The 2023 MDPI Annual Report has
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18 pages, 1840 KiB  
Article
Correlations of the CNR1 Gene with Personality Traits in Women with Alcohol Use Disorder
by Filip Maciocha, Aleksandra Suchanecka, Krzysztof Chmielowiec, Jolanta Chmielowiec, Andrzej Ciechanowicz and Agnieszka Boroń
Int. J. Mol. Sci. 2024, 25(10), 5174; https://doi.org/10.3390/ijms25105174 (registering DOI) - 9 May 2024
Abstract
Alcohol use disorder (AUD) is a significant issue affecting women, with severe consequences for society, the economy, and most importantly, health. Both personality and alcohol use disorders are phenotypically very complex, and elucidating their shared heritability is a challenge for medical genetics. Therefore, [...] Read more.
Alcohol use disorder (AUD) is a significant issue affecting women, with severe consequences for society, the economy, and most importantly, health. Both personality and alcohol use disorders are phenotypically very complex, and elucidating their shared heritability is a challenge for medical genetics. Therefore, our study investigated the correlations between the microsatellite polymorphism (AAT)n of the Cannabinoid Receptor 1 (CNR1) gene and personality traits in women with AUD. The study group included 187 female subjects. Of these, 93 were diagnosed with alcohol use disorder, and 94 were controls. Repeat length polymorphism of microsatellite regions (AAT)n in the CNR1 gene was identified with PCR. All participants were assessed with the Mini-International Neuropsychiatric Interview and completed the NEO Five-Factor and State-Trait Anxiety Inventories. In the group of AUD subjects, significantly fewer (AAT)n repeats were present when compared with controls (p = 0.0380). While comparing the alcohol use disorder subjects (AUD) and the controls, we observed significantly higher scores on the STAI trait (p < 0.00001) and state scales (p = 0.0001) and on the NEO Five-Factor Inventory Neuroticism (p < 0.00001) and Openness (p = 0.0237; insignificant after Bonferroni correction) scales. Significantly lower results were obtained on the NEO-FFI Extraversion (p = 0.00003), Agreeability (p < 0.00001) and Conscientiousness (p < 0.00001) scales by the AUD subjects when compared to controls. There was no statistically significant Pearson’s linear correlation between the number of (AAT)n repeats in the CNR1 gene and the STAI and NEO Five-Factor Inventory scores in the group of AUD subjects. In contrast, Pearson’s linear correlation analysis in controls showed a positive correlation between the number of the (AAT)n repeats and the STAI state scale (r = 0.184; p = 0.011; insignificant after Bonferroni correction) and a negative correlation with the NEO-FFI Openness scale (r = −0.241; p = 0.001). Interestingly, our study provided data on two separate complex issues, i.e., (1) the association of (AAT)n CNR1 repeats with the AUD in females; (2) the correlation of (AAT)n CNR1 repeats with anxiety as a state and Openness in non-alcohol dependent subjects. In conclusion, our study provided a plethora of valuable data for improving our understanding of alcohol use disorder and anxiety. Full article
(This article belongs to the Section Molecular Biology)
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20 pages, 4578 KiB  
Article
Distinctiveness of Femoral and Acetabular Mesenchymal Stem and Progenitor Populations in Patients with Primary and Secondary Hip Osteoarthritis Due to Developmental Dysplasia
by Mihovil Plečko, Nataša Kovačić, Danka Grčević, Alan Šućur, Andreja Vukasović Barišić, Tea Duvančić, Ivan Bohaček and Domagoj Delimar
Int. J. Mol. Sci. 2024, 25(10), 5173; https://doi.org/10.3390/ijms25105173 (registering DOI) - 9 May 2024
Abstract
Primary hip osteoarthritis (pOA) develops without an apparent underlying reason, whereas secondary osteoarthritis arises due to a known cause, such as developmental dysplasia of the hips (DDH-OA). DDH-OA patients undergo total hip arthroplasty at a much younger age than pOA patients (50.58 vs. [...] Read more.
Primary hip osteoarthritis (pOA) develops without an apparent underlying reason, whereas secondary osteoarthritis arises due to a known cause, such as developmental dysplasia of the hips (DDH-OA). DDH-OA patients undergo total hip arthroplasty at a much younger age than pOA patients (50.58 vs. 65 years in this study). Recently, mesenchymal stem and progenitor cells (MSPCs) have been investigated for the treatment of osteoarthritis due to their immunomodulatory and regenerative potential. This study identified cells in subchondral bone expressing common MSPC markers (CD10, CD73, CD140b, CD146, CD164, CD271, GD2, PDPN) in vivo and compared the proportions of these populations in pOA vs. DDH-OA, further correlating them with clinical, demographic, and morphological characteristics. The differences in subchondral morphology and proportions of non-hematopoietic cells expressing MSPC markers were noted depending on OA type and skeletal location. Bone sclerosis was more prominent in the pOA acetabulum (Ac) in comparison to the DDH-OA Ac and in the pOA Ac compared to the pOA femoral head (Fh). Immunophenotyping indicated diagnosis-specific differences, such as a higher proportion of CD164+ cells and their subsets in DDH-OA, while pOA contained a significantly higher proportion of CD10+ and GD2+ cells and subsets, with CD271+ being marginally higher. Location-specific differences showed that CD271+ cells were more abundant in the Fh compared to the Ac in DDH-OA patients. Furthermore, immunohistochemical characterization of stromal bone-adjacent cells expressing MSPC markers (CD10, CD164, CD271, GD2) in the Ac and Fh compartments was performed. This research proved that immunophenotype profiles and morphological changes are both location- and disease-specific. Furthermore, it provided potentially effective targets for therapeutic strategies. Future research should analyze the differentiation potential of subsets identified in this study. After proper characterization, they can be selectively targeted, thus enhancing personalized medicine approaches in joint disease management. Full article
(This article belongs to the Special Issue Osteoarthritis: From Molecular Mechanism to Novel Therapy)
13 pages, 564 KiB  
Article
Asymmetric Exchange Rate Effects on Trade Flows in India
by Niloufer Sohrabji
Economies 2024, 12(5), 114; https://doi.org/10.3390/economies12050114 (registering DOI) - 9 May 2024
Abstract
This paper examines the role of exchange rate changes on India’s trade. The drivers of exports and imports (income, exchange rate including sectoral differences, and exchange rate variability) are estimated for the short and long run including a structural break. Using annual data [...] Read more.
