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Simony Carvalho Mendonça, Brendo Araujo Gomes, Mariana Freire Campos, Thamirys Silva da Fonseca, Maria Eduarda Alves Esteves, Bruce Veiga Andriolo, Caio Felipe de Araujo Ribas Cheohen, Larissa Esteves Carvalho Constant, Stephany da Silva Costa, Pedro Telles Calil, Amanda Resende Tucci, Thamara Kelcya Fonseca de Oliveira, Alice dos Santos Rosa, Vivian Neuza dos Santos Ferreira, Julia Nilo Henrique Lima, Milene Dias Miranda, Luciana Jesus da Costa, Manuela Leal da Silva, Marcus Tullius Scotti, Diego Allonso, Gilda Guimarães Leitão and Suzana Guimarães Leitãoadd
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Pharmaceuticals2024, 17(4), 436; https://doi.org/10.3390/ph17040436 (registering DOI) - 28 Mar 2024
The LABEXTRACT plant extract bank, featuring diverse members of the Myrtaceae family from Brazilian hot spot regions, provides a promising avenue for bioprospection. Given the pivotal roles of the Spike protein and 3CLpro and PLpro proteases in SARS-CoV-2 infection, this study
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The LABEXTRACT plant extract bank, featuring diverse members of the Myrtaceae family from Brazilian hot spot regions, provides a promising avenue for bioprospection. Given the pivotal roles of the Spike protein and 3CLpro and PLpro proteases in SARS-CoV-2 infection, this study delves into the correlations between the Myrtaceae species from the Atlantic Forest and these targets, as well as an antiviral activity through both in vitro and in silico analyses. The results uncovered notable inhibitory effects, with Eugenia prasina and E. mosenii standing out, while E. mosenii proved to be multitarget, presenting inhibition values above 72% in the three targets analyzed. All extracts inhibited viral replication in Calu-3 cells (EC50 was lower than 8.3 µg·mL−1). Chemometric analyses, through LC-MS/MS, encompassing prediction models and molecular networking, identified potential active compounds, such as myrtucommulones, described in the literature for their antiviral activity. Docking analyses showed that one undescribed myrtucommulone (m/z 841 [M − H]−) had a higher fitness score when interacting with the targets of this study, including ACE2, Spike, PLpro and 3CLpro of SARS-CoV-2. Also, the study concludes that Myrtaceae extracts, particularly from E. mosenii and E. prasina, exhibit promising inhibitory effects against crucial stages in SARS-CoV-2 infection. Compounds like myrtucommulones emerge as potential anti-SARS-CoV-2 agents, warranting further exploration.
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Biomass is a renewable energy source gaining attention for its potential to replace fossil fuels. Biomass gasification can produce hydrogen-rich gas, offering an environmentally friendly fuel for power generation, transportation, and industry. Hydrogen is a promising energy carrier due to its high energy
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Biomass is a renewable energy source gaining attention for its potential to replace fossil fuels. Biomass gasification can produce hydrogen-rich gas, offering an environmentally friendly fuel for power generation, transportation, and industry. Hydrogen is a promising energy carrier due to its high energy density, low greenhouse gas emissions, and versatility. This study aims to develop a hydrogen generation plant using a dual fluidized bed gasifier, which employs steam as a gasifying agent, to convert olive pomace waste from the Lebanese olive oil industry into hydrogen. The process is simulated using Aspen Plus and Fortran coding, and it includes a drying unit, gasification unit, gas cleaning unit, steam methane reformer unit, water–gas shift reactor unit, and a pressure swing adsorption unit. The generated gas composition is verified against previous research. Sensitivity analyses are conducted to investigate the impacts of the steam-to-biomass ratio (STBR) and gasification temperature on gas composition, demonstrating a valid STBR range of 0.5 to 1 and a reasonable gasification temperature range of 700 °C to 800 °C. Further sensitivity analyses assess the impact of reformer temperature and the steam-to-carbon ratio (S/C) on the gas composition leaving the steam methane reformer.
