bluuebunny/crossref_metadata_2025 huggingface dataset:
UnbiasedDTI: Mitigating Real-World Bias of Drug-Target Interaction Prediction by Using Deep Ensemble-Balanced Learning
Authors: Tayebi Aida , Yousefi Niloofar , Yazdani-Jahromi Mehdi , Kolanthai Elayaraja , Neal Craig , Seal Sudipta , Garibay Ozlem
Published: May 2022

Drug-target interaction (DTI) prediction through in vitro methods is expensive and time-consuming. On the other hand, computational methods can save time and money while enhancing drug discovery efficiency. Most of the computational methods frame DTI prediction as a binary classification task. One important challenge is that the number of negative interactions in all DTI-related datasets is far greater than the number of positive interactions, leading to the class imbalance problem. As a result, a classifier is trained biased towards the majority class (negative class), whereas the minority class (interacting pairs) is of interest. This class imbalance problem is not widely taken into account in DTI prediction studies, and the few previous studies considering balancing in DTI do not focus on the imbalance issue itself. Additionally, they do not benefit from deep learning models and experimental validation. In this study, we propose a computational framework along with experimental validations to predict drug-target interaction using an ensemble of deep learning models to address the class imbalance problem in the DTI domain. The objective of this paper is to mitigate the bias in the prediction of DTI by focusing on the impact of balancing and maintaining other involved parameters at a constant value. Our analysis shows that the proposed model outperforms unbalanced models with the same architecture trained on the BindingDB both computationally and experimentally. These findings demonstrate the significance of balancing, which reduces the bias towards the negative class and leads to better performance. It is important to note that leaning on computational results without experimentally validating them and by relying solely on AUROC and AUPRC metrics is not credible, particularly when the testing set remains unbalanced.
Determination of Chiral Impurity of Naproxen in Different Pharmaceutical Formulations Using Polysaccharide-Based Stationary Phases in Reversed-Phased Mode
Authors: Papp Lajos-Attila , Krizbai Sarolta , Dobó Máté , Hancu Gabriel , Szabó Zoltán-István , Tóth Gergő
Published: May 2022

A novel, validated, reversed-phase (RP), chiral high performance liquid chromatography (HPLC) method was developed for the enantiopurity control analysis of naproxen, a frequently used non-steroidal anti-inflammatory agent using polysaccharide-type chiral stationary phase (CSP). In the screening phase of method development, seven columns were tested in polar organic (PO) mode using mobile phases consisting of 0.1% acetic acid in methanol, ethanol, 2-propanol, and acetonitrile. Enantiorecognition was observed only in five cases. The best enantioseparation was observed on a Lux Amylose-1 column with 0.1% (v/v) acetic acid in ethanol with a resolution (Rs) of 1.24. The enantiomer elution order was unfavorable, as the distomer eluted after the eutomer. When the ethanolic mobile phase was supplemented with water, enantiomer elution order reversal was observed, indicating a difference in the enantiorecognition mechanism upon switching from PO to RP mode. Furthermore, by changing ethanol to methanol, not only lower backpressure, but also higher resolution was obtained. Subsequent method optimization was performed using a face-centered central composite design (FCCD) to achieve higher chiral resolution in a shorter analysis time. Optimized parameters offering baseline separation were as follows: Lux Amylose-1 stationary phase, thermostated at 40 °C, and a mobile phase consisting of methanol:water:acetic acid 85:15:0.1 (v/v/v), delivered with 0.65 mL/min flow rate. Using these optimized parameters, a Rs = 3.21 ± 0.03 was achieved within seven minutes. The optimized method was validated according to the ICH guidelines and successfully applied for the analysis of different pharmaceutical preparations, such as film-coated tablets and gel, as well as fixed-dose combination tablets, containing both naproxen and esomeprazole.
Simultaneous Analysis of 19 Marker Components for Quality Control of Oncheong-Eum Using HPLC–DAD
Authors: Seo Chang-Seob , Shin Hyeun-Kyoo
Published: May 2022

Oncheong-eum (OCE) is a traditional herbal prescription made by combining Samul-tang and Hwangryunhaedok-tang. It is primarily used to treat gynecological disorders such as metrorrhagia and metrostaxis. In the present study, we focused on developing and validating a simultaneous assay for the quality control of OCE using 19 marker components (gallic acid, 5-(hydroxymethyl)furfural, chlorogenic acid, geniposide, coptisine chloride, jatrorrhizine chloride, paeoniflorin, berberine chloride, palmatine chloride, ferulic acid, nodakenin, benzoic acid, baicalin, benzoylpaeoniflorin, wogonoside, baicalein, wogonin, decursin, and decursinol angelate). This analysis was performed using high-performance liquid chromatography coupled with a diode array detector, and chromatographic separation of the 19 markers was carried out using a SunFireTM C18 reversed-phase column and gradient elution conditions with two mobile phases (0.1% aqueous formic acid–0.1% formic acid in acetonitrile). The developed analytical method was validated through linearity, limits of detection and quantification, recovery, and precision. Under this assay, 19 markers in OCE samples were detected at not detected–9.62 mg/g. The analytical methods developed and validated in our research will have value as basic data for the quality control of related traditional herbal prescriptions as well as OCE.
The Role of the Nucleotides in the Insertion of the bis-Molybdopterin Guanine Dinucleotide Cofactor into apo-Molybdoenzymes
Authors: Tiedemann Kim , Iobbi-Nivol Chantal , Leimkühler Silke
Published: May 2022

