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17 pages, 1296 KiB  
Review
Role of Magnesium in Skeletal Muscle Health and Neuromuscular Diseases: A Scoping Review
by Sara Liguori, Antimo Moretti, Marco Paoletta, Francesca Gimigliano and Giovanni Iolascon
Int. J. Mol. Sci. 2024, 25(20), 11220; https://doi.org/10.3390/ijms252011220 (registering DOI) - 18 Oct 2024
Abstract
Magnesium (Mg) is a vital element for various metabolic and physiological functions in the human body, including its crucial role in skeletal muscle health. Hypomagnesaemia is frequently reported in many muscle diseases, and it also seems to contribute to the pathogenesis of skeletal [...] Read more.
Magnesium (Mg) is a vital element for various metabolic and physiological functions in the human body, including its crucial role in skeletal muscle health. Hypomagnesaemia is frequently reported in many muscle diseases, and it also seems to contribute to the pathogenesis of skeletal muscle impairment in patients with neuromuscular diseases. The aim of this scoping review is to analyze the role of Mg in skeletal muscle, particularly its biological effects on muscle tissue in neuromuscular diseases (NMDs) in terms of biological effects and clinical implications. This scoping review followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. From the 305 studies identified, 20 studies were included: 4 preclinical and 16 clinical studies. Preclinical research has demonstrated that Mg plays a critical role in modulating pathways affecting skeletal muscle homeostasis and oxidative stress in muscles. Clinical studies have shown that Mg supplementation can improve muscle mass, respiratory muscle strength, and exercise recovery and reduce muscle soreness and inflammation in athletes and patients with various conditions. Despite the significant role of Mg in muscle health, there is a lack of research on Mg supplementation in NMDs. Given the potential similarities in pathogenic mechanisms between NMDs and Mg deficiency, further studies on the effects of Mg supplementation in NMDs are warranted. Overall, maintaining optimal Mg levels through dietary intake or supplementation may have important implications for improving muscle health and function, particularly in conditions associated with muscle weakness and atrophy. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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<p>Flow diagram of source selection process.</p>
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<p>Primary dietary sources of magnesium and its pleiotropic actions, focusing on skeletal muscle health.</p>
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14 pages, 12342 KiB  
Article
Structural Changes in Copper Slags during Slow Cooling
by Bulat Sukurov, Sergey Kvyatkovskiy, Sultanbek Kozhakhmetov, Anastassiya Semenova, Maral Dyussebekova and Marina Kvyatkovskaya
Metals 2024, 14(10), 1187; https://doi.org/10.3390/met14101187 (registering DOI) - 18 Oct 2024
Abstract
The objects of the study were converter slags from the Balkhash copper plant in their initial state and after heat treatment. Using mineralogical and X-ray phase analysis, scanning electron microscopy (SEM), and electron probe microanalysis (EPMA), it was found that the initial converter [...] Read more.
The objects of the study were converter slags from the Balkhash copper plant in their initial state and after heat treatment. Using mineralogical and X-ray phase analysis, scanning electron microscopy (SEM), and electron probe microanalysis (EPMA), it was found that the initial converter slag and its thermally treated samples have identical matrices with almost complete coincidence in mineral and phase compositions. The distinguishing feature is the quantitative ratio of mineral components in the slag mass. Almost all of the iron is oxidized and present in the form of fayalite, magnetite, and magnetite, with other elements (silicon, copper, zinc, and aluminum) incorporated into its lattice. The structure of all slag samples indicates an association of sulfur exclusively with copper. Copper in the slags was identified in both metallic and sulfide forms. Slow cooling of the converter slag after its remelting contributes to the reduction in the sulfide–metal suspension in the volume of the melt and its coarsening. During slow cooling, structural changes occur not only in the main oxide part of the slag but also in the polymetallic globules. Full article
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<p>X-ray patterns of converter slag samples (<b>a</b>,<b>b</b>).</p>
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<p>Optical micrograph of the slag sample, polished section, and reflected light: 1—metallic copper; 2—magnetite and iron oxide with silicon; 3—fayalite; and 4—silicate slag phase.</p>
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<p>Structure of the section of converter slag samples after slow cooling: 1—metallic copper; 2—chalcocite; 3—magnetite and iron oxide with silicon; 4—fayalite; 5—silicate slag phase; and 6—lead.</p>
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<p>WDS mapping of the slag sample section by elements.</p>
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<p>Thermograms of the slag sample: (<b>a</b>)—melting; (<b>b</b>)—cooling.</p>
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<p>Position of matte and slag in the crucible after slow cooling: 1—matte, 2—slag, and 3—shrinkage cavities.</p>
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<p>WDS mapping of the slag sample after slow cooling by elements.</p>
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<p>Fine structure of the polymetallic globule in converter slag after slow cooling.</p>
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<p>Composition of the “crown” shell around the lead droplet inside the polymetallic globule in the converter slag after slow cooling.</p>
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<p>Fragments of WDS mapping of the slag sample after slow cooling by elements.</p>
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26 pages, 2309 KiB  
Review
Natural Products and Their Neuroprotective Effects in Degenerative Brain Diseases: A Comprehensive Review
by Dong Wook Lim, Jung-Eun Lee, Changho Lee and Yun Tai Kim
Int. J. Mol. Sci. 2024, 25(20), 11223; https://doi.org/10.3390/ijms252011223 (registering DOI) - 18 Oct 2024
Abstract
As the global population ages, the incidence of neurodegenerative diseases such as Alzheimer’s and Parkinson’s is rapidly rising. These diseases present a significant public health challenge, as they severely impair cognitive and motor functions, ultimately leading to a substantial reduction in quality of [...] Read more.
As the global population ages, the incidence of neurodegenerative diseases such as Alzheimer’s and Parkinson’s is rapidly rising. These diseases present a significant public health challenge, as they severely impair cognitive and motor functions, ultimately leading to a substantial reduction in quality of life and placing a heavy burden on healthcare systems worldwide. Although several therapeutic agents have been developed to manage the symptoms of these diseases, their effectiveness is often limited, and there remains an urgent need for preventive strategies. Growing evidence indicates that bioactive compounds from natural products possess neuroprotective properties through antioxidant and anti-inflammatory effects, modulating key pathways such as phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and brain-derived neurotrophic factor–tropomyosin receptor kinase B–cAMP response element-binding protein (BDNF-TrkB-CREB), which are crucial for neuronal survival. These compounds may also reduce amyloid-beta and tau pathology, as well as enhance cholinergic neurotransmission by inhibiting acetylcholinesterase activity. By targeting oxidative stress, neuroinflammation, and neurodegeneration, natural products offer a promising approach for both prevention and treatment. These findings suggest that natural products may be promising for preventing and treating neurodegenerative diseases. This review aims to explore the pathogenesis of neurodegenerative diseases, the limitations of current therapies, and the potential role of natural products as therapeutic agents. Full article
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<p>Degenerative brain diseases that occur mainly in each major brain region and their representative symptoms.</p>
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<p>Oxidative stress and its role in the pathogenesis of degenerative brain diseases. Degenerative brain diseases are largely driven by oxidative stress caused by excessive ROS production, often triggered by factors like mitochondrial dysfunction, protein accumulation (Aβ, tau, α-synuclein), and genetic risk factors like APOE ε4. ROS impair neuronal survival, differentiation, and synaptic plasticity by disrupting key signaling pathways such as BDNF/TrkB and PI3K/AKT, leading to neuronal damage and cell death. They also activate microglia and inflammatory responses, creating a cycle of oxidative stress and inflammation. Additionally, ROS impair mitochondrial function and BBB integrity, further exacerbating neuronal damage and disease progression. sAPPα: soluble amyloid precursor protein alpha, sAPPβ: soluble amyloid precursor protein beta, N: N-terminus, CTFα: C-terminal fragment alpha, C: C-terminus, CTFβ: C-terminal fragment beta, AICD: amyloid precursor protein intracellular domain, Aβ: amyloid beta, ROS: reactive oxygen species, NF-κB: nuclear factor kappa B, IL-1β: Interleukin-1 beta, IL-6: Interleukin-6, TNF-α: Tumor necrosis factor alpha, BDNF: brain-derived neurotrophic factor, TrkB: tropomyosin receptor kinase B, AMPAR: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, NMDAR: N-methyl-D-aspartate Receptor, PI3K: phosphoinositide 3-Kinase, AKT: protein kinase B, RAS: Rat Sarcoma virus, MAPK: mitogen-activated protein kinase, CaMII: calcium/calmodulin-dependent protein kinase II, PKC: protein kinase C.</p>
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<p>A natural product with well-established neuroprotective potential can exert its effects through multiple mechanisms. These mechanisms include AChE inhibition to enhance cholinergic transmission, a reduction in Aβ peptide and tau protein levels, and activation of the PI3K-AKT-GSK-3β pathway to improve synaptic function. Additionally, antioxidant and anti-inflammatory properties contribute to neuronal protection, while activation of the BDNF-TrkB-CREB pathway promotes synaptic plasticity. Furthermore, natural products may ameliorate synaptic dysfunction caused by oxidative stress and ROS generation. BACE1: beta-site amyloid precursor protein cleaving enzyme 1, APP: amyloid precursor protein, sAPPβ: soluble amyloid precursor protein beta, APOE ε4: apolipoprotein E epsilon 4 allele, Ach: acetylcholine, AchE: acetylcholinesterase, P85: phosphoinositide 3-kinase regulatory subunit p85, P110: phosphoinositide 3-kinase catalytic subunit p110, PI3K: hosphoinositide 3-kinase, AKT: protein kinase B, GSK3-β: glycogen synthase kinase 3 beta, ROS: reactive oxygen species, BDNF: brain-derived neurotrophic factor, TrkB: tropomyosin receptor kinase B, ERK1/2: extracellular signal-regulated kinase 1/2, CREB: cAMP response element-binding protein.</p>
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21 pages, 2377 KiB  
Article
Adsorption Performance of Fe–Mn Polymer Nanocomposites for Arsenic Removal: Insights from Kinetic and Isotherm Models
by Jasmina Nikić, Malcolm Watson, Jovana Jokić Govedarica, Maja Vujić, Jovana Pešić, Srđan Rončević and Jasmina Agbaba
Materials 2024, 17(20), 5089; https://doi.org/10.3390/ma17205089 (registering DOI) - 18 Oct 2024
Abstract
Global concern over arsenic contamination in drinking water necessitates innovative and sustainable remediation technologies. This study evaluates the adsorption performance of Fe–Mn binary oxide (FMBO) nanocomposites developed by coating polyethylene (PE) and polyethylene terephthalate (PET) with FMBO for the removal of As(III) and [...] Read more.
