bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial Bioenergetics, Redox Balance, and Calcium Homeostasis Dysfunction with Defective Ultrastructure and Quality Control in the Hippocampus of Aged Female C57BL/6J Mice
Authors: Torres Angie K. , Jara Claudia , Llanquinao Jesús , Lira Matías , Cortés-Díaz Daniela , Tapia-Rojas Cheril
Published: March 2023

Aging is a physiological process that generates progressive decline in many cellular functions. There are many theories of aging, and one of great importance in recent years is the mitochondrial theory of aging, in which mitochondrial dysfunction that occurs at advanced age could be responsible for the aged phenotype. In this context, there is diverse information about mitochondrial dysfunction in aging, in different models and different organs. Specifically, in the brain, different studies have shown mitochondrial dysfunction mainly in the cortex; however, until now, no study has shown all the defects in hippocampal mitochondria in aged female C57BL/6J mice. We performed a complete analysis of mitochondrial function in 3-month-old and 20-month-old (mo) female C57BL/6J mice, specifically in the hippocampus of these animals. We observed an impairment in bioenergetic function, indicated by a decrease in mitochondrial membrane potential, O2 consumption, and mitochondrial ATP production. Additionally, there was an increase in ROS production in the aged hippocampus, leading to the activation of antioxidant signaling, specifically the Nrf2 pathway. It was also observed that aged animals had deregulation of calcium homeostasis, with more sensitive mitochondria to calcium overload and deregulation of proteins related to mitochondrial dynamics and quality control processes. Finally, we observed a decrease in mitochondrial biogenesis with a decrease in mitochondrial mass and deregulation of mitophagy. These results show that during the aging process, damaged mitochondria accumulate, which could contribute to or be responsible for the aging phenotype and age-related disabilities.
Prognostication of DNA Damage Response Protein Expression Patterns in Chronic Lymphocytic Leukemia
Authors: Griffen Ti’ara L. , Hoff Fieke W. , Qiu Yihua , Burger Jan , Wierda William , Kornblau Steven M.
Published: March 2023

Proteomic DNA Damage Repair (DDR) expression patterns in Chronic Lymphocytic Leukemia were characterized by quantifying and clustering 24 total and phosphorylated DDR proteins. Overall, three protein expression patterns (C1-C3) were identified and were associated as an independent predictor of distinct patient overall survival outcomes. Patients within clusters C1 and C2 had poorer survival outcomes and responses to fludarabine, cyclophosphamide, and rituxan chemotherapy compared to patients within cluster C3. However, DDR protein expression patterns were not prognostic in more modern therapies with BCL2 inhibitors or a BTK/PI3K inhibitor. Individually, nine of the DDR proteins were prognostic for predicting overall survival and/or time to first treatment. When looking for other proteins that may be associated with or influenced by DDR expression patterns, our differential expression analysis found that cell cycle and adhesion proteins were lower in clusters compared to normal CD19 controls. In addition, cluster C3 had a lower expression of MAPK proteins compared to the poor prognostic patient clusters thus implying a potential regulatory connection between adhesion, cell cycle, MAPK, and DDR signaling in CLL. Thus, assessing the proteomic expression of DNA damage proteins in CLL provided novel insights for deciphering influences on patient outcomes and expanded our understanding of the potential complexities and effects of DDR cell signaling.
Overview of BPH: Symptom Relief with Dietary Polyphenols, Vitamins and Phytochemicals by Nutraceutical Supplements with Implications to the Prostate Microbiome
Authors: Stewart Kendal L. , Lephart Edwin D.
Published: March 2023

Benign prostatic hyperplasia (BPH) is an age-related disorder, which is one of the most prevalent and costly benign neoplasms in men with over 94 million cases worldwide. Starting before or around 50 years of age, there is a linear increase in prostate volume and BPH symptoms, which are influenced by changes in hormonal, inflammatory, growth factors, cell receptor signaling, diet, physical activity, and the microbiome of the prostate that leads to cellular proliferation. While current pharmaceutical or surgical treatments are currently available, each treatment has serious side effects. This dilemma has motived men to seek treatment without negative side effects from medicinal plants such as botanicals, phytochemicals, and vitamins that have established safety records. This narrative overview focuses on several botanicals, phytochemicals and vitamins that are widely used in the treatment of BPH and emphasizes how, in some cases, combinations of these natural ingredients may provide better BPH symptom relief compared to utilization of a single medicinal plant product (monotherapy). Finally, this overview highlights in vitro, in vivo animal studies and mainly clinical data of journal reports published in the past 5 years from January 2018 to January 2023 on BPH and nutraceuticals. Notably, there is an evolving perspective or rethinking of the role that medicinal phytochemicals and natural vitamins usage play; that is, they may hold promise or are likely to alleviate BPH symptoms.
8-Oxoguanine DNA Glycosylase 1 Upregulation as a Risk Factor for Obesity and Colorectal Cancer
Authors: Pilo Jesús , García-Flores Libia Alejandra , Clemente-Postigo Mercedes , Arranz-Salas Isabel , Alcaide Julia , Ramos-Fernandez Maria , Lozano José , Boughanem Hatim , Kompella Pallavi , Macías-González Manuel
Published: March 2023

