bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogenesis and Treatment of Myeloma-Related Bone Disease
Authors: Gau Yuh-Ching , Yeh Tsung-Jang , Hsu Chin-Mu , Hsiao Samuel Yien , Hsiao Hui-Hua
Published: March 2022

Multiple myeloma is a hematologic malignancy of plasma cells that causes bone-destructive lesions and associated skeletal-related events (SREs). The pathogenesis of myeloma-related bone disease (MBD) is the imbalance of the bone-remodeling process, which results from osteoclast activation, osteoblast suppression, and the immunosuppressed bone marrow microenvironment. Many important signaling cascades, including the RANKL/RANK/OPG axis, Notch signaling, the Wnt/β-Catenin signaling pathways, and signaling molecules, such as DKK-1, sclerostin, osteopontin, activin A, chemokines, and interleukins are involved and play critical roles in MBD. Currently, bisphosphonate and denosumab are the gold standard for MBD prevention and treatment. As the molecular mechanisms of MBD become increasingly well understood, novel agents are being thoroughly explored in both preclinical and clinical settings. Herein, we will provide an updated overview of the pathogenesis of MBD, summarize the clinical management and guidelines, and discuss novel bone-modifying therapies for further management of MBD.
Exosomal Carboxypeptidase E (CPE) and CPE-shRNA-Loaded Exosomes Regulate Metastatic Phenotype of Tumor Cells
Authors: Hareendran Sangeetha , Albraidy Bassam , Yang Xuyu , Liu Aiyi , Breggia Anne , Chen Clark C. , Loh Y. Peng
Published: March 2022

Background: Exosomes promote tumor growth and metastasis through intercellular communication, although the mechanism remains elusive. Carboxypeptidase E (CPE) supports the progression of different cancers, including hepatocellular carcinoma (HCC). Here, we investigated whether CPE is the bioactive cargo within exosomes, and whether it contributes to tumorigenesis, using HCC cell lines as a cancer model. Methods: Exosomes were isolated from supernatant media of cancer cells, or human sera. mRNA and protein expression were analyzed using PCR and Western blot. Low-metastatic HCC97L cells were incubated with exosomes derived from high-metastatic HCC97H cells. In other experiments, HCC97H cells were incubated with CPE-shRNA-loaded exosomes. Cell proliferation and invasion were assessed using MTT, colony formation, and matrigel invasion assays. Results: Exosomes released from cancer cells contain CPE mRNA and protein. CPE mRNA levels are enriched in exosomes secreted from high- versus low-metastastic cells, across various cancer types. In a pilot study, significantly higher CPE copy numbers were found in serum exosomes from cancer patients compared to healthy subjects. HCC97L cells, treated with exosomes derived from HCC97H cells, displayed enhanced proliferation and invasion; however, exosomes from HCC97H cells pre-treated with CPE-shRNA failed to promote proliferation. When HEK293T exosomes loaded with CPE-shRNA were incubated with HCC97H cells, the expression of CPE, Cyclin D1, a cell-cycle regulatory protein and c-myc, a proto-oncogene, were suppressed, resulting in the diminished proliferation of HCC97H cells. Conclusions: We identified CPE as an exosomal bioactive molecule driving the growth and invasion of low-metastatic HCC cells. CPE-shRNA loaded exosomes can inhibit malignant tumor cell proliferation via Cyclin D1 and c-MYC suppression. Thus, CPE is a key player in the exosome transmission of tumorigenesis, and the exosome-based delivery of CPE-shRNA offers a potential treatment for tumor progression. Notably, measuring CPE transcript levels in serum exosomes from cancer patients could have potential liquid biopsy applications.
Comprehensive Analyses of Four PtoNF-YC Genes from Populus tomentosa and Impacts on Flowering Timing
Authors: Li Juan , Gao Kai , Yang Xiaoyu , Guo Bin , Xue Yinxuan , Miao Deyu , Huang Sai , An Xinmin
Published: March 2022

Flowering is an important link in the life process of angiosperms, and it is also an important sign of the transformation of plants from vegetative to reproductive growth. Although the flowering regulation network of Arabidopsis is well-understood, there has been little research on the molecular mechanisms of perennial woody plant flower development regulation. Populus tomentosa is a unique Chinese poplar species with fast growth, strong ecological adaptability, and a long lifecycle. However, it has a long juvenile phase, which seriously affects its breeding process. Nuclear factor-Y (NF-Y) is an important type of transcription factor involved in the regulation of plant flowering. However, there are few reports on PtoNF-Y gene flowering regulation, and the members of the PtNF-YC subfamily are unknown. In this study, four key genes were cloned and analyzed for sequence characteristics, gene structure, genetic evolution, expression patterns, and subcellular localization. The plant expression vector was further constructed, and transgenic Arabidopsis and P. tomentosa plants were obtained through genetic transformation and a series of molecular tests. The flowering time and other growth characteristics were analyzed. Finally, the expression level of flowering genes was detected by quantitative PCR, the interaction between PtoNF-YC and PtoCOL proteins was measured using the yeast two-hybrid system to further explain the flowering regulation mechanism, and the molecular mechanisms by which PtNF-YC6 and PtNF-YC8 regulate poplar flowering were discussed. These results lay the foundation for elucidating the molecular regulation mechanism of PtoNF-YC in flowering and furthering the molecular design and breeding of poplar, while providing a reference for other flowering woody plants.
Automatic Fake News Detection for Romanian Online News
Authors: Buzea Marius Cristian , Trausan-Matu Stefan , Rebedea Traian
Published: March 2022