This paper examines the role of exchange rate changes on India’s trade. The drivers of exports and imports (income, exchange rate including sectoral differences, and exchange rate variability) are estimated for the short and long run including a structural break. Using annual data from 1994 to 2022, the results of dynamic fixed effects estimation show that both exports and imports are income-elastic in the short and long run, but income elasticity is far stronger for exports. Moreover, exports are responsive to the real effective exchange rate in the short run but not in the long run, and the reverse is true for imports. Furthermore, exchange rates have asymmetric effects for high-volume and primary sectors for exports and imports. The combined impacts show the ineffectiveness of using currency depreciation to address trade imbalances. Full article
(This article belongs to the Special Issue Exchange Rates: Drivers, Dynamics, Impacts, and Policies)
12 pages, 270 KiB  
Article
Kernel-Based Multivariate Nonparametric CUSUM Multi-Chart for Detection of Abrupt Changes
by Lei Qiao and Bing Wang
Mathematics 2024, 12(10), 1473; https://doi.org/10.3390/math12101473 (registering DOI) - 9 May 2024
Abstract
In many cases, it is difficult to obtain precise distributional information on multivariate sequences. Therefore, there is a need to propose nonparametric methods for monitoring multivariate sequences. This article discusses the multivariate change detection problem and utilizes the kernel function as the statistic [...] Read more.
In many cases, it is difficult to obtain precise distributional information on multivariate sequences. Therefore, there is a need to propose nonparametric methods for monitoring multivariate sequences. This article discusses the multivariate change detection problem and utilizes the kernel function as the statistic to construct the nonparametric Multivariate Cumulative Sum multi-chart, under the assumption that there is prior information about the abrupt changes. Through theoretical and numerical analysis, we show that the proposed control chart is more effective compared to other existing control charts. The good monitoring effect of this method demonstrates a strong potential for application. Full article
(This article belongs to the Special Issue Advances in Statistical Process Monitoring and Wavelet Analysis)
18 pages, 1604 KiB  
Article
Enhancing Carbon Fiber Fabrics with ALD AlxOy Coatings: An Investigation of Thickness Effects on Weight, Morphology, Coloration, and Thermal Properties
by Vanessa Dias, Nierlly Galvão, Felipe Miranda, Mariana Fraga, Gilberto Petraconi, Homero Maciel and Rodrigo Pessoa
Coatings 2024, 14(5), 596; https://doi.org/10.3390/coatings14050596 (registering DOI) - 9 May 2024
Abstract
This study explores the impact of non-stoichiometric aluminum oxide (AlxOy) coatings applied via thermal atomic layer deposition (ALD) on carbon fiber fabrics (CFFs), emphasizing volume per cycle, FESEM analyses, color transitions, and thermal stability enhancements. Using trimethylaluminum and water [...] Read more.
This study explores the impact of non-stoichiometric aluminum oxide (AlxOy) coatings applied via thermal atomic layer deposition (ALD) on carbon fiber fabrics (CFFs), emphasizing volume per cycle, FESEM analyses, color transitions, and thermal stability enhancements. Using trimethylaluminum and water at 100 °C, AlxOy was deposited across a range of 1000 to 5000 ALD cycles, with film thicknesses extending up to 500 nm. This notable increase in the volume of material deposited per cycle was observed for the 3D CFFs, highlighting ALD’s capability to coat complex structures effectively. FESEM analyses revealed the morphological evolution of CFF surfaces post-coating, showing a transition from individual grains to a dense, continuous layer as ALD cycles increased. This morphological transformation led to significant color shifts from green to red to blue, attributed to structural coloration effects arising from variations in film thickness and surface morphology. Thermogravimetric analyses (TGA and dTG) indicated that the AlxOy coatings enhanced the thermal stability of CFFs, with a postponement in degradation onset observed in samples subjected to more ALD cycles. In essence, this research highlights the nuanced relationship between ALD processing parameters and their collective influence on both the aesthetic and functional properties of CFFs. This study illustrates ALD’s potential in customizing CFFs for applications requiring specific color and thermal resilience, balancing the discussion between the surface morphological changes and their implications for color and thermal behavior. Full article
(This article belongs to the Section Thin Films)
18 pages, 696 KiB  
Article
Development of the Food Acceptance Questionnaire for Thai Partial and Complete Edentulism
by Ketsupha Suwanarpa, Yoko Hasegawa, Jarin Paphangkorakit, Waranuch Pitiphat, Kazuhiro Hori and Takahiro Ono
Nutrients 2024, 16(10), 1432; https://doi.org/10.3390/nu16101432 (registering DOI) - 9 May 2024
Abstract
This study aimed to develop the Food Acceptance Questionnaire (FAQ) to assess the masticatory ability of Thai older adults (≥60 years). Fifty participants were interviewed using open-ended questions about food they regularly consumed and avoided due to difficulty chewing. From a list of [...] Read more.