DNA damage has been extensively studied as a potentially helpful tool in assessing and preventing cancer, having been widely associated with the deregulation of DNA damage repair (DDR) genes and with an increased risk of cancer. Adipose tissue and tumoral cells engage in a reciprocal interaction to establish an inflammatory microenvironment that enhances cancer growth by modifying epigenetic and gene expression patterns. Here, we hypothesize that 8-oxoguanine DNA glycosylase 1 (OGG1)—a DNA repair enzyme—may represent an attractive target that connects colorectal cancer (CRC) and obesity. In order to understand the mechanisms underlying the development of CRC and obesity, the expression and methylation of DDR genes were analyzed in visceral adipose tissue from CRC and healthy participants. Gene expression analysis revealed an upregulation of OGG1 expression in CRC participants (p < 0.005) and a downregulation of OGG1 in normal-weight healthy patients (p < 0.05). Interestingly, the methylation analysis showed the hypermethylation of OGG1 in CRC patients (p < 0.05). Moreover, expression patterns of OGG1 were found to be regulated by vitamin D and inflammatory genes. In general, our results showed evidence that OGG1 can regulate CRC risk through obesity and may act as a biomarker for CRC.
A Simultaneous Extraction/Derivatization Strategy for Quantitation of Vitamin D in Dried Blood Spots Using LC–MS/MS: Application to Biomarker Study in Subjects Tested for SARS-CoV-2
Authors: Chhonker Yashpal S. , Ahmed Nusrat , Johnston Christine M. , Barnabas Ruanne V. , Murry Daryl J.
Published: March 2023

Vitamin D plays a critical role in bone development and maintenance, and in other physiological functions. The quantitation of endogenous levels of individual vitamin D and its metabolites is crucial for assessing several disease state conditions. With cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leading to the coronavirus disease 2019 (COVID-19) pandemic, there are several studies that have associated lower levels of serum vitamin D with severity of infection in COVID-19 patients. In this context, we have developed and validated a robust LC–MS/MS method for simultaneous quantitation of vitamin D and its metabolites in human dried blood spot (DBS) obtained from participants tested for COVID-19. The chromatographic separation for vitamin D and metabolites was performed using an ACE Excel C18 PFP column protected with a C18 guard column (Phenomenex, Torrance, CA, USA). The mobile phase consisted of formic acid in water (0.1% v/v) as mobile phase A and formic acid in methanol (0.1% v/v) as mobile phase B, operated at a flow rate of 0.5 mL/min. Analysis was performed utilizing the LC–MS/MS technique. The method was sensitive with a limit of quantification of 0.78 ng/mL for all analytes, and had a large dynamic range (200 ng/mL) with a total run time of 11 min. The inter- and intraday accuracy and precision values met the acceptance criteria per the US Food and Drug Administration guidelines. Blood concentrations of 25(OH)D3, vitamin D3, 25(OH)D2, and vitamin D2 over a range of 2–195.6, 0.5–121.5, 0.6–54.9, and 0.5–23.9 ng/mL, respectively, were quantified in 909 DBS samples. In summary, our developed LC−MS/MS method may be used for quantification of vitamin D and its metabolites in DBS, and may be applied to investigations of the emerging role of these compounds in various physiological processes.
Pilot Study on the Impact of Polymorphisms Linked to Multi-Kinase Inhibitor Metabolism on Lenvatinib Side Effects in Patients with Advanced Thyroid Cancer
Authors: Cantara Silvia , Dalmiglio Cristina , Marzocchi Carlotta , Sagnella Alfonso , Brilli Lucia , Trimarchi Andrea , Maino Fabio , Valerio Laura , Castagna Maria Grazia
Published: March 2023

Multi-kinase inhibitors (MKIs) represent the best therapeutic option in advanced thyroid cancer patients. The therapeutic efficacy and toxicity of MKIs are very heterogeneous and are difficult to predict before starting treatment. Moreover, due to the development of severe adverse events, it is necessary to interrupt the therapy some patients. Using a pharmacogenetic approach, we evaluated polymorphisms in genes coding for proteins involved with the absorption and elimination of the drug in 18 advanced thyroid cancer patients treated with lenvatinib, and correlated the genetic background with (1) diarrhea, nausea, vomiting and epigastric pain; (2) oral mucositis and xerostomia; (3) hypertension and proteinuria; (4) asthenia; (5) anorexia and weight loss; (6) hand foot syndrome. Analyzed variants belong to cytochrome P450 (CYP3A4 rs2242480 and rs2687116 and CYP3A5 rs776746) genes and to ATP-binding cassette transporters (ABCB1 rs1045642, rs2032582 and rs2235048 and ABCG2 rs2231142). Our results suggest that the GG genotype for rs2242480 in CYP3A4 and CC genotype in rs776746 for CYP3A5 were both associated with the presence of hypertension. Being heterozygous for SNPs in the ABCB1 gene (rs1045642 and 2235048) implicated a higher grade of weight loss. The ABCG2 rs2231142 statistically correlated with a higher extent of mucositis and xerostomia (CC genotype). Heterozygous and rare homozygous genotypes for rs2242480 in CYP3A4 and for rs776746 for CYP3A5 were found to be statistically linked to a worse outcome. Evaluating the genetic profile before starting lenvatinib treatment may help to predict the occurrence and grade of some side effects, and may contribute to improving patient management.
Integrating Multiple Single-Cell RNA Sequencing Datasets Using Adversarial Autoencoders
Authors: Wang Xun , Zhang Chaogang , Wang Lulu , Zheng Pan
Published: March 2023