This paper proposes a supervised machine learning system to detect fake news in online sources published in Romanian. Additionally, this work presents a comparison of the obtained results by using recurrent neural networks based on long short-term memory and gated recurrent unit cells, a convolutional neural network, and a Bidirectional Encoder Representations from Transformers (BERT) model, namely RoBERT, a pre-trained Romanian BERT model. The deep learning architectures are compared with the results achieved by two classical classification algorithms: Naïve Bayes and Support Vector Machine. The proposed approach is based on a Romanian news corpus containing 25,841 true news items and 13,064 fake news items. The best result is over 98.20%, achieved by the convolutional neural network, which outperforms the standard classification methods and the BERT models. Moreover, based on irony detection and sentiment analysis systems, additional details are revealed about the irony phenomenon and sentiment analysis field which are used to tackle fake news challenges.
Delay Discounting in Gambling Disorder: Implications in Treatment Outcome
Authors: Mena-Moreno Teresa , Testa Giulia , Mestre-Bach Gemma , Miranda-Olivos Romina , Granero Rosario , Fernández-Aranda Fernando , Menchón José M. , Jiménez-Murcia Susana
Published: March 2022

Impulsive choice, measured by delay discounting (DD) tasks, has been shown in patients with gambling disorders (GD). However, the impact of DD and treatment outcome has been scarcely explored in GD patients. The aims of this study were: (1) to examine the baseline association between DD and clinical variables in GD patients depending on their age and gambling preferences (strategic vs. non-strategic); and (2) to estimate the predictive role of DD on poorer outcomes of cognitive-behavioral therapy (CBT) when considering also the effect of other clinical variables. 133 treatment-seeking male GD patients were evaluated at baseline with a DD task and measures of GD severity, personality traits and psychopathology. Treatment outcome was measured in terms of dropout from CBT and relapses. Results showed baseline associations between DD and GD severity (correlation coefficient R = 0.408 among strategic gamblers and R = 0.279 among mixed gamblers) and between DD and positive/negative urgency (R = 0.330 for the youngest patients, R = 0.244 for middle age, and around R = 0.35 for gamblers who reported preferences for strategic games). Other personality traits such as high harm avoidance and low cooperativeness were also related to DD at baseline (R = 0.606 among strategic gamblers). Regarding treatment outcome, a steeper discount rate predicted a higher risk of relapses in strategic gamblers (odds ratio OR = 3.01) and middle-age ones (OR = 1.59), and a higher risk of dropout in younger gamblers (OR = 1.89), non-strategic gamblers (OR = 1.70) and mixed gamblers (R = 4.74). GD severity mediated the associations between age, DD, personality traits and poor CBT outcome. In conclusion, impulsive choice affects treatment response in individuals with GD and may interfere with it to a significant extent. Considering DD in GD, patients seeking treatment could help control its impact on treatment adherence and relapses.
An Alternative Strategy for Screening and Confirmation of 330 Pesticides in Ground- and Surface Water Using Liquid Chromatography Tandem Mass Spectrometry
Authors: Tóth Edgár , Tölgyesi Ádám , Simon Andrea , Bálint Mária , Ma Xingmao , Sharma Virender K.
Published: March 2022

The presence of pesticide residues in water is a huge worldwide concern. In this paper we described the development and validation of a new liquid chromatography tandem mass spectrometric (LC-MS/MS) method for both screening and quantification of pesticides in water samples. In the sample preparation stage, the samples were buffered to pH 7.0 and pre-concentrated on polymeric-based cartridges via solid-phase extraction (SPE). Highly sensitive detection was carried out with mobile phases containing only 5 mM ammonium formate (pH of 6.8) as an eluent additive and using only positive ionization mode in MS/MS instrument. Hence, only 200-fold sample enrichment was required to set a screening detection limit (SDL) and reporting limit (RL) of 10 ng/L. The confirmatory method was validated at 10 and 100 ng/L spiking levels. The apparent recoveries obtained from the matrix-matched calibration (5–500 ng/L) were within the acceptable range (60–120%), also the precision (relative standard deviation, RSD) was not higher than 20%. During the development, 480 pesticides were tested and 330 compounds fulfilled the requirements of validation. The method was successfully applied to proficiency test samples to evaluate its accuracy. Moreover, the method robustness test was carried out using higher sample volume (500 mL) followed by automated SPE enrichment. Finally, the method was used to analyze 20 real samples, in which some compounds were detected around 10 ng/L, but never exceeded the assay maximum level.
Stability and Removal of Benzophenone-Type UV Filters from Water Matrices by Advanced Oxidation Processes
Authors: Imamović Belma , Trebše Polonca , Omeragić Elma , Bečić Ervina , Pečet Andrej , Dedić Mirza
Published: March 2022

