bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic Profiles of Pomegranate Juices during Fruit Development and the Redirection of Flavonoid Metabolism
Authors: Zhao Jianrong , Qi Xiaoxiao , Li Jiyu , Cao Zhen , Liu Xin , Yu Qing , Xu Yiliu , Qin Gaihua
Published: August 2023

The pomegranate (Punica granatum L.) fruit is favorable for its nutrient-rich benefits to human health. However, the global metabolic profiles of pomegranate juice and the metabolic mechanisms of its essential metabolites are poorly understood. In this study, we conducted a widely targeted metabolome, integrated with the transcriptome of juices (edible parts) of pomegranate fruits at 50, 95, and 140 days after flowering (DAF) to comprehensively investigate the metabolic profiles and potential metabolism of essential metabolites. Five hundred and nine metabolites, including 11 sugar and sugar alcohols, 17 common organic acids, 20 essential amino acids, and a variety of flavonoids, were detected in pomegranate juices. Among them, metabolites in the flavonoid biosynthesis pathway greatly changed during fruit development. Notably, the redirection of metabolite flux from catechin and its derivative synthesis to anthocyanin synthesis occurred at the later developmental stages. The increased expression of Pgr021399.1 encoding dihydroflavonol 4-reductase (DFR), Pgr017842.1 encoding anthocyanidin synthesis (ANS), Pgr015322.1 encoding anthocyanidin 3-O-glucosyltransferase (BZ1), Pgr000447.1 encoding UTG75C1, and the decreased expression of Pgr024128.1 encoding leucoanthocyanidin reductase (LAR) may trigger redirection. The results of this study provide a global view of the metabolic profiles of pomegranate juices and valuable information on the molecular mechanisms underlying the redirection of flavonoid metabolism. It also sheds light on the genetic regulation of flavonoid metabolism in pomegranate juices.
Genome-Wide Identification Reveals That BZR1 Family Transcription Factors Involved in Hormones and Abiotic Stresses Response of Lotus (Nelumbo)
Authors: Zhou Ping , Jiang Huiyan , Li Jingwen , Jin Qijiang , Wang Yanjie , Xu Yingchun
Published: August 2023

The brassinazole-resistant (BZR) transcription factors (TFs) are key components of brassinosteroid (BR) signaling, which play an important role in regulating plant growth and development as well as responding to abiotic stress. However, a functional study of BZR transcription factors in lotuses has not been reported. A total 10 BZR1 genes (four NnBZR1 and six NlBZR1) were identified from the genomes of two lotus species (Nelumbo nucifera and Nelumbo lutea). The construction of the phylogenetic tree showed that the 10 BZR1 genes of the lotus were divided into four groups; the NnBZR1s and NlBZR1s were unevenly distributed on three and four chromosomes, respectively. Gene structure analysis showed that motif 1 and motif 9 are highly conserved in the lotus BZR1 protein, which might be related to the conserved domain BES_N of BZR1. The analysis of promoter cis-acting elements showed that the promoters of most of the BZR1 genes in the lotus contained elements related to light-responsive, ABA-responsive and abiotic stress-responsive factors, indicating that the BZR1 gene of the lotus played an important role in its response to abiotic stress. The responses of BZR1 genes to BR, ABA and four abiotic stresses (Cold, PEG6000, Cd and NaCl) were analyzed by qRT-PCR. The qRT-PCR results further verified that the lotus BZR1 genes play an important role in responding to hormone signals and resisting abiotic stress. This study laid the foundation for further research on the function of lotus BZR1 genes and provided a theoretical basis for future breeding and horticultural applications.
Enhancing Horticultural Crops through Genome Editing: Applications, Benefits, and Considerations
Authors: Daniel Melvin A. , Sebastin Raveendar , Yu Ju-Kyung , Soosaimanickam Maria Packiam , Chung Jong Wook
Published: August 2023

Genome editing has emerged as a powerful tool for accelerating crop improvement in horticultural crops by enabling precise modifications to their genetic makeup. This review provides an in-depth exploration of the applications, methodologies, and potential impacts of genome editing in horticulture. The review focuses on three major genome editing tools in horticulture, CRISPR-Cas9, TALENs, and ZFNs. The underlying mechanisms, applications, and potential challenges associated with each tool are discussed in detail. CRISPR-Cas9, being a versatile and widely used system, has the potential to enhance traits such as disease resistance, abiotic stress tolerance, nutritional content, and yield in horticultural crops. TALENs and ZFNs, although less commonly used, offer alternative options for targeted DNA modifications, and have demonstrated success in specific applications. We emphasize the potential benefits of genome editing in horticulture, including improved crop productivity, quality, and nutritional value. However, challenges such as off-target effects, delivery methods, and regulatory frameworks need to be addressed for the full realization of this technology’s potential. This review serves as a valuable resource for researchers, policymakers, and stakeholders, providing insights into the opportunities and complexities associated with harnessing genome editing for enhanced traits in horticultural crops. By navigating these challenges, genome editing can contribute to sustainable advancements in horticulture, benefiting both producers and consumers worldwide.
Moringa oleifera Lam. Seed Extracts Improve the Growth, Essential Minerals, and Phytochemical Constituents of Lessertia frutescens L.
Authors: Buthelezi Nana Millicent Duduzile , Ntuli Nontuthuko Rosemary , Mugivhisa Liziwe Lizbeth , Gololo Sechene Stanley
Published: August 2023