Single-cell RNA sequencing (RNA-seq) has been demonstrated to be a proven method for quantifying gene-expression heterogeneity and providing insight into the transcriptome at the single-cell level. When combining multiple single-cell transcriptome datasets for analysis, it is common to first correct the batch effect. Most of the state-of-the-art processing methods are unsupervised, i.e., they do not utilize single-cell cluster labeling information, which could improve the performance of batch correction methods, especially in the case of multiple cell types. To better utilize known labels for complex dataset scenarios, we propose a novel deep learning model named IMAAE (i.e., integrating multiple single-cell datasets via an adversarial autoencoder) to correct the batch effects. After conducting experiments with various dataset scenarios, the results show that IMAAE outperforms existing methods for both qualitative measures and quantitative evaluation. In addition, IMAAE is able to retain both corrected dimension reduction data and corrected gene expression data. These features make it a potential new option for large-scale single-cell gene expression data analysis.
Radiofrequency Irradiation Attenuated UVB-Induced Skin Pigmentation by Modulating ATP Release and CD39 Expression
Authors: Byun Kyung-A , Kim Hyoung Moon , Oh Seyeon , Son Kuk Hui , Byun Kyunghee
Published: March 2023

Hyperpigmentation stimulated by ultraviolet (UV)-induced melanin overproduction causes various cosmetic problems. UV radiation’s activation of the cyclic adenosine monophosphate (cAMP)-mediated cAMP-dependent protein kinase (PKA)/cAMP response element-binding protein (CREB)/microphthalmia-associated transcription factor (MITF) pathway is the main pathway for melanogenesis. However, the secretion of adenosine triphosphate (ATP) from keratinocytes due to UV radiation also leads to melanogenesis. Adenosine, converted from ATP by CD39 and CD73, can activate adenylate cyclase (AC) activity and increase intracellular cAMP expression. cAMP-mediated PKA activation results in dynamic mitochondrial changes that affect melanogenesis via ERK. We evaluated whether radiofrequency (RF) irradiation could decrease ATP release from keratinocytes and suppress the expression of CD39, CD73, and A2A/A2B adenosine receptors (ARs) and the activity of AC and downregulate the PKA/CREB/MITF pathway, which would eventually decrease melanogenesis in vitro in UV-irradiated cells and animal skin. Our results indicate that RF decreased ATP release from UVB-irradiated keratinocytes. When conditioned media (CM) from UVB-irradiated keratinocytes (CM-UVB) were administered to melanocytes, the expressions of CD39, CD73, A2A/A2BARs, cAMP, and PKA increased. However, the expression of these factors decreased when CM from UVB and RF-irradiated keratinocytes (CM-UVB/RF) was administered to melanocytes. The phosphorylation of DRP1 at Ser637, which inhibits mitochondrial fission, increased in UVB-irradiated animal skin and was decreased by RF irradiation. The expression of ERK1/2, which can degrade MITF, was increased using RF treatment in UVB-irradiated animal skin. Tyrosinase activity and melanin levels in melanocytes increased following CM-UVB administration, and these increases were reversed after CD39 silencing. Tyrosinase activity and melanin levels in melanocytes were decreased by CM-UVB/RF irradiation. In conclusion, RF irradiation decreased ATP release from keratinocytes and the expressions of CD39, CD73, and A2A/A2BARs, which decreased AC activity in melanocytes. RF irradiation downregulated the cAMP-mediated PKA/CREB/MITF pathway and tyrosinase activity, and these inhibitory effects can be mediated via CD39 inhibition.
Safety and Immunogenicity of Recombinant Bacille Calmette-Guérin Strain VPM1002 and Its Derivatives in a Goat Model
Authors: Figl Julia , Köhler Heike , Wedlich Nadine , Liebler-Tenorio Elisabeth M. , Grode Leander , Parzmair Gerald , Krishnamoorthy Gopinath , Nieuwenhuizen Natalie E. , Kaufmann Stefan H. E. , Menge Christian
Published: March 2023

A more effective vaccine against tuberculosis than Bacille Calmette-Guérin (BCG) is urgently needed. BCG derived recombinant VPM1002 has been found to be more efficacious and safer than the parental strain in mice models. Newer candidates, such as VPM1002 Δpdx1 (PDX) and VPM1002 ΔnuoG (NUOG), were generated to further improve the safety profile or efficacy of the vaccine. Herein, we assessed the safety and immunogenicity of VPM1002 and its derivatives, PDX and NUOG, in juvenile goats. Vaccination did not affect the goats’ health in regards to clinical/hematological features. However, all three tested vaccine candidates and BCG induced granulomas at the site of injection, with some of the nodules developing ulcerations approximately one month post-vaccination. Viable vaccine strains were cultured from the injection site wounds in a few NUOG- and PDX- vaccinated animals. At necropsy (127 days post-vaccination), BCG, VPM1002, and NUOG, but not PDX, still persisted at the injection granulomas. All strains, apart from NUOG, induced granuloma formation only in the lymph nodes draining the injection site. In one animal, the administered BCG strain was recovered from the mediastinal lymph nodes. Interferon gamma (IFN-γ) release assay showed that VPM1002 and NUOG induced a strong antigen-specific response comparable to that elicited by BCG, while the response to PDX was delayed. Flow cytometry analysis of IFN-γ production by CD4+, CD8+, and γδ T cells showed that CD4+ T cells of VPM1002- and NUOG-vaccinated goats produced more IFN-γ compared to BCG-vaccinated and mock-treated animals. In summary, the subcutaneous application of VPM1002 and NUOG induced anti-tuberculous immunity, while exhibiting a comparable safety profile to BCG in goats.
Turning a Tumor Microenvironment Pitfall into Opportunity: Discovery of Benzamidoxime as PD-L1 Ligand with pH-Dependent Potency
Authors: Bianconi Elisa , Riccio Alessandra , Ruta Luana , Bigiotti Carlo , Carotti Andrea , Moretti Sonia , Cerra Bruno , Gioiello Antimo , Ferlin Simone , Puxeddu Efisio , Macchiarulo Antonio
Published: March 2023