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In today’s fast-paced and ever-changing environment, the need for algorithms with enhanced global optimization capability has become increasingly crucial due to the emergence of a wide range of optimization problems. To tackle this issue, we present a new algorithm called Random Particle Swarm
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In today’s fast-paced and ever-changing environment, the need for algorithms with enhanced global optimization capability has become increasingly crucial due to the emergence of a wide range of optimization problems. To tackle this issue, we present a new algorithm called Random Particle Swarm Optimization (RPSO) based on cosine similarity. RPSO is evaluated using both the IEEE Congress on Evolutionary Computation (CEC) 2022 test dataset and Convolutional Neural Network (CNN) classification experiments. The RPSO algorithm builds upon the traditional PSO algorithm by incorporating several key enhancements. Firstly, the parameter selection is adapted and a mechanism called Random Contrastive Interaction (RCI) is introduced. This mechanism fosters information exchange among particles, thereby improving the ability of the algorithm to explore the search space more effectively. Secondly, quadratic interpolation (QI) is incorporated to boost the local search efficiency of the algorithm. RPSO utilizes cosine similarity for the selection of both QI and RCI, dynamically updating population information to steer the algorithm towards optimal solutions. In the evaluation using the CEC 2022 test dataset, RPSO is compared with recent variations of Particle Swarm Optimization (PSO) and top algorithms in the CEC community. The results highlight the strong competitiveness and advantages of RPSO, validating its effectiveness in tackling global optimization tasks. Additionally, in the classification experiments with optimizing CNNs for medical images, RPSO demonstrated stability and accuracy comparable to other algorithms and variants. This further confirms the value and utility of RPSO in improving the performance of CNN classification tasks.
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This article puts forward the argument for the acute and urgent need to move from ecclesial self-sufficiency to ecclesial interdependency in the ecumenical process. The difficulties in ecumenical cooperation mirror those in the climate crisis, as despite a global crisis of relevance for
[...] Read more.
This article puts forward the argument for the acute and urgent need to move from ecclesial self-sufficiency to ecclesial interdependency in the ecumenical process. The difficulties in ecumenical cooperation mirror those in the climate crisis, as despite a global crisis of relevance for Christianity and for the ecumenical movement, individual Churches, much like individual states, fail to work together effectively as they negotiate their own internal challenges. Not dissimilar to the ecological climate breakdown, what we understand as the history-bound reality of the Church will not be safeguarded and will not be made relevant in a today’s globalised, pluralistic, interconnected, and dominantly secular, in many contexts, world, except by concerted action from all Churches.
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A new method for evaluating the effective flange width of simply supported rectangular box-girders in bending is illustrated. It aims to overcome the lack in the literature of a general method able to supply the effective flange width for a general distribution of
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A new method for evaluating the effective flange width of simply supported rectangular box-girders in bending is illustrated. It aims to overcome the lack in the literature of a general method able to supply the effective flange width for a general distribution of loads along the beam axis, not restricted, i.e., to the few cases reported in standard codes. The method consists of finding an analytical expression for the effective width under sinusoidal loads of arbitrary wavelength and combining the results in the framework of a Fourier analysis. The model allows investigating the shear-lag effects on displacements and stresses. The analytical formulation proposed is validated against numerical results supplied by refined Finite Element analyses.
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Edson Moreira de Abrantes, Luiz Guilherme Medeiros Pessoa, Luiz Filipe dos Santos Silva, Emanuelle Maria da Silva, José Orlando Nunes da Silva, Maria Betânia Galvão dos Santos Freire, Alexandre Campelo de Oliveira and Eurico Lustosa do Nascimento Alencar
Sustainability2024, 16(7), 2825; https://doi.org/10.3390/su16072825 (registering DOI) - 28 Mar 2024
Silicon is known to be an effective salt stress attenuator for crops, and evaluating its application effectiveness in combination with other salt stress attenuators is essential for crops and soils. This work aimed to assess whether applying organic matter (OM) and Trichoderma (T)
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Silicon is known to be an effective salt stress attenuator for crops, and evaluating its application effectiveness in combination with other salt stress attenuators is essential for crops and soils. This work aimed to assess whether applying organic matter (OM) and Trichoderma (T) potentiates silicon (Si) in mitigating soil salinization and promoting quinoa growth under salt stress. Quinoa plants were grown in pots under saline irrigation (3.12 dS m−1) and subjected to the following treatments: quinoa only; quinoa + Si; quinoa + Si + OM; quinoa + Si + T; and quinoa + Si + OM + T, at two levels of soil moisture—30 and 80% of the available water content (AWC). Sixty days after transplanting, soil and quinoa plants were collected from the pots. At 80% AWC, Si + OM and Si + OM + T promoted the highest fresh mass for quinoa—301.54 and 247.26 g, respectively. Si + OM + T significantly mitigated saline parameters (EC = 9.82 dS m−1; ESP = 32.27%). Si combined with OM and T was the most effective way to attenuate salt stress in quinoa and soil salinization and promote a more sustainable way to manage saline irrigation in semiarid regions.