This study aimed to develop the Food Acceptance Questionnaire (FAQ) to assess the masticatory ability of Thai older adults (≥60 years). Fifty participants were interviewed using open-ended questions about food they regularly consumed and avoided due to difficulty chewing. From a list of 140 items, 100 were recruited for a trial version of the FAQ. A total of 154 participants responded to the 5-point Likert scale on their chewing perception of each food item (1, impossible to chew; 5, most easily eaten). The average response of each food item was used as the chewing index (CI). The 100 food items were ranked and divided into five grades based on their CIs. Masticatory performance (MP) was objectively assessed by a visual scoring method using gummy jelly (UHA Mikakuto). Two foods from each grade that demonstrated the highest correlation with MP were selected to form the final 10-item FAQ. The FAQ score was calculated by summarizing the responses of 10 items. MP correlated strongly with the FAQ score (r = 0.57, p < 0.001), indicating its predictive validity. Furthermore, the FAQ indicates strong internal consistency (Cronbach’s alpha coefficient = 0.90), indicating high reliability. In conclusion, this newly developed 10-item FAQ is valid and reliable for assessing the masticatory ability of Thai older adults. Full article
16 pages, 1783 KiB  
Article
Efficient Removal of Water Soluble Fraction of Diesel Oil by Biochar Sorption Supported by Microbiological Degradation
by Zorica R. Lopičić, Tatjana D. Šoštarić, Jelena V. Milojković, Anja V. Antanasković, Jelena S. Milić, Snežana D. Spasić and Jelena S. Avdalović
Processes 2024, 12(5), 964; https://doi.org/10.3390/pr12050964 (registering DOI) - 9 May 2024
Abstract
The contamination of the water bodies by diesel oil (DO) and its water-soluble fraction (WSF) represents one of the most challenging tasks in the management of polluted water streams. This paper contains data related to the synthesis and characteristics of the plum stone [...] Read more.
The contamination of the water bodies by diesel oil (DO) and its water-soluble fraction (WSF) represents one of the most challenging tasks in the management of polluted water streams. This paper contains data related to the synthesis and characteristics of the plum stone biochar material (PmS-B), which was made from waste plum stones (PmS), along with its possible application in the sorption of the WSF of DO from contaminated water. Techniques applied in sample characterisation and comparisons were: Elemental Organic Analysis (EOA), Scanning Electron Microscopy−Energy Dispersive X-ray Spectroscopy (SEM-EDX), Fourier Transform Infrared Spectroscopy (FTIR), pH (pHsus) and point of zero charge (pHpzc). In order to increase the overall efficiency of the removal process, sorption and bioremediation were subsequently combined. Firstly, PmS-B was used as a sorbent of WSF, and then the remaining solution was additionally treated with a specific consortium of microorganisms. After the first treatment phase, the initial concentration of diesel WSF was reduced by more than 90%, where most of the aromatic components of DO were removed by sorption. The sorption equilibrium results were best fitted by the Sips isotherm model, where the maximum sorption capacity was found to be 40.72 mg/g. The rest of the hydrocarbon components that remained in the solution were further subjected to the biodegradation process by a consortium of microorganisms. Microbial degradation lasted 19 days and reduced the total diesel WSF concentration to 0.46 mg/L. In order to confirm the non-toxicity of the water sample after this two-stage treatment, eco-toxicity tests based on a microbial biosensor (Aliivibrio fischeri) were applied, confirming the high efficiency of the proposed method. Full article
(This article belongs to the Special Issue Thermochemical Conversion of Agricultural and Food Processing Waste)
26 pages, 3758 KiB  
Article
Unveiling a Microexon Switch: Novel Regulation of the Activities of Sugar Assimilation and Plant-Cell-Wall-Degrading Xylanses and Cellulases by Xlr2 in Trichoderma virens
by Cynthia Coccet Castañeda-Casasola, María Fernanda Nieto-Jacobo, Amanda Soares, Emir Alejandro Padilla-Padilla, Miguel Angel Anducho-Reyes, Chris Brown, Sereyboth Soth, Edgardo Ulises Esquivel-Naranjo, John Hampton and Artemio Mendoza-Mendoza
Int. J. Mol. Sci. 2024, 25(10), 5172; https://doi.org/10.3390/ijms25105172 (registering DOI) - 9 May 2024
Abstract
Functional microexons have not previously been described in filamentous fungi. Here, we describe a novel mechanism of transcriptional regulation in Trichoderma requiring the inclusion of a microexon from the Xlr2 gene. In low-glucose environments, a long mRNA including the microexon encodes a protein [...] Read more.
Functional microexons have not previously been described in filamentous fungi. Here, we describe a novel mechanism of transcriptional regulation in Trichoderma requiring the inclusion of a microexon from the Xlr2 gene. In low-glucose environments, a long mRNA including the microexon encodes a protein with a GAL4-like DNA-binding domain (Xlr2-α), whereas in high-glucose environments, a short mRNA that is produced encodes a protein lacking this DNA-binding domain (Xlr2-β). Interestingly, the protein isoforms differ in their impact on cellulase and xylanase activity. Deleting the Xlr2 gene reduced both xylanase and cellulase activity and growth on different carbon sources, such as carboxymethylcellulose, xylan, glucose, and arabinose. The overexpression of either Xlr2-α or Xlr2-β in T. virens showed that the short isoform (Xlr2-β) caused higher xylanase activity than the wild types or the long isoform (Xlr2-α). Conversely, cellulase activity did not increase when overexpressing Xlr2-β but was increased with the overexpression of Xlr2-α. This is the first report of a novel transcriptional regulation mechanism of plant-cell-wall-degrading enzyme activity in T. virens. This involves the differential expression of a microexon from a gene encoding a transcriptional regulator. Full article
(This article belongs to the Section Molecular Plant Sciences)
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16 pages, 6402 KiB  
Article
Scythian Jewelry Meshes and the Problem of Their Interpretation
by Oksana Lifantii
Arts 2024, 13(3), 85; https://doi.org/10.3390/arts13030085 (registering DOI) - 9 May 2024
Abstract
This article explores the phenomenon of a specific type of personal adornment worn by members of the Scythian elite in the North Black Sea region in the second half of the 5th century and throughout the 4th century BCE. The discussion juxtaposes the [...] Read more.