Global concern over arsenic contamination in drinking water necessitates innovative and sustainable remediation technologies. This study evaluates the adsorption performance of Fe–Mn binary oxide (FMBO) nanocomposites developed by coating polyethylene (PE) and polyethylene terephthalate (PET) with FMBO for the removal of As(III) and As(V) from water. Adsorption kinetics were rapid, with equilibrium achieved within 1–4 h depending on the material and pH. PET-FMBO and FMBO exhibited faster rates and higher arsenic removal (up to 96%) than PE-FMBO. Maximum As(III) adsorption capacities ranged from 4.76 to 5.75 mg/g for PE-FMBO, 7.2 to 12.0 mg/g for PET-FMBO, and up to 20.8 mg/g for FMBO, while capacities for As(V) ranged from 5.20 to 5.60 mg/g, 7.63 to 18.4 mg/g, and up to 46.2 mg/g, respectively. The results of the Dubinin–Radushkevich isotherm model, with free energy (Ea) values exceeding 16 kJ/mol, suggest chemisorption is the dominant mechanism, which is supported by the kinetics data. Given the effective removal of As(III), chemisorption likely proceeds through ligand exchange during the Mn oxide-mediated oxidation of As(III) and complexation with hydroxyl groups on the nanocomposite. These findings highlight the strong potential of Fe–Mn polymer nanocomposites, particularly PET-FMBO, for efficient arsenic removal during practical water treatment applications. Full article
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Graphical abstract

Graphical abstract
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<p>N<sub>2</sub> adsorption–desorption isotherm of (<b>a</b>) PE, (<b>b</b>) PE-FMBO, (<b>c</b>) PET, (<b>d</b>) PET-FMBO, and (<b>e</b>) FMBO.</p>
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<p>SEM/EDS of unmodified polymer and FMBO nanocomposite (<b>a</b>) PE and PE-FMBO; (<b>b</b>) PET and PET-FMBO.</p>
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<p>FTIR spectra of unmodified polymer and FMBO nanocomposite (<b>a</b>) PE and PE-FMBO, (<b>b</b>) PET and PET-FMBO, and (<b>c</b>) FMBO.</p>
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<p>XRD pattern of unmodified polymer and FMBO nanocomposite (<b>a</b>) PE and PE-FMBO, (<b>b</b>) PET and PET-FMBO, and (<b>c</b>) FMBO.</p>
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<p>Adsorption of (<b>a</b>) As(III) and (<b>b</b>) on FMBO, PE-FMBO, and PET-FMBO as a function of contact time (m = 0.5 g, V = 20 mL (0.1 M NaNO<sub>3</sub>), C<sub>0</sub> = 0.2 mg/L, pH = 6–8.</p>
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<p>Non-linear regressions of the pseudo-second-order kinetics model for (<b>a</b>) As(III) and (<b>b</b>) As(V) adsorption on FMBO, PE-FMBO, and PET-FMBO at pH 6, 7, and 8.</p>
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<p>Freundlich adsorption isotherms of (<b>a</b>) As(III) and (<b>b</b>) As(V) on FMBO, PE-FMBO and PET-FMBO (m = 0.5 g, V = 20 mL (0.1 M NaNO<sub>3</sub>), C<sub>0</sub> = 0.1–10 mg/L, pH = 6–8).</p>
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<p>Proposed removal mechanism on Fe–Mn polymer nanocomposites.</p>
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<p>Regeneration and reuse of (<b>a</b>) PE-FMBO and (<b>b</b>) PET-FMBO after As(III) and As(V) adsorption. Adsorption conditions: Initial As(III)/As(V) 0.2 mg/L; sorbent dose 0.5 g; pH 7.0 ± 0.2. Desorption conditions: 0.1 M NaOH.</p>
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11 pages, 1350 KiB  
Article
Protective Effects of Annona Atemoya Extracts on Inflammation, Oxidative Stress, and Renal Function in Cadmium-Induced Nephrotoxicity in Wistar Rats
by Alexandre Coelho Serquiz, Joana de Angelis da Costa Barros Gomes, Naisandra Bezerra da Silva Farias, Denise Mafra, Pietra Maria Pereira de Lima, Daniella de Oliveira Coutinho, Fernanda Priscila Barbosa Ribeiro, Hugo Alexandre de Oliveira Rocha and José Luiz de Brito Alves
Pharmaceuticals 2024, 17(10), 1393; https://doi.org/10.3390/ph17101393 (registering DOI) - 18 Oct 2024
Abstract
Background: Cadmium (Cd), a highly toxic heavy metal from agricultural activities, and its exposure can lead to impaired renal function by increasing reactive oxygen species. The atemoya fruit is known for its high phenolic and antioxidant compounds. This study aimed to evaluate the [...] Read more.