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Nonlinear photonic crystals with 3D orthorhombic lattice structures were fabricated using the femtosecond laser-poling technique in ferroelectric Sr0.28Ba0.72Nb2O6 (SBN) crystals. The crystals were used to demonstrate the possibility of generating cascaded third-harmonic waves in optically poled
[...] Read more.
Nonlinear photonic crystals with 3D orthorhombic lattice structures were fabricated using the femtosecond laser-poling technique in ferroelectric Sr0.28Ba0.72Nb2O6 (SBN) crystals. The crystals were used to demonstrate the possibility of generating cascaded third-harmonic waves in optically poled ferroelectric structures. The spectral response and conversion efficiency of the third-harmonic process were experimentally investigated. While the nonlinear cascading processes can be commonly realized in electric-field-poled ferroelectric crystals, their generation in optically poled ferroelectric domain structures have not been reported elsewhere. In addition to the fully phase-matched nonlinear interaction, Cherenkov-type third-harmonic generation that fulfills the longitudinal phase-matching condition was also experimentally studied. Our study contributes to exploring the full potential of optically induced nonlinear photonic crystals and provides a new choice of materials for third-harmonic generation.
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The use of a circular economy (CE) in a supply chain is conducive to remanufacturing. It can not only make the supply chain innovative but can also further ease resource consumption and lower pollution, thereby reducing carbon emissions. However, most current research remains
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The use of a circular economy (CE) in a supply chain is conducive to remanufacturing. It can not only make the supply chain innovative but can also further ease resource consumption and lower pollution, thereby reducing carbon emissions. However, most current research remains focused on the concept of integrating circular economy supply chains (CESCs); few studies have carried out practical research in industry, and research addressing issues regarding the rubber recycling industry is even rarer. Therefore, this study refined the existing framework by screening out key factors that a CESC applies to remanufacturing products. This study conducted an expert questionnaire survey using the FDM to select key factors. Since the 30 respondents selected for this study are all experts in related fields, the reliability and stability of the method and results can be ensured. Meanwhile, this study adopted the fuzzy DEMATEL method to rank the importance of the five selected aspects and nineteen criteria and clarified cause-and-effect relationships between the criteria. The results show that important aspects, including “the circular business model” and “enhancing the resource value in the supply chain”, are both classified as cause groups; there are four main criteria that need to be highlighted, namely, “optimizing the production process”, “effectively tracking and recycling products”, “redesigning remanufactured rubber products”, and “improving resource efficiency”. Therefore, when related industries build CESCs to manufacture remanufactured products, these criteria need to be considered first. This study combined a CESC with remanufactured products, constructed a new framework to expand the related literature, and further analyzed the rubber industry and the underlying rubber recycling industry. Accordingly, related industries can refer to the new framework and key factors to develop production strategies for remanufactured products when implementing a CESC.
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Kaviyon Sadrolashrafi, Lily Guo, Robin Kikuchi, Audrey Hao, Rebecca K. Yamamoto, Hannah C. Tolson, Sara N. Bilimoria, Danielle K. Yee and April W. Armstrong
Cells2024, 13(7), 587; https://doi.org/10.3390/cells13070587 (registering DOI) - 28 Mar 2024
The transmembrane glycoprotein OX40 receptor (OX40) and its ligand, OX40L, are instrumental modulators of the adaptive immune response in humans. OX40 functions as a costimulatory molecule that promotes T cell activation, differentiation, and survival through ligation with OX40L. T cells play an integral
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The transmembrane glycoprotein OX40 receptor (OX40) and its ligand, OX40L, are instrumental modulators of the adaptive immune response in humans. OX40 functions as a costimulatory molecule that promotes T cell activation, differentiation, and survival through ligation with OX40L. T cells play an integral role in the pathogenesis of several inflammatory skin conditions, including atopic dermatitis (AD). In particular, T helper 2 (TH2) cells strongly contribute to AD pathogenesis via the production of cytokines associated with type 2 inflammation (e.g., IL-4, IL-5, IL-13, and IL-31) that lead to skin barrier dysfunction and pruritus. The OX40-OX40L interaction also promotes the activation and proliferation of other T helper cell populations (e.g., TH1, TH22, and TH17), and AD patients have demonstrated higher levels of OX40 expression on peripheral blood mononuclear cells than healthy controls. As such, the OX40-OX40L pathway is a potential target for AD treatment. Novel therapies targeting the OX40 pathway are currently in development, several of which have demonstrated promising safety and efficacy results in patients with moderate-to-severe AD. Herein, we review the function of OX40 and the OX40-OX40L signaling pathway, their role in AD pathogenesis, and emerging therapies targeting OX40-OX40L that may offer insights into the future of AD management.