Benzophenone (BP) type UV filters are common environmental contaminants that are posing a growing health concern due to their increasing presence in water. Different studies have evidenced the presence of benzophenones (BP, BP-1, BP-2, BP-3, BP-4, BP-9, HPB) in several environmental matrices, indicating that conventional technologies of water treatment are not able to remove them. It has also been reported that these compounds could be associated with endocrine-disrupting activities, genotoxicity, and reproductive toxicity. This review focuses on the degradation kinetics and mechanisms of benzophenone-type UV filters and their degradation products (DPs) under UV and solar irradiation and in UV-based advanced oxidation processes (AOPs) such as UV/H2O2, UV/persulfate, and the Fenton process. The effects of various operating parameters, such as UV irradiation including initial concentrations of H2O2, persulfate, and Fe2+, on the degradation of tested benzophenones from aqueous matrices, and conditions that allow higher degradation rates to be achieved are presented. Application of nanoparticles such as TiO2, PbO/TiO2, and Sb2O3/TiO2 for the photocatalytic degradation of benzophenone-type UV filters was included in this review.
Anthelmintic Effect of Leucaena leucocephala Extract and Its Active Compound, Mimosine, on Vital Behavioral Activities in Caenorhabditis elegans
Authors: Widaad Amal , Zulkipli Ihsan Nazurah , Petalcorin Mark I. R.
Published: March 2022

Helminth infections continue to be a neglected global threat in tropical regions, and there have been growing cases of anthelmintic resistance reported towards the existing anthelmintic drugs. Thus, the search for a novel anthelmintic agent has been increasing, especially those derived from plants. Leucaena leucocephala (LL) is a leguminous plant that is known to have several pharmacological activities, including anthelmintic activity. It is widely known to contain a toxic compound called mimosine, which we believed could be a potential lead candidate that could exert a potent anthelmintic effect. Hence, this study aimed to validate the presence of mimosine in LL extract and to investigate the anthelmintic effect of LL extract and mimosine on head thrashing, egg-laying, and pharyngeal pumping activities using the animal model Caenorhabditis elegans (C. elegans). Mimosine content in LL extract was confirmed through an HPLC analysis of spiking LL extract with different mimosine concentrations, whereby an increasing trend in peak heights was observed at a retention time of 0.9 min. LL extract and mimosine caused a significant dose-dependent increase in the percentage of worm mortality, which produced LC50s of 73 mg/mL and 6.39 mg/mL, respectively. Exposure of C. elegans to different concentrations of LL extract and mimosine significantly decreased the head thrashing, egg-laying, and mean pump amplitude of pharyngeal pumping activity. We speculated that these behavioral changes are due to the inhibitory effect of LL extract and mimosine on an L-type calcium channel called EGL-19. Our findings provide evidential support for the potential of LL extract and its active compound, mimosine, as novel anthelmintic candidates. However, the underlying mechanism of the anthelmintic action has yet to be elucidated.
Antibacterial Properties of Non-Modified Wool, Determined and Discussed in Relation to ISO 20645:2004 Standard
Authors: Ivankovic Tomislav , Rajic Antonija , Ercegovic Razic Sanja , Rolland du Roscoat Sabine , Skenderi Zenun
Published: March 2022

Wool is considered to possibly exhibit antibacterial properties due to the ability of wool clothing to reduce the build-up of odor, which arises from the microbial activity of skin microbiota. Indeed, when tested with a widely used agar diffusion plate test method, even wool or other textiles not treated with any antimicrobial agent can be interpreted to show certain antibacterial effects due to the lack of growth under the specimen, as instructed in ISO 20645:2004 standard. Therefore, we analyzed in detail what happens to bacterial cells in contact with untreated wool and cotton fabric placed on inoculated agar plates by counting viable cells attached to the specimens after 1 and 24 h of contact. All wool and several cotton samples showed no growth under the specimen. Nevertheless, it was shown without a doubt that neither textile material kills bacteria or inhibits cell multiplication. A reasonable explanation is that bacterial cells firmly attach to wool fibers forming a biofilm during multiplication. When the specimen was lifted off the nutrient agar surface, the cells in the form of biofilm remained attached to the wool fibers, removing the biomass and resulting in a clear, no growth zone underneath it. By imaging the textile specimens with X-ray microtomography, we concluded that the degree of attachment could be dependent on surface topography. The results indicate that certain textiles, in this case, wool, could exhibit antibacterial properties by removing excess bacteria that grow on the textile/skin interface when taken off the body.
Influence of Soil Salinity on Selected Element Contents in Different Brassica Species
Authors: Zeiner Michaela , Juranović Cindrić Iva , Nemet Ivan , Franjković Karla , Salopek Sondi Branka
Published: March 2022

Climate changes in coastal regions cause increased soil salinity, a well-known type of environmental stress for a high number of agricultural crop species, including Brassicaceae, whose growth and development, and consequently the crop quality and yield, are affected by salinity stress. The aim of the present study is to investigate the effect of salt stress on micro- and macro-element homeostasis in different Brassica crops. Kale (Brassica oleracea var. acephala), white cabbage (B. oleracea var. capitata) and Chinese cabbage (B. rapa ssp. pekinensis) were grown hydroponically and treated with 200 mmol/L sodium chloride for 24 h to mimic short-term salt stress. The contents of Al, Ca, K, Mg, Na, B, Ba, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sr, V and Zn were determined in the roots and leaves of the salt-treated plants and corresponding controls by inductively coupled plasma atomic emission spectrometry and inductively coupled plasma mass spectrometry. While Al, Ca, K, Mg and Na were determined in the mg/g range, the contents of the other elements were found at the µg/g level. A statistical analysis of the obtained data showed that the applied salt treatment significantly influenced the single-element contents in different plant parts. The major elements Ca, K and Mg were mainly unaffected in the more-salt-tolerant kale and white cabbage under salinity stress, while K and Mg were significantly decreased in the more-sensitive Chinese cabbage. The levels of micro-elements were found to be species/variety specific. In general, potentially toxic elements were accumulated in the roots of salt-treated plants to a higher extent than in the corresponding controls.
Microbial Transformation and Biological Activities of the Prenylated Aromatic Compounds from Broussonetia kazinoki
Authors: Choi EunA , Han Fubo , Park Jisu , Lee Ik-Soo
Published: March 2022