The role of the GMP nucleotides of the bis-molybdopterin guanine dinucleotide (bis-MGD) cofactor of the DMSO reductase family has long been a subject of discussion. The recent characterization of the bis-molybdopterin (bis-Mo-MPT) cofactor present in the E. coli YdhV protein, which differs from bis-MGD solely by the absence of the nucleotides, now enables studying the role of the nucleotides of bis-MGD and bis-MPT cofactors in Moco insertion and the activity of molybdoenzymes in direct comparison. Using the well-known E. coli TMAO reductase TorA as a model enzyme for cofactor insertion, we were able to show that the GMP nucleotides of bis-MGD are crucial for the insertion of the bis-MGD cofactor into apo-TorA.
Comparative Study of Preparation, Evaluation, and Pharmacokinetics in Beagle Dogs of Curcumin β-Cyclodextrin Inclusion Complex, Curcumin Solid Dispersion, and Curcumin Phospholipid Complex
Authors: Song Wanrong , Chen Xizhao , Dai Chongshan , Lin Degui , Pang Xuelin , Zhang Di , Liu Gang , Jin Yipeng , Lin Jiahao
Published: May 2022

Curcumin is a natural acidic polyphenol extracted from turmeric with a wide range of biological and pharmacological effects. However, the application of curcumin for animal production and human life is limited by a low oral bioavailability. In this study, natural curcumin was prepared for the curcumin β-cyclodextrin inclusion complex (CUR-β-CD), curcumin solid dispersion (CUR-PEG-6000), and curcumin phospholipid complex (CUR-HSPC) using co-precipitation, melting, and solvent methods, respectively. Curcumin complex formations were monitored using scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR) techniques via the shifts in the microscopic structure, molecular structure, and crystalline state. Subsequently, twenty-four female beagle dogs were randomly divided into four groups to receive unmodified curcumin and three other curcumin preparations. The validated UPLC–MS assay was successfully applied to pharmacokinetic and bioavailability studies of curcumin in beagle dog plasma, which were collected after dosing at 0 min (predose), 5 min, 15 min, 30 min, 40 min, 50 min, 1.5 h, 3 h, 4.5 h, 5.5 h, 6 h, 6.5 h, 9 h, and 24 h. The relative bioavailabilities of CUR-β-CD, CUR-PEG-6000, and CUR-HSPC were 231.94%, 272.37%, and 196.42%, respectively. This confirmed that CUR-β-CD, CUR-HSPC, and especially CUR-PEG-6000 could effectively improve the bioavailability of curcumin.
Characterisation of a Novel Acetyl Xylan Esterase (BaAXE) Screened from the Gut Microbiota of the Common Black Slug (Arion ater)
Authors: Madubuike Henry , Ferry Natalie
Published: May 2022

Acetyl xylan esterases (AXEs) are enzymes capable of hydrolysing the acetyl bonds in acetylated xylan, allowing for enhanced activity of backbone-depolymerizing enzymes. Bioprospecting novel AXE is essential in designing enzyme cocktails with desired characteristics targeting the complete breakdown of lignocellulose. In this article, we report the characterisation of a novel AXE identified as Gene_id_40363 in the metagenomic library analysed from the gut microbiota of the common black slug. The conserved domain description was identified with an NCBI BLASTp search using the translated nucleotide sequence as a query. The activity of the recombinant enzyme was tested on various synthetic substrates and acetylated substrates. The protein sequence matched the conserved domain described as putative hydrolase and aligned closely to an uncharacterized esterase from Buttiauxella agrestis, hence the designation as BaAXE. BaAXE showed low sequence similarity among characterized CE family proteins with an available 3D structure. BaAXE was active on 4-nitrophenyl acetate, reporting a specific activity of 78.12 U/mg and a Km value of 0.43 mM. The enzyme showed optimal activity at 40 °C and pH 8 and showed high thermal stability, retaining over 40% activity after 2 h of incubation from 40 °C to 100 °C. BaAXE hydrolysed acetyl bonds, releasing acetic acid from acetylated xylan and β-D-glucose pentaacetate. BaAXE has great potential for biotechnological applications harnessing its unique characteristics. In addition, this proves the possibility of bioprospecting novel enzymes from understudied environments.
Comparison of the Nucleation Kinetics Obtained from the Cumulative Distributions of the Metastable Zone Width and Induction Time Data
Authors: Shiau Lie-Ding
Published: May 2022

A linearized integral model based on classical nucleation theory is applied in this work to determine the interfacial energy and pre-exponential factor using a linear plot from the cumulative distributions of the metastable zone width (MSZW) data for some systems reported in the literature, including isonicotinamide, butyl paraben, dicyandiamide, and salicylic acid. Based on the same criterion for the nucleation point, the interfacial energy and pre-exponential factor are determined using the conventional linear regression method from the cumulative distributions of the induction time data for the same systems. The results indicate that the interfacial energy and pre-exponential factor calculated from the MSZW data are consistent with those calculated from the induction time for the studied systems.
Identification and Optimization of a Novel Taxanes Extraction Process from Taxus cuspidata Needles by High-Intensity Pulsed Electric Field
Authors: Zhao Zirui , Zhang Yajing , Meng Huiwen , Li Wenlong , Wang Shujie
Published: May 2022

