, stable, and controlled delivery of the drug molecules. This study aimed to formulate an optimized formulation of berberine–phytantriol-loaded liquid crystalline nanoparticles (BP-LCNs) and to investigate the in vitro anti-cancer activity in a human lung adenocarcinoma A549 cell line. The BP-LCN formulation possessing optimal characteristics that was used in this study had a favorable particle size and entrapment efficiency rate (75.31%) and a superior drug release profile. The potential mechanism of action of the formulation was determined by measuring the mRNA levels of the tumor-associated genes PTEN, P53, and KRT18 and the protein expression levels with a human oncology protein array. BP-LCNs decreased the proliferation, migration, and colony-forming activity of A549 cells in a dose-dependent manner by upregulating the mRNA expression of PTEN and P53 and downregulating the mRNA expression of KRT18. Similarly, BP-LCNs also decreased the expression of proteins related to cancer cell proliferation and migration. This study highlights the utility of phytantriol-based LCNs in incorporating drug molecules with low GI absorption and bioavailability to increase their pharmacological effectiveness and potency in NSCLC.
New Amino Naphthoquinone Derivatives as Anti-Trypanosoma cruzi Agents Targeting Trypanothione Reductase
Authors: Espinosa-Bustos Christian , Ortiz Pérez Mariana , Gonzalez-Gonzalez Alonzo , Zarate Ana María , Rivera Gildardo , Belmont-Díaz Javier A. , Saavedra Emma , Cuellar Mauricio A. , Vázquez Karina , Salas Cristian O.
Published: May 2022

To develop novel chemotherapeutic alternatives for the treatment of Chagas disease, in this study, a set of new amino naphthoquinone derivatives were synthesised and evaluated in vitro on the epimastigote and trypomastigote forms of Trypanosoma cruzi strains (NINOA and INC-5) and on J774 murine macrophages. The design of the new naphthoquinone derivatives considered the incorporation of nitrogenous fragments with different substitution patterns present in compounds with activity on T. cruzi, and, thus, 19 compounds were synthesised in a simple manner. Compounds 2e and 7j showed the lowest IC50 values (0.43 µM against both strains for 2e and 0.19 µM and 0.92 µM for 7j). Likewise, 7j was more potent than the reference drug, benznidazole, and was more selective on epimastigotes. To postulate a possible mechanism of action, molecular docking studies were performed on T. cruzi trypanothione reductase (TcTR), specifically at a site in the dimer interface, which is a binding site for this type of naphthoquinone. Interestingly, 7j was one of the compounds that showed the best interaction profile on the enzyme; therefore, 7j was evaluated on TR, which behaved as a non-competitive inhibitor. Finally, 7j was predicted to have a good pharmacokinetic profile for oral administration. Thus, the naphthoquinone nucleus should be considered in the search for new trypanocidal agents based on our hit 7j.
Topical Film-Forming Chlorhexidine Gluconate Sprays for Antiseptic Application
Authors: Chamsai Benchawan , Soodvilai Sirima , Opanasopit Praneet , Samprasit Wipada
Published: May 2022

Topical film-forming sprays of chlorhexidine gluconate (CHG-FFS) were developed for antiseptic application. Various polymers and solvents were studied for their potential as film-forming polymers and solvent systems, respectively. To produce CHG-FFS, the optimal polymer and solvent were selected, and their physicochemical properties were evaluated. The in vivo evaluation of CHG-FFS was investigated for the satisfaction of the dosage forms, time required for the film formation, film appearance, and adhesion on the skin. Antibacterial activity was also studied in vitro and in vivo. The optimized formulation was assessed for the in vitro cell line evaluations of the cytotoxicity and wound healing. The results demonstrate that Eudragit® S100, Eudragit® L100, and polyvinyl alcohol (PVA) have the ability to be used as film-forming polymers in an ethanolic solution. A clear and flexible film was obtained from transparent homogenous solutions of CHG-FFS after actuation. They generated the fast thin film formation on the skin with the satisfaction of the dosage forms. Furthermore, the formulations inhibited the growth of Staphylococcus aureus in vitro and provided antiseptic activity in vivo. However, PVA was found to be an optimal film-forming polymer for promoting CHG adhesion on the skin. The CHG-FFS obtained from the PVA also provided a CHG film, which was non-toxic to human skin cells and did not interfere with the wound healing process. Therefore, the developed CHG-FFS could be a promising candidate for topical antiseptic application.
An Ultra-Broadband Polarization Beam Splitter Based on the Digital Meta-Structure at the 2 µm Waveband
Authors: Xu Jiefeng , Liu Yingjie , Guo Xiaoyuan , Du Jiangbing , Xu Ke
Published: May 2022

The 2 μm waveband is considered to have great potential in optical communications. Driven by the demands on high-performance functional devices in this spectral band, various integrated photonic components have been demonstrated. In this work, an analog and digital topology optimization method is proposed to design an ultra-broadband polarization beam splitter at the 2 μm waveband. Within an optical bandwidth of 213 nm, the excess losses of TE and TM modes are <0.53 dB and 0.3 dB, respectively. The corresponding polarization extinction ratios are >16.5 dB and 18.1 dB. The device has a very compact footprint of only 2.52 µm × 5.4 µm. According to our best knowledge, this is a benchmark demonstration of an ultra-broadband and ultra-compact polarization beam splitter enabled by the proposed optimization method.
Numerical Simulation of Heat Load for Multilayer Laue Lens under Exposure to XFEL Pulse Trains
Authors: Rek Zlatko , Chapman Henry N. , Šarler Božidar , Bajt Saša
Published: May 2022