Broussonetia kazinoki has been used as a traditional medicine for the treatment of burns and acne, and its extracts have been found to show tyrosinase inhibitory and anticancer activities. In this study, the tyrosinase inhibitory and cytotoxic activities of B. kazinoki were explored, leading to the isolation of kazinol C (1), kazinol E (2), kazinol F (3), broussonol N (4), and kazinol X (5), of which the compounds 4 and 5 have not been previously reported. Microbial transformation has been recognized as an efficient tool to generate more active metabolites. Microbial transformation of the major compounds 1 and 3 was conducted with Mucor hiemalis, where four glucosylated metabolites (6–9) were produced from 1, while one hydroxylated (10) and one glucosylated (11) metabolites were obtained from 3. Structures of the isolated metabolites were determined by extensive spectroscopic analyses. All compounds were evaluated for their tyrosinase inhibitory and cytotoxic activities. Compound 3 and its metabolites, kazinol Y (10) and kazinol F-4″-O-β-d-glucopyranoside (11), exhibited the most potent tyrosinase inhibitory activities with the IC50 values ranging from 0.71 to 3.36 µM. Meanwhile, none of the metabolites, except for kazinol C-2′,3″-di-O-β-d-glucopyranoside (7), showed moderate cytotoxic activities (IC50 17.80 to 24.22 µM) against A375P, B16F10 and B16F1 cell lines.
Pharmacokinetics of Nafamostat, a Potent Serine Protease Inhibitor, by a Novel LC-MS/MS Analysis
Authors: Oh Hyeon Seok , Kim Taehyung , Gu Dong-Hyeon , Lee Tae Suk , Kim Tae Hwan , Shin Soyoung , Shin Beom Soo
Published: March 2022

Nafamostat, a synthetic serine protease inhibitor, has been used for the treatment of inflammatory diseases such as pancreatitis. Recently, an increasing number of studies have shown the promising antiviral effects of nafamostat for the treatment of coronavirus disease-19 (COVID-19). This study aimed to develop a novel liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis and to characterize the pharmacokinetics of nafamostat in rats. Nafamostat in the rat plasma was extracted by solid phase extraction, and 13C6-nafamostat was used as an internal standard. The quantification limit of nafamostat in the rat plasma was 0.5 ng/mL. The LC-MS/MS method was fully validated and applied to characterize the pharmacokinetics of nafamostat in rats. Following intravenous injection (2 mg/kg), nafamostat in the plasma showed a multiexponential decline with an average elimination half-life (t1/2) of 1.39 h. Following oral administration of nafamostat solutions (20 mg/kg) in 10% dimethyl sulfoxide (DMSO) and in 10% DMSO with 10% Tween 80, nafamostat was rapidly absorbed, and the average oral bioavailability was 0.95% and 1.59%, respectively. The LC-MS/MS method and the pharmacokinetic information of nafamostat could be helpful for the further preclinical and clinical studies of nafamostat.
Rapid Degradation of SARS-CoV-2 Spike S Protein by A Specific Serine Protease
Authors: Liu Jiankai , Kan Mujie , Zhang Lianzhi , Yue Yuan , Wang Shaohua , Hong Min , Hong Xinyu
Published: March 2022

The S protein of SARS-CoV-2 is a crucial structural and functional component for virus entry. Due to the constant mutation of the virus, there are very limited ways to prevent and control COVID-19. This experiment used a macroscopic SDS-PAGE method and proved that the S protein of wild-type SARS-CoV-2 virus, especially the S1 subunit, is very sensitive to alkaline serine protease with acidic pI (ASPNJ), NJ represents Neanthes japonica (Izuka) from which ASP is purified). ASPNJ cleaves proteins when the carbonyl group of the peptide bond is contributed by arginine or lysine. ASPNJ can degrade the S protein very quickly and effectively in vitro with relative selectivity. It can be inferred that the S, S1 and RBD of SARS-CoV-2 variants can also be easily degraded by ASPNJ. This rapid and strong degradation of the S protein by ASPNJ may become a potential new treatment strategy.
Changes in Antioxidant Properties and Phenolics in Sweet Potatoes (Ipomoea batatas L.) Due to Heat Treatments
Authors: Franková Hana , Musilová Janette , Árvay Július , Šnirc Marek , Jančo Ivona , Lidiková Judita , Vollmannová Alena
Published: March 2022

Processing is one of the most crucial factors affecting polyphenol content in foods. Therefore, the study is aimed at the evaluation of heat treatment effects (microwaving, steaming, baking, and boiling) on the content of chlorogenic acids, total polyphenols, and antioxidant activity of three varieties of sweet potato with different flesh colors (Beauregard—orange-fleshed, O’Henry—white-fleshed, 414-purple—purple-fleshed). According to high performance liquid chromatography analysis, chlorogenic acid was the predominant chlorogenic acid in sweet potatoes. Obtained results also suggested the purple-fleshed variety (414-purple) had significantly (p < 0.05) higher total polyphenol content and thus the highest antioxidant activity. Heat treatment positively influenced the chlorogenic acid content, total polyphenols, and antioxidant activity of sweet potatoes. Among the used methods, steaming had the greatest effect on the chlorogenic acids and total polyphenols, while microwaved samples showed the highest antioxidant activity (DPPH). The content of chlorogenic acids and total polyphenols decreased in the order of steaming > baking > microwaving > boiling > raw. However, the individual varieties differed not only in the flesh color but also in the reaction to the used heat treatment methods. Spearman’s correlation coefficient showed a strong correlation between chlorogenic acid and antioxidant activity.
Euphormins A and B, New Pyranocoumarin Derivatives from Euphorbia formosana Hayata, and Their Anti-Inflammatory Activity
Authors: Lan Yu-Hsuan , Chen I-Hsiao , Lu Hsin-Hung , Guo Ting-Jing , Hwang Tsong-Long , Leu Yann-Lii
Published: March 2022