PD-1/PD-L1 protein complex is attracting a great deal of interest as a drug target for the design of immune therapies able to block its assembly. Although some biologic drugs have entered clinical use, their poor response rate in patients are demanding further efforts to design small molecule inhibitors of PD-1/PD-L1 complex with higher efficacy and optimal physicochemical properties. Dysregulation of pH in the tumor microenvironment is indeed one of the key mechanisms promoting drug resistance and lack of response in cancer therapy. Integrating computational and biophysical approaches, herein we report a screening campaign that has led to identifying VIS310 as a novel ligand of PD-L1, with physicochemical properties enabling a pH-dependent binding potency. Additional optimization efforts by analogue-based screening have been instrumental to disclosing VIS1201, which exhibits improved binding potency against PD-L1 and is able to inhibit PD-1/PD-L1 complex formation in a ligand binding displacement assay. While providing preliminary structure–activity relationships (SARs) of a novel class of PD-L1 ligands, our results lay the foundation for the discovery of immunoregulatory small molecules resilient to tumor microenvironmental conditions for escaping drug-resistance mechanisms.
Bidirectional Regulation of Sodium Acetate on Macrophage Activity and Its Role in Lipid Metabolism of Hepatocytes
Authors: Li Weiwei , Deng Mingjuan , Gong Jiahui , Hou Yichao , Zhao Liang
Published: March 2023

Short-chain fatty acids (SCFAs) are important metabolites of the intestinal flora that are closely related to the development of non-alcoholic fatty liver disease (NAFLD). Moreover, studies have shown that macrophages have an important role in the progression of NAFLD and that a dose effect of sodium acetate (NaA) on the regulation of macrophage activity alleviates NAFLD; however, the exact mechanism of action remains unclear. This study aimed to assess the effect and mechanism of NaA on regulating the activity of macrophages. RAW264.7 and Kupffer cells cell lines were treated with LPS and different concentrations of NaA (0.01, 0.05, 0.1, 0.5, 1, 1.5, 2, and 5 mM). Low doses of NaA (0.1 mM, NaA-L) significantly increased the expression of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin 1 beta (IL-1β); it also increased the phosphorylation of inflammatory proteins nuclear factor-κB p65 (NF-κB p65) and c-Jun (p < 0.05), and the M1 polarization ratio of RAW264.7 or Kupffer cells. Contrary, a high concentration of NaA (2 mM, NaA-H) reduced the inflammatory responses of macrophages. Mechanistically, high doses of NaA increased intracellular acetate concentration in macrophages, while a low dose had the opposite effect, consisting of the trend of changes in regulated macrophage activity. Besides, GPR43 and/or HDACs were not involved in the regulation of macrophage activity by NaA. NaA significantly increased total intracellular cholesterol (TC), triglycerides (TG), and lipid synthesis gene expression levels in macrophages and hepatocytes at either high or low concentrations. Furthermore, NaA regulated the intracellular AMP/ATP ratio and AMPK activity, achieving a bidirectional regulation of macrophage activity, in which the PPARγ/UCP2/AMPK/iNOS/IκBα/NF-κB signaling pathway has an important role. In addition, NaA can regulate lipid accumulation in hepatocytes by NaA-driven macrophage factors through the above-mentioned mechanism. The results revealed that the mode of NaA bi-directionally regulating the macrophages further affects hepatocyte lipid accumulation.
Sleeve Gastrectomy Improves Hepatic Glucose Metabolism by Downregulating FBXO2 and Activating the PI3K-AKT Pathway
Authors: Chen Ningyuan , Cao Ruican , Zhang Zhao , Zhou Sai , Hu Sanyuan
Published: March 2023

Type 2 diabetes mellitus (T2DM), a chronic metabolic disease, is a public health concern that seriously endangers human health. Sleeve gastrectomy (SG) can relieve T2DM by improving glucose homeostasis and enhancing insulin sensitivity. However, its specific underlying mechanism remains elusive. SG and sham surgery were performed on mice fed a high-fat diet (HFD) for 16 weeks. Lipid metabolism was evaluated via histology and serum lipid analysis. Glucose metabolism was evaluated using the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Compared with the sham group, the SG group displayed a reduction in liver lipid accumulation and glucose intolerance, and western blot analysis revealed that the AMPK and PI3K-AKT pathways were activated. Furthermore, transcription and translation levels of FBXO2 were reduced after SG. After liver-specific overexpression of FBXO2, the improvement in glucose metabolism observed following SG was blunted; however, the remission of fatty liver was not influenced by the over expression of FBXO2. Our study explores the mechanism of SG in relieving T2DM, indicating that FBXO2 is a noninvasive therapeutic target that warrants further investigation.
Antibody Assay and Anti-Inflammatory Function Evaluation of Therapeutic Potential of Different Intravenous Immunoglobulins for Alzheimer’s Disease
Authors: Fei Zhangcheng , Pei Renjun , Pan Bo , Ye Shengliang , Zhang Rong , Ma Li , Wang Zongkui , Li Changqing , Du Xi , Cao Haijun
Published: March 2023