Taxanes are a series of natural compounds with great application potential in antitumor therapy, whereas the lack of efficient taxanes extraction methods significantly hinders the development of taxanes. The high-intensity pulsed electric field (PEF) is a novel technology used to extract bioactive ingredients from food and other natural products. However, the prospect of using PEF for taxanes extraction remains to be elucidated. Herein, we extracted taxanes from Taxus cuspidata via PEF and explored the effects of seven extraction conditions on the yields of target compounds. The Placket–Burman design (PBD) assay revealed that electric field strength, pulse number, and particle size are key factors for taxanes extraction. The response surface methodology (RSM) and back-propagation neural network conjugated with genetic algorithm (GA-BP) were further used to model and predict the optimal extraction conditions, and GA-BP exerted higher reliability, leading to a maximum extraction yield of 672.13 μg/g under electric field strength of 16 kV/cm, pulse number of 8, particle size of 160 meshes, solid–liquid ratio of 1:60, a single extraction, centrifugal speed of 8000 r/min, and flow rate of 7 mL/min, which was 1.07–1.84 folds that of control, solid–liquid extraction (SL), and ultrasonic extraction (US) groups. Additionally, the scanning electron microscopy (SEM) results indicated that the sample particles extracted by PEF method exhibited a coarser surface morphology. Thus, we present for the first time that PEF is feasible for the extraction of taxanes from Taxus cuspidata and highlight the application value of the PBD, RSM, and GA-BP models in parameters optimization during extraction process.
The Beneficial Effects of Citrus kawachiensis Peel on Neurogenesis in the Hippocampus and Gut Microbiota Changes in a Chronic Unpredictable Mild Stress Mouse Model
Authors: Okuyama Satoshi , Kotani Maho , Ninomiya Fuga , Sawamoto Atsushi , Fujitani Mina , Ano Yoshitaka , Kishida Taro , Nakajima Mitsunari , Furukawa Yoshiko
Published: May 2022

We previously reported that the dried peel powder of Citrus kawachiensis, a citrus product of Japan, exerted anti-inflammatory and neuroprotective effects in the brains of transient global cerebral ischemia model mice. It also ameliorated the hyperphosphorylation of Tau protein and the suppression of neurogenesis in the brains of the senescence-accelerated mouse-prone 8 aging model. Chronic unpredictable mild stress (CUMS) induces anxiety-like behavior, changes the composition of the gut microbiota and suppresses neurogenesis in the hippocampus. Therefore, we herein examined the effects of the dried peel powder of C. kawachiensis in a CUMS mouse model: CUMS enhanced locomotor activity, shown as the distance travelled in the open field test at the beginning of the test, while the C. kawachiensis treatment suppressed this increase. The C. kawachiensis treatment also prevented CUMS-induced decreases in hippocampal neurogenesis. The CUMS treatment changed the composition of the gut microbiota by reducing the abundance of Lactobacillus and increasing that of Bacteroides, whereas the C. kawachiensis treatment attenuated these changes. Collectively, the present results suggest that the dried peel powder of C. kawachiensis exerts neuroprotective effects in the brain and maintains the condition of the microbiome under mild stress.
Characterization of the Spanish Pomegranate Germplasm Collection Maintained at the Agricultural Experiment Station of Elche to Identify Promising Breeding Materials
Authors: Zuriaga Elena , Pintová Jitka , Bartual Julián , Badenes María Luisa
Published: May 2022

Pomegranates were one of the first domesticated fruit crops, and their long history resulted in the development of local cultivars all over the world. Spain is one of the main producers and exporters of this crop in the Mediterranean Basin, but in order to maintain the competitiveness of this crop, new varieties should be developed. For this purpose, the pomegranate germplasm collection hold at the Agricultural Experiment Station of Elche, a public institution dependent on the Valencian regional government, is an interesting tool. However, the detailed characterization of any germplasm collection is a fundamental requirement to be able to make the most of these resources, allowing to identify putative promising accessions and to optimize the design of the future crosses. In this work, the genetic diversity of 94 accessions of this collection was analyzed using 19 microsatellite markers. As a result, 85 different genotypes were identified. These genetic profiles could be useful for varietal identification. Despite this genetic diversity, no clear substructure was observed, except for the ornamental accessions, that could be related to the vegetative propagation of the species. Additionally, the morphological characterization of this collection has made it possible to identify some materials that may be of interest as a source of traits for breeding. Results presented here pave the way for further genetic analyses, allowing the selection of parents to obtain segregating populations, as well as their descendants by the use of molecular assisted selection.
Presence of the Herbaceous Marsh Species Schoenoplectus americanus Enhances Surface Elevation Gain in Transitional Coastal Wetland Communities Exposed to Elevated CO2 and Sediment Deposition Events
Authors: Stagg Camille LaFosse , Laurenzano Claudia , Vervaeke William C. , Krauss Ken W. , McKee Karen L.
Published: May 2022