This article explores the phenomenon of a specific type of personal adornment worn by members of the Scythian elite in the North Black Sea region in the second half of the 5th century and throughout the 4th century BCE. The discussion juxtaposes the records from 19th-century and early 20th-century excavations with contextual analyses of very recent discoveries from Ukraine, which shed significant new light on the appearance, production, and meaning of Scythian jewelry. The reconstruction of the shape of the jewelry type in question is greatly complicated by two factors: the lack of relevant depictions in the contemporary corpus of Scythian and Greco-Scythian figure scenes and misleading scholarly references to supposed analogies in a Roman-era mosaic, which became the chief reason for the misinterpretations of the ornament’s appearance. Composed of numerous gold or gilded silver tubes; beads; pendants; and, sometimes, “buttons,” this jewelry type is reconstructed in two gender-specific variants in this article: one mesh-like and the other with a cross-chest form. For over a hundred years, scholars have considered only the mesh variant to be the correct reconstruction. As a result, many costume reconstructions of this jewelry form in specialist research and museum displays alike are still proposed without a sufficient evidentiary base. Full article
20 pages, 681 KiB  
Article
The Prevalence of Antibiotic Resistance Phenotypes and Genotypes in Multidrug-Resistant Bacterial Isolates from the Academic Hospital of Jaén, Spain
by Laura Morales, Antonio Cobo, María Pilar Frías, Antonio Gálvez and Elena Ortega
Antibiotics 2024, 13(5), 429; https://doi.org/10.3390/antibiotics13050429 (registering DOI) - 9 May 2024
Abstract
The heterogenicity of antimicrobial resistance genes described in clinically significant bacterial isolates and their potential role in reducing the efficacy of classically effective antibiotics pose a major challenge for global healthcare, especially in infections caused by Gram-negative bacteria. We analyzed 112 multidrug-resistant (MDR) [...] Read more.
The heterogenicity of antimicrobial resistance genes described in clinically significant bacterial isolates and their potential role in reducing the efficacy of classically effective antibiotics pose a major challenge for global healthcare, especially in infections caused by Gram-negative bacteria. We analyzed 112 multidrug-resistant (MDR) isolates from clinical samples in order to detect high resistance profiles, both phenotypically and genotypically, among four Gram-negative genera (Acinetobacter, Escherichia, Klebsiella, and Pseudomonas). We found that 9.8% of the total selected isolates were classified as extensively drug-resistant (XDR) (six isolates identified as A. baumannii and five among P. pneumoniae isolates). All other isolates were classified as MDR. Almost 100% of the isolates showed positive results for blaOXA-23 and blaNDM-1 genes among the A. baumannii samples, one resistance gene (blaCTX-M) among E. coli, and two genetic determinants (blaCTX-M and aac(6′)-Ib) among Klebsiella. In contrast, P. aeruginosa showed just one high-frequency antibiotic resistance gene (dfrA), which was present in 68.42% of the isolates studied. We also describe positive associations between ampicillin and cefotaxime resistance in A. baumannii and the presence of blaVEB and blaGES genes, as well as between the aztreonam resistance phenotype and the presence of blaGES gene in E. coli. These data may be useful in achieving a better control of infection strategies and antibiotic management in clinical scenarios where these multidrug-resistant Gram-negative pathogens cause higher morbidity and mortality. Full article
(This article belongs to the Special Issue ESKAPE Pathogen Infection and Antibiotic Resistance)
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14 pages, 960 KiB  
Review
The Role of Wheatgrass in Colorectal Cancer: A Review of the Current Evidence
by Magie Tamraz, Najib Al Ghossaini and Sally Temraz
Int. J. Mol. Sci. 2024, 25(10), 5166; https://doi.org/10.3390/ijms25105166 (registering DOI) - 9 May 2024
Abstract
The etiology of colon cancer is either genetic in nature or results from inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease; nevertheless, dietary habits play a crucial role in the disease. Wheatgrass is a dietary supplement that is rich in vitamins, [...] Read more.
The etiology of colon cancer is either genetic in nature or results from inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease; nevertheless, dietary habits play a crucial role in the disease. Wheatgrass is a dietary supplement that is rich in vitamins, minerals, and antioxidants which contribute to health promotion in cardiovascular diseases, liver disease, blood diseases, diabetes, and inflammatory bowel diseases, as well as in several types of cancers, such as oral squamous cell cancer, cervical cancer, and breast cancer. In colorectal cancer (CRC), the prospect that wheatgrass possesses anti-inflammatory, antioxidant, and anticancer properties, and its use as an adjunctive therapy, have been minimally investigated and evidence is still limited. In this review, we compiled the available evidence pertaining to wheatgrass and its likely impact on CRC, described the pathways of inflammation in which wheatgrass could possibly play a role, and identified future research needs on the subject. Full article
(This article belongs to the Special Issue Novel Molecular Pathways in Oncology 2.0)
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10 pages, 979 KiB  
Article
Non-Cicatricial Alopecia and Its Association with Anthropometric Measurements and Nutritional Laboratory Markers
by Katarzyna Wróblewska-Kończalik, Mariola Pawlaczyk, Jerzy Kolasiński, Małgorzata Kolenda, Izabela Miechowicz, Agnieszka Seraszek-Jaros, Anna Kroma-Szal and Justyna Gornowicz-Porowska
Life 2024, 14(5), 609; https://doi.org/10.3390/life14050609 (registering DOI) - 9 May 2024
Abstract
Alopecia constitutes one of the most common dermatological disorders, and its steadily increasing prevalence is a cause for concern. Alopecia can be divided into two main categories, cicatricial/scarring and non-cicatricial/non-scarring, depending on the causes of hair loss and its patterns. The aim of [...] Read more.