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Recently, with the remarkable advancements of deep learning in the field of image processing, convolutional neural networks (CNNs) have garnered widespread attention from researchers in the domain of hyperspectral image (HSI) classification. Moreover, due to the high performance demonstrated by the transformer architecture
[...] Read more.
Recently, with the remarkable advancements of deep learning in the field of image processing, convolutional neural networks (CNNs) have garnered widespread attention from researchers in the domain of hyperspectral image (HSI) classification. Moreover, due to the high performance demonstrated by the transformer architecture in classification tasks, there has been a proliferation of neural networks combining CNNs and transformers for HSI classification. However, the majority of the current methods focus on extracting spatial–spectral features from the HSI data of a single size for a pixel, overlooking the rich multi-scale feature information inherent to the data. To address this problem, we designed a novel transformer network with a CNN-enhanced cross-attention (TNCCA) mechanism for HSI classification. It is a dual-branch network that utilizes different scales of HSI input data to extract shallow spatial–spectral features using a multi-scale 3D and 2D hybrid convolutional neural network. After converting the feature maps into tokens, a series of 2D convolutions and dilated convolutions are employed to generate two sets of Q (queries), K (keys), and V (values) at different scales in a cross-attention module. This transformer with CNN-enhanced cross-attention explores multi-scale CNN-enhanced features and fuses them from both branches. Experimental evaluations conducted on three widely used hyperspectral image (HSI) datasets, under the constraint of limited sample size, demonstrate excellent classification performance of the proposed network.
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In this study, the fabrication of microfluidic chips through the bonding of poly (methyl methacrylate) (PMMA) boards featuring designed patterns to create a three-dimensional sandwich structure with embedded microchannels was explored. A key focus was optimization of the interface quality of bonded PMMA
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In this study, the fabrication of microfluidic chips through the bonding of poly (methyl methacrylate) (PMMA) boards featuring designed patterns to create a three-dimensional sandwich structure with embedded microchannels was explored. A key focus was optimization of the interface quality of bonded PMMA pairs by adjusting the solvent, such as such as acetone, alcohol, and their mixture. Annealing was conducted below 50 °C to leverage the advantages of low-temperature bonding. Because of the differences in the chemical reactivity of PMMA toward acetone, alcohol, and their combinations, the resulting defect densities at the bonding interfaces differed significantly under low-temperature annealing conditions. To achieve the optimal sealing integrity, bonding pressures of 30 N, 40 N, and 50 N were evaluated. The interface was analyzed through microstructural examination via optical microscopy and stress measurements were determined using digital photoelasticity, while the bonding strength was assessed through tensile testing.
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Since all policies address problems, they necessarily include implicit or explicit constructions of these problems. This paper explores how child maltreatment has been constructed in New Zealand’s child protection policies. It questions the underlying assumptions of this problem construction and seeks to shed
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Since all policies address problems, they necessarily include implicit or explicit constructions of these problems. This paper explores how child maltreatment has been constructed in New Zealand’s child protection policies. It questions the underlying assumptions of this problem construction and seeks to shed light on what has been omitted. Utilizing a qualitative content analysis of eight key policy documents, this study reveals the construction of child maltreatment has been dominated primarily by a child-centric, risk-focused approach. This approach assigns blame and shifts responsibilities onto parents and families. In addition, the vulnerability discourse and social investment approach underpinning this perspective have allowed important structural factors, such as poverty and inequality, to remain unaddressed. This paper also highlights the one-dimensional focus on the lower social class to control future liabilities. We suggest that the harm inflicted by corporations on children’s well-being is another form of child exploitation currently omitted from the problem construction. We suggest that child abuse should be defined and understood in policy as harm to children’s well-being and argue that the state should prevent and mitigate harm by addressing structural forces of the problem as well as protecting children against corporate harms.