Alzheimer’s disease (AD) is a common neurodegenerative disease that currently has no known cure. Intravenous immunoglobulin (IVIG), which contains AD-related antibodies and has anti-inflammatory properties, has shown potential as a treatment for AD. However, the efficacy of clinical trials involving AD patients treated with IVIG has been inconsistent. Our previous study found that different IVIGs had significantly varied therapeutic effects on 3xTg-AD mice. In order to investigate the relationship between the composition and function of IVIG and its efficacy in treating AD, we selected three IVIGs that showed notable differences in therapeutic effects. Then, the concentrations of specific antibodies against β-amyloid (Aβ)42, tau, and hyperphosphorylated tau (p-tau) in three IVIGs, as well as their effects on systemic inflammation induced by lipopolysaccharide (LPS) in Balb/c mice, were analyzed and compared in this study. The results indicated that these IVIGs differed greatly in anti-Aβ42/tau antibody concentration and anti-p-tau ratio, and improved LPS-stimulated peripheral inflammation, liver and kidney injury, and neuroinflammation in Balb/c mice to varying degrees. Combined with our previous results, the efficacy of IVIG against AD may be positively correlated with its level of AD-related antibodies and anti-inflammatory ability. AD-related antibody analysis and functional evaluation of IVIG should be given sufficient attention before clinical trials, as this may greatly affect the therapeutic effect of AD treatment.
Cardiac Functional and Structural Abnormalities in a Mouse Model of CDKL5 Deficiency Disorder
Authors: Loi Manuela , Bastianini Stefano , Candini Giulia , Rizzardi Nicola , Medici Giorgio , Papa Valentina , Gennaccaro Laura , Mottolese Nicola , Tassinari Marianna , Uguagliati Beatrice , Berteotti Chiara , Martire Viviana Lo , Zoccoli Giovanna , Cenacchi Giovanna , Trazzi Stefania , Bergamini Christian , Ciani Elisabetta
Published: March 2023

CDKL5 (cyclin-dependent kinase-like 5) deficiency disorder (CDD) is a severe neurodevelopmental disease that mostly affects girls, who are heterozygous for mutations in the X-linked CDKL5 gene. Mutations in the CDKL5 gene lead to a lack of CDKL5 protein expression or function and cause numerous clinical features, including early-onset seizures, marked hypotonia, autistic features, gastrointestinal problems, and severe neurodevelopmental impairment. Mouse models of CDD recapitulate several aspects of CDD symptomology, including cognitive impairments, motor deficits, and autistic-like features, and have been useful to dissect the role of CDKL5 in brain development and function. However, our current knowledge of the function of CDKL5 in other organs/tissues besides the brain is still quite limited, reducing the possibility of broad-spectrum interventions. Here, for the first time, we report the presence of cardiac function/structure alterations in heterozygous Cdkl5 +/− female mice. We found a prolonged QT interval (corrected for the heart rate, QTc) and increased heart rate in Cdkl5 +/− mice. These changes correlate with a marked decrease in parasympathetic activity to the heart and in the expression of the Scn5a and Hcn4 voltage-gated channels. Interestingly, Cdkl5 +/− hearts showed increased fibrosis, altered gap junction organization and connexin-43 expression, mitochondrial dysfunction, and increased ROS production. Together, these findings not only contribute to our understanding of the role of CDKL5 in heart structure/function but also document a novel preclinical phenotype for future therapeutic investigation.
Direct Z-Scheme CoFe2O4-Loaded g-C3N4 Photocatalyst with High Degradation Efficiency of Methylene Blue under Visible-Light Irradiation
Authors: Gebreslassie Gebrehiwot , Gebrezgiabher Mamo , Lin Bin , Thomas Madhu , Linert Wolfgang
Published: March 2023

Magnetically recyclable direct Z-scheme CoFe2O4-loaded g-C3N4 photocatalyst material was fabricated using a facile hydrothermal technique and subsequently characterized by XRD, VSM, PL, FT-IR, EDX, DRS, SEM, and BET techniques. The characterization results confirmed that nanoparticles of CoFe2O4 are loaded on the surface of g-C3N4 sheets. The optical band gap of g-C3N4 has been decreased from 2.65 eV to 1.30 eV by means of the loading of CoFe2O4 nanoparticles onto the nanosheets of g-C3N4. This has enhanced the separation process of electron-hole. Under visible light irradiation, the photocatalytic activity of the developed direct Z-scheme CoFe2O4-loaded g-C3N4 photocatalyst was evaluated for the photodegradation of methylene blue (MB); during this process the MB decomposed by up to 98.86% in 140 min. Meanwhile, under the same irradiation and time conditions, the g-C3N4 and CoFe2O4 themselves degraded MB up to 74.92% and 51.53%, respectively. The direct Z-scheme CoFe2O4-loaded g-C3N4 material was recovered from the solution after the photocatalytic activity using an external magnet and studied to determine its stability. It was shown that the photoactivity did not change significantly after five consecutive cycles.
Machine Learning Systems Detecting Illicit Drugs Based on Their ATR-FTIR Spectra
Authors: Darie Iulia-Florentina , Anton Stefan Razvan , Praisler Mirela
Published: March 2023