Euphormin-A (1) and euphormin-B (2), two new pyranocoumarin derivatives, and forty known compounds (3–42) were isolated from Euphorbia formosana Hayata (Euphorbiaceae). The chemical structures of all compounds were established based on spectroscopic analyses. Several isolates were evaluated for their anti-inflammatory activity. Compounds 1, 2, 10, 18, 25, and 33 significantly inhibited against superoxide anion generation and elastase release by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). Furthermore, compounds 25 and 33 displayed the most potent effects with IC50 values of 0.68 ± 0.18 and 1.39 ± 0.12 µM, respectively, against superoxide anion generation when compared with the positive control (2.01 ± 0.06 µM).
Synthesis and Structure Elucidation of Two Essential Metal Complexes: In-Vitro Studies of Their BSA/HSA-Binding Properties, Docking Simulations, and Anticancer Activities
Authors: Guo Jun-Li , Liu Guang-Yu , Wang Rui-Ying , Sun Shu-Xiang
Published: March 2022

Imidazole and tetrazole derivatives are widely used as clinical drugs since they possess a variety of pharmaceutical function. Zinc and iron are essential trace elements of the human body, with less toxicity and good biocompatibility. In this paper, two new essential metal mononuclear complexes [M(H2tmidc)2(H2O)2]·2H2O (M = Zn (1), Fe (2)) were synthesized through the reaction of 2-((1H-tetrazol-1-yl)methylene)-1H-imidazole-4,5-dicarboxylic acid (H3tmidc) and ZnSO4·7H2O or FeSO4·7H2O. The crystal structures were determined by means of the X-ray single crystal diffraction technique. Results from fluorescence investigations show that both complexes could interact with BSA as well as HSA through the static quenching mechanism. van der Waals forces and hydrogen bonds play important roles in the interaction of complexes and BSA/HSA since both ΔH and ΔS values are negative. The results of molecular docking are consistent with those in experimental studies. Furthermore, the anticancer activity of H3tmidc and both complexes against Eca-109 were preliminarily evaluated and the results show that both complexes have better anticancer activity than the corresponding ligand H3tmidc.
Validation of a Microwave-Assisted Derivatization Gas Chromatography-Mass Spectrometry Method for the Quantification of 2-Hydroxybutyrate in Human Serum as an Early Marker of Diabetes Mellitus
Authors: Rodríguez-García María , Fernández-Varo Guillermo , Hidalgo Susana , Rodríguez Gabriela , Martínez Irene , Zeng Muling , Casals Eudald , Morales-Ruiz Manuel , Casals Gregori
Published: March 2022

Circulating levels of 2-hydroxybutyrate (2HB) are highly related to glycemic status in different metabolomic studies. According to recent evidence, 2HB is an early biomarker of the future development of dysglycemia and type 2 diabetes mellitus and may be causally related to the progression of normal subjects to impaired fasting glucose or insulin resistance. In the present study, we developed and validated a simple, specific and sensitive gas chromatography-mass spectrometry (GC-MS) method specifically intended to quantify serum levels of 2HB. Liquid–liquid extraction with ethyl acetate was followed by 2 min of microwave-assisted derivatization. The method presented acceptable accuracy, precision and recovery, and the limit of quantification was 5 µM. Levels of 2HB were found to be stable in serum after three freeze-thaw cycles, and at ambient temperature and at a temperature of 4 °C for up to 24 h. Extracts derivatized under microwave irradiation were stable for up to 96 h. No differences were found in 2HB concentrations measured in serum or plasma EDTA samples. In summary, the method is useful for a rapid, precise and accurate quantification of 2HB in serum samples assessed for the evaluation of dysglycemia and diabetes mellitus.
Photothermally-Heated Superparamagnetic Polymeric Nanocomposite Implants for Interstitial Thermotherapy
Authors: Yeboah Ivan B. , Hatekah Selassie W. K. , Yaya Abu , Kan-Dapaah Kwabena
Published: March 2022

Photothermally-heated polymer-based superparamagnetic nanocomposite (SNC) implants have the potential to overcome limitations of the conventional inductively-heated ferromagnetic metallic alloy implants for interstitial thermotherapy (IT). This paper presents an assessment of a model SNC—poly-dimethylsiloxane (PDMS) and Fe3O4 nanoparticles (MNP)—implant for IT. First, we performed structural and optical characterization of the commercially purchased MNPs, which were added to the PDMS to prepare the SNCs (MNP weight fraction =10 wt.%) that were used to fabricate cubic implants. We studied the structural properties of SNC and characterized the photothermal heating capabilities of the implants in three different media: aqueous solution, cell (in-vitro) suspensions and agarose gel. Our results showed that the spherical MNPs, whose optical absorbance increased with concentration, were uniformly distributed within the SNC with no new bond formed with the PDMS matrix and the SNC implants generated photothermal heat that increased the temperature of deionized water to different levels at different rates, decreased the viability of MDA-MB-231 cells and regulated the lesion size in agarose gel as a function of laser power only, laser power or exposure time and the number of implants, respectively. We discussed the opportunities it offers for the development of a smart and efficient strategy that can enhance the efficacy of conventional interstitial thermotherapy. Collectively, this proof-of-concept study shows the feasibility of a photothermally-heated polymer-based SNC implant technique.
Nanomaterials for Membranes, Membrane Reactors, and Catalyst Systems
Authors: Nechifor Gheorghe
Published: March 2022