The exploring of biostimulant sources is important for sustainable agriculture. Although all parts of the moringa plant (Moringa oleifera Lam.) are rich in phytohormones and phytochemicals which may be utilised as a potential plant growth enhancer, most attention has been placed on its leaves as a possible biostimulant for enhancing productivity of plants. Little has been reported on moringa seed extract (MSE) as a growth enhancer on medicinal plants. Thus, this study investigated the efficacy of MSE doses (water spray as control, MSE at 2, 4, 6 and 8%) on growth attributes, mineral content and phytochemical compositions of cancer bush plants (Lessertia frutescens L.) grown during the winter–spring and spring–summer seasons of 2021. A gradual increase in growth characteristics, chlorophyll content, phenols and flavonoid contents was recorded in all concentrations of MSE-treated plants compared with controls. Furthermore, all levels of MSE effectively enhanced the concentrations of macronutrients such as calcium, magnesium, phosphorus, nitrogen and potassium as well as micronutrients comprising copper, zinc, iron, manganese and sodium of cancer bush plants relative to untreated plants. Both 6 and 8% MSE concentrations showed high productivity, minerals and phytochemical constituents in cancer bush plants in comparison with 2 and 4% MSE treatments. Overall, the findings of this study demonstrated that, even at low concentrations, MSE can be successfully applied as a biostimulant to improve the growth and biochemical attributes of cancer bush plants.
Nondestructive Detecting Maturity of Pineapples Based on Visible and Near-Infrared Transmittance Spectroscopy Coupled with Machine Learning Methodologies
Authors: Qiu Guangjun , Lu Huazhong , Wang Xu , Wang Chen , Xu Sai , Liang Xin , Fan Changxiang
Published: August 2023

Pineapple is mainly grown in tropical regions and consumed fresh worldwide due to its attractive flavor and health benefits. With increasing global production and trade volume, there is an urgent need for nondestructive techniques for accurate and efficient detection of the internal quality of pineapples. Therefore, this study is dedicated to developing a nondestructive method for real-time determining the internal quality of pineapples by using VIS/NIR transmittance spectroscopy technique and machine learning methodologies. The VIS/NIR transmittance spectrums ranging in 400–1100 nm of total 195 pineapples were collected from a dynamic experimental platform. The maturity grade and soluble solids content (SSC) of individual pineapples were then measured as indicators of internal quality. The qualitative model for discriminating maturity grades of pineapple achieved a high accuracy of 90.8% by the PLSDA model for unknown samples. Meanwhile, the quantitative model for determining SSC also reached a determination coefficient (RP2) of 0.7596 and a root mean square error of prediction (RMSEP) of 0.7879 °Brix by the ANN-PLS model. Overall, high model performance demonstrated that using VIS/NIR transmittance spectroscopy technique coupled with machine learning methodologies could be a feasible method for nondestructive and real-time detection of the internal quality of pineapples.
Evaluation of BOLAM Fine Grid Weather Forecasts with Emphasis on Hydrological Applications
Authors: Malamos Nikolaos , Koulouris Dimitrios , Tsirogiannis Ioannis L. , Koutsoyiannis Demetris
Published: August 2023

The evaluation of weather forecast accuracy is of major interest in decision making in almost every sector of the economy and in civil protection. To this, a detailed assessment of Bologna Limited-Area Model (BOLAM) seven days fine grid 3 h predictions is made for precipitation, air temperature, relative humidity, and wind speed over a large lowland agricultural area of a Mediterranean-type climate, characterized by hot summers and rainy moderate winters (plain of Arta, NW Greece). Timeseries that cover a four-year period (2016–2019) from seven agro-meteorological stations located at the study area are used to run a range of contingency and accuracy measures as well as Taylor diagrams, and the results are thoroughly discussed. The overall results showed that the model failed to comply with the precipitation regime throughout the study area, while the results were mediocre for wind speed. Considering relative humidity, the results revealed acceptable performance and good correlation between the model output and the observed values, for the early days of forecast. Only in air temperature, the forecasts exhibited very good performance. Discussion is made on the ability of the model to predict major rainfall events and to estimate water budget components as rainfall and reference evapotranspiration. The need for skilled weather forecasts from improved versions of the examined model that may incorporate post-processing techniques to improve predictions or from other forecasting services is underlined.
Healthcare Professionals and Noise-Generating Tools: Challenging Assumptions about Hearing Loss Risk
Authors: Alberti Giuseppe , Portelli Daniele , Galletti Cosimo
Published: August 2023

Hearing loss is a significant global health concern, affecting billions of people and leading to various physical, mental, and social consequences. This paper focuses on the risk of noise-induced hearing loss (NIHL) among specific healthcare professionals, especially ear surgeons, orthopaedic surgeons, dentists, and dental hygienists, who frequently use noisy instruments in their professions. While studies on these professionals’ noise exposure levels are limited, certain conditions and factors could pose a risk to their hearing. Measures such as engineering and administrative controls, regular audiometric testing, and the use of hearing protection devices are crucial in preventing NIHL. Early detection and intervention are also vital to mitigate further damage. This paper proposes the results of a modified screening protocol, including questionnaires, audiometry, and additional diagnostic tests to identify and address potential hearing disorders. Specific healthcare professionals should remain aware of the risks, prioritize hearing protection, and undergo regular monitoring to safeguard their long-term auditory well-being.
Presence of Perfluoroalkyl Substances in Landfill Adjacent Surface Waters in North Carolina
Authors: Walsh Aleah , Woods Courtney G.
Published: August 2023