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Tatyana Ageeva, Davran Sabirov, Albert Sufianov, Eldar Davletshin, Elizaveta Plotnikova, Rezeda Shigapova, Galina Sufianova, Anna Timofeeva, Yuri Chelyshev, Albert Rizvanov and Yana Mukhamedshina
Int. J. Mol. Sci.2024, 25(7), 3772; https://doi.org/10.3390/ijms25073772 (registering DOI) - 28 Mar 2024
Spinal cord injury (SCI) presents a complex challenge in neurorehabilitation, demanding innovative therapeutic strategies to facilitate functional recovery. This study investigates the effects of treadmill training on SCI recovery, emphasizing motor function enhancement, neural tissue preservation, and axonal growth. Our research, conducted on
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Spinal cord injury (SCI) presents a complex challenge in neurorehabilitation, demanding innovative therapeutic strategies to facilitate functional recovery. This study investigates the effects of treadmill training on SCI recovery, emphasizing motor function enhancement, neural tissue preservation, and axonal growth. Our research, conducted on a rat model, demonstrates that controlled treadmill exercises significantly improve motor functions post-SCI, as evidenced by improved scores on the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and enhanced electromyography readings. Notably, the training facilitates the preservation of spinal cord tissue, effectively reducing secondary damage and promoting the maintenance of neural fibers in the injured area. A key finding is the significant stimulation of axonal growth around the injury epicenter in trained rats, marked by increased growth-associated protein 43 (GAP43) expression. Despite these advancements, the study notes a limited impact of treadmill training on motoneuron adaptation and highlights minimal changes in the astrocyte and neuron–glial antigen 2 (NG2) response. This suggests that, while treadmill training is instrumental in functional improvements post-SCI, its influence on certain neural cell types and glial populations is constrained.
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Introduction: Food deserts are a major public health concern. Inadequate access to healthy food has been associated with poor nutrition and the development of dietary related chronic conditions. Objective: To determine the association between geographic access to nutritious food and preterm birth and
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Introduction: Food deserts are a major public health concern. Inadequate access to healthy food has been associated with poor nutrition and the development of dietary related chronic conditions. Objective: To determine the association between geographic access to nutritious food and preterm birth and whether gestational hypertension mediates this relationship. Methods: Food access data was retrieved from the U.S. Department of Agriculture Food Access Research Atlas (2019) and used to quantify the percentage of Census tracts within each county that were food deserts: low-income tracts with limited access to grocery stores, supermarkets, or other sources of healthy, nutritious foods. These data were merged with US birth records from 2018 to 2019 by using the maternal county of residence (n = 7,533,319). We fit crude and adjusted logistic regression models with generalized estimating equations to determine the association between living in a food desert and the odds of preterm birth. We conducted a secondary within-group analysis by stratifying the fully adjusted model by race for non-Hispanic White and non-Hispanic Black birthing people. Results: In the fully adjusted model, we found a dose–response relationship. As the prevalence of tract-level food deserts within counties increased, so did the likelihood of preterm birth (mid-range: odds ratio (OR) = 1.04, 95% confidence interval (C.I.) 1.01–1.07; high: OR = 1.07, 95% C.I. 1.03–1.11). Similar results were seen in the White–Black stratified models. However, a disparity remained as Black birthing people had the highest odds for preterm birth. Lastly, gestational hypertension appears to mediate the relationship between nutritious food access and preterm birth (natural indirect effect (NIE) = 1.01, 95% CI = 1.00, 1.01). Conclusion: It is salient, particularly for Black birthing people who experience high rates of adverse birth outcomes, that the role of food desert residency be explored within maternal and child health disparities.
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Studies have investigated heavy metal (HM) contamination in the Bohai Sea, but primarily in seawater and associated sediments, or in single rivers. For the first time, 31 major rivers discharging into the Bohai Sea were analyzed, along with 27 uniformly distributed coastal seawater
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Studies have investigated heavy metal (HM) contamination in the Bohai Sea, but primarily in seawater and associated sediments, or in single rivers. For the first time, 31 major rivers discharging into the Bohai Sea were analyzed, along with 27 uniformly distributed coastal seawater samples and selected invertebrates. The elements measured were As, Cd, Cr, Cu, Ni, Pb, V, and Zn. We calculated the ‘geo-accumulation index’, the ‘metal enrichment factor’, and the ‘contamination factor’, coupled with the ‘pollution load index’, and our findings suggested low-grade HM pollution, although two conspicuous associations of elements were found to stand out in particular: One is a combination of As, Cu, Cr, and V in seawater samples that may indicate pollution from intensive ship traffic. The other shows a significant pattern of Cr, Pb, and Zn in water samples from rivers discharging between Yantai and Weihai on the Shandong Peninsula at the south edge of the Bohai Sea. This is primarily a farming area, with a moderate share of industrial enterprises. Investigations including fertilizers and pesticides point to agricultural practices and textile printing/chrome tanneries as the causes of contamination. Overall, a significant decline was found in the HM load in the rivers, apart from those discharging into the Yellow Sea section.