Alopecia constitutes one of the most common dermatological disorders, and its steadily increasing prevalence is a cause for concern. Alopecia can be divided into two main categories, cicatricial/scarring and non-cicatricial/non-scarring, depending on the causes of hair loss and its patterns. The aim of this study was to investigate the relationship between anthropometric and nutritional laboratory parameters in Caucasian adult women and men with non-cicatricial alopecia. A total of 50 patients (37 with non-cicatricial alopecia and 13 healthy controls) were included in the study. Clinical examination and scalp trichoscopy were performed. The anthropometric and nutritional laboratory parameters were collected and analyzed. No statistically significant differences in the laboratory findings were found. The patients with non-cicatricial alopecia were statistically significantly younger as compared to the controls. An elevated risk of hair loss, which was detected among the younger participants, might be associated with a modern lifestyle and the so-called ‘Western diet’. It seems safe to assume that suboptimal nutrition and poor eating habits during childhood might constitute risk factors for early hair loss. Full article
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16 pages, 3363 KiB  
Article
Topotecan and Ginkgolic Acid Inhibit the Expression and Transport Activity of Human Organic Anion Transporter 3 by Suppressing SUMOylation of the Transporter
by Zhou Yu and Guofeng You
Pharmaceutics 2024, 16(5), 638; https://doi.org/10.3390/pharmaceutics16050638 (registering DOI) - 9 May 2024
Abstract
Organic anion transporter 3 (OAT3), expressed at the basolateral membrane of kidney proximal tubule cells, facilitates the elimination of numerous metabolites, environmental toxins, and clinically important drugs. An earlier investigation from our laboratory revealed that OAT3 expression and transport activity can be upregulated [...] Read more.
Organic anion transporter 3 (OAT3), expressed at the basolateral membrane of kidney proximal tubule cells, facilitates the elimination of numerous metabolites, environmental toxins, and clinically important drugs. An earlier investigation from our laboratory revealed that OAT3 expression and transport activity can be upregulated by SUMOylation, a post-translational modification that covalently conjugates SUMO molecules to substrate proteins. Topotecan is a semi-synthetic derivative of the herbal extract camptothecin, approved by the FDA to treat several types of cancer. Ginkgolic acid (GA) is one of the major components in the extract of Ginkgo biloba leaves that has long been used in food supplements for preventing dementia, high blood pressure, and supporting stroke recovery. Both topotecan and GA have been shown to affect protein SUMOylation. In the current study, we tested our hypothesis that topotecan and GA may regulate OAT3 SUMOylation, expression, and transport function. Our data show that the treatment of OAT3-expressing cells with topotecan or GA significantly decreases the SUMOylation of OAT3 by 50% and 75%, respectively. The same treatment also led to substantial reductions in OAT3 expression and the OAT3-mediated transport of estrone sulfate, a prototypical substrate. Such reductions in cell surface expression of OAT3 correlated well with an increased rate of OAT3 degradation. Mechanistically, we discovered that topotecan enhanced the association between OAT3 and the SUMO-specific protease SENP2, a deSUMOylation enzyme, which contributed to the significant decrease in OAT3 SUMOylation. In conclusion, this study unveiled a novel role of topotecan and GA in inhibiting OAT3 expression and transport activity and accelerating OAT3 degradation by suppressing OAT3 SUMOylation. During comorbidity therapies, the use of topotecan or Ginkgo biloba extract could potentially decrease the transport activity of OAT3 in the kidneys, which will in turn affect the therapeutic efficacy and toxicity of many other drugs that are substrates for the transporter. Full article
(This article belongs to the Special Issue New Insights into Transporters in Drug Development)
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10 pages, 526 KiB  
Article
Impact of Nutritional Status on Neutrophil-to-Lymphocyte Ratio as a Predictor of Efficacy and Adverse Events of Immune Check-Point Inhibitors
by Masahiko Sue, Yasuto Takeuchi, Shoichiro Hirata, Akinobu Takaki and Motoyuki Otsuka
Cancers 2024, 16(10), 1811; https://doi.org/10.3390/cancers16101811 (registering DOI) - 9 May 2024
Abstract
The neutrophil -to-lymphocyte ratio (NLR) is useful for predicting the effectiveness of treatment with immune checkpoint inhibitors (ICIs) and immune-related adverse events (irAEs). Because a growing body of evidence has recently shown that the number of lymphocytes that comprise NLR fluctuates according to [...] Read more.
