bluuebunny/crossref_metadata_2025 huggingface dataset:
Plant RNA Binding Proteins as Critical Modulators in Drought, High Salinity, Heat, and Cold Stress Responses: An Updated Overview
Authors: Muthusamy Muthusamy , Kim Jong-Hee , Kim Jin A , Lee Soo-In
Published: June 2021

Plant abiotic stress responses are tightly regulated by different players at multiple levels. At transcriptional or post-transcriptional levels, several RNA binding proteins (RBPs) regulate stress response genes through RNA metabolism. They are increasingly recognized as critical modulators of a myriad of biological processes, including stress responses. Plant RBPs are heterogeneous with one or more conservative RNA motifs that constitute canonical/novel RNA binding domains (RBDs), which can bind to target RNAs to determine their regulation as per the plant requirements at given environmental conditions. Given its biological significance and possible consideration as a potential tool in genetic manipulation programs to improve key agronomic traits amidst frequent episodes of climate anomalies, studies concerning the identification and functional characterization of RBP candidate genes are steadily mounting. This paper presents a comprehensive overview of canonical and novel RBPs and their functions in major abiotic stresses including drought, heat, salt, and cold stress conditions. To some extent, we also briefly describe the basic motif structure of RBPs that would be useful in forthcoming studies. Additionally, we also collected RBP genes that were modulated by stress, but that lacked functional characterization, providing an impetus to conduct further research.
The Role of Mitochondrial Mutations and Chronic Inflammation in Diabetes
Authors: Dabravolski Siarhei A. , Orekhova Varvara A. , Baig Mirza S. , Bezsonov Evgeny E. , Starodubova Antonina V. , Popkova Tatyana V. , Orekhov Alexander N.
Published: June 2021

Diabetes mellitus and related disorders significantly contribute to morbidity and mortality worldwide. Despite the advances in the current therapeutic methods, further development of anti-diabetic therapies is necessary. Mitochondrial dysfunction is known to be implicated in diabetes development. Moreover, specific types of mitochondrial diabetes have been discovered, such as MIDD (maternally inherited diabetes and deafness) and DAD (diabetes and Deafness). Hereditary mitochondrial disorders are caused by certain mutations in the mitochondrial DNA (mtDNA), which encodes for a substantial part of mitochondrial proteins and mitochondrial tRNA necessary for mitochondrial protein synthesis. Study of mtDNA mutations is challenging because the pathogenic phenotype associated with such mutations depends on the level of its heteroplasmy (proportion of mtDNA copies carrying the mutation) and can be tissue-specific. Nevertheless, modern sequencing methods have allowed describing and characterizing a number of mtDNA mutations associated with human disorders, and the list is constantly growing. In this review, we provide a list of mtDNA mutations associated with diabetes and related disorders and discuss the mechanisms of their involvement in the pathology development.
Diatom Biosilica Doped with Palladium(II) Chloride Nanoparticles as New Efficient Photocatalysts for Methyl Orange Degradation
Authors: Sprynskyy Myroslav , Szczyglewska Paulina , Wojtczak Izabela , Nowak Izabela , Witkowski Andrzej , Buszewski Bogusław , Feliczak-Guzik Agnieszka
Published: June 2021

A new catalyst based on biosilica doped with palladium(II) chloride nanoparticles was prepared and tested for efficient degradation of methyl orange (MO) in water solution under UV light excitation. The obtained photocatalyst was characterized by X-ray diffraction, TEM and N2 adsorption/desorption isotherms. The photocatalytic degradation process was studied as a function of pH of the solution, temperature, UV irradiation time, and MO initial concentration. The possibilities of recycling and durability of the prepared photocatalysts were also tested. Products of photocatalytic degradation were identified by liquid chromatography–mass spectrometry analyses. The photocatalyst exhibited excellent photodegradation activity toward MO degradation under UV light irradiation. Rapid photocatalytic degradation was found to take place within one minute with an efficiency of 85% reaching over 98% after 75 min. The proposed mechanism of photodegradation is based on the assumption that both HO• and O2•− radicals, as strongly oxidizing species that can participate in the dye degradation reaction, are generated by the attacks of photons emitted from diatom biosilica (photonic scattering effect) under the influence of UV light excitation. The degradation efficiency significantly increases as the intensity of photons emitted from biosilica is enhanced by palladium(II) chloride nanoparticles immobilized on biosilica (synergetic photonic scattering effect).
Treatment with the Bacterial Toxin CNF1 Selectively Rescues Cognitive and Brain Mitochondrial Deficits in a Female Mouse Model of Rett Syndrome Carrying a MeCP2-Null Mutation
Authors: Urbinati Chiara , Cosentino Livia , Germinario Elena Angela Pia , Valenti Daniela , Vigli Daniele , Ricceri Laura , Laviola Giovanni , Fiorentini Carla , Vacca Rosa Anna , Fabbri Alessia , De Filippis Bianca
Published: June 2021