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In 1992, a transcendental report suggested that the receptor of advanced glycation end-products (RAGE) functions as a cell surface receptor for a wide and diverse group of compounds, commonly referred to as advanced glycation end-products (AGEs), resulting from the non-enzymatic glycation of lipids
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In 1992, a transcendental report suggested that the receptor of advanced glycation end-products (RAGE) functions as a cell surface receptor for a wide and diverse group of compounds, commonly referred to as advanced glycation end-products (AGEs), resulting from the non-enzymatic glycation of lipids and proteins in response to hyperglycemia. The interaction of these compounds with RAGE represents an essential element in triggering the cellular response to proteins or lipids that become glycated. Although initially demonstrated for diabetes complications, a growing body of evidence clearly supports RAGE’s role in human diseases. Moreover, the recognizing capacities of this receptor have been extended to a plethora of structurally diverse ligands. As a result, it has been acknowledged as a pattern recognition receptor (PRR) and functionally categorized as the RAGE axis. The ligation to RAGE leads the initiation of a complex signaling cascade and thus triggering crucial cellular events in the pathophysiology of many human diseases. In the present review, we intend to summarize basic features of the RAGE axis biology as well as its contribution to some relevant human diseases such as metabolic diseases, neurodegenerative, cardiovascular, autoimmune, and chronic airways diseases, and cancer as a result of exposure to AGEs, as well as many other ligands.
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Artesunate belongs to a class of medications derived from the sweet wormwood plant (Artemisia annua) known as artemisinins. Artesunate has traditionally been used as a frontline treatment for severe malaria but has also demonstrated antineoplastic activity against various malignancies, including ovarian
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Artesunate belongs to a class of medications derived from the sweet wormwood plant (Artemisia annua) known as artemisinins. Artesunate has traditionally been used as a frontline treatment for severe malaria but has also demonstrated antineoplastic activity against various malignancies, including ovarian cancer. Data suggest that artesunate exacerbates cellular oxidative stress, triggering apoptosis. In the current study, we investigated the ability of navitoclax, an inhibitor of the antiapoptotic Bcl-2 protein family, to enhance artesunate efficacy in ovarian cancer cells. Artesunate and navitoclax both demonstrated antiproliferative effects on 2D and 3D ovarian cancer cell models as single agents. Upon combination of navitoclax with artesunate, antineoplastic drug synergy was also observed in each of the 2D cell lines and ovarian tumor organoid models tested. Further investigation of this drug combination using intraperitoneal CAOV3 xenograft models in BALB/scid mice showed that the artesunate/navitoclax doublet was superior to single-agent artesunate and vehicle control treatment. However, it did not outperform single-agent navitoclax. With optimization, this drug combination could provide a new therapeutic option for ovarian cancer and warrants further preclinical investigation.