The neutrophil -to-lymphocyte ratio (NLR) is useful for predicting the effectiveness of treatment with immune checkpoint inhibitors (ICIs) and immune-related adverse events (irAEs). Because a growing body of evidence has recently shown that the number of lymphocytes that comprise NLR fluctuates according to nutritional status, this study examined whether the usefulness of NLR varies in ICI treatment due to changes in nutritional status. A retrospective analysis was performed on 1234 patients who received ICI treatment for malignant tumors at our hospital. Progression-free survival (PFS) was significantly prolonged in patients with NLR < 4. Multivariate analysis revealed that the factors associated with the occurrence of irAE were NLR < 4 and the use of ipilimumab. However, when limited to cases with serum albumin levels <3.8 g/dL, lymphocyte counts significantly decreased, and the associations between NLR and PFS and between NLR and irAE occurrence disappeared. In contrast, when limited to the cases with serum albumin levels ≥3.8 g/dL, the associations remained, with significantly prolonged PFS and significantly increased irAE occurrence at NLR < 4. NLR may be a good predictive tool for PFS and irAE occurrence during ICI treatment when a good nutritional status is maintained. Full article
32 pages, 3996 KiB  
Article
Intelligent Geo-Tour Route Recommendation Algorithm Based on Feature Text Mining and Spatial Accessibility Model
by Xiao Zhou, Zheng Zhang, Xinjian Liang and Mingzhan Su
Electronics 2024, 13(10), 1845; https://doi.org/10.3390/electronics13101845 (registering DOI) - 9 May 2024
Abstract
In view of the problems in planning and recommending tour routes, this paper constructs a feature text mining (FTM) method and spatial accessibility model (SAM) as the key factors for scenic spot recommendation (SSR) and tour route recommendation (TRR). The scenic spot clustering [...] Read more.
In view of the problems in planning and recommending tour routes, this paper constructs a feature text mining (FTM) method and spatial accessibility model (SAM) as the key factors for scenic spot recommendation (SSR) and tour route recommendation (TRR). The scenic spot clustering algorithm (SSCA) based on FTM was constructed by tourists’ text evaluation data mining. Considering the spatial attributes of scenic spots, the scenic spot topology tree algorithm (SSTTA) based on dynamic buffer spatial accessibility (DBSA) was constructed. The optimal scenic spots were recommended based on interest matching and spatial accessibility optimization. As to the recommended scenic spots, this paper proposes an optimal tour route recommendation algorithm (TRRA) based on SSTTA, which aims to determine the optimal adjacent section path structure tree (ASPST) with the lowest cost under travel constraints and transportation modes. The experiment verifies that the proposed algorithm can recommend scenic spots that match tourists’ interests and have optimal spatial accessibility, and the optimal tour routes with the lowest costs under certain travel constraints. Compared with the searched sub-optimal tour routes, the optimal tour route recommended by the proposed algorithm produces the lowest travel costs, and all the scenic spots in the tour route meet the tourists’ interests. Compared with the commonly used BDMA and GDMA methods, the proposed algorithm can determine the optimal routes with lower travel costs. Full article
(This article belongs to the Special Issue Advances in Intelligent Systems and Networks, 2nd Edition)
23 pages, 516 KiB  
Article
A Net Present Value Analysis of Opportunity-Based Age Replacement Models in Discrete Time
by Jing Wu, Cunhua Qian and Tadashi Dohi
Mathematics 2024, 12(10), 1472; https://doi.org/10.3390/math12101472 (registering DOI) - 9 May 2024
Abstract
Two important opportunistic age replacement models, under replacement first and last disciplines, are generalized in discrete time. The net present value (NPV) is applied to formulate the expected total costs. The priority of multiple replacement options is considered to classify the cost model [...] Read more.
Two important opportunistic age replacement models, under replacement first and last disciplines, are generalized in discrete time. The net present value (NPV) is applied to formulate the expected total costs. The priority of multiple replacement options is considered to classify the cost model with discounting into six cases. Since the NPV method accurately calculates the expected replacement costs over an infinite horizon in an unstable economic environment, we discuss some optimal opportunistic age replacement policies which minimize the expected total discounted costs over an infinite time horizon. Furthermore, we formulate a unified model under each discipline, merging six discrete time replacement models with probabilistic priority. Finally, a case study on optimal replacement first and last policies for pole air switches in a Japanese power company is presented. Full article
(This article belongs to the Special Issue Reliability Estimation and Mathematical Statistics)
16 pages, 6741 KiB  
Article
Targeted Formation of Biofilms on the Surface of Graphite Electrodes as an Effective Approach to the Development of Biosensors for Early Warning Systems
by Anna Kharkova, Roman Perchikov, Saniyat Kurbanalieva, Kristina Osina, Nadezhda Popova, Andrey Machulin, Olga Kamanina, Evgeniya Saverina, Ivan Saltanov, Sergey Melenkov, Denis Butusov and Vyacheslav Arlyapov
Biosensors 2024, 14(5), 239; https://doi.org/10.3390/bios14050239 (registering DOI) - 9 May 2024
Abstract
Biofilms based on bacteria Pseudomonas veronii (Ps. veronii) and Escherichia coli (E. coli) and yeast Saccharomyces cerevisiae (S. cerevisiae) were used for novel biosensor creation for rapid biochemical oxygen demand (BOD) monitoring. Based on the electrochemical measurement [...] Read more.
Biofilms based on bacteria Pseudomonas veronii (Ps. veronii) and Escherichia coli (E. coli) and yeast Saccharomyces cerevisiae (S. cerevisiae) were used for novel biosensor creation for rapid biochemical oxygen demand (BOD) monitoring. Based on the electrochemical measurement results, it was shown that the endogenous mediator in the matrix of E. coli and Ps. veronii biofilms and ferrocene form a two-mediator system that improves electron transport in the system. Biofilms based on Ps. veronii and E. coli had a high biotechnological potential for BOD assessment; bioreceptors based on such biofilms had high sensitivity (the lower limits of detectable BOD5 concentrations were 0.61 (Ps. veronii) and 0.87 (E. coli) mg/dm3) and high efficiency of analysis (a measurement time 5–10 min). The maximum biosensor response based on bacterial biofilms has been observed in the pH range of 6.6–7.2. The greatest protective effect was found for biofilms based on E. coli, which has high long-term stability (151 days for Ps. veronii and 163 days for E. coli). The results of the BOD5 analysis of water samples obtained using the developed biosensors had a high correlation with the results of the standard 5-day method (R2 = 0.9820, number of tested samples is 10 for Ps. veronii, and R2 = 0.9862, number of tested samples is 10 for E. coli). Thus, biosensors based on Ps. veronii biofilms and E. coli biofilms could be a novel analytical system to give early warnings of pollution. Full article
(This article belongs to the Special Issue Cell-Based Biosensors for Rapid Detection and Monitoring)
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30 pages, 5408 KiB  
Article
Rainfall Potential and Consequences on Structural Soil Degradation of the Most Important Agricultural Region of Mexico
by Mariano Norzagaray Campos, Patricia Muñoz Sevilla, Jorge Montiel Montoya, Omar Llanes Cárdenas, María Ladrón de Guevara Torres and Luz Arcelia Serrano García
Atmosphere 2024, 15(5), 581; https://doi.org/10.3390/atmos15050581 (registering DOI) - 9 May 2024
Abstract
This study investigates the historical variability in annual average precipitation in the northwest region of Mexico, aiming to evaluate the cumulative impact of precipitation on soil degradation and associated risks posed by rainfall. Despite being known as “The Agricultural Heart of Mexico [...] Read more.