Coastal wetlands are dynamic ecosystems that exist along a landscape continuum that can range from freshwater forested wetlands to tidal marsh to mudflat communities. Climate-driven stressors, such as sea-level rise, can cause shifts among these communities, resulting in changes to ecological functions and services. While a growing body of research has characterized the landscape-scale impacts of individual climate-driven stressors, little is known about how multiple stressors and their potential interactions will affect ecological functioning of these ecosystems. How will coastal wetlands respond to discrete climate disturbances, such as hurricane sediment deposition events, under future conditions of elevated atmospheric CO2? Will these responses vary among the different wetland communities? We conducted experimental greenhouse manipulations to simulate sediment deposition from a land-falling hurricane under future elevated atmospheric CO2 concentrations (720 ppm CO2). We measured responses of net primary production, decomposition, and elevation change in mesocosms representing four communities along a coastal wetland landscape gradient: freshwater forested wetland, forest/marsh mix, marsh, and mudflat. When Schoenoplectus americanus was present, above- and belowground biomass production was highest, decomposition rates were lowest, and wetland elevation gain was greatest, regardless of CO2 and sediment deposition treatments. Sediment addition initially increased elevation capital in all communities, but post-deposition rates of elevation gain were lower than in mesocosms without added sediment. Together these results indicate that encroachment of oligohaline marshes into freshwater forested wetlands can enhance belowground biomass accumulation and resilience to sea-level rise, and these plant-mediated ecosystem services will be augmented by periodic sediment pulses from storms and restoration efforts.
Cryopreservation of Holm Oak Embryogenic Cultures for Long-Term Conservation and Assessment of Polyploid Stability
Authors: Martínez Maria Teresa , Suárez Sonia , Moncaleán Paloma , Corredoira Elena
Published: May 2022

Holm oak populations are severely affected by oak decline syndrome, and reliable methods of conserving the plant material are required. A vitrification-based cryopreservation method was used for the first time for the long-term conservation of holm oak embryogenic cultures. Successful cryopreservation was achieved after determining the best developmental stage of the somatic embryos used and the optimal incubation period in plant vitrification solution 2 (PVS2). Embryos were recovered from individual nodular embryogenic structures (NES) derived from four embryogenic lines after preculture on a medium containing 0.3 M sucrose, incubation in PVS2 vitrification solution for 15 min at 25 °C and direct immersion in liquid nitrogen (LN). Embryo recovery rates of 16.7–63.3% were obtained after cryostorage for four years in LN. In addition to the embryo developmental stage and the PVS2 treatment time, the genotype can also significantly affect embryo recovery after LN storage. There were no significant differences in plant regeneration or polyploid stability between somatic embryos and plants derived from control embryos (not cryopreserved) and cryopreserved embryos. The findings indicate that embryo proliferation, plant conversion and polyploid stability are maintained in material recovered from the vitrification solution and subsequently cryopreserved.
Quantification of Carbon Emission and Solid Waste from Pottery Production by Using Life-Cycle Assessment (LCA) Method in Yunnan, China
Authors: Li Yang , Sharaai Amir Hamzah , Ma Sining , Wafa Wafaurahman , He Zhijian , Ghani Latifah Abdul
Published: May 2022

Environmental pollution in the pottery industry is a severe problem, particularly dust and smoke pollution from the building-pottery industry. The main objectives of this study are to quantify the carbon emissions and solid-waste generation from the life cycle of pottery production in Yunnan. This study was carried out between November 2020 and May 2021. LCA was used, and 1 kg of pottery was used as the functional unit. There is a lot of literature to obtain data on the carbon emissions and solid waste generated in the process of pottery production for reference and calculation. This study forces the extraction of raw materials to the processing point, the device boundary of the pottery-production process. Carbon emissions in the pottery-production process account for about 80% of the whole pottery life cycle. Moreover, a large amount of solid waste is mainly produced as a result of the waste and production process. It is recommended that the serious pollution-causing combustion system should be reformed. The enterprise’s waste can be recycled. Most of the waste products can only be used as construction filling, and a small amount of the waste products can be used as hard materials in proportion after crushing.
Parameter Optimization and Experimental Study of Jet Mixing Device Based on CFD
Authors: Zhou Wei , Wang Shujie , Zhu Jinbo , Xie Jun , Cai Chuanchuan
Published: May 2022

The parameters of jet mixing devices have an important influence on the mixing process, particle movement and interface regulation. At present, jet mixing devices are widely used in the coal slime flotation field, and their variable parameters lack systematic optimization. In this paper, the performance of reagent mixing and the distribution characteristics of flow field are taken as the evaluation indexes, and computational fluid dynamics (CFD) software (FLUENT) is used to optimize the variable parameters of the device. The results show that when the area ratio Ar=1.96~3.24, the throat-nozzle distance Le=0.2Dh~0.6Dh, the suction tube is located 1/4~1/2 Lz to the left of the nozzle outlet and is symmetrically arranged, the length of the throat tube L is from 6Dz to 12Dz, the mixing performance of the jet mixing device was optimal. The flow field distribution characteristics showed that the area ratio has a more significant effect. The larger the area ratio is, the more favorable the mixing of the working fluid and the injection fluid is. The throat-nozzle distance has little effect on the flow field distribution, and its optimal value ranges from 0.3Dh to 0.6Dh. The fog droplet size test showed that the dispersion effect was the best when the area ratio Ar=3.24. The diameter size test of the injected bubbles was carried out to verify the performance of the jet mixing device after parameter optimization. The experimental results and the simulation results confirm each other, which proves the correctness of the numerical simulation results.
Neurological and Psychiatric Symptoms of COVID-19: A Narrative Review
Authors: Edinoff Amber N. , Chappidi Maithreyi , Alpaugh E. Saunders , Turbeville Bailey C. , Falgoust Evan P. , Cornett Elyse M. , Murnane Kevin S. , Kaye Adam M. , Kaye Alan D.
Published: May 2022