Rett syndrome (RTT) is a rare neurological disorder caused by mutations in the X-linked MECP2 gene and a major cause of intellectual disability in females. No cure exists for RTT. We previously reported that the behavioural phenotype and brain mitochondria dysfunction are widely rescued by a single intracerebroventricular injection of the bacterial toxin CNF1 in a RTT mouse model carrying a truncating mutation of the MeCP2 gene (MeCP2-308 mice). Given the heterogeneity of MECP2 mutations in RTT patients, we tested the CNF1 therapeutic efficacy in a mouse model carrying a null mutation (MeCP2-Bird mice). CNF1 selectively rescued cognitive defects, without improving other RTT-related behavioural alterations, and restored brain mitochondrial respiratory chain complex activity in MeCP2-Bird mice. To shed light on the molecular mechanisms underlying the differential CNF1 effects on the behavioural phenotype, we compared treatment effects on relevant signalling cascades in the brain of the two RTT models. CNF1 provided a significant boost of the mTOR activation in MeCP2-308 hippocampus, which was not observed in the MeCP2-Bird model, possibly explaining the differential effects of CNF1. These results demonstrate that CNF1 efficacy depends on the mutation beared by MeCP2-mutated mice, stressing the need of testing potential therapeutic approaches across RTT models.
Elevating Ascorbate in Arabidopsis Stimulates the Production of Abscisic Acid, Phaseic Acid, and to a Lesser Extent Auxin (IAA) and Jasmonates, Resulting in Increased Expression of DHAR1 and Multiple Transcription Factors Associated with Abiotic Stress Tolerance
Authors: Bulley Sean M. , Cooney Janine M. , Laing William
Published: June 2021

Gene expression and phytohormone contents were measured in response to elevating ascorbate in the absence of other confounding stimuli such as high light and abiotic stresses. Young Arabidopsis plants were treated with 25 mM solutions of l-galactose pathway intermediates l-galactose (l-gal) or l-galactono-1,4-lactone (l-galL), as well as L-ascorbic acid (AsA), with 25 mM glucose used as control. Feeding increased rosette AsA 2- to 4-fold but there was little change in AsA biosynthetic gene transcripts. Of the ascorbate recycling genes, only Dehydroascorbate reductase 1 expression was increased. Some known regulatory genes displayed increased expression and included ANAC019, ANAC072, ATHB12, ZAT10 and ZAT12. Investigation of the ANAC019/ANAC072/ATHB12 gene regulatory network revealed a high proportion of ABA regulated genes. Measurement of a subset of jasmonate, ABA, auxin (IAA) and salicylic acid compounds revealed consistent increases in ABA (up to 4.2-fold) and phaseic acid (PA; up to 5-fold), and less consistently certain jasmonates, IAA, but no change in salicylic acid levels. Increased ABA is likely due to increased transcripts for the ABA biosynthetic gene NCED3. There were also smaller increases in transcripts for transcription factors ATHB7, ERD1, and ABF3. These results provide insights into how increasing AsA content can mediate increased abiotic stress tolerance.
Overexpression of miR-125b in Osteoblasts Improves Age-Related Changes in Bone Mass and Quality through Suppression of Osteoclast Formation
Authors: Ito Shota , Minamizaki Tomoko , Kohno Shohei , Sotomaru Yusuke , Kitaura Yoshiaki , Ohba Shinsuke , Sugiyama Toshie , Aubin Jane E. , Tanimoto Kotaro , Yoshiko Yuji
Published: June 2021

We recently reported an unexpected role of osteoblast-derived matrix vesicles in the delivery of microRNAs to bone matrix. Of such microRNAs, we found that miR-125b inhibited osteoclast formation by targeting Prdm1 encoding a transcriptional repressor of anti-osteoclastogenesis factors. Transgenic (Tg) mice overexpressing miR-125b in osteoblasts by using human osteocalcin promoter grow normally but exhibit high trabecular bone mass. We have now further investigated the effects of osteoblast-mediated miR-125b overexpression on skeletal morphogenesis and remodeling during development, aging and in a situation of skeletal repair, i.e., fracture healing. There were no significant differences in the growth plate, primary spongiosa or lateral (periosteal) bone formation and mineral apposition rate between Tg and wild-type (WT) mice during early bone development. However, osteoclast number and medial (endosteal) bone resorption were less in Tg compared to WT mice, concomitant with increased trabecular bone mass. Tg mice were less susceptible to age-dependent changes in bone mass, phosphate/amide I ratio and mechanical strength. In a femoral fracture model, callus formation progressed similarly in Tg and WT mice, but callus resorption was delayed, reflecting the decreased osteoclast numbers associated with the Tg callus. These results indicate that the decreased osteoclastogenesis mediated by miR-125b overexpression in osteoblasts leads to increased bone mass and strength, while preserving bone formation and quality. They also suggest that, in spite of the fact that single miRNAs may target multiple genes, the miR-125b axis may be an attractive therapeutic target for bone loss in various age groups.
Eleutherine bulbosa (Mill.) Urb. Bulb: Review of the Pharmacological Activities and Its Prospects for Application
Authors: Kamarudin Ammar Akram , Sayuti Nor Hafiza , Saad Norazalina , Razak Nor Asma Ab. , Esa Norhaizan Mohd.
Published: June 2021

Natural product is an excellent candidate for alternative medicine for disease management. The bulb of E. bulbosa is one of the notable Iridaceae family with a variety therapeutic potential that is widely cultivated in Southeast Asia. The bulb has been used traditionally among the Dayak community as a folk medicine to treat several diseases like diabetes, breast cancer, nasal congestion, and fertility problems. The bulb is exceptionally rich in phytochemicals like phenolic and flavonoid derivatives, naphthalene, anthraquinone, and naphthoquinone. The electronic database was searched using various keywords, i.e., E. bulbosa, E. americana, E. palmifolia, E. platifolia, and others due to the interchangeably used scientific names of different countries. Scientific investigations revealed that various pharmacological activities were recorded from the bulb of E. bulbosa including anti-cancer, anti-diabetic, anti-bacterial, anti-fungi, anti-viral, anti-inflammatory, dermatological problems, anti-oxidant, and anti-fertility. The potential application of the bulb in the food industry and in animal nutrition was also discussed to demonstrate its great versatility. This is a compact study and is the first study to review the extensive pharmacological activities of the E. bulbosa bulb and its potential applications. The development of innovative food and pharma products from the bulb of E. bulbosa is of great interest.
Metabolic Dynamics in Short- and Long-Term Microgravity in Human Primary Macrophages
Authors: Thiel Cora S. , Vahlensieck Christian , Bradley Timothy , Tauber Svantje , Lehmann Martin , Ullrich Oliver
Published: June 2021