This study investigates the historical variability in annual average precipitation in the northwest region of Mexico, aiming to evaluate the cumulative impact of precipitation on soil degradation and associated risks posed by rainfall. Despite being known as “The Agricultural Heart of Mexico”, the region’s soil has experienced significant damage to its granulometric structure due to unpredictable rainfall patterns attributed to climate change. Sixteen historical series of average annual rainfall were analyzed as stationary stochastic processes for spectral analysis. The results revealed exponential decay curves in each radial spectrum, indicating a linear relationship between frequency and amplitude. These curves identified initial impulses correlated with moments of severity for structural damages caused by rainfall-induced degradation. The degradation process, exacerbated by water stress, accelerates, as evidenced by maps illustrating approximately 75% soil damage. In the context of climate change and the uncertainty surrounding soil responses to extreme meteorological events, understanding this phenomenon becomes crucial. Recognizing the dynamic nature of soil responses to environmental stressors is essential for effective soil management. Emphasizing the need to employ numerical processes tailored to new environmental considerations related to observed soil damages is crucial for sustainable soil management practices in any region. Full article
(This article belongs to the Section Biosphere/Hydrosphere/Land–Atmosphere Interactions)
19 pages, 1162 KiB  
Article
Fake User Detection Based on Multi-Model Joint Representation
by Jun Li, Wentao Jiang, Jianyi Zhang, Yanhua Shao and Wei Zhu
Information 2024, 15(5), 266; https://doi.org/10.3390/info15050266 (registering DOI) - 9 May 2024
Abstract
The existing deep learning-based detection of fake information focuses on the transient detection of news itself. Compared to user category profile mining and detection, transient detection is prone to higher misjudgment rates due to the limitations of insufficient temporal information, posing new challenges [...] Read more.
The existing deep learning-based detection of fake information focuses on the transient detection of news itself. Compared to user category profile mining and detection, transient detection is prone to higher misjudgment rates due to the limitations of insufficient temporal information, posing new challenges to social public opinion monitoring tasks such as fake user detection. This paper proposes a multimodal aggregation portrait model (MAPM) based on multi-model joint representation for social media platforms. It constructs a deep learning-based multimodal fake user detection framework by analyzing user behavior datasets within a time retrospective window. It integrates a pre-trained Domain Large Model to represent user behavior data across multiple modalities, thereby constructing a high-generalization implicit behavior feature spectrum for users. In response to the tendency of existing fake user behavior mining to neglect time-series features, this study introduces an improved network called Sequence Interval Detection Net (SIDN) based on Sequence to Sequence (seq2seq) to characterize time interval sequence behaviors, achieving strong expressive capabilities for detecting fake behaviors within the time window. Ultimately, the amalgamation of latent behavioral features and explicit characteristics serves as the input for spectral clustering in detecting fraudulent users. The experimental results on Weibo real dataset demonstrate that the proposed model outperforms the detection utilizing explicit user features, with an improvement of 27.0% in detection accuracy. Full article
(This article belongs to the Special Issue 2nd Edition of Information Retrieval and Social Media Mining)
25 pages, 1545 KiB  
Article
A Calculation Method for Reliability Index of a Deep–Bedded Karst Tunnel Construction with Cavity Located Ahead of Tunnel Working Face
by Bo Wu, Wentao Sun and Guowang Meng
Buildings 2024, 14(5), 1349; https://doi.org/10.3390/buildings14051349 (registering DOI) - 9 May 2024
Abstract
For the purpose of reliability quantitative assessment of the surrounding rock of the deeply embedded karst tunnel and the geological body around the cavern in the case of the cavern in the forepart of the tunnel face, on the basis of the upper [...] Read more.
For the purpose of reliability quantitative assessment of the surrounding rock of the deeply embedded karst tunnel and the geological body around the cavern in the case of the cavern in the forepart of the tunnel face, on the basis of the upper bound limit analysis method, the energy dissipation theory, as well as the reliability theory, the dimensionless performance function of each damage area of the deeply buried karst tunnels could be established in the case of the cavern in the front of the tunnel face. Subsequently, the probability of failure and the reliability index of each damage region of the deep–bedded karst tunnel in the case of the cavern in the front of this tunnel face should be calculated through the Monte Carlo simulation sampling approach. The investigation has demonstrated that the larger the cohesion of the geotechnical body and the larger the internal friction angle within the geotechnical body, the larger the reliability indexes of the geotechnical bodies around the tunnel. The larger the diameter of the cavern and the larger the tunnel burial depth, the greater the probability of failure in the left part of the geotechnical body around this cavern, and the smaller the reliability indexes of these damage areas. Full article
(This article belongs to the Section Construction Management, and Computers & Digitization)
26 pages, 12457 KiB  
Article
Analysis of Microwave-Induced Damage in Granite Aggregates Influenced by Mineral Texture
by Yuan Yuan and Shuang Zhao
Buildings 2024, 14(5), 1348; https://doi.org/10.3390/buildings14051348 (registering DOI) - 9 May 2024
Abstract
The use of microwave energy to recycle high-quality coarse aggregates from waste concrete or assist hard rock breakage in underground building engineering is promising. Controlling or promoting the damage of coarse aggregates, i.e., hard rocks, under microwave irradiation is a crucial issue faced [...] Read more.