Background: Cadmium (Cd), a highly toxic heavy metal from agricultural activities, and its exposure can lead to impaired renal function by increasing reactive oxygen species. The atemoya fruit is known for its high phenolic and antioxidant compounds. This study aimed to evaluate the effects of atemoya extracts on renal function, oxidative stress parameters, and inflammatory biomarkers in a cadmium-induced nephrotoxicity model. Methods: Three aqueous extracts were prepared from different parts of the atemoya fruit: seeds, peel, and pulp. Twenty-five male Wistar rats were allocated into four groups: control, seed, peel, and pulp extracts at 2 g/kg for 25 days. All treatment groups administered intraperitoneal injections of cadmium chloride (CdCl2) (2 mg/kg) to induce renal damage. Results: The cadmium-treated groups showed decreased creatinine clearance, SOD, CAT, and GPx activities (p < 0.05) and increased serum levels of TNF-α and IL-6 compared to the control group (p < 0.05). The treatment with seed, peel, and pulp extracts increased creatinine clearance (p < 0.05), increased SOD, CAT, and GPx activities (p < 0.05), and reduced serum levels of TNF-α and IL-6 compared to the Cd group (p < 0.05). Conclusions: This study supports the use of atemoya as a promising candidate for mitigating nephrotoxicity and highlights the importance of its antioxidant and anti-inflammatory properties in renal health. Full article
(This article belongs to the Special Issue Bioactive Substances, Oxidative Stress, and Inflammation)
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Graphical abstract

Graphical abstract
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<p>The administration of the peel, seed, and pulp extracts of atemoya improved renal function parameters. group (C) consisted of rats that were not exposed to any treatment (<span class="html-italic">n</span> = 5); cadmium group (Cd), the rats received intraperitoneal injections of cadmium (2 mg/kg); T-Se (rats treated with the lyophilized seed extract, <span class="html-italic">n</span> = 5); T-Pe (rats treated with the lyophilized bark extract, <span class="html-italic">n</span> = 5); T-Pu (rats treated with the lyophilized pulp extract, <span class="html-italic">n</span> = 5). All three groups received equal doses of different parts of atemoya (2 g/kg body weight). Administration of seed, peel and pulp extracts of atemoya reduced serum creatinine levels (<b>A</b>) and increased creatinine clearance (<b>B</b>) in cadmium-induced nephrotoxicity in Wistar rats. Results are expressed as mean ± SEM. The means of the groups were compared by one-way ANOVA followed by Tukey’s test: * <span class="html-italic">p</span> &lt; 0.05 versus control group; # <span class="html-italic">p</span> &lt; 0.05 versus Cd group.</p>
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<p>The administration of the peel, seed, and pulp extracts of atemoya increased antioxidant enzyme activities in serum and decreased serum inflammatory biomarkers. Groups: control group (C) consisted of rats that were not exposed to any treatment (<span class="html-italic">n</span> = 5); cadmium group (Cd), the rats received intraperitoneal injections of cadmium (2 mg/kg); T-Se (rats treated with the lyophilized seed extract, <span class="html-italic">n</span> = 5); T-Pe (rats treated with the lyophilized bark extract, <span class="html-italic">n</span> = 5); T-Pu (rats treated with the lyophilized pulp extract, <span class="html-italic">n</span> = 5). All three groups received equal doses of different parts of atemoya (2 g/kg body weight). Administration of seed, peel and pulp extracts of atemoya increased serum SOD, CAT and GPx activities (<b>A</b>–<b>C</b>) and decreased serum levels of TNF-α and IL-6 (<b>D</b>,<b>E</b>) in cadmium-induced nephrotoxicity in Wistar rats. Results are expressed as mean ± SEM. The means of the groups were compared by one-way analysis of variance followed by Tukey’s test: * <span class="html-italic">p</span> &lt; 0.05 vs. control group; # <span class="html-italic">p</span> &lt; 0.05 vs. Cd group; Ψ <span class="html-italic">p</span> &lt; 0.001 vs. T-Se group.</p>
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<p>Representative images illustrating the effects peel, seed, and pulp extracts of atemoya in cadmium-induced nephrotoxicity in Wistar rats. Groups: control group (<b>A</b>,<b>C</b>) consisted of rats that were not exposed to any treatment (<span class="html-italic">n</span> = 5); cadmium group (Cd) (<b>B</b>), the rats received intraperitoneal injections of cadmium (2 mg/kg); T-Se (<b>C</b>) (rats treated with the lyophilized seed extract, <span class="html-italic">n</span> = 5); T-Pe (<b>D</b>) (rats treated with the lyophilized bark extract, <span class="html-italic">n</span> = 5); T-Pu (<b>E</b>) (rats treated with the lyophilized pulp extract, <span class="html-italic">n</span> = 5). All three groups received equal doses of different parts of atemoya (2 g/kg body weight). Red arrows indicate glomerular hypercellularity and hyperemia. Black arrows indicate tubular dilation.</p>
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10 pages, 1380 KiB  
Protocol
A Dual-Labeled Multiplex Absolute Telomere Length Method to Measure Average Telomere Length
by Sue Rutherford Siegel, E. Alex Calcagni, Kelsey M. Draughon and Sheree F. Logue
DNA 2024, 4(4), 370-379; https://doi.org/10.3390/dna4040026 (registering DOI) - 18 Oct 2024
Abstract
Background/Objectives: Telomeres consist of repetitive nucleotide sequences and associated proteins that safeguard chromosome ends from degradation and fusion with neighboring chromosomes. As cells divide, telomeres shorten due to the end-replication problem and oxidative stress, ultimately contributing to cellular senescence. Telomeres therefore play a [...] Read more.
Background/Objectives: Telomeres consist of repetitive nucleotide sequences and associated proteins that safeguard chromosome ends from degradation and fusion with neighboring chromosomes. As cells divide, telomeres shorten due to the end-replication problem and oxidative stress, ultimately contributing to cellular senescence. Telomeres therefore play a role in cellular health and aging. Measuring telomere length has emerged as a significant biomarker in various fields of research, including aging, cancer, and chronic diseases. Accurate measurement of telomere length is critical for interpreting research findings and clinical applications. Variability in measurement techniques can lead to inconsistent results, underscoring the need for standardized protocols. Methods and Results: The Telomere Research Network (TRN), an initiative from the National Institute of Aging and National Institute of Environmental Health Sciences, has established recommended guidelines to standardize the measurement of telomere length using qPCR to ensure accuracy and reproducibility in population-based studies. The monochrome multiplex quantitative PCR (MMqPCR) assay has emerged as a robust method endorsed by the TRN for its accuracy and reproducibility in quantifying telomere length in epidemiology ad population based studies. The absolute telomere length (aTL) qPCR assay is currently being evaluated by the TRN for its capability to utilize an oligomer standard, enabling the generation of absolute telomere lengths. The oligomer feature facilitates a more direct comparison of results across experiments and laboratories. Conclusions: This paper outlines a novel dual-labeled multiplex aTL method by incorporating dual-labeled multiplex probes to measure average absolute telomere length, providing a clear advantage over the relative telomere length assay, which quantifies the ratio of telomeric repeats to single-copy gene numbers. Full article
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<p>Schematic representation of the primers and probes annealing to their targeted sequence (<b>a</b>) for the telomeric repeat oligomer probe mix and (<b>b</b>) for the <span class="html-italic">IFNB1</span> single-copy gene oligomer probe mix.</p>
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<p>Dual-labeled fluorescent standard curves (<b>a</b>) generated with the telomeric repeat oligomer probe mix and (<b>b</b>) generated with the <span class="html-italic">IFNB1</span> single-copy gene oligomer probe mix.</p>
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<p>Primer/probe annealing shows complementarity between the telomere probe and the TeloP1 primer.</p>
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17 pages, 3267 KiB  
Article
Dietary Probiotic Pediococcus acidilactici GKA4, Dead Probiotic GKA4, and Postbiotic GKA4 Improves Cisplatin-Induced AKI by Autophagy and Endoplasmic Reticulum Stress and Organic Ion Transporters
by Jaung-Geng Lin, Wen-Ping Jiang, You-Shan Tsai, Shih-Wei Lin, Yen-Lien Chen, Chin-Chu Chen and Guan-Jhong Huang
Nutrients 2024, 16(20), 3532; https://doi.org/10.3390/nu16203532 (registering DOI) - 18 Oct 2024
Abstract
Background/Objectives: Acute kidney injury (AKI) syndrome is distinguished by a quick decline in renal excretory capacity and usually diagnosed by the presence of elevated nitrogen metabolism end products and/or diminished urine output. AKI frequently occurs in hospital patients, and there are no existing [...] Read more.
Background/Objectives: Acute kidney injury (AKI) syndrome is distinguished by a quick decline in renal excretory capacity and usually diagnosed by the presence of elevated nitrogen metabolism end products and/or diminished urine output. AKI frequently occurs in hospital patients, and there are no existing specific treatments available to diminish its occurrence or expedite recovery. For an extended period in the food industry, Pediococcus acidilactici has been distinguished by its robust bacteriocin production, effectively inhibiting pathogen growth during fermentation and storage. Methods: In this study, the aim is to assess the effectiveness of P. acidilactici GKA4, dead probiotic GKA4, and postbiotic GKA4 against cisplatin-induced AKI in an animal model. The experimental protocol involves a ten-day oral administration of GKA4, dead probiotic GKA4, and postbiotic GKA4 to mice, with a cisplatin intraperitoneal injection being given on the seventh day to induce AKI. Results: The findings indicated the significant alleviation of the renal histopathological changes and serum biomarkers of GKA4, dead probiotic GKA4, and postbiotic GKA4 in cisplatin-induced nephrotoxicity. GKA4, dead probiotic GKA4, and postbiotic GKA4 elevated the expression levels of HO-1 and decreased the expression levels of Nrf-2 proteins. In addition, the administration of GKA4, dead probiotic GKA4, and postbiotic GKA4 significantly reduced the expression of apoptosis-related proteins (Bax, Bcl-2, and caspase 3), autophagy-related proteins (LC3B, p62, and Beclin1), and endoplasmic reticulum (ER) stress-related proteins (GRP78, PERK, ATF-6, IRE1, CHOP, and Caspase 12) in kidney tissues. Notably, GKA4, dead probiotic GKA4, and postbiotic GKA4 also upregulated the levels of proteins related to organic anion transporters and organic cation transporters. Conclusions: Overall, the potential therapeutic benefits of GKA4, dead probiotic GKA4, and postbiotic GKA4 are significant, particularly after cisplatin treatment. This is achieved by modulating apoptosis, autophagy, ER stress, and transporter proteins to alleviate oxidative stress. Full article
(This article belongs to the Special Issue What Is Proper Nutrition for Kidney Diseases?)