Microgravity acts on cellular systems on several levels. Cells of the immune system especially react rapidly to changes in gravity. In this study, we performed a correlative metabolomics analysis on short-term and long-term microgravity effects on primary human macrophages. We could detect an increased amino acid concentration after five minutes of altered gravity, that was inverted after 11 days of microgravity. The amino acids that reacted the most to changes in gravity were tightly clustered. The observed effects indicated protein degradation processes in microgravity. Further, glucogenic and ketogenic amino acids were further degraded to Glucose and Ketoleucine. The latter is robustly accumulated in short-term and long-term microgravity but not in hypergravity. We detected highly dynamic and also robust adaptative metabolic changes in altered gravity. Metabolomic studies could contribute significantly to the understanding of gravity-induced integrative effects in human cells.
Evaluation of Insulin-Like Activity of Novel Zinc Metal–Organics toward Adipogenesis Signaling
Authors: Gabriel Catherine , Tsave Olga , Yavropoulou Maria P. , Architektonidis Theodore , Raptopoulou Catherine P. , Psycharis Vassilis , Salifoglou Athanasios
Published: June 2021

Diabetes mellitus is a debilitating disease, plaguing a significant number of people around the globe. Attempts to develop new drugs on well-defined atoxic metalloforms, which are capable of influencing fundamental cellular processes overcoming insulin resistance, has triggered an upsurge in molecular research linked to zinc metallodrugs. To that end, meticulous efforts were launched toward the design and synthesis of materials with insulin mimetic potential. Henceforth, trigonelline and N-(2-hydroxyethyl)-iminodiacetic acid (HeidaH2) were selected as organic substrates seeking binding to zinc (Zn(II)), with new crystalline compounds characterized by elemental analysis, FT-IR, X-rays, thermogravimetry (TGA), luminescence, NMR, and ESI-MS spectrometry. Physicochemical characterization was followed by in vitro biochemical experiments, in which three out of the five zinc compounds emerged as atoxic, exhibiting bio-activity profiles reflecting enhanced adipogenic potential. Concurrently, well-defined qualitative–quantitative experiments provided links to genetic loci responsible for the observed effects, thereby unraveling their key involvement in signaling pathways in adipocyte tissue and insulin mimetic behavior. The collective results (a) signify the quintessential role of molecular studies in unearthing unknown facets of pathophysiological events in diabetes mellitus II, (b) reflect the close associations of properly configured molecular zincoforms to well-defined biological profiles, and (c) set the stage for further physicochemical-based development of efficient zinc antidiabetic metallodrugs.
Hybrid Methacrylated Gelatin and Hyaluronic Acid Hydrogel Scaffolds. Preparation and Systematic Characterization for Prospective Tissue Engineering Applications
Authors: Velasco-Rodriguez B. , Diaz-Vidal T. , Rosales-Rivera L. C. , García-González C. A. , Alvarez-Lorenzo C. , Al-Modlej A. , Domínguez-Arca V. , Prieto G. , Barbosa S. , Soltero Martínez J. F. A. , Taboada P.
Published: June 2021

Hyaluronic acid (HA) and gelatin (Gel) are major components of the extracellular matrix of different tissues, and thus are largely appealing for the construction of hybrid hydrogels to combine the favorable characteristics of each biopolymer, such as the gel adhesiveness of Gel and the better mechanical strength of HA, respectively. However, despite previous studies conducted so far, the relationship between composition and scaffold structure and physico-chemical properties has not been completely and systematically established. In this work, pure and hybrid hydrogels of methacroyl-modified HA (HAMA) and Gel (GelMA) were prepared by UV photopolymerization and an extensive characterization was done to elucidate such correlations. Methacrylation degrees of ca. 40% and 11% for GelMA and HAMA, respectively, were obtained, which allows to improve the hydrogels’ mechanical properties. Hybrid GelMA/HAMA hydrogels were stiffer, with elastic modulus up to ca. 30 kPa, and porous (up to 91%) compared with pure GelMA ones at similar GelMA concentrations thanks to the interaction between HAMA and GelMA chains in the polymeric matrix. The progressive presence of HAMA gave rise to scaffolds with more disorganized, stiffer, and less porous structures owing to the net increase of mass in the hydrogel compositions. HAMA also made hybrid hydrogels more swellable and resistant to collagenase biodegradation. Hence, the suitable choice of polymeric composition allows to regulate the hydrogels´ physical properties to look for the most optimal characteristics required for the intended tissue engineering application.
The C-Terminal Domain of LRRK2 with the G2019S Substitution Increases Mutant A53T α-Synuclein Toxicity in Dopaminergic Neurons In Vivo
Authors: Cresto Noémie , Gardier Camille , Gaillard Marie-Claude , Gubinelli Francesco , Roost Pauline , Molina Daniela , Josephine Charlène , Dufour Noëlle , Auregan Gwenaëlle , Guillermier Martine , Bernier Suéva , Jan Caroline , Gipchtein Pauline , Hantraye Philippe , Chartier-Harlin Marie-Christine , Bonvento Gilles , Van Camp Nadja , Taymans Jean-Marc , Cambon Karine , Liot Géraldine , Bemelmans Alexis-Pierre , Brouillet Emmanuel
Published: June 2021