The use of microwave energy to recycle high-quality coarse aggregates from waste concrete or assist hard rock breakage in underground building engineering is promising. Controlling or promoting the damage of coarse aggregates, i.e., hard rocks, under microwave irradiation is a crucial issue faced by these techniques. Understanding the damage mechanisms of hard rocks exposed to microwaves is thus urgent. Fracture toughness is a significant mechanical parameter of rocks that reflects their ability to resist crack propagation and damage evolution. In this study, the fracture toughness degradation of microwave-heated granite was investigated by combining experimental investigations and numerical simulations. A three-point-bending (TPB) experiment was conducted on granite specimens after microwave irradiation. A coupled electromagnetic–thermal–mechanical model considering the actual mineral texture of the granite specimen was established. The evolution of the temperature gradient and stress field near the initial notch tip were investigated. The results suggest that the microwave-induced maximum temperature gradient and stress in granite are at the plagioclase–quartz (Pl–Qtz) interfaces or inside the Pl near the boundary. The region of cracking initiation was defined as the damage zone, which could be obtained by comparing the microwave-induced thermal stress with the critical value. The fracture toughness degradation, which corresponds to the evolution of the damage zones, can be divided into two stages. A relatively rapid decrease in fracture toughness in the first stage is primarily caused by the spread of the scattered damage zones along the Pl–Qtz interfaces; subsequently, a gentler fracture toughness degradation results mainly from the extension of the previous damage zones. Full article
(This article belongs to the Section Construction Management, and Computers & Digitization)
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16 pages, 892 KiB  
Article
Enhancing Knowledge Graph Embedding with Hierarchical Self-Attention and Graph Neural Network Techniques for Drug-Drug Interaction Prediction in Virtual Reality Environments
by Lizhen Jiang and Sensen Zhang
Symmetry 2024, 16(5), 587; https://doi.org/10.3390/sym16050587 (registering DOI) - 9 May 2024
Abstract
In biomedicine, the critical task is to decode Drug–Drug Interactions (DDIs) from complex biomedical texts. The scientific community employs Knowledge Graph Embedding (KGE) methods, enhanced with advanced neural network technologies, including capsule networks. However, existing methodologies primarily focus on the structural details of [...] Read more.
In biomedicine, the critical task is to decode Drug–Drug Interactions (DDIs) from complex biomedical texts. The scientific community employs Knowledge Graph Embedding (KGE) methods, enhanced with advanced neural network technologies, including capsule networks. However, existing methodologies primarily focus on the structural details of individual entities or relations within Biomedical Knowledge Graphs (BioKGs), overlooking the overall structural context of BioKGs, molecular structures, positional features of drug pairs, and their critical Relational Mapping Properties. To tackle the challenges identified, this study presents HSTrHouse an innovative hierarchical self-attention BioKGs embedding framework. This architecture integrates self-attention mechanisms with advanced neural network technologies, including Convolutional Neural Network (CNN) and Graph Neural Network (GNN), for enhanced computational modeling in biomedical contexts. The model bifurcates the BioKGs into entity and relation layers for structural analysis. It employs self-attention across these layers, utilizing PubMedBERT and CNN for position feature extraction, and a GNN for drug pair molecular structure analysis. Then, we connect the position and molecular structure features to integrate them into the self-attention calculation of entity and relation. After that, the output of the self-attention layer is combined with the connected vectors of the position feature and molecular structure feature to obtain the final representation vector, and finally, to model the Relational Mapping Properties (RMPs), the representation vector is embedded into the complex vector space using Householder projections to obtain the BioKGs model. The paper validates HSTrHouse’s efficacy by comparing it with advanced models on three standard BioKGs for DDIs research. Full article
(This article belongs to the Section Computer)
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17 pages, 502 KiB  
Article
Nice for Whom? A Dangerous, Not-So-Nice, Critical Race Love Letter
by G. T. Reyes
Educ. Sci. 2024, 14(5), 508; https://doi.org/10.3390/educsci14050508 (registering DOI) - 9 May 2024
Abstract
In this article, I critically analyze and respond to empirical data in the form of racialized discourse—specifically, racist messages sent directly to me as a result of my previously published article entitled, “A Love Letter to Educational Leaders of Color: CREWing UP with [...] Read more.
In this article, I critically analyze and respond to empirical data in the form of racialized discourse—specifically, racist messages sent directly to me as a result of my previously published article entitled, “A Love Letter to Educational Leaders of Color: CREWing UP with Critical Whiteness Studies”. Being informed by a robust racial analysis of acts that reinforce white supremacy, this article will likely be perceived as not nice by those who benefit from and work to protect white supremacy. Likely, I will be the one accused of being hateful, divisive, and even racist. In order to interrogate the weaponization of this conception of “niceness”, my analysis will be driven by Critical Race Hermeneutics with white emotionality and whitelashing used as interpretive lenses. As this article’s engagement with these critical race frameworks poses a threat to those who benefit from racism, this is a dangerous, not-so-nice critical race love letter. Full article
(This article belongs to the Special Issue Niceness, Leadership and Educational Equity)
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