Landfills pose an important public health risk, especially in historically disenfranchised communities that are disproportionately sited for landfills and in rural areas where private wells may be impacted. Landfills are major sources of perfluoroalkyl substances (PFAS) that migrate into the surrounding environment. This study characterized PFAS in surface waters adjacent to two landfills, one in Sampson County (SC) and one in Orange County (OC) in North Carolina. In addition to municipal solid waste and construction and demolition waste, the landfill in SC accepts industrial sludge from a chemical plant that produces proprietary PFAS. Over four months, 35 surface water samples were collected at upstream, landfill-adjacent, and downstream/downgradient sites. Thirty-four PFAS were analyzed using liquid chromatography with tandem mass spectroscopy. Of those, six novel and six legacy PFAS were detected. Legacy PFAS were detected in surface water near both landfills, with the highest concentrations adjacent to the landfill. Novel PFAS were only detected in surface water near the SC landfill and showed the highest concentrations adjacent to the landfill, indicating offsite migration of PFAS. These findings support the need for more comprehensive and frequent monitoring of groundwater and surface water wells near landfills and stricter regulation regarding the landfilling of industrial materials.
Differential Magnitude of Resilience between Emotional Intelligence and Life Satisfaction in Mountain Sports Athletes
Authors: Sanz-Junoy Guillermo , Gavín-Chocano Óscar , Ubago-Jiménez José L. , Molero David
Published: August 2023

The field of mountain sports has its own characteristics, different from other sports modalities. Emotional intelligence and resilience not only refer to the adaptive capacity that can be developed after an adverse experience, but can also be factors that positively affect sporting performance in extreme conditions. In this study, 4818 athletes from the Spanish Federation of Mountain Sports and Climbing participated; 2696 were men (67.1%) and 1322 were women (32.9%), with a mean age of 49.42 years (±11.9). The Resilience Scale (RS-14), Wong Law Emotional Intelligence Scale (WLEIS-S) and Satisfaction with Life Scale (SWLS) were used. The aim was to provide evidence for the potential for resilience (personal competence and acceptance of self and life) among EI and life satisfaction in mountain and climbing athletes. The results showed that the coefficients of determination of personal competence [(Q2 = 0.286); (R2 = 0.578)], acceptance of self [(Q2 = 0.310); (R2 = 0.554)] and life satisfaction [(Q2 = 0.299); (R2 = 0.421)] for the estimation of the measurement model indicated a good model fit. In the future, it would be necessary to carry out specific studies discriminating by sport modality and methods for this area, with a large number of athletes and disciplines, as well as evaluating its possible applications for the improvement of emotional factors.
Efficacy of Pembrolizumab in Advanced Melanoma: A Narrative Review
Authors: Rizzetto Giulio , De Simoni Edoardo , Molinelli Elisa , Offidani Annamaria , Simonetti Oriana
Published: August 2023

Pembrolizumab has been shown to increase survival in patients with metastatic melanoma. Considering the numerous oncoming studies, we decided to conduct a narrative review of the latest efficacy evidence regarding the use of pembrolizumab, alone or in combination, in patients with metastatic melanoma. A search was conducted in PubMed using “pembrolizumab,” and “metastatic melanoma” as keywords, considering studies from 2022 onward. We reviewed pembrolizumab and associations, cost-effectiveness, virus, advanced acral melanoma, long-term outcomes, real-life data, biomarkers, obesity, and vaccines. In conclusion, pembrolizumab is a fundamental option in the therapy of metastatic melanoma. However, a certain group of patients do not respond and, therefore, new combination options need to be evaluated. In particular, the use of vaccines tailored to tumor epitopes could represent a breakthrough in the treatment of resistant forms. Further studies with larger sample numbers are needed to confirm the preliminary results.
Polarization of Melatonin-Modulated Colostrum Macrophages in the Presence of Breast Tumor Cell Lines
Authors: Silva Kenia Maria Rezende , França Danielle Cristina Honório , de Queiroz Adriele Ataídes , Fagundes-Triches Danny Laura Gomes , de Marchi Patrícia Gelli Feres , Morais Tassiane Cristina , Honorio-França Adenilda Cristina , França Eduardo Luzía
Published: August 2023

Human colostrum and milk contain diverse cells and soluble components that have the potential to act against tumors. In breast cancer, macrophages play a significant role in immune infiltration and contribute to the progression and spread of tumors. However, studies suggest that these cells can be reprogrammed to act as an antitumor immune response. This study aimed to evaluate the levels of melatonin and its receptors, MT1 (melatonin receptor 1) and MT2 (melatonin receptor 2), in colostrum and assess the differentiation and polarization of the colostrum macrophages modulated by melatonin in the presence of breast tumor cells. Colostrum samples were collected from 116 mothers and tested for their melatonin and receptor levels. The colostrum cells were treated with or without melatonin and then cultured for 24 h in the presence or absence of breast tumor cells. The results showed that melatonin treatment increased the expression of MT1 and MT2 in the colostrum cells. Furthermore, melatonin treatment increased the percentage of M1 macrophages and decreased the percentage of M2 macrophages. When the colostrum macrophages were cocultured with breast tumor cells, melatonin reduced the percentage of both macrophage phenotypes and the cytokines tumor necrosis factor-alpha (TNF-α) and interleukin 8 (IL-8). These data suggest that melatonin can regulate the inflammatory process via M1 macrophages in the tumor microenvironment and, simultaneously, the progression of M2 macrophages that favor tumorigenesis.
Pentylenetetrazole-Induced Seizures Are Increased after Kindling, Exhibiting Vitamin-Responsive Correlations to the Post-Seizures Behavior, Amino Acids Metabolism and Key Metabolic Regulators in the Rat Brain
Authors: Aleshin Vasily A. , Graf Anastasia V. , Artiukhov Artem V. , Ksenofontov Alexander L. , Zavileyskiy Lev G. , Maslova Maria V. , Bunik Victoria I.
Published: August 2023