Multilayer Laue lenses (MLLs) made from WC and SiC were previously used to focus megahertz X-ray pulse trains of the European XFEL free-electron laser, but suffered damage with trains of 30 pulses or longer at an incident fluence of about 0.13 J/cm2 per pulse. Here, we present numerical simulations of the heating of MLLs of various designs, geometry and material properties, that are exposed to such pulse trains. We find that it should be possible to focus the full beam of about 10 J/cm2 fluence of XFEL using materials of a low atomic number. To achieve high diffraction efficiency, lenses made from such materials should be considerably thicker than those used in the experiments. In addition to the lower absorption, this leads to the deposition of energy over a larger volume of the multilayer structure and hence to a lower dose, a lower temperature increase, and an improved dissipation of heat.
Enhancement of the Plant Grafting Technique with Dielectric Barrier Discharge Cold Atmospheric Plasma and Plasma-Treated Solution
Authors: Konchekov Evgeny M. , Kolik Leonid V. , Danilejko Yury K. , Belov Sergey V. , Artem’ev Konstantin V. , Astashev Maxim E. , Pavlik Tatiana I. , Lukanin Vladimir I. , Kutyrev Alexey I. , Smirnov Igor G. , Gudkov Sergey V.
Published: May 2022

A garden plant grafting technique enhanced by cold plasma (CAP) and plasma-treated solutions (PTS) is described for the first time. It has been shown that CAP created by a dielectric barrier discharge (DBD) and PTS makes it possible to increase the growth of Pyrus communis L. by 35–44%, and the diameter of the root collar by 10–28%. In this case, the electrical resistivity of the graft decreased by 20–48%, which indicated the formation of a more developed vascular system at the rootstock–scion interface. The characteristics of DBD CAP and PTS are described in detail.
Bioremoval of Yttrium (III), Cerium (III), Europium (III), and Terbium (III) from Single and Quaternary Aqueous Solutions Using the Extremophile Galdieria sulphuraria (Galdieriaceae, Rhodophyta)
Authors: Iovinella Manuela , Lombardo Francesco , Ciniglia Claudia , Palmieri Maria , di Cicco Maria Rosa , Trifuoggi Marco , Race Marco , Manfredi Carla , Lubritto Carmine , Fabbricino Massimiliano , De Stefano Mario , Davis Seth J.
Published: May 2022

The lanthanides are among the rare earth elements (REEs), which are indispensable constituents of modern technologies and are often challenging to acquire from natural resources. The demand for REEs is so high that there is a clear need to develop efficient and environmentally-friendly recycling methods. In the present study, living cells of the extremophile Galdieria sulphuraria were used to remove four REEs, Yttrium, Cerium, Europium, and Terbium, from single- and quaternary-metal aqueous solutions. Two different strains, SAG 107.79 and ACUF 427, were exposed to solutions buffered at pH 2.5, 3.5, 4.5, and 5.5. Our data demonstrated that the removal performances were strain and pH dependent for all metal ions. At lower pH, ACUF 427 outperformed SAG 107.79 considerably. By increasing the pH of the solutions, there was a significant surge in the aqueous removal performance of both strains. The same trend was highlighted using quaternary-metal solutions, even if the quantities of metal removed were significantly lower. The present study provided the first insight into the comparative removal capacity of the Galdieria sulphuraria strains. The choice of the appropriate operational conditions such as the pH of the metal solutions is an essential step in developing efficient, rapid, and straightforward biological methods for recycling REEs.
Electrospun Smart Oxygen Indicating Tag for Modified Atmosphere Packaging Applications: Fabrication, Characterization and Storage Stability
Authors: Panwar Shivam , Panjagari Narender , Singh Ashish , Deshwal Gaurav , Badola Richa , Minz Prashant , Goksen Gulden , Rusu Alexandru , Trif Monica
Published: May 2022

Pack integrity is essential for the success of modified atmosphere packaging of food products. Colorimetric oxygen leak indicators or tags are simple and smart tools that can depict the presence or absence of oxygen within a package. However, not many bio-based electrospun materials were explored for this purpose. Ultraviolet light-activated kappa-carrageenan-based smart oxygen indicating tag was developed using the electrospinning technique in this study and its stability during storage was determined. Kappa-carrageenan was used with redox dye, sacrificial electron donor, photocatalyst, and solvent for preparing oxygen indicating electrospun tag. Parameters of electrospinning namely flow rate of the polymer solution, the distance between spinneret and collector, and voltage applied were optimized using Taguchi L9 orthogonal design. Rheological and microstructural studies revealed that the electrospinning solution was pseudoplastic and the mat fibers were compact and non-woven with an average fiber size of 1–2 microns. Oxygen sensitivity at different oxygen concentrations revealed that the tag was sensitive enough to detect as low as 0.4% oxygen. The developed tag was stable for at least 60 days when stored in dark at 25 °C and 65% RH. The developed mat could be highly useful in modified atmosphere packaging applications to check seal integrity in oxygen devoid packages.