Recently dubbed Long COVID or Long-Haul COVID, those recovering from the initial COVID-19 infection may maintain clinical signs for longer than two or more weeks following the initial onset of the infection. The virus can gain entry into the CNS through axonal transport mediated through the olfactory nerve or hematogenous spread and can also cross the blood–brain barrier to access the temporal lobe and the brainstem. The neurologic and neuropsychiatric symptoms associated with COVID-19 patients are becoming a highly studied area due to the increased frequency of reported cases. Multiple hospital case series and observational studies have found a headache to be a common symptom among patients who are symptomatic with the SARS-CoV-2 virus. The headache described by many of these patients is similar to new daily persistent headache (NDPH). NDPH potentially develops in response to pro-inflammatory cytokines during a persistent systemic or CNS inflammation, mostly due to the initial infection. The treatments investigated were high-dose steroids, tetracycline derivatives, onabotulinum toxin type A, and long-term multidrug regimens. Among the identified symptoms of post-COVID-19 viral illness, fatigue appears to be the most ubiquitous. High-dose vitamin C is currently a suggested therapy proposed for its antioxidant, anti-inflammatory, and immunomodulatory properties. The mental health consequences of this diagnosis are being identified among large portions of COVID-19 survivors. Among these consequences, cases of major depressive disorder (MDD) and anxiety are being reported and closely examined. The aim of this narrative review is to highlight the neurological and psychiatric symptoms that have been associated with Long-Haul COVID and their possible treatments.
Multi-Layered Carbon-Black/Elastomer-Composite-Based Shielded Stretchable Capacitive Sensors for the Underactuated Robotic Hand
Authors: Yong Shi , Aw Kean
Published: May 2022

Soft and flexible strain sensors are becoming popular for many robotic applications. This article presents a stretchable capacitive sensor by combining a conductive filler of carbon black with elastomers and implementing shielding to reduce parasitic interference, applied to an underactuated robotic hand. Sensors with different configurations were explored. The results show that a shield introduced to the sensor does have some mitigation effect on external interference. Two sensor configurations were explored: longitudinal interdigitated capacitive (LIDC) sensor, where the interdigitated fingers lie along the same axis as the strain, and transverse interdigitated capacitive (TIDC) sensor, where the interdigitated fingers are orthogonal to the strain direction. The LIDC configuration had better performance than TIDC. The fabricated two-layered LIDC sensor had a gage factor of 0.15 pF/mm and the rates of capacitive creep of 0.000667 pF/s and 0.001 pF/s at loads of 120 g and 180 g, respectively. The LIDC sensors attached to an underactuated robotic hand demonstrate the sensors’ ability to determine the bending angles of the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints.
Multiracial Identities in the United States: Towards the Brazilian or South African Paths?
Authors: Daniel G. Reginald
Published: May 2022

Multiracial identities in Brazil, South Africa, and the United States all formed within White supremacist, White racist, and anti-Black social orders. Brazil and South Africa historically acknowledged multiracials in ternary racial orders with a structurally intermediate status somewhat higher than that of other nonWhites, particularly Blacks, but significantly lower than that of Whites. In contrast, in the United States, multiracial identities have historically been prohibited due to hypodescent and the monoracial imperative, which categorize multiracials according to their most subaltern racial background and necessitate single-racial identification. In the 1980s and 1990s, a U.S. multiracial movement challenged these norms. This article compares the multiracial phenomenon in the United States with historical formations in Brazil and South Africa using data from published literature, censuses, written correspondence with activists, and observations of public behavior in the United States. The objective is to theorize whether and to what extent U.S. multiracial identities function in ways similar to the historical formations of Brazil and South Africa, particularly with regards to questions of collective identity, anti-Blackness, and White adjacency.
Deposition of Organic-Inorganic Nanocomposite Coatings for Biomedical Applications
Authors: Wang Zhengzheng , Zhitomirsky Igor
Published: May 2022

Polymethylmethacrylate (PMMA) is a material of choice for many biomedical coating applications. However, such applications are limited due to the toxicity of the traditional solvents used for the solution processing of PMMA coatings and composites. This problem is addressed using an isopropanol-water co-solvent, which allows for the dissolution of high molecular mass PMMA and the fabrication of coatings by a dip-coating method from concentrated PMMA solutions. The use of the co-solvent offers a versatile strategy for PMMA solubilization and coating deposition, despite the insolubility of PMMA in water and isopropanol. Composite coatings are obtained, containing hydroxyapatite, silver oxide, zinc oxide, micron size silica and nanosilica. Such coatings are promising for the manufacturing of implants with enhanced biocompatibility, bioactivity and antimicrobial properties and the fabrication of biosensors. Ibuprofen, tetracycline and amoxicillin are used as model drugs for the fabrication of PMMA-drug composite coatings for drug delivery. The microstructure and composition of the coatings are analyzed. The versatile dip-coating method of this investigation provides a platform for various biomedical applications.
PGC-1α Methylation, miR-23a, and miR-30e Expression as Biomarkers for Exercise- and Diet-Induced Mitochondrial Biogenesis in Capillary Blood from Healthy Individuals: A Single-Arm Intervention
Authors: Krammer Ulrike D. B. , Sommer Alexandra , Tschida Sylvia , Mayer Anna , Lilja Stephanie V. , Switzeny Olivier J. , Hippe Berit , Rust Petra , Haslberger Alexander G.
Published: May 2022