Membranes are selective and highly productive nanostructures dedicated to developing separation, concentration, and purification processes with uses in the most diverse economic and social fields: industry, agriculture, transport, environment, health, and space exploration [...]
Relationship of Diet to Gut Microbiota and Inflammatory Biomarkers in People with HIV
Authors: Manzano Mónica , Talavera-Rodríguez Alba , Moreno Elena , Madrid Nadia , Gosalbes María José , Ron Raquel , Dronda Fernando , Pérez-Molina José A. , Lanza Val F. , Díaz Jorge , Moreno Santiago , Navia Beatriz , Serrano-Villar Sergio
Published: March 2022

While changes in microbiome composition have been associated with HIV, the effect of diet and its potential impact on inflammation remains unclear. Methods: Twenty-seven people living with HIV (PWH) on antiretroviral therapy (ART) were studied. A comprehensive dietary analysis was performed and two types of dietary patterns were determined. We explored the associations of each dietary pattern with gut microbiota and plasma inflammatory biomarkers. Results: We appreciated two dietary patterns, Mediterranean-like (MEL) and one Western-like (WEL). Compared to participants with the WEL pattern, participants with MEL pattern showed higher abundance of Lachnospira (p-value = 0.02) and lower levels of the inflammatory biomarkers D-dimer (p-value = 0.050) and soluble TNF-alpha receptor 2 (sTNFR2) (p-value = 0.049). Men who have sex with men (MSM) with MEL pattern had lower abundance of Erysipelotrichaceae (p-value < 0.001) and lower levels of D-dimer (p-value = 0.026) than MSM with WEL pattern. Conclusion: MEL pattern favours Lachnospira abundance, and protects against Erysipelotrichaceae abundance and higher levels of the inflammatory biomarkers D-dimer and sTNFR2, precursors of inflammatory processes in HIV-infected patients. Our study contributes to understanding the determinants of a healthier diet and its connections with gut microbiota and inflammation.
Effect of Gestational Diabetes on Postpartum Depression-like Behavior in Rats and Its Mechanism
Authors: Zhao Runlong , Zhou Yalin , Shi Hanxu , Ye Wanyun , Lyu Ying , Wen Zhang , Li Rui , Xu Yajun
Published: March 2022

Recent studies have reported a strong association between gestational diabetes mellitus (GDM) and postpartum depression (PPD), but little is known about the underlying physiological mechanism. In this study, a GDM rat model was used to evaluate the direct effect of GDM on PPD and to explore the mechanism. After parturition, the GDM dams were divided into two groups: blood glucose not recovered group (GH group) and blood glucose recovered group (GL group). Fasting plasma glucose (FPG), cortisol (COR) and serotonin (5-hydroxytryptamine, 5-HT) metabolism were continuously monitored during the lactation period, until postnatal day 21. PPD was evaluated by behavioral tests. At the endpoint, the expression of the key enzymes of Trp metabolic pathway in colon and brain tissues was analyzed by immunohistochemistry and western blot. The microbe composition of colonic contents was determined by 16S rDNA gene sequencing. The results showed that GDM induced postpartum depression-like behavior in rats. The HPA axis hormone did not show the typical stress state of depression, but the level of 5-HT decreased significantly in serum, prefrontal cortex and hippocampus, and the Kyn/Trp ratio increased significantly in serum and prefrontal cortex, implying the switch of the tryptophan (Trp) metabolism from the 5-HT pathway to the kynurenine (Kyn) pathway. The expression of Indoleamine 2,3-dioxygenase (IDO), a key rate-limiting enzyme in Kyn metabolism, was up-regulated in the colon and brain, which was an important reason for this switch. This switch was accelerated by a decrease in the expression of tryptophan hydroxylase (TPH), a key enzyme of the 5-HT production pathway, in the colon. GDM dams displayed significant changes in gut microbiome profiles, which were correlated with depression. The ratio of Firmicutes to Bacteroidetes decreased. Lactobacillus and Bacteroides were negatively correlated with 5-HT level and positively correlated with Kyn level, whereas Clostridium XlVa and Ruminococcus were positively correlated with 5-HT level. These results suggest that GDM disrupts both the Trp pathway and the composition of the gut microbiota, which provide a putative physiological basis for PPD.
Goji Berry: Health Promoting Properties
Authors: Skenderidis Prodromos , Leontopoulos Stefanos , Lampakis Dimitrios
Published: March 2022