Alpha-synuclein (α-syn) and leucine-rich repeat kinase 2 (LRRK2) play crucial roles in Parkinson’s disease (PD). They may functionally interact to induce the degeneration of dopaminergic (DA) neurons via mechanisms that are not yet fully understood. We previously showed that the C-terminal portion of LRRK2 (ΔLRRK2) with the G2019S mutation (ΔLRRK2G2019S) was sufficient to induce neurodegeneration of DA neurons in vivo, suggesting that mutated LRRK2 induces neurotoxicity through mechanisms that are (i) independent of the N-terminal domains and (ii) “cell-autonomous”. Here, we explored whether ΔLRRK2G2019S could modify α-syn toxicity through these two mechanisms. We used a co-transduction approach in rats with AAV vectors encoding ΔLRRK2G2019S or its “dead” kinase form, ΔLRRK2DK, and human α-syn with the A53T mutation (AAV-α-synA53T). Behavioral and histological evaluations were performed at 6- and 15-weeks post-injection. Results showed that neither form of ΔLRRK2 alone induced the degeneration of neurons at these post-injection time points. By contrast, injection of AAV-α-synA53T alone resulted in motor signs and degeneration of DA neurons. Co-injection of AAV-α-synA53T with AAV-ΔLRRK2G2019S induced DA neuron degeneration that was significantly higher than that induced by AAV-α-synA53T alone or with AAV-ΔLRRK2DK. Thus, mutated α-syn neurotoxicity can be enhanced by the C-terminal domain of LRRK2G2019 alone, through cell-autonomous mechanisms.
Necrotizing Enterocolitis: Overview on In Vitro Models
Authors: De Fazio Luigia , Beghetti Isadora , Bertuccio Salvatore Nicola , Marsico Concetta , Martini Silvia , Masetti Riccardo , Pession Andrea , Corvaglia Luigi , Aceti Arianna
Published: June 2021

Necrotizing enterocolitis (NEC) is a gut inflammatory disorder which constitutes one of the leading causes of morbidity and mortality for preterm infants. The pathophysiology of NEC is yet to be fully understood; several observational studies have led to the identification of multiple factors involved in the pathophysiology of the disease, including gut immaturity and dysbiosis of the intestinal microbiome. Given the complex interactions between microbiota, enterocytes, and immune cells, and the limited access to fetal human tissues for experimental studies, animal models have long been essential to describe NEC mechanisms. However, at present there is no animal model perfectly mimicking human NEC; furthermore, the disease mechanisms appear too complex to be studied in single-cell cultures. Thus, researchers have developed new approaches in which intestinal epithelial cells are exposed to a combination of environmental and microbial factors which can potentially trigger NEC. In addition, organoids have gained increasing attention as promising models for studying NEC development. Currently, several in vitro models have been proposed and have contributed to describe the disease in deeper detail. In this paper, we will provide an updated review of available in vitro models of NEC and an overview of current knowledge regarding its molecular underpinnings.
Metallacarborane Derivatives Effective against Pseudomonas aeruginosa and Yersinia enterocolitica
Authors: Swietnicki Wieslaw , Goldeman Waldemar , Psurski Mateusz , Nasulewicz-Goldeman Anna , Boguszewska-Czubara Anna , Drab Marek , Sycz Jordan , Goszczyński Tomasz M.
Published: June 2021

Pseudomonas aeruginosa is an opportunistic human pathogen that has become a nosocomial health problem worldwide. The pathogen has multiple drug removal and virulence secretion systems, is resistant to many antibiotics, and there is no commercial vaccine against it. Yersinia pestis is a zoonotic pathogen that is on the Select Agents list. The bacterium is the deadliest pathogen known to humans and antibiotic-resistant strains are appearing naturally. There is no commercial vaccine against the pathogen, either. In the current work, novel compounds based on metallacarborane cage were studied on strains of Pseudomonas aeruginosa and a Yersinia pestis substitute, Yersinia enterocolitica. The representative compounds had IC50 values below 10 µM against Y. enterocolitica and values of 20–50 μM against P. aeruginosa. Artificial generation of compound-resistant Y. enterocolitica suggested a common mechanism for drug resistance, the first reported in the literature, and suggested N-linked metallacarboranes as impervious to cellular mechanisms of resistance generation. SEM analysis of the compound-resistant strains showed that the compounds had a predominantly bacteriostatic effect and blocked bacterial cell division in Y. enterocolitica. The compounds could be a starting point towards novel anti-Yersinia drugs and the strategy presented here proposes a mechanism to bypass any future drug resistance in bacteria.
Dexamethasone for Severe COVID-19: How Does It Work at Cellular and Molecular Levels?
Authors: Kino Tomoshige , Burd Irina , Segars James H.
Published: June 2021