Epilepsy is characterized by recurrent seizures due to a perturbed balance between glutamate and GABA neurotransmission. Our goal is to reveal the molecular mechanisms of the changes upon repeated challenges of this balance, suggesting knowledge-based neuroprotection. To address this goal, a set of metabolic indicators in the post-seizure rat brain cortex is compared before and after pharmacological kindling with pentylenetetrazole (PTZ). Vitamins B1 and B6 supporting energy and neurotransmitter metabolism are studied as neuroprotectors. PTZ kindling increases the seizure severity (1.3 fold, p < 0.01), elevating post-seizure rearings (1.5 fold, p = 0.03) and steps out of the walls (2 fold, p = 0.01). In the kindled vs. non-kindled rats, the post-seizure p53 level is increased 1.3 fold (p = 0.03), reciprocating a 1.4-fold (p = 0.02) decrease in the activity of 2-oxoglutarate dehydrogenase complex (OGDHC) controlling the glutamate degradation. Further, decreased expression of deacylases SIRT3 (1.4 fold, p = 0.01) and SIRT5 (1.5 fold, p = 0.01) reciprocates increased acetylation of 15 kDa proteins 1.5 fold (p < 0.01). Finally, the kindling abrogates the stress response to multiple saline injections in the control animals, manifested in the increased activities of the pyruvate dehydrogenase complex, malic enzyme, glutamine synthetase and decreased malate dehydrogenase activity. Post-seizure animals demonstrate correlations of p53 expression to the levels of glutamate (r = 0.79, p = 0.05). The correlations of the seizure severity and duration to the levels of GABA (r = 0.59, p = 0.05) and glutamate dehydrogenase activity (r = 0.58, p = 0.02), respectively, are substituted by the correlation of the seizure latency with the OGDHC activity (r = 0.69, p < 0.01) after the vitamins administration, testifying to the vitamins-dependent impact of the kindling on glutamate/GABA metabolism. The vitamins also abrogate the correlations of behavioral parameters with seizure duration (r 0.53–0.59, p < 0.03). Thus, increased seizures and modified post-seizure behavior in rats after PTZ kindling are associated with multiple changes in the vitamin-dependent brain metabolism of amino acids, linked to key metabolic regulators: p53, OGDHC, SIRT3 and SIRT5.
Advances in the Properties of Incomptine A: Cytotoxic Activity and Downregulation of Hexokinase II in Breast Cancer Cell Lines
Authors: Arietta-García Angel Giovanni , Calzada Fernando , Ramírez-Sánchez Israel , Bautista Elihú , García-Hernandez Normand , Ordoñez-Razo Rosa María
Published: August 2023

Breast cancer treatments are limited by the cancer subtype and its selectivity towards tumor cells, hence the importance of finding compounds that increase the survival of healthy cells and target any subtype. Incomptine A (IA) is a sesquiterpene lactone with demonstrated cytotoxic activity. In this study, through in vitro assays, it was observed that IA has similar cytotoxic activity between the subtypes triple negative, HER2+, and luminal A of the breast cancer cell lines. IA cytotoxic activity is higher in cancer than in nontumorigenic cells, and its selectivity index for cancer cells is more than that of the drug doxorubicin. Molecular docking and its in silico comparison with the 2-Deoxyglucose inhibitor suggest that IA could bind to Hexokinase II (HKII), decreasing its expression. Since we did not find changes in the expression of the glycolytic pathway, we suppose that IA could affect the antiapoptotic function of HKII in cancer cells. The IA-HKII union would activate the voltage-gated anion channel 1 (VDAC1), resuming apoptosis. Therefore, we suggest that IA could be used against almost any subtype and that its cytotoxic effect could be due to the reactivation of apoptosis in breast cancer cells.
Enhancing Nasopharyngeal Carcinoma Cell Separation with Selective Fibronectin Coating and Topographical Modification on Polydimethylsiloxane Scaffold Platforms
Authors: Wang M. T. , Pang S. W.
Published: August 2023