Since ancient times, it has been noticed that Goji berry fruit juice, roots and leaves consist of ingredients that contain a wide variety of bioactive substances. The consumption of goji berry fruits results in properties which improve the subjective feeling of general well-being. The aim of this work is to present the information from the existing literature on the possible role of goji berry plant parts and their extracts as a functional food. Lycium barbarum Polysaccharides (LBP) and polyphenols are the most researched aspects of fruits associated with the promotion of human health. Goji berry fruits demonstrated anti-oxidative properties that are associated with age-related diseases such as diabetes, atherosclerosis and antitumor and immunoregulatory activities. Bioactive secondary metabolites contained in fruit lead to positive effects for human vision, while other biochemicals contained in the root bark have shown hepatoprotective and inhibitory actions on the rennin/angiotensin system. The results presented so far in the literature verify their use in traditional medicine.
Expression of the Nonclassical MHC Class I, Saha-UD in the Transmissible Cancer Devil Facial Tumour Disease (DFTD)
Authors: Hussey Kathryn , Caldwell Alison , Kreiss Alexandre , Skjødt Karsten , Gastaldello Annalisa , Pye Ruth , Hamede Rodrigo , Woods Gregory M. , Siddle Hannah V.
Published: March 2022

Devil facial tumour disease (DFTD) is a transmissible cancer that has circulated in the Tasmanian devil population for >25 years. Like other contagious cancers in dogs and devils, the way DFTD escapes the immune response of its host is a central question to understanding this disease. DFTD has a low major histocompatibility complex class I (MHC-I) expression due to epigenetic modifications, preventing host immune recognition of mismatched MHC-I molecules by T cells. However, the total MHC-I loss should result in natural killer (NK) cell activation due to the ‘missing self’. Here, we have investigated the expression of the nonclassical MHC-I, Saha-UD as a potential regulatory or suppressive mechanism for DFTD. A monoclonal antibody was generated against the devil Saha-UD that binds recombinant Saha-UD by Western blot, with limited crossreactivity to the classical MHC-I, Saha-UC and nonclassical Saha-UK. Using this antibody, we confirmed the expression of Saha-UD in 13 DFTD tumours by immunohistochemistry (n = 15) and demonstrated that Saha-UD expression is heterogeneous, with 12 tumours showing intratumour heterogeneity. Immunohistochemical staining for the Saha-UD showed distinct patterns of expression when compared with classical MHC-I molecules. The nonclassical Saha-UD expression by DFTD tumours in vivo may be a mechanism for immunosuppression, and further work is ongoing to characterise its ligand on immune cells.
Poly (Lactic-Co-Glycolic) Acid–Poly (Vinyl Pyrrolidone) Hybrid Nanoparticles to Improve the Efficiency of Oral Delivery of β-Carotene
Authors: Liu Wan-Yi , Hsieh Yun-Shan , Wu Yu-Tse
Published: March 2022

The aim of this study was to develop a nanoparticle formulation made of poly (vinyl pyrrolidone) (PVP) and poly (lactic-co-glycolic) acid (PLGA) for the oral delivery of β-carotene (BC). The hybrid nanoparticles were prepared by the interfacial deposition method, and the physicochemical properties of this formulation were characterized in terms of its morphology, particle size, size distribution, encapsulation efficiency, dissolution, intestinal permeability, and in vivo pharmacokinetics. Our results demonstrated that BC-loaded nanoformulation and PLGA nanoparticles (PNP) significantly enhanced a release 6.1 times higher than BC suspension. The fortification of PVP into PLGA nanoparticles, named PLGA–PVP hybrid nanoparticles (PPNP), significantly reduced the particle size, as well as led to an increase 1.9 times higher in the in vitro release of BC, compared with PNP. For the ex vivo intestinal permeability assessment, PNP and PPNP–K15 significantly enhanced the intestinal permeability by 2.7 and 6.5 times at the jejunum, and 2.3 and 4.5 times at the ileum, when compared with unformulated BC. According to the pharmacokinetic study, the optimized hybrid formulation significantly increased the peak plasma concentration (Cmax) and the area under the curve (AUC0-t), and the oral relative bioavailability showed a five-fold enhancement compared with that of the BC suspension. Our results indicate that the hybrid nanoparticulate delivery system is an efficient strategy for the oral delivery of BC.
Embedding a Sensitive Liquid-Core Waveguide UV Detector into an HPLC-UV System for Simultaneous Quantification of Differently Dosed Active Ingredients during Drug Release
Authors: Chamberlain Rebecca , Windolf Hellen , Burckhardt Bjoern B. , Breitkreutz Jörg , Fischer Björn
Published: March 2022

Individual dosing of pharmaceutics and personalized medicine have become important with regard to therapeutic safety. Dose adjustments, biorelevant drug release and combination of multiple active substances in one dosage form for the reduction in polymedication are essential aspects that increase the safety and acceptance of the patient’s pharmacotherapy. Therefore, not only innovative drug products but also new analytical methods are needed during the drug development phase and for quality control that can simultaneously determine different active ingredients and cover wide concentration ranges. We investigated a liquid-core waveguide UV absorbance flow cell detector coupled to an existing HPLC-UV system. A Teflon AF 2400 capillary tubing of 20 cm length was connected in series to the HPLC flow line and enabled a lower limit of quantification of 1 ng/mL pramipexole (increase in sensitivity by 20 compared to common 0.9 cm flow cells). This allowed the low-concentration of pramipexole and the higher concentrations of levodopa and benserazide occurring during drug release to be determined in a single chromatographic run within 22.5 min.
Inhaled Antifungal Agents for Treatment and Prophylaxis of Bronchopulmonary Invasive Mold Infections
Authors: Brunet Kévin , Martellosio Jean-Philippe , Tewes Frédéric , Marchand Sandrine , Rammaert Blandine
Published: March 2022