We present a comparative study aiming to determine the most efficient multivariate model screening for the main drugs of abuse based on their ATR-FTIR spectra. A preliminary statistical analysis of selected spectra data extracted from the public SWGDRUG IR Library was first performed. The results corroborated those of an exploratory analysis that was based on several dimensionality reduction methods, i.e., Principal Component Analysis (PCA), Independent Component Analysis (ICA), and autoencoders. Then, several machine learning methods, i.e., Support Vector Machines (SVM), eXtreme Gradient Boosting (XGB), Random Forest, Gradient Boosting, and K-Nearest Neighbors (KNN), were used to assign the drug class membership. In order to account for the stochastic nature of these machine learning methods, both models were evaluated 10 times on a randomly distributed subset of the whole SWGDRUG IR Library, and the results were compared in detail. Finally, their performance in assigning the class identity of three classes of drugs of abuse, i.e., hallucinogenic (2C-x, DOx, and NBOMe) amphetamines, cannabinoids, and opioids, were compared based on confusion matrices and various classification parameters, such as balanced accuracy, sensitivity, and specificity. The advantages of each of the illicit drug-detecting systems and their potential as forensic screening tools used in field scenarios are also discussed.
Sexual Dysfunction in People with Multiple Sclerosis: The Role of Disease Severity, Illness Perception, and Depression
Authors: Scandurra Cristiano , Rosa Laura , Carotenuto Antonio , Moccia Marcello , Arena Sebastiano , Ianniello Antonio , Nozzolillo Agostino , Turrini Mariavittoria , Streito Lidia , Abbadessa Gianmarco , Ferraro Elisabetta , Mattioli Manuela , Chiodi Alessandro , Maldonato Nelson , Bonavita Simona , Clerico Marinella , Cordioli Cinzia , Moiola Lucia , Patti Francesco , Lavorgna Luigi , Filippi Massimo , Borriello Giovanna , D’Amico Emanuele , Pozzilli Carlo , Brescia Morra Vincenzo , Petracca Maria , Lanzillo Roberta
Published: March 2023

Despite being a common issue in people with multiple sclerosis (pwMS), sexual dysfunction is still underinvestigated. This work aims to assess the potential determinants of sexual dysfunction in pwMS by considering its relationship with disease severity (in terms of global disability), illness perception, and depressive symptoms. In this multicenter study, 1010 pwMS responded to an online survey. A serial mediation model considering negative illness perception and depressive symptoms as mediators of the relationship between disease severity and sexual dysfunction was conducted using the SPSS PROCESS Macro with bias-corrected bootstrapping (5000 samples). Disease severity exerts an indirect effect on sexual dysfunction via illness perception, both independently and through depressive symptoms. However, the results indicated that illness perception plays a more crucial role in sexual dysfunction in pwMS with mild disability than in pwMS with moderate-severe disability. This study suggests that higher disability increases its magnitude by enhancing negative illness perception, that, in turn, affects sexual dysfunction both directly and through depressive symptoms, especially in pwMS with mild disability. Modulating the effect of illness perception by favoring adaptive coping strategies might represent a valid approach to mitigate sexual dysfunction symptoms in MS.
Longitudinal Optical Coherence Tomography Measurement of Retinal Ganglion Cell and Nerve Fiber Layer to Assess Benign Course in Multiple Sclerosis
Authors: Al-Hawasi Abbas , Lagali Neil , Fagerholm Per , Huang-Link Yumin
Published: March 2023

A benign form of multiple sclerosis (BMS) is not easily diagnosed, but changes of the retinal ganglion cell layer-inner plexiform layer (GCL-IPL) and retinal nerve fiber layer (RNFL) may be sensitive to the disease. The aim of this study was to use optical coherence tomography (OCT) to investigate longitudinal changes of GCL-IPL and RNFL in BMS. Eighteen patients with BMS and 22 healthy control (HC) subjects were included, with a mean follow-up period of 32.1 months in BMS and 34.3 months in HC. Mean disease duration in BMS was 23.3 years, with 14 patients left untreated. Unilateral optic neuritis (ON) was found in eight patients. Non-ON eyes showed thinner GCL-IPL layer in the BMS group relative to HC (p < 0.001). The thinning rate of GCL-IPL in non-ON BMS, however, was −0.19 ± 0.15 µm/year vs. 0 ± 0.11 µm/year for HC (p = 0.573, age-adjusted). Thinning rate of RNFL in non-ON BMS was −0.2 ± 0.27 µm/year vs. −0.05 ± 0.3 µm/year for HC (p = 0.454, age adjusted). Conclusions: Thinning rate of the GCL-IPL and RNFL in BMS is similar to the healthy population but differs from the thinning rate in relapsing-remitting MS, presenting a non-invasive OCT-based criterion for assessing a benign course in multiple sclerosis.
Closed-Loop Composite Welding and Bonding System Using Radio-Frequency Heating and Pressure
Authors: Enriquez Ian , Noronha Colin , Teo Katrina , Sarmah Anubhav , Gupta Surabhit , Nandi Ankush , Fishbeck Blake , Green Micah J. , Vashisth Aniruddh
Published: March 2023