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<p>The experimental framework (<b>A</b>) and the renoprotective efficacy of GKA4, dead probiotic GKA4, and postbiotic GKA4 alleviates neurotoxicity induced by cisplatin treatment. Oral administration of GKA4, dead probiotic GKA4, and postbiotic GKA4 at 250 mg/kg was carried out daily for 10 consecutive days, with cisplatin being administered one hour after the seventh dose. The sacrifice of the mice occurred on the eleventh day. The levels of BUN (<b>B</b>) and CRE in the serum (<b>C</b>), the renal sections stained with H&amp;E (400×) (<b>D</b>), and the renal injury scale (<b>E</b>) were assessed. Means ± S.E.M (<span class="html-italic">n</span> = 5) are shown in the presentation of the data. Statistical significance (<span class="html-italic">p</span> &lt; 0.001) is indicated by <sup>###</sup> when compared with the control group sample. Statistical significance at *** <span class="html-italic">p</span> &lt; 0.001 was evident in contrast to the cisplatin group.</p>
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<p>The experimental framework (<b>A</b>) and the renoprotective efficacy of GKA4, dead probiotic GKA4, and postbiotic GKA4 alleviates neurotoxicity induced by cisplatin treatment. Oral administration of GKA4, dead probiotic GKA4, and postbiotic GKA4 at 250 mg/kg was carried out daily for 10 consecutive days, with cisplatin being administered one hour after the seventh dose. The sacrifice of the mice occurred on the eleventh day. The levels of BUN (<b>B</b>) and CRE in the serum (<b>C</b>), the renal sections stained with H&amp;E (400×) (<b>D</b>), and the renal injury scale (<b>E</b>) were assessed. Means ± S.E.M (<span class="html-italic">n</span> = 5) are shown in the presentation of the data. Statistical significance (<span class="html-italic">p</span> &lt; 0.001) is indicated by <sup>###</sup> when compared with the control group sample. Statistical significance at *** <span class="html-italic">p</span> &lt; 0.001 was evident in contrast to the cisplatin group.</p>
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<p>GKA4, dead probiotic GKA4, and postbiotic GKA4 alleviate oxidative stress in cisplatin-challenged AKI. The levels of MDA (<b>A</b>) and GSH (<b>B</b>) were assessed through specific assays for MDA and GSH. Means ± S.E.M (<span class="html-italic">n</span> = 5) are shown in the presentation of the data. Statistical significance (<span class="html-italic">p</span> &lt; 0.001) is indicated by <sup>###</sup> when compared with the control group sample. *** <span class="html-italic">p</span> &lt; 0.001 compared with the cisplatin group.</p>
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<p>The effects of GKA4, dead probiotic GKA4, and postbiotic GKA4 on cisplatin-induced protein expression, including that of HO-1 and Nrf2, were investigated in kidney tissues. The expression of HO-1 and Nrf2 proteins in renal homogenates was assessed via Western blot analysis after exposure to cisplatin. Densitometric analysis was employed to assess the protein bands. The experiments were conducted independently at least three times and representative images were presented.</p>
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<p>GKA4, dead probiotic GKA4, and postbiotic GKA4 administration resulted in changes in the expression levels of Bax, Bcl-2, and caspase-3 proteins after exposure to cisplatin. Antibodies specific to Bax, Bcl-2, caspase-3, and β-actin were used to conduct a Western blot analysis on kidney tissue lysates. A densitometric analysis was employed to assess the protein bands. The experiments were conducted independently at least three times, and representative images were presented.</p>
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<p>GKA4, dead probiotic GKA4, and postbiotic GKA4 resulted in a reduction in the levels of LC3B, P62, and Beclin 1 protein following exposure to cisplatin. Antibodies specific to LC3B, P62, Beclin 1, and β-actin were employed for a Western blot analysis of kidney tissue lysates. Protein bands were analyzed via densitometric analysis. The experiments were replicated at least three times, and representative images were displayed.</p>
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<p>GKA4, dead probiotic GKA4, and postbiotic GKA4 modulated the expression of ER stress proteins in mice with cisplatin-induced AKI. A Western blot analysis was performed on kidney tissue lysates to evaluate protein expression using antibodies specific to GRP78, PERK, ATF-6, IRE1, CHOP, and caspase 12. Densitometric analysis was employed to assess the protein bands. The experiments were conducted independently at least three times, and representative images were presented.</p>
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<p>GKA4, dead probiotic GKA4, and postbiotic GKA4 regulated renal transporter expressions following exposure to cisplatin in mice. A Western blot analysis was performed on kidney tissue lysates to evaluate protein expression using antibodies specific to OAT1, OAT3, OCT3, and MATE1. A densitometric analysis was employed to assess the protein bands. The experiments were conducted independently at least three times, and representative images were presented.</p>
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29 pages, 7135 KiB  
Review
Oxidative Processes and Xenobiotic Metabolism in Plants: Mechanisms of Defense and Potential Therapeutic Implications
by Caterina Vicidomini, Rosanna Palumbo, Maria Moccia and Giovanni N. Roviello
J. Xenobiot. 2024, 14(4), 1541-1569; https://doi.org/10.3390/jox14040084 (registering DOI) - 18 Oct 2024
Abstract
Plants are continuously exposed to environmental challenges, including pollutants, pesticides, and heavy metals, collectively termed xenobiotics. These substances induce oxidative stress by generating reactive oxygen species (ROS), which can damage cellular components such as lipids, proteins, and nucleic acids. To counteract this, plants [...] Read more.
Plants are continuously exposed to environmental challenges, including pollutants, pesticides, and heavy metals, collectively termed xenobiotics. These substances induce oxidative stress by generating reactive oxygen species (ROS), which can damage cellular components such as lipids, proteins, and nucleic acids. To counteract this, plants have evolved complex metabolic pathways to detoxify and process these harmful compounds. Oxidative stress in plants primarily arises from the overproduction of hydrogen peroxide (H2O2), superoxide anions (O2•−), singlet oxygen (1O2), and hydroxyl radicals (OH), by-products of metabolic activities such as photosynthesis and respiration. The presence of xenobiotics leads to a notable increase in ROS, which can result in cellular damage and metabolic disruption. To combat this, plants have developed a strong antioxidant defense mechanism that includes enzymatic antioxidants that work together to eliminate ROS, thereby reducing their harmful effects. In addition to enzymatic defenses, plants also synthesize various non-enzymatic antioxidants, including flavonoids, phenolic acids, and vitamins. These compounds effectively neutralize ROS and help regenerate other antioxidants, offering extensive protection against oxidative stress. The metabolism of xenobiotic substances in plants occurs in three stages: the first involves modification, which refers to the chemical alteration of xenobiotics to make them less harmful. The second involves conjugation, where the modified xenobiotics are combined with other substances to increase their solubility, facilitating their elimination from the plant. The third stage involves compartmentalization, which is the storage or isolation of conjugated xenobiotics in specific parts of the plant, helping to prevent damage to vital cellular functions. Secondary metabolites found in plants, such as alkaloids, terpenoids, and flavonoids, play a vital role in detoxification and the defense against oxidative stress. Gaining a deeper understanding of the oxidative mechanisms and the pathways of xenobiotic metabolism in plants is essential, as this knowledge can lead to the formulation of plant-derived strategies aimed at alleviating the effects of environmental pollution and enhancing human health by improving detoxification and antioxidant capabilities, as discussed in this review. Full article
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<p>Diagram showing the ameliorative effects of <span class="html-italic">Solanum aethiopicum</span> (photo courtesy of Giovanni N. Roviello) on anemia induced by the xenobiotic compound phenylhydrazine. The 3D structure of AST is freely available at the link <a href="https://www.rcsb.org/structure/1AAM" target="_blank">https://www.rcsb.org/structure/1AAM</a> (accessed on 8 August 2024).</p>
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<p>Vitamin C, Vitamin A, and Glutathione (GSH) are some of the main non-enzymatic antioxidants that play significant roles in maintaining redox homeostasis. The 3D structure of GSH is freely available at the link <a href="https://pubchem.ncbi.nlm.nih.gov/compound/448041#section=3D-Conformer" target="_blank">https://pubchem.ncbi.nlm.nih.gov/compound/448041#section=3D-Conformer</a> (accessed on 8 August 2024).</p>
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<p>(<b>a</b>) Representation of the Fenton reaction and the production of hydroxyl radicals (<sup>•</sup>OH), which play a crucial role in the development of oxidative stress-related diseases and conditions; (<b>b</b>) diagram showing hydroquinone, a harmful intermediate produced after xenobiotic exposure, which leads to cellular damage and oxidative stress.</p>
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<p>(<b>a</b>) Diagram illustrating the ameliorating effects of ISL, a natural chalcone-type flavonoid with antioxidant, anti-allergic, anti-inflammatory, anti-tumor, and estrogenic properties, against the developmental toxicity of BDE47, an abundant polybrominated diphenyl ether; the 3D structure of caspase 9 is freely available at the link <a href="https://www.rcsb.org/structure/3V3K" target="_blank">https://www.rcsb.org/structure/3V3K</a> (accessed on 8 August 2024) (<b>b</b>) 3D views of the human microsomal cytochrome P450 2E1 (CYP2E1) structure in complex with the inhibitor 4-methylpyrazole. CYP2E1 is involved in the monooxygenation of over 70 low molecular weight xenobiotic compounds. The structure can be freely accessed at <a href="https://www.rcsb.org/3d-view/3E4E/1" target="_blank">https://www.rcsb.org/3d-view/3E4E/1</a> (accessed on 27 July 2024).</p>
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<p>Diagram showing how <span class="html-italic">Beta vulgaris</span> L. (beetroot), known for its minerals and vitamins, counteracts chlorpyrifos (CPF) nephrotoxicity by restoring antioxidants and limiting oxidative stress. Beetroot products have effects that increase nuclear factor erythroid 2-related factor 2 (Nrf2), which is crucial in promoting the expression of defensive enzymes.</p>
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<p>Flowcharts (<b>A</b>–<b>C</b>). Flowchart (<b>A</b>) describes the protective effects of a group of natural products, including barley grass, carrot, and citrus fruit, highlighting their antioxidant chemicals and mechanisms. Flowchart (<b>B</b>) reports on another group of natural products: eleuthero root, ginkgo leaf, and grape seed/skin, emphasizing their protective chemicals and actions against oxidative damage. Flowchart (<b>C</b>) shows the mechanisms of action for a further group of natural products, such as kudzu root, milk thistle seed, rosemary leaf, Schisandra fruit, tomato, and turmeric root, detailing their specific chemicals and how they inhibit inflammation and enhance antioxidant defenses.</p>
Full article ">Scheme 2
<p>This diagram illustrates the intersection of plant metabolites, xenobiotics, and plant responses, showcasing the complex interactions where phytochemicals mitigate the adverse effects of harmful substances. It highlights how plants adapt through stress responses and gene expression changes, enhancing their resilience against environmental pollutants.</p>
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19 pages, 3985 KiB  
Article
Removal of Ibuprofen from Aqueous Solutions by Using Graphene Oxide@MgO
by Natalia Malouchi, Athanasia K. Tolkou, Konstantinos N. Maroulas, Ioannis A. Katsoyiannis and George Z. Kyzas
J. Compos. Sci. 2024, 8(10), 434; https://doi.org/10.3390/jcs8100434 (registering DOI) - 18 Oct 2024
Abstract
In this study, a new composite adsorbent, namely magnesium oxide modified graphene oxide (hereafter abbreviated GO@MgO), was prepared for the removal of Ibuprofen (IBU), a non-steroidal anti-inflammatory drug (NSAID) compound. Graphene oxide was modified with MgO to improve its properties. Several factors important [...] Read more.