The coronavirus disease 2019 (COVID-19) caused by infection of the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) significantly impacted human society. Recently, the synthetic pure glucocorticoid dexamethasone was identified as an effective compound for treatment of severe COVID-19. However, glucocorticoids are generally harmful for infectious diseases, such as bacterial sepsis and severe influenza pneumonia, which can develop respiratory failure and systemic inflammation similar to COVID-19. This apparent inconsistency suggests the presence of pathologic mechanism(s) unique to COVID-19 that renders this steroid effective. We review plausible mechanisms and advance the hypothesis that SARS-CoV-2 infection is accompanied by infected cell-specific glucocorticoid insensitivity as reported for some other viruses. This alteration in local glucocorticoid actions interferes with undesired glucocorticoid to facilitate viral replication but does not affect desired anti-inflammatory properties in non-infected organs/tissues. We postulate that the virus coincidentally causes glucocorticoid insensitivity in the process of modulating host cell activities for promoting its replication in infected cells. We explore this tenet focusing on SARS-CoV-2-encoding proteins and potential molecular mechanisms supporting this hypothetical glucocorticoid insensitivity unique to COVID-19 but not characteristic of other life-threatening viral diseases, probably due to a difference in specific virally-encoded molecules and host cell activities modulated by them.
Comparative Anti-Inflammatory Effects of Salix Cortex Extracts and Acetylsalicylic Acid in SARS-CoV-2 Peptide and LPS-Activated Human In Vitro Systems
Authors: Le Nguyen , Herz Corinna , Gomes João , Förster Nadja , Antoniadou Kyriaki , Mittermeier-Kleßinger Verena , Mewis Inga , Dawid Corinna , Ulrichs Christian , Lamy Evelyn
Published: June 2021

The usefulness of anti-inflammatory drugs as an adjunct therapy to improve outcomes in COVID-19 patients is intensely discussed. Willow bark (Salix cortex) has been used for centuries to relieve pain, inflammation, and fever. Its main active ingredient, salicin, is metabolized in the human body into salicylic acid, the precursor of the commonly used pain drug acetylsalicylic acid (ASA). Here, we report on the in vitro anti-inflammatory efficacy of two methanolic Salix extracts, standardized to phenolic compounds, in comparison to ASA in the context of a SARS-CoV-2 peptide challenge. Using SARS-CoV-2 peptide/IL-1β- or LPS-activated human PBMCs and an inflammatory intestinal Caco-2/HT29-MTX co-culture, Salix extracts, and ASA concentration-dependently suppressed prostaglandin E2 (PGE2), a principal mediator of inflammation. The inhibition of COX-2 enzyme activity, but not protein expression was observed for ASA and one Salix extract. In activated PBMCs, the suppression of relevant cytokines (i.e., IL-6, IL-1β, and IL-10) was seen for both Salix extracts. The anti-inflammatory capacity of Salix extracts was still retained after transepithelial passage and liver cell metabolism in an advanced co-culture model system consisting of intestinal Caco-2/HT29-MTX cells and differentiated hepatocyte-like HepaRG cells. Taken together, our in vitro data suggest that Salix extracts might present an additional anti-inflammatory treatment option in the context of SARS-CoV-2 peptides challenge; however, more confirmatory data are needed.
Polyphenols as Food Supplement Improved Food Consumption and Longevity of Honey Bees (Apis mellifera) Intoxicated by Pesticide Thiacloprid
Authors: Hýbl Marian , Mráz Petr , Šipoš Jan , Hoštičková Irena , Bohatá Andrea , Čurn Vladislav , Kopec Tomáš
Published: June 2021

Malnutrition is one of the main problems related to the global mass collapse of honey bee colonies, because in honey bees, malnutrition is associated with deterioration of the immune system and increased pesticide susceptibility. Another important cause of mass bee colonies losses is the use of pesticides. Therefore, the goal of this study was to verify the influence of polyphenols on longevity, food consumption, and cytochrome P450 gene expression in worker bees intoxicated by thiacloprid. The tests were carried out in vitro under artificial conditions (caged bees). A conclusively lower mortality rate and, in parallel, a higher average food intake, were observed in intoxicated bees treated using a mixture of phenolic acids and flavonoids compared to untreated intoxicated bees. This was probably caused by increased detoxification capacity caused by increased expression level of genes encoding the cytochrome P450 enzyme in the bees. Therefore, the addition of polyphenols into bee nutrition is probably able to positively affect the detoxification capacity of bees, which is often reduced by the impact of malnutrition resulting from degradation of the environment and common beekeeping management.
Feasibility of Secondary Follicle Isolation, Culture and Achievement of In-Vitro Oocyte Maturation from Superovulated Ovaries: An Experimental Proof-of-Concept Study Using Mice
Authors: Hao Xia , Anastácio Amandine , Rodriguez-Wallberg Kenny A.
Published: June 2021

Fertility preservation through ovarian stimulation, aiming at cryopreserving mature oocytes or embryos, is sometimes unsuccessful. This clinical situation deserves novel approaches to overcome infertility following cancer treatment in patients facing highly gonadotoxic treatment. In this controlled experimental study, we investigated the feasibility of in-vitro culturing secondary follicles isolated from superovulated ovaries of mice recently treated with gonadotropins. The follicle yields of superovulated ovaries were 45.9% less than in unstimulated controls. Follicles from superovulated ovaries showed faster growth pace during the initial 7 days of culture and secreted more 17β-estradiol by the end of culture vs controls. Parameters reflecting the outcome of follicular development and oocyte maturation competence in vitro were similar between superovulated and control groups, with a similar follicle size at the end of culture and around 70% survival. Nearly half of cultured follicles met the criteria for in-vitro maturation in both groups and approximately 60% of those achieved a mature MII oocyte, similarly in both groups. Over 60% of obtained MII oocytes displayed normal-looking spindle and chromosome configurations, without significant differences between the groups. Using a validated follicle culture system, we demonstrated the feasibility of secondary follicle isolation, in-vitro culture and oocyte maturation with normal spindle and chromosome configurations obtained from superovulated mice ovaries.
The Potential of Non-Invasive Biomarkers for Early Diagnosis of Asymptomatic Patients with Endometriosis
Authors: Kimber-Trojnar Żaneta , Pilszyk Aleksandra , Niebrzydowska Magdalena , Pilszyk Zuzanna , Ruszała Monika , Leszczyńska-Gorzelak Bożena
Published: June 2021