Polymer parts often replace traditional metallic parts in load-bearing applications due to their high strength-to-weight ratio, with thermoplastics at the forefront. Conventional manufacturing processes rely on using fasteners or adhesives to hold composite assemblies together, but thermoplastics can be welded together. Ultrasonic welding is widely used but becomes challenging for complex geometries, and new parameters need to be developed for different polymers and specimen geometries. In this work, we developed a closed-loop welding machine that employs the recent discovery of radio-frequency (RF) heating of carbonaceous materials. The machine is successfully able to weld polylactic acid (PLA) coupons with graphitic RF susceptors at the bondline in less than 2 min and using less than 50 W of input RF power. We found that a higher areal density of the graphitic paint lowers the mechanical properties of the weld because the carbonaceous materials hinder polymer chain diffusion. A significant change was not observed in weld properties for welding pressure ranges between 0 and 0.3 MPa. However, increasing out-of-plane welding displacement increased the modulus and strength of the weld. This work provides an interesting new automated system for welding polymer composites using RF fields, with potential applications in various manufacturing industries.
Hyperparameter Optimization of a Convolutional Neural Network Model for Pipe Burst Location in Water Distribution Networks
Authors: Antunes André , Ferreira Bruno , Marques Nuno , Carriço Nelson
Published: March 2023

The current paper presents a hyper parameterization optimization process for a convolutional neural network (CNN) applied to pipe burst locations in water distribution networks (WDN). The hyper parameterization process of the CNN includes the early stopping termination criteria, dataset size, dataset normalization, training set batch size, optimizer learning rate regularization, and model structure. The study was applied using a case study of a real WDN. Obtained results indicate that the ideal model parameters consist of a CNN with a convolutional 1D layer (using 32 filters, a kernel size of 3 and strides equal to 1) for a maximum of 5000 epochs using a total of 250 datasets (using data normalization between 0 and 1 and tolerance equal to max noise) and a batch size of 500 samples per epoch step, optimized with Adam using learning rate regularization. This model was evaluated for distinct measurement noise levels and pipe burst locations. Results indicate that the parameterized model can provide a pipe burst search area with more or less dispersion depending on both the proximity of pressure sensors to the burst or the noise measurement level.
Young Creators: Perceptions of Creativity by Primary School Students in Malta
Authors: Mangion Margaret , Riebel Jasmin Antonia
Published: March 2023

Policymakers and employers insist that educational institutions prepare workforce-ready candidates fluent in the application of 21st Century Skills such as creativity. So far, only a few studies have explored the self-perceived creativity of students. This paper addresses this gap in literature by providing an understanding of how young students in upper primary feel about themselves as creative beings. Data for the present study was collected through an anonymous online survey that 561 students, aged 9–11 years and residing in Malta (EU), completed. In-depth responses were collected from a subset of the original sample made up of 101 students through an anonymous online form containing a set of questions. Data was analysed using regression analysis for the quantitative component and through thematic analysis for the qualitative part. Results indicate that, overall, students in Year 6 felt less creative than students in Year 5. Furthermore, findings show that the type of school attended impacted the students’ perception of creativity. From a qualitative perspective, findings led to insights into (i) the interpretation of the term creativity and (ii) the impact of the school environment and how timetabling impacted students’ creativity. The findings suggest that the student’s perceived creative personal identity and the concrete manifestations that they engage in are influenced by environmental factors.
Correction: McCutchan, A.L.; Johnson, B.A. Laboratory Experiments on Ice Melting: A Need for Understanding Dynamics at the Ice-Water Interface. J. Mar. Sci. Eng. 2022, 10, 1008
Authors: McCutchan Aubrey Lynn , Johnson Blair Anne
Published: March 2023

In the original publication [...]
A Hybrid Multi-Criteria Decision-Making Framework for Ship-Equipment Suitability Evaluation Using Improved ISM, AHP, and Fuzzy TOPSIS Methods
Authors: Chen Cheng , Zhang Xiangrui , Wang Guo , Feng Feng , Sun Cong , He Qin
Published: March 2023

The inherent complexity of large ships makes it challenging to evaluate ship designs systematically and scientifically. Knowledge-based expert systems can be reasonable solutions. However, this problem needs more rationality and better operability, especially in complicated ship-equipment suitability evaluation problems with numerous indicators and complex structures. This paper presents a hybrid multi-criteria decision-making (MCDM) framework to extend the ship-equipment suitability evaluation to group decision-making settings, where individual consistency and group consensus are thoroughly investigated to improve rationality and operability. As a result, an improved Interpretive Structural Modeling (ISM) method is developed to construct the evaluation index systems. Furthermore, based on an applicability analysis of the selected MCDM methods, an improved Analytical Hierarchy Process (AHP) method is proposed to distribute the index weights, and an applicable Fuzzy Technique for Order Preference by Similarity to Ideal Solution (Fuzzy TOPSIS) method is utilized to evaluate and select appropriate ship designs. Finally, a ship-equipment environmental suitability evaluation case is examined. The results indicate that the proposed framework improves the rationality and operability of the decision-making process and provides practical support to decision-makers for the systematic and scientific evaluation of ship designs. Therefore, it can also be applied to other ship design evaluation and selection problems.
Small Combustion Chamber for Marine Fuel Oil and Analysis of Exhaust Gas Characteristics of Marine Gas Oil
Authors: Lee Tae-Ho , Kang Il-Seok
Published: March 2023