In this study, a new composite adsorbent, namely magnesium oxide modified graphene oxide (hereafter abbreviated GO@MgO), was prepared for the removal of Ibuprofen (IBU), a non-steroidal anti-inflammatory drug (NSAID) compound. Graphene oxide was modified with MgO to improve its properties. Several factors important for the evolution of the adsorption process were investigated, such as the dose of the adsorbent, the pH, and the initial IBU content, as well as the duration of the procedure and temperature. According to the results obtained, it was found that at pH 3.0 ± 0.1, by applying 0.5 g/L GO@MgO to 100 mg/L IBU, more than 80% was removed, reaching 96.3% with the addition of 1.5 g/L adsorbent in 24 h. After 30 min, the equilibrium was reached (77% removal) by adding 0.5 g/L of GO@MgO. This study proves that GO@MgO is capable of economical and efficient adsorption. The IBU kinetic data followed the pseudo-second-order kinetic model. Langmuir and Freundlich isotherm models were used to interpret the adsorption, but the Freundlich model described the adsorption method more accurately. The positive values of ΔH0 (14.465 kJ/mol) confirm the endothermic nature of the adsorption. Due to the increase of ΔG0 values with temperature, the adsorption of IBU on GO@MgO is considered to be spontaneous. Full article
(This article belongs to the Special Issue Recent Progress in Hybrid Composites)
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Graphical abstract

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<p>Ibuprofen (IBU) structure [<a href="#B5-jcs-08-00434" class="html-bibr">5</a>].</p>
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<p>(<b>a</b>) SEM image before adsorption, (<b>b</b>) SEM image after adsorption, and (<b>c</b>) FTIR spectra of GO, GO@MgO, GO-MgO-IBU, (<b>d</b>) SEM-EDS analysis of GO@MgO.</p>
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<p>Effect of pH on the adsorption of IBU on GO@MgO and GO for comparison reason; IBU <span class="html-italic">C</span><sub>0</sub> 100 mg/L, dose 0.5 g/L, pH 2.0–9.0 ± 0.1, <span class="html-italic">T</span> = 298 K, <span class="html-italic">t</span> = 24 h.</p>
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<p>Determination of pH<sub>pzc</sub> of GO@MgO and GO by using pH change according to the drift method [<a href="#B55-jcs-08-00434" class="html-bibr">55</a>].</p>
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<p>Effect of GO@MgO and GO dose on IBU adsorption (<b>a</b>) regarding removal rate (%) and (<b>b</b>) regarding adsorption capacity (mg/g); IBU <span class="html-italic">C</span><sub>0</sub> 100 mg/L, pH 3.0 ± 0.1, <span class="html-italic">T</span> = 298 K, <span class="html-italic">t</span> = 24 h.</p>
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<p>Effect of contact time on the adsorption of IBU on GO and GO@MgO; IBU <span class="html-italic">C</span><sub>0</sub> 100 mg/L, dose 0.5 g/L, pH 3.0 ± 0.1, <span class="html-italic">T</span> = 298 K.</p>
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<p>Kinetic of pseudo-first and pseudo-second order model for the adsorption of IBU on GO@MgO; IBU <span class="html-italic">C</span><sub>0</sub> 100 mg/L, dose 0.5 g/L, pH 3.0 ± 0.1, <span class="html-italic">T</span> = 298 K.</p>
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<p>Langmuir and Freundlich isotherm models for the adsorption of IBU on GO@MgO; IBU <span class="html-italic">C</span><sub>0</sub> 20–500 mg/L, dose 0.5 g/L, pH 3.0 ± 0.1, <span class="html-italic">T</span> = 298 K, t = 2 h.</p>
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<p>Effect of temperature on the adsorption of IBU onto GO@MgO; IBU C<sub>0</sub> 100 mg/L, dose 0.5 g/L, pH 3.0 ± 0.1, contact time 30 min.</p>
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<p>(<b>a</b>) Adsorption of IBU onto GO@MgO; IBU C<sub>0</sub> 100 mg/L, dose 0.5 g/L, pH 3.0 ± 0.1, contact time 30 min, for six adsorption–desorption cycles after regeneration at pH 10 ± 0.1, by using 0.1 M NaOH treatment, (<b>b</b>) Loss of adsorbent weight after each cycle.</p>
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<p>Stability of GO@MgO at different pH values.</p>
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19 pages, 13480 KiB  
Article
The Identification of Microstructural Changes in High-Temperature Superconducting Tapes for Superconducting Fault Current Limiters
by Sylwia Hajdasz, Adam Kempski, Katarzyna Arkusz, Mariusz Michalski and Paweł Szczesniak
Appl. Sci. 2024, 14(20), 9520; https://doi.org/10.3390/app14209520 (registering DOI) - 18 Oct 2024
Abstract
HTS 2G tapes used in Superconducting Fault Current Limiters (SFCLs) have properties that allow for the effective limitation of short-circuit currents; however, due to the specificity of the device operation, they should be characterized by the high stability of the parameters when repeatedly [...] Read more.