Healthy mitochondria and their epigenetic control are essential to maintaining health, extending life expectancy, and improving cardiovascular performance. Strategies to maintain functional mitochondria during aging include training; cardiovascular exercise has been suggested as the best method, but strength training has also been identified as essential to health and healthy aging. We therefore investigated the effects of concurrent exercise training and dietary habits on epigenetic mechanisms involved in mitochondrial (mt) functions and biogenesis. We analyzed epigenetic biomarkers that directly target the key regulator of mitochondrial biogenesis, PGC-1α, and mtDNA content. Thirty-six healthy, sedentary participants completed a 12-week concurrent training program. Before and after the intervention, dried blood spot samples and data on eating habits, lifestyle, and body composition were collected. MiR-23a, miR-30e expression, and mtDNA content were analyzed using real-time quantitative polymerase chain reaction (qPCR) analysis. PGC-1α methylation was analyzed using bisulfite pyrosequencing. MiR-23a, miR-30e expression, and PGC-1α methylation decreased after the intervention (p < 0.05). PGC-1α methylation increased with the consumption of red and processed meat, and mtDNA content increased with the ingestion of cruciferous vegetables (p < 0.05). Our results indicate that concurrent training could improve mitochondrial biogenesis and functions by altering the epigenetic regulation. These alterations can also be detected outside of the skeletal muscle and could potentially affect athletic performance.
Development and Testing of a Low-Cost Inactivation Buffer That Allows for Direct SARS-CoV-2 Detection in Saliva
Authors: Bustos-Garcia Brandon , Garza-Manero Sylvia , Cano-Dominguez Nallely , Lopez-Sanchez Dulce Maria , Salgado-Montes de Oca Gonzalo , Salgado-Aguayo Alfonso , Recillas-Targa Felix , Avila-Rios Santiago , Valdes Victor Julian
Published: May 2022

Massive testing is a cornerstone in efforts to effectively track infections and stop COVID-19 transmission, including places with good vaccination coverage. However, SARS-CoV-2 testing by RT-qPCR requires specialized personnel, protection equipment, commercial kits, and dedicated facilities, which represent significant challenges for massive testing in resource-limited settings. It is therefore important to develop testing protocols that are inexpensive, fast, and sufficiently sensitive. Here, we optimized the composition of a buffer (PKTP), containing a protease, a detergent, and an RNase inhibitor, which is compatible with the RT-qPCR chemistry, allowing for direct SARS-CoV-2 detection from saliva without extracting RNA. PKTP is compatible with heat inactivation, reducing the biohazard risk of handling samples. We assessed the PKTP buffer performance in comparison to the RNA-extraction-based protocol of the US Centers for Disease Control and Prevention in saliva samples from 70 COVID-19 patients finding a good sensitivity (85.7% for the N1 and 87.1% for the N2 target) and correlations (R = 0.77, p < 0.001 for N1, and R = 0.78, p < 0.001 for N2). We also propose an auto-collection protocol for saliva samples and a multiplex reaction to minimize the PCR reaction number per patient and further reduce costs and processing time of several samples, while maintaining diagnostic standards in favor of massive testing.
Immunological Aspects of Human Papilloma Virus-Related Cancers Always Says, “I Am like a Box of Complexity, You Never Know What You Are Gonna Get”
Authors: Soleymaninejadian Ehsan , Zelini Paola , Cassaniti Irene , Baldanti Fausto , Dominoni Mattia , Gritti Andrea , Gardella Barbara
Published: May 2022

The human papillomavirus (HPV) can cause different cancers in both men and women. The virus interferes with functions of the cervix, vulva, vagina, anus in the anogenital area, breast, and head and neck cancer due to the local lesions. The tumors lead to death if not treated as a result of distant metastasis to internal organs and brain. Moreover, HPV attenuates the immune system during chronic infection and releases viral antigens into the tumor microenvironment. The tumors know how difficult is to win the battle with a strong united army of immune cells that are equipped with cytokines and enzymes. They confuse the immune cells with secreting viral antigens. The immune system is equipped with cytokines, a complement system, antibodies, and other secretory proteins to overcome the foreign invaders and viral antigens. However, the majority of the time, tumors win the battle without having all the equipment of the immune cells. Thus, in this review, we describe the recent progression in cellular and humoral immunity studies during the progression of HPV-related cancers. First of all, we describe the role of B, plasmoid cells, and B regulatory cells (Breg) in their functions in the tumor microenvironment. Then, different subtypes of T cells such as T CD8, CD4, T regulatory (Treg) cells were studied in recently published papers. Furthermore, NK cells and their role in tumor progression and prevention were studied. Finally, we indicate the breakthroughs in immunotherapy techniques for HPV-related cancers.
Maurizio Moro: «Imagine del Salvatore dal Pordenon Pittor famoso dipinta».
Authors: BORTONE MILENA
Published: May 2022

In the essay Note sulla tradizione spirituale e religiosa Quondam denounced the prejudice which for a long time excluded from the field of “literature” the experiences of religious poetry of the pre-baroque era. The issue is greater in the field of figurative arts, where sacred poetry and those who dealt with it still find it hard to establish themselves as sources for the knowledge of works and artistic languages. This is the case of the Venetian Maurizio Moro, a canon and scholar who lived between the 16th and 17th centuries, known above all as the author of the commentary verses on Dürer’s Little Passion (Venice, 1612). The essay discusses the author’s composition on the «Imagine del Salvatore, dal Pordenon pittor famoso dipinta». The text, published in 1609 within the Amorosi stimoli dell’anima penitente and still unknown to those who have treated the Friulan painter, bears witness to a work not otherwise known, re-evaluating Moro as a precious source for art history and criticism.
Spiritismo e Positivismo nella narrativa breve di Luigi Capuana
Authors: Bellinzani Debora
Published: May 2022