The extracellular matrix (ECM) serves as a complex scaffold with diverse physical dimensions and surface properties influencing NPC cell migration. Polydimethylsiloxane (PDMS), a widely used biocompatible material, is hydrophobic and undesirable for cell seeding. Thus, the establishment of a biomimetic model with varied topographies and surface properties is essential for effective NPC43 cell separation from NP460 cells. This study explored how ECM surface properties influence NP460 and NPC43 cell behaviors via plasma treatments and chemical modifications to alter the platform surface. In addition to the conventional oxygen/nitrogen (O2/N2) plasma treatment, O2 and argon plasma treatments were utilized to modify the platform surface, which increased the hydrophilicity of the PDMS platforms, resulting in enhanced cell adhesion. (3-aminopropyl)triethoxysilane and fibronectin (FN) were used to coat the PDMS platforms uniformly and selectively. The chemical coatings significantly affected cell motility and spreading, as cells exhibited faster migration, elongated cell shapes, and larger spreading areas on FN-coated surfaces. Furthermore, narrower top layer trenches with 5 µm width and a lower concentration of 10 µg/mL FN were coated selectively on the platforms to limit NP460 cell movements and enhance NPC43 cell separation efficiency. A significantly high separation efficiency of 99.4% was achieved on the two-layer scaffold platform with 20/5 µm wide ridge/trench (R/T) as the top layer and 40/10 µm wide R/T as the bottom layer, coupling with 10 µg/mL FN selectively coated on the sidewalls of the top and bottom layers. This work demonstrated an innovative application of selective FN coating to direct cell behavior, offering a new perspective to probe into the subtleties of NPC cell separation efficiency. Moreover, this cost-effective and compact microsystem sets a new benchmark for separating cancer cells.
Design, Synthesis, and Biological Evaluation of New Potential Unusual Modified Anticancer Immunomodulators for Possible Non-Teratogenic Quinazoline-Based Thalidomide Analogs
Authors: Mabrouk Reda , Abdallah Abdallah , Mahdy Hazem , El-Kalyoubi Samar , Kamal Omar , Abdelghany Tamer , Zayed Mohamed , Alshaeri Heba , Alasmari Moudi , El-Zahabi Mohamed
Published: August 2023

Sixteen new thalidomide analogs were synthesized. The new candidates showed potent in vitro antiproliferative activities against three human cancer cell lines, namely hepatocellular carcinoma (HepG-2), prostate cancer (PC3), and breast cancer (MCF-7). It was found that compounds XII, XIIIa, XIIIb, XIIIc, XIIId, XIVa, XIVb, and XIVc showed IC50 values ranging from 2.03 to 13.39 µg/mL, exhibiting higher activities than thalidomide against all tested cancer cell lines. Compound XIIIa was the most potent candidate, with an IC50 of 2.03 ± 0.11, 2.51 ± 0.2, and 0.82 ± 0.02 µg/mL compared to 11.26 ± 0.54, 14.58 ± 0.57, and 16.87 ± 0.7 µg/mL for thalidomide against HepG-2, PC3, and MCF-7 cells, respectively. Furthermore, compound XIVc reduced the expression of NFκB P65 levels in HepG-2 cells from 278.1 pg/mL to 63.1 pg/mL compared to 110.5 pg/mL for thalidomide. Moreover, compound XIVc induced an eightfold increase in caspase-8 levels with a simultaneous decrease in TNF-α and VEGF levels in HepG-2 cells. Additionally, compound XIVc induced apoptosis and cell cycle arrest. Our results reveal that the new candidates are potential anticancer candidates, particularly XIIIa and XIVc. Consequently, they should be considered for further evaluation for the development of new anticancer drugs.
Cannabidiol and Cannabigerol Modify the Composition and Physicochemical Properties of Keratinocyte Membranes Exposed to UVA
Authors: Wroński Adam , Dobrzyńska Izabela , Sękowski Szymon , Łuczaj Wojciech , Olchowik-Grabarek Ewa , Skrzydlewska Elżbieta
Published: August 2023

The action of UVA radiation (both that derived from solar radiation and that used in the treatment of skin diseases) modifies the function and composition of keratinocyte membranes. Therefore, this study aimed to assess the effects of phytocannabinoids (CBD and CBG), used singly and in combination, on the contents of phospholipids, ceramides, lipid rafts and sialic acid in keratinocyte membranes exposed to UVA radiation, together with their structure and functionality. The phytocannabinoids, especially in combination (CBD+CBG), partially prevented increased levels of phosphatidylinositols and sialic acid from occurring and sphingomyelinase activity after the UVA exposure of keratinocytes. This was accompanied by a reduction in the formation of lipid rafts and malondialdehyde, which correlated with the parameters responsible for the integrity and functionality of the keratinocyte membrane (membrane fluidity and permeability and the activity of transmembrane transporters), compared to UVA-irradiated cells. This suggests that the simultaneous use of two phytocannabinoids may have a protective effect on healthy cells, without significantly reducing the therapeutic effect of UV radiation used to treat skin diseases such as psoriasis.
Cancer-Associated Fibroblasts Influence Survival in Pleural Mesothelioma: Digital Gene Expression Analysis and Supervised Machine Learning Model
Authors: Borchert Sabrina , Mathilakathu Alexander , Nath Alina , Wessolly Michael , Mairinger Elena , Kreidt Daniel , Steinborn Julia , Walter Robert F. H. , Christoph Daniel C. , Kollmeier Jens , Wohlschlaeger Jeremias , Mairinger Thomas , Brcic Luka , Mairinger Fabian D.
Published: August 2023