HTS 2G tapes used in Superconducting Fault Current Limiters (SFCLs) have properties that allow for the effective limitation of short-circuit currents; however, due to the specificity of the device operation, they should be characterized by the high stability of the parameters when repeatedly leaving the superconducting state. During the operation of SFCLs, a situation may occur in which the parameters of the HTS tapes used will change several times as a result of the action of short-circuit currents that exceed the critical current IC of the superconductor of the tape used. This paper presents the results of microstructural tests of 2G HTS tapes intended for SFCLs, subjected to surge currents corresponding to prospective short-circuit currents with values higher than their critical currents IC and for which IC changes were observed. The HTS tapes were examined using a JEOL 7600F field emission scanning electron microscope (SEM), and their chemical composition was analyzed using Energy-Dispersive X-ray Spectroscopy (EDS). The test results indicate the possibility of micro-damage in the form of cracks in the superconductor layer, as well as the interruption of the buffer layers and the oxidation of the silver layers. The analysis of the chemical composition of the HTS tape layers may indicate the occurrence of diffusion processes. Full article
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Figure 1

Figure 1
<p>Construction of the 2nd generation HTS YBCO tape by SuperPower.</p>
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<p>R(T) characteristics of the 2G HTS SF 12100-CF tapes.</p>
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<p>Measurement system: (<b>a</b>) diagram of the measurement system; (<b>b</b>) view of the measurement station.</p>
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<p>Method of attaching the HTS tapes to the measuring holder.</p>
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<p>Current and voltage waveforms for the HTS tape: (<b>a</b>) the sample in the superconducting state; (<b>b</b>) the sample in the resistive state.</p>
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<p>Sample oscillogram of the test current pulse waveform for the SF12100-CF tape with a 4 µm silver layer illustrating the principle of short-circuit limitation by the SFCL.</p>
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<p>Measuring station with the scanning electron microscope.</p>
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<p>Samples of cross-sections of HTS tapes embedded in conductive resin.</p>
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<p>Cross-sectional photos of the HTS tapes taken using an electron microscope: (<b>a</b>) control sample; (<b>b</b>) sample exposed to prospective short-circuit currents.</p>
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<p>Sample photos of the HTS tape cross-section (4 µm Ag)—control sample: (<b>a</b>) the entire width of the cross-sectional area, (<b>b</b>) the upper Ag layer, (<b>c</b>) the YBCO layer, and (<b>d</b>) the lower Ag layer.</p>
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<p>Sample photos of the HTS tape cross-section (4 µm Ag)—control sample: (<b>a</b>) the entire width of the cross-sectional area, (<b>b</b>) the upper Ag layer, (<b>c</b>) the YBCO layer, and (<b>d</b>) the lower Ag layer.</p>
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<p>Photos of the SF12100-CF tape with a 4 μm silver layer: (<b>a</b>) cross-section photo of the control sample; (<b>b</b>) cross-section photo of the sample exposed to the prospective short-circuit currents with marked changes in the YBCO layer.</p>
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<p>Changes in the sample of the HTS tapes SF12100-CF (2 μm Ag) exposed to prospective short-circuit currents.</p>
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<p>SEM images of the cross-section of the HTS tape (4 μm Ag)—the control sample—and EDS spectra for the evaluation of the elemental composition: (<b>a</b>–<b>c</b>) the area corresponding to the silver layer, (<b>d</b>) the superconductor layer, and (<b>e</b>) the buffer layers.</p>
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<p>SEM images of the cross-section of the HTS tape (4 μm Ag)—the control sample—and EDS spectra for the evaluation of the elemental composition: (<b>a</b>–<b>c</b>) the area corresponding to the silver layer, (<b>d</b>) the superconductor layer, and (<b>e</b>) the buffer layers.</p>
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<p>SEM images of the HTS tape cross-section (4 μm Ag) and EDS spectra for the elemental composition assessment—the sample with reduced critical current value: (<b>a</b>) the area corresponding to the silver layer, (<b>b</b>) the area of the elements from the silver and superconductor layers, (<b>c</b>) the superconductor layer, and (<b>d</b>,<b>e</b>) the buffer layers.</p>
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<p>SEM images of the HTS tape cross-section (4 μm Ag) and EDS spectra for the elemental composition assessment—the sample with reduced critical current value: (<b>a</b>) the area corresponding to the silver layer, (<b>b</b>) the area of the elements from the silver and superconductor layers, (<b>c</b>) the superconductor layer, and (<b>d</b>,<b>e</b>) the buffer layers.</p>
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<p>SEM images of the cross-section of the HTS tape (2 μm Ag)—the control sample—and the EDS spectra and elemental composition evaluations: (<b>a</b>) the area corresponding to the silver layer, (<b>b</b>,<b>c</b>) the superconductor layer, and (<b>d</b>,<b>e</b>) the buffer layers.</p>
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<p>SEM images of the cross-section of the HTS tape (2 μm Ag)—the control sample—and the EDS spectra and elemental composition evaluations: (<b>a</b>) the area corresponding to the silver layer, (<b>b</b>,<b>c</b>) the superconductor layer, and (<b>d</b>,<b>e</b>) the buffer layers.</p>
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<p>SEM images of the HTS tape cross-section (2 μm Ag) and EDS spectra for the elemental composition assessment—the sample with reduced critical current value: (<b>a</b>) the area corresponding to the silver layer, (<b>b</b>) the area of elements from the silver and superconductor layers, (<b>c</b>) the superconductor layer, and (<b>d</b>,<b>e</b>) the buffer layers.</p>
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<p>SEM images of the HTS tape cross-section (2 μm Ag) and EDS spectra for the elemental composition assessment—the sample with reduced critical current value: (<b>a</b>) the area corresponding to the silver layer, (<b>b</b>) the area of elements from the silver and superconductor layers, (<b>c</b>) the superconductor layer, and (<b>d</b>,<b>e</b>) the buffer layers.</p>
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17 pages, 11033 KiB  
Article
Nitidine Chloride Alleviates Hypoxic Stress via PINK1-Parkin-Mediated Mitophagy in the Mammary Epithelial Cells of Milk Buffalo
by Zhiwei Kong, Haichang Pan, Zi Wang, Alida Abla and Yingming Wei
Animals 2024, 14(20), 3016; https://doi.org/10.3390/ani14203016 (registering DOI) - 18 Oct 2024
Abstract
Hypoxia in the mammary gland epithelial cells of milk buffalo (BMECs) can affect milk yield and composition, and it can even cause metabolic diseases. Nitidine chloride (NC) is a natural alkaloid with antioxidant properties that can scavenge excessive reactive oxygen species (ROS). However, [...] Read more.
Hypoxia in the mammary gland epithelial cells of milk buffalo (BMECs) can affect milk yield and composition, and it can even cause metabolic diseases. Nitidine chloride (NC) is a natural alkaloid with antioxidant properties that can scavenge excessive reactive oxygen species (ROS). However, the effect of NC on the hypoxic injury of BMECs and its molecular mechanisms are still unknown. Here, an immunofluorescence assay, transmission electron microscopy (TEM), and flow cytometry, combined with untargeted metabolomics, were used to investigate the protective effect of NC on hypoxic stress injury in BMECs. It was found that NC can significantly reduce cell activity (p < 0.05) and inhibit cellular oxidative stress (p < 0.05) and cell apoptosis (p < 0.05). A significant decrease in mitophagy mediated by the PINK1-Parkin pathway was observed after NC pretreatment (p < 0.05). In addition, a metabolic pathway enrichment analysis demonstrated that the mechanisms of NC against hypoxic stress may be related to the downregulation of pathways involving aminoacyl tRNA biosynthesis; arginine and proline metabolism; glycine, serine, and threonine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; and phenylalanine metabolism. Thus, NC has a protective effect on hypoxic mitochondria, and it can regulate amino acid metabolism in response to hypoxic stress. The present study provides a reference for the application of nitidine chloride to regulate the mammary lactation function of milk buffalo. Full article
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Figure 1
<p>Changes in cell proliferation and apoptosis. (<b>A</b>) EDU proliferation assay was used to detect proliferating on each group of cells. Scale bar = 50 um. Blue represents the staining of the nucleus and red represents the staining of the DNA. (<b>B</b>) Apoptosis rate under hypoxia and NC conditions detected via flow cytometer. * <span class="html-italic">p</span> &lt; 0.05, represents a significant difference.</p>