Endometriosis is a disease that affects women of reproductive age and has a significantly negative impact on their well-being. The main symptoms are dysmenorrhoea, chronic pelvic pain and infertility. In many patients the diagnostic process is very long and can take up to 8–12 years. Laparoscopy, an invasive method, is still necessary to confirm the diagnosis. Therefore, development of more effective diagnostic markers appears to be of the utmost importance for early diagnosis of endometriosis and provision of appropriate treatment. From a clinical point of view, detection of early-stage endometriosis in asymptomatic patients is an ideal situation since early diagnosis of endometriosis may delay the onset of symptoms as well as prevent progression and complications. In the meantime, Cancer Antigen 125 (CA-125) is still the most frequently studied and used marker. Other glycoproteins, growth factors and immune markers seem to play an important role. However, the search for an ideal endometriosis marker is still underway. Further studies into the pathogenesis of endometriosis will help to identify biomarkers or sets of biomarkers with the potential to improve and speed up the diagnostic process in a non-invasive way.
The Impact of COVID-19 and the Pandemic on Tinnitus: A Systematic Review
Authors: Beukes Eldre , Ulep Alyssa Jade , Eubank Taylor , Manchaiah Vinaya
Published: June 2021

This review aimed to systematically review what has been published regarding tinnitus during the coronavirus disease 2019 (COVID-19) pandemic up to March 2021 by performing both narrative and quantitative meta-analyses. Of the 181 records identified, 33 met the inclusion criteria, which generally had a fair risk of overall bias. In the included, 28 studies focused on the impact of the COVID-19 virus on tinnitus and 5 studies focused on the impact of the pandemic on tinnitus. From the studies identifying the impact of COVID-19 on tinnitus, there were 17 cross-sectional studies (n = 8913) and 11 case series or case report studies (n = 35). There were 2 cross-sectional studies (n = 3232) and 3 pre-post-test design studies (n = 326) focusing on the impact of the pandemic on tinnitus. No consistent patterns were found regarding the presentation of the tinnitus or additional factors that could have tinnitus developing in the disease impact studies. For the pandemic impact studies, the associated stress and anxiety of the pandemic were consistently suggested to contribute to tinnitus experiences. The pooled estimated prevalence of tinnitus post COVID-19 was 8% (CI: 5 to 13%). Medical professionals should be aware that tinnitus might be more problematic following the pandemic or after having COVID-19.
Numerical Modelling of Bond Strength in Overmoulded Thermoplastic Composites
Authors: Behrens Bernd-Arno , Dröder Klaus , Brunotte Kai , Wester Hendrik , Hürkamp André , Ossowski Tim , Lorenz Ralf
Published: June 2021

Overmoulding of thermoplastic composites combines the steps of thermoforming and injection moulding in an integrated manufacturing process. The combination of continuous fibre-reinforced thermoplastics with overmoulded polymer enables the manufacturing of highly functionally integrated structures with excellent mechanical properties. When performed as a one-shot process, an economically efficient manufacturing of geometrical complex lightweight parts within short cycle times is possible. However, a major challenge in the part and process design of overmoulded thermoplastic composites (OTC) is the assurance of sufficient bond strength between the composite and the overmoulded polymers. Within the framework of a simulation-based approach, this study aims to develop a methodology for predicting the bond strength in OTC using simulation data and a numerical model formulation of the bonding mechanisms. Therefore, a modelling approach for the determination of the bond strength depending on different process parameters is presented. In order to validate the bond strength model, specimens are manufactured with different process settings and mechanical tests are carried out. Overall, the results of the numerical computation are in good agreement with the experimentally determined bond strength. The proposed modelling approach enables the prediction of the local bond strength in OTC, considering the interface conditions and the processing history.
Modern Challenges for Early-Phase Clinical Trial Design and Biomarker Discovery in Metastatic Non-Small-Cell Lung Cancer
Authors: Rossi Antonio , Pilotto Sara , Carbognin Luisa , Ferrara Miriam Grazia , Belluomini Lorenzo , Daniele Gennaro , Bria Emilio
Published: June 2021

Oncology research has changed extensively due to the possibility to categorize each cancer type into smaller subgroups based on histology and particularly on different genetic alterations due to their heterogeneity. The consequences of this heterogeneity are particularly evident in the management of metastatic non-small-cell lung cancer (NSCLC). This review will discuss the benefits and challenges of incorporating precision medicine into early- through late-phase metastatic NSCLC clinical trials, discussing examples of drug development programs in oncogene- and non-oncogene-addicted NSCLC. The experiences of clinical development of crizotinib, gefitinib and osimertinib are depicted showing that when a targeted drug is administrated in a study population not selected by any biomarker, trials could produce negative results. However, the early detection of biomarker-driven biology helps to obtain a greater benefit for a selected population and can reduce the required time for drug approval. Early clinical development programs involving nivolumab, pembrolizumab and avelumab, immune checkpoint inhibitors, taught us that, beyond safety and activity, the optimal selection of patients should be based on pre-specified biomarkers. Overall, the identification of predictive biomarkers is one of the greatest challenges of NSCLC research that should be optimized with solid methodological trial designs to maximize the clinical outcomes.
Homeostatic Functions of Tecrem, a CD46-Like Regulatory Protein of Complement Activation, on Epithelial Cells in Carp Fish
Authors: Prakash Harsha , Motobe Shiori , Nagasawa Takahiro , Somamoto Tomonori , Nakao Miki
Published: June 2021