A small combustion chamber was developed and manufactured for empirical combustion testing of several alternative fuels developed to meet IMO emission limits for fuel oil used in ships. The combustion chamber consists of four independent tanks and a circulation system with a two-stage heating function owing to the high viscosity and temperature of ship fuel. A gun-type burner is mounted on the side of the combustion chamber, which possesses a cylindrical shape and a capacity of less than 300 L. This device was manufactured in accordance with several variables such that the basic stage performance and simulation tests of each fuel could be sufficiently completed before performing the combustion test to simulate the engines of large ships. To conduct an initial experiment using the developed combustion chamber, low-sulfur MGO with a sulfur content less than or equal to 0.05% was chosen, and ideal operating parameters were selected according to the measurement tests based on load control. The exhaust gas temperature differed by approximately 10.7% as a result of burning MGO at a burner load state of 80–100%. The use of a normal oxygen concentration of 4% helped remove approximately 14.31 ppm of nitrogen oxide and 1.91% of carbon dioxide. The maximum combustion efficiency was 70.17%, indicating the chamber’s potential for use in a variety of combustion tests of alternative fuels for ships in the forthcoming years.
Evaluation of Cua Lo Estuary’s Morpho-Dynamic Evolution and Its Impact on Port Planning
Authors: Quang Dinh Nhat , Anh Nguyen Quang Duc , Tam Ho Sy , Tinh Nguyen Xuan , Tanaka Hitoshi , Viet Nguyen Trung
Published: March 2023

Coastal erosion and accretion along the Quang Nam coast in Vietnam have been increasing in recent years, causing negative impacts on the inhabitants and local ecology. The Cua Lo estuary in Nui Thanh district has a complex hydrodynamic regime owing to its connection with two estuaries and three different tributaries. Therefore, a detailed study of the mechanisms and processes of these phenomena is crucial to understand the potential impact of a proposed 50,000-ton cargo port. In this study, the Delft3D model is employed to evaluate the morpho-dynamic changes in the area of Cua Lo under monsoon wave climate, storm, and flood conditions both before and after port and navigation channel construction. Results indicate that in the absence of the port, tidal currents and waves during monsoon storms cause significant erosion on the south bank and accretion on the north bank. Furthermore, the GenCade model is utilized to predict the future shoreline changes after the construction of two jetties. The model reveals that after 50 years of operation, the shoreline modifications will extend 449 m towards the sea, in comparison to natural conditions. However, the design of the northern jetty will ensure safe and proper operation without impacting the navigation channel. This study offers valuable insights into the morphological changes in the Cua Lo area and their potential implications, which can aid in the development of sustainable coastal management strategies for the region.
Wave Runup Prediction and Alongshore Variability on a Pocket Gravel Beach under Fetch-Limited Wave Conditions
Authors: Bujak Damjan , Ilic Suzana , Miličević Hanna , Carević Dalibor
Published: March 2023

Most empirical equations used for wave runup predictions have been developed from measurements at straight sandy beaches in unlimited fetch environments. While there are empirical equations to predict wave runup on gravel beaches, they have not been tested for prediction of wave runup on pocket gravel beaches, in limited-fetch environment, which can be found around Mediterranean. This paper addresses this lack of measurements on this type of beaches and examines the alongshore variability of wave runup. Wave runup measurements were made using video observations along 3 cross-sectional profiles on the pocket beach of Ploče, Croatia. The measurements have shown that the wave runup can vary for about 71% even around the centerline of the pocket beach. This variability is due to beach orientation and alignment of beach profiles to the prevailing wave direction, as well as difference in beach slope. Comparison of wave runup predictions from five well-known empirical equations and field measurements showed significant underprediction (up to NBIAS = −0.33) for energetic wave events, and overall high scatter (up to NRMSE = 0.38). The best performing wave runup equation was used for further refinement outside the original parameter space by including the Goda wave peakedness parameter (Qp). The newly developed empirical equation for wave runup reduced the NBIAS to 0 and the NRMSE by 31% compared to the original equation (developed equation metrics: R = 0.91, NBIAS = 0, NRMSE = 0.2, HH = 0.2 on the study site). This empirical equation can potentially be used for design of coastal structures and artificial beaches in similar environments, but further measurements are needed to test its applicability to a range of forcing and environmental conditions.
Yeast Ribonucleotide Reductase Is a Direct Target of the Proteasome and Provides Hyper Resistance to the Carcinogen 4-NQO
Authors: Spasskaya Daria S. , Kulagin Kirill A. , Grineva Evgenia N. , Osipova Pamila J. , Poddubko Svetlana V. , Bubis Julia A. , Kazakova Elizaveta M. , Kusainova Tomiris T. , Gorshkov Vladimir A. , Kjeldsen Frank , Karpov Vadim L. , Tarasova Irina A. , Karpov Dmitry S.
Published: March 2023

Various external and internal factors damaging DNA constantly disrupt the stability of the genome. Cells use numerous dedicated DNA repair systems to detect damage and restore genomic integrity in a timely manner. Ribonucleotide reductase (RNR) is a key enzyme providing dNTPs for DNA repair. Molecular mechanisms of indirect regulation of yeast RNR activity are well understood, whereas little is known about its direct regulation. The study was aimed at elucidation of the proteasome-dependent mechanism of direct regulation of RNR subunits in Saccharomyces cerevisiae. Proteome analysis followed by Western blot, RT-PCR, and yeast plating analysis showed that upregulation of RNR by proteasome deregulation is associated with yeast hyper resistance to 4-nitroquinoline-1-oxide (4-NQO), a UV-mimetic DNA-damaging drug used in animal models to study oncogenesis. Inhibition of RNR or deletion of RNR regulatory proteins reverses the phenotype of yeast hyper resistance to 4-NQO. We have shown for the first time that the yeast Rnr1 subunit is a substrate of the proteasome, which suggests a common mechanism of RNR regulation in yeast and mammals.