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Basudev Chowdhury, Swati Garg, Wei Ni, Martin Sattler, Dana Sanchez, Chengcheng Meng, Taisei Akatsu, Richard Stone, William Forrester, Edmund Harrington, Sara J. Buhrlage, James D. Griffin and Ellen Weisberg
Cancers2024, 16(7), 1319; https://doi.org/10.3390/cancers16071319 (registering DOI) - 28 Mar 2024
Progress in the treatment of multiple myeloma (MM) has resulted in improvement in the survival rate for younger patients but not for patients >65. Thus, there is a need for more efficacious therapies. We and others have shown that bromodomain-containing protein 9 (BRD9),
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Progress in the treatment of multiple myeloma (MM) has resulted in improvement in the survival rate for younger patients but not for patients >65. Thus, there is a need for more efficacious therapies. We and others have shown that bromodomain-containing protein 9 (BRD9), a member of the non-canonical SWI/SNF chromatin remodeling complex, plays a role in MM cell survival, and targeting BRD9 selectively blocks MM cell proliferation and synergizes with IMiDs. We found that synergy in vitro is associated with the downregulation of MYC and Ikaros proteins, including IKZF3, and overexpression of IKZF3 or MYC could partially reverse synergy. RNA-seq analysis revealed synergy to be associated with the suppression of pathways associated with MYC and E2F target genes and pathways, including cell cycle, cell division, and DNA replication. Stimulated pathways included cell adhesion and immune and inflammatory response. Importantly, combining IMiD treatment and BRD9 targeting, which leads to the downregulation of MYC protein and upregulation of CRBN protein, was able to override IMiD resistance of cells exposed to iberdomide in long-term culture. Taken together, our results support the notion that combination therapy based on agents targeting BRD9 and IKZF3, two established dependencies in MM, represents a promising novel therapeutic strategy for MM and IMiD-resistant disease.
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Software evolution is driven by changes made during software development and maintenance. While source control systems effectively manage these changes at the commit level, the intent behind them are often inadequately documented, making understanding their rationale challenging. Existing commit intent classification approaches, largely
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Software evolution is driven by changes made during software development and maintenance. While source control systems effectively manage these changes at the commit level, the intent behind them are often inadequately documented, making understanding their rationale challenging. Existing commit intent classification approaches, largely reliant on commit messages, only partially capture the underlying intent, predominantly due to the messages’ inadequate content and neglect of the semantic nuances in code changes. This paper presents a novel method for extracting semantic features from commits based on modifications in the source code, where each commit is represented by one or more fine-grained conjoint code changes, e.g., file-level or hunk-level changes. To address the unstructured nature of code, the method leverages a pre-trained transformer-based code model, further trained through task-adaptive pre-training and fine-tuning on the downstream task of intent classification. This fine-tuned task-adapted pre-trained code model is then utilized to embed fine-grained conjoint changes in a commit, which are aggregated into a unified commit-level vector representation. The proposed method was evaluated using two BERT-based code models, i.e., CodeBERT and GraphCodeBERT, and various aggregation techniques on data from open-source Java software projects. The results show that the proposed method can be used to effectively extract commit embeddings as features for commit intent classification and outperform current state-of-the-art methods of code commit representation for intent categorization in terms of software maintenance activities undertaken by commits.
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Shrimp processing generates substantial waste, which is rich in valuable components such as polysaccharides, proteins, carotenoids, and fatty acids. This review provides a comprehensive overview of the valorization of shrimp waste, mainly shrimp shells, focusing on extraction methods, bioactivities, and potential applications of
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Shrimp processing generates substantial waste, which is rich in valuable components such as polysaccharides, proteins, carotenoids, and fatty acids. This review provides a comprehensive overview of the valorization of shrimp waste, mainly shrimp shells, focusing on extraction methods, bioactivities, and potential applications of these bioactive compounds. Various extraction techniques, including chemical extraction, microbial fermentation, enzyme-assisted extraction, microwave-assisted extraction, ultrasound-assisted extraction, and pressurized techniques are discussed, highlighting their efficacy in isolating polysaccharides, proteins, carotenoids, and fatty acids from shrimp waste. Additionally, the bioactivities associated with these compounds, such as antioxidant, antimicrobial, anti-inflammatory, and antitumor properties, among others, are elucidated, underscoring their potential in pharmaceutical, nutraceutical, and cosmeceutical applications. Furthermore, the review explores current and potential utilization avenues for these bioactive compounds, emphasizing the importance of sustainable resource management and circular economy principles in maximizing the value of shrimp waste. Overall, this review paper aims to provide insights into the multifaceted aspects of shrimp waste valorization, offering valuable information for researchers, industries, and policymakers interested in sustainable resource utilization and waste-management strategies.