Fish mucosal surface is a significant interface for pathogens to infect from an aqueous environment. In addition to mucosal innate and adaptive immune factors, epithelial cells are considered as a significant physical barrier against microbial invasion. Previously, we identified a mammalian CD46-like complement regulatory protein (Tecrem) in teleost and detected its expression on epithelial cells derived from fin, suggesting its physiological role on the fish surface. This study examines the homeostatic roles of Tecrem in maintaining the fish epithelium, by analyzing the expression behavior of Tecrem on the fin-derived epithelial cell lines (KF-1 from the common carp and CFS from ginbuna crucian carp) using monoclonal and polyclonal anti-Tecrem antibodies. Expression of KF-1 protein was associated with the adhesion of KF-1, and the adhesion was enhanced by anti-Tecrem treatments of the cells. Stimulation of the epithelial cells with anti-Tecrem enhanced wound healing, protein expression of tight-junction proteins, and cell density of the KF-1 and CFS monolayer culture. These results suggest that Tecrem on epithelial cells play a homeostatic role in maintaining intactness of the surface epithelial barrier, implying that modification of Tecrem expression may develop a novel tool to improve the first-line defense against pathogens in aquaculture.
Continuous Contract Based Verification of Updates in Maritime Shipboard Equipment
Authors: Hake Georg , Hohl Carl Philipp , Hahn Axel
Published: June 2021

Modern control systems in the maritime domain are increasingly controlled by software systems and become subject to updates and configuration changes during operation. Moreover, with the shift to autonomous vessels and cars, these software-based systems are taking on more and more safety-critical tasks, so the risks associated with system failures are increasing. Unlike before, it becomes necessary to verify the continuously adapting modules of a vehicle not only before deployment, but to establish continuous verification capabilities during all phases of the product lifecycle, from the design to the system in operation. Hence, in case of an update, deviations from the expected behavior can be automatically detected and relevant measures can be initiated. In this work, a contract-based verification framework is presented that includes automatable and formally analyzable behavioral descriptors in form of assumption-guarantee contracts for all phases of the software lifecycle to provide static and dynamic verification capabilities alongside a dynamically changing system composition. By utilizing contractually defined behavior descriptions, classic test procedures, such as simulations, are supplemented by a formally testable level that is applied to all phases of the update process. A conceptual-deductive methodology was chosen, building on the identified requirements to develop an overarching update framework that adds contractual descriptions to the traditional development case. Based on the presented framework, the verifiable modification of a safety-critical software system is demonstrated. The approach is evaluated using a maritime collision-avoidance system and the verification steps are evaluated along the update process. The framework offers a novel approach to complement existing test procedures by enabling formal impact analysis and incremental verification of updates.
Nanocarriers of Miconazole or Fluconazole: Effects on Three-Species Candida Biofilms and Cytotoxic Effects In Vitro
Authors: Caldeirão Anne Caroline Morais , Araujo Heitor Ceolin , Arias Laís Salomão , Ramírez Carmona Wilmer , Miranda Gustavo Porangaba , Oliveira Sandra Helena Penha , Pessan Juliano Pelim , Monteiro Douglas Roberto
Published: June 2021

The contribution of different Candida species in oral fungal infections has stimulated the search for more effective therapies. This study assessed the antibiofilm effects of nanocarriers of miconazole (MCZ) or fluconazole (FLZ) on Candida biofilms, and their cytotoxic effects on murine fibroblasts. Three-species biofilms (Candida albicans/Candida glabrata/Candida tropicalis) were formed on 96-well plates, and they were treated with nanocarriers (iron oxide nanoparticles coated with chitosan—“IONPs-CS”) of MCZ or FLZ at 39/78/156 µg/mL; antifungals alone at 156 µg/mL and artificial saliva were tested as positive and negative controls, respectively. Biofilms were analyzed by colony forming units (CFU), biomass, metabolic activity, and structure/viability. The cytotoxicity (L929 cells) of all treatments was determined via 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) reduction assay. Data were submitted to one- or two-way ANOVA, followed by Tukey’s or Fisher LSD’s tests (p < 0.05). IONPs-CS-MCZ at 78 µg/mL promoted similar antibiofilm and cytotoxic effects compared with MCZ at 156 µg/mL. In turn, IONPs-CS-FLZ at 156 µg/mL was overall the most effective FLZ antibiofilm treatment, surpassing the effects of FLZ alone; this nanocarrier was also less cytotoxic compared with FLZ alone. It can be concluded that both nanocarriers are more effective alternatives to fight Candida biofilms compared with their respective positive controls in vitro, being a promising alternative for the treatment of oral fungal infections.
Relationship between Physical Environment Satisfaction, Neighborhood Satisfaction, and Quality of Life in Gyeonggi, Korea
Authors: Lee Kyung-Young
Published: June 2021