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<p>The anti-oxidative stress effects of NC on hypoxia-induced BMEC cell injury. (<b>A</b>) Fluorescence intensity of ROS under hypoxia and NC conditions detected via flow cytometry. (<b>B</b>) Effects on MDA, SOD, GSH-PX, CAT, and T-AOC levels in BMECs under hypoxia and NC conditions. * = <span class="html-italic">p</span>. * <span class="html-italic">p</span> &lt; 0.05, represents a significant difference; ** <span class="html-italic">p</span> &lt; 0.01, represents an extremely significant difference.</p>
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<p>Effect of NC on mitochondrial structure and function in BMECs. (<b>A</b>) Fluorescence intensity of LC3 and TOM20 under hypoxia and NC conditions detected via immunofluorescence. (<b>B</b>) Changes in mitochondrial ultrastructure of BMEC s under hypoxia and NC conditions. (<b>C</b>) Fluorescence intensity of mitochondrial function under hypoxia and NC conditions detected via flow cytometry. (<span class="html-italic">n</span> = 3, * <span class="html-italic">p &lt;</span> 0.05 means significant, ** <span class="html-italic">p &lt;</span> 0.01 means extremely significant) Note: NC, nitidine chloride. The red arrows in this figure are autophagic vesicles or autophagic lysosomes, and the yellow arrows are vacuolated structures. Note: NC, nitidine chloride.</p>
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<p>Effect of NC on mitochondrial structure and function in BMECs. (<b>A</b>) Fluorescence intensity of LC3 and TOM20 under hypoxia and NC conditions detected via immunofluorescence. (<b>B</b>) Changes in mitochondrial ultrastructure of BMEC s under hypoxia and NC conditions. (<b>C</b>) Fluorescence intensity of mitochondrial function under hypoxia and NC conditions detected via flow cytometry. (<span class="html-italic">n</span> = 3, * <span class="html-italic">p &lt;</span> 0.05 means significant, ** <span class="html-italic">p &lt;</span> 0.01 means extremely significant) Note: NC, nitidine chloride. The red arrows in this figure are autophagic vesicles or autophagic lysosomes, and the yellow arrows are vacuolated structures. Note: NC, nitidine chloride.</p>
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<p>Protein expression of the mitophagy pathway-related receptors. (<span class="html-italic">n</span> = 3, * <span class="html-italic">p &lt;</span> 0.05 means significant, ** <span class="html-italic">p &lt;</span> 0.01 means extremely significant).</p>
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<p>Graph of OPLS-DA scores. (<b>A</b>) Differences between hypoxic and control groups. (<b>B</b>) Differences between NC and control groups. (<b>C</b>) Differences between hypoxic and NC groups.</p>
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<p>(<b>A</b>–<b>C</b>): Volcano plot of differential metabolite screening. Scatter size corresponds to VIP value size. Red indicates significantly upregulated metabolites, blue indicates significantly downregulated metabolites, and gray indicates non-significantly different metabolites. (<b>A</b>) Comparison of hypoxia and control groups. (<b>B</b>) Comparison of NC and control groups. (<b>C</b>) Comparison of hypoxia and NC groups. (<b>D</b>–<b>F</b>) Heatmap visualization of metabolomic alterations induced by NC. Red indicates high expression of the substance content, and blue indicates low expression of the substance content. (<b>D</b>) Comparison of hypoxia and control groups. (<b>E</b>) Comparison of NC and control groups. (<b>F</b>) Comparison of hypoxia and NC groups.</p>
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<p>(<b>A</b>–<b>C</b>): Volcano plot of differential metabolite screening. Scatter size corresponds to VIP value size. Red indicates significantly upregulated metabolites, blue indicates significantly downregulated metabolites, and gray indicates non-significantly different metabolites. (<b>A</b>) Comparison of hypoxia and control groups. (<b>B</b>) Comparison of NC and control groups. (<b>C</b>) Comparison of hypoxia and NC groups. (<b>D</b>–<b>F</b>) Heatmap visualization of metabolomic alterations induced by NC. Red indicates high expression of the substance content, and blue indicates low expression of the substance content. (<b>D</b>) Comparison of hypoxia and control groups. (<b>E</b>) Comparison of NC and control groups. (<b>F</b>) Comparison of hypoxia and NC groups.</p>
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<p>Plot of pathway analysis. Horizontal coordinates and bubble sizes indicate the magnitude of the influencing factor of the pathway. Vertical coordinates and bubble colors indicate the <span class="html-italic">p</span>-value (−ln(<span class="html-italic">p</span>)) of the enrichment analysis. The darker the color, the smaller the <span class="html-italic">p</span>-value and the more significant the enrichment. (<b>A</b>) Comparison of hypoxia and control groups. (<b>B</b>) Comparison of NC and control groups. (<b>C</b>) Comparison of hypoxia and NC groups.</p>
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12 pages, 4415 KiB  
Article
A Novel Mechanism Based on Oxygen Vacancies to Describe Isobutylene and Ammonia Sensing of p-Type Cr2O3 and Ti-Doped Cr2O3 Thin Films
by Pengfei Zhou, Jone-Him Tsang, Chris Blackman, Yanbai Shen, Jinsheng Liang, James A. Covington, John Saffell and Ehsan Danesh
Chemosensors 2024, 12(10), 218; https://doi.org/10.3390/chemosensors12100218 (registering DOI) - 18 Oct 2024
Abstract
Gas sensors based on metal oxide semiconductors (MOS) have been widely used for the detection and monitoring of flammable and toxic gases. In this paper, p-type Cr2O3 and Ti-doped Cr2O3 (CTO) thin films were synthesized using an [...] Read more.
Gas sensors based on metal oxide semiconductors (MOS) have been widely used for the detection and monitoring of flammable and toxic gases. In this paper, p-type Cr2O3 and Ti-doped Cr2O3 (CTO) thin films were synthesized using an aerosol-assisted chemical vapor deposition (AACVD) method. Detailed analysis of the thin films deposited, including structural information, their elemental composition, oxidation state, and morphology, was investigated using XRD, Raman analysis, SEM, and XPS. All the gas sensors based on pristine Cr2O3 and CTO exhibited a reversible response and good sensitivity to isobutylene (C4H8) and ammonia (NH3) gases. Doping Ti into the Cr2O3 lattice improves the response of the CTO-based sensors to C4H8 and NH3. We describe a novel mechanism for the gas sensitivity of p-type metal oxides based on variations in the oxygen vacancy concentration. Full article
(This article belongs to the Special Issue Advanced Chemical Sensors for Gas Detection)
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<p>Schematic diagram of an aerosol-assisted CVD.</p>
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<p>(<b>a</b>) Photograph of sensor platform, and (<b>b</b>) schematic diagram of a sensor connected to nickel pins via platinum wires.</p>
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<p>XRD patterns of (<b>a</b>) Cr<sub>2</sub>O<sub>3</sub> thin film-based sensors exposed to different annealing temperatures and (<b>b</b>) CTO thin film-based sensors subjected to different annealing times.</p>
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<p>Raman spectra of the Cr<sub>2</sub>O<sub>3</sub> and CTO thin films.</p>
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<p>(<b>a</b>) High-resolution and (<b>b</b>) low-resolution SEM images of the CTO thin film.</p>
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<p>XPS spectra of the CTO film: (<b>a</b>) survey scan, (<b>b</b>) Ti 2p, (<b>c</b>) Cr 2p, and (<b>d</b>) O 1s.</p>
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<p>Change in resistance of the (<b>a</b>) Cr<sub>2</sub>O<sub>3</sub>-based sensors and (<b>b</b>) CTO-based sensors to C<sub>4</sub>H<sub>8</sub> gas.</p>
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<p>R<sub>g</sub>/R<sub>a</sub> against C<sub>4</sub>H<sub>8</sub> concentration for each Cr<sub>2</sub>O<sub>3</sub> and CTO sensor at different temperatures: (<b>a</b>) 400 °C; (<b>b</b>) 450 °C.</p>
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<p>Change in resistance of the (<b>a</b>) Cr<sub>2</sub>O<sub>3</sub>-based sensors and (<b>b</b>) CTO-based sensors to NH<sub>3</sub>.</p>
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<p>Schematic illustration of the possible sensing mechanism for Cr<sub>2</sub>O<sub>3</sub> and CTO thin films when exposed to C<sub>4</sub>H<sub>8</sub> or NH<sub>3</sub>.</p>
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32 pages, 10079 KiB  
Article
Deciphering the Landscape of GATA-Mediated Transcriptional Regulation in Gastric Cancer
by Rodiola Begolli, Anastasia Patouna, Periklis Vardakas, Anastasia Xagara, Kleanthi Apostolou, Demetrios Kouretas and Antonis Giakountis
Antioxidants 2024, 13(10), 1267; https://doi.org/10.3390/antiox13101267 (registering DOI) - 18 Oct 2024
Abstract
Gastric cancer (GC) is an asymptomatic malignancy in early stages, with an invasive and cost-ineffective diagnostic toolbox that contributes to severe global mortality rates on an annual basis. Ectopic expression of the lineage survival transcription factors (LS-TFs) GATA4 and 6 promotes stomach oncogenesis. [...] Read more.