The exact mechanism of desmoplastic stromal reaction (DSR) formation is still unclear. The interaction between cancer cells and cancer-associated fibroblasts (CAFs) has an important role in tumor progression, while stromal changes are a poor prognostic factor in pleural mesothelioma (PM). We aimed to assess the impact of CAFs paracrine signaling within the tumor microenvironment and the DSR presence on survival, in a cohort of 77 PM patients. DSR formation was evaluated morphologically and by immunohistochemistry for Fibroblast activation protein alpha (FAP). Digital gene expression was analyzed using a custom-designed CodeSet (NanoString). Decision-tree-based analysis using the “conditional inference tree” (CIT) machine learning algorithm was performed on the obtained results. A significant association between FAP gene expression levels and the appearance of DSR was found (p = 0.025). DSR-high samples demonstrated a statistically significant prolonged median survival time. The elevated expression of MYT1, KDR, PIK3R1, PIK3R4, and SOS1 was associated with shortened OS, whereas the upregulation of VEGFC, FAP, and CDK4 was associated with prolonged OS. CIT revealed a three-tier system based on FAP, NF1, and RPTOR expressions. We could outline the prognostic value of CAFs-induced PI3K signaling pathway activation together with FAP-dependent CDK4 mediated cell cycle progression in PM, where prognostic and predictive biomarkers are urgently needed to introduce new therapeutic strategies.
CC5 and CC8, Two Disintegrin Isoforms from Cerastes cerastes Snake Venom Decreased Inflammation Response In Vitro and In Vivo
Authors: Morjen Maram , Zakraoui Ons , Abdelkafi-Koubaa Zaineb , Srairi-Abid Najet , Marrakchi Naziha , Essafi-Benkhadir Khadija , Jebali Jed
Published: August 2023

Inflammation is associated with many pathology disorders and the malignant progression of most cancers. Therefore, targeting inflammatory pathways could provide a promising strategy for disease prevention and treatment. In this study, we experimentally investigated the anti-inflammatory effect of CC5 and CC8, two disintegrin isoforms isolated from Cerastes cerastes snake venom, on LPS-stimulated macrophages, both on human THP-1 and mouse RAW264.7 cell adherence and their underlying mechanisms by measuring cytokine release levels and Western blot assay. Equally, both molecules were evaluated on a carrageenan-induced edema rat model. Our findings suggest that CC5 and CC8 were able to reduce adhesion of LPS-stimulated macrophages both on human THP-1 and mouse RAW264.7 cells to fibrinogen and vitronectin through the interaction with the αvβ3 integrin receptor. Moreover, CC5 and CC8 reduced the levels of reactive oxygen species (ROS) mediated by the NF-κB, MAPK and AKT signaling pathways that lead to decreased production of the pro-inflammatory cytokines TNF-α, IL-6 and IL-8 and increased secretion of IL-10 in LPS-stimulated THP-1 and RAW264.7 cells. Interestingly, both molecules potently exhibited an anti-inflammatory effect in vivo by reducing paw swelling in rats. In light of these results, we can propose the CC5 and CC8 disintegrins as interesting tools to design potential candidates against inflammatory-related diseases.
Differential Modulation of the Phosphoproteome by the MAP Kinases Isoforms p38α and p38β
Authors: Melamed Kadosh Dganit , Beenstock Jonah , Engelberg David , Admon Arie
Published: August 2023

The p38 members of the mitogen-activated protein kinases (MAPKs) family mediate various cellular responses to stress conditions, inflammatory signals, and differentiation factors. They are constitutively active in chronic inflammatory diseases and some cancers. The differences between their transient effects in response to signals and the chronic effect in diseases are not known. The family is composed of four isoforms, of which p38α seems to be abnormally activated in diseases. p38α and p38β are almost identical in sequence, structure, and biochemical and pharmacological properties, and the specific unique effects of each of them, if any, have not yet been revealed. This study aimed to reveal the specific effects induced by p38α and p38β, both when transiently activated in response to stress and when chronically active. This was achieved via large-scale proteomics and phosphoproteomics analyses using stable isotope labeling of two experimental systems: one, mouse embryonic fibroblasts (MEFs) deficient in each of these p38 kinases and harboring either an empty vector or vectors expressing p38αWT, p38βWT, or intrinsically active variants of these MAPKs; second, induction of transient stress by exposure of MEFs, p38α−/−, and p38β−/− MEFs to anisomycin. Significant differences in the repertoire of the proteome and phosphoproteome between cells expressing active p38α and p38β suggest distinct roles for each kinase. Interestingly, in both cases, the constitutive activation induced adaptations of the cells to the chronic activity so that known substrates of p38 were downregulated. Within the dramatic effect of p38s on the proteome and phosphoproteome, some interesting affected phosphorylation sites were those found in cancer-associated p53 and Hspb1 (HSP27) proteins and in cytoskeleton-associated proteins. Among these, was the stronger direct phosphorylation by p38α of p53-Ser309, which was validated on the Ser315 in human p53. In summary, this study sheds new light on the differences between chronic and transient p38α and p38β signaling and on the specific targets of these two kinases.
Management of Spodoptera frugiperda J.E. Smith Using Recycled Virus Inoculum from Larvae Treated with Baculovirus under Field Conditions
Authors: Mweke Allan , Rwomushana Ivan , Okello Arthur , Chacha Duncan , Guo Jingfei , Luke Belinda
Published: August 2023

Fall armyworm (FAW) is a major pest of maize and causes huge losses. Chemical pesticides are the commonly used control strategy among farmers. The efficacy of baculoviruses against FAW has been proven; however, farmers may not be able to afford the products. The use of farmer-produced baculovirus mixtures could provide an opportunity for a nature-based solution for FAW at a low cost. This study evaluated the potential of recycled virus inoculum from FAW larvae treated with a commercial baculovirus (Littovir) for the management of FAW under laboratory and field conditions. In the laboratory, the virus from 25, 50, 75 and 100 FAW larvae caused variable mortality among FAW instars. The highest mortality (45%) among 1st–3rd instars was caused by Littovir followed by recycled virus inoculum from 100 FAW larvae (36%). Under field conditions, even though recycled virus inoculum did not offer adequate protection against FAW damage, the maize yield was comparable to that of commercial insecticide-treated plots and similar to that of control plots. This study has shown the potential use of recycled virus inoculum from infected larvae for the management of FAW. This would offer the farmers a sustainable and affordable option for the management of FAW as it would require the farmers to purchase the commercial baculovirus once and collect larvae from treated plots for repeat applications.
Subclinical Atrial Fibrillation on Prolonged ECG Holter Monitoring: Results from the Multicenter Real-World SAFARI (Silent Atrial Fibrillation ANCE-Sicily Research Initiative) Study
Authors: de Gregorio Cesare , Di Franco Antonino , Panno Antonio Vittorio , Di Franco Marco , Scaccianoce Giuseppe , Campanella Francesca , Novo Giuseppina , Galassi Alfredo Ruggero , Novo Salvatore ,   the SAFARI Study Group
Published: August 2023