This study examined the relationship between physical environment satisfaction, neighborhood satisfaction, and quality of life (QoL) in Gyeonggi, Korea. As previous QoL studies have rarely dealt with residential environments or examined the interactions between the physical and social factors in residential environments, to close these knowledge gaps, this study took physical and social environment satisfaction factors as relevant influences on QoL. This study also verified the moderating effect of neighborhood satisfaction on QoL through physical environment satisfaction. This study analyzed a Quality of Life Survey that was conducted in Gyeonggi, Korea. The total number of samples in the survey was 20,000, covering all 31 districts in Gyeonggi Province. In addition, multistage stratified sampling based on the number of household members and housing types was applied to the sample design. This increases the representation of the data. As a result, it was found that higher satisfaction with the physical and neighborhood factors positively affected QoL, with satisfaction with the facilities having the most obvious effect. Neighborhood satisfaction was found to have a moderating effect between safety satisfaction and QoL. Many developing countries have tended to pursue quantitative growth with a focus on economic aspects, which has undermined overall urban sustainability. However, recent urban management has also emphasized qualitative growth, such as resident QoL, as being just as important for urban sustainability. Therefore, this study’s results have important policy implications for qualitative urban growth.
Definiteness, Information Structure, and Indirect Modification in the Kunbarlang Noun Phrase
Authors: Kapitonov Ivan
Published: June 2021

Kunbarlang shows considerable variation in the word order patterns of nominal expressions. This paper investigates these patterns, concentrating on the distribution of noun markers (articles) and on attributive modification. Based on examination of spontaneous discourse and elicitation, I identify two main contributions of the noun marker: definiteness and predicative reading of modifiers. Furthermore, the order of adjectives with respect to the head noun is shown to correlate with information-structural effects. Taken together, these facts strongly support a hierarchical structure analysis of the NP in Kunbarlang. In the second part of the paper, Kunbarlang data are compared to the typology of determiner spreading phenomena. Finally, I entertain the prospects of a more formal analysis of the data presented and indicate their theoretical and typological relevance, including expression of information structure below the clausal level, typology of adnominal elements, and architecture of attributive modification.
Optimized Zirconia 3D Printing Using Digital Light Processing with Continuous Film Supply and Recyclable Slurry System
Authors: Sarwar Waqas Ahmed , Kang Jin-Ho , Yoon Hyung-In
Published: June 2021

Stereolithography (SL) can fabricate complex ceramic parts layer by layer using computer-aided design (CAD) models. The traditional SL system utilizes a vat filled with ceramic slurry with a high solid content, which for ceramics contributes to several limitations and operational difficulties, and further renders it nonrecyclable mainly due to the presence of printed residue and its high viscosity. In this study, we utilized a continuous film supply (CFS) system integrated with a tape-casting type digital light processing (DLP) printer to fabricate zirconia prototypes with a solid content of 45 volume percent (vol.%). Various printing and postprocessing parameters were studied for optimization, to achieve a relative density of 99.02% ± 0.08% with a microhardness of 12.59 ± 0.47 GPa. Slurry reusability was also demonstrated by printing with recycled slurry to produce consistent relative density values in the range of 98.86% ± 0.02% to 98.94% ± 0.03%. This method provides new opportunities for material recycling and the fabrication of dense complex ceramic products, reducing the consumption of the material.
Indentation Response of Calcium Aluminoborosilicate Glasses Subjected to Humid Aging and Hot Compression
Authors: Ren Xiangting , Liu Pengfei , Rzoska Sylwester J. , Lucznik Boleslaw , Bockowski Michal , Smedskjaer Morten M.
Published: June 2021

Aluminoborosilicate glasses find a wide range of applications, which require good mechanical reliability such as surface damage resistance. Calcium aluminoborosilicate (CABS) glasses have recently been found to exhibit so-called intermediate behavior in terms of their response to sharp contact loading. That is, these glasses deform with less shear than normal glass and less densification than anomalous glasses. This deformation mechanism is believed to give rise to high crack initiation resistance of certain CABS glasses. In order to further improve and understand the micromechanical properties of this glass family, we studied the indentation response of different CABS glasses subjected to two types of post-treatment, namely hot compression and humid aging. Upon hot compression, density, elastic moduli, and hardness increased. Specifically, elastic modulus increased by as much as 20% relative to the as-made sample, while the largest change in hardness was 1.8 GPa compared to the as-made sample after hot compression. The pressure-induced increase in these properties can be ascribed to the increase in network connectivity and bond density. On the other hand, the crack initiation resistance decreased, as the hot compression increased the residual stress driving the indentation cracking. Humid aging had only a minor impact on density, modulus, and hardness, but an observed decrease in crack initiation resistance. We discuss the correlations between hardness, density, crack resistance, and deformation mechanism and our study thus provides guidelines for tailoring the mechanical properties of oxide glasses.
Applications of AOTF Spectrometers in In Situ Lunar Measurements
Authors: Li Jinning , Gui Yuhua , Xu Rui , Zhang Zehong , Liu Wei , Lv Gang , Wang Meizhu , Li Chunlai , He Zhiping
Published: June 2021

Spectrometers based on acousto-optic tunable filters (AOTFs) have several advantages, such as stable temperature adaptability, no moving parts, and wavelength selection through electrical modulation, compared with the traditional grating and Fourier transform spectrometers. Therefore, AOTF spectrometers can realize stable in situ measurement on the lunar surface under wide temperature ranges and low light environments. AOTF imaging spectrometers were first employed for in situ measurement of the lunar surface in the Chinese Chang’e project. The visible and near-infrared imaging spectrometer and the lunar mineralogical spectrometer have been successfully deployed on board the Chang’e-3/4 and Chang’e-5 missions. In this review, we investigate the performance indicators, structural design, selected AOTF performance parameters, data acquisition of the three lunar in situ spectral instruments used in the Chang’e missions. In addition, we also show the scientific achievement of lunar technology based on in situ spectral data.