Luigi Capuana credeva nell'immortalità dell'anima come concepita dalle teorie teosofiche, nonché nella percettibilità delle manifestazioni degli spiriti. Allo stesso tempo, i suoi racconti e saggi riflettono la sua fiducia nell'approccio positivistico e nelle scienze sperimentali. In un periodo che vede il proliferare di sedute spiritiche evocatrici di spiriti, Capuana scrive i suoi unici quattro racconti che descrivono la manifestazione percettibile di un fantasma. In Creazione (1901), La evocatrice, Forze occulte (1902) e Un vampiro (1904), gli spiriti compaiono e mostrano una notevole originalità rispetto a quelli che infestano le storie di fantasmi contemporanee. Esaminando la struttura del mistero attraverso il "perturbante" di Freud ed esplorando il contenuto delle storie attraverso i concetti chiave della scienza di Capuana, l'analisi dimostrerà come la sottrazione del mistero e la riflessione sulla scienza creino un terreno letterario comune in cui lo spiritismo e il positivismo possono sorprendentemente coesistere. Su questo terreno emerge attraverso la forza di rassicuranti fantasmi l'apertura scientifica alle scoperte del Novecento.
L’evoluzione delle strategie referenziali e predicative nei dibattiti parlamentari delle leggi italiane in materia d’immigrazione
Authors: Katona-Kovács Lili Krisztina
Published: May 2022

L'articolo presenta l'evoluzione dell'uso di due parole nei dibattiti parlamentari, immigrato ed extracomunitario, usate frequentemente in lingua italiana in riferimento a uno straniero che entra nel Paese con l'obiettivo di rimanervi. Il corpus è costituito dai testi trascritti dei dibattiti parlamentari relativi a otto leggi sull'immigrazione tra il 1986 e il 2019, analizzati con metodi sia quantitativi che qualitativi. Vengono prese in considerazione le collocazioni e le co-occorrenze con verbi e aggettivi, così come il linguaggio figurativo.
Effect of hypericum perforatum tea on renal histology and function
Authors: Mustafa Adil A. , Salim Moamin J. , Ahmad Khalaf N. , Ahmed Mohammed F. , Hadi Azzawi M.
Published: May 2022

Introduction:
Hypericum perforatum consists of several biologically active compounds that may affect cell physiology. Objectives: This study attempted to estimate the effect and safety of a tea that was prepared from H. perforatum on renal histology and function. Materials and Methods: A double-blind controlled experimental trial was conducted on 25 male rats. These animals were divided into four groups. Three of them were labeled as the study groups, and each consisted of seven animals. The fourth group was labeled as the control group consisting of four animals that lived in the same environment and consumed the same food as the other groups. The animals in each study group consumed a prepared tea with a different concentration for each group. The herbal tea of H. perforatum was made as recommended by the local traditional preparation method. Doses of 3, 6, and 9 cc/kg/d were calculated and selected according to the recommendation. Each of these doses was given to each group of the experiment for four weeks mixed with water. Results: A slight increase in blood urea and serum creatinine and a decrease in serum albumin levels were noticed in the experimental groups compared to the control group. In addition, the weight of the kidneys in the study groups was more than the control group. There were microscopical changes in the renal histology that was noticed in the higher doses of H. perforatum tea. Conclusion: Higher doses of H. perforatum tea can induce damage to the renal tissue.
Benefits and risks of dual inhibition of the renin– angiotensin aldosterone system for kidney disease
Authors: Nourimajalan Nader , Shajari Ahmad , Moghadasimousavi Sarasadat
Published: May 2022

A In most cases, neither angiotensin converting enzyme (ACE) inhibitor therapy nor angiotensin II receptor blockers (ARBs) therapy alone inhibits completely the renin-angiotensin aldosterone system (RAAS). The drawbacks of ACE inhibitors are the ACE escape and aldosterone escape phenomenon, which are related to the tissue construction of angiotensin II and aldosterone by enzymes besides ACE. Combination of RAAS inhibition may avoid the ACE and aldosterone escape events that increases the efficiency of ACE inhibitors and ARBs and obstruct all angiotensin II and aldosterone actions accordingly. ONTARGET, largest trial of combination against alone RAAS blockade therapy in patients with vascular diseases or diabetes along with disease of such organs displayed that combination therapy advised no extra-benefit in reducing advance to end-stage renal disease in diabetic patients and decreasing the risk of cardiovascular. Certainly, in this trial, the administration of dual RAAS blockade therapy of an ACE inhibitor plus ARB was correlated with a higher degree of side effects in comparison to monotherapy. In addition to the study of ONTARGET, the ORIENT, VALIANT, VA NEPHRON-D and HALT-PKD trials also proved this finding. Adverse events associated with combination therapy of ACE inhibitor plus ARB is including hyperkalemia, low blood pressure, acute kidney injury (AKI) and withdrawal because of side effects.
Late Quaternary palaeo-oceanography of the Denmark Strait overflow pathway, South-East Greenland margin
Authors: Kuijpers Antoon , Jensen Jørn Bo , Troelstra Simon R . , Logachev and RV Dana And shipboard scientific party of RV Professor
Published: May 2022