Gastric cancer (GC) is an asymptomatic malignancy in early stages, with an invasive and cost-ineffective diagnostic toolbox that contributes to severe global mortality rates on an annual basis. Ectopic expression of the lineage survival transcription factors (LS-TFs) GATA4 and 6 promotes stomach oncogenesis. However, LS-TFs also govern important physiological roles, hindering their direct therapeutic targeting. Therefore, their downstream target genes are particularly interesting for developing cancer-specific molecular biomarkers or therapeutic agents. In this work, we couple inducible knockdown systems with chromatin immunoprecipitation and RNA-seq to thoroughly detect and characterize direct targets of GATA-mediated transcriptional regulation in gastric cancer cells. Our experimental and computational strategy provides evidence that both factors regulate the expression of several coding and non-coding RNAs that in turn mediate for their cancer-promoting phenotypes, including but not limited to cell cycle, apoptosis, ferroptosis, and oxidative stress response. Finally, the diagnostic and prognostic potential of four metagene signatures consisting of selected GATA4/6 target transcripts is evaluated in a multi-cancer panel of ~7000 biopsies from nineteen tumor types, revealing elevated specificity for gastrointestinal tumors. In conclusion, our integrated strategy uncovers the landscape of GATA-mediated coding and non-coding transcriptional regulation, providing insights regarding their molecular and clinical function in gastric cancer. Full article
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<p>Analysis of GATA4 and 6 expression in cancer patients. (<b>A</b>) Normalized expression of GATA4 (upper plot) and GATA6 (lower plot) in RNA-seq data from a multi-cancer panel of TCGA tumors. Dots correspond to average expression and grey density plots to its distribution for each cancer type. Cancer types are aligned from left to right according to decreasing levels of GATA4 expression for both plots. (<b>B</b>) Violin plots comparing the expression of GATA4 (upper plot) and GATA6 (lower plot) in staged gastroesophageal tumors from TCGA compared to normal biopsies. (<b>C</b>) Representative immunostaining images of GATA4 and GATA6 protein levels in gastric tumors (1 mm) from the Human Protein Atlas. The number of tissue sections with high or medium expression is shown above each image compared to the total. None of the available sections had low or non-detected levels of GATA4, while only 2 out of 11 sections had low/not-detected levels of GATA6. (<b>D</b>) Kaplan–Meier analysis for comparing lymph node invasion between patients with high (red curve) and low (green curve) levels of GATA4 (left plot, log2rank = 0.021) or GATA6 (right plot, log2rank = 0.007). (<b>E</b>) Bar plot demonstrating the expression of GATA4 (upper plot) or GATA6 (lower plot) from RNA-seq experiments in all available gastric cancer cell lines from the Cancer Cell Line Encyclopedia. Expression of both factors in AGS gastric cancer cells is marked with orange or blue, and cell lines are ranked from left to right according to decreasing levels of GATA expression.</p>
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<p>ChIP-seq analysis of GATA4 and 6 along with histone modifications in AGS cells. (<b>A</b>) Global heatmap analysis of ChIP-seq peak distribution around the TSS. (<b>B</b>) TSS distribution plot summarizing the percentage of peaks across all genomic annotations. (<b>C</b>) GATA4 and 6 peak distribution across genic annotations (left panel) and relative peak enrichment analysis over background for all genomic annotations. (<b>D</b>) Sea motif enrichment analysis for GATA4 and 6 peaks divided for all peaks (left), protein-coding promoters (middle), and non-coding promoters. Color indicates statistical significance; dot size indicates enrichment score. (<b>E</b>) Dot plot summarizing the disease enrichment results from the annotated ChIP-seq peaks. First panel on the left corresponds to results from all GATA peaks, the second panel corresponds to promoter peaks only, the third panel to the promoter peaks of all GATA upregulated genes, and the fourth panel to the promoter peaks of all GATA downregulated genes. Color indicates statistical significance; dot size indicates gene ratio for each category.</p>
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<p>Transcriptome analysis following inducible GATA RNAi in AGS cells. (<b>A</b>) Heatmap summarizing the normalized expression (z-score) of the commonly affected differentially expressed genes (DEGs) across all samples. (<b>B</b>) Deregulogram depicting the correlation of expression in GATA4 KD (x-axis) vs GATA6 KD (y-axis). Colors represent the level of statistical significance across both datasets. (<b>C</b>) Venn diagrams summarizing the number of commonly affected DEGs between both datasets across coding and non-coding biotypes. (<b>D</b>) Deregulogram highlighting the association between GATA presence at gene loci with the deregulation of the corresponding transcripts. Bottom plot ranks all genes according to their GATA regulatory score, upper plot highlights the smoothed pattern of deregulation (fold change) of the same sorted genes for GATA4 (shown with blue) and GATA6 KD (shown with yellow). (<b>E</b>) GSEA analysis summarizing the enrichment of genes involved in cell cycle regulation (left) and upper gastrointestinal cancer (right). Heatmaps at the bottom highlight the expression of each enriched gene (indicated via entrez ID at the bottom) across all RNA-set data from both datasets, shown at the right of each heatmap. (<b>F</b>) UCSC browser snap-shot highlighting the E2F8 locus as an example of a GATA-deregulated target. Green tracks summarize GATA ChIP-seq peak, blue/orange tracks summarize control and KD RNA-seq expression for GATA4, while pink/purple tracks summarize control and KD RNA-seq expression for GATA6.</p>
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<p>Phenotypic analysis of GATA KD in gastric cancer cells. (<b>A</b>) Colony formation assay following inducible knockdown of GATA4 and 6 in AGS cells. An inducible scrambled shRNA is also shown as a control. (<b>B</b>) Wound healing assay across a two-day time course of GATA4 and 6 knockdown in AGS cells vs the scrambled control. Magnification is 10x. (<b>C</b>) Cell cycle profiling of GATA4 and 6 downregulation in AGS cells align with the scrambled control. Black bars represent G1/G0, grey bars represent S phase, and green bars represent G2/M phase. (<b>D</b>) Analysis of anti-oxidation effects associated with scrambled shRNA expression or shRNA-mediated impairment of GATA4 and 6 function in AGS cells. * <span class="html-italic">p</span>-value ≤ 0.05, ** <span class="html-italic">p</span>-value ≤ 0.01, *** <span class="html-italic">p</span>-value ≤ 0.001, n.s: not significant, n.d: not detectable.</p>
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<p>GATA meta-signature clinomic footprint in cancer biopsies. (<b>A</b>) Heatmap summarizing the normalized expression (z-score) of the commonly affected differentially expressed genes (DEGs) across all TCGA STAD samples. Violin plots at the bottom summarize the expression of the up- and downregulated DEGs across all tumor stages. Statistical significance refers to normal vs rest and was calculated with the Kruskal–Wallis test. (<b>B</b>) Beeswarm plot summarizing the distribution of ROC AUC across all gastric tumor stages for all 104 DEGs from (<b>A</b>), divided according to their expression (up- or downregulated). (<b>C</b>) ROC curve analysis highlighting the diagnostic power of the four selected meta-signatures. Average AUC performance is indicated along with 95% confidence intervals and sensitivity/specificity values. (<b>D</b>) Boxplots comparing the expression of the four selected meta-signatures in normal (grey) vs tumor (red) biopsies across various gastrointestinal tumors. * <span class="html-italic">p</span>-value ≤ 0.05.</p>
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14 pages, 1075 KiB  
Review
Research Progress on the Effect and Mechanism of Superchilling Preservation Technology on Meat Quality Control
by Bo Wang, Jiamin Liang, Changyu Zhou, Jiamin Zhang, Lili Ji, Congyan Li, Xiuli Mei and Hongyue Chen
Foods 2024, 13(20), 3309; https://doi.org/10.3390/foods13203309 (registering DOI) - 18 Oct 2024
Abstract
During storage and transportation, meat is susceptible to the effects of microorganisms, endogenous enzymes, and oxygen, leading to issues such as moisture loss, spoilage, and deterioration. Superchilling, as a preservation method that combines the benefits of refrigeration and freezing, can effectively slow the [...] Read more.
During storage and transportation, meat is susceptible to the effects of microorganisms, endogenous enzymes, and oxygen, leading to issues such as moisture loss, spoilage, and deterioration. Superchilling, as a preservation method that combines the benefits of refrigeration and freezing, can effectively slow the growth and reproduction of microorganisms, control protein and lipid oxidation, reduce water loss, and maintain the quality and sensory properties of meat. This paper reviews the current application status of superchilling technology in meat preservation, focusing on the mechanisms of ice crystal formation, water retention, tenderness preservation, protein and fat oxidation control, and microbial growth inhibition under superchilling conditions. Additionally, it summarizes the research progress on the combined application of superchilling with emerging technologies such as electric fields, magnetic fields, and electron beams in meat preservation and explores its potential and future prospects for improving meat quality. The aim is to provide scientific evidence and technical support for the application of superchilling technology in enhancing meat quality. Full article
(This article belongs to the Special Issue Factors Impacting Meat Product Quality: From Farm to Table)
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<p>Process of ice crystal formation in superchilling meat.</p>
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<p>Structure of muscle.</p>
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<p>Mechanisms and outcomes of lipid and protein oxidation during superchilling storage of meat.</p>
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21 pages, 1019 KiB  
Review
Amyotrophic Lateral Sclerosis: Insights and New Prospects in Disease Pathophysiology, Biomarkers and Therapies
by Jameel M. Al-Khayri, Mamtha Ravindran, Akshatha Banadka, Chendanda Devaiah Vandana, Kushalva Priya, Praveen Nagella and Kowshik Kukkemane
Pharmaceuticals 2024, 17(10), 1391; https://doi.org/10.3390/ph17101391 (registering DOI) - 18 Oct 2024
Abstract
Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disorder marked by the gradual loss of motor neurons, leading to significant disability and eventual death. Despite ongoing research, there are still limited treatment options, underscoring the need for a deeper understanding of the disease’s [...] Read more.
Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disorder marked by the gradual loss of motor neurons, leading to significant disability and eventual death. Despite ongoing research, there are still limited treatment options, underscoring the need for a deeper understanding of the disease’s complex mechanisms and the identification of new therapeutic targets. This review provides a thorough examination of ALS, covering its epidemiology, pathology, and clinical features. It investigates the key molecular mechanisms, such as protein aggregation, neuroinflammation, oxidative stress, and excitotoxicity that contribute to motor neuron degeneration. The role of biomarkers is highlighted for their importance in early diagnosis and disease monitoring. Additionally, the review explores emerging therapeutic approaches, including inhibitors of protein aggregation, neuroinflammation modulators, antioxidant therapies, gene therapy, and stem cell-based treatments. The advantages and challenges of these strategies are discussed, with an emphasis on the potential for precision medicine to tailor treatments to individual patient needs. Overall, this review aims to provide a comprehensive overview of the current state of ALS research and suggest future directions for developing effective therapies. Full article
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<p>Comprehensive Overview of ALS: Diagnosis, Treatment, Pathophysiology, and Genetic Mutations.</p>
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<p>Complex neuronal mechanisms driving ALS progression and development.</p>
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