Background: The detection of subclinical/silent atrial fibrillation (SAF) in the general population is of the utmost importance, given its potential adverse consequences. Incident AF has been observed in 30% to 70% of patients with implanted devices, but its prevalence may indeed be lower in the general population. The prospective, multicentric, observational Silent Atrial Fibrillation ANCE Research Initiative (SAFARI) study aimed at assessing the SAF prevalence in a real-world outpatient setting by the means of a small, wearable, prolonged ECG Holter monitoring (>5 days) device (CGM HI 3-Lead ECG; CGM TELEMEDICINE, Piacenza, Italy). Methods: Patients ≥ 55 years of age at risk for AF were screened according to the inclusion criteria to undergo prolonged 3-lead ECG Holter monitoring. SAF episodes were classified as follows: Class A, <30 s; Class B, 30 to 299 s; and Class C, ≥300 s. Results: In total, 119 patients were enrolled (64 men; median age 71 (IQR 55–85) years). At a median of 13.5 (IQR 5–21) days of monitoring, SAF episodes were found in 19 patients (16%). A total of 10,552 arrhythmic episodes were registered, 6901 in Class A (n = 7 patients), 2927 in Class B (n = 3), and 724 in Class C (n = 9), (Class A vs. B and C, p < 0.001). This latter group had multiple (all-class) episodes, and two patients had >1000 episodes. There were no clinical, echocardiographic, or laboratory findings able to discriminate patients with SAF from those in sinus rhythm in univariate and multivariable analyses; of note is that the Class C patients showed a higher diastolic blood pressure, resting heart rate, and indexed LA volume. Conclusions. Over a median of 13 days of Holter monitoring, the SAFARI study confirmed the usefulness of small wearable devices in detecting SAF episodes in real-world outpatients at risk for, but with no prior history of, AF.
Novel Biomarkers for the Assessment of the Cardio-Renal Syndrome—A Paradigm Shift
Authors: Shacham Yacov
Published: August 2023

Among patients admitted to medical wards, a growing number have various degrees of cardiac and renal dysfunction [...]
Combination of Cross-Correlation-Based Analysis and Ultrasonic GW Tomography for Barely Visible Impact Damage Detection Preliminary Assessment
Authors: Ciminello Monica , Boffa Natalino Daniele , Ameduri Salvatore , Monaco Ernesto
Published: August 2023

Statistical based reconstruction methods and signal processing tooling techniques are implemented and used to detect delaminations or debondings within composite complex items with very high precision. From the literature, it appears that although a single procedure for the estimation of structural health is a fast solution, multiple analyses based on different reconstruction methods or different damage parameters are the way to achieve maturation assessments of the methodology. This highlights the fact that the hardware and software parts of an SHM system need two different assessment and maturation ways. This work focuses on the software part by proposing a way to start assessing the outcomes. In this paper, the damage detection and localization strategy in CFRP plate-like structures with elastic guided waves excited and acquired with a circular array PWAS network is considered. Previous outcomes are compared by new analyses using a new post-processing approach based on a cross-correlation-based technique in terms of the BVID (Barely Visible Impact Damage) surface position and its center of mass. The advantage of this specific study is hopefully to enable confidence in the transition from R&D to field implementation. In addition, this work tries to evidence an improvement in terms of cost efficiency and reduced complexity while maintaining the same accuracy.
Sex Differences in Resting Metabolic Rate among Athletes and Association with Body Composition Parameters: A Follow-Up Investigation
Authors: Jagim Andrew R. , Jones Margaret T. , Askow Andrew T. , Luedke Joel , Erickson Jacob L. , Fields Jennifer B. , Kerksick Chad M.
Published: August 2023

The purpose of this study was to examine sex differences in resting metabolic rate (RMR) and associations between measured RMR and body composition parameters in athletes. One-hundred and ninety collegiate men (n = 98; age: 20.1 ± 1.6 yr.; body mass: 92.7 ± 17.5 kg; height: 181.6 ± 6.2 cm, body mass index: 28.0 ± 4.7 kg/m2) and women (n = 92; age: 19.4 ± 1.1 yr.; body mass: 65.2 ± 11.0 kg; height: 168.0 ± 6.6 cm, body mass index: 23.0 ± 3.6 kg/m2) athletes volunteered to participate in this study. Athletes completed a body composition assessment using air displacement plethysmography and RMR using indirect calorimetry. Assessments were completed in a fasted state and after refraining from intense physical activity > 24 h prior to testing. Data were collected during the 2016–2019 seasons. Men had a higher RMR compared to women (2595 ± 433 vs. 1709 ± 308 kcals; p < 0.001); however, when adjusted for body mass (p = 0.064) and fat-free mass (p = 0.084), the observed differences were not significant. Height, body mass, body mass index, fat-free mass, and fat mass were positively associated with RMR in both men and women athletes (r = 0.4–0.8; p < 0.001). Body mass (men: β = 0.784; women: β = 0.832)) was the strongest predictor of RMR. Men athletes have a higher absolute RMR compared to their women counterparts, which is influenced by greater body mass and fat-free mass. Body mass is the strongest predictor of RMR in both men and women athletes.
The Influence of Injection Temperature and Pressure on Pattern Wax Fluidity
Authors: Bazhenov Viacheslav E. , Sannikov Andrey V. , Kovyshkina Elena P. , Koltygin Andrey V. , Bazlov Andrey I. , Belov Vladimir D. , Dmitriev Dmitry N.
Published: August 2023