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Environmental monitoring and the detection of antibiotic contaminants require expensive and time-consuming techniques. To overcome these challenges, gold nanoparticle-mediated fluorometric “turn-on” detection of Polymyxin B (PMB) in an aqueous medium was undertaken. The molecular weight of polyethyleneimine (PEI)-dependent physicochemical tuning of gold nanoparticles
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Environmental monitoring and the detection of antibiotic contaminants require expensive and time-consuming techniques. To overcome these challenges, gold nanoparticle-mediated fluorometric “turn-on” detection of Polymyxin B (PMB) in an aqueous medium was undertaken. The molecular weight of polyethyleneimine (PEI)-dependent physicochemical tuning of gold nanoparticles (PEI@AuNPs) was achieved and employed for the same. The three variable molecular weights of branched polyethyleneimine (MW 750, 60, and 1.3 kDa) molecules controlled the nano-geometry of the gold nanoparticles along with enhanced stabilization at room temperature. The synthesized gold nanoparticles were characterized through various advanced techniques. The results revealed that polyethyleneimine-stabilized gold nanoparticles (PEI@AuNP-1-3) were 4.5, 7.0, and 52.5 nm in size with spherical shapes, and the zeta potential values were 29.9, 22.5, and 16.6 mV, respectively. Accordingly, the PEI@AuNPs probes demonstrated high sensitivity and selectivity, with a linear relationship curve over a concentration range of 1–6 μM for polymyxin B. The limit of detection (LOD) was calculated as 8.5 nM. This is the first unique report of gold nanoparticle nano-geometry-dependent FRET-based turn-on detection of PMB in an aqueous medium. We believe that this approach would offer a complementary strategy for the development of a highly sophisticated and advanced sensing system for PMB and act as a template for the development of new nanomaterial-based engineered sensors for rapid antibiotic detection in environmental as well as biological samples.
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Real-time reconstruction of ocean surface currents is a challenge due to the complex, non-linear dynamics of the ocean, the small number of in situ measurements, and the spatio-temporal heterogeneity of satellite altimetry observations. To address this challenge, we introduce HIRES-CURRENTS-Net, an operational real-time
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Real-time reconstruction of ocean surface currents is a challenge due to the complex, non-linear dynamics of the ocean, the small number of in situ measurements, and the spatio-temporal heterogeneity of satellite altimetry observations. To address this challenge, we introduce HIRES-CURRENTS-Net, an operational real-time convolutional neural network (CNN) model for daily ocean current reconstruction. This study focuses on the Mediterranean Sea, a region where operational models have great difficulty predicting surface currents. Notably, our model showcases higher accuracy compared to commonly used alternative methods. HIRES-CURRENTS-Net integrates high-resolution measurements from the infrared or visible spectrum—high resolution Sea Surface Temperature (SST) or chlorophyll (CHL) images—in addition to the low-resolution Sea Surface Height (SSH) maps derived from satellite altimeters. In the first stage, we apply a transfer learning method which uses a high-resolution numerical model to pre-train our CNN model on simulated SSH and SST data with synthetic clouds. The observation of System Simulation Experiments (OSSEs) offers us a sufficient training dataset with reference surface currents at very high resolution, and a model trained on this data can then be applied to real data. In the second stage, to enhance the real-time operational performance of our model over previous methods, we fine-tune the CNN model on real satellite data using a novel pseudo-labeling strategy. We validate HIRES-CURRENTS-Net on real data from drifters and demonstrate that our data-driven approach proves effective for real-time sea surface current reconstruction with potential operational applications such as ship routing.
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Using multi-color flow cytometry analysis, we studied the immunophenotypical differences between leukemic cells from patients with AML/MDS and hematopoietic stem and progenitor cells (HSPCs) from patients in complete remission (CR) following their successful treatment. The panel of markers included CD34, CD38, CD45RA, CD123
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Using multi-color flow cytometry analysis, we studied the immunophenotypical differences between leukemic cells from patients with AML/MDS and hematopoietic stem and progenitor cells (HSPCs) from patients in complete remission (CR) following their successful treatment. The panel of markers included CD34, CD38, CD45RA, CD123 as representatives for a hierarchical hematopoietic stem and progenitor cell (HSPC) classification as well as programmed death ligand 1 (PD-L1). Rather than restricting the evaluation on a 2- or 3-dimensional analysis, we applied a t-distributed stochastic neighbor embedding (t-SNE) approach to obtain deeper insight and segregation between leukemic cells and normal HPSCs. For that purpose, we created a t-SNE map, which resulted in the visualization of 27 cell clusters based on their similarity concerning the composition and intensity of antigen expression. Two of these clusters were “leukemia-related” containing a great proportion of CD34+/CD38− hematopoietic stem cells (HSCs) or CD34+ cells with a strong co-expression of CD45RA/CD123, respectively. CD34+ cells within the latter cluster were also highly positive for PD-L1 reflecting their immunosuppressive capacity. Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.
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