Direct interaction between the atmosphere and the deep ocean basins takes place today only in the Southern Ocean near the Antarctic continent and in the northern extremity of the North Atlantic Ocean, notably in the Norwegian–Greenland Sea and Labrador Sea. Cooling and evaporation cause surface waters in the latter region to become dense and sink. At depth, further mixing occurs with Arctic water masses from adjacent polar shelves. Export of these water masses from the Norwegian–Greenland Sea (Norwegian Sea Overflow Water) to the North Atlantic basin occurs via two major gateways, the Denmark Strait system and the Faeroe– Shetland Channel and Faeroe Bank Channel system (e.g. Dickson et al. 1990; Fig.1). Deep convection in the Labrador Sea produces intermediate waters (Labrador Sea Water), which spreads across the North Atlantic. Deep waters thus formed in the North Atlantic (North Atlantic Deep Water) constitute an essential component of a global ‘conveyor’ belt extending from the North Atlantic via the Southern and Indian Oceans to the Pacific. Water masses return as a (warm) surface water flow. In the North Atlantic this is the Gulf Stream and the relatively warm and saline North Atlantic Current. Numerous palaeo-oceanographic studies have indicated that climatic changes in the North Atlantic region are closely related to changes in surface circulation and in the production of North Atlantic Deep Water. Abrupt shut-down of the ocean-overturning and subsequently of the conveyor belt is believed to represent a potential explanation for rapid climate deterioration at high latitudes, such as those that caused the Quaternary ice ages. Here it should be noted, that significant changes in deep convection in Greenland waters have also recently occurred. While in the Greenland Sea deep water formation over the last decade has drastically decreased, a strong increase of deep convection has simultaneously been observed in the Labrador Sea (Sy et al. 1997).
ANTOCIANINAS EN UVA (Vitis vinifera L.) Y SU RELACIÓN CON EL COLOR
Authors: Del Valle-Leguizamón Graciela , González-León Alberto , Báez-Sañudo Reginaldo
Published: May 2022

Las antocianinas son compuestos fenólicos que se encuentran principalmente en frutos, flores y hojas de las plantas, y son las responsables de conferir los colores rojo, azul y violeta. Se sintetizan a  partir de la conversión de los precursores fenilalanina y acetato, vía el metabolismo del fenil propanoide, y se acumulan en las vacuolas de las células hipodermales. Las enzimas de la biosíntesis son reguladas a nivel de transcripción, y en uvas su punto crítico está a la altura del gen que codifica para la enzima UDP glucosa: flavonoide-3-glucosil transferasa (UFGT), lo que implica una regulación más tardía que en otras especies. Se sintetizan durante el cambio de color de la baya y son los pigmentos más importantes en las uvas coloreadas. Su estructura corresponde a heterociclos formados por la combinación de una aglicona y un azúcar. En Vitis vinifera esta se fija en la posición 3, y en otras Vitis son diglucósidos. Tienen una alta capacidad antioxidante, y han sido difíciles de estudiar debido a su inestabilidad, a pesar que la acetilación contribuye a su estabilización y son estas las que se almacenan más eficientemente en vacuolas. Su función se asocia con la coloración de la fruta y con la protección ante el estrés lumínico, como parte del sistema antioxidante. De ahí lo importante de su estudio. La concentración y perfil de antocianinas varían entre especies, cultivares, estados de madurez, condiciones estacionales, áreas de producción, prácticas culturales y niveles de rendimiento. La luminosidad y la temperatura son las principales variables ambientales que regulan síntesis de estos compuestos; la primera la estimula y las altas temperaturas parecen inhibirla. En el presente trabajo se hizo una revisión de los avances en la investigación sobre distintos aspectos de las antocianinas, tales como su naturaleza, ruta biosintética y regulación, además de los efectos que la luminosidad y la temperatura ejercen sobre ellas, en especial relación con uvas.
Research on the application of collaborative learning in the practice
teaching of garment 3D virtual fitting
Authors: CHEN LILI , ZHOU RUI , HONG YAN , LOU LIQIN
Published: May 2022

With the integration of information science into the fashion field, both industry and university expect more informatics
technology to be utilized in the fashion-related course and teaching of practical exercises. Among this informatics
technology, virtual simulation, as an important experiment tool, has become very popular support for fashion students
since it is possible to validate design ideas very efficiently and fast. However, because virtual simulation is quite
technical, and it is very difficult to gain all the essential skills about the operation of the virtual simulation software within
a short time, in the process of virtual simulation exercises, students largely rely on the guidance of teachers, which leads
to the negative impact on students’ learning motivation. To optimize the application of virtual simulation in the
fashion-related course and teaching of practical exercises, this paper proposes a teaching method based on
collaborative learning for fashion virtual simulation exercise teaching. 3D virtual fitting exercises realized by virtual
simulation were adopted as the research object to verify its effectiveness. Two groups of students were involved in the
experiments. One group was taught traditionally while another group was taught by the proposed collaborative learning.
Through a set of learning and teaching process evaluation, experiment results demonstrated that collaborative learning
will be beneficial to improving students’ learning interest, efficiency, quality and facilitate the comprehensive capacity of
autonomous learning, communication and cooperation, reduce the individual distinction and enhance self-confidence.
This paper provides support for the future application of collaborative learning in other fashion related virtual simulation
courses and exercises.