In the investment casting process, the pattern made of wax is obtained in a die for further formation of a shell mold. The problem of die-filling by pattern wax is significant because it influences the quality of the final casting. This work investigates three commercial pattern waxes’ fluidity with a newly developed injection fluidity test. It was shown that the fluidity of waxes increased with increasing injection temperature and pressure, and the simultaneous increase in temperature and pressure gives a much more significant enhancement of fluidity than an increase in temperature or pressure separately. The rheological behavior of the waxes was also investigated at different temperatures using a rotational viscosimeter, and temperature dependences of waxes’ dynamic viscosity were determined. It was shown that wax viscosity is increased more than ten times with decreasing temperature from 90 to 60 °C. A good correlation between wax fluidity and its viscosity is observed, which is different from metallic alloys, where the solidification behavior is more critical. The difference in wax flow behavior in comparison with metallic melts is associated with the difference in dynamic viscosity, which for investigated waxes and metallic melts is 3000–27,000 mPa·s and 0.5–6.5 mPa·s, respectively. The difference in investigated filled waxes’ fluidity is observed, which can be associated with the type and amount of filler. The twice-increasing fraction of cross-linked polystyrene decreases fluidity twice. At the same time, terephthalic acid has a minor influence on wax fluidity.
Advancements in Designing the DEMO Driver Blanket System at the EU DEMO Pre-Conceptual Design Phase: Overview, Challenges and Opportunities
Authors: Hernández Francisco A. , Arena Pietro , Boccaccini Lorenzo V. , Cristescu Ion , Del Nevo Alessandro , Sardain Pierre , Spagnuolo Gandolfo A. , Utili Marco , Venturini Alessandro , Zhou Guangming
Published: August 2023

The EU conducted the pre-conceptual design (PCD) phase of the demonstration reactor (DEMO) during 2014–2020 under the framework of the EUROfusion consortium. The current strategy of DEMO design is to bridge the breeding blanket (BB) technology gaps between ITER and a commercial fusion power plant (FPP) by playing the role of a “Component Test Facility” for the BB. Within this strategy, a so-called driver blanket, with nearly full in-vessel surface coverage, will aim at achieving high-level stakeholder requirements of tritium self-sufficiency and power extraction for net electricity production with rather conventional technology and/or operational parameters, while an advanced blanket (or several of them) will aim at demonstrating, with limited coverage, features that are deemed necessary for a commercial FPP. Currently, two driver blanket candidates are being investigated for the EU DEMO, namely the water-cooled lithium lead and the helium-cooled pebble bed breeding blanket concepts. The PCD phase has been characterized not only by the detailed design of the BB systems themselves, but also by their holistic integration in DEMO, prioritizing near-term solutions, in accordance with the idea of a driver blanket. This paper summarizes the status for both BB driver blanket candidates at the end of the PCD phase, including their corresponding tritium extraction and removal (TER) systems, underlining the main achievements and lessons learned, exposing outstanding key system design and R&D challenges and presenting identified opportunities to address those risks during the conceptual design (CD) phase that started in 2021.
A Whole-Genome Assembly for Hyaloperonospora parasitica, A Pathogen Causing Downy Mildew in Cabbage (Brassica oleracea var. capitata L.)
Authors: Wu Yuankang , Zhang Bin , Liu Shaobo , Zhao Zhiwei , Ren Wenjing , Chen Li , Yang Limei , Zhuang Mu , Lv Honghao , Wang Yong , Ji Jialei , Han Fengqing , Zhang Yangyong
Published: August 2023

Hyaloperonospora parasitica is a global pathogen that can cause leaf necrosis and seedling death, severely threatening the quality and yield of cabbage. However, the genome sequence and infection mechanisms of H. parasitica are still unclear. Here, we present the first whole-genome sequence of H. parasitica isolate BJ2020, which causes downy mildew in cabbage. The genome contains 4631 contigs and 9991 protein-coding genes, with a size of 37.10 Mb. The function of 6128 genes has been annotated. We annotated the genome of H. parasitica strain BJ2020 using databases, identifying 2249 PHI-associated genes, 1538 membrane transport proteins, and 126 CAZy-related genes. Comparative analyses between H. parasitica, H.arabidopsidis, and H. brassicae revealed dramatic differences among these three Brassicaceae downy mildew pathogenic fungi. Comprehensive genome-wide clustering analysis of 20 downy mildew-causing pathogens, which infect diverse crops, elucidates the closest phylogenetic affinity between H. parasitica and H. brassicae, the causative agent of downy mildew in Brassica napus. These findings provide important insights into the pathogenic mechanisms and a robust foundation for further investigations into the pathogenesis of H. parasitica BJ2020.