Pulmonary mold infections are life-threatening diseases with high morbi-mortalities. Treatment is based on systemic antifungal agents belonging to the families of polyenes (amphotericin B) and triazoles. Despite this treatment, mortality remains high and the doses of systemic antifungals cannot be increased as they often lead to toxicity. The pulmonary aerosolization of antifungal agents can theoretically increase their concentration at the infectious site, which could improve their efficacy while limiting their systemic exposure and toxicity. However, clinical experience is poor and thus inhaled agent utilization remains unclear in term of indications, drugs, and devices. This comprehensive literature review aims to describe the pharmacokinetic behavior and the efficacy of inhaled antifungal drugs as prophylaxes and curative treatments both in animal models and humans.
Care Ethics, Bruno Latour, and the Anthropocene
Authors: Flower Michael , Hamington Maurice
Published: March 2022

Bruno Latour is one of the founding figures in social network theory and a broadly influential systems thinker. Although his work has always been relational, little scholarship has engaged the relational morality, ontology, and epistemology of feminist care ethics with Latour’s actor–network theory. This article is intended as a translation and a prompt to spur further interactions. Latour’s recent publications, in particular, have focused on the new climate regime of the Anthropocene. Care theorists are just beginning to address posthuman approaches to care. The argument here is that Latourian analysis is helpful for such explorations, given that caring for the earth and its inhabitants is the dire moral challenge of our time. The aim here is not to characterize Latour as a care theorist but rather as a provocative scholar who has much to say that is significant to care thinking. We begin with a brief introduction to Latour’s scholarship and lexicon, followed by a discussion of care theorist Puig de la Bellacasa’s work on Latour. We then explore recent work on care and the environment consistent with a Latourian approach. The conclusion reinforces the notion that valuing relationality across humans and non-human matter is essential to confronting the Anthropocene.
ADMM-SVNet: An ADMM-Based Sparse-View CT Reconstruction Network
Authors: Wang Sukai , Li Xuan , Chen Ping
Published: March 2022

In clinical medical applications, sparse-view computed tomography (CT) imaging is an effective method for reducing radiation doses. The iterative reconstruction method is usually adopted for sparse-view CT. In the process of optimizing the iterative model, the approach of directly solving the quadratic penalty function of the objective function can be expected to perform poorly. Compared with the direct solution method, the alternating direction method of multipliers (ADMM) algorithm can avoid the ill-posed problem associated with the quadratic penalty function. However, the regularization items, sparsity transform, and parameters in the traditional ADMM iterative model need to be manually adjusted. In this paper, we propose a data-driven ADMM reconstruction method that can automatically optimize the above terms that are difficult to choose within an iterative framework. The main contribution of this paper is that a modified U-net represents the sparse transformation, and the prior information and related parameters are automatically trained by the network. Based on a comparison with other state-of-the-art reconstruction algorithms, the qualitative and quantitative results show the effectiveness of our method for sparse-view CT image reconstruction. The experimental results show that the proposed method performs well in streak artifact elimination and detail structure preservation. The proposed network can deal with a wide range of noise levels and has exceptional performance in low-dose reconstruction tasks.
Light Microscopy of Medium-Density Rigid Polyurethane Foams Filled with Nanoclay
Authors: Beverte Ilze , Cabulis Ugis , Andersons Janis , Kirpluks Mikelis , Skruls Vilis , Cabulis Peteris
Published: March 2022

Practical applications and mathematical modelling of the physical and mechanical properties of medium-density rigid polyurethane foams require knowledge of their structure. It is necessary to determine structural characteristics without destroying the foams and measuring each element. A methodology is described for the use of light microscopy on environmentally sustainable, medium-density rigid polyurethane foams (in the density region of ≈210–230 kg/m3), by the analysis of two types of light microscopy images: (1) Cutting surface images; and (2) Through-cutting surface images. The dimensions of structural elements of polyurethane foams, filled with the nanoclay Cloisite-30B at concentrations of 0.0%, 0.25%, 0.50%, 1.0%, 2.0%, 3.0%, and 5.0% from the mass of the filled reacting mixture, are estimated. Probability density functions of projections of bubbles’ diameters and struts’ length are determined using images in three mutually perpendicular planes. A mathematical model is developed for the restoration of the actual dimensions of bubbles’ diameters using data of cutting circles’ diameters. Intercalation and exfoliation of the filler’s Cloisite-30B mono-layers is evaluated via the basal spacing by X-ray diffraction at a 5 wt.% concentration of nanoclay.
Influence of Filament Winding Tension on the Deformation of Composite Flywheel Rotors with H-Shaped Hubs
Authors: Chen Xiaodong , Li Yong , Huan Dajun , Liu Hongquan , Li Lisa , Li Yanrui
Published: March 2022

The residual stress plays an important role in composite flywheel rotors composed of filament windings. The fiber tension during high-prestressed winding is the main source of the rotor deformation and residual stress of composite layers. In this study, the effect of the winding tension gradient on deformation was monitored in real-time. Two types of in-plane winding tension fluctuation methods were developed to investigate the effect of tension on deformation. Online and offline measurements were performed for the strain acquisition. A wireless strain instrument was used for online deformation monitoring and a laser scanner was used for the offline surface reconstruction. Additionally, different filament winding strategies were carried out to improve the efficiency of the winding tension by finite element analysis. The results indicated that the deviation between numerical and experimental results was within 8%. Based on the proposed numerical method, the influence of the in-plane and out-of-plane winding tension gradient distributions on the rotation process of the H-shaped rotor was analyzed. An in-plane winding strategy with variable tension was developed, which increased the initial failure speed by 160%.